Search

Objectives: To assess whether drug regulatory agencies decided on applications for extended-release methylphenidate for use in adult ADHD based on select samples of trials. Study design and setting: Case series of publicly available regulatory documents. We matched an index of extended-release methylphenidate trials for adult ADHD with trials appearing in regulatory documents of extended-release methylphenidate applications. Trials and regulatory documents were identified as part of this systematic review (https://doi.org/10.1002/14651858.CD012857). We sought to identify missing trials in the regulatory documents and to clarify regulatory submission requirements. Results: We indexed 18 trials and matched those with 13 drug applications (11 approved, 2 rejected) published by 7 agencies. There were trials missing in 7 (54%) of 13 applications, median 4 trials (range 1-6). The median proportion of missing trial participants was 45% (range 23% - 72%). Regulators seemingly require that all trials must be included in new drug applications, but wording is ambiguous. Conclusion: In this sample of extended-release methylphenidate drug applications for adult ADHD, 7 of 13 regulatory decisions were missing entire trials according to public documents, even though regulatory requirements seem to stipulate that all available trials should be included in drug applications.

Objectives: We analyzed patient-reported sleep parameters for an extended-release methylphenidate formulation (PRC-063) in adolescents with attention-deficit/hyperactivity disorder. Methods: Clinic...

Aim The aim of this study was to evaluate the effect of viloxazine extended-release capsules (viloxazine ER; Qelbree™) on executive function deficits (EFDs) in pediatric subjects (6–17 years of age) with attention-deficit/hyperactivity disorder (ADHD). Methods Data from four phase III placebo-controlled trials of 100–600 mg/day viloxazine ER (6–8 weeks of treatment) were used to evaluate the change from baseline (CFB) in the Conners 3rd Edition Parent Short Form—Executive Function (C3PS-EF) content scale T-score. Subjects were defined as EFD responders if they had C3PS-EF T-score > 70 at baseline and < 65 at end of study. ADHD symptoms were assessed with ADHD Rating Scale 5th Edition (ADHD-RS-5). Subjects were defined as ADHD symptom responders if they had a ≥ 50% reduction in CFB ADHD-RS-5 Total score at Week 6. The number needed to treat (NNT) and Cohen’s d effect sizes were estimated for EFD and ADHD symptoms. Results A total of 1154 subjects were included in the analysis. Statistically significant improvements in EFDs were observed with viloxazine ER versus placebo (p = 0.0002). There were 52.5% of EFD or ADHD symptom responders in the viloxazine ER treatment group and 35.4% in the placebo group (p

To assess extended release/long acting (ER/LA) opioid prescribing patterns among ophthalmic plastic surgeons in the Centers for Medicare and Medicaid Services (CMS) Part D database.A retrospective observational cohort study was conducted on oculoplastic surgeons in the CMS Part D database who prescribed ER/LA opioids from 2013 to 2017. American Society of Ophthalmic Plastics and Reconstructive Surgery (ASOPRS) and non-ASOPRS surgeons were analyzed as groups. Prescribers were also analyzed based on gender and practice experience.Oculoplastic surgeons (64 ASOPRS and 78 non-ASOPRS) were responsible for 1,177 ER/LA opioid prescriptions from 2013 to 2017. ASOPRS members accounted for 4.6% and non-ASOPRS members accounted for 7.5% of all ER/LA opioids prescribed by ophthalmologists over the study period (ER/LA opioids are indicated for treatment of chronic pain and may be appropriately prescribed by the oculoplastic surgeon in certain circumstances, however due to the higher risk of overdose injury, those circumstances must be defined and justified. While a relatively small number of oculoplastic surgeons (10.6% ASOPRS and 19.6% non-ASOPRS) prescribed ER/LA opioids from 2013 to 2017, non-ASOPRS oculoplastic surgeons wrote 23.5% more ER/LA opioid prescriptions over the study period. Over the 5-year study period there was a general decline in the prescribing of ER/LA opioids by oculoplastic surgeons. Reviewing the prescribing practices of oculoplastic specialists, regardless of professional affiliation, is necessary to understand the role of ER/LA opioids for all of ophthalmology.

Objective To evaluate efficacy of gliclazide extended release (XR) 60 mg + metformin XR 500 mg fixed-dose combination (FDC) with metformin as add-on (as needed) in real-world clinical practice. Methods This prospective observational study was performed in patients with type 2 diabetes mellitus uncontrolled on metformin (group M) or on conventional gliclazide XR 60 mg + metformin XR 500 mg (group GM); and newly diagnosed or untreated patients with HbA1c >9% (group U) at 6 out-patient diabetes care units. Patients received gliclazide XR 60 mg + metformin XR 500 mg FDC and metformin (as needed) at baseline for 30 days. Up-titration with gliclazide capped at 120 mg and metformin every 30 days till day-90. Proportion of patients achieving target FPG was primary endpoint. Results Of 455 patients (mean age:51.9±11.3 years; mean BMI 26.7±6.2 kg/m2), 261 patients had family history of diabetes and 161 patients had hypertension. Target FPG was achieved with 1 tablet each of gliclazide XR 60 mg + metformin XR 500 mg FDC and metformin by 73.09%, 74.26%, and 60.66% patients in groups M, GM, and U, respectively. Only 29.23% patients required up-titration to 1 tablet of FDC + 2 tablets each of metformin and FDC at days 60 and 90. Mean FPG, PPG and HbA1c significantly reduced at day-90 (P3 out-of 5 patients achieved target glycemic control within 30 days in all groups.

Supplemental Digital Content is Available in the Text., Opioids relieve acute pain, but there is little evidence to support the stability of the benefit over long-term treatment of chronic noncancer pain. Previous systematic reviews consider only group level published data which did not provide adequate detail. Our goal was to use patient-level data to explore the stability of pain, opioid dose, and either physical function or pain interference in patients treated for 12 months with abuse deterrent formulations of oxycodone and hydrocodone. All available studies in the Food and Drug Administration Document Archiving, Reporting, and Regulatory Tracking System were included. Patient-level demographics, baseline data, exposure, and outcomes were harmonized. Individual patient slopes were calculated from a linear model of pain, physical function, and pain interference to determine response over time. Opioid dose was summarized by change between baseline and the final month of observation. Patients with stable or less pain, stable or lower opioid dose, and stable or better physical function (where available) met our prespecified criteria for maintaining long-term benefit from chronic opioids. Of the complete data set of 3192 patients, 1422 (44.5%) maintained their pain level and opioid dose. In a secondary analysis of 985 patients with a measured physical function, 338 (34.3%) maintained their physical function in addition to pain and opioid dose. Of 2040 patients with pain interference measured, 788 (38.6%) met criteria in addition. In a carefully controlled environment, about one-third of patients successfully titrated on opioids to treat chronic noncancer pain demonstrated continued benefit for up to 12 months.

