Odanacatib in the treatment of postmenopausal women with low bone mineral density: Five years of continued therapy in a phase 2 study |
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| Authors: | Bente Langdahl Neil Binkley Henry Bone Nigel Gilchrist Heinrich Resch Jose Rodriguez Portales Andrew Denker Antonio Lombardi Celine Le Bailly De Tilleghem Carolyn DaSilva Elizabeth Rosenberg Albert Leung |
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| Institution: | 1. Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark;2. Osteoporosis Clinical Center & Research Program, University of Wisconsin, Madison, WI, USA;3. Michigan Bone and Mineral Clinic, Detroit, MI, USA;4. Canterbury Geriatric Medical Research Trust, Princess Margaret Hospital, Christchurch, New Zealand;5. Rheumatology/Osteology & Gastroenterology, Medical University Vienna, Vienna, Austria;6. Departamento de Endocrinología, School of Medicine, Pontificia Universidad Catolica de Chile, Santiago, Chile;7. Merck Sharp & Dohme, Whitehouse Station, NJ, USA;8. Merck Sharp & Dohme, Brussels, Belgium |
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| Abstract: | Odanacatib (ODN) is a selective inhibitor of the collagenase cathepsin K that is highly expressed by osteoclasts. In this 2‐year, phase 2, dose‐ranging trial, postmenopausal women with bone mineral density (BMD) T‐scores ?2.0 to ?3.5 at spine or hip were randomized to weekly placebo or ODN 3, 10, 25, or 50 mg plus vitamin D3 and calcium. Prespecified trial‐extensions continued through 5 years. In year 3, all women were re‐randomized to ODN 50 mg or placebo. For years 4 and 5, women who received placebo or ODN 3 mg in years 1 and 2 and placebo in year 3 received ODN 50 mg; others continued year 3 treatments. Endpoints included lumbar spine (primary), hip, 1/3 radius, and total body BMD; markers of bone metabolism; and safety. Women in the year 4 to 5 extension receiving placebo (n = 41) or ODN 50 mg (n = 100) had similar baseline characteristics. For women who received ODN (10–50 mg) for 5 years, spine and hip BMD increased over time. With ODN 50 mg continually for 5 years (n = 13), mean lumbar spine BMD percent change from baseline (95% confidence interval CI]) was 11.9% (7.2% to 16.5%) versus ?0.4% (?3.1% to 2.3%) for women who were switched from ODN 50 mg to placebo after 2 years (n = 14). In pooled results of women receiving continuous ODN (10–50 mg, n = 26–29), year 5 geometric mean percent changes from baseline in bone resorption markers cross‐linked N‐telopeptide of type I collagen (NTX)/creatinine and cross‐linked C‐telopeptide (CTX) were approximately ?55%, but near baseline for bone formation markers bone‐specific alkaline phosphatase (BSAP) and amino‐terminal propeptide of type I procollagen (P1NP). In women switched from ODN 10 to 50 mg to placebo after 2 years (n = 25), bone turnover markers were near baseline. In summary, women receiving combinations of ODN (10–50 mg) for 5 years had gains in spine and hip BMD and showed larger reductions in bone resorption than bone formation markers. Discontinuation of ODN resulted in reversal of treatment effects. Treatment with ODN for up to 5 years was generally well‐tolerated. © 2012 American Society for Bone and Mineral Research. |
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| Keywords: | BMD BONE TURNOVER CATHEPSIN K ODANACATIB OSTEOPOROSIS |
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