Tramadol Hydrochloride Extended-Release Once-Daily in the Treatment of Osteoarthritis of the Knee and/or Hip: A Double-Blind, Randomized, Dose-Ranging Trial

AbstractObjectiveAssess cardiovascular effects of once-daily mixed amphetamine salts extended release (MAS XR) in adolescents (13–17 years of age) with attention-deficit/hyperactivity disorder (ADHD).MethodsBlood pressure (BP), pulse, and electrocardiograms were assessed in 327 healthy subjects during a 4-week, randomized, double-blind, placebo-controlled, forced dose-titration study. Placebo (n=69) or once-daily MAS XR(10, 20, 30, or 40 mg) was administered to subjects ≤75 kg (n=233); 50- and 60-mg MAS XR was administered to subjects >75 kg (n=25). One hundred thirty-eight subjects participated in a 6-month, open-label extension study.FindingsChanges in BP and QTcB (Bazett's formula) intervals at 4 weeks with MAS XR were not significantly different from the placebo group. Pulse increased by 5.0 and 8.5 bpm after 3 weeks with MAS XR 20 and 50 mg/day, respectively (P≤.002). After 6 months of open-label MAS XR treatment, mean increases in systolic BP (1.7 mm Hg; P=.0252) and pulse (4.4 bpm; P<.0001) were statistically, but not clinically, significant diastolic BP was not significantly changed (0.6 mm Hg) A decrease in QTcB interval (-4.6±19.9 msec) was statistically (P=.009), but not clinically, significant. There were no serious cardiovascular adverse events.ConclusionCardiovascular effects of short- and long-term MAS XR treatment (≤60 mg/day) were minimal in otherwise healthy adolescents with ADHD.

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Safety and efficacy of ADS-5102 (amantadine) extended release capsules to improve walking in multiple sclerosis: A randomized, placebo-controlled, phase 2 trial

Multiple Sclerosis Journal ◽

10.1177/1352458518754716 ◽

2018 ◽

Vol 25 (4) ◽

pp. 601-609 ◽

Cited By ~ 3

Author(s):

Jeffrey A Cohen ◽

Samuel F Hunter ◽

Theodore R Brown ◽

Mark Gudesblatt ◽

Ben W Thrower ◽

...

Keyword(s):

Multiple Sclerosis ◽

Extended Release ◽

The United States ◽

Timed Up And Go ◽

Double Blind ◽

Once Daily ◽

Safety And Efficacy ◽

Phase 2 Trial ◽

Minute Walk

Background: Walking impairment causes disability and reduced quality of life in patients with multiple sclerosis (MS). Objective: Characterize the safety and efficacy of ADS-5102 (amantadine) extended release capsules, 274 mg administered once daily at bedtime in patients with MS with walking impairment. Methods: This randomized, double-blind, placebo-controlled, 4-week study was conducted at 14 trial sites in the United States. Study objectives included safety and tolerability of ADS-5102, and efficacy assessments (Timed 25-Foot Walk (T25FW), Timed Up and Go (TUG), 2-Minute Walk Test, and Multiple Sclerosis Walking Scale-12). Fatigue, depression, and cognition also were assessed. Results: A total of 60 patients were randomized (30 to ADS-5102 and 30 to placebo); 59 of whom were treated. The most frequent adverse events (AEs) were dry mouth, constipation, and insomnia. Five ADS-5102 patients and no placebo patients discontinued treatment due to AEs. One patient in the ADS-5102 group experienced a serious AE—suspected serotonin syndrome. A 16.6% placebo-adjusted improvement was seen in the T25FW test ( p < 0.05). A 10% placebo-adjusted improvement in TUG was also observed. No changes in fatigue, depression, or cognition were observed. Conclusion: ADS-5102 was generally well tolerated. These data demonstrate an effect of ADS-5102 on walking speed. Further studies are warranted to confirm these observations.

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A Double-Blind, Randomized Study of Extended-Release Molindone for Impulsive Aggression in ADHD

Journal of Attention Disorders ◽

10.1177/1087054720909084 ◽

2020 ◽

pp. 108705472090908 ◽

Cited By ~ 1

Author(s):

Gianpiera Ceresoli-Borroni ◽

Azmi Nasser ◽

Toyin Adewole ◽

Tesfaye Liranso ◽

Jiahong Xu ◽

...

