A Phase I, Multiple-Dose, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate Pharmacokinetics, Safety, and Tolerability of Etelcalcetide Administered Intravenously to Chinese Patients With Chronic Kidney Disease Undergoing Hemodialysis.

ABSTRACT

PURPOSE: This study reports data from the first evaluation of etelcalcetide treatment in Chinese adults with chronic kidney disease and secondary hyperparathyroidism. METHODS: This phase I, randomized study compared thrice-weekly etelcalcetide (5 mg per dose intravenously) and placebo in 33 Chinese adults (aged 18-70 years) receiving hemodialysis. Patients in both treatment groups received standard-of-care treatment with a total of 12 doses of the investigational product during a 4-week treatment period, followed by 4 weeks of washout and follow-up. Pharmacokinetic (PK) parameters (primary endpoint), tolerability (secondary endpoint), and changes in intact parathyroid hormone (iPTH) and corrected calcium (cCa) concentrations (exploratory endpoints) were assessed. PK parameters, ie, the maximum plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC0-last), assessed over the interdialytic interval following the first and last doses were evaluated. The incidence of treatment-emergent adverse events (AEs) and anti-etelcalcetide antibodies was assessed. FINDINGS: Etelcalcetide administered to 25 patients was compared with placebo administered to 8 patients. Etelcalcetide exposure, assessed by Cmax and AUC0-last, increased after multiple-dose administration of etelcalcetide through day 27, with a mean (SD) accumulation ratio of 3.02 (0.61) based on AUC. At least one AE was reported for all patients in the etelcalcetide group and for 87.5% of patients in the placebo group. Serious AEs were reported in 12% of patients in the etelcalcetide group only. No deaths occurred, and a single discontinuation because of patient withdrawal of consent was reported in the etelcalcetide group. Preexisting anti-etelcalcetide antibodies were detected in one patient. The mean serum cCa level for all patients was maintained at >1.75 mmol/L. The iPTH and cCa concentrations decreased as expected, and a maximum mean decrease from baseline of 35.13% in iPTH levels was detected on day 27. IMPLICATIONS Multiple doses of 5 mg etelcalcetide were well tolerated, and observed etelcalcetide PK and safety profiles were similar to those in reports in adults of ethnicities other than Chinese. Changes in serum iPTH and serum calcium levels were consistent with expected responses to etelcalcetide. ClinicalTrials.gov identifier NCT03283098.