ESPN 50th Annual Meeting

ESPN 2017


 
A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of Cinacalcet in Pediatric Subjects With Chronic Kidney Disease and Secondary Hyperparathyroidism Receiving Dialysis
BRADLEY WARADY 1 JAN ILES 2 GEMA ARICETA 3 BASTIAN DEHMEL 2 GUILLERMO HIDALGO 4 XUN JIANG 2 BENJAMIN LASKIN 5 SHAHNAZ SHAHINFAR 2 FRANZ SCHAEFER 6

1- CHILDRENS MERCY HOSPITAL, DIVISION OF NEPHROLOGY, KANSAS CITY, MO USA
2- AMGEN INC, THOUSAND OAKS, CA USA
3- VAIL DHEBRON HOSPITAL, BARCELONA, SPAIN
4- BRODY SCHOOL OF MEDICINE-ECU, DEPT OF PEDIATRICS, NEPHROLOGY, GREENVILL, NC USA
5- CHILDRENS HOSPITAL OF PHILADELPHIA, CHOP PEDIATRIC CARE, PHILADELPHIA, PA USA
6- HEIDELBERG UNIVERSITY HOSPITAL, DIVISION OF PEDIATRIC NEPHROLOGY, HEIDELBERG, GERMANY
 
Introduction:

This study evaluated the efficacy of cinacalcet for reducing plasma intact parathyroid hormone(iPTH), the impact on albumin-corrected Ca(cCa) and phosphorus(P); safety and tolerability of cinacalcet. 

Material and methods:

Eligible subjects (6to<18 years) on chronic dialysis2 months, with PTH>300pg/mL, Ca8.8mg/dL and P4.0mg/dL (6to<12 years) or ≥3.5mg/dL (12to<18 years) were randomized 1:1 to cinacalcet or placebo stratified by age group (<12and12 years). Cinacalcet was started at 0.20mg/kg/day and titrated (max 4.2mg/kg/day) once every 4 weeks over 24 weeks followed by a 6-week efficacy assessment phase (EAP). Plasma iPTH, serum cCa, and P were collected bi-weekly during titration and EAP. 

Results:

43/100 planned subjects were enrolled and received ≥1 dose of investigational product (22 cinacalcet; 21 placebo).  The study was terminated early after consultation with regulatory authorities following a fatality in a subject with severe hypocalcemia receiving cinacalcet. The cause of death was determined to be multifactorial, but a causal role for hypocalcemia could not be excluded. Baseline demographics and disease characteristics were balanced. 54.5%(12/22) cinacalcet and 19.0%(4/21) placebo subjects achieved ≥30% reduction from baseline in mean PTH during the EAP (study primary endpoint), with a difference of 35.5%(95%CI: 8.76%, 62.24%), based on last observation carried forward imputation (CMH test p=0.017). Numerically reduced cCa and similar P were observed in subjects who received cinacalcet. Adverse events (AE), including hypocalcemia, were reported in similar proportions in the cinacalcet and placebo arms during the double-blind phase. 

Conclusions:

The observed treatment effect of cinacalcet in reducing plasma iPTH was clinically meaningful and statistically significant despite early termination of the study. The observed AEs were generally consistent with the known safety profile for cinacalcet.