Pharmacologic and Pharmacodynamic Equivalence of 2 Formulations of Orlistat

Abstract

We sought to establish the bioequivalence of 2 weight-loss aids: orlistat 27-mg chewable tablet and orlistat 60-mg capsule, measured pharmacodynamically as percentage fecal fat excretion. Two open-label, single-center, randomized, 3-period, 3-treatment crossover studies were conducted in adults with body mass index 25-33kg/m2 . For each 9-day treatment period, subjects received orlistat 27-mg chewable tablet, 60-mg capsule, or 120-mg capsules (2 60-mg capsules) 3 times daily; a 2-day washout separated treatments. Primary bioequivalence analyses were based on 2 1-sided tests of the 90% CI of the ratio of geometric means using log-transformed data (study 1) and by the dose-scale method to calculate bias-corrected and accelerated 90% CI of relative bioavailability (f) using nontransformed data (study 2). Bioequivalence was established if 90% CIs fell within 0.80-1.25. In total, 48 and 144 subjects were randomized in study 1 and study 2, respectively. Bioequivalence between the formulations was established in both studies: study 1 ratio of geometric means of percentage fecal fat excretion was 0.96 (2 1-sided tests, 90% CI 0.87-1.06); study 2-point estimate of f was 1.09 (bias-corrected and accelerated 90% CI 0.98-1.22). Tolerability of the 27-mg tablet was consistent with the 60-mg capsule; mild gastrointestinal effects were most common.