23 results on '"Voors-Pette, C"'
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2. 1791P A phase I pharmacology study of the dual MDMX/MDM2 inhibitor, ALRN 6924, in healthy volunteers
- Author
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Voors-Pette, C., primary, Aalders, W., additional, Brill, M., additional, Ferrari, D., additional, Annis, A., additional, Steidl, U., additional, Aivado, M., additional, and Vukovic, V., additional
- Published
- 2021
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3. Effect of Sitagliptin on Cardiovascular Outcomes in Type 2 Diabetes
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Green JB, Bethel MA, Armstrong PW, Buse JB, Engel SS, Garg J, Josse R, Kaufman KD, Koglin J, Korn S, Lachin JM, McGuire DK, Pencina MJ, Standl E, Stein PP, Suryawanshi S, Van de Werf F, Peterson ED, Holman RR, Josse RG, Califf RM, Goldstein BJ, Shapiro DR, Silverman R, Bethel A, Green J, Hayden S, Hannan K, Quintero K, Rorick T, Berdan L, Leloudis D, Califf S, Wilson M, McFarron D, Trollinger K, Pesarchick J, Eskenazi L, Campbell C, Townes O, Tolsma D, Keenan J, Milton J, Athwal R, Darbyshire J, Doran Z, Kennedy I, Gregory V, Lokhnygina Y, Prather K, Wolfley A, Usman M, Tajjar A, Gray R, Pfeffer MA, Gerstein HC, Groop L, McMurray JJ, Pocock SJ, Clayton T, Sinay I, Brieger D, Stranks S, Scheen A, Lopes R, Tankova T, Hramiak I, Grado CR, Wenying Y, Ge J, Aschner P, Skrha J, Ambos A, Strandberg T, Travert F, Hanefeld M, Riefflin A, Chan JC, Ofner P, Reddy NK, Christopher J, Mathur A, Arambam P, Mittal S, Manchanda M, Wainstein J, Ambrosio G, Pirags V, Jakuboniene N, Mohamed M, Scott R, White H, Cornel J, Halvorsen S, Tykarski A, Veresiu IA, Dreval AV, Misinkova I, Tai E, Krahulec B, Distiller L, Park Y, Rovira A, Alversson M, Chuang LM, Delibasi T, Adler A, Rodbard HW, Marre M, Goff D, Chacra A, DeVore A, Beaven A, Shah B, Hirsch B, Batch B, Bushnell C, Patel C, Melloni C, Henshaw C, Kong D, Bernecki G, Tillman H, Kang HJ, Hawes J, Strickler J, Piccini J, Wilder J, Alexander K, Mahaffey K, Patel K, Hyland K, Newby K, Jackson L, Cooper L, Armaganijan L, Szczeh L, Koshizaka M, Roe M, Morse M, Guimaraes P, Hess P, Tricoci P, Mehta R, Mathews R, Kociol R, Harrison R, Mentz R, Pokorney S, Leblanc T, Lazzarini V, Eapen Z, Truffa A, Fosbol E, Brito F, Katz M, Bahit M, Santos M, Barros P, Bernardez S, Alvarisqueta AF, Arias P, Cagide AL, Calella PR, Cantero MC, Canella JP, Cipullo MA, de Loredo L, Gelersztein ES, Gorban de Lapertosa SB, Klyver MI, Maffei LE, Maldonado N, Oviedo AI, Piskorz DL, Ridruejo MC, Saavedra SS, Sessa HA, Sinay IR, Sposetti GD, Ulla MR, Vico ML, Waitman JN, Binnekamp M, Carroll P, Cheung W, Colman P, Davis T, De Looze F, dEmden M, Fulcher G, Gerstman M, Hamilton A, Lehman S, Moses R, Proietto J, Roberts A, Shaw J, Simpson R, Sinha A, Tan Y, Topliss D, Vora P, Waites J, Crenier L, Descamps O, Keymeulen B, Mathieu C, Nobels F, Van den Bruel A, Van Gaal L, Borges JL, Costa e Forti A, Eliaschewitz FG, Felício JS, Griz LH, Hissa MN, Leite S, Panarotto D, Pimentel Filho P, Rassi N, Saraiva JK, Sgarbi JA, Silva RP, Tambascia M, Weber Silva DM, Bobeva R, Bostandzhieva R, Cinlikov I, Georgieva M, Iliev D, Ilieva E, Kovacheva S, Liubenova L, Nikitov Z, SHeinikova G, Slavcheva A, Spasova V, Temelkova-Kurktschiev T, Velichka D, Yakov A, Carpentier A, Chiasson JL, Constance C, Dumas R, Filteau P, Garceau C, Huynh T, Kaiser S, Kornder J, Leiter L, Mereu L, Miller D, Pandey S, Punthakee Z, Rabasa-Lhoret R, Robitaille Y, Saunders K, Sigal R, Sigalas J, Vizel S, Weisnagel S, Woo V, Yale JF, Yared K, Zinman B, Bunster Balocchi LB, Escobar Cerda EE, Garces Flores EE, Lanas Zanetti FT, Larrazabal Miranda Adel P, Morales Alvarado JM, Olivares Cañon CM, Potthoff Cárdenas SH, Raffo Grado CA, Rodriguez Venegas ME, Saavedra Gajardo VA, Westerberg Maldonado BH, Chen LL, Dong J, Guo X, Li QM, Shi B, Tang XL, Yang T, Yang WY, Zheng SX, Aschner Montoya P, Botero Lopez R, Coronel Arroyo JA, Cure CA, Gómez Medina AM, Molina DI, Perez Amador GA, Reyes Rincon A, Urina Triana MA, Valenzuela Rincon A, Vélez Pelaez S, Yupanqui Lozno H, Brabec T, Brychta T, Hasalova Zapletalova J, Havelkova J, Hejnicova K, Hola O, Hornackova M, Hrdina T, Kafkova D, Kellnerova I, Krystl T, Kutejova V, Mikulkova I, Nevrla J, Pantlikova C, Petr M, Racicka E, Sarbochova R, Smolenakova K, Turcinek R, Urbancova K, Vejvodova J, Vondrakova M, Zachoval R, Alt I, Kaasik Ü, Kiiroja K, Lanno R, Märtsin K, Past M, Vides H, Viitas L, Kantola I, Nieminen S, Perhonen M, Strand J, Valle T, Clergeot A, Couffinhal T, Courreges JP, Gouet D, Moulin P, Ziegler O, Badenhoop K, Behnke T, Bender G, Braun M, Dshabrailov J, Hamann A, Himpel-Boenninghoff A, Kamke W, Kasperk C, Luedemann J, Mayr P, Merkel M, Oerter EM, Ohlow MA, Ott P, Overhoff U, Paschen B, Remppis R, Rose L, Schumm-Draeger PM, Segiet T, Strotmann HJ, Stuchlik G, Stürmer W, Thinesse-Mallwitz M, Tytko A, Wendisch U, Wurziger J, Ho AY, Kam G, Kong AP, Lam YY, Lau EY, Lee S, Siu SC, Tomlinson B, Tsang CC, Yeung VT, Dezső E, Dudás M, Földesi I, Fülöp T, Késmárki N, Koranyi L, Nagy K, Oroszlán T, Pécsvárady Z, Ples Z, Taller A, Agarwal P, Ambulkar S, Aravind S, Balaji V, Kalra S, Kesavadev J, Kudalkar H, Kumar A, Misra A, Mithal A, Mohan V, Pitale S, Ramu M, Reddy N, Shah S, Shamanna P, Sharda A, Sharma A, Shunmugavelu M, Srikanta S, Suryaprakash G, Abramov G, Adawi F, Bashkin A, Darawsha M, Fuchs S, Harman-Boehm I, Hayek T, Jaffe A, Knobler H, Minuchin O, Mosseri M, Shechter M, Shimon I, Stern N, Tsur A, Vishlitzky V, Alfonsi F, Cavalot F, Del Vecchio L, Frisinghelli A, Gambardella S, Lauro D, Lembo G, Leotta S, Mondillo S, Novo S, Pedrinelli R, Piatti P, Salvioni A, Tritto I, Zavaroni DZ, Ahn KJ, Choi KM, Chung C, Han SJ, Kim DM, Kim IJ, Kim MH, Lee IK, Nam M, Park IeB, Park KS, Park TS, Rhee EJ, Yoo SJ, Andersone I, Balode A, Eglite R, Gersamija A, Kakurina N, Jegere B, Leitane I, Pastare S, Stalte V, Teterovska D, Baltramonaitiene K, Barsiene L, Ceponis J, Lasiene J, Levinger A, Sirutaviciene A, Sulskiene M, Urbanaviciene L, Valius L, Varanauskiene E, Velickiene D, Mahendran KA, Abu Hassan MR, Aziz NA, Hussein Z, Ismail IS, Kamaruddin NA, Nordin Z, Nayar SK, Ramanathan GR, Sothiratnam R, Beijerbacht H, Breedveld R, Cornel JH, Den Hartog F, Hermans W, Kietselaer B, Kooy A, Lenderink T, Nierop P, Remmen J, Rojas Lingan G, Ronner E, Van der Heijden R, Van Hessen M, van Kempen W, Voors-Pette C, Westendorp I, Baker J, Benatar J, Cutfield R, Krebs J, Leikis R, Lunt H, Manning P, Williams M, Birkeland K, Claudi T, Istad H, Karlsson T, Ossum Gronert J, Arciszewska M, Artemiuk E, Blach E, Blicharski T, Cypryk K, Dabrowska M, Górny G, Górska M, Jakubowska I, Jazwinska-Tarnawska E, Karczmarczyk A, Kitowska-Koterla J, Koltowski L, Krzyzagorska E, Pasternak D, Pentela-Nowicka J, Piesiewicz W, Przekwas-Jaruchowska M, Rajzer M, Salamon-Ferenc A, Sawicki A, Skowron T, Śmiałowski A, Albota A, Alexandru C, Crisan C, Dumitrescu A, Ferariu IE, Lupusoru DA, Munteanu M, Negru D, Nicolau A, Pintiliei E, Popescu A, Serban G, Voitec M, Babenko A, Barbarash O, Bondar I, Chizhov P, Demin A, Dora S, Dreval A, Ershova O, Gratsiansky N, Ketova G, Kotelnikov M, Levashov S, Morugova T, Mustafina S, Pekarskiy S, Raskina T, Rechkova E, Samoylova Y, Sazonova O, Sherenkov A, Shilkina N, Stetsyuk O, Tretyakova T, Turova E, Valeeva F, Zadionchenko V, Dalan R, Tan RS, Tay L, Buganova I, Fabry J, Jan C, Toserova E, Zak R, Zimanova J, Badat A, Bester F, Burgess L, De Jong D, Ellis G, Fouche L, Govender P, Govind U, Naidoo V, Nieuwoudt G, Nortje H, Rheeder P, Robertson L, Siddique N, Stapelberg AM, Trinder Y, Van Der Merwe A, Van Zyl L, Viljoen M, Wilhase A, Botella M, Civeira Murillo F, de Teresa L, Del Cañizo FJ, Extremera BG, Gimeno EJ, Martin-Hidalgo A, Morales C, Nubiola A, Tinahones Madueño F, Tranche S, Trescolí Serrano C, Alvarsson M, Eizyk E, Gillblad A, Johansson P, Löndahl M, Ohlsson-Önerud Å, Rautio A, Sundström U, Torstensson I, Chen JF, Chou CW, Ho LT, Hsieh IC, Huang BH, Huang CL, Huang CN, Lai WT, Lo PH, Pei D, Sheu WH, Wang SY, Araz M, Bakiner O, Comlekci A, Guler S, Sahin I, Sarac F, Tarkun I, Ukinc K, Yilmaz M, Abdulhakim E, Abraham P, Adamson K, Blagden M, Bundy C, Daly M, Davies M, Deshpande M, Gillings S, Harvey P, Horvathova V, Hristova D, Jaap A, Johnson A, Jones H, Kerrane J, Kilvert A, Ko T, Kumar J, Lindsay R, Litchfield J, McCrimmon R, McKnight J, Millward B, Oyesile B, Purewal T, Ravikumar C, Robinson A, Sathyapalan T, Simpson H, Thomas H, Turner W, Weaver J, Wilding J, Wiles P, Adkins K, Akpunonu B, Albu J, Anagnostis G, Anastasi L, Argoud G, Aroda V, Azizad M, Banerji MA, Bartkowiak A Jr, Bays H, Behn P, Bergenstal R, Bhargava A, Bias D, Bolster E, Buchanan P, Busch R, Chadha C, Chang M, Cheng C, Cohen A, Cohen J, Cole B, Connery L, Cooperman M, Cushman W, DAgostino R, Dayamani P, De Lemos J, De Meireles M, Dean J, DeHart D, Detweiler R, Donovan D, Dugano-Daphnis P, Dulin M, Dunn F, Eaton C, Erickson B, Estevez R, Feinglos M, Fonseca V, Force R, Forker A, Fox D, Gabriel J, Garcia R, Garvey T, Gaudiani L, Getaneh A, Goldberg A, Goldman S, Hairston K, Harris R, Haught W, Hidalgo H Jr, Higgins A, Houchin V, Ison R, Jacobs G, Jaffrani N, Jafry B, Kapsner P, Kaye W, Labroo A, Levinson L, Lewis S, Lillestol M, Luttrell L, Madu I, McNeill R, Merrick B, Metzger F, Nadar V, Nagelberg S, Nash S, Oparil S, Osei K, Papademetriou V, Patel N, Pedley C, Prentiss A, Radbill M, Raisinghani A, Rassouli N, Reddy R, Rees P, Rendell M, Robbins D, Rodbard H, Rohlf J, Roseman H, Rudolph L, Sadler L, Schnall A, Schramm R, Schubart U, Seneviratne T, Shanik M, Snyder H, Sorli C, Stich M, Sweeney ME, Tsao J, Ukwade P, Viswanath D, Vo A, Vogel C, Voyce S, Weintraub H, White J, Wood M, Wu P, Wysham C, Zimmerman R, Pathology/molecular and cellular medicine, Diabetes Pathology & Therapy, and Green JB, Bethel MA, Armstrong PW, Buse JB, Engel SS, Garg J, Josse R, Kaufman KD, Koglin J, Korn S, Lachin JM, McGuire DK, Pencina MJ, Standl E, Stein PP, Suryawanshi S, Van de Werf F, Peterson ED, Holman RR, Holman RR, Peterson ED, Holman RR, Peterson ED, Armstrong PW, Buse JB, Josse RG, Kaufman KD, Koglin J, Korn S, Lachin JM, McGuire DK, Standl E, Stein PP, Suryawanshi S, Van de Werf F, Engel SS, Califf RM, Goldstein BJ, Shapiro DR, Silverman R, Bethel A, Green J, Hayden S, Hannan K, Quintero K, Rorick T, Berdan L, Leloudis D, Califf S, Wilson M, McFarron D, Trollinger K, Pesarchick J, Eskenazi L, Campbell C, Townes O, Tolsma D, Keenan J, Milton J, Athwal R, Darbyshire J, Doran Z, Kennedy I, Gregory V, Garg J, Lokhnygina Y, Prather K, Wolfley A, Usman M, Tajjar A, Gray R, Pfeffer MA, Gerstein HC, Groop L, McMurray JJ, Pocock SJ, Clayton T, Sinay I, Brieger D, Stranks S, Scheen A, Lopes R, Tankova T, Hramiak I, Grado CR, Wenying Y, Ge J, Aschner P, Skrha J, Ambos A, Strandberg T, Travert F, Hanefeld M, Riefflin A, Chan JC, Ofner P, Reddy NK, Christopher J, Mathur A, Arambam P, Mittal S, Manchanda M, Wainstein J, Ambrosio G, Pirags V, Jakuboniene N, Mohamed M, Scott R, White H, Cornel J, Halvorsen S, Tykarski A, Veresiu IA, Dreval AV, Misinkova I, Tai E, Krahulec B, Distiller L, Park Y, Rovira A, Alversson M, Chuang LM, Delibasi T, Adler A, Rodbard HW, Marre M, Goff D, Chacra A, DeVore A, Beaven A, Shah B, Hirsch B, Batch B, Bushnell C, Patel C, Melloni C, Henshaw C, Kong D, McFarron D, Bernecki G, Tillman H, Kang HJ, Green J, Hawes J, Strickler J, Piccini J, Wilder J, Alexander K, Mahaffey K, Patel K, Hyland K, Newby K, Jackson L, Cooper L, Armaganijan L, Szczeh L, Koshizaka M, Roe M, Morse M, Guimaraes P, Hess P, Tricoci P, Mehta R, Lopes R, Mathews R, Kociol R, Harrison R, Mentz R, Pokorney S, Leblanc T, Lazzarini V, Eapen Z, Truffa A, Fosbol E, Brito F, Katz M, Bahit M, Santos M, Barros P, Bernardez S, Alvarisqueta AF, Arias P, Cagide AL, Calella PR, Cantero MC, Canella JP, Cipullo MA, de Loredo L, Gelersztein ES, Gorban de Lapertosa SB, Klyver MI, Maffei LE, Maldonado N, Oviedo AI, Piskorz DL, Ridruejo MC, Saavedra SS, Sessa HA, Sinay IR, Sposetti GD, Ulla MR, Vico ML, Waitman JN, Binnekamp M, Carroll P, Cheung W, Colman P, Davis T, De Looze F, dEmden M, Fulcher G, Gerstman M, Hamilton A, Lehman S, Moses R, Proietto J, Roberts A, Shaw J, Simpson R, Sinha A, Stranks S, Tan Y, Topliss D, Vora P, Waites J, Crenier L, Descamps O, Keymeulen B, Mathieu C, Nobels F, Scheen A, Van den Bruel A, Van Gaal L, Borges JL, Costa e Forti A, Eliaschewitz FG, Felício JS, Griz LH, Hissa MN, Leite S, Panarotto D, Pimentel Filho P, Rassi N, Saraiva JK, Sgarbi JA, Silva RP, Tambascia M, Weber Silva DM, Bobeva R, Bostandzhieva R, Cinlikov I, Georgieva M, Iliev D, Ilieva E, Kovacheva S, Liubenova L, Nikitov Z, SHeinikova G, Slavcheva A, Spasova V, Tankova T, Temelkova-Kurktschiev T, Velichka D, Yakov A, Carpentier A, Chiasson JL, Constance C, Dumas R, Filteau P, Garceau C, Hramiak I, Huynh T, Kaiser S, Kornder J, Leiter L, Mereu L, Miller D, Pandey S, Punthakee Z, Rabasa-Lhoret R, Robitaille Y, Saunders K, Sigal R, Sigalas J, Vizel S, Weisnagel S, Woo V, Yale JF, Yared K, Zinman B, Bunster Balocchi LB, Escobar Cerda EE, Garces Flores EE, Lanas Zanetti FT, Larrazabal Miranda Adel P, Morales Alvarado JM, Olivares Cañon CM, Potthoff Cárdenas SH, Raffo Grado CA, Rodriguez Venegas ME, Saavedra Gajardo VA, Westerberg Maldonado BH, Chen LL, Dong J, Guo X, Li QM, Shi B, Tang XL, Yang T, Yang WY, Zheng SX, Aschner Montoya P, Botero Lopez R, Coronel Arroyo JA, Cure CA, Gómez Medina AM, Molina DI, Perez Amador GA, Reyes Rincon A, Urina Triana MA, Valenzuela Rincon A, Vélez Pelaez S, Yupanqui Lozno H, Brabec T, Brychta T, Hasalova Zapletalova J, Havelkova J, Hejnicova K, Hola O, Hornackova M, Hrdina T, Kafkova D, Kellnerova I, Krystl T, Kutejova V, Mikulkova I, Nevrla J, Pantlikova C, Petr M, Racicka E, Sarbochova R, Skrha J, Smolenakova K, Turcinek R, Urbancova K, Vejvodova J, Vondrakova M, Zachoval R, Alt I, Ambos A, Kaasik Ü, Kiiroja K, Lanno R, Märtsin K, Past M, Vides H, Viitas L, Kantola I, Nieminen S, Perhonen M, Strand J, Strandberg T, Valle T, Clergeot A, Couffinhal T, Courreges JP, Gouet D, Moulin P, Travert F, Ziegler O, Badenhoop K, Behnke T, Bender G, Braun M, Dshabrailov J, Hamann A, Hanefeld M, Himpel-Boenninghoff A, Kamke W, Kasperk C, Luedemann J, Mayr P, Merkel M, Oerter EM, Ohlow MA, Ott P, Overhoff U, Paschen B, Remppis R, Riefflin A, Rose L, Schumm-Draeger PM, Segiet T, Strotmann HJ, Stuchlik G, Stürmer W, Thinesse-Mallwitz M, Tytko A, Wendisch U, Wurziger J, Ho AY, Kam G, Kong AP, Lam YY, Lau EY, Lee S, Siu SC, Tomlinson B, Tsang CC, Yeung VT, Dezső E, Dudás M, Földesi I, Fülöp T, Késmárki N, Koranyi L, Nagy K, Ofner P, Oroszlán T, Pécsvárady Z, Ples Z, Taller A, Agarwal P, Ambulkar S, Aravind S, Balaji V, Christopher J, Kalra S, Kesavadev J, Kudalkar H, Kumar