Background: Bicalutamide is an oral nonsteroidal antiandrogen drug used during hormone ablation therapy for prostate cancer. A new generic formulation of bicalutamide has been developed.
Objectives: This study was conducted to meet Korean and US regulatory requirements for the marketing of the generic 50-mg tablet formulation of bicalutamide. To this end, the pharmacokinetic properties of the new (test) formulation were compared with those of the currently marketed (reference) formulation. Tolerability was also evaluated.
Methods: An open-label, randomized-sequence, single-dose, 2-period crossover study was conducted in healthy Korean male volunteers. Subjects received either the test or reference formulation of bicalutamide 50-mg tablets in the first period and crossed over to the alternative formulation in the second period. Serial blood samples for pharmacokinetic analysis were taken over 672 hours after dosing. Plasma concentrations of bicalutamide were measured by HPLC-MS/MS. Pharmacokinetic parameters, including AUC(0-672h), were determined by noncompartmental analysis. Log-transformed C(max) and AUC(0-672h) for the 2 formulations were compared. Tolerability was monitored based on laboratory tests, ECGs, vital signs, and physical examinations.
Results: Of the 34 subjects initially enrolled, 33 completed the study. The mean (SD) age, height, and weight of participants were 25.8 (4.1) years, 173.6 (5.7) cm, and 68.9 (7.8) kg, respectively. The median T(max) was 36.0 hours for both formulations. The mean (SD) t(1/2), C(max), and AUC(0-672h) for the reference formulation were 135.4 (28.6) hours, 933.2 (169.2) microg/L, and 215,680.1 (48,753.4) microg x h/L, respectively. Corresponding values for the test formulation were 134.3 (30.7) hours, 946.7 (179.9) microg/L, and 221,708.8 (54,935.1) microg x h/L. The 90% CIs for the mean ratios (test/reference) of log-transformed C(max) and AUC(0-672h) were 0.97 to 1.06 and 0.98 to 1.07, respectively. Twelve adverse events were reported for each formulation, none of which were considered drug related in the test-formulation group and 4 of which were considered drug related in the reference-formulation group (3 cases of headache, 1 case of erythematous rash).
Conclusions: In this single-dose study in healthy Korean male subjects, the new formulation of bicalutamide 50-mg tablets met Korean and US regulatory criteria for assumption of bioequivalence with the currently marketed formulation. Both formulations were generally well tolerated, with no clinically relevant safety concerns.
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