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J Am Soc Nephrol 14:575-583, 2003
© 2003 American Society of Nephrology

The Calcimimetic AMG 073 as a Potential Treatment for Secondary Hyperparathyroidism of End-Stage Renal Disease

L. Darryl Quarles*, Donald J. Sherrard{dagger}, Stephen Adler{ddagger}, Steven J. Rosansky§, Laura C. McCary, Wei Liu, Stewart A. Turner and David A. Bushinsky#

*Duke University Medical Center, Durham, North Carolina; {dagger}Puget Sound Health Care Systems, VA Hospital, Seattle, Washington; {ddagger}Westchester Medical Center, New York Medical College, Valhalla, New York; §WJB Dorn Veterans Hospital, Columbia, South Carolina; Amgen Inc., Thousand Oaks, California; and #University of Rochester School of Medicine, Rochester, New York.

Correspondence to L. Darryl Quarles, Professor of Medicine, Director, Duke Center for Bone and Mineral Disorders, P. O. Box 3036 DUMC, Durham, NC 27710. Phone: 919-660-6855; Fax: 919-684-4476;

ABSTRACT. Current treatment of secondary hyperparathyroidism in chronic kidney failure with calcium and active vitamin D is potentially limited by hypercalcemia and hyperphosphatemia. AMG 073 represents a new class of compounds for the treatment of hyperparathyroidism known as calcimimetics, which reduce parathyroid hormone (PTH) synthesis and secretion by increasing the sensitivity of the parathyroid calcium-sensing receptor (CaR) to extracellular calcium. The current study evaluates the efficacy and safety of AMG 073 when added to conventional treatment of secondary hyperparathyroidism in end-stage renal disease (ESRD). Seventy-one hemodialysis patients with uncontrolled secondary hyperparathyroidism, despite standard therapy with calcium, phosphate binders, and active vitamin D sterols, were treated in this 18-wk, dose-titration study with single daily oral doses of AMG 073/placebo up to 100 mg. Changes in plasma PTH, serum calcium, serum phosphorus, and calcium x phosphorus levels were compared between AMG 073 and placebo groups. Mean PTH decreased by 33% in the AMG 073 patients compared with an increase of 3% in placebo patients (P = 0.001). A significantly greater proportion of AMG 073 patients (44%) had a mean PTH <= 250 pg/ml compared with placebo patients (20%; P = 0.029). Also, a significantly greater proportion of AMG 073 patients (53%) had a decrease in PTH >=30% compared with placebo patients (23%; P = 0.009). Calcium x phosphorus levels decreased by 7.9% in AMG 073 patients compared with an increase of 11.3% in placebo patients (P = 0.013). Adverse event rates were low and mostly mild to moderate in severity; however, the incidence of vomiting was higher in AMG 073 patients. In this study, the calcimimetic AMG 073 at doses up to 100 mg for 18 wk provided a safe and effective means to attain significant reductions in PTH and calcium x phosphorus levels in ESRD patients. AMG 073 represents a novel and promising therapy to improve the management of secondary hyperparathyroidism. E-mail: Quarl001@mc.duke.edu




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