Effect of a Multi-Layer, Extended-Release Methylphenidate Formulation (PRC-063) on Sleep in Adults with ADHD: A Randomized, Double-Blind, Forced-Dose, Placebo-Controlled Trial Followed by a 6-month Open-Label Extension

BACKGROUND: The effects of stimulant treatment on sleep in adults with attention-deficit/hyperactivity disorder (ADHD) are complex and varied, with some individuals experiencing worsening of sleep but others experiencing improvement. METHODS: Data from previously reported trials of the clinical efficacy and safety of the long-acting methylphenidate formulation PRC-063 (Adhansia XR(®) in the USA; Foquest(®) in Canada) in adults with ADHD were used to evaluate patient-reported sleep outcomes, as captured using the Pittsburgh Sleep Quality Index (PSQI) and adverse events of insomnia. The trials comprised 4 weeks of randomized, forced-dose PRC-063 treatment at a dose of 0 (placebo), 25, 45, 70, or 100 mg/day followed by an optional 6 months of open-label PRC-063 treatment at an individually optimized dose of 25–100 mg/day. RESULTS: At the end of double-blind treatment, PRC-063 (all doses combined; N = 297) showed no significant difference versus placebo (N = 78) in least squares mean change in global PSQI score from baseline (− 0.7 vs. − 1.3; P = 0.0972) or in scores for each of the seven subscales of the PSQI. For patients enrolled in the open-label extension (N = 184), mean ± standard deviation global PSQI score improved from 7.8 ± 3.55 at the end of double-blind treatment to 5.8 ± 3.11 at 1 month and 5.4 ± 3.21 at 6 months (P < 0.0001). A greater proportion of patients were good sleepers (global PSQI score ≤ 5) at the end of the open-label extension (57.3%) than at baseline (20.9%) or at the end of double-blind treatment (26.0%). In a logistic regression analysis, baseline global PSQI score (odds ratio 1.491; P < 0.0001), but not randomized study treatment (P = 0.1428), was a significant predictor of poor sleep (global PSQI score > 5) at the end of double-blind treatment. Adverse event rates for insomnia (15.8 vs. 3.8%) and initial insomnia (6.1 vs. 1.3%) during double-blind treatment were higher for PRC-063 (all doses combined) than for placebo. Two patients receiving PRC-063 in the double-blind study and one patient in the open-label study were withdrawn because of insomnia adverse events. CONCLUSIONS: Our findings indicate that, on average, PRC-063 had no significant impact on overall sleep quality in adults with ADHD. Although insomnia was observed as an adverse event, when sleep was measured over time as an outcome in its own right for patients receiving dose-optimized PRC-063 open-label, more patients showed improvement in sleep than deterioration. CLINICALTRIALS.GOV IDENTIFER: NCT02139124 and NCT02168127. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40263-021-00814-z.