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

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.