Cinacalcet is approved in Europe for treatment of secondary hyperparathyroidism (SHPT) in children aged 3 years and older on dialysis, but not in the United States. Now results from a new study suggest cinacalcet may meet “an unmet medical need for this population,” according to researchers.
In a phase 3 study, investigators randomly assigned 43 patients aged 6 to 18 years from 9 countries to receive cinacalcet (starting dose 0.20 mg/kg or less) or placebo. Over 19 months, 55% of the cinacalcet group and 19% of the placebo group had a 30% or more reduction in mean intact parathyroid hormone (iPTH), Bradley A. Warady, MD, of Children’s Mercy Kansas City, and collaborators reported in Pediatric Nephrology. For 27% of cinacalcet recipients and 24% of placebo recipients, iPTH fell to 300 pg/mL or less. The percentage changes for total serum calcium (C), phosphorus (P), and Ca × P were −4%, −6%, and −10% for cinacalcet vs placebo patients. Cinacalcet was administered at a maximum dose of 0.99 mg/kg/day.
With respect to safety and tolerability, 82% of the cinacalcet group and 86% of the placebo group experienced a treatment-emergent adverse event. The most common were vomiting (32% vs 24%, respectively), hypocalcemia (23% vs 19%), nausea (18% vs 14%), and hypertension (14% vs 24%). Investigators halted the trial early (at 19 months) after a teen with a prolonged QT interval died. Multiple factors were blamed for the death, but researchers could not rule out hypocalcemia. Current drug labeling suggests weekly measurement of serum calcium levels.
“These data suggest that cinacalcet may meet an unmet medical need for the pediatric dialysis population,” Dr Warady’s team concluded. “Due to the premature discontinuation of the trial, uncertainties remain regarding the long-term effects of cinacalcet on growth and development in the pediatric population, and close supervision and monitoring for hypocalcemia and its secondary effects is warranted.”
The study was funded by Amgen, which manufactures cinacalcet.
Warady BA, Iles JN, Ariceta G, et al. A randomized, double-blind, placebo-controlled study to assess the efficacy and safety of cinacalcet in pediatric patients with chronic kidney disease and secondary hyperparathyroidism receiving dialysis. Ped Nephrol. DOI:10.1007/s00467-018-4116-y