6.49 PHARMACOKINETICS OF A NOVEL, EXTENDED-RELEASE FORMULATION OF METHYLPHENIDATE (PRC-063) IN ADOLESCENTS WITH ATTENTION-DEFICIT/HYPERACTIVITY DISORDER AND IN HEALTHY ADULTS AT STEADY STATE

Objectives: Two studies sought to compare the pharmacokinetics of PRC- 063 with immediate-release methylphenidate (IR MPH): Study A a single-dose crossover study in adolescents with ADHD; and Study B a 5-day steady-state crossover study in healthy adults. Methods: Study A involved adolescents (12-17 years) with a DSM-5 diagnosis of ADHD and receiving a stable dose of MPH. Subjects took a single daily dose of PRC-063 or IR MPH (tid) that was approximate to their pre-study dose. Plasma samples were collected prior to dosing and at 0.5 through to 30 h post-dose. Study B involved healthy adults 18 years of age or older. Subjects received either 100mg of PRC-063 or 60mg of IR MPH (20mg tid) for 5 days. Plasma samples were collected prior to dosing at Day 1, 3, 4 and 5, and on Day 5 at 0.5 through to 36 hours post-dose. Results: Study A enrolled 17 patients (3 female, 14 male, age 14.0±1.0 yrs). The mean daily dose was 62.9 mg/day of PRC-063 and 54.7 mg/day of IR MPH. For d-methylphenidate non-dose-normalised data, the ratios of leastsquares means of PRC-063:IR MPH for ln-transformed AUC0-t, AUC0-inf and Cmax were 96.66%, 100.76% and 67.06%, respectively. Residual levels of MPH at 24 h post dose were 3.28 ng/mL for PRC-063 and 0.53 ng/mL for IR MPH. Study B enrolled 21 subjects (9 female, 12 male, age 32±8 yrs). There were two distinct peak plasma levels of MPH for PRC-063 (1.5 and 12 h post dose) and three for IR MPH (2, 5.5 and 10 h post dose). Fluctuation Index was 131.5±31.9% for PRC-063 and 243.53±34.0% for IR MPH. For d-methylphenidate dose-normalised data, the ratios of least-squares means of PRC-063:IR MPH for AUC0-24, Cmax and Cmin were 88.57 percent, 59.35 percent and 274.15 percent, respectively. Steady-state was achieved for PRC-063 by Day 3. No new safety signals were identified in these studies. Conclusions: In both studies, the extent of absorption was comparable between PRC-063 administered as a single dose and IR MPH administered three times; however, the rate of absorption was lower for PRC-063. No evidence of unusually rapid release was observed compared to IR MPH. PRC-063 provides a once-daily alternative to tid administration of MPH with less peak to trough fluctuation and higher plasma levels from hour 12 to the end of the day.