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The Calcimimetic Cinacalcet Normalizes Serum Calcium in Subjects with Primary Hyperparathyroidism

Department of Medicine (D.M.S.), Veterans Affairs Medical Center, University of California-San Francisco, San Francisco, California 94121; Department of Medicine (J.P.B.), College of Physicians and Surgeons, Columbia University, New York, New York 10032; Amgen Inc. (S.A.T., L.C.M., M.D.G.), Thousand Oaks, California 91320; and Department of Medicine (M.P.), Indiana University School of Medicine, Indianapolis, Indiana 46202

Address all correspondence and requests for reprints to: Dolores Shoback, M.D., University of California-San Francisco, San Francisco Veterans Affairs Medical Center, Endocrine Unit–111N, 4150 Clement Street, San Francisco, California 94121. E-mail: address: Dolores{at}itsa.ucsf.edu

Calcimimetics increase the sensitivity of the calcium-sensing receptor (CaR) to circulating serum calcium, reducing the secretion of PTH and the serum calcium concentration. We evaluated the calcimimetic cinacalcet, a novel therapy for the management of primary hyperparathyroidism. In this randomized, double-blind, dose-finding study, patients (n = 22) with primary hyperparathyroidism were given cinacalcet (30, 40, or 50 mg) or placebo twice daily for 15 d and observed for an additional 7 d. Serum calcium, plasma PTH, and 24-h and fasting urine calcium were measured. Baseline mean serum calcium was 10.6 mg/dl for the combined cinacalcet-treated patients (normal range, 8.4–10.3 mg/dl), compared with 10.4 mg/dl for the placebo group. Mean PTH at baseline was 102 pg/ml (normal range, 10–65 pg/ml) for the combined cinacalcet-treated patients, compared with 100 pg/ml in the placebo group. Serum calcium normalized after the second dose on d 1 and remained normal through d 15 in all cinacalcet dose groups. Maximum decreases in PTH of over 50% occurred 2–4 h after dosing in all cinacalcet-treated groups. The fasting and 24-h urine calcium to creatinine ratios were similar in the cinacalcet and placebo groups. This study demonstrates that cinacalcet safely normalized serum calcium and lowered PTH concentrations without increasing urinary calcium excretion in the study subjects, indicating the potential benefit of cinacalcet as a medical treatment for primary hyperparathyroidism.

This work was supported by Amgen Inc.

Abbreviation: CaR, Calcium-sensing receptor.

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