scholarly journals Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Adult Laboratory Classroom Study of the Efficacy and Safety of PRC-063 (Extended-Release Methylphenidate) for the Treatment of ADHD

2021 ◽  
pp. 108705472110256
Author(s):  
Ann Childress ◽  
Andrew J. Cutler ◽  
Andrea H. Marraffino ◽  
Sailaja Bhaskar ◽  
Graeme Donnelly
Keyword(s):  
Extended Release ◽  
Symptom Relief ◽  
Primary Outcome Measure ◽  
Dose Optimization ◽  
Post Dose ◽  
Double Blind ◽  
Duration Of Action ◽  
T Score ◽  
Laboratory Classroom ◽  
Measure Of Performance

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.

scholarly journals 88 The Efficacy and Safety of Amphetamine Extended-Release Oral Suspension (AMPH EROS) in Children with Attention-Deficit/Hyperactivity Disorder

CNS Spectrums ◽  
2019 ◽  
Vol 24 (1) ◽  
pp. 219-220
Author(s):  
Judith C. Kando ◽  
Thomas King ◽  
Antonio Pardo ◽  
Barry K. Herman
Keyword(s):  
Attention Deficit Hyperactivity Disorder ◽  
Extended Release ◽  
Dose Optimization ◽  
Primary Efficacy ◽  
Primary Efficacy Endpoint ◽  
Efficacy And Safety ◽  
Post Dose ◽  
Double Blind ◽  
Hyperactivity Disorder ◽  
Laboratory Classroom

AbstractOBJECTIVESTo determine the efficacy and safety of amphetamine extended-release oral suspension (AMPH EROS) in the treatment of attention-deficit/hyperactivity disorder (ADHD) compared with placebo in a dose-optimized, randomized, double-blind study.METHODSThe efficacy of AMPH EROS was evaluated in a laboratory classroom study conducted in 108 pediatric patients (aged 6–12 years) with ADHD. The study began with an open-label dose optimization (5weeks) with an initial AMPH EROS dose of 2.5 or 5mg once daily in the morning. The dose could be titrated every 4–7 days in increments of 2.5–10mg until an optimal dose or the maximum dose of 20mg/day was reached. Subjects were required to tolerate a minimal dose of 10mg/day. Subjects then entered a 1-week randomized, double-blind treatment phase with the individually optimized dose or placebo. At the end of the week, raters evaluated the attention and behavior of the subjects in a laboratory classroom using the Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP-C) rating scale. SKAMP-C is a 13-item teacher-rated scale that assesses manifestations of ADHD in a classroom setting.The primary efficacy endpoint was change from pre-dose in the SKAMP-C score at 4hours post dose. The key secondary endpoint efficacy parameters were onset and duration of clinical effect. The change scores from pre-dose SKAMP-C scores at post dose time points (1, 2, 6, 8, 10, 12 and 13hours) were used to evaluate the key secondary efficacy endpoints.RESULTSMore boys (68.7%) than girls participated in the study. The study population was 55.6% white, most patients had inattentive or combined type ADHD presentations. The primary efficacy endpoint, the change from pre-dose SKAMP-C score at 4hours post dose was statistically significantly improved (p<0.0001) compared with placebo. Each of the secondary efficacy endpoints were also significantly improved (p<0.0001 at each time point) compared with placebo. Adverse events reported (frequency >5%) reported during the dose optimization phase were decreased appetite, insomnia, affect lability, upper abdominal pain, mood swings, and headache.CONCLUSIONSAMPH EROS was effective in reducing symptoms or ADHD from 1 to 13hours after dosing. Adverse events reported were consistent with those of other amphetamine products.Funding Acknowledgements: This study was supported by Tris Pharma, Inc.

scholarly journals 87 Efficacy Measures in an Open-label Dose-Optimization of an Amphetamine Extended-Release Oral Suspension in Children with Attention-Deficit/Hyperactivity Disorder

CNS Spectrums ◽  
2019 ◽  
Vol 24 (1) ◽  
pp. 218-219
Author(s):  
Andrew Cutler ◽  
Antonio Pardo ◽  
Thomas R. King ◽  
Judith C. Kando ◽  
Barry K. Herman
Keyword(s):  
Primary Endpoint ◽  
Extended Release ◽  
Rating Scale ◽  
Oral Suspension ◽  
Dose Optimization ◽  
Open Label ◽  
Parent Rating ◽  
Post Dose ◽  
Duration Of Action ◽  
Label Dose

