Bioequivalence of Alendronate and Vitamin D3 in a Combination Tablet Versus Corresponding-Dose Individual Tablets in Healthy Taiwanese Volunteers, Determined Using a Novel Plasma Alendronate Assay

D Hamish Wright; Ramon Mols; Kevin R Brown; Geng-Chang Yeh; Eric Woolf; Lisa Hickey; Stefan Zajic

doi:10.1016/j.curtheres.2015.10.001

Bioequivalence of Alendronate and Vitamin D3 in a Combination Tablet Versus Corresponding-Dose Individual Tablets in Healthy Taiwanese Volunteers, Determined Using a Novel Plasma Alendronate Assay

Curr Ther Res Clin Exp. 2015 Oct 14:77:116-21. doi: 10.1016/j.curtheres.2015.10.001. eCollection 2015 Dec.

Authors

D Hamish Wright¹, Ramon Mols², Kevin R Brown³, Geng-Chang Yeh⁴, Eric Woolf¹, Lisa Hickey³, Stefan Zajic¹

Affiliations

¹ Merck Research Laboratories, Merck & Co., Inc., Kenilworth, New Jersey.
² 3D-PharmXchange Maidstone, 48a 5026SK Tilburg, the Netherlands.
³ Former employee of Merck & Co., Inc., Kenilworth, New Jersey.
⁴ Clinical Research Center, Department of Pediatrics, Taipei Medical University Hospital, Taipei, Taiwan.

Abstract

Objective: This study was designed to demonstrate that alendronate (ALN)/vitamin D3 combination tablets (ALN/D5600) are bioequivalent to corresponding doses of ALN and vitamin D3 as individual tablets in healthy Taiwanese volunteers.

Methods: In this open-label, randomized, 2-period, crossover study, 68 volunteers were randomized to a single ALN/D5600 combination tablet or corresponding doses of 70 mg ALN + 5600 IU vitamin D3 (2 × 2800 IU), followed by a 12-day washout period and administration of the alternate formulation. Plasma ALN levels were measured using a newly developed assay. Geometric mean ratios of ALN AUC0-last, AUC0-∞, and Cmax, and unadjusted vitamin D3 AUC0-80h and Cmax were compared and considered bioequivalent if the 90% CI was within 0.8 to 1.25.

Results: The geometric mean ratios were: AUC0-last, 1.084 (90% CI, 0.937-1.253); AUC0-∞, 1.081 (90% CI, 0.935-1.249); and Cmax, 1.112 (90% CI, 0.959-1.289) for ALN, and AUC0-80h 0.953 (90% CI, 0.827-1.098) and Cmax, 0.982 (90% CI, 0.854-1.130) for vitamin D3 unadjusted for endogenous levels.

Conclusions: The combination tablet was considered bioequivalent to coadministration based on ALN AUC0-∞ and unadjusted vitamin D3 parameters. Slight differences for ALN AUC0-last and Cmax (upper 90% CIs outside the bounds) were not considered clinically significant. The combination tablet was well tolerated. No serious adverse experiences were reported. © 2015. The Authors. Published by Elsevier Inc. All rights reserved.

Keywords: Taiwan; alendronate; bioequivalence; vitamin D.