A novel buprenorphine (BUP) extended-release formulation (BUP-XR) produced as a lipid-encapsulated, low viscosity BUP suspension for SC injection to control pain was evaluated for pharmacokinetics and safety in Sprague–Dawley rats given either 0.65 mg/kg (low dose) or 1.30 mg/kg (high dose). The 2 dosage groups each contained 6 male and 6 female rats to determine whether BUP-XR behaved differently in male or female animals. Blood samples were obtained from each animal before BUP-XR administration and at 6, 24, 48, 72, 96, and 168 h after administration. For necropsy and injection-site histopathology evaluation, 3 animals of each sex from each test group were euthanized on day 8, with the remaining animals euthanized on day 15. Mean plasma BUP concentration peaked from 6 to 24 h in all test groups, then declined in a linear fashion. Quantifiable plasma BUP was measured in all male rats at all time points except for one low dose group sample taken at 168 h. Female rats had quantifiable plasma BUP at all time points except for 1 low dose group sample at 72 and 96 h, and 2 low dose group samples at 168 h. The low dose groups, whether male or female, had lower mean plasma BUP levels at all time points as compared with their high dose counterparts, and female rats had lower mean plasma BUP levels than male rats at all time points. Results indicate that a single BUP-XR dose at either dose concentration can reliably provide plasma levels of BUP reported in the literature to be therapeutically relevant for up to 72 h, although lower plasma BUP levels can be anticipated in female rats compared with male counterparts. Mild to moderate injection-site granulomatous inflammation was observed in 6 of 12 rats in the low dose group and 7 of 12 in the high dose group. This reaction is characteristic of lipid material designed to persist in situ.

Objective: The Before School Functioning Questionnaire and Parent Rating of Evening and Morning Behavior–Revised assess early morning (BSFQ, PREMB-R AM subscale) and late afternoon/evening (PREMB-R PM subscale) functional impairment in children with ADHD. Clinically meaningful improvements were identified and applied to a trial of delayed-release and extended-release methylphenidate (DR/ER-MPH) in children with ADHD (NCT02520388) to determine if the statistically-determined improvements in functional impairment were also clinically meaningful. Method: Clinically meaningful improvements in BSFQ/PREMB-R were established post hoc by receiver operating characteristics curves, using anchors of Clinical Global Impression–Improvement (CGI-I) = 1 and CGI-I ≤ 2. Percentages of participants achieving these thresholds were calculated. Results: Thresholds for CGI-I = 1/CGI-I ≤ 2, respectively, were 27/20 (BSFQ), 5/3 (PREMB-R AM), and 9/5 (PREMB-R PM)-point decreases. More children achieved clinically meaningful improvements with DR/ER-MPH versus placebo (all p Conclusion: DR/ER-MPH increased proportions of children achieving clinically meaningful improvements in BSFQ and PREMB-R.

Effective control of pain management has the potential to significantly decrease the need for prescription opioids following a surgical procedure. While extended release products for pain management are available commercially, the implementation of a device that safely and reliably provides extended analgesia and is sufficiently flexible to facilitate a diverse array of release profiles would serve to advance patient comfort, quality of care and compliance following surgical procedures. Herein, we review current polymeric systems that could be utilized in new, controlled post-operative pain management devices and highlight where opportunities for improvement exist., Pain management is an extremely important topic both medically and socio-economically. Here the authors offer an overview of the use of degrading polymeric materials for delivery of pharmaceutical agents for pain management and offer a perspective of the future directions of the field.

Objective: To determine the safety and efficacy of PRC-063, a once-daily, multilayer, extended-release (ER) formulation of methylphenidate (MPH) hydrochloride, in the treatment of attention-deficit/hyperactivity disorder (ADHD) in children in a randomized, double-blind, parallel group, dose-optimized, placebo-controlled phase 3 study. Methods: Boys and girls aged 6–12 years diagnosed with ADHD were enrolled. During a 6-week, open-label, dose-optimization phase, subjects began treatment at 25 mg/day of PRC-063 and were titrated until an optimal dose (maximum 85 mg/day) was reached. During the double-blind period, subjects were randomized to receive treatment with their optimal dose of PRC-063 or placebo for 1 week. Efficacy was assessed in a laboratory classroom setting on the final day of the double-blind treatment using the Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Rating Scale and Permanent Product Measure of Performance (PERMP). Safety was assessed measuring adverse events (AEs), vital signs, and electrocardiograms. Results: The study was completed by 147 subjects. In the primary efficacy analysis, significant improvements were demonstrated with PRC-063 versus placebo (p

Injection of high-viscosity fluids into subcutaneous tissues may lead to a granulomatous reaction called sclerosing lipogranuloma (SL). Poly-(d,l-lactide-co-glycolide) (PLG or PLGA) microspheres are used as vehicles for extended-release drugs. Here we describe the histopathologic features of a case of SL induced by exenatide extended-release injections, and the staining pattern of PLG microspheres and microsphere remnants with carbol fuchsin.

Tacrolimus extended-release pharmacokinetics and its once-daily formulation provide beneficial properties, and its use has been evaluated in the adult kidney transplant population. Here, we report a case of successful conversion from tacrolimus immediate-release capsules to tacrolimus extended-release tablets in a pediatric kidney transplant recipient.

Objective: To compare the therapeutic effects of solifenacin succinate with extendedrelease tolterodine for the treatment of overactive bladder (OAB) in Bangladeshi patients. Methods: A prospective, randomized, single-blind, two-arm, parallel-group, clinicaltrial was conducted in the department of Urology, Bangabandhu Sheikh Mujib MedicalUniversity (BSMMU), Dhaka from January 2013 to June 2014. A total of 65 patientswith OAB were treated with solifenacin succinate 5 mg (experimental group, n=33)and extended release tolterodine 4 mg (control group, n=32), both at night daily for 12weeks. Efficacy and safety variables were assessed and compared with baseline and at 12weeks treatment in between the two groups. Results: At week 12, solifenacin succinate and extended release tolterodine demonstratedreduction in the mean number of micturition (50% vs. 51%), urgency (87% vs. 73%),urge incontinence (89% vs. 71%), nocturia (89% vs. 74%), usage of pads (90% vs.71%) per 24 hours. There was increased in the mean voided volume of each micturitionin both the groups without any difference in between them. The incidence of major adverseevents were dry mouth (15.2% vs. 9.4%), constipation (9.1% vs. 15.6%), and blurredvision (6.1% vs. 3.1%) respectively. Conclusions: Solifenacin succinate had greater efficacy to extended release tolterodine intreating overactive bladder. There were no significant treatment difference between the twogroups in decreasing the number of micturition and increasing the voided volume of eachmicturition and the incidence of major adverse events. All the adverse effects were mild andtransient in nature and discontinuation of medication due to adverse effects were low. Bangladesh Journal of Urology, Vol. 23, No. 1, January 2020 p.76-81

Type 2 diabetes mellitus is currently the main cause of chronic kidney disease, leading to end-stage renal disease in most countries around the world. Metformin is the most commonly prescribed oral antihyperglycaemic in the world and after approval by the U.S. Food and Drug Administration (FDA) in 1994, it is currently recommended as the first-line pharmacological agent for newly diagnosed Type 2 diabetes mellitus by many professional diabetes associations. In this review, the authors analysed efficacy and safety of metformin in patients with chronic kidney disease.