A, Misra A, Mithal A, Mohan V, Pitale S, Ramu M, Reddy N, Shah S, Shamanna P, Sharda A, Sharma A, Shunmugavelu M, Srikanta S, Suryaprakash G, Abramov G, Adawi F, Bashkin A, Darawsha M, Fuchs S, Harman-Boehm I, Hayek T, Jaffe A, Knobler H, Minuchin O, Mosseri M, Shechter M, Shimon I, Stern N, Tsur A, Vishlitzky V, Wainstein J, Alfonsi F, Cavalot F, Del Vecchio L, Frisinghelli A, Gambardella S, Lauro D, Lembo G, Leotta S, Mondillo S, Novo S, Pedrinelli R, Piatti P, Salvioni A, Tritto I, Zavaroni DZ, Ahn KJ, Choi KM, Chung C, Han SJ, Kim DM, Kim IJ, Kim MH, Lee IK, Nam M, Park IeB, Park KS, Park TS, Park Y, Rhee EJ, Yoo SJ, Andersone I, Balode A, Eglite R, Gersamija A, Kakurina N, Jegere B, Leitane I, Pastare S, Pirags V, Stalte V, Teterovska D, Baltramonaitiene K, Barsiene L, Ceponis J, Jakuboniene N, Lasiene J, Levinger A, Sirutaviciene A, Sulskiene M, Urbanaviciene L, Valius L, Varanauskiene E, Velickiene D, Mahendran KA, Abu Hassan MR, Aziz NA, Hussein Z, Ismail IS, Kamaruddin NA, Mohamed M, Nordin Z, Nayar SK, Ramanathan GR, Sothiratnam R, Beijerbacht H, Breedveld R, Cornel JH, Den Hartog F, Hermans W, Kietselaer B, Kooy A, Lenderink T, Nierop P, Remmen J, Rojas Lingan G, Ronner E, Van der Heijden R, Van Hessen M, van Kempen W, Voors-Pette C, Westendorp I, Baker J, Benatar J, Cutfield R, Krebs J, Leikis R, Lunt H, Manning P, Scott R, Williams M, Birkeland K, Claudi T, Halvorsen S, Istad H, Karlsson T, Ossum Gronert J, Arciszewska M, Artemiuk E, Blach E, Blicharski T, Cypryk K, Dabrowska M, Górny G, Górska M, Jakubowska I, Jazwinska-Tarnawska E, Karczmarczyk A, Kitowska-Koterla J, Koltowski L, Krzyzagorska E, Pasternak D, Pentela-Nowicka J, Piesiewicz W, Przekwas-Jaruchowska M, Rajzer M, Salamon-Ferenc A, Sawicki A, Skowron T, Śmiałowski A, Tykarski A, Albota A, Alexandru C, Crisan C, Dumitrescu A, Ferariu IE, Lupusoru DA, Munteanu M, Negru D, Nicolau A, Pintiliei E, Popescu A, Serban G, Veresiu IA, Voitec M, Babenko A, Barbarash O, Bondar I, Chizhov P, Demin A, Dora S, Dreval A, Ershova O, Gratsiansky N, Ketova G, Kotelnikov M, Levashov S, Morugova T, Mustafina S, Pekarskiy S, Raskina T, Rechkova E, Samoylova Y, Sazonova O, Sherenkov A, Shilkina N, Stetsyuk O, Tretyakova T, Turova E, Valeeva F, Zadionchenko V, Dalan R, Tan RS, Tay L, Buganova I, Fabry J, Jan C, Krahulec B, Toserova E, Zak R, Zimanova J, Badat A, Bester F, Burgess L, De Jong D, Distiller L, Ellis G, Fouche L, Govender P, Govind U, Naidoo V, Nieuwoudt G, Nortje H, Rheeder P, Robertson L, Siddique N, Stapelberg AM, Trinder Y, Van Der Merwe A, Van Zyl L, Viljoen M, Wilhase A, Botella M, Civeira Murillo F, de Teresa L, Del Cañizo FJ, Extremera BG, Gimeno EJ, Martin-Hidalgo A, Morales C, Nubiola A, Rovira A, Tinahones Madueño F, Tranche S, Trescolí Serrano C, Alvarsson M, Eizyk E, Gillblad A, Johansson P, Löndahl M, Ohlsson-Önerud Å, Rautio A, Sundström U, Torstensson I, Chen JF, Chou CW, Chuang LM, Ho LT, Hsieh IC, Huang BH, Huang CL, Huang CN, Lai WT, Lo PH, Pei D, Sheu WH, Wang SY, Araz M, Bakiner O, Comlekci A, Delibasi T, Guler S, Sahin I, Sarac F, Tarkun I, Ukinc K, Yilmaz M, Abdulhakim E, Abraham P, Adamson K, Adler A, Blagden M, Bundy C, Daly M, Davies M, Deshpande M, Gillings S, Harvey P, Horvathova V, Horvathova V, Hristova D, Jaap A, Johnson A, Jones H, Kerrane J, Kilvert A, Ko T, Kumar J, Lindsay R, Litchfield J, McCrimmon R, McKnight J, Millward B, Oyesile B, Purewal T, Ravikumar C, Robinson A, Sathyapalan T, Simpson H, Thomas H, Turner W, Weaver J, Wilding J, Wiles P, Adkins K, Akpunonu B, Albu J, Anagnostis G, Anastasi L, Argoud G, Aroda V, Azizad M, Banerji MA, Bartkowiak A Jr, Bays H, Behn P, Bergenstal R, Bhargava A, Bias D, Bolster E, Buchanan P, Busch R, Chadha C, Chang M, Cheng C, Cohen A, Cohen J, Cole B, Connery L, Cooperman M, Cushman W, DAgostino R, Davies M, Dayamani P, De Lemos J, De Meireles M, Dean J, DeHart D, Detweiler R, Donovan D, Dugano-Daphnis P, Dulin M, Dunn F, Eaton C, Erickson B, Estevez R, Feinglos M, Fonseca V, Force R, Forker A, Fox D, Gabriel J, Garcia R, Garvey T, Gaudiani L, Getaneh A, Goff D, Goldberg A, Goldman S, Hairston K, Harris R, Haught W, Hidalgo H Jr, Higgins A, Houchin V, Ison R, Jacobs G, Jaffrani N, Jafry B, Kapsner P, Kaye W, Labroo A, Levinson L, Lewis S, Lillestol M, Luttrell L, Madu I, McNeill R, Merrick B, Metzger F, Nadar V, Nagelberg S, Nash S, Oparil S, Osei K, Papademetriou V, Patel N, Pedley C, Prentiss A, Radbill M, Raisinghani A, Rassouli N, Reddy R, Rees P, Rendell M, Robbins D, Rodbard H, Rohlf J, Roseman H, Rudolph L, Sadler L, Schnall A, Schramm R, Schubart U, Seneviratne T, Shanik M, Snyder H, Sorli C, Stich M, Sweeney ME, Tsao J, Ukwade P, Viswanath D, Vo A, Vogel C, Voyce S, Weintraub H, White J, Wood M, Wu P, Wysham C, Zimmerman R
- Subjects
Oral ,medicine.medical_specialty ,Heart diseases ,Glycosylated ,Administration, Oral ,heart failure ,Type 2 diabetes ,Dipeptidyl peptidase-4 inhibitor ,Kaplan-Meier Estimate ,Placebo ,Sitagliptin Phosphate ,Sitagliptin, Cardiovascular Outcomes ,chemistry.chemical_compound ,Drug Therapy ,Double-Blind Method ,Internal medicine ,Diabetes Mellitus ,medicine ,Humans ,Hypoglycemic Agents ,Glycated Hemoglobin ,Hemoglobin A, Glycosylated ,Cardiovascular Diseases ,Diabetes Mellitus, Type 2 ,Drug Therapy, Combination ,Follow-Up Studies ,Heart Diseases ,Heart Failure ,Hospitalization ,Pyrazines ,Triazoles ,Medicine (all) ,business.industry ,Semaglutide ,Hemoglobin A ,General Medicine ,ta3121 ,medicine.disease ,Surgery ,Cardiovascular diseases ,chemistry ,Sitagliptin ,Administration ,Combination ,Glycated hemoglobin ,business ,Type 2 ,Alogliptin ,medicine.drug - Abstract
BACKGROUND: Data are lacking on the long-term effect on cardiovascular events of adding sitagliptin, a dipeptidyl peptidase 4 inhibitor, to usual care in patients with type 2 diabetes and cardiovascular disease. METHODS: In this randomized, double-blind study, we assigned 14,671 patients to add either sitagliptin or placebo to their existing therapy. Open-label use of antihyperglycemic therapy was encouraged as required, aimed at reaching individually appropriate glycemic targets in all patients. To determine whether sitagliptin was noninferior to placebo, we used a relative risk of 1.3 as the marginal upper boundary. The primary cardiovascular outcome was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. RESULTS: During a median follow-up of 3.0 years, there was a small difference in glycated hemoglobin levels (least-squares mean difference for sitagliptin vs. placebo, -0.29 percentage points; 95% confidence interval [CI], -0.32 to-0.27). Overall, the primary outcome occurred in 839 patients in the sitagliptin group (11.4%; 4.06 per 100 person-years) and 851 patients in the placebo group (11.6%; 4.17 per 100 person-years). Sitagliptin was noninferior to placebo for the primary composite cardiovascular outcome (hazard ratio, 0.98; 95% CI, 0.88 to 1.09; P
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- 2015
4. 136 (PB126) - ALRN 6924 induces cell cycle arrest in bone marrow stem cells and hair follicles with dose-dependent degree and duration of effects after a single infusion in healthy volunteers
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Henkelman, S., Voors-Pette, C., Aalders, W., de Jong, A., Brugman, R., Randall, K., Will, B., Steidl, U., Aivado, M., Vukovic, V., and Annis, A.
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- 2022
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5. Effects of once-weekly exenatide on cardiovascular outcomes in type 2 diabetes
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Holman, Rr, Bethel, Ma, Mentz, Rj, Thompson, Vp, Lokhnygina, Y, Buse, Jb, Chan, Jc, Choi, J, Gustavson, Sm, Iqbal, N, Maggioni, Ap, Marso, Sp, Öhman, P, Pagidipati, Nj, Poulter, N, Ramachandran, A, Zinman, B, Hernandez, Af, EXSCEL Study Group, : Califf RM, Patel, R, George, J, Sourij, H, Wong, Yw, Hannan, K, Sellers, Ma, Gottlieb, P, Lavender, P, Leloudis, D, Meadows, Y, Larson, D, Anderson, H, Elkins, M, Stone, A, Tisch, A, Perkins, L, Sanders, K, Campbell, C, Kennedy, I, Heal, P, Masterson, M, Darbyshire, J, Mumtaz, L, Athwal, R, Ferch, A, Batra, P, Durborow, L, Vincent, J, Woodall, A, Flanagan, T, Katona, B, Reicher, B, Pozzi, E, Oulhaj, A, Coleman, R, Rouleau, Jl, Pocock, Sj, Gorelick, F, Mcmurray, J, Riddle, M, Gagel, R, Collier, T, Markovic, T, Kong, Aps, Hian, Sk, Scott, R, Panelo, A, Yoon, Kh, Sheu, W, Sritara, P, Linong, J, Pan, C, Yong, H, Schernthaner, G, Mathieu, C, Tankova, T, Widimsky, P, Hanefeld, M, Keltai, M, Wainstein, J, del Prato, S, Pirags, V, Jakuboniene, N, Kooy, A, Dziemidok, P, Veresiu, Ia, Dreval, Av, Murin, J, Torello, Al, Sattar, N, Parkhomenko, O, Omar, M, Diaz, R, Lopes, R, Lanas, F, Urina Triana, M, Leiva-Pons, Jl, Aguliera, D, Bergenstal, R, Goodman, S, Yale, Jf, Caterson, I, Weng, J, Hu, D, Junbo, G, Zannad, F, Anoop, M, Ambrish, M, Gallegos, Ja, Green, Jb, Akerblom, A, Alexander, K, Al-Khatib, S, Armaganijan, L, Barros, P, Batit, M, Bernacki, G, Bernandez, S, Bloomfield, G, Clausen, E, De Souza Brito, F, Devore, A, Dombrowski, K, Eapen, Z, Gellad, Z, George, D, Guimaraes, P, Halim, S, Harrison, R, Hawes, J, Hess, C, Hyland, K, Jackson, L, Jones, S, Jordan, D, Katz, M, Kong, D, Koshizaka, M, Lakey, W, Leblanc, T, Leonardi, S, Luo, N, Mahaffey, K, Mandawat, A, Mehta, R, Melloni, C, Morse, M, Pagidpati, N, Patel, C, Patel, K, Pokorney, S, Posvic, T, Rao, M, Roe, M, Shah, B, Tillmann, H, Truffa, A, Zazula, A, Zeitler, E, Sicer, M, Ulla, Mr, Maffei, L, Klyver, Mi, Calella, P, Alvarisqueta, A, De La Fuente RL, Aizenberg, D, Roque, F, Cruciani, A, Frechtel, G, Gelersztein, E, Villarino, A, Mallagray, M, Nardone, L, Zaidman, C, Novaretto, L, Bartolacci, I, de Salvo, M, Delcourt, C, Crimmins, D, Jackson, R, O’Neal, D, Colman, P, Jeffries, W, Mah, Pm, Wittert, G, Proietto, J, Amerena, J, Marks, S, Tan, R, Colquhoun, D, Pieber, T, Drexel, H, Prager, R, Schnack, C, Hoppichler, F, Fasching, P, Francesconi, C, Luger, A, Schoenherr, Hr, Ebenbichler, C, Paulweber, B, Shernthaner, G, Verhaegen, A, Vanuytsel, J, Thissen, Jp, e Silva P, Barros, Gonzaga, C, Borges, J, Hissa, M, Rea, R, Rossi, P, Chacra, A, Eliaschewitz, F, Garbelini, B, Felicio, J, Rassi, N, Rossi, F, Nunes dos Santos, M, e Farias F, Bandeira, Lisboa, H, e Forti A, Costa, Saraiva, Jk, Kovacheva, S, Levterov, G, Sheinkova, G, Ilieva, E, Lyubenova, L, Damyanova, V, Gushterova, V, Mincheva, L, Illiev, D, Ivanov, V, Bobeva, R, Nikitov, Z, Shumkova, R, Lefterov, In, Zaharieva, S, Videva, V, Yakov, A, Cheung, S, Elliott, T, Mehta, P, Ross, S, Sigal, R, Woo, V, Jaffer, S, Kuritsky, R, Bell, A, Dumas, R, Gosselin, G, Robitaille, Y, Greenspoon, A, Lochnan, H, Tytus, R, Leiter, L, Pandey, A, Punthakee, Z, Dube, F, Sigalas, J, Pearce, M, Woodford, T, Paul, P, Bourgeois, R, Conway, R, Mazza, G, Hatheway, R, Misterski, J, Raffo, C, Olivares, C, Godoy, J, Potthoff, S, Santibañez, C, Larenas Yanez GJ, Gu, W, Shen, F, Ma, J, Guo, X, Li, Q, Du, Y, Hu, J, Ji, L, Li, Y, Deng, H, Feng, Y, Liu, L, Mu, Y, Ma, C, Qu, S, Wang, J, Wang, Y, Yuan, Z, Zhang, L, Zhou, S, Yang, T, Dong, Y, Liu, D, Coronel Arroyo, J, Perez Amador, G, Botero Lopes, R, Jaramilo, C, Orozco Linares, A, Cure Cure CA, Hernandez Triana, E, Molina de Salazar DI, Marin, Cr, Jaramilo Gomez CJ, Kellinerova, I, Adamkova, V, Krami, P, Brychta, T, Havelkova, J, Pantikova, K, Schoper, F, Pohl, W, Schumm-Draeger, Pm, Julius, U, Tschöpe, D, Hamann, A, Seissler, J, Schellong, S, Rose, L, Becker, B, Linn, T, Oerter, Em, Strotmann, Hj, Mölle, A, Pfutzner, A, Forst, T, Schäufele, T, Mugge, A, Lehrke, M, Meyer-Pannwitt, U, Mehling, H, Simon-Wagner, I, Schenkenberger, I, Busch, K, Hermes, S, Milek, K, Landers, B, Grueneberg, M, Braun, M, Nothroff, J, Kamke, W, Hergdt, G, Duengen, Hd, Kleinertz, K, Kuesters, D, Boenninghoff, Ah, Appel, Kf, Schaefer, A, Bieler, T, Ozaki, R, Luk, Aoy, Chu, Dw, Cheung-Wong, Mm, Siu, Dc, Yan, Bpy, Kung, K, Wong, Sys, Tsang, Cc, Yeung, Vt, Cheung, Bm, Tse, Hf, Hodi, G, Nagy, K, Lippai, J, Takacs, J, Fulop, T, Gaal, Z, Pauker, Z, Foldesi, I, Simon, J, Oroszan, T, Futo, L, Bezzegh, K, Nagy, A, Vandorfi, G, Kiss, J, Kesmarki, N, Kis, E, Papp, A, Kovacs, A, Szakal, I, Palinkas, A, Czegany, Z, Voros, P, Reiber, I, Kerenyi, Z, Dezso, E, Wittman, I, Penzes, J, Ples, Z, Taller, A, Farago, K, Kis, Jt, Zilahi, Z, Molnar, M, Barkai, L, Mileder, M, Szentpeteri, I, Peterfai, E, Lovasz, O, Mosenzon, O, Minuchin, O, Jaffe, A, Vishlitsky, V, Shimon, I, Bashkin, A, Stern, N, Elias, N, Bental, T, Butnaru, A, Lewis, B, Adawi, F, Nseir, W, Klainman, E, Herskovits, T, Cignarelli, M, Rotella, Cm, Ambrosio, G, Pozzilli, P, Genovese, S, Cavarape, A, Salvioni, A, Sokolova, J, Strautina, I, Teterovska, D, Stalte, V, Pastare, S, Leitane, I, Lagzdina, L, Andersone, I, Eglite, R, Stelmane, I, Levinger, A, Barsiene, L, Sulskiene, M, Varanauskiene, E, Danyte, E, Urbanaviciene, E, Urbanavicius, V, Zabuliene, L, Juskiene, R, Velaviciene, A, Kakariekiene, V, Augusteniene, A, Velickiene, D, Lasiene, J, Dauksiene, D, Caponis, J, Tan, At, Ramanathan, L, Hassan, Mra, Tan, F, Ong, Tk, Foo, Sh, Ghani, Ra, Cheah, Wk, Sanchez Mijangos JH, Cabrera Jardines, R, Barrientos Perez, M, Sauque Reyna, L, Alcocer Gamba MA, Villeda Espinosa, E, Tamez Perez HE, De La Garza Hernandez NE, Lopes, Sm, Ramirez Diaz SP, Reyes Sanchez, R, Márquez-Rodriguez, E, Köse, V, Voors-Pette, C, Oldenburg-Ligtenberg, Pc, van Kempen WW, Cox, K, Hoogendyk, J, Swinkels-Diepenmaat, L, Rojas-Lingan, G, Kentgens, S, Schipperen, S, de Valk HW, Swart, H, van Bemmel, B, Hoogslag, Pam, Diamant, M, Serné, Eh, Hamer, A, Wilson, S, Fisher, N, Dixon, P, Chaudhri, O, Crawford, V, Quinn, D, Nirmalaraj, K, Dunn, P, Gillies, J, Cutfield, R, Krebs, J, Helm, C, Kerr, J, Pryke, J, Ebo, G, Denopol, M, Ang, E, Uy, N, Jimeno, C, Mirasoi, R, Paz Pacheco, E, Custodio, M, Nicodemus, N Jr, Catindig, Ea, Magno, M, Tirador, L, Cylkowska, B, Stasinksa, T, Silwinska, T, Sroka, M, Piepiorka, M, Korzeniak, R, Mirecka, H, Zaluska, R, Pupek-Musialik, D, Homenda, W, Grabowska, A, Okopien, B, Niegowska, J, Pogorzelska, H, Mikolajczyk-Swatko, A, Sikorski, M, Sowinski, D, Tahk, Sj, Kim, Yn, Nam, Cw, Rim, Sj, Kim, Cj, Choi, Km, Lee, Ik, Kim, Ij, Namgung, J, Moon, Kw, Kim, Ks, Oh, Bh, Lee, Wy, Choi, Sh, Kim, Es, Moon, S, Mindrescu, Nm, Aron, G, Graur, M, Hancu, N, Mlitaru, C, Nafornita, V, Szilagyi, I, Popa, Ar, Angelescu, Lm, Negrisanu, Gd, Zaharie, Dg, Culman, Mi, Vacaru, G, Munteanu, M, Constantinescu, S, Tivadar, S, Dreval, A, Barbarash, O, Strongin, L, Dogadin, S, Suplotova, L, Izmozherova, N, Marasaev, V, Khokhlov, A, Repin, A, Turova, E, Bondar, I, Samoylova, Y, Sherenkov, A, Smolenskaya, O, Zrahevskiy, K, Koshelskaya, O, Obrezan, A, Dzupina, A, Stevlik, J, Buganova, I, Pella, D, Vinanska, D, Jascur, J, Micko, K, Sosovec, D, Philippiova, A, Olexa, P, Fedacko, J, Selecky, J, Nicolau, J, Mediavilla