Abstract: FR-PO291

An Open-Label, Single-Arm Study to Assess the Safety, Tolerability, and Efficacy of Cinacalcet in Addition to Standard of Care in Pediatric Subjects Ages 28 Days to <6 Years

Session Information

Category: Mineral Disease

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

Authors

  • Goodman, William G., Amgen, Inc., CALABASAS, California, United States
  • Iles, Jan, Amgen Inc, Thousand Oaks, Colorado, United States
  • Yang, Jun, Amgen, Thousand Oaks, California, United States
  • Ertik, Bella, Amgen, Thousand Oaks, California, United States
  • Sohn, Winnie, Amgen, Thousand Oaks, California, United States
  • Vondrak, Karel, University Hospital Prague-Motol, Prague 5, Czechia
  • Schmitt, Claus P., Center for Pediatric and Adolescent Medicine, Heidelberg, Germany
  • Salusky, Isidro B., Mattel Children's Hospital, Los Angeles, California, United States
Background

Data are limited on the safety, tolerability, and efficacy of cinacalcet (CIN) in children with secondary hyperparathyroidism (SHPT) on dialysis. In this phase 2, multicenter, 26-week, single-arm, open-label study, we evaluated CIN+standard of care that includes vitamin D sterols in pediatric subjects with SHPT on dialysis.

Methods

Pediatric subjects ages 28d to <6yrs with SHPT on dialysis with parathyroid hormone (PTH) levels≥300pg/mL and serum corrected Ca≥9.4mg/dL (28d to <2yrs) or ≥8.8mg/dL (2 to <6yrs) were evaluated. The daily starting and maximum dose of CIN were changed during the study from 0.25mg/kg and 4.2mg/kg to 0.20mg/kg and 2.5mg/kg or 60mg maximum, whichever was lower. Primary endpoint: the proportion of subjects who developed cCa<9.0mg/dL (28d to <2yrs) and <8.4mg/dL (≥2 to <6yrs); secondary endpoints: percent change of plasma PTH from baseline, ≥30% reduction from baseline in PTH, PTH<300pg/mL, and cCa<8.8mg/dL. Nature, frequency, and severity of adverse events (AEs) were summarized.

Results

17/18 enrolled subjects received ≥1dose of CIN; 66.7% were boys, 83.3% white, and mean age was 35.9mos. Mean CIN exposure time was 86.7days and the maximum daily dose of CIN was 30mg (2 subjects). Mean (SD) weight-adjusted daily starting dose and maximum dose during the study was 0.18(0.07)mg/kg and 0.73(0.66)mg/kg, respectively. No subject had cCa<9.0 or <8.4mg/dL for the 2 groups and 2 subjects (2 to <6yrs group) had cCa<8.8mg/dL. Overall, 70.6% of subjects showed reductions in PTH≥30% and 52.9% subjects achieved PTH<300pg/mL during the study. All subjects received therapy with vitamin D sterols during the study. 94.1% of subjects had ≥1 treatment-emergent AE. The most common AEs were cough, hypertension, upper respiratory tract infection, and vomiting. There were no treatment-related serious AEs, fatal AEs nor AE leading to the discontinuation of CIN.

Conclusion

No subject had a Ca value below the threshold for the primary endpoint. Data show a downward trend in PTH from baseline after CIN administration. Safety data were consistent with the known safety profile.

Funding

  • Commercial Support