Objective: To examine the effectiveness of four doses of psychostimulant medication, combining extended-release methylphenidate (ER-MPH) in the morning with immediate-release MPH (IR-MPH) in the afternoon, on cognitive task performance. Method: The sample comprised 24 children (19 boys and 5 girls) who met the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition Text Revision (DSM-IV-TR) criteria for an autism spectrum disorder (ASD) on the Autism Diagnostic Interview-R and the Autism Diagnostic Observation Schedule, and had significant symptoms of attention-deficit/hyperactivity disorder (ADHD). This sample consisted of elementary school-age, community-based children (mean chronological age = 8.8 years, SD = 1.7; mean intelligence quotient = 85; SD = 16.8). Effects of placebo and three dose levels of ER-MPH (containing 0.21, 0.35, and 0.48 mg/kg equivalent of IR-MPH) on cognitive task performance were compared using a within-subject, crossover, placebo-controlled design. Each of the four MPH dosing regimens (placebo, low-dose MPH, medium-dose MPH, and high-dose MPH) was administered for 1 week; the dosing order was counterbalanced across children. Results: MPH treatment was associated with significant performance gains on cognitive tasks tapping sustained attention, selective attention, and impulsivity/inhibition. Dose/response was generally linear in the dose range studied, with no evidence of deterioration in performance at higher MPH doses in the dose range studied. Conclusion: The results of this study suggest that MPH formulations are associated with significant improvements on cognitive task performance in children with ASD and ADHD.

Purpose We conducted exposure-response modeling and simulations to compare the predicted efficacy of extended-release oxcarbazepine (OXC-XR), an oral once-daily (qd) antiepileptic drug, with that of immediate-release (IR) OXC twice-daily (bid) when the agents are used as monotherapy or adjunctive therapy in patients with epilepsy characterized by partial-onset seizures (POS). Methods Modeling assessed percent change from baseline 28-day seizure frequency (PCH) as a function of minimum concentration (Cmin) of monohydroxy derivative (MHD), the clinically relevant metabolite of OXC. For OXC-IR, the model used historical data; values for OXC-XR were derived from observed data. The model was simulated (N=100) to predict PCH at MHD Cmin concentrations achieved with 1200 and 2400 mg/day in adults and children receiving OXC-XR qd or OXC-IR bid. Mean PCH and 95% confidence intervals (CIs) were generated and compared. Results Predicted efficacy was not different (ie, 95% CI of mean PCH overlapped) for OXC-XR qd vs OXC-IR bid at mean MHD Cmin concentrations achieved with 1200 and 2400 mg/day adjunctive OXC-XR (47.4 and 76.4 µmol/L) and at target MHD Cmin concentrations for OXC-IR monotherapy (59.1 and 112 µmol/L) in adults. Predicted efficacy in adults vs children was not different between formulations. Depending on MHD Cmin, the predicted mean PCH in adults ranged from -51.4% to -73.4% with OXC-XR qd and -53.2% to -78.5% with OXC-IR bid. In children, the predicted mean PCH ranged from -48.4% to -58.1% (OXC-XR qd) and -32.5% to -70.4% (OXC-IR bid). Conclusion This model-based analysis predicted comparable efficacy for OXC-XR qd vs OXC-IR bid at MHD Cmin concentrations corresponding to 1200 and 2400 mg/day as monotherapy or adjunctive therapy. Based on this analysis, the US Food & Drug Administration approved OXC-XR for use as monotherapy in adults and children ≥6 years of age with POS.

Background: Carbidopa (CD) and levodopa (LD) extended release (CD-LD ER) capsules are designed to combine both immediate and extended release pharmacokinetics. In the phase 3, randomized, double-blind, ADVANCE-PD trial, patients randomized to CD-LD ER experienced a 1.17-hour greater reduction in OFF time compared to patients randomized to CD-LD IR (p

Endoscopic bariatric and metabolic therapies (EBMT) are rarely used in the United States. Compared with EBMTs alone, combining EBMTs with obesity pharmacotherapy may increase the magnitude and durability of weight loss and ultimately may contribute to increased patient satisfaction and EBMT utilization. Though combination therapy is frequently used in clinical practice, few published studies of combination EBMT/pharmacotherapy are available. Available studies and abstracts suggest that combination strategies are promising, but further research and clinical trials are needed. This article will review available obesity pharmacotherapy options and describe current data on combining EBMT and pharmacotherapy.

OBJECTIVE To assess the efficacy of the non-stimulant guanfacine extended release (GXR) on attention-deficit/hyperactivity disorder (ADHD) symptoms in children and adolescents, with and without comorbid oppositional defiant disorder (ODD). METHODS Data were derived from 4 phase 3, randomized, placebo-controlled trials of dose-optimized GXR monotherapy, in which at least 10% of participants had a diagnosis of comorbid ODD. SPD503-312 and SPD503-316 were 10- to 13-week studies of GXR (1-7 mg/d). SPD503-314 and SPD503-307 were 8-week studies of GXR (1-4 mg/d). Efficacy was assessed using the ADHD Rating Scale IV (ADHD-RS-IV) total scores. RESULTS In total, 1,084 participants were included (SPD503-312 and SPD503-316, n = 537; SPD503-314, n = 333; and SPD503-307, n = 214). GXR was associated with significant improvements in ADHD core symptoms at endpoint in participants with and without ODD (p < 0.01 in all studies). Placebo-adjusted least-squares mean (95% confidence interval) changes from baseline to endpoint in the ADHD-RS-IV total scores in participants with and without ODD were -8.6 (-14.4, -2.8) and -7.3 (-9.5, -5.0) in the pooled data from SPD503-312 and SPD503-316, -12.6 (-19.6, -5.7) and -8.7 (-11.8, -5.5) in SPD503-314, and -12.7 (-17.3, -8.1) and -11.8 (-19.3, -4.4) in SPD503-307, respectively. The corresponding effect sizes were 0.688 and 0.598 in SPD503-312 and SPD503-316, 0.876 and 0.729 in SPD503-314, and 0.962 and 0.842 in SPD503-307. CONCLUSION The findings demonstrate the efficacy of GXR for treating ADHD in children and adolescents with comorbid ODD.

