Search

Your search keyword '"Mc Neeley, David F"' showing total 3 results
Start Over Author "Mc Neeley, David F"
3 results on '"Mc Neeley, David F"'

1. Towards earlier inclusion of Children in Tuberculosis (TB) drugs trials: Consensus statements from an Expert Panel

Author

Nachman, Sharon, Ahmed, Amina, Amanullah, Farhana, Becerra, Mercedes C, Botgros, Radu, Brigden, Grania, Browning, Renee, Gardiner, Elizabeth, Hafner, Richard, Hesseling, Anneke, How, Cleotilde, Jean-Philippe, Patrick, Lessem, Erica, Makhene, Mamodikoe, Mbelle, Nontombi, Marais, Ben, McIlleron, Helen, Mc Neeley, David F, Mendel, Carl, Murray, Stephen, Navarro, Eileen, Oramasionwu, Gloria E, Porcalla, Ariel R, Powell, Clydette, Powell, Mair, Rigaud, Mona, Rouzier, Vanessa, Samson, Pearl, Schaaf, H. Simon, Shah, Seema, Starke, Jeff, Swaminathan, Soumya, Wobudeya, Eric, and Worrell, Carol

Subjects
new anti-TB drugs, Adult, Male, childhood TB, Clinical Trials as Topic, Consensus, Adolescent, drug resistant TB, Age Factors, Antitubercular Agents, Infant, Newborn, Infant, clinical trial, ethics, Article, Child, Preschool, Humans, Tuberculosis, Female, Child, pharmacokinetics
Abstract

Children represent a significant proportion of the global tuberculosis (TB) burden, and may be disproportionately more affected by its most severe clinical manifestations. Currently available treatments for pediatric drug-susceptible (DS) and drug-resistant (DR) TB, albeit generally effective, are hampered by high pill burden, long duration of treatment, coexistent toxicities, and an overall lack of suitable, child-friendly formulations. The complex and burdensome nature of administering the existing regimens to treat DS TB also contributes to the rise of DR TB strains. Despite the availability and use of these therapies for decades, a dearth of dosing evidence in children underscores the importance of sustained efforts for TB drug development to better meet the treatment needs of children with TB. Several new TB drugs and regimens with promising activity against both DS and DR TB strains have recently entered clinical development and are in various phases of clinical evaluation in adults or have received marketing authorization for adults. However, initiation of clinical trials to evaluate these drugs in children is often deferred, pending the availability of complete safety and efficacy data in adults or after drug approval. This document summarizes consensus statements from an international panel of childhood TB opinion leaders which support the initiation of evaluation of new TB drugs and regimens in children at earlier phases of the TB Drug development cycle.

Published
2015

3. The diarylquinoline TMC207 for multidrug-resistant tuberculosis.

Author

Diacon AH, Pym A, Grobusch M, Patientia R, Rustomjee R, Page-Shipp L, Pistorius C, Krause R, Bogoshi M, Churchyard G, Venter A, Allen J, Palomino JC, De Marez T, van Heeswijk RP, Lounis N, Meyvisch P, Verbeeck J, Parys W, de Beule K, Andries K, and Mc Neeley DF

Subjects
Adolescent, Adult, Antitubercular Agents adverse effects, Antitubercular Agents pharmacokinetics, Colony Count, Microbial, Diarylquinolines, Drug Therapy, Combination, Female, Humans, Male, Microbial Sensitivity Tests, Middle Aged, Mycobacterium tuberculosis enzymology, Mycobacterium tuberculosis growth & development, Quinolines adverse effects, Quinolines pharmacokinetics, Young Adult, Antitubercular Agents therapeutic use, Mycobacterium tuberculosis drug effects, Proton-Translocating ATPases antagonists & inhibitors, Quinolines therapeutic use, Tuberculosis, Multidrug-Resistant drug therapy
Abstract

Background: The diarylquinoline TMC207 offers a new mechanism of antituberculosis action by inhibiting mycobacterial ATP synthase. TMC207 potently inhibits drug-sensitive and drug-resistant Mycobacterium tuberculosis in vitro and shows bactericidal activity in patients who have drug-susceptible pulmonary tuberculosis., Methods: In the first stage of a two-stage, phase 2, randomized, controlled trial, we randomly assigned 47 patients who had newly diagnosed multidrug-resistant pulmonary tuberculosis to receive either TMC207 (400 mg daily for 2 weeks, followed by 200 mg three times a week for 6 weeks) (23 patients) or placebo (24 patients) in combination with a standard five-drug, second-line antituberculosis regimen. The primary efficacy end point was the conversion of sputum cultures, in liquid broth, from positive to negative., Results: The addition of TMC207 to standard therapy for multidrug-resistant tuberculosis reduced the time to conversion to a negative sputum culture, as compared with placebo (hazard ratio, 11.8; 95% confidence interval, 2.3 to 61.3; P=0.003 by Cox regression analysis) and increased the proportion of patients with conversion of sputum culture (48% vs. 9%). The mean log(10) count of colony-forming units in the sputum declined more rapidly in the TMC207 group than in the placebo group. No significant differences in average plasma TMC207 concentrations were noted between patients with and those without culture conversion. Most adverse events were mild to moderate, and only nausea occurred significantly more frequently among patients in the TMC207 group than among patients in the placebo group (26% vs. 4%, P=0.04)., Conclusions: The clinical activity of TMC207 validates ATP synthase as a viable target for the treatment of tuberculosis. (ClinicalTrials.gov number, NCT00449644.), (2009 Massachusetts Medical Society)

Published
2009
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results