AbstractObjectivesReport the efficacy of open-label amphetamine extended-release oral suspension (AMPH EROS) for the treatment of children with ADHD.AMPH EROS has a 1-hr onset of effect and a duration of action of 13hours and was approved by FDA for treatment of ADHD in children aged 6–17 years based on a double-blind, placebo-controlled efficacy and safety study in children aged 6–12 years with ADHD. A significant treatment difference in change from pre-dose SKAMP-combined score was observed at the primary endpoint of 4hours post-dose (p<0.0001) and each post-dose time point assessed (1, 2, 4, 6, 8, 10, 12, 13hours).Data reported here are from the 5-week, open-label dose optimization period. These efficacy data support the primary endpoint result.MethodsMales and females aged 6 to 12 years with ADHD enrolled and began open-label treatment with 2.5 mg or 5mg/day of AMPH EROS titrated in 2.5–10mg/day increments until optimal dose (maximum 20mg/day). Doses could be decreased for tolerability. Subjects took morning AMPH EROS for 5weeks. Other efficacy outcomes during the open-label dose optimization phase: ADHD-RS (ADHD-Rating Scale), CGI-S (Clinical Global Impression of Severity), CGI-I (CGI-of Improvement) and CPRS (Conners’ Parent Rating Scale). All subjects were assessed for safety.ResultsFor the ITT population (n=99): treatment with AMPH EROS was associated with a mean change in ADHD-RS-IV (baseline to end of the open-label dose optimization; week 6) of 28.2 (±9.03) (Baseline score = 41.3±7.95). 90.9% of subjects had a change from baseline to open-label week 6 of ≥50% in the ADHD-RS-IV total score and were defined as responders. The CGI-S scores decreased continuously from baseline, with a high 4.8 at baseline to a low of 2.0 at open-label week 6. The percentage of subjects classified as moderately ill or greater correspondingly decreased from 97% at Baseline to 1% at open-label week 6. The decrease in the CGI-I over the study was similar to the change in CGI-S scores. CPRS for most categories decreased continuously from Baseline to open-label week 6. Mean change from baseline to open-label week 6 on the CPRS inattention T-score subscale was –25.3 (±14.38) and –24.4 (±13.87).Adverse events (>5%) reported during dose optimization were decreased appetite, insomnia, affect lability, upper abdominal pain, mood swings and headache.ConclusionAMPH EROS was effective in reducing symptoms of ADHD in this open-label dose optimization. The AE profile of AMPH EROS was consistent with those of other amphetamine products.Funding Acknowledgements: This work was funded by Tris Pharma, Inc.

The Time Course of Effect of Multilayer-Release Methylphenidate Hydrochloride Capsules: A Randomized, Double-Blind Study of Adults With ADHD in a Simulated Adult Workplace Environment

2016 ◽  
Vol 24 (3) ◽  
pp. 373-383 ◽  
Author(s):  
Sharon B. Wigal ◽  
Tim Wigal ◽  
Ann Childress ◽  
Graeme A. E. Donnelly ◽  
Joseph L. Reiz
Keyword(s):  
Time Course ◽  
Primary Outcome Measure ◽  
Double Blind Study ◽  
Post Dose ◽  
Double Blind ◽  
Workplace Environment ◽  
Crossover Phase ◽  
Dose Study ◽  
Duration Of Efficacy ◽  
Measure Of Performance

Objective: The aim of this study is to assess the onset and duration of efficacy of multilayer-release methylphenidate (PRC-063) over 16 hr compared with placebo in adults with ADHD using the simulated adult workplace environment. Method: After dose-optimization with PRC-063, participants entered a double-blind, placebo-controlled, crossover phase. Primary outcome measure was the Permanent Product Measure of Performance (PERMP) total score measured pre-dose and from 1 to 16 hr post-dose. Results: Of the 59 randomized participants, 45 participants completed the study. While receiving PRC-063, adults had greater mean PERMP total scores across all time points compared with placebo (268.7 ± 11.24 vs. 255.6 ± 10.87; p = .0064). Common adverse events were decreased appetite, headache, and insomnia. There was no significant impact on overall sleep quality ( p = .9542). Conclusion: PRC-063 significantly improved PERMP scores with an onset within 1 hr post-dose, and maintained improvement throughout the 16 hr post-dose study period compared with placebo in adults with ADHD.

scholarly journals 111 Phase 3, Randomized, Double-Blind, Placebo-Controlled Study (P301) Assessing Efficacy and Safety of Extended-Release Viloxazine in Children with ADHD

