Cinacalcet normalizes serum calcium in a double-blind randomized, placebo-controlled study in patients with primary hyperparathyroidism with contraindications to surgery

Abstract

Objective: Primary hyperparathyroidism (PHPT) is diagnosed by the presence of hypercalcemia and elevated or non-suppressed parathyroid hormone (PTH) levels. Although surgery is usually curative, some individuals fail or are unable or unwilling to undergo parathyroidectomy. In such individuals, targeted medical therapy may be of value. Cinacalcet normalized calcium and lowered PTH in patients with PHPT in several phase 2 and open-label studies. We compared cinacalcet and placebo in subjects with PHPT unable to undergo parathyroidectomy. Design: Phase 3, double-blind, multi-centred, randomized, placebo-controlled study. Methods: Sixty-seven subjects (78% women) with moderate PHPT were randomized (1:1) to cinacalcet or placebo for </=28 weeks. Main outcome measure: Achievement of a normal mean corrected total serum calcium concentration of </=10.3 mg dl-1 (2.575 mmol l-1). Results: Baseline median (Q1, Q3) serum PTH was 164.0 (131.0, 211.0) pg ml-1 and mean (SD) serum Ca was 11.77 (0.46) mg dl-1. Serum Ca normalized (</=10.3 mg dl-1) in 75.8% of cinacalcet- vs. 0% placebo-treated subjects (p<0.001). Corrected serum Ca decreased by >/=1.0 mg dl-1 from baseline in 84.8% of cinacalcet- vs. 5.9% of placebo-treated subjects (p<0.001). Least squares mean (SEM) plasma PTH change from baseline was 23.80% (4.18%) (cinacalcet) vs. 1.01% (4.05%) (placebo) (p<0.001). Similar numbers of subjects in the cinacalcet and placebo groups reported adverse events (27 vs. 20) and serious adverse events (3 vs. 4). Most commonly reported AEs were nausea and muscle spasms. Conclusions: These results demonstrate that cinacalcet normalizes serum calcium in this PHPT population and appears to be well tolerated.