MP361EFFICACY AND SAFETY OF A NOVEL INTRAVENOUS CALCIMIMETIC, ONO-5163 (ETELCALCETIDE) IN JAPANESE HEMODIALYSIS PATIENTS WITH SECONDARY HYPERPARATHYROIDISM : RESULTS OF A PLACEBO CONTROLLED PHASE III STUDY

Abstract

Introduction and Aims: Secondary hyperparathyroidism (SHPT) is a popular complication in patients with chronic kidney disease (CKD). A placebo‐controlled Phase III study was conducted to evaluate the efficacy and safety of ONO‐5163 (etelcalcetide), a novel intravenous calcium receptor agonist, for the treatment of SHPT in patients on hemodialysis. Methods: In the present multicenter, randomized, double‐blind, placebo‐controlled, parallel‐group study in Japan, a total of 155 hemodialysis patients with serum intact parathyroid hormone (iPTH) levels ≥300 pg/mL were assigned to receive either ONO‐5163 (n=78) or placebo (n=77). ONO‐5163 was administered three times a week intravenously for 12 weeks at an initial dose of 5 mg, which was subsequently adjusted to doses between 2.5 and 15 mg by considering serum levels of iPTH and calcium corrected for albumin (cCa) . The primary endpoint was the proportion of patients whose serum iPTH levels were reduced toward the target range proposed by Japanese Society for Dialysis Therapy (60‐240 pg/mL). The secondary endpoints were the proportion of patients who achieved ≥30% reductions in serum iPTH level from baseline. Time courses of changes in serum iPTH, cCa, phosphorus (P), and intact fibroblast growth factor‐23 (iFGF‐23) levels were evaluated through the course. Results: The proportion of patients who achieved the primary endpoint was significantly higher with ONO‐5163 (59.0%) versus placebo (1.3%). Similarly, the proportion of patients who achieved ≥30% reductions in serum iPTH level was significantly higher with ONO‐5163 (76.9%) versus placebo (5.2%). Serum cCa, P, and iFGF‐23 levels decreased in the ONO‐5163 group. As for the safety, mild or moderate vomiting, nausea and symptomatic hypocalcemia were observed in the ONO‐5163 group. No serious adverse events possibly related to ONO‐5163 were observed. Conclusions: The study demonstrated the efficacy and safety of ONO‐5163. As the only intravenous calcium receptor agonist available, ONO‐5163 is likely to provide a new option for the treatment of hemodialysis patients with SHPT.