TY - JOUR
T1 - Randomized, controlled trial to assess the safety and efficacy of odanacatib in the treatment of men with osteoporosis
AU - Binkley, N.
AU - Orwoll, E.
AU - Chapurlat, R.
AU - Langdahl, B. L.
AU - Scott, B. B.
AU - Giezek, H.
AU - Santora, A. C.
N1 - Funding Information:
Funding for this research was provided by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Acknowledgments
Funding Information:
Medical writing, under the direction of the authors, was provided by Annette Smith, PhD, of CMC AFFINITY, McCann Health Medical Communications, in accordance with Good Publication Practice (GPP3) guidelines. This assistance was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. We also acknowledge Steven Doleckyj for prior clinical trial, data and operations management.
Publisher Copyright:
© 2020, International Osteoporosis Foundation and National Osteoporosis Foundation.
PY - 2021/1
Y1 - 2021/1
N2 - Summary: Odanacatib (ODN) was investigated as an osteoporosis treatment in 292 men. Compared with placebo, odanacatib improved bone mineral density and led to sustained bone resorption decreases while producing relatively little bone formation reduction that leveled off with time. However, increased risk of stroke in another study stopped further odanacatib development. Introduction: ODN, a selective oral cathepsin K inhibitor, was in development for osteoporosis treatment. This phase 3, double-blind, randomized, placebo-controlled, 24-month study investigated ODN safety and efficacy in men with osteoporosis. Methods: Men with idiopathic osteoporosis or osteoporosis due to hypogonadism and a lumbar spine or hip (total hip [TH], femoral neck [FN], or trochanter) bone mineral density (BMD) T-score of ≤ − 2.5 to ≥ − 4.0 without prior vertebral fracture or ≤ − 1.5 to ≥ − 4.0 with one prior vertebral fracture were randomized (1:1) to once-weekly ODN 50 mg or placebo. All received 5600 IU vitamin D3 weekly and calcium supplementation as needed (≥ 1200 mg daily). The primary efficacy outcome was changed from baseline in lumbar spine BMD versus placebo. Results: Overall, 292 men, mean age 68.8 years, were randomly assigned to ODN or placebo. Versus placebo, ODN increased BMD from baseline at the lumbar spine, TH, FN, and trochanter by 5.6%, 2.0%, 1.7%, and 2.1%, respectively (all p < 0.01), and decreased uNTx/Cr (68%, p < 0.001), sCTx (77%, p < 0.001), sP1NP (16%, p = 0.001), and sBSAP (8%, p = 0.019). The between-group bone formation marker decrease peaked at 3 months, then returned toward baseline. The safety profile, including cardiovascular events, was similar between groups. Conclusion: Though a promising osteoporosis therapy for men, ODN development was discontinued due to increased risk of stroke in the LOFT phase 3 trial. Trial registration: Clinicaltrials.gov NCT01120600 (registered May 11, 2010).
AB - Summary: Odanacatib (ODN) was investigated as an osteoporosis treatment in 292 men. Compared with placebo, odanacatib improved bone mineral density and led to sustained bone resorption decreases while producing relatively little bone formation reduction that leveled off with time. However, increased risk of stroke in another study stopped further odanacatib development. Introduction: ODN, a selective oral cathepsin K inhibitor, was in development for osteoporosis treatment. This phase 3, double-blind, randomized, placebo-controlled, 24-month study investigated ODN safety and efficacy in men with osteoporosis. Methods: Men with idiopathic osteoporosis or osteoporosis due to hypogonadism and a lumbar spine or hip (total hip [TH], femoral neck [FN], or trochanter) bone mineral density (BMD) T-score of ≤ − 2.5 to ≥ − 4.0 without prior vertebral fracture or ≤ − 1.5 to ≥ − 4.0 with one prior vertebral fracture were randomized (1:1) to once-weekly ODN 50 mg or placebo. All received 5600 IU vitamin D3 weekly and calcium supplementation as needed (≥ 1200 mg daily). The primary efficacy outcome was changed from baseline in lumbar spine BMD versus placebo. Results: Overall, 292 men, mean age 68.8 years, were randomly assigned to ODN or placebo. Versus placebo, ODN increased BMD from baseline at the lumbar spine, TH, FN, and trochanter by 5.6%, 2.0%, 1.7%, and 2.1%, respectively (all p < 0.01), and decreased uNTx/Cr (68%, p < 0.001), sCTx (77%, p < 0.001), sP1NP (16%, p = 0.001), and sBSAP (8%, p = 0.019). The between-group bone formation marker decrease peaked at 3 months, then returned toward baseline. The safety profile, including cardiovascular events, was similar between groups. Conclusion: Though a promising osteoporosis therapy for men, ODN development was discontinued due to increased risk of stroke in the LOFT phase 3 trial. Trial registration: Clinicaltrials.gov NCT01120600 (registered May 11, 2010).
KW - Bone mineral density
KW - Bone turnover markers
KW - Men
KW - Odanacatib
KW - Osteoporosis
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U2 - 10.1007/s00198-020-05701-9
DO - 10.1007/s00198-020-05701-9
M3 - Article
C2 - 33200257
AN - SCOPUS:85096064832
SN - 0937-941X
VL - 32
SP - 173
EP - 184
JO - Osteoporosis International
JF - Osteoporosis International
IS - 1
ER -