Objectives There was higher frequency of breakthrough seizures during immediate-release phenytoin capsule usage than during extended-release phenytoin capsule usage by epilepsy patients. This study aimed to estimate the total budget of using extended-release phenytoin compared with immediate-release phenytoin capsules. Methods A decision tree model was developed for 3 scenarios in Thailand where (1) extended-release phenytoin, (2) immediate-release phenytoin, and (3) both forms, as per the market share, were prescribed. All parameters were derived from the literature reviews and hospital database and analyzed from payer and societal perspectives. Results Of 95 613 patients receiving phenytoin, the total budget impact of scenarios 1 to 3 ranged from $45 214 915 to $50 209 357, $104 298 093 to $111 846 317, and $61 167 373 to $66 851 336 from payer and societal perspectives, respectively. Conclusion Prescribing extended-release phenytoin showed the lowest total budget impact in Thailand. A healthcare policy recommendation developed from this research would help in solving the antiepileptic drug issue.

The US FDA has encouraged the development of abuse-deterrent formulations (ADFs) of opioid analgesics as one component in a comprehensive effort to combat prescription opioid abuse. Guidance issued by the FDA outlines three types of premarket studies for evaluating abuse deterrence: laboratory-based in vitro manipulation and extraction studies, pharmacokinetic studies and human abuse potential studies. After approval, postmarket studies are needed to evaluate the impact of an ADF product on abuse in real-world settings. This review summarizes the regulatory issues involved in the development of ADF opioids and clarifies abuse-deterrence claims in product labels, in order to assist clinicians in critically evaluating the available evidence pertaining to the abuse-deterrent features of opioid analgesics.

Background Development of abuse-deterrent formulations (ADFs) of prescription opioids (RxO) is an important step toward reducing misuse and abuse. Morphine-ARER (MorphaBond™ ER) is an extended-release (ER) morphine sulfate tablet formulated to deter misuse/abuse via intravenous (IV) and intranasal (IN) routes of administration. Objective A model was developed to estimate the budget impact to a hypothetical commercial health plan of 10 million members 2 years after adding morphine-ARER to drug formulary. Methods We analyzed incremental health care resource use (HCRU) associated with RxO misuse/abuse based on a health plan's RxO formulary coverage and patterns of misuse/abuse. Misuse/abuse rates, incremental HCRU and associated costs were based on the 2015 National Survey on Drug Use and Health, an analysis of claims from OptumHealth Care Solutions, Inc. (2013-2015) and published literature. RxO formulary shares were based on 2016-2017 Symphony Retail Prescription data. Morphine-ARER was assumed to capture 20 and 30 percent from branded and 0.3 and 0.6 percent from generic non-ADF ER morphine, in the first and second years, respectively. Proportions of misuse/abuse deterred by physical/chemical properties of morphine-ARER were assumed to be 90 percent via IV and 60 percent via IN administration, with further IN deterrence based on results from morphine-ARER's human abuse liability study. Results Adding morphine-ARER to formulary resulted in a potential decrease in abuse-related healthcare costs by $557,321 (-$0.00232 per-member per-month [PMPM]), offsetting a pharmacy cost increase of $217,045 (+$0.00090 PMPM), resulting in net cost-savings of $0.00142 PMPM over 2 years, based on certain model assumptions. Conclusion Placing morphine-ARER on a health plan's drug formulary may result in reduced misuse/abuse and overall cost savings.

Objective: To assess treatment patterns, health care resource utilization, and health care costs associated with use of atypical antipsychotics (AAPs) or the nonstimulant guanfacine extended release (GXR) after stimulant therapy for attention-deficit/hyperactivity disorder (ADHD). In Canada, GXR is approved as a monotherapy for children and adolescents with ADHD or as an adjunct to stimulants, and AAPs are commonly used off-label as an adjunct to stimulants. Methods: Health care claims data (January 1, 2007 to March 31, 2016) from Quebec's provincial health plan were assessed for individuals with ADHD, 6–17 years of age, who received ≥1 stimulant followed by a first AAP or GXR prescription (index medication), without a diagnosis for which AAPs are indicated. Results: Overall, 1327 individuals were included (AAPs, 1098; GXR, 229). Rates of discontinuation, augmentation, or switching of the index medication did not differ between AAPs and GXR during the first follow-up year. Discontinuation rates were significantly lower with GXR than with AAPs during the second year (22.0% vs. 35.9%; p = 0.03). GXR and AAPs resulted in similar increases in total health care cost. In GXR users, the increase in prescription drug cost after 6 months was higher than in AAP users, whereas the increase in overall medical cost was higher with AAPs than GXR, owing to more psychiatric department visits. Conclusions: In children and adolescents with ADHD who used AAPs or GXR after stimulants, secondary treatment changes were similar with both treatments after 1 year, but discontinuation rates were significantly lower with GXR than with AAPs in the second year. The greater increase in prescription cost with GXR was balanced by a greater increase in overall medical costs with AAPs, resulting in no overall difference in total health care cost between the two treatments.

Background and Purpose: Several formulations of tacrolimus are available, but evidence of the benefit of changing to the most recent formulations is lacking. Tacrolimus intra-patient variability (tacrolimus IPV) is an emerging risk factor associated with poor graft outcomes after solid organ transplantations. Here, we examined the modifications of tacrolimus IPV after switching to a different formulation of tacrolimus.Experimental Approach: We identified 353 solid organ transplant recipients that were switched in our center from immediate-release (IR-tacrolimus) or prolonged-release tacrolimus (PR-tacrolimus) to extended-release, LCP-tacrolimus (LCP-tacrolimus). Among them, 54 patients underwent at least 3 available tacrolimus blood concentrations before and after the switch, allowing us to investigate tacrolimus IPV.Key Results: The switch was considered as a safe procedure since only four of the 353 patients presented a graft rejection after the switch, and no patient was hospitalized for tacrolimus overdose. The tacrolimus IPV estimated by the coefficient of variation (CV-IPV) was stable before and after the switch to LCP-tacrolimus (CV-IPV: 29.0% (IQR 25–75 (15.5; 38.5) before and 24.0% (15.8; 36.5) after the switch, p = 0.65).Conclusion and Implications: Switching from IR- or PR-tacrolimus to LCP-tacrolimus is a safe procedure. However, the CV-tacrolimus IPV was not impacted by the change of formulation.