Garcia, J, Botella Serrano, M, Lecube, A, Arguelles, I, Sabán, J, Gómez Cerezo, F, Soto, A, Bellido, D, Sucunza Alfonso, N, Vendrell Ortega, J, Alvarez, L, Garcia Puig, J, Angustias Quesada, M, Contreras Gilbert, J, Almeida, Ca, Tinahones, Fj, Garcia Ortiz, L, Gómez Marcos MA, Aomar, I, Fernández Balsells, M, Distiller, L, Padayachee, T, Badat, A, Ebrahim, I, Naiker, P, Ranjith, N, Kelfkens, Y, Makan, H, Mogashoa, S, Fulat, M, Carim-Ganey, N, Coetzee, K, Govender, T, Nortje, H, Wilhase, A, Seedat, S, Gani, M, Ellis, G, Rheeder, P, Wing, J, Blignaut, S, Kaplan, H, Lottering, H, Pillai, P, Louw, C, Coetzer, T, Sheu, Whh, Chen, Jf, Yang, Cy, Tseng, St, Wang, Cy, Lai, Wt, Hung, Yj, Hsieh, Ic, Su, Sl, Pei, D, Benjasuratwong, Y, Purewal, T, Milward, A, Dimitropoulos, I, Kumar, S, Barber, T, Wiles, P, Dang, C, Adler, A, Philip, S, Bellary, S, Price, D, Oelbaum, R, Heller, S, Sathayapalan, T, Clark, J, Leese, G, Simpson, H, Kilvert, A, Dawson, A, Hall, T, Takhar, A, Bundy, C, Harvey, P, Maxwell, S, Asamoah-Owusu, Nj, Mcknight, J, Chatterjee, S, Calvert, J, Wright, A, Macrury, S, Macfarlane, D, Johnson, A, Litchfield, J, Field, B, Koval, O, Larin, O, Levchenko, O, Martynyuk, L, Maslyanko, V, Rudyk, I, Suprun, Y, Tseluyko, V, Botsyurko, V, Vatutin, M, Fushtey, I, Grishyna, O, Kuskalo, P, Panina, S, Pererva, L, Prysupa, L, Teliatnikova, Z, Sokolova, L, Vlasenko, M, Berenfus, V, Gyrina, O, Kopytsya, M, Vizir, V, Vayda, M, Shanik, M, Headapohl, D, Pahl, J, Aronoff, S, Bartkowiak, A Jr, Chang, A, Gaudiani, L, Kayne, D, Look, M, Patel, N, Moran, J, Stout, E, Tsao, J, Struble, R, Fishman, N, Rodbard, H, Lucas, K, Dugano-Daphnis, P, Merrick, B, Nadar, V, Severa, L, Sorli, C, Chang, M, Reed, J III, Grunberger, G, Bain, C, Bestermann, W Jr, Morawski, E, White, J, Azizad, M, Ukwade, P, Anekwe, A, Jimenez, A, Weiss, D, Green, S, Overcash, J, Eaton, C, Roseman, H, Soler, N, Mikell, F, Manos, P, Levinson, L, Claxton, E Jr, Weiss, R, Argoud, G, Bickel, L, Wilson, J, Short, B, Webster, B, Mcneill, R, Schnall, A, Force, R, Phillips, L, Bybee, K, Forker, A, Denham, D, Vonderhaar, T, Pullman, J, Kruger, D, Whitehouse, F, Wysham, C, Baron, M, Kravitz, A, Dushkin, H, Manning, Mb, Wine, A, Jaffrani, N, Chadha, C, Sperl-Hillen, J, Busch, R, Estevez, R, Robbins, D, Rassouli, N, Garvey, T, Oparil, S, Eckel, R, Mcdermott, M, Rasouli, N, Mcgill, J, Corder, C, Klonoff, D, Mills, R, Earl, J, Kessel, J, Cuddihy, R, Zimmerman, R, Dayamani, P, Oral, E, Zimering, M, Marks, J, Farnsworth, K, Sugimoto, D, Toth, P, Bhargava, A, Mcguire, D, Rohatgi, A, Davies, M, Peden, E, Wyne, K, Alfonso, L, Seyoum, B, Akpunonu, B, Feinglos, M, Reaven, P, Soule, J, Luttrell, L, Schactman, B, Canadas, R, Boggs, B, Abbott, L, Herring, C, Roberts, L, Hage-Korban, E, Schubart, U, Taylon, A, Tannenbaum, A, Kingsley, J, Lenhard, J, Biscoveanu, M, Cohen, J, Donovan, D, Laferrere, B, Thompson, N, Wade, T, Detweiler, R, Henson, B, White, A, Cavale, A, Ravi, C, Thomas, A, Goodman, H, Kalen, V, Fox, D, Dauber, I, Rizvi, S, Marcus, A, Mulford, M, Higgins, A, Chane, M, Bland, V, Osunkoya, A, Suresh, D, Khan, S, Anastasi, L, Bajaj, M, Eisen, H, Mudaliar, Sr, Powell, S, Carr, K, Tripathy, D, Azad, N, Wakefield, P, Acheatel, R, Bressler, P, Dean, J, El Shahawy, M, Gilbert, J, Haque, I, Humiston, D, Ison, R, Karounos, D, Lillestol, M, Ferrier, N, Labroo, A, Vo, A, D’Agostino, R, Dulin, M, Mcwilliams, A, Hargrove, J, Blumberg, E, Jackson, B, Staniloae, C, Salacata, A, Hidalgo, H Jr, Nicol, P, Digiovanna, M, Soufer, J, Mahabadi, V, Akinboboye, O, Arauz-Pacheco, C, Neutel, J, Dungan, K, Benson, M, Powell, T, Gandy, W, Rovner, S, Berk, M, Khan, A, Ledesma, G, Madu, I, Erickson, B, Radbill, M, Graves, M, Kaczmarek, G, Giep, S, Baldauf, C, Golden, G, Lesh, K, Davis, C, Godbole, N, Kirby, W, Razzaque, N, Bhatt, B, Wilson, M., Internal medicine, ACS - Diabetes & metabolism, and ACS - Microcirculation
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Male ,medicine.medical_specialty ,EXSCEL Study Group ,Injections, Subcutaneous ,030209 endocrinology & metabolism ,Type 2 diabetes ,Kaplan-Meier Estimate ,030204 cardiovascular system & hematology ,Placebo ,Article ,Drug Administration Schedule ,GLP1-agonists ,03 medical and health sciences ,0302 clinical medicine ,Double-Blind Method ,Interquartile range ,Internal medicine ,Diabetes mellitus ,General & Internal Medicine ,medicine ,Humans ,Hypoglycemic Agents ,Least-Squares Analysis ,Aged ,Glycated Hemoglobin ,business.industry ,Venoms ,Semaglutide ,Incidence ,Type 2 diabetes, GLP1-agonists, exenatide, cardiovascular effects ,General Medicine ,11 Medical And Health Sciences ,Middle Aged ,medicine.disease ,Surgery ,Albiglutide ,Editorial ,Diabetes Mellitus, Type 2 ,Cardiovascular Diseases ,Exenatide ,Dulaglutide ,Female ,business ,Peptides ,cardiovascular effects ,medicine.drug - Abstract
BACKGROUND: The cardiovascular effects of adding once-weekly treatment with exenatide to usual care in patients with type 2 diabetes are unknown. METHODS: We randomly assigned patients with type 2 diabetes, with or without previous cardiovascular disease, to receive subcutaneous injections of extended-release exenatide at a dose of 2 mg or matching placebo once weekly. The primary composite outcome was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The coprimary hypotheses were that exenatide, administered once weekly, would be noninferior to placebo with respect to safety and superior to placebo with respect to efficacy. RESULTS: In all, 14,752 patients (of whom 10,782 [73.1%] had previous cardiovascular disease) were followed for a median of 3.2 years (interquartile range, 2.2 to 4.4). A primary composite outcome event occurred in 839 of 7356 patients (11.4%; 3.7 events per 100 person-years) in the exenatide group and in 905 of 7396 patients (12.2%; 4.0 events per 100 person-years) in the placebo group (hazard ratio, 0.91; 95% confidence interval [CI], 0.83 to 1.00), with the intention-to-treat analysis indicating that exenatide, administered once weekly, was noninferior to placebo with respect to safety (P
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- 2017
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6. Efficacy and safety of alirocumab in reducing lipids and cardiovascular events
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Robinson, Jg, Farnier, M, Krempf, M, Bergeron, J, Luc, G, Averna, M, Stroes, Es, Langslet, G, Raal, Fj, El Shahawy, M, Koren, Mj, Lepor, Ne, Lorenzato, C, Pordy, R, Chaudhari, U, Kastelein, Jj, Caccavo, A, Codutti, O, Gelersztein, E, Vico, M, Zaidman, C, Majul, C, Balthazar, Y, Capiau, L, Vrolix, M, Vermeersch, P, Gotchev, D, Todorov, G, Tumbev, H, Tzekova, M, Gronkova, N, Dimov, B, Nikolaeva, A, Devedzhiev, T, Mincheva, V, D'Ignazio, G, Dzongowski, P, Elliott, T, Hart, R, Hoag, G, Martinho, V, O'Mahony, M, Tellier, G, Pandey, S, Heaton, K, Constance, C, Phaneuf, Dc, Shu, D, Narvaez, Nc, Cañon, Co, Cardenas, Sp, Loayza, Ms, de Salazar, Dm, Lopez, Rb, Gomez, Ji, Mendoza, Ja, Cure, Cc, Ceska, R, Zidkova, E, Jansky, P, Egstrup, K, Klausen, Ib, Lomholdt, J, Gislason, G, Torp Pedersen, C, Poulsen, S, Kuusela, M, Kekki, S, Nieminen, S, Tuomilehto, J, Boye, A, Bruckert, E, Cadinot, D, Lejay, D, Revol, T, Schaupp, T, Bonnet, J, Paillard, F, Moulin, P, Junggeburth, J, Isermann, B, Zühlke, M, Züchner, D, Theis, E, Stößel, J, König, Hj, Rinke, A, Piechatzek, R, Contzen, C, Lappo, M, Himpel Boenninghoff, Aa, Meissner, G, Maus, O, Degtyareva, E, Schulze, Ed, Horacek, T, Marten, I, Becher, P, Matoltsy, A, Nyirati, G, Paragh, G, Zilahi, Z, Nagy, K, Kanakaridisz, N, Beke, E, Biro, J, Schnabel, R, Elias, M, Gavish, D, Francis, A, Nseir, W, Zimlichman, R, Pozzi, C, Lembo, G, Bucci, M, Mezzetti, A, De Pellegrin, Am, Salvioni, A, De Cesare, N, Briones, Ir, Campos, Pf, Rosas, El, Espinosa, Ev, Salazar, Ma, Ruiz, Ab, Furusho, Lc, Olvera, I, Stroes, E, van den Berg, R, Basart, D, Köse, V, Kentgens, S, Peeters, M, Hoogendijk, J, Voors Pette, C, Agous, I, van Kempen, W, Lingan, Gr, Kooy, A, Troquay, R, Herrman, J, Hoivik, H, Norheim, P, Risberg, K, Høivik, Ho, Elle, S, Derezinski, T, Miekus, P, Ogorek, M, Szymkowiak, K, Cesar, M, Gawron, A, Dabrowska, M, Blach, E, Konieczny, M, Sidor, M, Matias, F, da Silva, Pm, Carvalho, D, Mendonca, I, Andor, M, Andrei, L, Podoleanu, C, Pop, C, Chizhov, P, Chumakova, G, Goloschekin, B, Libov, I, Paltsman, Z, Strutinskiy, A, Koziolova, N, Breedt, J, Ebrahim, I, Ellis, G, Fulat, M, van Rensburg, Dj, Raal, F, van Dyk, C, Vally, T, van der Walt, E, Kotzé, H, Landman, C, Tayob, M, Caixas, A, García, Lr, Fernandez Cruz, A, Gil Extremera, B, Grijalvo, Om, Plana, N, Fuentes, F, Valdivielso, P, Fraile, B, Borgencrantz, B, Larnefeldt, H, Tengmark, Bo, Eriksson, M, Olsson Önerud, Å, Amalyan, W, Dyadyk, O, Koval, O, Kushnir, M, Svintsitskiy, A, Kovalyov, O, Bondarchuk, O, Tashchuk, V, Barna, O, Prokhorov, O, Karpenko, O, Stanciu, D, Pawa, R, Balaji, H, Doig, F, Harvey, P, Ranganath, L, Massalski, W, Hassanin, H, Timmis, H, Pavel Knox, I, Abdulhakim, E, Oyesile, B, Horvathova, V, Donnachie, H, Kondagunta, V, Shaw, H, Thomas, H, Kadr, H, Gunstone, A, Lip, G, Ellery, A, Kerrane, J, Sarker, A, Wong, Yk, Soran, H, Maw, K, Andersen, J, Blair Britt, L, Huffman, C, Kivitz, A, Marple, R, Patron, A, Schear, M, Allegar, N, Awasty, V, Casanova, R, Chaykin, L, Cohen, L, Collins, H, Collins, G, Elkin, G, Reyes, H, Feld, L, Fuller, G, Glover, R, Greenwald, J, Herrod, J, Kaye, W, Kimmel, M, Kolettis, E, Lakin, G, Lorch, D, Palatnik, M, Patel, R, Reichman, A, Rohlf, J, Shockey, G, Shore, K, Radin, D, Alvarado, O, Bellingar, B, Egelhof, R, Mcknight, T, Plevin, S, Pritchard, J, Reddy, R, Velazquez, F, Bolster, E, Broker, R, Butuk, D, Cheung, D, Cohen, K, Golden, G, Murray, A, Naccarato, T, Uusinarkaus, K, Pudi, K, Graff, A, Blumberg, V, Dunn, F, Toth, P, Anspach, R, Chuang, R, Meli, J, Nevins, B, Wayne, J, Schmidt, L, Levinsky, D, Rubino, J, Shealy, N, Torres, D, West, J, Jain, R, Vardi, G, Singh, N, Thew, S, Lo, E, Heitner, J, Gerber, J, Malik, A, Weinstein, D, Prashad, R, Koren, M, Ghitis, A, David, W, Reis, G, Kinzfogl, G, Haught, H, Kantaros, L, O'Dea, D, Weiss, D, Kassas, S, Hunter, J, Mollod, M, Khan, N, Henderson, D, Gatien, L, Schramm, R, Madder, R, Voyce, S, Nadar, V, Stich, M, Kumar, M, Black, R, Treasure, C, Lebeis, M, Mccullough, P, Lepor, N, Moriarty, P, Waxler, A, Talreja, D, Gen, M, Dohad, S, East, C, Conrad, G, Asbill, B, Roberts, J, Robinson, J, Zarich, S, Davis, B, Krolick, M, Sherman, H, Thompson, P., RUBBA, PAOLO OSVALDO FEDERICO, Robinson, Jg, Farnier, M, Krempf, M, Bergeron, J, Luc, G, Averna, M, Stroes, E, Langslet, G, Raal, Fj, El Shahawy, M, Koren, Mj, Lepor, Ne, Lorenzato, C, Pordy, R, Chaudhari, U, Kastelein, Jj, Caccavo, A, Codutti, O, Gelersztein, E, Vico, M, Zaidman, C, Majul, C, Balthazar, Y, Capiau, L, Vrolix, M, Vermeersch, P, Gotchev, D, Todorov, G, Tumbev, H, Tzekova, M, Gronkova, N, Dimov, B, Nikolaeva, A, Devedzhiev, T, Mincheva, V, D'Ignazio, G, Dzongowski, P, Elliott, T, Hart, R, Hoag, G, Martinho, V, O'Mahony, M, Tellier, G, Pandey, S, Heaton, K, Constance, C, Phaneuf, Dc, Shu, D, Narvaez, Nc, Cañon, Co, Cardenas, Sp, Loayza, M, de Salazar, Dm, Lopez, Rb, Gomez, Ji, Mendoza, Ja, Cure, Cc, Ceska, R, Zidkova, E, Jansky, P, Egstrup, K, Klausen, Ib, Lomholdt, J, Gislason, G, Torp Pedersen, C, Poulsen, S, Kuusela, M, Kekki, S, Nieminen, S, Tuomilehto, J, Boye, A, Bruckert, E, Cadinot, D, Lejay, D, Revol, T, Schaupp, T, Bonnet, J, Paillard, F, Moulin, P, Junggeburth, J, Isermann, B, Zühlke, M, Züchner, D, Theis, E, Stößel, J, König, Hj, Rinke, A, Piechatzek, R, Contzen, C, Lappo, M, Himpel Boenninghoff, Aa, Meissner, G, Maus, O, Degtyareva, E, Schulze, Ed, Horacek, T, Marten, I, Becher, P, Matoltsy, A, Nyirati, G, Paragh, G, Zilahi, Z, Nagy, K, Kanakaridisz, N, Beke, E, Biro, J, Schnabel, R, Elias, M, Gavish, D, Francis, A, Nseir, W, Zimlichman, R, Pozzi, C, Lembo, G, Bucci, M, Mezzetti, A, Rubba, PAOLO OSVALDO FEDERICO, De Pellegrin, Am, Salvioni, A, De Cesare, N, Briones, Ir, Campos, Pf, Rosas, El, Espinosa, Ev, Salazar, Ma, Ruiz, Ab, Furusho, Lc, Olvera, I, van den Berg, R, Basart, D, Köse, V, Kentgens, S, Peeters, M, Hoogendijk, J, Voors Pette, C, Agous, I, van Kempen, W, Lingan, Gr, Kooy, A, Troquay, R, Herrman, J, Hoivik, H, Norheim, P, Risberg, K, Høivik, Ho, Elle, S, Derezinski, T, Miekus, P, Ogorek, M, Szymkowiak, K, Cesar, M, Gawron, A, Dabrowska, M, Blach, E, Konieczny, M, Sidor, M, Matias, F, da Silva, Pm, Carvalho, D, Mendonca, I, Andor, M, Andrei, L, Podoleanu, C, Pop, C, Chizhov, P, Chumakova, G, Goloschekin, B, Libov, I, Paltsman, Z, Strutinskiy, A, Koziolova, N, Breedt, J, Ebrahim, I, Ellis, G, Fulat, M, van Rensburg, Dj, Raal, F, van Dyk, C, Vally, T, van der Walt, E, Kotzé, H, Landman, C, Tayob, M, Caixas, A, García, Lr, Fernandez Cruz, A, Gil Extremera, B, Grijalvo, Om, Plana, N, Fuentes, F, Valdivielso, P, Fraile, B, Borgencrantz, B, Larnefeldt, H, Tengmark, Bo, Eriksson, M, Olsson Önerud, Å, Amalyan, W, Dyadyk, O, Koval, O, Kushnir, M, Svintsitskiy, A, Kovalyov, O, Bondarchuk, O, Tashchuk, V, Barna, O, Prokhorov, O, Karpenko, O, Stanciu, D, Pawa, R, Balaji, H, Doig, F, Harvey, P, Ranganath, L, Massalski, W, Hassanin, H, Timmis, H, Pavel Knox, I, Abdulhakim, E, Oyesile, B, Horvathova, V, Donnachie, H, Kondagunta, V, Shaw, H, Thomas, H, Kadr, H, Gunstone, A, Lip, G, Ellery, A, Kerrane, J, Sarker, A, Wong, Yk, Soran, H, Maw, K, Andersen, J, Blair Britt, L, Huffman, C, Kivitz, A, Marple, R, Patron, A, Schear, M, Allegar, N, Awasty, V, Casanova, R, Chaykin, L, Cohen, L, Collins, H, Collins, G, Elkin, G, Reyes, H, Feld, L, Fuller, G, Glover, R, Greenwald, J, Herrod, J, Kaye, W, Kimmel, M, Kolettis, E, Lakin, G, Lorch, D, Palatnik, M, Patel, R, Reichman, A, Rohlf, J, Shockey, G, Shore, K, Radin, D, Alvarado, O, Bellingar, B, Egelhof, R, Mcknight, T, Plevin, S, Pritchard, J, Reddy, R, Velazquez, F, Bolster, E, Broker, R, Butuk, D, Cheung, D, Cohen, K, Golden, G, Murray, A, Naccarato, T, Uusinarkaus, K, Pudi, K, Graff, A, Blumberg, V, Dunn, F, Toth, P, Anspach, R, Chuang, R, Meli, J, Nevins, B, Wayne, J, Schmidt, L, Levinsky, D, Rubino, J, Shealy, N, Torres, D, West, J, Jain, R, Vardi, G, Singh, N, Thew, S, Lo, E, Heitner, J, Gerber, J, Malik, A, Weinstein, D, Prashad, R, Koren, M, Ghitis, A, David, W, Reis, G, Kinzfogl, G, Haught, H, Kantaros, L, O'Dea, D, Weiss, D, Kassas, S, Hunter, J, Mollod, M, Khan, N, Henderson, D, Gatien, L, Schramm, R, Madder, R, Voyce, S, Nadar, V, Stich, M, Kumar, M, Black, R, Treasure, C, Lebeis, M, Mccullough, P, Lepor, N, Moriarty, P, Waxler, A, Talreja, D, Gen, M, Dohad, S, East, C, Conrad, G, Asbill, B, Roberts, J, Robinson, J, Zarich, S, Davis, B, Krolick, M, Sherman, H, and Thompson, P.