Keyword(s):

Extended Release ◽

Low Dose ◽

Behavioral Therapy ◽

Randomized Study ◽

High Dose ◽

Double Blind ◽

Impulsive Aggression ◽

Pediatric Populations ◽

Dose Ranging ◽

Medium Dose

Objective: To evaluate efficacy and safety of SPN-810 (extended-release molindone) in a Phase-2b, randomized, double-blind, placebo-controlled, dose-ranging study of children (6–12 years) with ADHD and persistent impulsive aggression (IA). Method: After lead-in, children were randomized to (a) placebo ( N = 31); (b) low-dose ( N = 29, 12/18 mg/day); (c) medium-dose ( N = 30, 24/36 mg/day); and (4) high-dose ( N = 31, 36/54 mg/day) groups. Treatment included ~2.5-week titration, 3-week maintenance, and 1-week tapering/conversion, alongside existing monotherapy (stimulants/nonstimulants) and behavioral therapy. The primary endpoint was change in Retrospective-Modified Overt Aggression Scale (R-MOAS) score at end of study, with safety monitored. Results: A total of 95 (78.5%) children completed the study. Aggression (R-MOAS) improved with low and medium doses (low dose: p = .031; medium dose: p = .024; high dose: p = .740). The most common adverse events were headache (10.0%), sedation (8.9%), and increased appetite (7.8%). Conclusion: These results suggest SPN-810 may be effective in reducing residual IA behaviors in children with ADHD. Research is still needed to support the benefit–risk profile of SPN-810 in pediatric populations.

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A randomized, 29-day, dose-ranging, efficacy and safety study of daprodustat, administered three times weekly in patients with anemia on hemodialysis

BMC Nephrology ◽

10.1186/s12882-019-1547-z ◽

2019 ◽

Vol 20 (1) ◽

Cited By ~ 4

Author(s):

Christine K. Bailey ◽

Stephen Caltabiano ◽

Alexander R. Cobitz ◽

Chun Huang ◽

Kelly M. Mahar ◽

...

Keyword(s):

Dose Range ◽

Hypoxia Inducible Factor ◽

Conversion Ratio ◽

Controlled Study ◽

Efficacy And Safety ◽

Double Blind ◽

Once Daily ◽

Human Erythropoietin ◽

Dose Ranging ◽

Baseline Hemoglobin

Abstract Background Daprodustat is a hypoxia-inducible factor-prolyl hydroxylase inhibitor currently being investigated as a treatment for anemia of chronic kidney disease (CKD) in both dialysis and nondialysis patients. In clinical studies to date, daprodustat has been administered orally as a once-daily regimen. This randomized, double-blind, placebo-controlled study characterized the initial dose-hemoglobin response as well as the efficacy and safety of three times weekly (TIW) daprodustat in hemodialysis patients switched from stable recombinant human erythropoietin (rhEPO), in accordance with a TIW hemodialysis schedule. Methods 103 patients on hemodialysis with baseline hemoglobin of 9.0 to 11.5 g/dL and previously receiving a stable dose of rhEPO or its analogs were randomized 1:1:1:1:1 to receive daprodustat 10, 15, 25, or 30 mg or placebo TIW over 29 days. Results Mean baseline hemoglobin was 10.6 g/dL for the placebo group and each daprodustat cohort. Daprodustat produced dose-dependent changes in mean hemoglobin from baseline to day 29. Using a Bayesian approach, the estimated dose conversion ratio between once-daily and TIW daprodustat was ~ 2.0 across the evaluated dose range using an Emax model. Daprodustat was generally well tolerated, with an adverse event (AE) profile consistent with the hemodialysis population. Conclusions These data help inform the appropriate dose conversion ratio to be applied to daily doses to obtain equivalent daprodustat TIW doses and suggest TIW treatment with daprodustat can treat anemia of CKD safely, supporting future long-term studies for this indication using a TIW dosing regimen. Trial registration ClinicalTrials.gov Identifier: NCT02689206; date registered: 02/11/2016.