BACKGROUND Best practices in the management of ileostomies include use of immediate release (IR) medications and elimination of enteric coated and prokinetic agents. Extended-release (ER) potassium chloride is designed for postpyloric release rather than colonic absorption and is postulated to be an appropriate option for potassium repletion in this patient subset. CASE We present a patient with an ileostomy who received intravenous ER and IR oral potassium chloride supplementation following diverting loop ileostomy. Clinical responsiveness to ER potassium chloride was poor; 15 to 40 mEq was required to replace 0.1 mEq/L of potassium. However, upon transition to IR potassium chloride, only 6.67 mEq was required to replace 0.1 mEq/L of potassium. CONCLUSIONS Our experience in this case suggests that patients with surgical alterations to their gastrointestinal tracts who fail to have expected rises in serum potassium levels may benefit from early conversion to IR potassium chloride.

Background: ADS-5102, a delayed-release, extended-release (DR/ER) amantadine, improved walking speed in MS in a Phase 2 trial. Objective: The aim of this study was to present primary results of a Phase 3, double-blind, ADS-5102 trial (INROADS) for walking speed. Methods: Adult participants with MS and walking impairment, not currently using amantadine or dalfampridine, underwent 4-week placebo run-in before randomization 1:1:1 to placebo, 137 or 274 mg/day ADS-5102 for 12 weeks. Primary outcome was the proportion of responders (20% increase in Timed 25-Foot Walk (T25FW) speed) for 274 mg ADS-5102 versus placebo at end of double-blind (Study Week 16). Additional measures included Timed Up and Go (TUG), 2-Minute Walk Test (2MWT), and 12-item Multiple Sclerosis Walking Scale (MSWS-12). Results: In total, 558 participants were randomized and received double-blind treatment. Significantly more participants responded with 274 mg ADS-5102 (21.1%) versus placebo (11.3%). Mean T25FW speed also significantly improved (0.19 ft/s) versus placebo (0.07 ft/s). Other measures were not significant using prespecified hierarchical testing procedure. Adverse events led to discontinuation for 3.8% (placebo), 6.4% (137 mg ADS-5102), and 20.5% (274 mg ADS-5102). Conclusion: INROADS met its primary endpoint, showing a significantly greater proportion of participants with meaningful improvement in walking speed for 274 mg ADS-5102 versus placebo. Numeric dose response was seen for some secondary efficacy outcomes and adverse events.

Background Opioid agonist treatment (OAT) is an effective intervention for opioid dependence. Extended-release buprenorphine injections (BUP-XR) may have additional potential benefits over sublingual buprenorphine. This single-arm trial evaluated outcomes among people receiving 48 weeks of BUP-XR in diverse community healthcare settings in Australia, permitting examination of outcomes when BUP-XR is delivered in standard practice. Methods Participants were recruited from a network of specialist public drug treatment services, primary care and some private practices in three states. Following a minimum 7 days on 8–32 mg of sublingual buprenorphine (±naloxone), participants received monthly subcutaneous BUP-XR injections administered by a healthcare practitioner and completed monthly research interviews. The primary endpoint was retention in treatment at 48 weeks. Findings Participants (n = 100) were 28% women, mean age 44 years with a long history of OAT (median 5.8 years); heroin was the most common opioid of concern (58%). Treatment retention at 24 and 48 weeks was 86% and 75%, respectively. Participants with past-month injecting drug use (OR 0.23; 95%CI: 0.09–0.61) or heroin use (OR 0.23; 95%CI: 0.08–0.65) at baseline had lower odds of being retained in treatment to 48 weeks. Reductions in multiple forms of extra-medical drug use were observed. Improvements in quality of life, participation in employment, and treatment satisfaction measures were also observed. Interpretation This real-world implementation study of BUP-XR demonstrated high retention and treatment satisfaction. This study provides important additional data on the uptake and experience of clients, with relevance for policy makers, health service planners, administrators, and practitioners. Funding Indivior. Trial registration ClinicalTrials.gov Identifier: NCT03809143

Objective: To evaluate the efficacy, safety, and duration of action of the once-daily extended-release methylphenidate formulation PRC-063 for the treatment of ADHD in an adult laboratory classroom (ALC). Method: After dose optimization with PRC-063 over 7 weeks, adults with ADHD were randomized to 1 week of double-blind treatment with PRC-063 or placebo that ended with an ALC evaluation. The primary outcome measure was Permanent Product Measure of Performance-Total (PERMP-T) score. Results: Of 288 subjects enrolled, 221 completed the ALC visit. PERMP-T score was significantly higher for PRC-063 versus placebo at every assessment from 1 to 16 hours post-dose at the ALC visit and when averaged over 16 hours post-dose (least-squares mean difference 16.3, 95% confidence interval 7.6–24.9). The most frequent adverse events during dose optimization were headache, decreased appetite, and insomnia. Conclusion: PRC-063 provided rapid and sustained symptom relief in adults with ADHD and was well tolerated. NCT03618030.

Takayasu’s arteritis (TAK), a chronic inflammatory disorder mainly affecting the aorta and its major branches, can cause vascular injury with thickened walls, luminal stenosis, aneurysmal changes, ...

Background: Manufacturer recommendations for conversion from immediate-release to extended-release tacrolimus, Envarsus XR®, suggests 80% of the total daily dose of the immediate-release formulation. This conversion has not consistently achieved therapeutic levels in the kidney transplant population. Objectives: To determine if a reliable weight-based dosing strategy could be utilized to transition kidney transplant patients from immediate-release to extended-release tacrolimus. This may help establish a safe protocol to guide transition between formulations. Methods: Retrospective, single-center study of adult kidney transplant recipients between July 2015 and December 2018. Excluded patients received dual organs, lacked appropriately drawn tacrolimus levels, or were prescribed interacting medications. Patients were identified by querying prescriptions for extended-release tacrolimus and chart review was performed to exclude any patients without sufficient follow-up after transition. Results: 30 patients who transitioned from immediate-release tacrolimus to tacrolimus XR were included in the final analysis. The median weight-based dose of tacrolimus XR that achieved a therapeutic level among the cohort was 0.158 mg/kg/day (Q1-Q3: 0.0587-0.221), which was about 80% of the original median weight-based immediate-release tacrolimus dose. Therapeutic dosing strategies were widely variable, represented by an R2 of 0.33 on linear regression. There was a statistically significant difference in median weight-based dosing strategies among patients of various racial backgrounds (p = 0.0148). Conclusions: A weight-based dose of tacrolimus XR could not reliably predict a therapeutic level among the total cohort due to the wide inter-patient variability. The median weight-based rate of conversion from immediate-release to extended-release tacrolimus was 80%.

