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

PURPOSE/BACKGROUND: PRC-063 is a once-daily, extended-release oral formulation of methylphenidate hydrochloride developed to provide early and prolonged symptom improvement in patients with attention-deficit/hyperactivity disorder. METHODS/PROCEDURES: We conducted 3 randomized, open-label crossover studies of the pharmacokinetics of PRC-063 in healthy, nonobese men and women aged 18 to 45 years. PRC-063 (100 mg/d) was compared with immediate-release methylphenidate (20 mg, 3 times daily) when administered on a single day under fasted and fed conditions and at steady state (day 5 of repeat dosing under fasted conditions). The pharmacokinetics of PRC-063 administered as capsule contents sprinkled on apple sauce, yoghurt, or ice cream were also investigated. FINDINGS/RESULTS: PRC-063 demonstrated biphasic absorption, with 2 distinct peak plasma concentrations. Intake of a high-fat, high-calorie meal did not increase the peak plasma methylphenidate concentration (C(max)) or extent of absorption (area under the curve), however; it resulted in slower uptake versus a fasted state. During repeated dosing, steady state was reached with no further accumulation of methylphenidate from day 3. At steady state, PRC-063 gave higher evening and trough plasma methylphenidate levels than immediate-release methylphenidate (3 times daily). The pharmacokinetics of PRC-063 sprinkled on food were comparable to that of intact capsules. Reported adverse events (AEs) were consistent with the established safety profile of methylphenidate. There were no serious AEs, but 3 subjects discontinued the repeat-dosing study because of AEs assessed as possibly related to study treatment. IMPLICATIONS/CONCLUSIONS: Our data indicate that PRC-063 can be taken with or without food or by sprinkling capsule contents on food.