Bioequivalence Assessment Between Two Cariprazine Hard Capsule Formulations

This was a single-dose, open-label, randomized, two-sequence, two-period crossover bioequivalence study conducted under fasting conditions at Advanced Research Center (ARC), Cairo, Egypt in 2024. The study compared the bioequivalence of Vocarzine 1.5 mg hard capsule (Test) with Reagila® 1.5 mg hard capsule (Reference), both formulations containing cariprazine. Study Design Participants were randomized in a 1:1 ratio to receive the test or reference product across two study periods, separated by a 4-week washout. Each subject received a single oral dose (equivalent to 1.5 mg cariprazine) under fasting conditions. A standardized diet was provided during each period, and fluid intake was controlled pre- and post-dosing to maintain consistency. Blood Sampling Details In each period, 22 blood samples (5 mL each) were collected to characterize the plasma concentration-time profile. A forearm vein cannula was used for samples up to 24 hours; later samples were collected via venipuncture. Samples were centrifuged at 3500 rpm for 5 minutes at 4°C. Plasma was separated and stored at -80°C pending analysis. Pharmacokinetic and Bioanalytical Methods Plasma cariprazine concentrations were quantified using a validated LC-MS/MS method with a calibration range of 0.05-5 ng/mL. The primary PK parameters included Cmax and AUC₀-₇₂, while secondary parameters were Tmax, t½, and ke. PK analysis was conducted using Phoenix WinNonlin (v8.3.4), with calculations based on actual sampling times. Bioequivalence Evaluation Bioequivalence was determined if the 90% confidence intervals (CIs) for the geometric mean ratios (GMRs) of Cmax and AUC₀-₇₂ fell within the 80-125% range. ANOVA was applied to log-transformed data for Cmax and AUC, and Wilcoxon signed-rank test was used for Tmax comparisons. Safety Evaluation Subjects were monitored for adverse events throughout the study. Vital signs were assessed at multiple time points (pre-dose, and 3, 6, 12, and 72 hours post-dose). Complete blood counts were performed at the study's end. Statistical Analysis was performed using R (v4.2.1). The Two One-Sided Tests (TOST) procedure was applied to log-transformed PK parameters to assess bioequivalence.