A randomized, open-label, single-dose, two-way crossover study to assess the pharmacokinetics between two tablets of fixed-dose combination formulation with raloxifene and cholecalciferol and concomitant administration of each agents in healthy male volunteers

Abstract

A new fixed-dose combination (FDC) formulation of raloxifene 60 mg and cholecalciferol 800 IU was developed to improve the medication compliance and overall efficacy of raloxifene treatment in postmenopausal osteoporosis patients. The aim of this study was to compare the pharmacokinetics between two tablets of FDC formulation of raloxifene/cholecalciferol and the two products administered concomitantly at respective doses. This randomized, open-label, single-dose, two-treatment, two-way crossover study included 46 volunteers. During each treatment period, subjects received the test formulation (FDC formulation containing raloxifene and cholecalciferol) or the reference formulation (co-administration of raloxifene and cholecalciferol), with a 14-d washout period. Serial blood samples were collected periodically over 96 hours after drug intake. In total, 46 subjects completed the study. The geometric mean ratios and its 90% confidence intervals of the FDC to the single agents for the area under the concentration-time curve from zero to the last quantifiable time point and the maximum plasma concentration met the regulatory criteria for bioequivalence: 1.1364 (1.0584-1.2201) and 1.1010 (0.9945-1.2188) for raloxifene and 1.0266 (0.9591-1.0989) and 1.0354 (0.9816-1.0921) for baseline-corrected cholecalciferol, respectively. Both formulations were well tolerated. No significant differences was observed in the incidence of adverse events between the two treatments. It was concluded that two tablets of the newly developed FDC formulation of raloxifene and cholecalciferol and the corresponding two agents administered concomitantly at respective doses were bioequivalent.

Trial registration: ClinicalTrials.gov Identifier: NCT03010267.

Keywords: Cholecalciferol; Osteoporosis; Pharmacokinetics; Raloxifene.

Conflict of interest statement

Conflict of Interest: B. L. is an employee of Alvogen Korea Co. Ltd. The authors have indicated that they have no other conflicts of interest regarding the content of this article. The sponsor did not participate in the execution of the study or analysis of the data.

Copyright © 2022 Translational and Clinical Pharmacology.

Figures

Figure 1. Mean plasma concentration-time profiles of raloxifene and cholecalciferol after administering a single oral dose of raloxifene 120 mg and cholecalciferol 1,600 IU as fixed dose combination or individual agents concomitantly. (A) Raloxifene (semilog scale); (B) Cholecalciferol, baseline-corrected (semilog scale). Error bars denote the standard deviations.