Attention Deficit/Hyperactivity Disorder (ADHD - Pediatric)

May 1, 2017

Sunovion Pharmaceuticals reported results of a phase III study of dasotraline evaluated in children 6 to 12 years of age with attention deficit hyperactivity disorder (ADHD). The SEP360-305 study was a two-week, randomized, double-blind, multicenter, placebo-controlled, fixed-dose study comparing dasotraline with placebo in 112 children in the U.S. Dasotraline 4mg or placebo was administered once daily. In this study, children experienced statistically significant and clinically meaningful improvement compared to placebo on the primary endpoint, change from baseline at day 15 in ADHD symptoms as measured by mean Swanson, Kotkin, Agler, M-Flynn and Pelham Scale Combined Score (SKAMP-CS) obtained from an average of seven assessments collected over the 12-hour classroom day, 12 to 24 hours post-dose (least squares [LS] mean change from baseline at day 15: -3.19 [95% CI: -5.06, -1.32] vs 1.99 [0.11, 3.88], respectively; effect size (ES) = 0.85, p<0.0001). Dasotraline maintained significant separation from placebo on the SKAMP-CS over time, 12 to 24 hours post-dose, supporting up to 24-hour duration of effect. Dasotraline 4mg/day was generally well-tolerated with an adverse event profile consistent with completed studies in children and adults. The most common treatment-emergent adverse events (reported in 5% or more of patients and greater than placebo) included insomnia, decreased appetite, affect lability (rapid change in emotion), headache and irritability.

January 23, 2017

Sunovion Pharmaceuticals announced results of a phase II/III study of dasotraline for attention deficit hyperactivity disorder (ADHD). SEP360-202 was a six-week, randomized, double-blind, multicenter, placebo-controlled, parallel-group efficacy and safety trial that compared dasotraline with placebo in children ages 6 to 12 years with a primary diagnosis of ADHD (DSM-5 criteria), ADHD RS-IV HV score of =28 and CGI-S score of =4 at study baseline. Of those enrolled, 342 patients were randomized 1:1:1 to receive dasotraline 2mg/day (n=111) or 4mg/day (n=115), or placebo (n=116) once daily. Patients in the 4mg/day arm started at the 2mg/day dose for the first week of the trial and were increased to 4mg/day at week two. Children taking dasotraline 4mg/day experienced a statistically significant improvement in ADHD symptoms compared to placebo, as measured by the ADHD Rating Scale IV: Home Version (ADHD RS-IV HV) total score (least squares [LS] mean change from baseline at week six: -17.53 [95% CI:-20.12, -14.95] vs -11.36 [-13.89, -8.83], respectively; effect size (ES)=0.48, p<0.001). This statistically significant and clinically relevant improvement over placebo was maintained each week through week six. Improvements in Clinical Global Impression-Severity of Illness Scale (CGI-S) scores were also statistically significant in the 4mg/day dose arm compared to placebo. The 2mg/day dose arm did not demonstrate a statistically significant difference from placebo in the ADHD RS-IV total score and did not statistically separate from placebo in the CGI-S scores. Both dasotraline 4mg and 2mg arms were generally well-tolerated with an adverse event (AE) profile consistent with completed adult dasotraline studies. The most common treatment-emergent adverse events (TEAE) (reported in 5% or more of patients and greater than placebo) included insomnia, decreased appetite and decreased weight. Pending successful completion of ongoing studies and discussions with the FDA, Sunovion intends to submit a New Drug Application (NDA) to the FDA in 2017 for ADHD in children and adults.

April 18, 2016

Shire released results of a phase III, randomized, double-blind, multicenter, placebo-controlled, dose-optimization, safety and efficacy study of SHP465 in children and adolescents aged 6 to 17 years with Attention-Deficit/Hyperactivity Disorder (ADHD). The primary efficacy analysis of study 305 demonstrated that SHP465, administered as a daily morning dose, was superior to placebo on the change from baseline in ADHD-RS-IV (ADHD rating scale) total score, with a Least Squares (LS) mean difference from placebo at Week 4 of -9.9 (95% CI: -13.0 to -6.8, p<0.001), suggesting a significant improvement in ADHD symptoms. SHP465 was also superior to placebo in the key secondary efficacy analysis on the clinical global impression improvement scale (CGI-I), with an LS mean difference from placebo at Week 4 of -0.8 (95% CI: -1.1 to -0.5, p<0.001), indicating a significantly higher proportion of patients were rated improved on the CGI-I rating scale. Treatment-emergent adverse events ≥ 5% for SHP 465-305 were decreased appetite, headache, insomnia, irritability, nausea, weight decrease and dizziness. Adverse events were generally mild to moderate in severity and similar to those observed in previous SHP465 studies and with other amphetamine compounds. Once a pharmacokinetic study and an additional safety and efficacy phase III trial in adults currently under way are complete later this year, Shire plans to add these study results to its existing SHP465 data set to submit a Class 2 resubmission for FDA approval for ADHD.