CNS Spectrums ◽  
2020 ◽  
Vol 25 (2) ◽  
pp. 272-272 ◽  
Author(s):  
Azmi Nasser ◽  
Joseph T. Hull ◽  
Fatima A. Chowdhry ◽  
Toyin Adewole ◽  
Tesfaye Liranso ◽  
...  
Keyword(s):  
Clinical Global Impression ◽  
Extended Release ◽  
Rating Scale ◽  
Controlled Study ◽  
Average Score ◽  
Efficacy And Safety ◽  
Phase 3 ◽  
Double Blind ◽  
T Score ◽  
Total Average

Abstract:Study Objective:SPN-812 (extended-release viloxazine) is a structurally distinct, bicyclic, Serotonin Norepinephrine Modulating Agent (SNMA) in development as a treatment for attention-deficit/hyperactivity disorder (ADHD) in children and adolescents. This Phase 3, randomized, double-blind study (P301) evaluated the efficacy and safety of once-daily SPN-812 at doses of 100 and 200 mg compared to placebo in children ages 6-11yrs with ADHD.Method:Inclusion criteria required subjects have a confirmed Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) ADHD diagnosis, ADHD-Rating Scale-5 (ADHD-RS-5) score ≥28, a Clinical Global Impression-Severity score ≥4, and be free of ADHD medication ≥1 week before randomization. This investigation was conducted at 34 study sites in the United States. Subjects (N=477) were randomized 1:1:1 to placebo:100 mg SPN-812:200 mg SPN-812. The 6-week treatment period included up to 1 week of titration and 5 weeks of maintenance (intent-to-treat population: N=460; placebo=155, 100 mg=147, 200 mg=158). The primary efficacy endpoint was the change from baseline (CFB) at end of study (EOS) in ADHD-RS-5 total score. Key secondary endpoints included Clinical Global Impression-Improvement (CGI-I) scores at EOS, and CFB at EOS in Conners 3-Parent Short Form (Conners 3-PS) Composite T-score and in Weiss Functional Impairment Rating Scale-Parent Version (WFIRS-P) total average score. Safety assessments included adverse events (AEs), laboratory tests, vital signs, physical exams, electrocardiograms, and the Columbia-Suicide Severity Rating Scale.Results:Compared to placebo, a significantly greater improvement in ADHD-RS-5 total score was observed in the 100 mg and 200 mg SPN-812 treatment groups beginning at week 1 (p=0.0004, p=0.0244; respectively) through EOS (p=0.0004, p<0.0001; respectively). Significant improvement at EOS for both 100 mg and 200 mg SPN-812 compared to placebo was also observed in CGI-I score (p=0.0020, p<0.0001; respectively), Connors 3-PS Composite T-score (p=0.0003, p=0.0002; respectively), and in WFIRS-P total average score (p=0.0019, p=0.0002, respectively). The most common (≥5%) treatment-related AEs reported were somnolence, decreased appetite, and headache.Conclusions:In this study, SPN-812 at 100 mg and 200 mg doses met the primary and secondary objectives with statistical significance. AE-related dropouts were ≤5%, indicating SPN-812 treatment was well tolerated.This study is an encore of a poster presentation at the 2019 Annual Meeting of the American Academy of Child and Adolescent Psychiatry (AACAP).Funding Acknowledgements:This research was funded by Supernus Pharmaceuticals, Inc., Rockville, MD.

scholarly journals 112 A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study (P302): Efficacy and Safety of Extended-Release Viloxazine in Adolescents with ADHD

CNS Spectrums ◽  
2020 ◽  
Vol 25 (2) ◽  
pp. 272-273 ◽  
Author(s):  
Azmi Nasser ◽  
Joseph T. Hull ◽  
Fatima A. Chowdhry ◽  
Toyin Adewole ◽  
Tesfaye Liranso ◽  
...  
Keyword(s):  
Clinical Global Impression ◽  
Extended Release ◽  
Rating Scale ◽  
Controlled Study ◽  
Average Score ◽  
Efficacy And Safety ◽  
Phase 3 ◽  
Double Blind ◽  
T Score ◽  
Total Average

