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Bridging analysis of the efficacy and safety of bazedoxifene in Japanese and global populations of postmenopausal women with osteoporosis

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Abstract

This study examined whether the global clinical data for bazedoxifene could be extrapolated to a Japanese population by evaluating the results of a phase 2 study in postmenopausal Japanese women with osteoporosis as compared to those of a pivotal, phase 3 study. The efficacy of bazedoxifene 20 and 40 mg versus placebo on lumbar spine bone mineral density (BMD), bone turnover markers, lipid profile, incidence of fractures, and safety parameters was compared between the Japanese phase 2 study (N = 429) and the global phase 3 study (N = 7,492) during a 2-year period. In the primary population for assessment of bridging, differences in the mean percent change from baseline in lumbar spine BMD at 2 years relative to placebo were greater for women treated with bazedoxifene 20 and 40 mg in the phase 2 study than in the phase 3 study. BMD changes in the bazedoxifene groups were confirmed to be similar between the phase 2 study population and a subset of the phase 3 study population with similar baseline characteristics. The effects of bazedoxifene on incidence of fractures, bone turnover markers, and lipid metabolism were similar between studies. There were no major differences in safety parameters between studies. The greater improvement in lumbar spine BMD and similar results in bone turnover markers, fracture incidence, and safety profile observed with bazedoxifene in the phase 2 study compared with the phase 3 study confirmed the feasibility of extrapolating the global clinical data to a Japanese population.

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References

  1. Johnell O, Kanis JA (2006) An estimate of the worldwide prevalence and disability associated with osteoporotic fractures. Osteoporos Int 17:1726–1733

    Article  CAS  PubMed  Google Scholar 

  2. National Osteoporosis Foundation (2010) Fast Facts on Osteoporosis. http://www.nof.org/node/40. Accessed 17 Nov 2011

  3. Finkelstein JS, Brockwell SE, Mehta V, Greendale GA, Sowers MR, Ettinger B, Lo JC, Johnston JM, Cauley JA, Danielson ME, Neer RM (2008) Bone mineral density changes during the menopause transition in a multiethnic cohort of women. J Clin Endocrinol Metab 93:861–868

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  4. Lau EM (2009) The epidemiology of osteoporosis in Asia. IBMS BoneKEy 6:190–193

    Article  Google Scholar 

  5. International Osteoporosis Foundation (2009) The Asian Audit. Epidemiology, costs and burden of osteoporosis in Asia 2009. http://www.iofbonehealth.org/publications/asian-audit-2009.html. Accessed 25 Oct 2010

  6. Hagino H, Furukawa K, Fujiwara S, Okano T, Katagiri H, Yamamoto K, Teshima R (2009) Recent trends in the incidence and lifetime risk of hip fracture in Tottori, Japan. Osteoporos Int 20:543–548

    Article  CAS  PubMed  Google Scholar 

  7. North American Menopause Society (2010) Management of osteoporosis in postmenopausal women: 2010 position statement of The North American Menopause Society. Menopause 17:25–54

    Article  Google Scholar 

  8. Papaioannou A, Kennedy CC, Dolovich L, Lau E, Adachi JD (2007) Patient adherence to osteoporosis medications: problems, consequences and management strategies. Drugs Aging 24:37–55

    Article  CAS  PubMed  Google Scholar 

  9. Miller PD, Chines AA, Christiansen C, Hoeck HC, Kendler DL, Lewiecki EM, Woodson G, Levine AB, Constantine G, Delmas PD (2008) Effects of bazedoxifene on BMD and bone turnover in postmenopausal women: 2-yr results of a randomized, double-blind, placebo-, and active-controlled study. J Bone Miner Res 23:525–535

    Article  CAS  PubMed  Google Scholar 

  10. Silverman SL, Christiansen C, Genant HK, Vukicevic S, Zanchetta JR, de Villiers TJ, Constantine GD, Chines AA (2008) Efficacy of bazedoxifene in reducing new vertebral fracture risk in postmenopausal women with osteoporosis: results from a 3-year, randomized, placebo-, and active-controlled clinical trial. J Bone Miner Res 23:1923–1934

