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

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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.

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Acknowledgments

This study was sponsored by Wyeth, which was acquired by Pfizer Inc in October 2009. Medical writing support for this manuscript was provided by Bo Choi, Ph.D., of MedErgy and was funded by Wyeth. Members of the independent adjudication boards included Geno Merli, MD, of Thomas Jefferson Hospital; Michael Ezekowitz, MD, Ph.D., of Lankenau Hospital; George Tzanis, MD, of Thomas Jefferson Hospital; Linda Bagley, MD, of Penn Radiology at Pennsylvania Hospital; Rodney Bell, MD, of Thomas Jefferson Hospital; and Scott Kasner, MD, of the University of Pennsylvania Hospital.

Conflicts of interest

Dr. de Villiers has served as an advisory board member and/or consultant for MSD, Novartis, Servier, and Wyeth. Dr. Palacios has been a symposium speaker or advisory board member for Bayer-Schering, Novo Nordisk, Servier, Lilly, Daiichi-Sankyo, Sanofi-Aventis, MSD, and Procter & Gamble. He has also received research grants and/or consulting fees from Wyeth, Servier, Lilly, Daiichi-Sankyo, Amgen, Arkochim, and Bayer-Schering. Dr. Lips has received research grants and/or honoraria from Eli Lilly, Merck, Procter & Gamble, Servier, and Wyeth. Dr. Brown is an investigator for Wyeth and has served as a consultant for and/or received honoraria or research funding from Abbott, Amgen, Arthrolab, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Merck Frosst, Novartis, Nycomed, Pfizer, Procter & Gamble, Roche, Sanofi-Aventis, Servier, and Wyeth. Drs. Chines, Levine, and Kelepouris were employees of Wyeth, which was acquired by Pfizer Inc in October 2009.

Author information

Authors and Affiliations

  1. Panorama MediClinic and University of Stellenbosch, Room 118 Parow 7500, Cape Town, South Africa

    T. J. de Villiers

  2. Pfizer Inc, Collegeville, PA, USA

    A. A. Chines, A. B. Levine & N. Kelepouris

  3. Palacios Institute of Women’s Health, Madrid, Spain

    S. Palacios

  4. VU University Medical Center, Amsterdam, The Netherlands

    P. Lips

  5. Warsawian Center of Osteoporosis and Calcium Metabolism, Warsaw, Poland

    A. Z. Sawicki

  6. Center for Rheumatic Diseases, Bucharest, Romania

    C. Codreanu

  7. CHUL Research Centre, Laval University, Quebec City, QC, Canada

    J. P. Brown

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  1. T. J. de Villiers
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  2. A. A. Chines
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  3. S. Palacios
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  4. P. Lips
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  6. A. B. Levine
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  7. C. Codreanu
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  9. J. P. Brown
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Correspondence to T. J. de Villiers.

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de Villiers, T.J., Chines, A.A., Palacios, S. et al. Safety and tolerability of bazedoxifene in postmenopausal women with osteoporosis: results of a 5-year, randomized, placebo-controlled phase 3 trial. Osteoporos Int 22, 567–576 (2011). https://doi.org/10.1007/s00198-010-1302-6

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  • DOI: https://doi.org/10.1007/s00198-010-1302-6

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