Abstract:Study Objective:SPN-812 (extended-release viloxazine) is a structurally distinct, bicyclic, Serotonin Norepinephrine Modulating Agent (SNMA) in development as a treatment for attention-deficit/hyperactivity disorder (ADHD) in children and adolescents. This Phase 3, randomized, double-blind study (P302) evaluated the efficacy and safety of once-daily SPN-812 at doses of 200 and 400 mg compared to placebo in adolescents ages 12-17yrs with ADHD.Method:Inclusion criteria required subjects have a confirmed Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) ADHD diagnosis, ADHD-Rating Scale-5 (ADHD-RS-5) score ≥28, Clinical Global Impression-Severity score ≥4, and be free of ADHD medication ≥1 week before randomization. This investigation was conducted at 34 study sites in the United States. Subjects (N=310) were randomized 1:1:1 to placebo:200 mg SPN-812:400 mg SPN-812. The treatment period included up to 1 week of titration and 5 weeks of maintenance (intent-to-treat population: N=301; placebo=104, 200 mg=94, 400 mg=103). The primary efficacy endpoint was change from baseline (CFB) at end of study (EOS) in ADHD-RS-5 total score. Key secondary endpoints included Clinical Global Impression-Improvement (CGI-I) score at EOS, and CFB at EOS in Conners 3-Parent Short Form (Conners 3-PS) Composite T-score and Weiss Functional Impairment Rating Scale-Parent Form (WFIRS-P) total average score. Safety assessments included adverse events (AEs), laboratory tests, vital signs, physical exams, electrocardiograms, and the Columbia-Suicide Severity Rating Scale.Results:Compared to placebo, a significantly greater improvement in ADHD-RS-5 total score was observed in the 200 mg and 400 mg SPN-812 treatment group at EOS (p=0.0232, p=0.0091; respectively). Significant improvement in CGI-I score at EOS for both 200 mg and 400 mg SPN-812 compared to placebo was also observed (p=0.0042, p=0.0003; respectively). No significant change was observed at either dose compared to placebo in the Conners 3-PS Composite T-score (p=0.6854, p=0.0518; respectively), or the WFIRS-P total average score (p=0.2062, p=0.0519; respectively). The most common (≥5%) treatment-related AEs were somnolence, decreased appetite, fatigue, headache, and nausea.Conclusions:In this study, SPN-812 met the primary objective for both the 200 and 400 mg doses, and a key secondary objective (CGI-I) for both the 200 and 400 mg doses. AE-related dropouts were ≤5%, indicating SPN-812 treatment was well tolerated.This study is an encore of a poster presentation at the 2019 Annual Meeting of the American Academy of Child and Adolescent Psychiatry (AACAP).Funding Acknowledgements:This research was funded by Supernus Pharmaceuticals, Inc., Rockville, MD.

scholarly journals Efficacy and Safety of Dasotraline in Children With ADHD: A Laboratory Classroom Study

2019 ◽  
Vol 24 (2) ◽  
pp. 192-204 ◽  
Author(s):  
Sharon B. Wigal ◽  
Seth C. Hopkins ◽  
Kenneth S. Koblan ◽  
Ann Childress ◽  
Justine M. Kent ◽  
...  
Keyword(s):  
Symptom Severity ◽  
Test Results ◽  
Efficacy And Safety ◽  
Double Blind ◽  
Once Daily ◽  
Children With Adhd ◽  
Laboratory Classroom ◽  
Classroom Study ◽  
Math Test ◽  
Measure Of Performance

Objective: To evaluate the efficacy and safety of dasotraline for treatment of ADHD in children. Method: Children (ages 6-12 years; N = 112) with ADHD were randomized, double-blind, to 14 days of once-daily evening doses of dasotraline 4 mg or placebo. ADHD symptom severity was measured at baseline and Day 15 in seven, 30-min classroom sessions using the Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) and the Permanent Product Measure of Performance (PERMP) math test. Results: Significant improvement was observed for dasotraline versus placebo in the SKAMP-combined score (−3.2 vs. +2.0; p < .001; effect size = 0.85) and SKAMP and PERMP subscale scores. The three most common adverse events for dasotraline (vs. placebo) were insomnia (19.6% vs. 3.6%), headache (10.7% vs. 8.9%), and decreased appetite (10.7% vs. 3.6%). Conclusion: In this laboratory classroom study, dasotraline 4 mg was found to be an efficacious and generally well-tolerated treatment for ADHD in children aged 6 to 12 years.

scholarly journals 32 Early-Onset Efficacy and Safety Pilot Study of Amphetamine Extended-Release Oral Suspension (AMPH EROS) in the Treatment of Children with Attention-Deficit/Hyperactivity Disorder