- Published
- 2015
7. Characterization of the hormonal response to the novel kisspeptin analog, MVT-602, in the follicular phase of healthy premenopausal women
- Author
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Johnson, B., primary, Collins, J., additional, Smith, M., additional, Jones, L., additional, Fan, X., additional, Berman, L., additional, and Voors-Pette, C., additional
- Published
- 2018
- Full Text
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8. Saxagliptin and Cardiovascular Outcomes in Patients with Type 2 Diabetes Mellitus
- Author
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Scirica, B, Bhatt, D, Braunwald, E, Steg, P, Davidson, J, Hirshberg, B, Ohman, P, Frederich, R, Wiviott, S, Hoffman, E, Cavender, M, Udell, J, Desai, N, Mosenzon, O, Mcguire, D, Ray, K, Leiter, L, Raz, I, Abrahamsen, T, Grossman, M, Morin, S, Im, K, Gabovitch, D, Pricken, A, Buskila, A, Stahre, C, Price, D, Billing-Clason, S, Sabel, K, Monyak, J, Sjostrand, M, Wei, C, Lu, J, Miller, E, Raichlen, J, Fitt, S, Iqbal, N, Donovan, M, Aguilar-Salinas, C, Alvarsson, M, Amerena, J, Ardissino, D, Averkov, O, Avogaro, A, Barnett, A, Bretzel, R, Chiang, C, Codoceo, V, Corbalan, R, Dalby, A, Darius, H, Deerochanawong, C, Dellborg, M, Eliaschewitz, F, Garcia-Castillo, A, Gomis, R, Henry, P, Hoekstra, J, Jermendy, G, Kastelein, J, Keech, A, Kiss, R, Krempf, M, Laakso, M, Leitersdorf, E, Lewis, B, Litwak, L, Lopez-Sendon, J, Ma, R, Medina, F, Moses, R, Nicolau, J, Opolski, G, Ophuis, T, Paolasso, E, Ruda, M, Kumar, K, Shestakova, M, Sheu, W, Smahelova, A, Bhupathiraju, B, Spinar, J, Sritata, P, 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L, Mitha, I, Moore, R, Conradie, M, Horak, A, Pillay, S, Wellmann, H, Berg, E, Pillai, P, Padayachee, T, Corbett, C, Makan, H, Wing, J, Vawda, Z, Ebrahim, I, Mitha, E, Bhorat, A, Fernandez, J, Munoz, C, Cortada, J, Conde, A, Calvo, C, Extremera, B, Delgado, E, Masmiquel, L, Puig, J, Parreno, L, Mauricio, D, Redon, J, Brito, M, Lopez, C, de la Morera, J, Linderfalk, C, Larnefeldt, H, Olsson, A, Lonneborg, L, Ekelund, M, Samad, B, Borgencrantz, B, Nilsson, J, Berglund, O, Svensson, M, Mooe, T, Curiac, D, Albin, J, Angesjo, E, Lannemyr, O, Chen, J, Tien, K, Ueng, K, Lai, W, Yin, W, Hung, Y, Shyu, K, Hou, J, Lam, H, Laothavorn, P, Kuanprasert, S, Khovidhunkit, W, Benjasuratwong, Y, Chotinaiwattarakul, C, Mamanasiri, S, Suraamornkul, S, Pratipanawatr, T, Nitiyanant, W, Heller, S, Pieters, R, Strang, C, Bodalia, B, Middleton, A, Hall, T, Chapman, G, Calvert, J, Reed, R, Tam, D, Butcher, G, Jones, N, Takhar, A, Turner, W, Mcnally, D, Corey, O, Chapman, J, Mohr, S, Edwards, S, Ocampo, A, Kandath, D, Aude, Y, Ervin, W, Savin, V, Anderson, R, Littlefield, R, Oberoi, M, Platt, G, Yazdani, S, Mangoo-Karim, R, Walder, J, Gogia, H, Chandrashekhar, Y, Boccalandro, F, Rogers, W, Bilazarian, S, Zieve, F, Siage, Y, O'Connor, T, Mudaliar, S, Nikas, A, Giusti, R, Glover, R, Chilka, S, French, W, Roth, E, Singh, N, Christofferson, R, Stich, M, Dagogo-Jack, S, Allison, J, Zengotita, G, Ison, R, Iteld, B, Sulistio, M, Gonzalez, E, Gorman, T, Hage-Korban, E, Reddy, R, Byars, W, Antonishen, M, Benjamin, S, First, B, Rosado, J, Bruschetta, H, Poling, T, Rosendorff, C, Kerstein, H, Saba, F, Willis, J, Adams, K, Vazquez, E, Ellison, H, Kahn, B, Kereiakes, D, Powell, S, Raskin, P, Smith, K, Varma, S, Whittier, F, Casanova, R, Isserman, S, Kaye, W, Mcguinn, W, Bartkowiak, A, Dworkin, L, Labrador, C, Podlecki, D, Popovtzer, M, Aronoff, S, Ballantyne, C, Ortiz, E, Mora, A, Pitts, T, Reinhardt, S, Soucie, G, Wainwright, W, Henson, B, Sklaver, N, Arakaki, R, Brown, J, Chalavarya, G, Chochinov, R, Dixon, T, Kutner, M, Perlman, R, Raisinghani, A, Salacata, A, Awasty, V, Elinoff, V, George, W, LaRochelle-Gryseels, A, Mercado, A, Miller, G, Qureshi, M, Steljes, A, Wefald, F, Wilson, J, Chinn, J, Chuang, R, Comulada-Rivera, A, Hartman, I, Narayan, P, Pacheco, T, Weiss, R, Beavins, J, Creevy, J, Hamroff, G, Hodson, R, Kosinski, E, Krichmar, P, Patel, R, Schneider, R, Shapiro, J, Sharp, D, Speer, J, Stegemoller, R, Waxman, F, Chang, F, Braun, E, Eder, F, Minor, S, Albert, M, Carr, K, Diaczok, B, Gastman, I, Gupta, V, Longshaw, K, Gonzalez-Campoy, J, Raikhel, M, Thomas, J, Wood, K, Diab, I, Furda, J, Gelernt, M, Halter, M, House, B, Kaster, S, Raad, G, Stamatin, R, Barker, B, Blonder, R, Bloomberg, R, Calderon, R, Carrol, A, Comerota, A, Feinglos, M, Henderson, D, Kastelic, R, Stonesifer, L, Talano, J, Lee, P, Brosseau, J, Clark, W, Cohen, E, Fialkow, J, Horton, K, Kozman, H, Mcgill, J, Mihills, C, Poonawala, R, Shore, K, Tejada, L, Torres, R, Wright, W, Calatayud, G, Chandna, H, Drozdiak, R, Fink, R, Gill, R, Glandt, M, Gottlieb, D, Hack, T, Kay, J, Mansouri, V, Mcknight, T, Mostel, E, Schmidt, L, Seide, H, Sonel, E, Taylor, R, Velasquez, M, Bretton, E, Feldman, R, Hartman, A, Hershon, K, Leach, C, Martin, E, Mohiuddin, F, Naygandhi, Y, Riske, T, Schima, S, Uzoaga, E, Ward, H, Weinstock, R, Williams, T, Altschuller, A, Aoki, T, Blumenthal, S, Cash, A, Eisner, G, Gutmann, J, Hagan, M, Kabour, A, Markus, T, Mckenzie, W, Moursi, M, Mystkowski, P, Ovalle, F, Perkins, R, Popeil, L, Saniuk, R, Sierra, Y, Alvarado, O, Anderson, J, Bajaj, M, Blank, R, Chu, A, Levinsky, L, Levy, P, Osborne, J, Pavon, H, Sanderlin, D, Schaer, G, Zarich, S, Atassi, K, Bayron, C, Casagrande, M, Das, D, Gimness, M, Handel, F, Kinstrey, T, Leu, S, Osei, K, Nouel, J, Soltani, Z, Sussman, H, Chiu, K, Duda, R, Farnsworth, K, Lano, M, Lee, F, Levin, P, Pratt, S, Richwine, R, Ruiz-Rivera, L, Turner, J, Wood, J, Zigrang, W, Baquerizo, H, Colon, C, Demattia, J, Desai, V, Fitz-Patrick, D, Goral, S, Odhav, A, Prentiss, A, Ruff, C, Wu, W, Wyne, K, Abbott, L, Applegate, R, Cabral, J, Kotha, P, Ortega, P, Simmons, D, Scirica BM, Bhatt DL, Braunwald E, Steg PG, Davidson J, Hirshberg B, Ohman P, Frederich R, Wiviott SD, Hoffman EB, Cavender MA, Udell JA, Desai NR, Mosenzon O, McGuire DK, Ray KK, Leiter LA, Raz I, Desai N, Abrahamsen T, Grossman M, Morin S, Im K, Hoffman E, Gabovitch D, Pricken A, Buskila A, Stahre C, Price D, Billing-Clason S, Sabel K, Monyak J, Sjostrand M, Wei C, Lu J, Miller E, Raichlen J, Fitt S, Iqbal N, Donovan M, Davidson JA, Aguilar-Salinas C, Alvarsson M, Amerena J, Ardissino D, Averkov O, Avogaro A, Barnett A, Bretzel R, Chiang CE, Codoceo V, Corbalan R, Dalby A, Darius H, Deerochanawong C, Dellborg M, Eliaschewitz F, Garcia-Castillo A, Gomis R, Henry P, Hoekstra J, Jermendy G, Kastelein J, Keech A, Kiss R, Krempf M, Laakso M, Leiter L, Leitersdorf E, Lewis B, Litwak L, Lopez-Sendon J, Ma R, McGuire D, Medina F, Moses R, Nicolau JC, Opolski G, Ophuis TO, Paolasso E, Ruda M, Kumar KMP, Shestakova M, Sheu WHH, Smahelova A, Bhupathiraju BSR, Spinar J, Sritata P, Strojeck K, Villena-Chavez JE, Jia WP, Huo Y, Lowe C, Awtry E, Berger C, Desai AS, Gelfand E, Leeman D, Link M, Ruberg F, Vita J, Rost N, Silverman S, Greenberger NJ, Lerch MM, Gersh B, Nesto R, Del Prato S, Tuomilehto J, Kelsey S, Alvarisqueta A, Cuadrado J, Rista L, Hermida S, Baccaro C, Luquez C, Lagrutta M, Maffei L, Bartolacci I, Montana O, Cutuli H, Berli M, Lorenzatti A, Frechtel G, La Greca R, Fretes O, Diaz M, Papini NR, Farias E, Issa C, Elbert A, Lehman R, Arya M, Singh B, Colquhoun D, Jayasinghe R, de Looze F, Blombery P, Ward G, Szto G, Abhayaratna W, Borges J, Russo L, Felicio J, Santos F, Guimaraes F, Castro ML, Rossi P, Armaganijan D, Leaes P, Bandeira F, Franken M, Rassi N, Rea R, Zanella M, Amodeo C, Cesar L, Betti R, Chacra A, Schmid H, Bell A, Syan G, Zadra R, Conter H, Dumas R, Borts D, Dattani I, Poirier P, Cha J, Dzongowski P, Labonte R, St Pierre B, Gaudet D, Kouz S, Lamy A, Tishler S, Chehayeb R, Bedard J, Hramiak I, Teitelbaum I, Fortin C, Woo V, Conway J, Mehta P, Robinson S, Sussex B, Chiasson J, Muirhead N, Bose S, Ouellet A, Yale J, Bhargava R, Lau D, Tobe S, Perron P, Sigalas J, Bilodeau L, Tytus R, Achyuthan G, Pearce M, Steele A, Bailey G, Ma P, St-Maurice F, Rupka D, Houlden R, Bailey A, Rewa G, Sohal P, Ting R, Prieto J, Rodriguez M, Godoy G, Larenas G, Pincetti C, Cobos L, Saavedra V, Varleta P, Lucero F, Kuzmanic O, Acevedo M, Aguirre M, Florenzano F, Ma J, Bao Y, Jiang M, Xu W, Shi Y, Zheng M, Li Y, Dong Y, Zhao W, Sun M, Lei M, Wang J, Pistek Z, Rihacek I, Kucera D, Brada M, Naplava R, Karasova J, Vlasicova H, Skopecek J, Spinarova L, Raclavska L, Sarbochova R, Okenka L, Racicka E, Urbancova K, Oznerova M, Lorenc Z, Wasserburger B, Zahumensky E, Grunfeldova H, Hradec J, Lukac M, Svacina S, Podzimek J, Hemzsky L, Mikulkova I, Pavlickova J, Brychta T, Chochola J, Couffinhal T, Elbaz M, Petit C, Faller B, Marechaud R, Moulin P, Fendri S, Nazeyrollas P, Wendisch U, Busch K, Klausmann G, Duengen H, Appel K, Toursarkissian N, Jung T, Ott P, Schenkenberger I, Kuesters D, Landers B, Nischik R, Fischer H, Tschoepe D, Paschen B, Krause K, Derwahl K, Wenzl-Bauer V, Hamann A, Strotmann H, Milek K, Mueller S, Chu D, Tan K, Kung K, Tsang C, Tomlinson B, Koranyi L, Kerenyi Z, Benczur B, Illyes L, Hidvegi T, Somogyi A, Valco J, Ferenczi S, Rapi J, Voros P, Winkler G, Sydo T, Hetey M, Simon K, Penzes J, Kempler P, Bako B, Lengyel Z, Witmann I, Dudas M, Vandorfi G, Takacs J, Matoltsy A, Ladanyi E, Gyimesi A, Sadikot S, Parikh K, Jain S, Yajnik C, Sosale A, Shamanna P, Srikanta S, Shah S, Srinivas A, Banker D, Shah P, Sharda A, Makkar B, Rais N, Mardikar H, Mishra A, Bhupati S, Menon J, Sathe S, Gupta R, Sharma V, Darawsha M, Herskovits T, Hamoud S, Nikolsky E, Adawi F, Zimlichman R, Tsalihin D, Wainstein J, Klainman E, Mosseri M, Yerushalmi Y, Karnieli E, Knobler H, Benchetrit S, Tsur A, Yagil Y, Atar S, Beberashvili I, Fuchs S, Stern N, Pollak A, Chajek-Shaul T, Rozenman Y, Biton A, Bramucci E, Fiscella A, Grassia V, Piatti P, De Cosmo S, Di Lorenzo L, Merlini P, Mannucci E, Frontoni S, Trevisan R, Zenari L, Lambiase C, Salvioni A, Silvestri O, Ambrosio G, Di Bartolo P, Fattore L, Presbitero P, Calabrese M, Evola R, Gamba MA, Ibarra MOD, Munoz EC, Sanchez DR, Herrera CH, Rios JP, Llamas EB, Esperon GL, Cantu EG, Fragoso JN, Gonzalez JG, Martinez GR, Padilla FP, Mier GM, Marmolejo DH, Ruiz JG, Portilla NC, Rosas EL, Machado GM, Ramos JC, Briones IR, van Hessen MWJ, Strikwerda S, The SHK, Kooy A, Ronner E, Nierop PR, Remmen JJ, Groenemeijer BE, Hamer BJB, Basart DCG, van Lennep HWOR, Nieuwdorp M, van Dijk MPM, Kentgens S, van Kempen WW, Hoogendijk J, Spiering W, Voors-Pette C, Kose V, de Waard DEP, Gonkel F, Kaasjager HAH, Lingan GMR, Agous I, Kruik HJ, Imholz BPM, Pieterse M, Manrique H, Villena J, Leon L, Kundert K, Minchola J, Pinto M, Heredia J, Rodriguez A, Guerreros C, Berrospi P, Zubiate C, Allemant A, Arbanil H, Ponciano W, Calderon J, Lisson R, Segura L, Sidorowicz-Bialynicka A, Sciborski R, Fares I, Mader P, Skierkowska J, Stasinska T, Pomiecko W, Skorski M, Krzyzagorska E, Polaszewska-Muszynska M, Sowinski D, Strojek K, Rosinska-Migda J, Romanczuk P, Golebiowski G, Kubica J, Mazurek T, Wojnowski L, Pasternak D, Stachlewski P, Trzepla E, Bogdanowicz G, Uzunow A, Potakowska I, Miszczyszyn Z, Waszyrowski T, Smolenskaya O, Lukyanov Y, Vorokhobina N, Khalimov Y, Orlikova O, Rebrov A, Kukharchuk V, Boldueva S, Arkhipov M, Zhelninova T, Pavlysh E, Antsiferov M, Panov A, Pavlova M, Shustov S, Demchenko E, Galyavich A, Malakhina E, Semenova O, Kobalava Z, Kotova S, Gavrisheva I, Oschepkova E, Karpov Y, Sidorenko B, Kislyak O, Ametov A, Dreval A, Grineva E, Mkrtumyan A, Tyurina T, Sazonova O, Bonnici F, Ranjith N, Burgess L, Nortje H, Distiller L, Mitha I, Moore R, Conradie M, Horak A, Pillay S, Wellmann H, Berg E, Pillai P, Padayachee T, Corbett C, Makan H, Wing J, Vawda Z, Ebrahim I, Mitha E, Bhorat A, Fernandez JC, Munoz C, Cortada JB, Conde AC, Calvo C, Extremera BG, Delgado E, Masmiquel L, Puig JG, Parreno LD, Mauricio D, Redon J, Brito M, Lopez C, de la Morera JS, Linderfalk C, Larnefeldt H, Olsson A, Lonneborg L, Ekelund M, Samad B, Borgencrantz B, Nilsson J, Berglund O, Svensson M, Mooe T, Curiac D, Albin J, Angesjo E, Lannemyr O, Chiang C, Sheu W, Chen J, Tien K, Ueng K, Lai W, Yin W, Hung Y, Shyu K, Hou J, Lam H, Laothavorn P, Kuanprasert S, Khovidhunkit W, Benjasuratwong Y, Chotinaiwattarakul C, Mamanasiri S, Suraamornkul S, Pratipanawatr T, Nitiyanant W, Heller S, Ray K, Pieters R, Strang C, Bodalia B, Middleton A, Hall T, Chapman G, Calvert J, Reed R, Tam D, Butcher G, Jones N, Takhar A, Turner W, McNally D, Corey O, Chapman J, Mohr S, Edwards S, Bhatt D, Ocampo A, Kandath D, Aude Y, Ervin W, Savin V, Anderson R, Littlefield R, Oberoi M, Platt GE, Yazdani S, Mangoo-Karim R, Walder J, Gogia H, Chandrashekhar Y, Boccalandro F, Rogers W, Bilazarian S, Zieve F, Siage Y, O'Connor T, Mudaliar S, Nikas A, Giusti R, Glover R, Chilka S, French W, Roth E, Singh N, Christofferson R, Stich M, Dagogo-Jack S, Allison J, Zengotita GA, Ison R, Iteld B, Sulistio M, Gonzalez E, Gorman T, Hage-Korban E, Reddy R, Byars W, Antonishen M, Benjamin S, First B, Rosado J, Bruschetta H, Poling T, Rosendorff C, Kerstein HJ, Saba F, Willis J, Adams K, Vazquez EC, Ellison H, Kahn B, Kereiakes D, Powell S, Raskin P, Smith K, Varma S, Whittier F, Casanova R, Isserman S, Kaye W, McGuinn W, Bartkowiak