What is known and objective Extended-release topiramate (TPM-XR) was recently approved for the treatment of epilepsy, but there is only limited real-world information on the clinical usefulness of TPM-XR in epilepsy patients. We investigated the usefulness of TPM-XR in clinical practice by analysing the retention of TPM-XR in adult epilepsy patients. Methods We performed a single-centre retrospective study covering two years. Epilepsy patients taking TPM-XR were included in the study and classified into one of three groups: the monotherapy group, in which patients took only TPM-XR; the adjunctive therapy group, in which patients took TPM-XR concomitant with other AEDs; and the switching AED regimen group, in which patient's AED was switched from immediate-release TPM (TPM-IR) to TPM-XR. We evaluated the retention rates of TPM-XR and analysed the differences in retention rate among the three patient groups. Results and discussion We included 164 epilepsy patients who received TPM-XR for the treatment of epilepsy. The overall retention rate of TPM-XR was generally favourable: 79.1% after one year and 77.7% after two years. The switching AED regimen group had a better retention rate than the other two groups (p = 0.04), with a one-year retention rate of 90.6% and a two-year retention rate of 88.1%. What is new and conclusion The favourable retention rate of TPM-XR shows that TPM-XR can be an effective treatment option for epilepsy patients, as either a monotherapy or as an adjunctive therapy. Additionally, switching AED regimen to TPM-XR from TPM-IR can be considered in selected epilepsy patients with poor adherence to TPM-IR.

Azmi Nasser,1 Joseph T Hull,1 Tesfaye Liranso,2 Gregory D Busse,3 Zare Melyan,3 Ann C Childress,4 Frank A Lopez,5 Jonathan Rubin6 1Department of Clinical Research, Supernus Pharmaceuticals, Inc., Rockville, MD, USA; 2Department of Biostatistics, Supernus Pharmaceuticals, Inc., Rockville, MD, USA; 3Department of Medical Affairs, Supernus Pharmaceuticals, Inc., Rockville, MD, USA; 4Center for Psychiatry and Behavioral Medicine, Inc., Las Vegas, NV, USA; 5Children’s Developmental Center, Winter Park, FL, USA; 6Supernus Pharmaceuticals, Inc., Rockville, MD, USACorrespondence: Azmi NasserDepartment of Clinical Research, Supernus Pharmaceuticals, Inc., 9715 Key West Ave, Rockville, MD, 20850, USAEmail anasser@supernus.comPurpose: The ADHD Rating Scale (ADHD-RS) assesses 18 symptoms of inattention and hyperactivity/impulsivity and has been used in many clinical trials to evaluate the treatment effect of drugs on ADHD. The fifth edition of this scale (ADHD-RS-5) also assesses the impact of inattention and hyperactivity/impulsivity symptoms on six domains of functional impairment (FI): family relationships, peer relationships, completing/returning homework, academic performance at school, controlling behavior at school, and self-esteem. Here, we report the effect of viloxazine extended-release capsules (viloxazine ER), a novel nonstimulant treatment for ADHD in children and adolescents (ages 6– 17 years), on FI from a post hoc analysis of four randomized, double-blind, placebo-controlled Phase 3 clinical trials (N=1354).Patients and Methods: ADHD-RS-5 investigator ratings of ADHD symptoms and FIs were conducted at baseline and weekly post-baseline for 6– 8 weeks in the four trials. Change from baseline (CFB) in ADHD-RS-5 FI scores (Total score [sum of 12 FI items] and Inattention and Hyperactivity/Impulsivity subscale scores [sum of 6 corresponding FI items]) and the 30% and 50% Responder Rates (ADHD-RS-5 FI Total score) were compared between viloxazine ER and placebo.Results: The reduction (improvement) in ADHD-RS-5 FI scores (Total and subscale scores) and the percentage of responders (30% and 50%) at Week 6 were significantly greater in each viloxazine ER dose group vs placebo. In the 100– 400 mg/day viloxazine ER groups, improvements were found as early as Week 1 (100-mg/day) or Week 2 (200-, 400-mg/day) of treatment. Analysis of individual items of ADHD-related FIs demonstrated that the effect of viloxazine ER was observed across all domains of impairment.Conclusion: Significant improvements observed in ADHD-related FIs are consistent with the reduction in inattention and hyperactivity/impulsivity symptoms demonstrated in the viloxazine ER Phase 3 pediatric trials. Therefore, viloxazine ER provides clinically meaningful improvement of ADHD symptoms and functioning in children and adolescents with ADHD, starting as early as Week 1– 2 of treatment.Keywords: impairment domains, academic performance, behavior, self-esteem

Purpose RBP-7000 (PERSERIS™) is a once-monthly subcutaneous extended-release risperidone formulation approved by the United States Food and Drug Administration for the treatment of schizophrenia in adults. The objective of this study was to describe the long-term impact of RBP-7000 on health-related quality of life (HRQoL), subjective well-being, treatment satisfaction and medication preference in patients with schizophrenia. Patients and methods HRQoL was derived from a 52-week multicentre Phase III single-arm open-label outpatient study that assessed the safety and efficacy of RBP-7000 (120 mg) in patients with schizophrenia. HRQoL was measured using the EuroQol EQ-5D-5L and Short-Form Survey SF-36 version 2; well-being using the Subjective Well-being Under Neuroleptic Treatment - Short Version (SWN-S); satisfaction using the Medication Satisfaction Questionnaire and medication preference using the Preference of Medication questionnaire. Results Of 482 participants at baseline, 234 remained through the end of study (EOS; week 52). Mean HRQoL and well-being scores remained stable between baseline (EQ-5D-5L index: 0.83; SF-36v2 Physical Component Score: 50; SF-36v2 Mental Component Score: 46; total SWN-S score: 89) and EOS (EQ-5D-5L index: 0.86; SF-36v2 Physical Component Score: 49; SF-36v2 Mental Component Score: 47; total SWN-S score: 90). The proportion of participants reporting satisfaction increased between week 4 (66%) and EOS (81%), with a similar trend for the preference of RBP-7000 over previous treatment (week 4: 66%; EOS: 72%). Sensitivity analyses suggested a minor effect of dropout on characterization of change over time in patient-reported outcomes (PRO) measures. Conclusion Study participants attained mean HRQoL scores near that of the general US population. Over two-thirds reported high satisfaction with and preference for RBP-7000 across the study period. Additional research is needed to confirm whether these PRO translate into improved outcomes such as adherence and ultimately fewer relapses in patients with schizophrenia.

Summary Antiretroviral agents with long-acting properties have potential to improve treatment outcomes substantially for people living with HIV. In November 2017, the Long acting/Extended Release Antiretroviral Resource Program (LEAP) convened a workshop with the aim of shaping the research agenda and promoting early development of long-acting or extended release products for key populations: pregnant and lactating women, children aged up to 10 years, and adolescents aged 10–19 years. Goals included strategies and principles to ensure that the needs of children, adolescents, and pregnant and lactating women are considered when developing long-acting formulations. Research should focus not only on how best to transition long-acting products to these populations, but also on early engagement across sectors and among stakeholders. A parallel rather than sequential approach is needed when establishing adult, adolescent, and paediatric clinical trials and seeking regulatory approval. Pregnant and lactating women should be included in adult clinical trials. Adolescent-friendly trial design is needed to improve recruitment and retention of young people.

