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

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)116-121
Number of pages6
JournalCurrent Therapeutic Research - Clinical and Experimental
Volume77
DOIs
Publication statusPublished - Dec 1 2015

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Alendronate
Therapeutic Equivalency
Cholecalciferol
Tablets
Healthy Volunteers
Cross-Over Studies
Volunteers

Keywords

  • Alendronate
  • Bioequivalence
  • Taiwan
  • Vitamin D

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology

Cite this

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

In: Current Therapeutic Research - Clinical and Experimental, Vol. 77, 01.12.2015, p. 116-121.

Research output: Contribution to journalArticle

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title = "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",
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.",
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AU - Wright, D. Hamish

AU - Mols, Ramon

AU - Brown, Kevin R.

AU - Yeh, Geng Chang

AU - Woolf, Eric

AU - Hickey, Lisa

AU - Zajic, Stefan

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N2 - 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.

AB - 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.

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