Phase 2b study of evocalcet (KHK7580), a novel calcimimetic, in Japanese patients with secondary hyperparathyroidism undergoing hemodialysis: A randomized, double-blind, placebo-controlled, dose-finding study

BACKGROUND: Evocalcet has been developed as a new calcimimetic agent for hemodialysis (HD) patients with secondary hyperparathyroidism (HDSHPT), eliciting fewer gastrointestinal symptoms and drug interactions. We evaluated the efficacy, safety, and optimal starting dose of evocalcet in HDSHPT. METHODS: In this 3-week, Phase 2b, randomized, double-blind, placebo-controlled, multicenter, parallel-group, dose-finding study, Japanese HDSHPT with intact parathyroid hormone (iPTH) ≥240 pg/mL and serum calcium level corrected for albumin ≥8.4 mg/dL were randomized to evocalcet 0.5, 1, 2 mg/day administered orally or placebo under double-blind conditions, and cinacalcet 25 mg/day (open-label conditions). RESULTS: In total, 152 HDSHPT were randomized. The mean ± standard deviation (median, interquartile range) of percent changes in iPTH from baseline to end of treatment were −8.40±25.43% (−12.16, 39.60), −10.56±22.86% (−14.24, 27.85), and −20.16±34.23% (−23.83, 39.05) in the evocalcet 0.5, 1, and 2 mg/day groups and 5.44±25.85% (3.52, 35.39) and −25.86±27.76% (−29.79, 34.15) in the placebo and cinacalcet groups, respectively. The dose-response profile for each evocalcet group vs placebo showed statistically significant differences for all contrast patterns. Whole PTH, corrected calcium, ionized calcium, phosphorus, and intact fibroblast growth factor 23 decreased after treatment initiation in the evocalcet and cinacalcet groups. Adverse events were observed in 30%–50% of patients (all groups). Incidence of adverse events was similar among all groups except for decreased calcium, which occurred more frequently in the evocalcet 2 mg and cinacalcet groups. CONCLUSIONS: The dose response and safety of all administered doses of evocalcet were confirmed, as well as the efficacy of evocalcet ≥1 mg in a strictly Japanese sample of HDSHPT. Therefore, evocalcet 1 mg was considered appropriate as an initial dose for HDSHPT.