The Single-Dose Pharmacokinetics of NWP06, a Novel Extended-Release Methylphenidate Oral Suspension

Abstract

Objective: To determine the single-dose pharmacokinetics of 60 mg NWP06, a novel extended-release (ER) liquid formulation of methylphenidate (MPH) compared with 30 mg immediate-release (IR) liquid MPH, dosed at Hours 0 and 6, in adults. Methods: After institutional review board approval, 30 healthy subjects aged 18 to 68 years were enrolled in this open-label, crossover study and randomly assigned to receive NWP06/IR MPH after an overnight fast. Blood samples were collected prior to dose at Hour 0 and at post-dose hours 0.5, 1, 1.33, 1.67, 2, 2.5, 3, 4, 5, 6, 6.5, 7, 7.33, 7.67, 8, 8.5, 9, 10, 12, 14, 16, 24, and 36. Plasma concentrations of d- and l-MPH were determined and pharmacokinetic parameters were calculated. Safety assessments included vital signs, electrocardiogram, laboratory evaluations, adverse event (AE) collection, and suicidality assessment. Results: Twenty-eight subjects completed the study. The AUC0-∞ of d-MPH for NWP06 and IR MPH were 143.65 and 153.31 ng-hr/mL, respectively. The peak plasma concentration, Cmax (ng/mL), was 13.61 for NWP06 and 20.94 for IR MPH. The half-life of NWP06 was 5.65 hours and Tmax was 5 hours. For IR MPH, the half-life was 3.74 hours and Tmax was 7.33 hours. Vital sign changes were in the expected range for MPH and there were no clinically significant laboratory or ECG changes. The most common AEs reported were headache, dizziness, palpitations, nausea, and nervousness. Conclusions: A single dose of 60 mg NWP06 is equally bioavailable to two 30-mg doses of IR MPH. NWP06 has a lower peak concentration than IR MPH. Both study treatments were well tolerated, as all AEs were rated as mild in this healthy adult population.