Comparative fasting bioavailability of dispersible and conventional tablets of risperidone: a single-dose, randomized-sequence, open-label, two-period crossover study in healthy male Chinese volunteers

Abstract

Background: Risperidone (RIS), an atypical antipsychotic drug, is used for the treatment of psychoses associated with schizophrenia and other psychiatric disorders in adult and pediatric populations. An oral dispersible tablet formulation of risperidone has been developed. This study was conducted to provide support for marketing authorization of this drug in China.

Objective: This study was designed to compare the pharmacokinetic (PK) properties and bioavailability of 2 RIS formulations-the dispersible formulation (test) and a branded formulation (reference) in healthy male Chinese volunteers.

Methods: This single-dose, randomized-sequence, open-label, 2-period crossover study involved 22 healthy male Chinese volunteers. Equal numbers of eligible participants were randomly assigned to receive either the test drug (2 mg) or the same dose of the reference formulation, followed by a 2-week washout period and administration of the alternate formulation. The study drugs were administered after a 10-hour overnight fast. Blood samples were collected before dosing and at 0.33, 0.67, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 15, 24, 36, 48, 72, and 96 hours after dosing. Plasma concentrations of RIS and its active metabolite, 9-hydroxyrisperidone (9-OH-RIS), were measured using LC-MS/MS. The safety profile was evaluated by recording adverse events (AEs), assessed using physical examination including vital signs, spontaneous reporting, and clinical laboratory results. The 2 formulations were considered to have met the requirements for bioequivalence if the 90% CIs for the log-transformed C(max) and AUC values were within the predetermined ranges of 75% to 133% and 80% to 125%, respectively, according to the guidelines of the State Food and Drug Administration (SFDA) of China.

Results: All 22 volunteers (mean [SD] age, 22.2 [1.98] years; weight, 64.07 [5.93] kg; height, 173 [5] cm; and body mass index, 21.2 [1.67] kg/m(2)) that were enrolled completed the study. For RIS, the 90% CIs for the ratios of C(max), AUC(0-t), and AUC(0-∞) were 93.2% to 116.7%, 97.9% to 111.3%, and 98.0% to 111.6%, respectively. For 9-OH-RIS, the 90% CIs were 95.8% to 113.9%, 100.2% to 109.7%, and 100.5% to 110.3%, respectively. All values were within the predetermined bioequivalence range. Seven AEs were reported somnolence (4 subjects [9.1%]) and dizziness (3 subjects [6.8%]). All AEs were transient and considered mild by physicians.

Conclusions: The test (dispersible) and reference tablets met the regulatory criteria for bioequivalence as defined by the SFDA. Both formulations were well tolerated. Chinese Clinical Trials registration number: ChiCTR-TRC-12001996.