November 24, 2014

Ironshore Pharmaceuticals & Development issued results of a phase III study of HLD- 200 in pediatric subjects with attention-deficit hyperactivity disorder (ADHD). The trial enrolled 43 pediatric patients aged six to 12. Following a six-week, open-label, treatment-optimization phase, subjects then entered into a doubleblind, placebo-controlled, one-week randomized, parallel-group test period designed to assess the safety and efficacy of HLD-200 treatment. Patients on HLD-200 treatment showed a statistically significant improvement in ADHD symptoms (p<0.0027) compared to placebo over this period. Patients treated with HLD-200 showed a statistically significant improvement at 6:00pm (p=0.0022) and a trend toward significance at 8:00pm (p=0.168). Patients in the HLD-200 group showed a 58.5% improvement relative to their baseline Before School Functioning Questionnaire (BSFQ) scores. There were no serious adverse events throughout the study. The company plans to conduct a pivotal trial in the first half of 2015.

February 1, 2010

Supernus reported positive results from a phase IIa trial of SPN810 for the treatment of ADHD and persistent serious conduct problems. This proof-of-concept, open-label study enrolled pediatrics 6 to 12 years of age. The subjects were randomized according to weight and titrated to receive one of four doses over a six-week treatment period. All doses of SPN810 showed a statistically significant reduction versus baseline in conduct problems, with aggression as a key feature. SPN180 showed reductions of 32% at the lowest tested dose and 55% at the highest tested dose. Treatment was safe and well tolerated.

November 27, 2006

Shire reported positive results from a phase III trial of guanfacine XR for the treatment of ADHD symptoms in pediatrics aged 6 to 17. The double-blind trial enrolled 345 subjects who underwent a one week washout period, then were randomized to receive placebo or 2, 3 or 4 mg of guanfacine extended release, once daily, for eight weeks. Guanfacine XR was titrated in 1 mg increments per week, from 1 mg per day during the first week to a maximum of 4 mg daily in weeks four and five according to randomization. Guanfacine XR was then decreased at the same weekly rate starting in weeks six and seven. Treatment was well tolerated with no serious adverse events reported. The most commonly reported events included somnolence, headache and fatigue. Efficacy was based on ADHD Rating Scale (ADHD-RS-IV) measurements. The guanfacine XR treated group had an average reduction in ADHD-RS-IV total scores of 16.7 points versus 8.9 points for placebo (P < .0001). Significance was observed in all secondary endpoints as well, which included scores on various other ADHD diagnostic scales. A NDA is currently under review for guanfacine extended release.

March 7, 2005

New River Pharmaceuticals has announced results of a phase II trial of NRP104, for the treatment of pediatric Attention Deficit Hyperactivity Disorder (ADHD). Results from the study met their primary efficacy endpoint, with a significant improvement in symptom severity score on the SKAMP (Swanson, Kotkin, Agler, M.Flynn and Pelham) rating scale at all 3 trial doses, vs. placebo (p<0.0001). These results were non-inferior to those observed in subjects receiving approved therapy with Adderall XR, vs. placebo. This double-blind, placebo- and active- controlled, randomized, 3-treatment, 3-period crossover study enrolled 52 children (ages 6-12) with ADHD, who received one of 3 regimens of NRP104, Adderall XR, or placebo.

October 28, 2002

Celltech reported positive preliminary results from a comparative phase IV clinical trial of Metadate (methylphenidate HCl, USP) and McNeil's Concerta (methylphenidate HCl). Both drugs are indicated for the treatment of attention deficit hyperactivity disorder (ADHD). The randomized, double blind, placebo-controlled study consisted of 184 pediatric subjects at 10 sites throughout the U.S. Both drugs were shown to achieve better symptom control than placebo throughout the 7.5-hour observation period. Treatment with Metadate resulted in a 41% greater improvement in symptom scores relative to Concerta during this period. Subjects were evaluated during an actual laboratory classroom day on days 7, 14 and 21. Classroom activities were completed, and a SKAMP deportment evaluation was performed as the primary outcome measure at 1.5-hour intervals until the 7.5-hour time point following dosage administration.

September 23, 2002

Cephalon announced positive results from a four-week randomized, double-blind, placebo-controlled parallel design study of Provigil Tablets for the treatment of Attention Deficit Hyperactivity Disorder (ADHD). 248 subjects between the ages of six and thirteen were assigned to one of four dose regimens of Provigil daily or placebo. The primary efficacy endpoint was the teacher completed school version of the ADHD Rating Scale IV. All of the groups treated with Provigil showed a reduction in symptoms of ADHD with 300 mg of Provigil once a day demonstrating the most significant reduction compared to placebo.

June 10, 2002

Study results show that a once-daily morning dose of Elan and Novartis' Ritalin LA (methylphenidate HCl) extended-release capsules reduces attention deficit/hyperactivity disorder (ADHD) symptoms in both home and school settings. The double-blind, randomized, placebo-controlled trial included 160 ADHD subjects between the ages of six and 12. The presence of ADHD symptoms in school and home environments was evaluated to determine efficacy. In this analysis, the primary outcome was measured by the change from baseline in the Conners ADHD/DSM-IV total subscale for teachers (CADS-T). Results showed that Ritalin LA was statistically superior to placebo in managing ADHD symptoms in all primary and secondary efficacy variables.