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

Comparative Pharmacokinetic Profiles of a Novel Low‐Dose Micronized Formulation of Raloxifene 45 mg (AD‐101) and the Conventional Raloxifene 60 mg in Healthy Subjects

“…The intersubject variability (%CV) values of AUC 0-t , AUC 0-∞ , C max , and t 1/2 obtained from the conventional formulation in our study were comparable to the values from our earlier studies (36.9%-50.8%, 44.3%-49.0%, 40.5%-48.9%, and 37.4%-64.8%, respectively). 15,18 Although this study indicated that the test formulation had larger intersubject %CV values of AUC 0-t , AUC 0-∞ , C max , and t 1/2 (53.4%, 101.8%, 62.6%, and 108.4%, respectively) than those from the reference formulation, the 90% CIs of the GMRs (test/reference) for AUC 0-t , AUC 0-∞ , and C max fell within the bioequivalence range, as presented in Table 3. The GMR (90% CI) for t 1/2 was 0.96 (0.86-1.07).…”