Osteoporosis International

, Volume 22, Issue 2, pp 567–576

Safety and tolerability of bazedoxifene in postmenopausal women with osteoporosis: results of a 5-year, randomized, placebo-controlled phase 3 trial

  • T. J. de Villiers
  • A. A. Chines
  • S. Palacios
  • P. Lips
  • A. Z. Sawicki
  • A. B. Levine
  • C. Codreanu
  • N. Kelepouris
  • J. P. Brown
Original Article

DOI: 10.1007/s00198-010-1302-6

Cite this article as:
de Villiers, T.J., Chines, A.A., Palacios, S. et al. Osteoporos Int (2011) 22: 567. doi:10.1007/s00198-010-1302-6

Abstract

Summary

Findings from this 5-year phase 3 study of postmenopausal women with osteoporosis showed that bazedoxifene was associated with an overall favorable safety and tolerability profile, with no evidence of endometrial or breast stimulation. Overall, the results at 5 years were consistent with those seen at 3 years.

Introduction

We report safety and tolerability findings from a 5-year randomized, double-blind, phase 3 study of bazedoxifene in postmenopausal women with osteoporosis.

Methods

In the core study, healthy postmenopausal women with osteoporosis (N = 7,492; mean age, 66.4 years) were randomized to daily doses of bazedoxifene 20 or 40 mg, raloxifene 60 mg, or placebo for 3 years. During the 2-year study extension, the raloxifene 60-mg treatment arm was discontinued after the 3-year database was finalized, and subjects receiving bazedoxifene 40 mg were transitioned in a blinded manner to bazedoxifene 20 mg (bazedoxifene 40-/20-mg group) after 4 years. Safety and tolerability data are reported for subjects in the bazedoxifene 20- and 40-/20-mg and placebo groups; efficacy findings are reported elsewhere.

Results

A total of 3,146 subjects in the bazedoxifene 20- and 40-mg and placebo groups were enrolled in the extension study (years 4 and 5). Overall, the 5-year incidence of adverse events (AEs), serious AEs, and discontinuations due to AEs were similar among groups. The incidence of hot flushes and leg cramps was higher with bazedoxifene compared with placebo. Venous thromboembolic events, primarily deep vein thrombosis, were more frequently reported in the bazedoxifene groups compared with the placebo group. Reports of cardiac disorders and cerebrovascular events were few and evenly distributed among groups. Bazedoxifene showed a neutral effect on the breast and endometrium.

Conclusion

Bazedoxifene was associated with an overall favorable safety and tolerability profile in postmenopausal women with osteoporosis over 5 years of therapy, consistent with findings at 3 years.

Keywords

BazedoxifeneOsteoporosisPostmenopausalSafetySERMsTolerability

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2010

Authors and Affiliations

  • T. J. de Villiers
    • 1
  • A. A. Chines
    • 2
  • S. Palacios
    • 3
  • P. Lips
    • 4
  • A. Z. Sawicki
    • 5
  • A. B. Levine
    • 2
  • C. Codreanu
    • 6
  • N. Kelepouris
    • 2
  • J. P. Brown
    • 7
  1. 1.Panorama MediClinic and University of StellenboschCape TownSouth Africa
  2. 2.Pfizer IncCollegevilleUSA
  3. 3.Palacios Institute of Women’s HealthMadridSpain
  4. 4.VU University Medical CenterAmsterdamThe Netherlands
  5. 5.Warsawian Center of Osteoporosis and Calcium MetabolismWarsawPoland
  6. 6.Center for Rheumatic DiseasesBucharestRomania
  7. 7.CHUL Research CentreLaval UniversityQuebec CityCanada