Attention Deficit/Hyperactivity Disorder (ADHD - Adults)

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.

December 3, 2012

Supernus Pharmaceuticals reported results from a phase IIb trial of SPN-810 for the treatment of impulsive aggression in attention deficit and hyperactivity disorder (ADHD). This multi-center, randomized, double-blind, placebo-controlled study enrolled 121 patients ages six to 12 diagnosed with ADHD and characterized by impulsive aggression that was not controlled by optimal stimulant and psychosocial treatment. Subjects received low, medium or high doses of SPN-810, or placebo. Results showed that for all patients, low and medium doses of SPN-810 met the efficacy endpoint of rate of remission of aggression and showed statistical significance versus placebo with p-values of 0.009 and 0.043 and percent of patients with R-MOAS remission of 51.9% and 40.0%, respectively. The low and medium doses showed a reduction in score for the R-MOAS of 62.6% and 57.9%, respectively, with p-values of 0.071 and 0.115. For patients of 30kg or more in weight, the low and medium doses of SPN-810 showed statistical significance versus placebo on the change in R-MOAS primary endpoint with p-values of 0.024 and 0.049, and high percent reduction in the R-MOAS scores of 80.9% and 75.2%, respectively. The drug well tolerated. Based on these data, Supernus Pharmaceuticals will meet with the FDA to discuss the design and protocol for a phase III trial of SPN-810 in impulsive aggression in ADHD.

September 12, 2011

Teva Pharmaceuticals and Alcobra reported results from a phase II trial of MG01CI for adults with attention deficit hyperactivity disorder. This six-week randomized, double-blind, placebo-controlled study enrolled 120 subjects who received 1400 mg of MG01CI or placebo. MG01CI met the primary efficacy outcome, demonstrating a significant improvement on the Conners' Adult ADHD Rating Scale-Investigator Rated Total ADHD Symptoms Score (CAARS-INV) compared to placebo. In the MG01CI treatment arm, 56% of subjects experienced an improvement in their CAARS-INV score of at least 25 percent, compared to 36% of subjects in the placebo arm (p<0.03). In addition, 44% of the subjects treated with MG01CI demonstrated an improvement of more than 40 percent in their CAARS-INV score versus 25% in treated with placebo (p<0.04). MG01CI was well tolerated, with no drug-related serious adverse events.

August 1, 2011

Chelsea Therapeutics reported preliminary results from a phase II trial of droxidopa in combination with carbidopa for adults with attention deficit hyperactivity disorder (ADHD). Following six weeks of open-label treatment with droxidopa and carbidopa, 20 subjects were randomized into a two-week double-blind, placebo-controlled withdrawal period. The mean baseline ADHD Investigator Symptom Rating Scale (AISRS) score was 34. After three weeks of open-label droxidopa monotherapy (titration from 200mg-600mg TID), the mean AISRS score decreased by approximately 47% to 19 (p<0.0001). The reduction in AISRS score was maintained with the addition of carbidopa (25mg or 50mg) for another three weeks. Eleven subjects continued into the two-week withdrawal period. The subjects withdrawn to placebo after prolonged droxidopa treatment continued to experience therapeutic benefits. However, no statistically significant difference was observed between treatment and placebo arms at the end of the two-week randomized period. Droxidopa was well tolerated with no serious adverse events observed.

November 5, 2007

Shire reported positive results from a phase III trial of Vyvanse for the treatment of adult Attention Deficit Hyperactivity Disorder (ADHD). This double-blind, placebo-controlled, four-week study enrolled 414 adult subjects who received Vyvanse (30 mg, 50 mg, 70 mg) or placebo. All doses of Vyvanse showed improvements in the average change in the ADHD rating scale scores as measured from baseline to the end of treatment. The reduction in scores ranged from 16.2 to 18.6 points. Improvements on the Clinical Global Impressions-Improvement (CGI-I) scale were also observed, with 57% to 61% rated improved across all doses. Treatment was well tolerated, with all adverse events mild to moderate in nature. An sNDA is currently under review by the FDA for this indication.