A, Dworkin L, Labrador CA, Podlecki D, Popovtzer M, Aronoff S, Ballantyne C, Ortiz EG, Mora A, Pitts T, Reinhardt S, Soucie G, Wainwright W, Henson B, Sklaver N, Arakaki R, Brown J, Chalavarya G, Chochinov R, Dixon T, Kutner M, Perlman R, Raisinghani A, Salacata A, Awasty V, Elinoff V, George W, LaRochelle-Gryseels A, Mercado A, Miller G, Qureshi M, Steljes A, Wefald F, Wilson J, Chinn J, Chuang RB, Comulada-Rivera A, Hartman I, Narayan P, Pacheco T, Weiss R, Beavins J, Creevy J, Hamroff G, Hodson R, Kosinski E, Krichmar P, Patel R, Schneider R, Shapiro J, Sharp D, Speer J, Stegemoller R, Waxman F, Chang FY, Braun E, Eder F, Minor S, Albert M, Carr KW, Diaczok B, Gastman I, Gupta V, Longshaw K, Gonzalez-Campoy JM, Raikhel M, Thomas J, Wood K, Diab I, Furda J, Gelernt M, Halter M, House B, Kaster S, Raad G, Stamatin R, Barker B, Blonder R, Bloomberg RJ, Calderon RB, Carrol A, Comerota A, Feinglos M, Henderson D, Kastelic R, Stonesifer LD, Talano J, Lee PV, Brosseau J, Clark W, Cohen E, Fialkow J, Horton K, Kozman H, McGill J, Mihills C, Poonawala R, Shore K, Tejada L, Torres R, Wright W, Calatayud G, Chandna H, Drozdiak R, Fink R, Gill R, Glandt M, Gottlieb DW, Hack T, Kay J, Mansouri V, McKnight T, Mostel E, Schmidt L, Seide H, Sonel E, Taylor R, Velasquez M, Bretton E, Feldman R, Hartman A, Hershon K, Leach CR, Martin E, Mohiuddin F, Naygandhi Y, Riske T, Schima S, Uzoaga ER, Ward H, Weinstock R, Williams T, Altschuller A, Aoki T, Blumenthal S, Cash A, Eisner G, Gutmann J, Hagan M, Kabour A, Markus T, McKenzie W, Moursi M, Mystkowski P, Ovalle F, Perkins R, Popeil L, Saniuk R, Sierra Y, Alvarado O, Anderson J, Bajaj M, Blank R, Chu A, Levinsky L, Levy P, Osborne J, Pavon H, Sanderlin D, Schaer G, Zarich S, Atassi K, Bayron C, Casagrande M, Das D, Gimness M, Handel F, Kinstrey T, Leu S, Osei K, Nouel JS, Soltani Z, Sussman H, Chiu K, Duda R, Farnsworth K, Lano M, Lee F, Levin P, Pratt S, Richwine R, Ruiz-Rivera L, Turner J, Wood J, Zigrang WD, Baquerizo HR, Colon CB, Demattia J, Desai V, Fitz-Patrick D, Goral S, Odhav A, Prentiss A, Ruff C, Wu W, Wyne K, Abbott LG, Applegate R, Cabral J, Kotha P, Ortega P, and Simmons D
- Abstract
BACKGROUND: The cardiovascular safety and efficacy of many current antihyperglycemic agents, including saxagliptin, a dipeptidyl peptidase 4 (DPP-4) inhibitor, are unclear. METHODS: We randomly assigned 16,492 patients with type 2 diabetes who had a history of, or were at risk for, cardiovascular events to receive saxagliptin or placebo and followed them for a median of 2.1 years. Physicians were permitted to adjust other medications, including antihyperglycemic agents. The primary end point was a composite of cardiovascular death, myocardial infarction, or ischemic stroke. RESULTS: A primary end-point event occurred in 613 patients in the saxagliptin group and in 609 patients in the placebo group (7.3% and 7.2%, respectively, according to 2-year Kaplan-Meier estimates; hazard ratio with saxagliptin, 1.00; 95% confidence interval [CI], 0.89 to 1.12; P=0.99 for superiority; P<0.001 for noninferiority); the results were similar in the "on-treatment" analysis (hazard ratio, 1.03; 95% CI, 0.91 to 1.17). The major secondary end point of a composite of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, coronary revascularization, or heart failure occurred in 1059 patients in the saxagliptin group and in 1034 patients in the placebo group (12.8% and 12.4%, respectively, according to 2-year Kaplan-Meier estimates; hazard ratio, 1.02; 95% CI, 0.94 to 1.11; P=0.66). More patients in the saxagliptin group than in the placebo group were hospitalized for heart failure (3.5% vs. 2.8%; hazard ratio, 1.27; 95% CI, 1.07 to 1.51; P=0.007). Rates of adjudicated cases of acute and chronic pancreatitis were similar in the two groups (acute pancreatitis, 0.3% in the saxagliptin group and 0.2% in the placebo group; chronic pancreatitis, <0.1% and 0.1% in the two groups, respectively). CONCLUSIONS: DPP-4 inhibition with saxagliptin did not increase or decrease the rate of ischemic events, though the rate of hospitalization for heart failure was
- Published
- 2013
9. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus
- Author
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Scirica BM, Bhatt DL, Braunwald E, Steg PG, Davidson J, Hirshberg B, Ohman P, Frederich R, Wiviott SD, Hoffman EB, Cavender MA, Udell JA, Desai NR, Mosenzon O, McGuire DK, Ray KK, Leiter LA, Raz I, Desai N, Abrahamsen T, Grossman M, Morin S, Im K, Hoffman E, Gabovitch D, Pricken A, Buskila A, Stahre C, Price D, Billing-Clason S, Sabel K, Monyak J, Sjostrand M, Wei C, Lu J, Miller E, Raichlen J, Fitt S, Iqbal N, Donovan M, Davidson JA, Aguilar-Salinas C, Alvarsson M, Amerena J, Ardissino D, Averkov O, Avogaro A, Barnett A, Bretzel R, Chiang CE, Codoceo V, Corbalan R, Dalby A, Darius H, Deerochanawong C, Dellborg M, Eliaschewitz F, Garcia-Castillo A, Gomis R, Henry P, Hoekstra J, Jermendy G, Kastelein J, Keech A, Kiss R, Krempf M, Laakso M, Leiter L, Leitersdorf E, Lewis B, Litwak L, Lopez-Sendon J, Ma R, McGuire D, Medina F, Moses R, Nicolau JC, Opolski G, Ophuis TO, Paolasso E, Ruda M, Kumar KMP, Shestakova M, Sheu WHH, Smahelova A, Bhupathiraju BSR, Spinar J, Sritata P, Strojeck K, Villena-Chavez JE, Jia WP, Huo Y, Lowe C, Awtry E, Berger C, Desai AS, Gelfand E, Leeman D, Link M, Ruberg F, Vita J, Rost N, Silverman S, Greenberger NJ, Lerch MM, Gersh B, Nesto R, Del Prato S, Tuomilehto J, Kelsey S, Alvarisqueta A, Cuadrado J, Rista L, Hermida S, Baccaro C, Luquez C, Lagrutta M, Maffei L, Bartolacci I, Montana O, Cutuli H, Berli M, Lorenzatti A, Frechtel G, La Greca R, Fretes O, Diaz M, Papini NR, Farias E, Issa C, Elbert A, Lehman R, Arya M, Singh B, Colquhoun D, Jayasinghe R, de Looze F, Blombery P, Ward G, Szto G, Abhayaratna W, Borges J, Russo L, Felicio J, Santos F, Guimaraes F, Castro ML, Rossi P, Armaganijan D, Leaes P, Bandeira F, Franken M, Rassi N, Rea R, Zanella M, Amodeo C, Cesar L, Betti R, Chacra A, Schmid H, Bell A, Syan G, Zadra R, Conter H, Dumas R, Borts D, Dattani I, Poirier P, Cha J, Dzongowski P, Labonte R, St Pierre B, Gaudet D, Kouz S, Lamy A, Tishler S, Chehayeb R, Bedard J, Hramiak I, Teitelbaum I, Fortin C, Woo V, Conway J, Mehta P, Robinson S, Sussex B, Chiasson J, Muirhead N, Bose S, Ouellet A, Yale J, Bhargava R, Lau D, Tobe S, Perron P, Sigalas J, Bilodeau L, Tytus R, Achyuthan G, Pearce M, Steele A, Bailey G, Ma P, St-Maurice F, Rupka D, Houlden R, Bailey A, Rewa G, Sohal P, Ting R, Prieto J, Rodriguez M, Godoy G, Larenas G, Pincetti C, Cobos L, Saavedra V, Varleta P, Lucero F, Kuzmanic O, Acevedo M, Aguirre M, Florenzano F, Ma J, Bao Y, Jiang M, Xu W, Shi Y, Zheng M, Li Y, Dong Y, Zhao W, Sun M, Lei M, Wang J, Pistek Z, Rihacek I, Kucera D, Brada M, Naplava R, Karasova J, Vlasicova H, Skopecek J, Spinarova L, Raclavska L, Sarbochova R, Okenka L, Racicka E, Urbancova K, Oznerova M, Lorenc Z, Wasserburger B, Zahumensky E, Grunfeldova H, Hradec J, Lukac M, Svacina S, Podzimek J, Hemzsky L, Mikulkova I, Pavlickova J, Brychta T, Chochola J, Couffinhal T, Elbaz M, Petit C, Faller B, Marechaud R, Moulin P, Fendri S, Nazeyrollas P, Wendisch U, Busch K, Klausmann G, Duengen H, Appel K, Toursarkissian N, Jung T, Ott P, Schenkenberger I, Kuesters D, Landers B, Nischik R, Fischer H, Tschoepe D, Paschen B, Krause K, Derwahl K, Wenzl-Bauer V, Hamann A, Strotmann H, Milek K, Mueller S, Chu D, Tan K, Kung K, Tsang C, Tomlinson B, Koranyi L, Kerenyi Z, Benczur B, Illyes L, Hidvegi T, Somogyi A, Valco J, Ferenczi S, Rapi J, Voros P, Winkler G, Sydo T, Hetey M, Simon K, Penzes J, Kempler P, Bako B, Lengyel Z, Witmann I, Dudas M, Vandorfi G, Takacs J, Matoltsy A, Ladanyi E, Gyimesi A, Sadikot S, Parikh K, Jain S, Yajnik C, Sosale A, Shamanna P, Srikanta S, Shah S, Srinivas A, Banker D, Shah P, Sharda A, Makkar B, Rais N, Mardikar H, Mishra A, Bhupati S, Menon J, Sathe S, Gupta R, Sharma V, Darawsha M, Herskovits T, Hamoud S, Nikolsky E, Adawi F, Zimlichman R, Tsalihin D, Wainstein J, Klainman E, Mosseri M, Yerushalmi Y, Karnieli E, Knobler H, Benchetrit S, Tsur A, Yagil Y, Atar S, Beberashvili I, Fuchs S, Stern N, Pollak A, Chajek-Shaul T, Rozenman Y, Biton A, Bramucci E, Fiscella A, Grassia V, Piatti P, De Cosmo S, Di Lorenzo L, Merlini P, Mannucci E, Frontoni S, Trevisan R, Zenari L, Lambiase C, Salvioni A, Silvestri O, Ambrosio G, Di Bartolo P, Fattore L, Presbitero P, Calabrese M, Evola R, Gamba MA, Ibarra MOD, Munoz EC, Sanchez DR, Herrera CH, Rios JP, Llamas EB, Esperon GL, Cantu EG, Fragoso JN, Gonzalez JG, Martinez GR, Padilla FP, Mier GM, Marmolejo DH, Ruiz JG, Portilla NC, Rosas EL, Machado GM, Ramos JC, Briones IR, van Hessen MWJ, Strikwerda S, The SHK, Kooy A, Ronner E, Nierop PR, Remmen JJ, Groenemeijer BE, Hamer BJB, Basart DCG, van Lennep HWOR, Nieuwdorp M, van Dijk MPM, Kentgens S, van Kempen WW, Hoogendijk J, Spiering W, Voors-Pette C, Kose V, de Waard DEP, Gonkel F, Kaasjager HAH, Lingan GMR, Agous I, Kruik HJ, Imholz BPM, Pieterse M, Manrique H, Villena J, Leon L, Kundert K, Minchola J, Pinto M, Heredia J, Rodriguez A, Guerreros C, Berrospi P, Zubiate C, Allemant A, Arbanil H, Ponciano W, Calderon J, Lisson R, Segura L, Sidorowicz-Bialynicka A, Sciborski R, Fares I, Mader P, Skierkowska J, Stasinska T, Pomiecko W, Skorski M, Krzyzagorska E, Polaszewska-Muszynska M, Sowinski D, Strojek K, Rosinska-Migda J, Romanczuk P, Golebiowski G, Kubica J, Mazurek T, Wojnowski L, Pasternak D, Stachlewski P, Trzepla E, Bogdanowicz G, Uzunow A, Potakowska I, Miszczyszyn Z, Waszyrowski T, Smolenskaya O, Lukyanov Y, Vorokhobina N, Khalimov Y, Orlikova O, Rebrov A, Kukharchuk V, Boldueva S, Arkhipov M, Zhelninova T, Pavlysh E, Antsiferov M, Panov A, Pavlova M, Shustov S, Demchenko E, Galyavich A, Malakhina E, Semenova O, Kobalava Z, Kotova S, Gavrisheva I, Oschepkova E, Karpov Y, Sidorenko B, Kislyak O, Ametov A, Dreval A, Grineva E, Mkrtumyan A, Tyurina T, Sazonova O, Bonnici F, Ranjith N, Burgess L, Nortje H, Distiller L, Mitha I, Moore R, Conradie M, Horak A, Pillay S, Wellmann H, Berg E, Pillai P, Padayachee T, Corbett C, Makan H, Wing J, Vawda Z, Ebrahim I, Mitha E, Bhorat A, Fernandez JC, Munoz C, Cortada JB, Conde AC, Calvo C, Extremera BG, Delgado E, Masmiquel L, Puig JG, Parreno LD, Mauricio D, Redon J, Brito M, Lopez C, de la Morera JS, Linderfalk C, Larnefeldt H, Olsson A, Lonneborg L, Ekelund M, Samad B, Borgencrantz B, Nilsson J, Berglund O, Svensson M, Mooe T, Curiac D, Albin J, Angesjo E, Lannemyr O, Chiang C, Sheu W, Chen J, Tien K, Ueng K, Lai W, Yin W, Hung Y, Shyu K, Hou J, Lam H, Laothavorn P, Kuanprasert S, Khovidhunkit W, Benjasuratwong Y, Chotinaiwattarakul C, Mamanasiri S, Suraamornkul S, Pratipanawatr T, Nitiyanant W, Heller S, Ray K, Pieters R, Strang C, Bodalia B, Middleton A, Hall T, Chapman G, Calvert J, Reed R, Tam D, Butcher G, Jones N, Takhar A, Turner W, McNally D, Corey O, Chapman J, Mohr S, Edwards S, Bhatt D, Ocampo A, Kandath D, Aude Y, Ervin W, Savin V, Anderson R, Littlefield R, Oberoi M, Platt GE, Yazdani S, Mangoo-Karim R, Walder J, Gogia H, Chandrashekhar Y, Boccalandro F, Rogers W, Bilazarian S, Zieve F, Siage Y, O'Connor T, Mudaliar S, Nikas A, Giusti R, Glover R, Chilka S, French W, Roth E, Singh N, Christofferson R, Stich M, Dagogo-Jack S, Allison J, Zengotita GA, Ison R, Iteld B, Sulistio M, Gonzalez E, Gorman T, Hage-Korban E, Reddy R, Byars W, Antonishen M, Benjamin S, First B, Rosado J, Bruschetta H, Poling T, Rosendorff C, Kerstein HJ, Saba F, Willis J, Adams K, Vazquez EC, Ellison H, Kahn B, Kereiakes D, Powell S, Raskin P, Smith K, Varma S, Whittier F, Casanova R, Isserman S, Kaye W, McGuinn W, Bartkowiak A, Dworkin L, Labrador CA, Podlecki D, Popovtzer M, Aronoff S, Ballantyne C, Ortiz EG, Mora A, Pitts T, Reinhardt S, Soucie G, Wainwright W, Henson B, Sklaver N, Arakaki R, Brown J, Chalavarya G, Chochinov R, Dixon T, Kutner M, Perlman R, Raisinghani A, Salacata A, Awasty V, Elinoff V, George W, LaRochelle-Gryseels A, Mercado A, Miller G, Qureshi M, Steljes A, Wefald F, Wilson J, Chinn J, Chuang RB, Comulada-Rivera A, Hartman I, Narayan P, Pacheco T, Weiss R, Beavins J, Creevy J, Hamroff G, Hodson R, Kosinski E, Krichmar P, Patel R, Schneider R, Shapiro J, Sharp D, Speer J, Stegemoller R, Waxman F, Chang FY, Braun E, Eder F, Minor S, Albert M, Carr KW, Diaczok B, Gastman I, Gupta V, Longshaw K, Gonzalez-Campoy JM, Raikhel M, Thomas J, Wood K, Diab I, Furda J, Gelernt M, Halter M, House B, Kaster S, Raad G, Stamatin R, Barker B, Blonder R, Bloomberg RJ, Calderon RB, Carrol A, Comerota A, Feinglos M, Henderson D, Kastelic R, Stonesifer LD, Talano J, Lee PV, Brosseau J, Clark W, Cohen E, Fialkow J, Horton K, Kozman H, McGill J, Mihills C, Poonawala R, Shore K, Tejada L, Torres R, Wright W, Calatayud G, Chandna H, Drozdiak R, Fink R, Gill R, Glandt M, Gottlieb DW, Hack T, Kay J, Mansouri V, McKnight T, Mostel E, Schmidt L, Seide H, Sonel E, Taylor R, Velasquez M, Bretton E, Feldman R, Hartman A, Hershon K, Leach CR, Martin E, Mohiuddin F, Naygandhi Y, Riske T, Schima S, Uzoaga ER, Ward H, Weinstock R, Williams T, Altschuller A, Aoki T, Blumenthal S, Cash A, Eisner G, Gutmann J, Hagan M, Kabour