    Article  CAS  PubMed  Google Scholar 

  11. Xu L, Tsai KS, Kim GS, Wu Y, Vincendon P, Chines AA, Constantine GD (2011) Efficacy and safety of bazedoxifene in postmenopausal Asian women. Osteoporos Int 22:559–565

    Article  CAS  PubMed  Google Scholar 

  12. Itabashi A, Yoh K, Chines AA, Miki T, Takada M, Sato H, Gorai I, Sugimoto T, Mizunuma H, Ochi H, Constantine GD, Ohta H (2011) Effects of bazedoxifene on bone mineral density, bone turnover, and safety in postmenopausal Japanese women with osteoporosis. J Bone Miner Res 26:519–529

    Article  CAS  PubMed  Google Scholar 

  13. Orimo H, Sugioka Y, Fukinaga M, Muto Y, Hotokebuchi T, Gorai I, Nakamura T, Kushida K, Tanaka H, Ikai T, Oh-Hashi Y (1998) Diagnostic criteria of primary osteoporosis. J Bone Miner Metab 16:139–150

    Article  Google Scholar 

  14. D’Agostino RB Jr (1998) Propensity score methods for bias reduction in the comparison of a treatment to a non-randomized control group. Stat Med 17:2265–2281

    Article  PubMed  Google Scholar 

  15. Sarkar S, Watts S, Ohashi Y, Carroll RJ, Uesaka H, Mason TM, Rivera C (2002) Bridging data between two ethnic populations. A new application of matched case-control methodology. Drug Inf J 36:349–356

    Google Scholar 

  16. Mizuno S, Yamaguchi T, Fukushima A, Matsuyama Y, Ohashi Y (2005) Overlap coefficient for assessing the similarity of pharmacokinetic data between ethnically different populations. Clin Trials 2:174–181

    Article  PubMed  Google Scholar 

  17. National Osteoporosis Foundation (2010) Clinician’s guide to prevention and treatment of osteoporosis. http://www.nof.org/professionals/pdfs/NOF_ClinicianGuide2009_v7.pdf. Accessed 23 July 2010

  18. Kuchuk NO, van Schoor NM, Pluijm SM, Chines A, Lips P (2009) Vitamin D status, parathyroid function, bone turnover and bone mineral density in postmenopausal women with osteoporosis in global perspective. J Bone Miner Res 24:693–701

    Article  CAS  PubMed  Google Scholar 

  19. Bischoff-Ferrari HA, Dietrich T, Orav EJ, Dawson-Hughes B (2004) Positive association between 25-hydroxy vitamin D levels and bone mineral density: a population-based study of younger and older adults. Am J Med 116:634–639

    Article  CAS  PubMed  Google Scholar 

  20. Chandran M, Hoeck HC, Wong HC, Zhang RF, Dimai HP (2010) Vitamin D status and its relationship with bone mineral density and parathyroid hormone in South-East Asian adults with low bone density. Endocr Pract 17:226–234

    Article  Google Scholar 

  21. Ettinger B, Black DM, Mitlak BH, Knickerbocker RK, Nickelsen T, Genant HK, Christiansen C, Delmas PD, Zanchetta JR, Stakkestad J, Gluer CC, Krueger K, Cohen FJ, Eckert S, Ensrud KE, Avioli LV, Lips P, Cummings SR, for the Multiple Outcomes of Raloxifene Evaluation (MORE) Investigators (1999) Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: results from a 3-year randomized clinical trial. JAMA 282:637–645

    Article  CAS  PubMed  Google Scholar 

  22. Bauer DC, Black DM, Garnero P, Hochberg M, Ott S, Orloff J, Thompson DE, Ewing SK, Delmas PD (2004) Change in bone turnover and hip, non-spine, and vertebral fracture in alendronate-treated women: the fracture intervention trial. J Bone Miner Res 19:1250–1258

    Article  PubMed  Google Scholar 

  23. Eastell R, Barton I, Hannon RA, Chines A, Garnero P, Delmas PD (2003) Relationship of early changes in bone resorption to the reduction in fracture risk with risedronate. J Bone Miner Res 18:1051–1056