November 6, 2006

Shire issued positive results from two phase III trials, dubbed study 201 and 203, of Adderall XR (SDP465) for the treatment of adult Attention Deficit/Hyperactivity Disorder. In both trials subjects received Adderall XR or placebo at doses of 25, 50 or 75 mg during three, seven day treatments. Subjects were tested on improvements in ADHD symptoms, as measured by the Permanent Product Measure of Performance (PERMP) and ADHD Rating Scale scores at 5.5, 11 and 16.5 hours post treatment. Results revealed that treatment with Adderall XR led to significantly higher scores than placebo on both measurements at all test times (P < .0001). A NDA for this indication is currently under review by the FDA.

May 30, 2005

New River Pharmaceuticals has announced positive results of a phase III trial of NRP104, their amino- acid-conjugated stimulant under investigation for the treatment of pediatric attention deficit hyperactivity disorder (ADHD). Trial data met both primary and secondary efficacy endpoints, with all trial doses producing significant improvements in symptom severity score on both the ADHD Rating Scale and the Conners' Parent Rating System, vs. placebo (p<0.0001). Overall safety and tolerability profiles were considered positive and predictable. This randomized double-blind, placebo-controlled study enrolled 285 pediatric ADHD patients ages 6-12 across 45 sites, who received one of three oral doses of NRP104 or placebo. The company announced that these results would serve to support NDA filing by the end of 2005.

Shire Pharmaceuticals has issued combined results of a pair of phase III trials of Equetro (carbamazepine ER), for the treatment of refractory bipolar I disorder at the Annual Meeting of the American Psychiatric Association. Equetro was approved for this indication in December 2004. The pooled data have indicated that the drug was efficacious in improving manic symptom severity score on the Young Mania Rating Scale (YMRS). Specifically, subjects refractory to valproate who received Equetro experienced a mean score reduction of 10.8 points, vs. 5.7 points for placebo (p=0.04); subjects refractory to lithium experienced a mean score reduction of 11.6 points on Equetro, vs. 4.0 points for placebo (p=0.03). The pooled analysis of these randomized double-blind, placebo-controlled studies considered data from 115 subjects.

May 26, 2003

Cephalon reported positive results from two-phase II trials investigating Provigil (modafinil), a previously approved wake-promoting agent for the new indication of attention deficit/hyperactivity disorder (ADHD). During one 4-week study, 248 children with ADHD were randomized to Provigil in different combinations of 300 mg doses or placebo. Results showed that the 300 mg regimen of Provigil significantly improved symptoms as measured by the teacher- rated ADHD Rating scale. In a second four-week double blind, placebo-controlled, crossover study, 48 children were randomized to receive placebo or Provigil 100, 200, 300, or 400 mg. The most significant improvements were seen in subjects receiving the 300 or 400 mg dose of Provigil as assessed in the home environment by the parent-rated ADHD Rating Scale.

Sepracor reported positive results from a phase III trial investigating Estorra (eszopiclone), a non-benzodiazepine compound for the treatment of insomnia. Results showed that the eszopiclone arm demonstrated statistically significant improvements in sleep maintenance measures, sleep latency, total sleep time and sleep quality relative to placebo. Data showed no evidence of tolerance was observed over the course of the trial and eszopiclone was well tolerated. The randomized, multi-center, placebo-controlled study enrolled 788 subjects 21-69 years of age with chronic insomnia. Subjects received nightly treatment of either eszopiclone or placebo (3 mg) for 6 months. The results were presented at the American Psychiatric Association meeting in San Francisco.

February 3, 2003

Celltech Pharmaceuticals reported positive results from a phase IV trial investigating Metadate CD, a biphasic formulation of methylphenidate for the treatment of Attention Deficit Hyperactivity Disorder (ADHD). Results showed that 71% of subjects, previously treated with standard medications, rated Metadate CD as better or much better than previous treatments. A total of 65% of subjects were classified as responders to Metadate CD, which was defined as much improved or very much improved on the Clinical Global Impression (CGI) scale. Treatment related adverse events occurred in 27 % of subjects, with the most commonly reported event being headache, stomachache, insomnia and loss of appetite.