Abstract: FR-PO292

A Phase 3, Multicenter, Randomized, Open-Label, Controlled Study to Assess the Efficacy, Safety, and Tolerability of Cinacalcet in Addition to Standard of Care in Pediatric Subjects Ages 6 to 17 Years

Session Information

Category: Mineral Disease

  • 1202 Mineral Disease: Vitamin D, PTH, FGF-23

Authors

  • Schaefer, Franz S., University of Heidelberg, Heidelberg, BW, Germany
  • Drozdz, Dorota, Jagiellonian University Medical College, Krakow, Poland
  • Fouqueray, Bruno L., None, ZUG, ZG, Switzerland
  • Iles, Jan, Amgen Inc, Thousand Oaks, Colorado, United States
  • Ma, Xiaoye, Amgen.Inc, San Bruno, California, United States
  • Rheault, Michelle N., University of Minnesota, Minneapolis, Minnesota, United States
  • Stefanidis, Constantinos J., A. and P. Kyriakou Childrens Hospital Athens, Greece, Athens, Greece
  • Rodig, Nancy MacDonald, Children's Hospital Boston, Boston, Massachusetts, United States
  • Warady, Bradley A., The Children's Mercy Hospital, Kansas City, Missouri, United States
Background

Standard of care (SoC) for secondary hyperparathyroidism for children on dialysis includes vitamin D sterols, calcium (Ca) supplementation, and phosphate (P) binders, while cinacalcet (CIN) has been shown to reduce parathyroid hormone (PTH), Ca, and P. Efficacy and safety data for CIN are limited in the pediatric chronic kidney disease population.

Methods

Pediatric subjects ages 6 to<18yrs were randomized 1:1 CIN+SoC:SoC stratified by age (6 to<12 & 12 to<18 yrs) to evaluate the efficacy of CIN+SoC for reducing mean plasma PTH by ≥30% from baseline during the efficacy assessment phase (EAP) wks 17-20. Eligible subjects had 2 consecutive PTH levels≥300pg/mL at entry and albumin corrected Ca (cCa) ≥8.8mg/dL. CIN was administered once daily starting at 0.20mg/kg/day and adjusted once monthly up to 2.5mg/kg/day or 180mg, whichever was lower, based on PTH, cCa, ionized Ca (iCa), and safety. CIN was held if cCa<8mg/dL or iCa<1mmol/L. Nature, frequency, and severity of adverse events (AEs) were assessed.

Results

22/27 CIN+SoC (56% boys) and 25/28 SoC (46% boys) randomized subjects received ≥12wks of treatment. Mean age was 12.6yrs with more subjects in the 12 to<18yrs group. The proportion of subjects who achieved PTH reduction ≥30% was not significant: 22.2%(6/27) CIN; 32.1%(9/28) SoC (p=0.42 stratified by age). Mean(SD) duration of exposure to CIN was 112.8(41.0)days with average weight-adjusted daily dose of 0.398(0.467)mg/kg/day during EAP. 21(84.0%) CIN and 17(56.7%) SoC subjects had ≥1 AE during the study with most ≤grade 2 in severity. The most common CIN AEs were hypocalcemia(24.0%), muscle spasms(12.0%), nausea(12.0%) and headache(4.0%).

Conclusion

Efficacy of CIN was not demonstrated likely due to inadequate exposure. Safety data were consistent with the known safety profile.

Funding

  • Commercial Support