Over the last several decades, long-acting injections have been studied in order to overcome such problems as low bioavailability in the oral route, the short durations of action in conventional injection, and the poor medication adherence in patients. The authors classified long-acting injections into three categories, namely, molecular modification, nanovehicle carriers, and stimuli-responsive hydrogels. The mechanisms and practical cases of these long acting injectable formulations, including conventional and recent technologies, were described and discussed in this review. Long-acting injection formulations has been proven to be useful from a number of preclinical and clinical studies. Therefore, the long-acting injection technologies can be promising strategy for precision and personalized medicine if the characteristics of formulation such as extended release and the drug-targeting are used appropriately.

Opioids with abuse-deterrent properties may reduce widespread abuse, misuse, and diversion of these products. This study aimed to quantify misuse, abuse, dependence, and health resource use of extended-release morphine sulfate with sequestered naltrexone hydrochloride (ER-MSN; EMBEDA®), compared with non-abuse-deterrent extended-release morphine (ERM) products in Medicaid non-cancer patients.Administrative medical and pharmacy claims data were analyzed for 10 Medicaid states from 1 January 2015, to 30 June 2016. Patients were included if they received a prescription for ER-MSN or any oral, non-abuse-deterrent ERM. Index date was the date of first prescription for an ER-MSN or ERM. Abuse/dependence, non-fatal overdose, emergency department (ED) visits, and ED/inpatient readmissions were determined for each participant. An overall measure of misuse and abuse was also calculated. To account for differences in follow-up, all counts are expressed per 100 patient-years.There were 4,857 patients who received ER-MSN and 10,357 who received an ERM. The average age in the two cohorts was approximately 45 years old. From pre-index to follow-up, the number of patients per 100 patient-years with a diagnosis code indicating abuse or dependence increased by 0.91 (95% confidence interval [CI]: 0.85, 0.97) in the ER-MSN cohort and 2.23 (95% CI: 2.14, 2.32) in the ERM cohort. The number of patients per 100 patient-years with an opioid-related non-fatal overdose increased by 0.05 (95% CI: 0.04, 0.06) in the ER-MSN cohort compared with 0.11 (95% CI: 0.09, 0.13) in the ERM cohort. The opioid abuse overall composite score increased by 1.36 (95% CI: 1.24, 1.48) in the post-index period in the ER-MSN cohort compared to 3.21 (95% CI: 3.10, 3.32) in the ERM cohort.Misuse, abuse, and dependence events were numerically lower in patients receiving ER-MSN compared with those receiving ERM products.

Background A new extended release levodopa capsule (C/L ERC), Rytary®, has demonstrated improved "on" time in fluctuating Parkinson's disease patients, compared to optimally dosed immediate release levodopa. The milligram dosing, however, differs markedly and no empiric ratio or formula for dose conversion currently exists. Objective To determine the most effective conversion strategy from C/L to C/L ERC. Methods We reviewed fluctuating PD patients with problematic "off" time who were converted to C/L ERC using a semi-structured dose titration schedule, and collected data regarding basic efficacy, tolerability, and dosing, in order to determine an empirically based dose conversion formula. We collected demographics, PD historic data, and other medication use. Results Eighty fluctuating PD patients were given C/L ERC samples, 68 took at least one dose [46 male (67.6%), age 66.6±10.3 y], and 62 had adequate data for dose convergence calculations. At a mean follow-up of 119±101 days, [Range: 24-355 days], 43/68 (63.3%) remained on C/L ERC. CGI-I of "much improved" or "very much improved" was reported by 27/62 (43.5%) and dyskinesia scores from the Movement Disorder Society Unified Parkinson's Disease Rating Scale item 4.1, (0-4 range)) tended to improve from 0.9±1.1 to 0.5±0.6, P = 0.08. The mean individual daily ratio was 2.0±0.6 : 1, [range 1.0-3.5]. A lower number of baseline daily L-dopa doses predicted a higher conversion ratio, but pre-conversion dyskinesia did not. Conclusions This retrospective study found that C/L ERC was generally well tolerated and preferred by many patients. The mean total daily conversion ratio is 2 : 1.

Background: Overactive Bladder (OAB) is a debilitating medical condition having the symptoms of urinary frequency and urgency with or without urge incontinence. Tolterodine was the first drug developed specifically for the treatment of OAB. It is a competitive muscarinic antagonist that exhibits similar affinities for muscarinic receptor subtypes M1 to M3. Tolterodine may be a more target specific drug that possesses stronger selectivity for the urinary bladder than for the salivary glands. In a pilot study in healthy volunteers, tolterodine was well-tolerated and showed greater function than on salivation. Objectives: To study the efficacy of tolterodine (ER) in relieving symptoms of overactive bladder with its adverse effects to determine the safety of the drug. Methods: This study was conducted at the Department of Urology, Chittagong Medical College Hospital, Chittagong, Bangladesh, from March, 2014 to June, 2015. Purposive sampling was done. Bladder diary was used for evaluating the symptoms of the patient during baseline and 08 weeks follow up. Perceived level of benefit of the patients was assessed and graded using Likert scale. Data analysis was conducted by SPSS version-21. Results: Out of 80 patients, 19 (23.75%) were male and 62 (76.25%) were female with a male: female ratio 1:3.2. The study revealed that the most of the patients, 48 (60.0%) were subjected to much benefit followed by 23 (28.75%) patients experienced little benefit and 09 (11.25%) patients with no benefit from the treatment. Conclusion: With mild form of side effects tolterodine showed a significant level of efficacy on overactive bladder. Chatt Maa Shi Hosp Med Coll J; Vol.17 (1); Jan 2018; Page 34-37