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Randomized, double-blind, multicenter evaluation of pramipexole extended release once daily in early Parkinson's disease

Movement Disorders ◽

10.1002/mds.23317 ◽

2010 ◽

Vol 25 (15) ◽

pp. 2542-2549 ◽

Cited By ~ 57

Author(s):

Robert A. Hauser ◽

Anthony H.V. Schapira ◽

Olivier Rascol ◽

Paolo Barone ◽

Yoshikuni Mizuno ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Extended Release ◽

Double Blind ◽

Once Daily ◽

Early Parkinson’S Disease

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6.22 A Double-Blind, Placebo-Controlled, Dose-Ranging Study of Extended-Release Viloxazine (SPN-812 ER) in Children With Attention-Deficit/Hyperactivity Disorder (ADHD)

Journal of the American Academy of Child & Adolescent Psychiatry ◽

10.1016/j.jaac.2017.09.367 ◽

2017 ◽

Vol 56 (10) ◽

pp. S283-S284

Author(s):

Janet K. Johnson ◽

Keith Saylor ◽

Scott T. Brittain ◽

Gabriela Tulloch ◽

Tesfaye Liranso

Keyword(s):

Attention Deficit Hyperactivity Disorder ◽

Attention Deficit ◽

Extended Release ◽

Double Blind ◽

Double Blind Placebo ◽

Hyperactivity Disorder ◽

Dose Ranging

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Efficacy and tolerability of quetiapine XR 400/600/800mg/day in acute schizophrenia: a post-hoc analysis of data from two pooled randomised studies

European Psychiatry ◽

10.1016/s0924-9338(11)73116-9 ◽

2011 ◽

Vol 26 (S2) ◽

pp. 1411-1411

Author(s):

R. Kahn ◽

A. Kalali ◽

U. Gustafsson ◽

S. Nyberg

Keyword(s):

Dose Response ◽

Extended Release ◽

Efficacy And Safety ◽

Double Blind ◽

Once Daily ◽

Quetiapine Fumarate ◽

Post Hoc Analysis ◽

Response Efficacy ◽

Quetiapine Xr ◽

Post Hoc

IntroductionData from two, identically designed, placebo-controlled, randomised, double-blind clinical trials (D1444C00132+D1444C00133) for once-daily extended-release quetiapine fumarate (QTP-XR) were pooled and analysed.ObjectiveEvaluate dose response, efficacy and safety for QTP-XR in schizophrenia.MethodsPost-hoc analysis of data from patients receiving QTP-XR 400, 600, 800 mg/day or placebo. Endpoints: least squares means (LSM) change from baseline to Day 42 in PANSS total and positive and negative subscale scores. No corrections for multiplicity were performed. Adverse events (AEs) were recorded.Results914 patients were included; PANSS scores were assessed in the MITT population (n = 889). LSM change from baseline in PANSS total score diverged significantly from placebo at: Day 14 for QTP-XR 800 mg/day (-15.3 vs -12.1 for placebo; p = 0.018); Day 21 for 600 mg/day (-17.3 vs -14.2; p = 0.039); Day 42 for 400 mg/day (-19.2 vs -15.4; p = 0.033).Jonckheere-Terpstra analysis of change in PANSS total score at Day 42 showed a significant QTP-XR dose response (p = 0.0196; p < 0.001 with placebo). PANSS positive scores diverged by Day 21 for both QTP-XR 800 (-5.7 vs -4.8; p = 0.049) and 600 mg/day (-5.8 vs -4.8; p = 0.046). PANSS negative scores diverged by Day 21 (-4.0 vs -3.2; p = 0.040) and 42 (-4.8 vs -3.6; p = 0.009) for QTP-XR 800 and 600 mg/day, respectively. AEs occurred in 59.4%, 66.5%, 62.1% and 56.2% of patients in the QTP-XR 800, 600, 400 mg/day and placebo groups, respectively. Most common AEs were somnolence, dry mouth, sedation, insomnia, dizziness, headache, constipation and nausea.ConclusionsQTP-XR was generally well tolerated and demonstrated efficacy that increased with dose in schizophrenia.Financial support: AstraZeneca.

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