Relative Bioavailability and Tolerability of Two Formulations of Bicalutamide 50-mg Tablets: A Randomized-Sequence, Open-Label, Two-Period Crossover Study in Healthy Korean Male Subjects

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Background Bicalutamide is an oral nonsteroidal antiandrogenic drug used in the treatment of prostate cancer. A new generic 50-mg tablet formulation of bicalutamide has recently been developed. Objective This study evaluated the relative bioavailability and tolerability of the new generic formulation of bicalutamide 50-mg tablets (test) and the currently marketed formulation (reference) in healthy Korean male subjects. The study was conducted to meet Korean regulatory requirements for authorization to market the generic formulation. Methods This was a randomized-sequence, open-label study in which healthy Korean male subjects (aged 20–55 years) received single doses of the test and reference formulations in a 2-period crossover fashion, with a 6-week washout period between doses. Blood samples for the determination of plasma bicalutamide concentrations were obtained at regular intervals over 672 hours after dose administration. Pharmacokinetic parameters were determined using noncompartmental methods. Relative bioavailability was evaluated by comparing the log-transformed C max and AUC 0–672 of the 2 formulations; Korean regulatory requirements for the assumption of bioequivalence were met if the 90% CIs fell within the range of 0.80 to 1.25. Tolerability was assessed based on physical examinations, vital signs, clinical laboratory tests, electrocardiograms (ECGs), and adverse events (AEs) (spontaneously reported or observed by investigators). Results Of 47 volunteers screened for inclusion, 38 were enrolled and 32 completed the study (mean [SD] age, 24.9 [3.7] years; mean height, 173.8 [6.2] cm; mean weight, 66.1 [7.1] kg). Median T max was 24 hours for both formulations. The C max of the test and reference formulations was 1176.2 (191.6) and 1118.9 (209.5) μg/L, respectively. The corresponding values for AUC 0–672 were 277,503 (66,865) and 271,961 (75,597) μg · h/L. The 90% CIs for the geometric mean ratios of log-transformed C max and AUC 0–672 were 1.00 to 1.11 and 0.99 to 1.07, respectively. Thirty-three AEs were reported, including 17 events in 9 subjects who received the test formulation and 16 events in 12 subjects who received the reference formulation. All AEs were mild, and no subjects discontinued the study because of AEs. Conclusions In this single-dose study in healthy Korean male subjects, the pharmacokinetic parameters of the new generic formulation of bicalutamide 50-mg tablets did not differ significantly from those of the reference formulation. The new generic formulation met Korean regulatory criteria for the assumption of bioequivalence to the currently marketed formulation. Both formulations were well tolerated. Korea Food and Drug Administration registration number: PSPD 3057.