Randomized, controlled trial to assess the safety and efficacy of odanacatib in the treatment of men with osteoporosis.

Abstract

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. 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 50mg or placebo. All received 5600IU vitamin D3 weekly and calcium supplementation as needed (≥ 1200mg daily). The primary efficacy outcome was changed from baseline in lumbar spine BMD versus placebo. Overall, 292 men, mean age 68.8years, 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 3months, then returned toward baseline. The safety profile, including cardiovascular events, was similar between groups. Though a promising osteoporosis therapy for men, ODN development was discontinued due to increased risk of stroke in the LOFT phase 3 trial. Clinicaltrials.gov NCT01120600 (registered May 11, 2010).