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

AimsThis 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®.MethodsThis 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 (AUC0–t) is within the 80.00–125.00 % interval. Prospectively, a scaled average bioequivalence approach for maximum serum concentration (Cmax) was established.Results153 healthy volunteers were enrolled and randomized. After the test formulation (T) and first and second Bonviva® (R) dosing, the Cmax was 96.71 ± 90.19 ng/mL, 92.67 ± 91.48 ng/mL and 87.94 ± 60.20 ng/mL and the AUC0–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 AUC0–t, 100.90 % (94.37–107.88) for AUC0–inf and 102.56 % (95.05–110.67) for Cmax.ConclusionsTest formulation of ibandronic acid is bioequivalent in rate and extent of absorption to Bonviva® following a 150-mg dose, under fasting conditions.

Pharmacokinetics and Bioequivalence of Fixed‐Dose Combination of Simvastatin and Ezetimibe Tablets: A Randomized, Crossover, Open‐Label Study in Healthy Volunteers

“…In this case, applying a 3-period crossover scheme in the replicate design study is acceptable. 23 The partial replicate design with 3 periods, including 2 administrations of the reference formulation in each sequence, provides the advantage of reducing the sample size of subjects required to demonstrate BE between the 2 formulations. 23 This design was also reported in the literature to assess the BE of highly variable drugs such as ibandronic acid, 23 telmisaratan, 24 and eperisone.…”

“…23 The partial replicate design with 3 periods, including 2 administrations of the reference formulation in each sequence, provides the advantage of reducing the sample size of subjects required to demonstrate BE between the 2 formulations. 23 This design was also reported in the literature to assess the BE of highly variable drugs such as ibandronic acid, 23 telmisaratan, 24 and eperisone. 25 Employing a 3-sequence, 3-period, 2-treatment partially replicated crossover design was shown to offer greater practicality and efficiency compared with a 4-way, fully replicated crossover design.…”

“…The high variability in simvastatin pharmacokinetics 22 qualifies for widening the confidence intervals. In this case, applying a 3‐period crossover scheme in the replicate design study is acceptable 23 . The partial replicate design with 3 periods, including 2 administrations of the reference formulation in each sequence, provides the advantage of reducing the sample size of subjects required to demonstrate BE between the 2 formulations 23 .…”

Assessment the equivalence of the bioanalogue insulin lizpro biphasic 25 (Geropharm-bio, Russia) and Humalog® Mix 25 (Lilly France, France) using the euglycemic hyperinsulinum clamp method on healthy volonters

“…Совокупность этих факторов с тем, что и сам AUC ins.0-12 укладывается в границы эквивалентности, позволяет сделать вывод об отсутствии клинической значимости выявленных ФК-различий AUC ins.0-12 . Данные статистические различия могут быть связаны с величиной выборки, которая позволяет найти различия между эквивалентными препаратами [27]. Так, выборка для этого исследования рассчитывалась для наиболее вариабельного параметра AUC ins и предполагался коэффициент вариабельности (CV) 38%, в то время как в исследовании CV был 20,87%.…”