Secondary hyperparathyroidism (SHPT) leads to cardiovascular calcification, which affects survival and quality of life in patients with
chronic kidney disease.
Cinacalcet is used to control SHPT, but it may induce gastrointestinal symptoms, resulting in lower adherence and insufficient dosages. Therefore, a need exists to develop new calcimimetics that cause fewer gastrointestinal symptoms. Here we conducted a phase 3, randomized, double-blind, double-dummy trial for a head-to-head comparison of the efficacy and safety of
evocalcet, a new oral calcimimetic, to the established
cinacalcet. Japanese patients with SHPT on
hemodialysis were randomized to receive
evocalcet or
cinacalcet (317 patients each) for 30 weeks. The primary efficacy endpoint was non-inferiority of
evocalcet to
cinacalcet in the proportion of patients achieving a mean intact
parathyroid hormone level of 60 to 240 pg/mL from week 28 to 30 (non-inferiority margin, -15%, per protocol set analyses). In the
evocalcet and
cinacalcet groups, 72.7% and 76.7%, respectively, achieved the target intact
parathyroid hormone level (between-group difference: -4.0% [95% confidence interval -11.4%, 3.5%], for non-inferiority). The incidence of gastrointestinal-related adverse events was 18.6% and 32.8%, respectively (between-group difference: -14.2% [-20.9%, -7.5%], significant for superiority). Thus, the non-inferiority of
evocalcet to
cinacalcet in suppressing intact
parathyroid hormone with fewer gastrointestinal-related adverse events was demonstrated. Hence,
evocalcet may be a favorable alternative to existing calcimimetics for management of SHPT.