Dose determination of cinacalcet hydrochloride in Japanese hemodialysis patients with secondary hyperparathyroidism.

Cinacalcet hydrochloride is a calcimimetic agent that activates the calcium-sensing receptor on the surface of parathyroid cells and inhibits parathyroid hormone (PTH) secretion. To manage secondary hyperparathyroidism, cinacalcet, which lowers PTH levels without increasing serum calcium, phosphorus and calcium-phosphorus product (Ca x P) levels, may provide a new potential therapy. To identify the optimal starting dose of cinacalcet for Japanese hemodialysis patients with secondary hyperparathyroidism, this double-blind, placebo-controlled, parallel, dose-finding study was conducted. One hundred and twenty Japanese hemodialysis patients with intact PTH levels greater than or equal to 300 pg/mL were randomized into four groups: placebo, and 12.5, 25 and 50 mg of cinacalcet. The treatment period was three weeks followed by a two-week follow-up observation period. Cinacalcet decreased serum intact PTH levels in a dose-dependent manner, and also decreased serum calcium, phosphorus, Ca x P, tartrate-resistant acid phosphatase and osteocalcin levels. The treatment with cinacalcet was generally well tolerated in this study. However, the incidence of treatment-related adverse events, such as gastrointestinal disorders and hypocalcemia, and the rate of withdrawal from the study due to treatment-related adverse events were higher in the 50 mg dose group than in the other groups. On the basis of both efficacy and safety results, 25 mg has been identified as the optimal starting dose of cinacalcet for Japanese hemodialysis patients with secondary hyperparathyroidism.