Ronacaleret HCl (SB-751689) is a small molecule CaSR antagonist for the treatment of endocrine and metabolic diseases, skin and musculoskeletal disorders.

For 569 postmenopausal women with low BMD offered open-label 20 μg teriparatide sc once daily or were randomized to 100, 200, 300, or 400 mg oral Ronacaleret HCl once daily, 70 mg alendronate once weekly, or placebo and were followed for up to 12 months.Results: With Ronacaleret HCl, the increases in lumbar spine BMD at 12 months (0.3-1.6%) were significantly lower than those attained with teriparatide (9.1%) or alendronate (4.5%). There were small decreases in total hip, femoral neck, and trochanter BMD at month 12 with Ronacaleret HCl compared with increases in the teriparatide and alendronate arms. Bone turnover markers increased in the Ronacaleret HCland teriparatide arms and decreased in the alendronate arm. PTH elevations with Ronacaleret HCl were prolonged relative to those previously reported with teriparatide. Conclusion: The densitometric findings in the context of prolonged PTH elevation and increased bone turnover suggest Ronacaleret HClinduces mild hyperparathyroidism. Ronacaleret HCl only modestly increased lumbar spine BMD and decreased BMD at hip sites.[1]