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Effect of the cathepsin K inhibitor odanacatib administered once weekly on bone mineral density in Japanese patients with osteoporosis—a double-blind, randomized, dose-finding study

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Abstract

Summary

The efficacy and safety of oral placebo or odanacatib 10, 25, or 50 mg once weekly for 52 weeks were evaluated in a double-blind, randomized, multi-center study in Japanese female and male patients with osteoporosis.

Introduction

Odanacatib is a selective and reversible cathepsin K inhibitor that decreases bone resorption and increases bone mineral density (BMD).

Methods

The primary efficacy endpoint was percent change from baseline to week 52 in lumbar spine BMD. Secondary endpoints included percent change in total hip, femoral neck, and trochanter BMD and in bone biomarkers after treatment for 52 weeks.

Results

In this study, 286 patients [94 % female, mean age (SD) 68.2 (7.1) years] were included in the analysis. The least-squares mean percent changes from baseline to week 52 in the groups receiving placebo, 10, 25 and 50 mg of odanacatib for lumbar spine (L1∼L4) BMD were 0.5, 4.1, 5.7, and 5.9 % and for total hip BMD were −0.4, 1.3, 1.8, and 2.7 %, respectively. The changes in femoral neck and trochanter BMD were similar to those at the total hip. Bone turnover markers were reduced in a dose-dependent manner. However, the effects of odanacatib on bone formation markers were less compared with the effects on bone resorption markers. Tolerability and safety profiles were similar among all treatment groups with no dose-related trends in any adverse events.

Conclusions

Weekly odanacatib treatment for 52 weeks increased BMD at the lumbar spine and at all hip sites in a dose-dependent manner and was well tolerated in Japanese patients with osteoporosis.

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Acknowledgments

We thank Drs. Albert T. Leung, Antonio Lombardi, and Keith Kaufman, Merck Research Laboratories, Rahway, New Jersey, for their kind comments and advice on the manuscript. We are also indebted to Mr. Jun Matsumoto, MSD.K.K, for his scientific and technical support. The following primary investigators and clinical sites in Japan participated in this study: T. Okano, Tottori University Hospital; T. Yamaguchi, Shimane University Hospital; H. Fukunishi, Shinsuma General Hospital; R. Takayanagi, Kyushu University Hospital; S. Okamoto, SORF Okamoto Clinic; K. Shigenobu, Hakodate Central General Hospital; T. Ohta, Ohta Orthopaedic Clinic; M. Takahashi, Takahashi Orthopedics Clinic; T. Oguma, Sapporo Orthopaedic Hospital; S. Mori, Mori’s clinic of orthopedic rheumatic; S. Nakajo, Nakajo Orthopedic Clinic; E. Nakamura, University of Occupational and Environmental Health Japan; S. Okamoto, KS Okamoto Clinic; K. Kuroda, Kuroda Orthopedic Clinic; T. Okada, Okada Orthopedic Clinic; Y. Nakatani, Nakatani Hospital; T. Higuchi, Hirosaki University School of Medicine & Hospital; K. Sugiyasu, Kirishima Sugiyasu Hospital; A. Tomonaga, Tana Orthopedics Clinic; K. Watanabe, Kitashinyokohama Orthopedic Clinic; H. Yamane, Toyooka Daiichi Hospital; K. Kinoshita, Seijo Kinoshita Hospital; K. Akazawa, Akazawa Ladies’ Clinic; Y. Fujii, Fujii Medical Clinic; Y. Miki, Medical Juridical Person Sanpoukai Nanko-Hospital; H. Kaneko, National Hospital Organization Saitama National Hospital; S. Ichikawa, Cardiovascular Hospital of Central Japan; Y. Somekawa, Toride Kyodo General Hospital; T. Hanaoka, Yamabeonsen Hanaoka Orthopedic Clinic; M. Fujimori, Keyakidori Orthopedics; H. Hanashi, New Medical Research System Clinic; R. Suto, Yokohama Shin-Midori General Hospital; K. Sakamoto, Nishikamata Seikeigeka; H. Tanaka, Moji Rosai Hospital; H. Miyajima, Meguro You + I Clinic; K. Sato, Nagoya Daini Red Cross Hospital; S. Muraki, The University of Tokyo Hospital; H. Takagi, Nagoya Kyouritsu Clinic; H. Shimizu, Shimizu Orthopedic Clinic; T. Mori, Sapporo Tokushukai medical center; A. Itabashi, Kubojima Clinic; H. Ito, Ito Orthopedic Surgery Clinic.

Conflicts of interest

Authors Santora, Tsai, Fujimoto, Nakagomi, Tsubouchi, E. Rosenberg, and Uchida are employed by, and may hold stock options with, Merck Sharp & Dohme, a subsidiary of Merck & Co. Inc. Nakamura has received research grants/consulting fees from Merck. Shiraki reports consultant/speaker’s bureau fees from Merck. The remaining authors report no financial relationships with Merck Sharp & Dohme, the sponsor of this study.

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Authors and Affiliations

  1. National Center for Global Health and Medicine, Shinjuku-ku Tokyo, 162-8655, Japan

    T. Nakamura

  2. Research Institute and Practice for Involutional Diseases, Nagano, Japan

    M. Shiraki

  3. Kawasaki Medical School, Okayama, Japan

    M. Fukunaga & T. Tomomitsu

  4. Merck Sharp and Dohme Corp, Whitehouse Station, NJ, USA

    A. C. Santora & E. Rosenberg

  5. Clinical Development Institute, MSD.K.K, Tokyo, Japan

    R. Tsai, G. Fujimoto, M. Nakagomi, H. Tsubouchi & S. Uchida

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  1. T. Nakamura
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  2. M. Shiraki
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Correspondence to T. Nakamura.

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Nakamura, T., Shiraki, M., Fukunaga, M. et al. Effect of the cathepsin K inhibitor odanacatib administered once weekly on bone mineral density in Japanese patients with osteoporosis—a double-blind, randomized, dose-finding study. Osteoporos Int 25, 367–376 (2014). https://doi.org/10.1007/s00198-013-2398-2

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  • DOI: https://doi.org/10.1007/s00198-013-2398-2

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