Cinacalcet lowers parathyroid hormone levels and improves calcium-phosphorus homeostasis in patients receiving hemodialysis who have uncontrolled secondary hyperparathyroidism.

Calcimimetics increase the sensitivity of parathyroid calcium-sensing receptors to extracellular calcium, thereby reducing PTH secretion. This multicenter, randomized, double-blind, placebo-controlled study assessed the ability of the oral calcimimetic cinacalcet HCl to achieve long-term reductions in serum calcium and PTH concentrations in patients with primary hyperparathyroidism (HPT). Patients (n = 78) were randomized to cinacalcet or placebo. Cinacalcet was titrated from 30-50 mg twice daily during a 12-wk dose-titration phase. Efficacy was assessed during 12-wk maintenance and 28-wk follow-up phases. The primary endpoint was the achievement of normocalcemia [serum calcium

In subjects on dialysis with secondary HPT, cinacalcet facilitates achievement of the K/DOQI-recommended targets for PTH, calcium, phosphorus, and Ca x P.

The calcimimetic R-568 rapidly and markedly lowers plasma PTH levels in patients with secondary hyperparathyroidism caused by end-stage renal disease.

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, dosetitration study with single daily oral doses of AMG 073/ placebo up to 100 mg. Changes in plasma PTH, serum calcium, serum phosphorus, and calcium ϫ 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 ϭ 0.001). A significantly greater proportion of AMG 073 patients (44%) had a mean PTH Յ 250 pg/ml compared with placebo patients (20%; P ϭ 0.029). Also, a significantly greater proportion of AMG 073 patients (53%) had a decrease in PTH Ն30% compared with placebo patients (23%; P ϭ 0.009). Calcium ϫ phosphorus levels decreased by 7.9% in AMG 073 patients compared with an increase of 11.3% in placebo patients (P ϭ 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 ϫ phosphorus levels in ESRD patients. AMG 073 represents a novel and promising therapy to improve the management of secondary hyperparathyroidism.The current standard treatment for secondary hyperparathyroidism in ESRD uses calcium supplementation, phosphate binders, and active vitamin D sterols in various combinations to attempt correction of hypocalcemia, hyperphosphatemia, and 1,25 (OH) 2 vitamin D 3 deficiency (1,2). Each component of this combined treatment strategy addresses abnormalities responsible for the pathogenesis of hyperparathyroidism, but each has limitations due to potential undesirable side effects at doses required to effectively suppress PTH hypersecretion (3-6). In this regard, treatment with vitamin D sterols is often complicated by hypercalcemia and hyperphosphatemia (7-10), resulting in elevate calcium ϫ phosphorus levels, predisposition to soft tissue calcification, and increased mortality risk in the ESRD population (11-15). Large doses of orally administered calcium to control hyperphosphatemia also predispose patients to episodes of hypercalcemia, chronic positive calcium balance, and increased soft tissue calcification in dialysis patients (15,...