Bioequivalence and Bioavailability Forum

Hi Udaya,

» We need clarification on study design of BE of Bicalutamide 50mg tablets since, its long half life is around 150 hours and most of the available literatures have shown as parallel BE study with last time point as 672 hours and two-way cross over study with last time point as 672 hours.

I can only give what I found in my study: Parallel, 60 subjects (30 per arm), 2 dropouts. We aimed at very similar demographics, e.g., the median body weights differed only ½ kg between groups.
Sampling: Pre-dose, 1, 2, 4, 6, 8, 10, 12, 18, 24, 30, 36, 42, 48, 72, 168, 336, 504, and 672 hours. End of hospitalization 48 hours.
Bioanalytics: LC/MS-MS, LLOQ 10 ng/mL for R(–) bicalutamide and 5 ng/mL for S(+) bicalutamide. ULOQ 1 µg/mL R(–) and 100 ng/mL (S+).
R(–) was confirmatory and S(+) exploratory. The CVs were ~21% for AUC and ~10% for C_max (yes, lower than AUC…). x̃ of t_max was 36 h for both treatments with some subjects having t_max at 72 h. Given such late t_max-values I don’t expect that regulators will accept pAUC_0–72 as the primary metric of extent of absorption (instead of AUC_0–t). I suggest to add ad least sampling at 96 h.