A, Markus T, McKenzie W, Moursi M, Mystkowski P, Ovalle F, Perkins R, Popeil L, Saniuk R, Sierra Y, Alvarado O, Anderson J, Bajaj M, Blank R, Chu A, Levinsky L, Levy P, Osborne J, Pavon H, Sanderlin D, Schaer G, Zarich S, Atassi K, Bayron C, Casagrande M, Das D, Gimness M, Handel F, Kinstrey T, Leu S, Osei K, Nouel JS, Soltani Z, Sussman H, Chiu K, Duda R, Farnsworth K, Lano M, Lee F, Levin P, Pratt S, Richwine R, Ruiz-Rivera L, Turner J, Wood J, Zigrang WD, Baquerizo HR, Colon CB, Demattia J, Desai V, Fitz-Patrick D, Goral S, Odhav A, Prentiss A, Ruff C, Wu W, Wyne K, Abbott LG, Applegate R, Cabral J, Kotha P, Ortega P, Simmons D, General Internal Medicine, Vascular Medicine, Other departments, Scirica, B, Bhatt, D, Braunwald, E, Steg, P, Davidson, J, Hirshberg, B, Ohman, P, Frederich, R, Wiviott, S, Hoffman, E, Cavender, M, Udell, J, Desai, N, Mosenzon, O, Mcguire, D, Ray, K, Leiter, L, Raz, I, Abrahamsen, T, Grossman, M, Morin, S, Im, K, Gabovitch, D, Pricken, A, Buskila, A, Stahre, C, Price, D, Billing-Clason, S, Sabel, K, Monyak, J, Sjostrand, M, Wei, C, Lu, J, Miller, E, Raichlen, J, Fitt, S, Iqbal, N, Donovan, M, Aguilar-Salinas, C, Alvarsson, M, Amerena, J, Ardissino, D, Averkov, O, Avogaro, A, Barnett, A, Bretzel, R, Chiang, C, Codoceo, V, Corbalan, R, Dalby, A, Darius, H, Deerochanawong, C, Dellborg, M, Eliaschewitz, F, Garcia-Castillo, A, Gomis, R, Henry, P, Hoekstra, J, Jermendy, G, Kastelein, J, Keech, A, Kiss, R, Krempf, M, Laakso, M, Leitersdorf, E, Lewis, B, Litwak, L, Lopez-Sendon, J, Ma, R, Medina, F, Moses, R, Nicolau, J, Opolski, G, Ophuis, T, Paolasso, E, Ruda, M, Kumar, K, Shestakova, M, Sheu, W, Smahelova, A, Bhupathiraju, B, Spinar, J, Sritata, P, Strojeck, K, Villena-Chavez, J, Jia, W, Huo, Y, Lowe, C, Awtry, E, Berger, C, Desai, A, Gelfand, E, Leeman, D, Link, M, Ruberg, F, Vita, J, Rost, N, Silverman, S, Greenberger, N, Lerch, M, Gersh, B, Nesto, R, Del Prato, S, Tuomilehto, J, Kelsey, S, Alvarisqueta, A, Cuadrado, J, Rista, L, Hermida, S, Baccaro, C, Luquez, C, Lagrutta, M, Maffei, L, Bartolacci, I, Montana, O, Cutuli, H, Berli, M, Lorenzatti, A, Frechtel, G, La Greca, R, Fretes, O, Diaz, M, Papini, N, Farias, E, Issa, C, Elbert, A, Lehman, R, Arya, M, Singh, B, Colquhoun, D, Jayasinghe, R, de Looze, F, Blombery, P, Ward, G, Szto, G, Abhayaratna, W, Borges, J, Russo, L, Felicio, J, Santos, F, Guimaraes, F, Castro, M, Rossi, P, Armaganijan, D, Leaes, P, Bandeira, F, Franken, M, Rassi, N, Rea, R, Zanella, M, Amodeo, C, Cesar, L, Betti, R, Chacra, A, Schmid, H, Bell, A, Syan, G, Zadra, R, Conter, H, Dumas, R, Borts, D, Dattani, I, Poirier, P, Cha, J, Dzongowski, P, Labonte, R, St Pierre, B, Gaudet, D, Kouz, S, Lamy, A, Tishler, S, Chehayeb, R, Bedard, J, Hramiak, I, Teitelbaum, I, Fortin, C, Woo, V, Conway, J, Mehta, P, Robinson, S, Sussex, B, Chiasson, J, Muirhead, N, Bose, S, Ouellet, A, Yale, J, Bhargava, R, Lau, D, Tobe, S, Perron, P, Sigalas, J, Bilodeau, L, Tytus, R, Achyuthan, G, Pearce, M, Steele, A, Bailey, G, Ma, P, St-Maurice, F, Rupka, D, Houlden, R, Bailey, A, Rewa, G, Sohal, P, Ting, R, Prieto, J, Rodriguez, M, Godoy, G, Larenas, G, Pincetti, C, Cobos, L, Saavedra, V, Varleta, P, Lucero, F, Kuzmanic, O, Acevedo, M, Aguirre, M, Florenzano, F, Ma, J, Bao, Y, Jiang, M, Xu, W, Shi, Y, Zheng, M, Li, Y, Dong, Y, Zhao, W, Sun, M, Lei, M, Wang, J, Pistek, Z, Rihacek, I, Kucera, D, Brada, M, Naplava, R, Karasova, J, Vlasicova, H, Skopecek, J, Spinarova, L, Raclavska, L, Sarbochova, R, Okenka, L, Racicka, E, Urbancova, K, Oznerova, M, Lorenc, Z, Wasserburger, B, Zahumensky, E, Grunfeldova, H, Hradec, J, Lukac, M, Svacina, S, Podzimek, J, Hemzsky, L, Mikulkova, I, Pavlickova, J, Brychta, T, Chochola, J, Couffinhal, T, Elbaz, M, Petit, C, Faller, B, Marechaud, R, Moulin, P, Fendri, S, Nazeyrollas, P, Wendisch, U, Busch, K, Klausmann, G, Duengen, H, Appel, K, Toursarkissian, N, Jung, T, Ott, P, Schenkenberger, I, Kuesters, D, Landers, B, Nischik, R, Fischer, H, Tschoepe, D, Paschen, B, Krause, K, Derwahl, K, Wenzl-Bauer, V, Hamann, A, Strotmann, H, Milek, K, Mueller, S, Chu, D, Tan, K, Kung, K, Tsang, C, Tomlinson, B, Koranyi, L, Kerenyi, Z, Benczur, B, Illyes, L, Hidvegi, T, Somogyi, A, Valco, J, Ferenczi, S, Rapi, J, Voros, P, Winkler, G, Sydo, T, Hetey, M, Simon, K, Penzes, J, Kempler, P, Bako, B, Lengyel, Z, Witmann, I, Dudas, M, Vandorfi, G, Takacs, J, Matoltsy, A, Ladanyi, E, Gyimesi, A, Sadikot, S, Parikh, K, Jain, S, Yajnik, C, Sosale, A, Shamanna, P, Srikanta, S, Shah, S, Srinivas, A, Banker, D, Shah, P, Sharda, A, Makkar, B, Rais, N, Mardikar, H, Mishra, A, Bhupati, S, Menon, J, Sathe, S, Gupta, R, Sharma, V, Darawsha, M, Herskovits, T, Hamoud, S, Nikolsky, E, Adawi, F, Zimlichman, R, Tsalihin, D, Wainstein, J, Klainman, E, Mosseri, M, Yerushalmi, Y, Karnieli, E, Knobler, H, Benchetrit, S, Tsur, A, Yagil, Y, Atar, S, Beberashvili, I, Fuchs, S, Stern, N, Pollak, A, Chajek-Shaul, T, Rozenman, Y, Biton, A, Bramucci, E, Fiscella, A, Grassia, V, Piatti, P, De Cosmo, S, Di Lorenzo, L, Merlini, P, Mannucci, E, Frontoni, S, Trevisan, R, Zenari, L, Lambiase, C, Salvioni, A, Silvestri, O, Ambrosio, G, Di Bartolo, P, Fattore, L, Presbitero, P, Calabrese, M, Evola, R, Gamba, M, Ibarra, M, Munoz, E, Sanchez, D, Herrera, C, Rios, J, Llamas, E, Esperon, G, Cantu, E, Fragoso, J, Gonzalez, J, Martinez, G, Padilla, F, Mier, G, Marmolejo, D, Ruiz, J, Portilla, N, Rosas, E, Machado, G, Ramos, J, Briones, I, van Hessen, M, Strikwerda, S, The, S, Kooy, A, Ronner, E, Nierop, P, Remmen, J, Groenemeijer, B, Hamer, B, Basart, D, van Lennep, H, Nieuwdorp, M, van Dijk, M, Kentgens, S, van Kempen, W, Hoogendijk, J, Spiering, W, Voors-Pette, C, Kose, V, de Waard, D, Gonkel, F, Kaasjager, H, Lingan, G, Agous, I, Kruik, H, Imholz, B, Pieterse, M, Manrique, H, Villena, J, Leon, L, Kundert, K, Minchola, J, Pinto, M, Heredia, J, Rodriguez, A, Guerreros, C, Berrospi, P, Zubiate, C, Allemant, A, Arbanil, H, Ponciano, W, Calderon, J, Lisson, R, Segura, L, Sidorowicz-Bialynicka, A, Sciborski, R, Fares, I, Mader, P, Skierkowska, J, Stasinska, T, Pomiecko, W, Skorski, M, Krzyzagorska, E, Polaszewska-Muszynska, M, Sowinski, D, Strojek, K, Rosinska-Migda, J, Romanczuk, P, Golebiowski, G, Kubica, J, Mazurek, T, Wojnowski, L, Pasternak, D, Stachlewski, P, Trzepla, E, Bogdanowicz, G, Uzunow, A, Potakowska, I, Miszczyszyn, Z, Waszyrowski, T, Smolenskaya, O, Lukyanov, Y, Vorokhobina, N, Khalimov, Y, Orlikova, O, Rebrov, A, Kukharchuk, V, Boldueva, S, Arkhipov, M, Zhelninova, T, Pavlysh, E, Antsiferov, M, Panov, A, Pavlova, M, Shustov, S, Demchenko, E, Galyavich, A, Malakhina, E, Semenova, O, Kobalava, Z, Kotova, S, Gavrisheva, I, Oschepkova, E, Karpov, Y, Sidorenko, B, Kislyak, O, Ametov, A, Dreval, A, Grineva, E, Mkrtumyan, A, Tyurina, T, Sazonova, O, Bonnici, F, Ranjith, N, Burgess, L, Nortje, H, Distiller, L, Mitha, I, Moore, R, Conradie, M, Horak, A, Pillay, S, Wellmann, H, Berg, E, Pillai, P, Padayachee, T, Corbett, C, Makan, H, Wing, J, Vawda, Z, Ebrahim, I, Mitha, E, Bhorat, A, Fernandez, J, Munoz, C, Cortada, J, Conde, A, Calvo, C, Extremera, B, Delgado, E, Masmiquel, L, Puig, J, Parreno, L, Mauricio, D, Redon, J, Brito, M, Lopez, C, de la Morera, J, Linderfalk, C, Larnefeldt, H, Olsson, A, Lonneborg, L, Ekelund, M, Samad, B, Borgencrantz, B, Nilsson, J, Berglund, O, Svensson, M, Mooe, T, Curiac, D, Albin, J, Angesjo, E, Lannemyr, O, Chen, J, Tien, K, Ueng, K, Lai, W, Yin, W, Hung, Y, Shyu, K, Hou, J, Lam, H, Laothavorn, P, Kuanprasert, S, Khovidhunkit, W, Benjasuratwong, Y, Chotinaiwattarakul, C, Mamanasiri, S, Suraamornkul, S, Pratipanawatr, T, Nitiyanant, W, Heller, S, Pieters, R, Strang, C, Bodalia, B, Middleton, A, Hall, T, Chapman, G, Calvert, J, Reed, R, Tam, D, Butcher, G, Jones, N, Takhar, A, Turner, W, Mcnally, D, Corey, O, Chapman, J, Mohr, S, Edwards, S, Ocampo, A, Kandath, D, Aude, Y, Ervin, W, Savin, V, Anderson, R, Littlefield, R, Oberoi, M, Platt, G, Yazdani, S, Mangoo-Karim, R, Walder, J, Gogia, H, Chandrashekhar, Y, Boccalandro, F, Rogers, W, Bilazarian, S, Zieve, F, Siage, Y, O'Connor, T, Mudaliar, S, Nikas, A, Giusti, R, Glover, R, Chilka, S, French, W, Roth, E, Singh, N, Christofferson, R, Stich, M, Dagogo-Jack, S, Allison, J, Zengotita, G, Ison, R, Iteld, B, Sulistio, M, Gonzalez, E, Gorman, T, Hage-Korban, E, Reddy, R, Byars, W, Antonishen, M, Benjamin, S, First, B, Rosado, J, Bruschetta, H, Poling, T, Rosendorff, C, Kerstein, H, Saba, F, Willis, J, Adams, K, Vazquez, E, Ellison, H, Kahn, B, Kereiakes, D, Powell, S, Raskin, P, Smith, K, Varma, S, Whittier, F, Casanova, R, Isserman, S, Kaye, W, Mcguinn, W, Bartkowiak, A, Dworkin, L, Labrador, C, Podlecki, D, Popovtzer, M, Aronoff, S, Ballantyne, C, Ortiz, E, Mora, A, Pitts, T, Reinhardt, S, Soucie, G, Wainwright, W, Henson, B, Sklaver, N, Arakaki, R, Brown, J, Chalavarya, G, Chochinov, R, Dixon, T, Kutner, M, Perlman, R, Raisinghani, A, Salacata, A, Awasty, V, Elinoff, V, George, W, LaRochelle-Gryseels, A, Mercado, A, Miller, G, Qureshi, M, Steljes, A, Wefald, F, Wilson, J, Chinn, J, Chuang, R, Comulada-Rivera, A, Hartman, I, Narayan, P, Pacheco, T, Weiss, R, Beavins, J, Creevy, J, Hamroff, G, Hodson, R, Kosinski, E, Krichmar, P, Patel, R, Schneider, R, Shapiro, J, Sharp, D, Speer, J, Stegemoller, R, Waxman, F, Chang, F, Braun, E, Eder, F, Minor, S, Albert, M, Carr, K, Diaczok, B, Gastman, I, Gupta, V, Longshaw, K, Gonzalez-Campoy, J, Raikhel, M, Thomas, J, Wood, K, Diab, I, Furda, J, Gelernt, M, Halter, M, House, B, Kaster, S, Raad, G, Stamatin, R, Barker, B, Blonder, R, Bloomberg, R, Calderon, R, Carrol, A, Comerota, A, Feinglos, M, Henderson, D, Kastelic, R, Stonesifer, L, Talano, J, Lee, P, Brosseau, J, Clark, W, Cohen, E, Fialkow, J, Horton, K, Kozman, H, Mcgill, J, Mihills, C, Poonawala, R, Shore, K, Tejada, L, Torres, R, Wright, W, Calatayud, G, Chandna, H, Drozdiak, R, Fink, R, Gill, R, Glandt, M, Gottlieb, D, Hack, T, Kay, J, Mansouri, V, Mcknight, T, Mostel, E, Schmidt, L, Seide, H, Sonel, E, Taylor, R, Velasquez, M, Bretton, E, Feldman, R, Hartman, A, Hershon, K, Leach, C, Martin, E, Mohiuddin, F, Naygandhi, Y, Riske, T, Schima, S, Uzoaga, E, Ward, H, Weinstock, R, Williams, T, Altschuller, A, Aoki, T, Blumenthal, S, Cash, A, Eisner, G, Gutmann, J, Hagan, M, Kabour, A, Markus, T, Mckenzie, W, Moursi, M, Mystkowski, P, Ovalle, F, Perkins, R, Popeil, L, Saniuk, R, Sierra, Y, Alvarado, O, Anderson, J, Bajaj, M, Blank, R, Chu, A, Levinsky, L, Levy, P, Osborne, J, Pavon, H, Sanderlin, D, Schaer, G, Zarich, S, Atassi, K, Bayron, C, Casagrande, M, Das, D, Gimness, M, Handel, F, Kinstrey, T, Leu, S, Osei, K, Nouel, J, Soltani, Z, Sussman, H, Chiu, K, Duda, R, Farnsworth, K, Lano, M, Lee, F, Levin, P, Pratt, S, Richwine, R, Ruiz-Rivera, L, Turner, J, Wood, J, Zigrang, W, Baquerizo, H, Colon, C, Demattia, J, Desai, V, Fitz-Patrick, D, Goral, S, Odhav, A, Prentiss, A, Ruff, C, Wu, W, Wyne, K, Abbott, L, Applegate, R, Cabral, J, Kotha, P, Ortega, P, and Simmons, D
- Subjects
Male ,Adamantane ,Dipeptidyl peptidase-4 inhibitor ,Type 2 diabetes ,Kaplan-Meier Estimate ,Saxagliptin ,chemistry.chemical_compound ,80 and over ,glucose ,saxagliptin ,Aged, 80 and over ,Medicine (all) ,Hazard ratio ,11 Medical And Health Sciences ,General Medicine ,Dipeptides ,Middle Aged ,Hospitalization ,Cardiovascular Diseases ,Female ,Aged ,Diabetes Mellitus, Type 2 ,Dipeptidyl-Peptidase IV Inhibitors ,Double-Blind Method ,Heart Failure ,Humans ,Hypoglycemia ,Hypoglycemic Agents ,Pancreatitis ,Alogliptin ,Type 2 ,medicine.drug ,insulin ,medicine.medical_specialty ,General & Internal Medicine ,Internal medicine ,Diabetes mellitus ,medicine ,Empagliflozin ,Diabetes Mellitus ,Intensive care medicine ,glycosylated hemoglobin ,business.industry ,Semaglutide ,SAVOR-TIMI 53 Steering Committee and Investigators ,medicine.disease ,chemistry ,placebo ,business - Abstract
BACKGROUND: The cardiovascular safety and efficacy of many current antihyperglycemic agents, including saxagliptin, a dipeptidyl peptidase 4 (DPP-4) inhibitor, are unclear. METHODS: We randomly assigned 16,492 patients with type 2 diabetes who had a history of, or were at risk for, cardiovascular events to receive saxagliptin or placebo and followed them for a median of 2.1 years. Physicians were permitted to adjust other medications, including antihyperglycemic agents. The primary end point was a composite of cardiovascular death, myocardial infarction, or ischemic stroke. RESULTS: A primary end-point event occurred in 613 patients in the saxagliptin group and in 609 patients in the placebo group (7.3% and 7.2%, respectively, according to 2-year Kaplan-Meier estimates; hazard ratio with saxagliptin, 1.00; 95% confidence interval [CI], 0.89 to 1.12; P=0.99 for superiority; P
- Published
- 2013
10. Excess coronary heart disease in Familial Combined Hyperlipidemia, in relation to genetic factors and central obesity
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Voors-Pette, C. and Bruin, T. W. de
- Published
- 2001
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11. Noninferior Immunogenicity and Consistent Safety of Respiratory Syncytial Virus Prefusion F Protein Vaccine in Adults 50-59 Years Compared to ≥60 Years of Age.
