ESPN 50th Annual Meeting

ESPN 2017


 
An Open-label, Single-dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Cinacalcet in Pediatric Subjects Aged 28 Days to < 6 Years With Chronic Kidney Disease Receiving Dialysis
BRADLEY WARADY 1 ANTHONY PORTALE 2 HAO ZHANG 3 LUCY YAN 3 BELLA ERTIK 3 EDWARD LEE 3 SHAHNAZ SHAHINFAR 3 BASTIAN DEHMEL 3 WINNIE SOHN 3

1- CHILDRENS MERCY HOSPITAL, DIVISION OF NEPHROLOGY, KANSAS CITY, MO USA
2- UCSF SCHOOL OF MEDICINE, DEPARTMENT OF PEDIATRICS, SAN FRANCISCO, CA USA
3- AMGEN INC, THOUSAND OAKS, CA USA
 
Introduction:

We evaluated the safety, tolerability, pharmacokinetics(PK), and pharmacodynamics(PD) of a single dose of cinacalcet in children with secondary hyperparathyroidism(sHPT) receiving dialysis.

Material and methods:

Twelve subjects (28 days to <6 years old) received a single 0.25mg/kg dose of cinacalcet. The dose was administered orally (syringe) or by nasogastric or gastric (NG/G) tube. Subjects were randomized 1:1 to two parathyroid hormone [PTH] and serum calcium sampling sequences post-dose: (1) 2, 8, and 48 hours; or (2) 2, 12, and 48 hours. Subjects were followed for 72 hours after dosing for the study assessments.

Results:

Cinacalcet median tmax was 1 hour (range: 0.50 to 4.0 hours). Plasma cinacalcet mean (SD) Cmax and AUClast were 2.83(1.98)ng/mL and 11.8(8.74)hr•ng/mL, respectively. The mean (SD) half-life (t1/2,z) was 3.70(2.57)hours. Subject age, weight, body surface area, and BMI did not have an effect on the PK of cinacalcet. Reductions in serum PTH concentrations from baseline were observed at 2 hours and 8 hours post-dose (median: ‑10.8% and ‑29.6%, respectively), and returned to near baseline levels at 72 hours (‑5.4%). These reductions correlated with changes in plasma cinacalcet concentrations. Safety findings were similar to safety profile observed in adults.

Conclusions:

A single dose of cinacalcet was well-tolerated in pediatric patients. Cinacalcet was rapidly absorbed and eliminated with no notable effects of age, weight, body surface area, and BMI on cinacalcet PK. Discernable reductions in serum iPTH were observed up to 8 hours after a single 0.25mg/kg dose of cinacalcet and returned to baseline by 72hours.  Results from this study indicate that a 0.25mg/kg dose of cinacalcet is deemed an appropriate safe starting dose in children 28 days to <6 years of age.