Bioequivalence of alendronate and vitamin D 3 in an alendronate/vitamin D 3 combination tablet (1053.2)

Le résumé fourni par la source

FOSAMAX® PLUS D is a once‐weekly alendronate (ALN) 70‐mg / vitamin D 3 (vit‐D 3 ) 5600 IU combination tablet developed by Merck & Co., Inc. A single‐dose, open‐label, randomized, 2‐period, crossover study was conducted to test bioequivalence between FOSAMAX® PLUS D combination tablets and co‐administration of corresponding doses of ALN 70‐mg (FOSAMAX®) and vit‐D 3 5600 IU (2x 2800 IU) as individual tablets in healthy male and female Asian subjects to support registration in Taiwan. Results: the 90%CI of the GMR for ALN AUC 0‐∞ fell within the pre‐specified bioequivalence bounds of 0.8 to 1.25, but slightly exceeded 1.25 for ALN AUC 0‐last and Cmax. The 90% CI of the GMR for vit‐D 3, unadjusted for endogenous vit‐D 3 , was also contained within the pre‐specified bioequivalence bounds. Thus, the combination tablet was bioequivalent based on ALN AUC 0‐∞ and vit‐D 3 unadjusted for endogenous levels. However, it was not bioequivalent to co‐administration with respect to ALN AUC 0‐last and Cmax . In conclusion, the small differences between the combination tablet and co‐administration of individual doses for ALN AUC 0‐last and Cmax are not considered to be clinically significant, as slightly increased ALN concentrations are unlikely to meaningfully affect the safety profile. TFDA accepted these results and considered them supportive for registration of the combination tablet in Taiwan.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.