IMPORTANCE: Patient-reported outcomes in the treatment of opioid dependence may differ between subcutaneously administered depot buprenorphine and daily sublingual buprenorphine. OBJECTIVE: To compare patient satisfaction between depot buprenorphine and sublingual buprenorphine in adult outpatients with opioid dependence. DESIGN, SETTING, AND PARTICIPANTS: This open-label, randomized clinical trial was conducted among adult patients with opioid dependence at 6 outpatient clinical sites in Australia from October 2018 to September 2019. Data analysis was conducted from October 2019 to May 2020. INTERVENTIONS: Participants were randomized to receive treatment with weekly or monthly depot buprenorphine or daily sublingual buprenorphine over 24 weeks. MAIN OUTCOMES AND MEASURES: The primary end point was the difference in global treatment satisfaction, assessed by the Treatment Satisfaction Questionnaire for Medication (TSQM) version 1.4 (range, 0-100; higher score indicates greater satisfaction) at week 24. Secondary end points included other patient-reported outcomes, including quality of life, treatment burden, and health-related outcomes, as well as measures of opioid use, retention in treatment, and safety. RESULTS: A total of 119 participants (70 [58.8%] men; mean [SD] age, 44.4 [10.5] years) were enrolled, randomized to, and received either depot buprenorphine (60 participants [50.4%]) or sublingual buprenorphine (59 participants [49.6%]). From the initial sample of 120, a participant (0.8%) in the sublingual buprenorphine group withdrew consent and did not receive study treatment. All participants were receiving sublingual buprenorphine when enrolled. The mean TSQM global satisfaction score was significantly higher for the depot group compared with the sublingual group at week 24 (mean [SE] score, 82.5 [2.3] vs 74.3 [2.3]; difference, 8.2; 95% CI, 1.7 to 14.6; P = .01). Improved outcomes were also observed for several secondary end points after treatment with depot buprenorphine (eg, mean [SE] treatment burden assessed by the Treatment Burden Questionnaire global score, on which lower scores indicate lower burden: 13.2 [2.6] vs 28.6 [2.5]; difference, −15.4; 95% CI, −22.6 to −8.2; P

Cabenuva-an injectable formulation of cabotegravir and rilpivirine and the first injectable complete therapy for adults with HIV-1-is now approved.It is administered once a month as two intramuscular injections following a month of treatment with the oral forms of these drugs.

Purpose To investigate the contralateral effect of extended release steroid implants on cystoid macular edema (CME). Methods Retrospective study of patients with bilateral CME receiving intravitreal injections of long-acting intravitreal corticosteroid implants. Changes in CME and central subfield thickness (CST) in the contralateral eye on optical coherence tomography (OCT) were compared to an untreated control group. Results Thirteen study patients and 14 controls were included in the study. In the treatment group CST remained stable in all of the patients. Of the controls, CST worsened in 21.4% and remained stable in 78.6%. The mean CST (6.3 ± 30.3 vs. 27.5 ± 66.1 µm, p = 0.2) and the mean macular volume (0.08 ± 0.34 vs. -0.05 ± 0.21 mm3, P = 0.8) were not statistically different between the treatment group and control group. Conclusion In this study there was no statistically significant effect on CME of contralateral intravitreal corticosteroid implants.

Exenatide is used to treat Type 2 Diabetes Mellitus. The current regimen is a 2mg extended release (ER) weekly injection. The aim of our study is to prove the efficacy of exenatide ER if administered once-monthly. Method The proposed monthly dose was based on an excel simulation using pharmacokinetic parameters extracted using Plot Digitizer® (version 2.6.8) from Cirincione et al (Cirincione et al., 2017), as well as accounting for the exenatide ER formulation characteristics, in vivo and in vitro exenatide stability. A PBPK model of exenatide molecule was developed using (Simcyp® version 19) based on data from in vitro and clinical PK studies. The model was used to confirm the excel simulation findings of the effectiveness of the exenatide ER monthly in maintaining the plasma level above the minimum effective concentration (MEC). Results Our simulation from Excel and Simcyp® showed that the drug plasma levels of the ER once monthly dose maintained a steady state concentration (Css) above the MEC. The simulated Excel plasma level was ranging from Cmin to Cmax of 60 - 130ng/L, respectively. The exenatide compound was successfully modeled and used to predict the Css of the ER monthly dose. The Simcyp® simulated Css of the ER was 117ng/L. Conclusions A monthly exenatide ER dose provides a plasma level within the therapeutic range. This new proposed dose has a significant pharmacoeconomic benefit and could as well improve patient adherence. This article is protected by copyright. All rights reserved.

Background Quality of life (QOL) can be significantly impacted by symptoms of overactive bladder (OAB). Vibegron is a highly selective β3‐adrenergic receptor agonist that showed efficacy in treatment of symptoms of OAB in the randomised, double‐blind, placebo‐ and active‐controlled phase 3 EMPOWUR trial. Here we report patient‐reported QOL outcomes from the EMPOWUR trial. Methods Patients were randomly assigned 5:5:4 to receive vibegron 75 mg, placebo or tolterodine 4 mg extended release, respectively, for 12 weeks. Patients completed the OAB questionnaire (OAB‐q) at baseline and at week 12 and the patient global impression (PGI) scales for severity, control, frequency and leakage at baseline and at weeks 4, 8 and 12. Change from baseline at week 12 and responder rates (OAB‐q: patients achieving a ≥10‐point improvement; PGI: patients reporting best possible response) were assessed. Vibegron was compared with placebo, and no comparisons were made between vibegron and tolterodine. Results Of the 1518 patients randomised, 1463 (placebo, n = 520; vibegron, n = 526; tolterodine, n = 417) had evaluable data for efficacy measures and were included in the analysis. Mean baseline OAB‐q and PGI scores were comparable among treatment groups. At week 12, patients receiving vibegron had greater improvements from baseline in OAB‐q subscores of coping, concern, sleep, health‐related QOL total and symptom bother (P

Background. The introduction of carbidopa-levodopa extended-release (CD-LD ER) capsules (Rytary®) did not go as smoothly as expected, largely due to difficulty around dose conversion from available immediate-release (IR) levodopa (LD) formulations. The dose conversion table in the CD-LD ER prescribing information was similar to the table used in the pivotal clinical trial and is considered by many prescribing HCPs to be less than optimal. By the end of the dose conversion period in that trial, dosing in 76% of subjects was adjusted for symptom control; roughly 60% of patients required a higher dose and about half required more frequent administration than the recommended TID dosing. Objective. The primary objective of our nationwide (US) survey was to determine the dose conversion strategy most commonly employed by CD-LD ER frequent prescribers. The survey also aimed to explore additional features regarding CD-LD ER use in clinical practice. Methods. A survey consisting of 21 multiple-choice questions was developed and administered to experts in the use of CD-LD ER, based on prescription volume. Results. Of the 394 HCPs who were invited to participate, 90 (23%) HCPs completed the survey. All respondents were aware of the dose conversion table; the largest group did not find the table to be helpful and did not use it to convert patients to CD-LD ER. The most common strategy in calculating the CD-LD ER dose was based on the total daily LD IR dose, with the majority of that group initiating dose conversion by doubling the total daily LD dose from CD-LD IR and administering CD-LD ER one less time per day. Conclusion. Overall, most survey respondents agreed that a good starting point for CD-LD ER conversion could be doubling the daily LD IR dose and administering it one time less frequently. Moreover, rapid patient follow-up after initial dose conversion to allow for further dose adjustments plays a critical role in achieving success. Gaining experience over time is important for satisfactory conversion.