Efficacy and Safety of PRC-063, Extended-Release Multilayer Methylphenidate in Adults with ADHD Including 6-Month Open-Label Extension

Abstract

Objective: To evaluate the efficacy and safety of a 16-hr multilayer-release methylphenidate (PRC-063) in a community-based adult ADHD population. Method: In a double-blind study, 375 participants were randomized to one of four fixed doses of PRC-063 or placebo. The primary outcome was the ADHD-Rating Scale-5 (RS). The first 50% of double-blind completers were invited to participate in a 6-month dose-optimized open-label study to assess response and safety. Results: In total, 333 participants completed the double-blind trial; 184 entered the open-label study. PRC-063 produced greater symptom reduction in ADHD-RS-5 total score from baseline compared with placebo in the double-blind study (least-square [LS] mean = −4.7 [−7.7, −1.6], p = .003). The most frequent adverse events were headache, insomnia, and decreased appetite. No significant sleep quality impact was observed ( p = .123). Significant improvements in ADHD-RS-5 scores from baseline continued through the open-label study ( p < .0001), coincident with dose optimization. Conclusion: PRC-063 was well tolerated and significantly improved ADHD symptomatology in adults.

Randomized Controlled Crossover Trials of the Pharmacokinetics of PRC-063, a Novel Multilayer Extended-Release Formulation of Methylphenidate, in Healthy Adults

“…Compared with placebo, PRC-063 demonstrated significantly greater improvements in ADHD Rating Scale 5 total score. 23 Similar efficacy results were obtained in children aged 12 to 17 years with ADHD (NCT02139111: unpublished data). In the adult study, similar proportions of PRC-063–treated and placebo-treated adult ADHD patients discontinued treatment because of adverse reactions.…”

“…This is higher than the rate of 12% for insomnia-related AEs for IR methylphenidate in study II and higher than the rate of 6% and 12% for initial insomnia for PRC-063 in previously reported clinical trials in adults with ADHD. 23 It should be noted that participants in this PK study received PRC-063 at a daily dose of 100 mg—the highest available dose—whereas patients are individually titrated to their optimal dose. Moreover, the participants were healthy subjects not previously exposed to stimulant treatment, which may have contributed to their sleep problems.…”

“…Insomnia is a common adverse effect of stimulant treatment, 30 and previous clinical trials in adult patients with ADHD have reported higher rates of insomnia during treatment with stimulants versus placebo. 23 , 31 However, evidence suggests that multiple daily dosing may have a greater impact on sleep than long-acting stimulant treatment 32 and that stimulants may improve sleep parameters in some patients with ADHD. 33 , 34 For these reasons, it is anticipated that persistence of PRC-063–derived methylphenidate in the blood until evening would maintain symptom relief without causing significant sleep problems.…”

“…Indeed, randomized, double-blind, placebo-controlled studies in adult ADHD patients have shown no significant impact of PRC-063 on overall sleep quality. 20 , 23 …”

“…In the adult study, similar proportions of PRC-063–treated and placebo-treated adult ADHD patients discontinued treatment because of adverse reactions. 23 …”