Effect of a Multilayer, Extended-Release Methylphenidate Formulation (PRC-063) on Sleep in Adolescents with Attention-Deficit/Hyperactivity Disorder: A Randomized, Double-Blind, Fixed-Dose, Placebo-Controlled Trial Followed by a 6-Month Open-Label Follow-Up.

We analyzed patient-reported sleep parameters for an extended-release methylphenidate formulation (PRC-063) in adolescents with attention-deficit/hyperactivity disorder. Clinical efficacy and long-term safety/tolerability data from a 4-week, double-blind, placebo-controlled, fixed-dose study (NCT02139111) and a subsequent 6-month, optimized-dose, open-label extension (OLE) study (NCT02168127) were used. In the double-blind study, participants were randomly assigned 1:1:1:1:1 to one of four doses of PRC-063 (25, 45, 70, or 85 mg/day) or placebo. In both the double-blind and OLE studies, sleep outcomes were assessed using the Pittsburgh Sleep Quality Index (PSQI). During double-blind treatment, no statistically significant least-squares mean difference in change from baseline between PRC-063 (all doses combined;  = 293) and placebo ( = 74) was found for either global PSQI score (-0.3 vs. -0.5;  = 0.6110) or scores for any of the seven PSQI subscales. Compared with the placebo group, a marginally higher proportion of patients in the PRC-063 group (all doses combined) went from being poor to good sleepers (global PSQI score ≤5; 14.4% vs. 11.3%). In a logistic regression analysis, study treatment was not a predictor of poor sleep ( = 0.5368) at the end of the double-blind study. In the OLE study, there was a trend of improvement in sleep after 1 month of individualized dosing that was maintained through 6 months. Sleep efficiency (time asleep as a proportion of time in bed) showed improvement at the end of the OLE study. While individual patients may experience changes in sleep as an adverse event, group data evaluating sleep as an outcome found there were no differences between PRC-063 and placebo in self-reported sleep outcomes on the PSQI.