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Ferguson M, Schwarz TF, Núñez SA, Rodríguez-García J, Mital M, Zala C, Schmitt B, Toursarkissian N, Mazarro DO, Großkopf J, Voors-Pette C, Mehta H, Hailemariam HA, de Heusch M, Salaun B, Damaso S, David MP, Descamps D, Hill J, Vandermeulen C, and Hulstrøm V
- Subjects
- Humans, Middle Aged, Male, Female, Aged, Antibodies, Neutralizing blood, Immunogenicity, Vaccine, Viral Fusion Proteins immunology, Age Factors, Vaccination, Immunity, Cellular, Respiratory Syncytial Virus Vaccines immunology, Respiratory Syncytial Virus Vaccines adverse effects, Respiratory Syncytial Virus Vaccines administration & dosage, Respiratory Syncytial Virus Infections prevention & control, Respiratory Syncytial Virus Infections immunology, Antibodies, Viral blood, Respiratory Syncytial Virus, Human immunology
- Abstract
Background: The adjuvanted respiratory syncytial virus (RSV) prefusion F protein-based vaccine (RSVPreF3 OA) is approved in adults aged ≥60 years. We evaluated RSVPreF3 OA immunogenicity and safety in adults aged 50-59 years without or with increased risk for RSV disease due to specific chronic medical conditions., Methods: This observer-blind, phase 3, noninferiority trial included adults aged 50-59 years, stratified into 2 subcohorts: those with and those without predefined, stable, chronic medical conditions leading to an increased risk for RSV disease. Participants in both subcohorts were randomized 2:1 to receive RSVPreF3 OA or placebo. A control group of adults aged ≥60 years received RSVPreF3 OA. Primary outcomes were RSV-A and RSV-B neutralization titers (geometric mean titer ratios and sero-response rate differences) 1 month post-vaccination in 50-59-year-olds versus ≥60-year-olds. Cell-mediated immunity and safety were also assessed., Results: The exposed population included 1152 participants aged 50-59 years and 381 participants aged ≥60 years. RSVPreF3 OA was immunologically noninferior in 50-59-year-olds versus ≥60-year-olds; noninferiority criteria were met for RSV-A and RSV-B neutralization titers in those with and those without increased risk for RSV disease. Frequencies of RSVPreF3-specific polyfunctional CD4+ T cells increased substantially from pre- to 1 month post-vaccination. Most solicited adverse events had mild-to-moderate intensity and were transient. Unsolicited and serious adverse event rates were similar in all groups., Conclusions: RSVPreF3 OA was immunologically noninferior in 50-59-year-olds compared to ≥60-year-olds, in whom efficacy was previously demonstrated. The safety profile in 50-59-year-olds was consistent with that in ≥60-year-olds., Clinical Trial Registration: ClinicalTrials.gov: NCT05590403., Competing Interests: Potential conflicts of interest . H. A. H., M. d. H., B. S., S. D., M.-P. D., D. D., J. H., C. V., and V. H. are/were GSK employees at the time when the study was designed and/or conducted. H. A. H., M. d. H., B. S., S. D., M.-P. D., D. D., J. H., and V. H. hold shares in GSK as part of their employee remuneration. M.-P. D. is a co-applicant on a pending patent filed by GSK. M. F. received study-related payments for training and study conduct from GSK. T. F. S. received honoraria for lectures from AstraZeneca, Bavarian Nordic, Biogen, CSL-Seqirus, GSK, Janssen-Cilag, Merck-Serono, Moderna, Novavax, MSD, Pfizer, Roche, Sanofi-Aventis, and Takeda; he participated on advisory boards for Bavarian Nordic, CSL-Seqirus, BioNTech, GSK, Moderna, Novavax, and Takeda. S. A. N. declares study-related payments to his institution from GSK and support from GSK to attend investigators meetings. J. R.-G. declares study-related payments from GSK and honoraria and support for attending meetings and/or travel from GSK, Pfizer, and Sanofi-MSD; he also participated on data and safety monitoring boards or advisory boards from GSK and Pfizer. C. Z. received grants from GSK for the conduct of this study and support from GSK for attending meetings. J. G. declares study-related payments from GSK; grants from Novartis, Pharmalog, New Amsterdam Pharma, Syneos, Winecker Pharma, and Lilly; and consulting fees, honoraria, payment for expert testimony, and support for attending meetings and/or travel from GSK. C. V.-P. is a former employee of QPS Netherlands B.V. The other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)
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- 2024
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12. Pharmacokinetics, pharmacodynamics and safety of the novel C-X-C chemokine receptor 3 antagonist ACT-777991: Results from the first-in-human study in healthy adults.
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Boof ML, Géhin M, Voors-Pette C, Hsin CH, Sippel V, Strasser DS, and Dingemanse J
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- Adult, Humans, Male, Female, Dose-Response Relationship, Drug, Area Under Curve, Double-Blind Method, Healthy Volunteers, Administration, Oral, Half-Life
- Abstract
Aims: The C-X-C chemokine receptor 3 (CXCR3) axis is highly upregulated in the tissue of patients with type 1 diabetes. Antagonizing CXCR3 may reduce the migration of CXCR3-expressing cells to the pancreas. The pharmacokinetics (PKs), target engagement (TE) (inhibition of CXCR3 internalization) and safety of single- and multiple-ascending doses (SADs and MADs) of ACT-777991, a novel orally available potent CXCR3 antagonist, were assessed in a double-blind, randomized, placebo-controlled phase 1 study., Methods: Doses up to 100 mg (SAD part) and 40 mg twice daily (MAD part) were investigated in a total of 70 male and female healthy participants. Food effect was integrated as an SAD subpart. PK, TE, safety and tolerability data were collected up to 4 days after (last) dosing., Results: In both SAD and MAD parts, ACT-777991 was rapidly absorbed with a time to reach maximum concentration between 0.5 and 1.5 h post dose, followed by a biphasic disposition with a terminal half-life between 9.7 and 10.3 h. Increase in exposure and maximum concentration of ACT-777991 were dose-proportional. Steady state was reached after 48 h with minimal accumulation. The rate but not the extent of absorption was modified by food intake. A dose-dependent TE was demonstrated in both SAD and MAD parts. ACT-777991 was well tolerated. Neither a treatment-related pattern nor a dose-response relationship was determined for adverse events or any safety variable. No QT prolongation liability of regulatory concern was detected., Conclusions: In this first-in-human study, ACT-777991 showed good tolerability for all doses tested and a PK and TE profile suitable for further clinical development., (© 2023 British Pharmacological Society.)
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- 2024
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13. Endocrine profile of the kisspeptin receptor agonist MVT-602 in healthy premenopausal women with and without ovarian stimulation: results from 2 randomized, placebo-controlled clinical tricals.
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Abbara A, Ufer M, Voors-Pette C, Berman L, Ezzati M, Wu R, Lee TY, Ferreira JCA, Migoya E, and Dhillo WS
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- Female, Humans, Fertilization in Vitro methods, Gonadotropin-Releasing Hormone agonists, Luteinizing Hormone, Ovulation Induction methods, Adolescent, Young Adult, Adult, Kisspeptins pharmacology, Triptorelin Pamoate
- Abstract
Background: Kisspeptin is an essential regulator of hypothalamic gonadotropin-releasing hormone release and is required for physiological ovulation. Native kisspeptin-54 can induce oocyte maturation during in vitro fertilization treatment, including in women who are at high risk of ovarian hyperstimulation syndrome. MVT-602 is a potent kisspeptin receptor agonist with prospective utility to treat anovulatory disorders by triggering oocyte maturation and ovulation during medically assisted reproduction (MAR). Currently, the endocrine profile of MVT-602 during ovarian stimulation is unreported., Objective: To determine the endocrine profile of MVT-602 in the follicular phase of healthy premenopausal women (phase-1 trial), and after minimal ovarian stimulation to more closely reflect the endocrine milieu encountered during MAR (phase-2a trial)., Design: Two randomized, placebo-controlled, parallel-group, dose-finding trials., Setting: Clinical trials unit., Patients: Healthy women aged 18-35 years, either without (phase-1; n = 24), or with ovarian stimulation (phase-2a; n = 75)., Interventions: Phase-1: single subcutaneous dose of MVT-602 (0.3, 1.0, or 3.0 μg) or placebo, (n = 6 per dose). Phase-2a: single subcutaneous dose of MVT-602 (0.1, 0.3, 1.0, or 3.0 μg; n = 16-17 per dose), triptorelin 0.2 mg (n = 5; active comparator), or placebo (n = 5)., Main Outcome Measures: Phase-1: safety/tolerability; pharmacokinetics; and pharmacodynamics (luteinizing hormone [LH] and other reproductive hormones). Phase-2a: safety/tolerability; pharmacokinetics; pharmacodynamics (LH and other reproductive hormones); and time to ovulation assessed by transvaginal ultrasound., Results: In both the trials, MVT-602 was safe and well tolerated across the entire dose range. It was rapidly absorbed and eliminated, with a mean elimination half-life of 1.3-2.2 hours. In the phase-2a trial, LH concentrations increased dose dependently; mean maximum change from baseline of 82.4 IU/L at 24.8 hours was observed after administration of 3 μg MVT-602 and remained >15 IU/L for 33 hours. Time to ovulation after drug administration was 3.3-3.9 days (MVT-602), 3.4 days (triptorelin), and 5.5 days (placebo). Ovulation occurred within 5 days of administration in 100% (3 μg), 88% (1 μg), 82% (0.3 μg), and 75% (0.1 μg), of women after MVT-602, 100% after triptorelin and 60% after placebo., Conclusions: MVT-602 induces LH concentrations of similar amplitude and duration as the physiological midcycle LH surge with potential utility for induction of oocyte maturation and ovulation during MAR., Clinical Trial Registration Number: EUDRA-CT: 2017-003812-38, 2018-001379-20., Competing Interests: Declaration of interests A.A. reports Myovant Sciences Ltd Consultancy Fee and NIHR Clinician Scientist Fellowship for the submitted work. M.U. has nothing to disclose. C.V.-P. is an employee of QPS Netherlands BV. L.B. reports contracting consultant to Myovant Sciences outside the submitted work. M.E. has nothing to disclose. R.W. has nothing to disclose. T.-Y.L. has nothing to disclose. J.C.A.F. has nothing to disclose. E.M has nothing to disclose. W.S.D. reports consulted for Myovant Sciences Ltd. for the submitted work; NIHR research professorship; consulting fees from Myovant Sciences outside the submitted work., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2024
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14. First-in-Man Safety, Tolerability, and Pharmacokinetics of a Novel and Highly Selective Inhibitor of Matrix Metalloproteinase-12, FP-025: Results from Two Randomized Studies in Healthy Subjects.
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Abd-Elaziz K, Voors-Pette C, Wang KL, Pan S, Lee Y, Mao J, Li Y, Chien B, Lau D, and Diamant Z
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- Adult, Area Under Curve, Dose-Response Relationship, Drug, Double-Blind Method, Female, Humans, Male, Matrix Metalloproteinase Inhibitors adverse effects, Matrix Metalloproteinase Inhibitors pharmacokinetics, Young Adult, Matrix Metalloproteinase 12 drug effects, Matrix Metalloproteinase Inhibitors administration & dosage
- Abstract
Background and Objectives: Matrix metalloproteinases (MMPs) are proteases with different biological and pathological activities, and many have been linked to several diseases. Targeting individual MMPs may offer a safer therapeutic potential for several diseases. We assessed the safety, tolerability, and pharmacokinetics of FP-025, a novel, highly selective oral matrix metalloproteinase-12 inhibitor, in healthy subjects., Methods: Two randomized, double-blind, placebo-controlled studies were conducted. Study I was a first-in-man study, evaluating eight single ascending doses (SADs) (50-800 mg) in two formulations: i.e., neat FP-025 in capsule (API-in-Capsule) and in an amorphous solid dispersion (ASD-in-Capsule) formulation. In Study II, three multiple ascending doses (MADs) (100, 200, and 400 mg, twice daily) of FP-025 (ASD-in-Capsule) were administered for 8 days, including a food-effect evaluation., Results: Ninety-six subjects were dosed. Both formulations were well tolerated with one adverse event (AE) reported in the 800 mg API-in-Capsule SAD group and seven AEs throughout the MAD groups. The exposure to FP-025 was low with the API-in-Capsule formulation; it increased dose-dependently with the ASD-in-Capsule formulation, with which exposure to FP-025 increased in a greater-than-dose-proportional manner at lower doses (≤ 100 mg) but less proportionally at higher doses. The elimination half-life (t
1/2 ) was between 6 (Study I) and 8 h (Study II). Accumulation of FP-025 was approximately 1.7-fold in the MAD study. Food intake delayed the rate of absorption, but without effect in the extent of absorption or bioavailability., Conclusion: FP-025 was well tolerated and showed a favorable pharmacokinetic profile following ASD-in-Capsule dosing. Efficacy studies in target patient populations, including asthma, chronic obstructive pulmonary disease (COPD), and pulmonary fibrosis, are warranted., Trial Registration Number: www.clinicaltrials.gov : NCT02238834 (Study I); NCT03304964 (Study II). Trial registration date: Study I was registered on 12 September 2014 while study II was registered on 9 October 2017.- Published
- 2021
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15. The effect of the glucosylceramide synthase inhibitor lucerastat on cardiac repolarization: results from a thorough QT study in healthy subjects.
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Mueller MS, Sidharta PN, Voors-Pette C, Darpo B, Xue H, and Dingemanse J
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- 1-Deoxynojirimycin analogs & derivatives, Cross-Over Studies, Dose-Response Relationship, Drug, Double-Blind Method, Glucosyltransferases, Healthy Volunteers, Heart Rate, Humans, Electrocardiography
- Abstract
Background: Fabry disease is a rare inherited glycosphingolipid storage disorder caused by deleterious mutations in the GLA gene coding for the lysosomal enzyme α-galactosidase A. The glucosylceramide synthase inhibitor lucerastat is an iminosugar with potential to provide oral substrate reduction therapy in Fabry disease, regardless of the patient´s underlying mutation. Since lucerastat exhibits systemic exposure and many patients with Fabry disease suffer from rhythm and conduction abnormalities its effects on cardiac repolarization were evaluated in a thorough QT study., Methods: In Part A of this randomized, double-blind, placebo-controlled phase 1 study, single oral doses of 2000 and 4000 mg lucerastat were investigated to determine the supratherapeutic dose for Part B. The latter was a four-way crossover study to demonstrate that lucerastat at single oral therapeutic and supratherapeutic doses had no effect on the QTc interval > 10 ms using concentration-QTc modeling as primary analysis. The primary ECG endpoint was placebo-corrected change-from-baseline (ΔΔ) in Fridericia-corrected QTc (ΔΔQTcF). Open-label moxifloxacin served as positive control., Results: The effect of lucerastat on ΔΔQTcF was predicted as 0.39 ms (90% confidence interval [CI] - 0.13 to 0.90) and 1.69 ms (90% CI 0.33-3.05) at lucerastat peak plasma concentration after dosing with 1000 mg (5.2 µg/mL) and 4000 mg (24.3 µg/mL), respectively. A QTcF effect > 10 ms was excluded up to lucerastat plasma concentrations of approximately 34.0 µg/mL. Lucerastat did not exert an effect on other ECG parameters. Across doses, absorption of lucerastat was rapid, its elimination half-life ranged from 8.0 to 10.0 h, and the pharmacokinetics (PK) of lucerastat were dose-proportional. Moxifloxacin PK were in line with published data and assay sensitivity was demonstrated by the moxifloxacin QTc response. Lucerastat was safe and well tolerated., Conclusions: Lucerastat up to a dose of 4000 mg has no clinically relevant liability to prolong the QT interval or any clinically relevant effect on other ECG parameters. This will be an important factor in the overall benefit-risk assessment of lucerastat in the potential treatment of Fabry disease. Trial registration The study was registered with the ClinicalTrials.gov identifier NCT03832452 (February 6th, 2019, https://clinicaltrials.gov/ct2/show/NCT03832452 ) and the EudraCT number 2018-004546-42 (December 17th, 2018).
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- 2020
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16. Effect of Rifampin-Mediated OATP1B1 and OATP1B3 Transporter Inhibition on the Pharmacokinetics of the P2Y12 Receptor Antagonist Selatogrel.
