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    ASBMR 2010 Annual Meeting

    Effect of Odanacatib on Bone Density and Bone Turnover Markers in Postmenopausal Women with Low Bone Mineral Density: Year 4 Results

    Category: Osteoporosis - Treatment (Clinical)

    Oral Presentations, Presentation Number: 1247
    Session: Concurrent Oral Session 42: Osteoporosis Treatment: Pharmacologic and Non-Pharmacologic
    Monday, October 18, 2010 4:30 PM - 4:45 PM, Metro Toronto Convention Centre, South Building, South Building: Hall G

    * , UNITED STATES, , UNITED STATES, , AUSTRALIA, , GB, , DENMARK, , NEW ZEALAND, , AUSTRIA, Jose Rodriguez Portales, Pontificia Universidad Católica de Chile, Romana Petrovic, Merck Sharpe & Dohme, , UNITED STATES, Carolyn DaSilva, Merck, , UNITED STATES, , UNITED STATES

    The selective cathepsin K inhibitor odanacatib (ODN) reduced bone resorption markers and progressively increased bone mineral density (BMD) during 3 years of treatment in a Phase 2b study. This study was extended for 2 additional years to further assess ODN efficacy and long-term safety.
    In the 2-year base study, postmenopausal women with BMD T-scores between -2.0 and -3.5 at the lumbar spine, femoral neck, trochanter or total hip received placebo or ODN at 3, 10, 25 or 50 mg weekly. In Year 3, participants were re-randomized to ODN 50 mg weekly or placebo. In Years 4/5, women who received placebo or 3 mg ODN in Years 1/2 and placebo in Year 3 were switched to 50 mg ODN for Years 4/5; all others continued with their Year 3 regimen. 141 women entered the extension, and 133 completed 4 years. Endpoints were BMD at the lumbar spine (primary), total hip and hip subregions, and 1/3 radius; levels of biochemical bone turnover markers; and assessments of safety.
    Overall, 100 women received 50 mg ODN during Year 4 and 41 received placebo. Continuous treatment with 50 mg ODN for 4 years induced significant BMD increases from baseline at the spine (10.7%), total hip (8.3%), femoral neck (8.9%), and trochanter (10.3%) and maintained BMD (-0.1%) at the 1/3 radius; BMD changes from Year 3 were 2.8% (spine), 2.5% (total hip), 3.9% (femoral neck), and 2.9% (trochanter). Serum CTx remained low at Year 4 (-41%), whereas BSAP was relatively unchanged (-2%) from baseline. Women who received active treatment for 2 years and switched to placebo for 2 years experienced bone loss, with BMD near baseline for most sites and decreased by 4.5% at the 1/3 radius at the end of Year 4. Levels of bone turnover markers in women who discontinued active treatment after 2 years rose in the first month off-treatment, but all levels returned to baseline by the end of Year 4. ODN was generally well tolerated.
    In summary, 4 years of ODN treatment increased lumbar spine and hip BMD and was generally well-tolerated in postmenopausal women with low bone mass. Bone formation markers remained relatively unaffected. Discontinuation of ODN after 2 years of treatment was promptly followed by resolution of effects on bone turnover and density such that BMD and bone biomarker levels at Year 4 were at or near baseline.

    Disclosures: D. Hosking, Merck: Research Grants. R. Petrovic, Merck Sharpe & Dohme: Employment (full or part-time). J. Rodriguez Portales, Merck: Research Grants. C. Hustad, Merck: Employment (full or part-time). H. Bone, Merck: Research Grants. I. Reid, Merck: Research Grants. B. Langdahl, Merck: Research Grants. C. Hustad, Merck: Stock options or bond holdings in a for-profit corporation or self-directed pension plan. A. Lombardi, Merck: Stock options or bond holdings in a for-profit corporation or self-directed pension plan. H. Resch, Merck: Research Grants. A. Lombardi, Merck: Employment (full or part-time). R. Petrovic, Merck Sharpe & Dohme: Stock options or bond holdings in a for-profit corporation or self-directed pension plan. C. DaSilva, Merck: Stock options or bond holdings in a for-profit corporation or self-directed pension plan. N. Binkley, Merck: Research Grants. A. Santora, Merck: Employment (full or part-time). C. DaSilva, Merck: Employment (full or part-time). A. Santora, Merck: Stock options or bond holdings in a for-profit corporation or self-directed pension plan. J. Eisman, Merck: Research Grants.

    * Presenting Authors(s): , UNITED STATES

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