CNS Spectrums ◽  
2019 ◽  
Vol 24 (1) ◽  
pp. 191-192
Author(s):  
Ann C. Childress ◽  
Antonio Pardo ◽  
Thomas R. King ◽  
Judith C. Kando ◽  
Barry K. Herman
Keyword(s):  
Pilot Study ◽  
Adverse Events ◽  
Extended Release ◽  
Rating Scale ◽  
Upper Respiratory Tract ◽  
Open Label ◽  
Double Blind ◽  
Hyperactivity Disorder ◽  
Laboratory Classroom ◽  
Open Label Phase

ObjectiveTo determine whether amphetamine extended-release oralsuspension (AMPH EROS) has an onset of effect at 30minutes postdose inchildren with ADHD.MethodsThis randomized, double-blind, 2-treatment, 2-sequence, placebo-controlled crossover pilot study enrolled subjects aged 6 to 12 years withattention-deficit/hyperactivity disorder (ADHD) and ADHD-Rating Scale-5 scores of ≥90th percentile for sex and age. A dose of 5 to 20mg/day of AMPH EROS was determined during a 1-week open-label phase based on medication history, symptom control, and tolerability. Subjects completed a practice laboratory classroom then received one day of double-blind active drug or placebo each in random sequence during 2 double-blind laboratory classroom days. Subjects completed the first double-blind laboratory classroom session, returned to open label drug for 5days then crossed over on day 6 during a second double-blind laboratory classroom session. DB dose was fixed at AMPH EROS 15, 17.5, or 20mg . The primary endpoint was change from predose in the Swanson, Kotkin, Agler, M-Flynn, Pelham rating scale-combined score (SKAMP-C) at 30minutes postdose on two DB days. The key secondary endpoint was change from predose in the SKAMP-C score at 3hours postdose for AMPH EROS compared with placebo. Safety assessments included vital signs and adverse events.ResultsEighteen subjects were enrolled in the study (14 males and 4 females) with a mean age of 9 years. At both 30minutes and 3hours postdose, changes from baseline in SKAMP-C for AMPH EROS vs. placebo were statistically significant (p<0.01 and p=0.0002, respectively) with corresponding effect sizes of 0.96 and 1.57. Adverse events (>10%) during the open-label phase included upper respiratory tract infection, fatigue, upper abdominal pain, headache, decreased appetite, and affect lability.ConclusionsAMPH EROS was effective in reducing ADHD symptoms at 30minutes postdose. AEs were mild or moderate and consistent with those of other extended-release amphetamines.Funding Acknowledgements: Support was provided by Tris Pharma, Inc.

scholarly journals Randomized, Placebo-controlled Crossover Study of Dalfampridine Extended-release in Transverse Myelitis

2017 ◽  
Vol 3 (4) ◽  
pp. 205521731774014 ◽  
Author(s):  
Kateryna Schwartz ◽  
Nicholas F Wymbs ◽  
Hwa Huang ◽  
Maureen A Mealy ◽  
Carlos A Pardo ◽  
...  
Keyword(s):  
Crossover Study ◽  
Extended Release ◽  
Walking Speed ◽  
Transverse Myelitis ◽  
Primary Outcome Measure ◽  
Placebo Control ◽  
Double Blind ◽  
Disability Status ◽  
Study Participants ◽  
To Receive

Background Dalfampridine has the potential to be effective in patients with transverse myelitis (TM) as this rare disorder shares some clinical and pathogenic similarities with multiple sclerosis. Methods This is a randomized, double-blind, placebo-controlled crossover study of dalfampridine extended-release (D-ER, Ampyra®). Sixteen adult study participants with monophasic TM confirmed by MRI were enrolled if their baseline timed 25-foot walking speed was between 5 and 60 seconds. Participants were randomized to receive 10 mg twice-daily doses of either D-ER or placebo control for eight weeks, then crossed over to the second arm of placebo or dalfampridine for eight weeks. The primary outcome measure was the timed 25-foot walk. Results Of 16 enrolled participants, three withdrew and 13 completed the trial. Among the 13 completers, nine individuals showed an average timed walk that was faster in the D-ER arm compared to the placebo arm, but only four participants met the stricter statistical threshold to be classified as a responder. Analyses of secondary clinical outcome measures including strength, balance assessments, spasticity, and Expanded Disability Status Scale (EDSS) score showed trends toward improvement with D-ER. Conclusions D-ER may be beneficial in TM to improve walking speed and other neurological functions.

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