    Article  CAS  PubMed  Google Scholar 

  24. Bjarnason NH, Sarkar S, Duong T, Mitlak B, Delmas PD, Christiansen C (2001) Six and twelve month changes in bone turnover are related to reduction in vertebral fracture risk during 3 years of raloxifene treatment in postmenopausal osteoporosis. Osteoporos Int 12:922–930

    Article  CAS  PubMed  Google Scholar 

  25. Ito M, Nishida A, Uetani M, Hayashi K (2001) Osteoporosis in the Japanese population. Semin Musculoskelet Radiol 5:121–126

    Article  CAS  PubMed  Google Scholar 

  26. Koh LK (2002) An Asian perspective to the problem of osteoporosis. Ann Acad Med Singapore 31:26–29

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

These studies and analysis were sponsored by Wyeth Research, Collegeville, PA, USA, and Wyeth K. K., Tokyo, Japan, which were acquired by Pfizer Inc in October 2009. Medical writing support was provided by Katie Gersh, PhD, of MedErgy and was funded by Pfizer Inc.

Conflict of interest

Dr. Itabashi reports serving as a consultant for Wyeth, Chugai, and Ohtsuka. Dr. Yoh reports serving as a consultant for Wyeth. Dr. Miki reports serving as a consultant for Wyeth. Dr. Takada and Dr. Sato have no relevant conflicts of interest to report. Dr. Gorai reports serving as a consultant for Wyeth. Dr. Sugimoto reports serving as a consultant for Wyeth, Asahi Kasei, and Daiichi-Sankyo. Dr. Mizunuma reports serving as a consultant for Wyeth, Chugai, Shiseido, Ono, and Aska. Dr. Ohta reports serving as a consultant for Pola-Pharma, Otsuka, Teijin Pharma, and Takeda. Dr. Ochi is a current employee of Pfizer Inc. Drs. Chines and Constantine were previously employees of Pfizer Inc. Dr. Chines is a stockholder in Pfizer Inc.

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Authors and Affiliations

  1. Saitama Center for Bone Research, Kubojima Clinic, 1785-2 Kubojima, Kumagaya, Saitama, 360-0831, Japan

    Akira Itabashi

  2. Hyogo College of Medicine, Sasayama Medical Center, Sasayama, Hyogo, Japan

    Kousei Yoh

  3. Pfizer Inc, Collegeville, PA, USA

    Arkadi A. Chines & Ginger D. Constantine

  4. Osaka City University Medical School, Osaka, Osaka, Japan

    Takami Miki

  5. Shiga University of Medical Science, Otsu, Shiga, Japan

    Masahiko Takada

  6. Niigata University of Health and Welfare, Niigata, Niigata, Japan

    Hiroshi Sato

  7. International University of Health and Welfare, Atami Hospital, Atami, Shizuoka, Japan

    Itsuo Gorai

  8. Hori Hospital, Yokohama, Kanagawa, Japan

    Itsuo Gorai

  9. Shimane University Faculty of Medicine, Izumo, Shimane, Japan

    Toshitsugu Sugimoto

  10. Hirosaki University School of Medicine, Hirosaki, Aomori, Japan

    Hideki Mizunuma

  11. Pfizer Inc, Tokyo, Japan

    Hiroshi Ochi

  12. International University of Health and Welfare, Sanno Medical Center, Tokyo, Japan

    Hiroaki Ohta

Authors
  1. Akira Itabashi
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  2. Kousei Yoh
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  3. Arkadi A. Chines
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  4. Takami Miki
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  5. Masahiko Takada
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  6. Hiroshi Sato
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  7. Itsuo Gorai
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  8. Toshitsugu Sugimoto
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  9. Hideki Mizunuma
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  10. Hiroshi Ochi
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  11. Ginger D. Constantine
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  12. Hiroaki Ohta
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Corresponding author

Correspondence to Akira Itabashi.

Additional information

A. A. Chines and G. D. Constantine are no longer affiliated with Wyeth/Pfizer.

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Itabashi, A., Yoh, K., Chines, A.A. et al. Bridging analysis of the efficacy and safety of bazedoxifene in Japanese and global populations of postmenopausal women with osteoporosis. J Bone Miner Metab 33, 61–72 (2015). https://doi.org/10.1007/s00774-013-0554-6

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  • DOI: https://doi.org/10.1007/s00774-013-0554-6

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