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Schilling U, Dingemanse J, Voors-Pette C, Romeijn C, Dogterom P, and Ufer M
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- Adolescent, Adult, Aged, Cross-Over Studies, Double-Blind Method, Drug Administration Schedule, Drug Interactions, Female, Half-Life, Healthy Volunteers, Humans, Liver-Specific Organic Anion Transporter 1 antagonists & inhibitors, Liver-Specific Organic Anion Transporter 1 metabolism, Male, Middle Aged, Organophosphonates administration & dosage, Purinergic P2Y Receptor Antagonists administration & dosage, Pyrimidines administration & dosage, Receptors, Purinergic P2Y12 metabolism, Rifampin administration & dosage, Solute Carrier Organic Anion Transporter Family Member 1B3 antagonists & inhibitors, Solute Carrier Organic Anion Transporter Family Member 1B3 metabolism, Young Adult, Organophosphonates pharmacokinetics, Purinergic P2Y Receptor Antagonists pharmacokinetics, Pyrimidines pharmacokinetics, Rifampin pharmacokinetics
- Abstract
In vitro studies have indicated that the P2Y12 receptor antagonist selatogrel is a substrate of organic anion-transporting-polypeptide (OATP)1B1 and OATP1B3 that are known to mediate hepatic uptake. Selatogrel is primarily eliminated via the biliary route. Therefore, the study aim was to investigate the effect of rifampin-mediated OATP1B1 and OATP1B3 inhibition on the pharmacokinetics (PK) of selatogrel. This was a randomized, double-blind, placebo-controlled, two-period, crossover study in 14 healthy subjects. In each period, a single subcutaneous dose of 4 mg selatogrel was administered, either immediately after a single intravenous 30 minutes infusion of 600 mg rifampin or after placebo. Plasma samples were collected for 36 hours and analyzed using a validated liquid chromatography-tandem mass spectrometry method. PK parameters of selatogrel were calculated using noncompartmental analysis. The effect of rifampin was explored based on geometric mean peak plasma concentration (C
max ) and area under the concentration curve from zero to infinity (AUC0-∞ ) ratios and for time of maximum plasma concentration (Tmax ) by Wilcoxon signed rank test. In addition, the safety and tolerability of the study treatments were evaluated. The geometric mean ratios of Cmax and AUC0-∞ were 1.19 (90% confidence interval (CI) 1.11-1.28) and 1.43 (90% CI 1.36-1.51), respectively, indicating a minor selatogrel exposure increase when administered after an infusion of rifampin compared with placebo. Rifampin administration did not affect terminal half-life (t½ ) or Tmax of selatogrel. All study treatments were safe and well-tolerated. A single dose of 600 mg rifampin, a potent OATP1B1/1B3 inhibitor, did not impact the PK of selatogrel to a clinically relevant extent suggesting that OATP1B1 and OATP1B3 transporters do not play a major role in the elimination of selatogrel., (© 2020 Idorsia Pharmaceuticals Ltd. Clinical and Translational Science published by Wiley Periodicals, Inc. on behalf of the American Society for Clinical Pharmacology and Therapeutics.)- Published
- 2020
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17. Population Pharmacokinetic/Pharmacodynamic Modeling of Glenzocimab (ACT017) a Glycoprotein VI Inhibitor of Collagen-Induced Platelet Aggregation.
- Author
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Renaud L, Lebozec K, Voors-Pette C, Dogterom P, Billiald P, Jandrot Perrus M, Pletan Y, and Machacek M
- Subjects
- Adult, Age Factors, Antibodies, Monoclonal, Humanized administration & dosage, Antibodies, Monoclonal, Humanized blood, Body Weight, Clinical Trials, Phase I as Topic, Collagen adverse effects, Computer Simulation, Creatinine blood, Dose-Response Relationship, Drug, Female, Healthy Volunteers, Humans, Infusions, Intravenous, Male, Middle Aged, Models, Biological, Platelet Aggregation Inhibitors administration & dosage, Platelet Aggregation Inhibitors blood, Young Adult, Antibodies, Monoclonal, Humanized pharmacokinetics, Antibodies, Monoclonal, Humanized pharmacology, Platelet Aggregation drug effects, Platelet Aggregation Inhibitors pharmacokinetics, Platelet Aggregation Inhibitors pharmacology, Platelet Membrane Glycoproteins antagonists & inhibitors
- Abstract
Glenzocimab (ACT017) is a humanized monoclonal antigen-binding fragment (Fab) directed against the human platelet glycoprotein VI, a key receptor for collagen and fibrin that plays a major role in thrombus growth and stability. Glenzocimab is being developed as an antiplatelet agent to treat the acute phase of ischemic stroke. During a phase I study in healthy volunteers, the population pharmacokinetics (PK) and pharmacodynamics (PD) of glenzocimab were modeled using Monolix software. The PK/PD model thus described glenzocimab plasma concentrations and its effects on ex vivo collagen-induced platelet aggregation. Glenzocimab was found to have dose-proportional, 2-compartmental PK with a central distribution volume of 4.1 L, and first and second half-lives of 0.84 and 9.6 hours. Interindividual variability in clearance in healthy volunteers was mainly explained by its dependence on body weight. The glenzocimab effect was described using an immediate effect model with a dose-dependent half maximal inhibitory concentration: Larger doses resulted in a stronger effect at the same glenzocimab plasma concentration. The mechanism of the overproportional concentration effect at higher doses remained unexplained. PK/PD simulations predicted that 1000-mg glenzocimab given as a 6-hour infusion reduced platelet aggregation to 20% in 100% of subjects at 6 hours and in 60% of subjects at 12 hours after dosing. Simulations revealed a limited impact of creatinine clearance on exposure, suggesting that no dose adjustments were required with respect to renal function. Future studies in patients with ischemic stroke are now needed to establish the relationship between ex vivo platelet aggregation and the clinical effect., (© 2020 The Authors. The Journal of Clinical Pharmacology published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology.)
- Published
- 2020
- Full Text
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18. Association Between Vomiting and QT Hysteresis: Data from a TQT Study with the Endothelin A Receptor Antagonist Clazosentan.
- Author
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Juif PE, Dingemanse J, Voors-Pette C, and Ufer M
- Subjects
- Adult, Cross-Over Studies, Dioxanes administration & dosage, Double-Blind Method, Endothelin A Receptor Antagonists administration & dosage, Female, Humans, Male, Middle Aged, Pyridines administration & dosage, Pyrimidines administration & dosage, Sulfonamides administration & dosage, Tetrazoles administration & dosage, Young Adult, Dioxanes adverse effects, Endothelin A Receptor Antagonists adverse effects, Heart Conduction System drug effects, Long QT Syndrome chemically induced, Pyridines adverse effects, Pyrimidines adverse effects, Sulfonamides adverse effects, Tetrazoles adverse effects, Vomiting chemically induced
- Abstract
This study investigated the potential QT liability of the selective endothelin-1 A receptor antagonist clazosentan at a therapeutic (20 mg/h) and supratherapeutic (60 mg/h) intravenous (i.v.) dose. A randomized, placebo- and moxifloxacin-controlled, double-blind, 3-period, crossover study was conducted in 36 healthy subjects receiving clazosentan (20 mg/h followed by 60 mg/h i.v. for 3 h each), placebo (i.v. for 6 h), and moxifloxacin (single oral dose of 400 mg concomitantly with placebo i.v. for 6 h). At least three replicate ECGs were extracted from Holter recordings at predefined time points from 1 h pre-dose to 24 h after end of infusion. Pharmacokinetic blood sampling was performed for concentration/QT analysis (primary endpoint). For moxifloxacin, the lower bound of the 90% confidence interval (CI) of baseline- and placebo-corrected QTcF (ΔΔQTcF) was > 5 ms at its maximum plasma concentration together with a positive slope of the concentration/QT regression line demonstrating assay sensitivity. For clazosentan, time of peak exposure preceded maximum ΔΔQTcF by 4 h indicating delayed QT-prolonging effects leading to invalidity of the concentration/QT analysis. The secondary by-time-point analysis revealed QT liability of clazosentan (i.e., upper bound of 90% CI ∆∆QTcF > 10 ms). Delayed QT prolongation (i.e., hysteresis) was predominantly observed in subjects with nausea and vomiting, potentially caused by vagal reaction and/or decreases in potassium concentration. By contrast, there was no association with other adverse events, food intake, or concomitant medication. In conclusion, clazosentan at therapeutic and supratherapeutic doses has QT liability with hysteresis effects being associated with nausea and vomiting.
- Published
- 2020
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19. Influence of Rifampin-Mediated Organic Anion-Transporting Polypeptide 1B1/1B3 Inhibition on the Pharmacokinetics of Clazosentan.
- Author
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Juif PE, Voors-Pette C, Ufer M, Dogterom P, and Dingemanse J
- Subjects
- Adult, Dioxanes adverse effects, Humans, Liver-Specific Organic Anion Transporter 1 metabolism, Male, Middle Aged, Pyridines adverse effects, Pyrimidines adverse effects, Solute Carrier Organic Anion Transporter Family Member 1B3 metabolism, Sulfonamides adverse effects, Tetrazoles adverse effects, Dioxanes pharmacokinetics, Liver-Specific Organic Anion Transporter 1 antagonists & inhibitors, Pyridines pharmacokinetics, Pyrimidines pharmacokinetics, Rifampin pharmacology, Solute Carrier Organic Anion Transporter Family Member 1B3 antagonists & inhibitors, Sulfonamides pharmacokinetics, Tetrazoles pharmacokinetics
- Abstract
Clazosentan is a selective endothelin A receptor antagonist in development for the prevention and treatment of vasospasm postsubarachnoid hemorrhage. It is a substrate of organic anion-transporting polypeptide 1B1/1B3 based on preclinical data. This randomized, double-blind, two-period, cross-over study investigated the pharmacokinetics, safety, and tolerability of an intravenous infusion of clazosentan (15 mg/hour for 3 hours) after the intravenous administration of placebo or rifampin (600 mg/100 mL in 30 minutes). A total of 14 healthy male participants were enrolled resulting in 13 completers. Clazosentan exposure was three to four times higher after organic anion-transporting polypeptide 1B1/1B3 inhibition, as reflected by the geometric mean ratio (90% confidence interval) of area under the plasma concentration-time curve from zero to infinity: 3.88 (3.24-4.65). Clearance and volume of distribution decreased to a similar extent. Elimination half-life was not affected. A similar pattern but a higher incidence and frequency of adverse events were observed when clazosentan was given with rifampin than with placebo., (© 2019 Idorsia Pharmaceuticals Ltd. Clinical and Translational Science published by Wiley Periodicals, Inc. on behalf of the American Society for Clinical Pharmacology and Therapeutics.)
- Published
- 2019
- Full Text
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20. Safety and Tolerability, Pharmacokinetics, and Pharmacodynamics of ACT017, an Antiplatelet GPVI (Glycoprotein VI) Fab.
- Author
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Voors-Pette C, Lebozec K, Dogterom P, Jullien L, Billiald P, Ferlan P, Renaud L, Favre-Bulle O, Avenard G, Machacek M, Plétan Y, and Jandrot-Perrus M
- Subjects
- Adult, Dose-Response Relationship, Drug, Double-Blind Method, Drug Administration Schedule, Female, Healthy Volunteers, Humans, Infusions, Intravenous, Male, Maximum Tolerated Dose, Drug Tolerance, Patient Safety, Platelet Aggregation Inhibitors administration & dosage, Platelet Aggregation Inhibitors pharmacokinetics
- Abstract
Objective- ACT017 is a novel, first in class, therapeutic antibody to platelet GPVI (glycoprotein VI) with potent and selective antiplatelet effects. This first-in-human, randomized, placebo-controlled phase 1 study was conducted to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of ACT017 in healthy subjects. Approach and Results- Six cohorts of 8 healthy male and female subjects each received ascending single doses of ACT017 (n=6) or placebo (n=2) as a 6-hour intravenous infusion, with ¼ of the total dose administered within 15 minutes and the rest of the dose (¾ of the total dose) administered within 5 hours and 45 minutes. The 6 investigated doses ranged from 62.5 to 2000 mg. All doses of ACT017 were well tolerated, and no serious adverse events occurred during the study. None of the subjects reported an infusion site reaction. Template bleeding time was not affected in a clinically significant manner by any of the ACT017 doses. Plasma concentrations, determined by liquid chromatography-tandem mass spectrometry, increased linearly with the dose received as were the established pharmacokinetics values. There was no change in the platelet count, platelet GPVI expression assessed by flow cytometry, or plasma levels of soluble GPVI assessed by ELISA. In contrast, administration of ACT017 inhibited collagen-induced platelet aggregation measured by light transmission aggregometry on platelet-rich plasma, and the extent and duration of the effect were dose-dependent. Conclusions- The novel antiplatelet agent ACT017 has consistent pharmacokinetic/pharmacodynamic properties and favorable safety and tolerability profiles warranting further clinical development.
- Published
- 2019
- Full Text
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21. Abdominal obesity and expression of familial combined hyperlipidemia.
- Author
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van der Kallen CJ, Voors-Pette C, and de Bruin TW
- Subjects
- Adult, Aging, Apolipoproteins B blood, Body Mass Index, Female, Humans, Hyperlipidemia, Familial Combined physiopathology, Logistic Models, Male, Middle Aged, Obesity physiopathology, Odds Ratio, Sex Characteristics, Spouses, Waist-Hip Ratio, Abdomen, Hyperlipidemia, Familial Combined genetics, Obesity genetics
- Abstract
Objective: To investigate the role of abdominal and body obesity on the prevalence of hyperlipidemia, in particular, hypertriglyceridemia, hypercholesterolemia, and high apolipoprotein B levels, in familial combined hyperlipidemia (FCHL) relatives and their spouses., Research Methods and Procedures: In FCHL relatives (n = 618) and spouses (n = 297), prevalence data of hyperlipidemia and high apolipoprotein B levels and their age and gender-corrected odds ratios (ORs) were calculated for sex-adjusted categories of waist-to-hip ratio (WHR), waist circumference, and BMI., Results: Increments of BMI, waist circumference, and WHR increased the frequency of hyperlipidemia. In the whole study population (relatives and spouses combined), frequency of hypertriglyceridemia showed a significant interaction only between WHR categories and FCHL. This was studied further after stratification of relatives by multivariable logistic regression analyses corrected for age and gender. Predominant expression of hypertriglyceridemia was observed with higher categories of WHR in FCHL relatives (prevalence up to 57.6%, OR 8.48 in highest vs. lowest WHR category, p < 0.001) but not in spouses (up to 32.9%, OR 1.05 in highest vs. lowest WHR category, not significant)., Discussion: Both in spouses and FCHL relatives, increments in BMI and waist circumference increased the prevalence of hyperlipidemia. Specifically, in FCHL relatives, WHR was the most informative determinant of the expression of hyperlipidemia, in particular, hypertriglyceridemia. The data indicate that FCHL develops against a background of abdominal obesity.
- Published
- 2004
- Full Text
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22. Evidence of insulin resistant lipid metabolism in adipose tissue in familial combined hyperlipidemia, but not type 2 diabetes mellitus.
- Author
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van der Kallen CJ, Voors-Pette C, Bouwman FG, Keizer HA, Lu JY, van de Hulst RR, Bianchi R, Janssen MJ, Keulen ET, Boeckx WD, Rotter JI, and de Bruin TW
- Subjects
- Adipocytes drug effects, Adipocytes metabolism, Adipose Tissue drug effects, Adult, Biopsy, Needle, Case-Control Studies, Cells, Cultured, Diabetes Mellitus, Type 2 physiopathology, Female, Glucose Clamp Technique, Humans, Hyperlipidemia, Familial Combined physiopathology, Insulin pharmacology, Lipid Metabolism, Male, Middle Aged, Probability, Prospective Studies, Reference Values, Sensitivity and Specificity, Statistics, Nonparametric, Adipose Tissue metabolism, Catecholamines pharmacology, Diabetes Mellitus, Type 2 metabolism, Hyperlipidemia, Familial Combined metabolism, Insulin metabolism, Insulin Resistance, Lipolysis physiology
- Abstract
In patients with familial combined hyperlipidemia (FCHL) and type 2 diabetes (DM2) organ-specific differences in insulin resistance may exist. In FCHL and DM2 in vivo insulin mediated muscle glucose uptake and inhibition of lipolysis were studied by euglycemic hyperinsulinemic clamp. Insulin mediated glucose uptake was impaired to the same extent in both FCHL and DM2. Only FCHL subjects showed no reduction in plasma glycerol concentrations during insulin infusion and incomplete suppression of plasma free fatty acid (FFA) concentrations combined. This finding indicated that insulin-induced suppression of lipolysis, or glycerol/FFA utilization, or both, were impaired in FCHL, in contrast to DM2 or control subjects. To analyze these possibilities in more detail, control, FCHL, and DM2 adipocytes were studied in vitro. In contrast to adipocytes from DM2 or control subjects, no reduction in medium FFA concentration was detected with FCHL adipocytes after incubation with insulin. This finding indicated impaired intracellular FFA utilization, most likely impaired FFA re-esterification. Genetic linkage analysis in 18 Dutch families with FCHL revealed no evidence for involvement of LIPE, the hormone sensitive lipase gene, indicating that genetic variation in adipocyte lipolysis by LIPE is not the key defect in FCHL. In conclusion, FCHL as well as DM2 subjects exhibited in vivo insulin resistance to glucose disposal, which occurs mainly in muscle. FCHL subjects showed insulin resistant adipose tissue lipid metabolism, in contrast to DM2 and controls. The different pattern of organ-specific insulin resistance in FCHL versus DM2 advances our understanding of differences and similarities in phenotypes between these disorders.
- Published
- 2002
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23. Familial dyslipidemic hypertension syndrome: familial combined hyperlipidemia, and the role of abdominal fat mass.
- Author
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Keulen ET, Voors-Pette C, and de Bruin TW
- Subjects
- Adult, Aging physiology, Female, Humans, Hyperlipidemia, Familial Combined genetics, Hypertension physiopathology, Male, Middle Aged, Syndrome, Abdomen, Adipose Tissue physiopathology, Hyperlipidemia, Familial Combined complications, Hyperlipidemia, Familial Combined physiopathology, Hyperlipidemias etiology, Hypertension etiology
- Abstract
Familial combined hyperlipidemia (FCHL) is the most frequent genetic lipid abnormality in humans, with a 5- to 10-fold increased risk of early myocardial infarction. Familial combined hyperlipidemia has been proposed as the leading cause of dyslipidemia in familial dyslipidemic hypertension (FDH). It was the objective of this study to quantify and analyze the simultaneous occurrence of hypertension and hyperlipidemia in FCHL families. We assessed blood pressure (BP) and hyperlipidemia in 27 families with FCHL (235 relatives and 140 spouses, aged 30 to 60 years). Hypertension was defined as a BP more than 140/90 mm Hg, or the use of antihypertensive medication. Multiple backward linear regression analysis was used to derive a biological formula describing BP in FCHL families. One-third of 27 FCHL families were diagnosed with FDH. Sixty-four of 235 (27.2%) relatives had dyslipidemic hypertension (DH), compared to 20 of 140 (14.3%) spouses (P = .005); odds ratio = 2.25 (95% confidence interval 1.29-3.91). Multiple linear regression analysis showed that age, FCHL status, and waist circumference significantly contributed to systolic blood pressure (SBP) in female FCHL relatives. In conclusion, in FCHL we defined age, waist circumference, and hyperlipidemia as predictors of SBP. This study indicates that visceral adipose tissue strongly contributes to the high prevalence of DH in FCHL families. Reduction of visceral fat should be tested as a potential therapeutic intervention for hyperlipidemia and hypertension in FCHL individuals.
- Published
- 2001
- Full Text
- View/download PDF
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