Bioequivalence study of two formulations of ibandronic acid 150-mg film-coated tablets in healthy volunteers under fasting conditions: A randomized, open-label, three-way, reference-replicated crossover study

Abstract

Aims: This bioequivalence study aimed to compare rate and extent of absorption of a generic medicinal product of ibandronic acid 150-mg film-coated tablet versus Bonviva®. Methods: This was a single-centre, open-label, randomized, three-way, three-sequence, reference-replicated, crossover bioequivalence study, under fasting conditions. A single oral dose of ibandronic acid as one 150-mg film-coated tablet was administered in each study period. Each washout period lasted 14 days. Blood samples were collected according to a predefined sampling schedule and up to 48.0 hours after administraton in each period. Plasma concentrations of ibandronic acid were measured using a liquid chromatograph-mass spectrometry/mass spectrometry method. Bioequivalence between generic and reference medicinal products is acceptable if the 90 % confidence intervals (CI) of ratio of least-squares means between the test and the reference product of ln-transformed area under the serum concentration-time curve from time zero to time of last measurable concentration (AUC 0-t) is within the 80.00-125.00 % interval. Prospectively, a scaled average bioequivalence approach for maximum serum concentration (C max) was established. Results: 153 healthy volunteers were enrolled and randomized. After the test formulation (T) and first and second Bonviva® (R) dosing, the C max was 96.71 ± 90.19 ng/mL, 92.67 ± 91.48 ng/mL and 87.94 ± 60.20 ng/mL and the AUC 0-t was 390.83 ± 287.27 ng·h/mL, 388.54 ± 356.76 ng·h/mL and 383.53 ± 246.72, respectively. Ratios of T/R and 90 % CI were 100.92 % (94.35-107.94) for AUC 0-t, 100.90 % (94.37-107.88) for AUC 0-inf and 102.56 % (95.05-110.67) for C max. Conclusions: Test formulation of ibandronic acid is bioequivalent in rate and extent of absorption to Bonviva® following a 150-mg dose, under fasting conditions. © 2014 The Author(s).