Bioequivalence evaluation of two cariprazine hard capsule formulations

Abstract

Cariprazine, a third-generation antipsychotic, is indicated for schizophrenia and bipolar I disorder. Affordable formulations are essential for improving access and adherence, particularly in resource-limited settings. We aimed to assess the bioequivalence, safety, and tolerability of a newly developed generic hard capsule Vocarzine (1.5 mg) compared to a branded reference product of cariprazine hard capsule (Reagila®) under fasting conditions in healthy adult participants. In a randomized, open-label, single-dose, two-period, two-sequence crossover design, 30 healthy male and female participants received a single oral dose of either the test or reference product, with 4-week washout period. Pharmacokinetics were evaluated using validated LC-MS/MS methods. Bioequivalence was concluded if the 90% confidence intervals (CIs) for the geometric mean ratios (GMRs) of peak plasma concentration (C_max) and area under the concentration-time curve from time zero to 72 h (AUC_0-72h) fell within 80-125%. Twenty-nine participants completed the study. The GMR (90% CI) for C_max was 91.92% (85.07-99.33%) and for AUC_0-72h was 92.85% (88.86-97.02%), both within the bioequivalence acceptance range (80-125%). Both formulations were well tolerated; mild nausea was the most common adverse event, and no serious adverse events were reported. The two hard capsule formulations were bioequivalent, in terms of rate and extent of absorption, with a comparable safety profile, supporting the use of vocarzine as a safe, effective, and potentially cost-saving alternative. Clinical trial number: The ClinicalTrials.gov registration number is NCT07121868, retrospectively registered on August 13, 2025.