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Abstract: TH-PO761

Phase 1, Single-Dose Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Etelcalcetide in Pediatric Subjects with Secondary Hyperparathyroidism Receiving Hemodialysis

Session Information

  • Pediatric CKD
    November 07, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Pediatric Nephrology

  • 1700 Pediatric Nephrology

Authors

  • Sohn, Winnie, Amgen Inc., Thousand Oaks, California, United States
  • Salusky, Isidro B., David Geffen School of Medicine at UCLA, Los Angeles, California, United States
  • Schmitt, Claus peter, Center for Pediatric and Adolescent Medicine, Heidelberg, Germany
  • Taylan, Christina, University Hospital of Cologne, Cologne, Germany
  • Vande walle, Johan, UZGent, Gent, Belgium
  • Ngang, Jude A., Amgen Inc., Thousand Oaks, California, United States
  • Yan, Lucy, Amgen Inc., Thousand Oaks, California, United States
  • Warady, Bradley A., Children's Mercy Kansas City, Kansas City, Missouri, United States
Background

The calcimimetic etelcalcetide is approved for treatment of sHPT in adult patients receiving hemodialysis. However, there are limited data on etelcalcetide safety and efficacy in pediatric patients.

Methods

This Phase 1 study (NCT02833857) evaluated the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of etelcalcetide after single-dose administration (0.035 mg/kg IV, corresponding to the approved lowest dose of 2.5 mg) in pediatric hemodialysis subjects in 2 cohorts (cohort 1: aged 12–<18 y; cohort 2: aged 2–<12 y). Treatment-emergent adverse events (AEs) were assessed. Etelcalcetide PK/PD was assessed post-dose on D1 at 10 min and 4 h, on multiple days until D10, and at the end of study (D30).

Results

Etelcalcetide administered to 11 subjects (mean [SD] age=10.3 [4.3] y; cohort 1, n=6; cohort 2, n=5) was well tolerated and reported AEs were consistent with the known etelcalcetide safety profile. One subject each in both cohorts reported treatment-related AEs (cohort 1: hypocalcemia; cohort 2: headache, paresthesia, and vomiting) and no serious AEs or deaths were observed. Mean serum corrected Ca (cCa) for all subjects was maintained >2.25 mmol/L.
After dosing, PK exposures declined over time in both cohorts (Table). Median percent change in serum intact parathyroid hormone (iPTH) from baseline (cohort 1: 51.2 pmol/L; cohort 2: 84.0 pmol/L) reached the nadir on D1 at 4 h (cohort 1: −33.4%; cohort 2: −64.2%). In both cohorts, mean total Ca and cCa reached nadirs on D3 at 2.4 mmol/L, and mean ionized Ca on D1 at 4 h (1.1 mmol/L). Serum iPTH and cCa levels returned to baseline as etelcalcetide concentrations declined prior to the end of study in all subjects.

Conclusion

A single dose of 0.035 mg/kg was well tolerated, with no new safety concerns and PK/PD response was as expected. Given the high inter-subject variability, overlap in etelcalcetide concentrations, and small sample size, the differences in etelcalcetide exposures between the age groups were not likely to be clinically meaningful.

Pharmacokinetic parameterCohort 1 (age 12 – <18 y)
N=6
Cohort 2 (age 2 – <12 y)
N=5
Mean
(SD)
Coefficient of variation (%)Mean
(SD)
Coefficient of variation (%)
Cmax (ng/mL)67.0 (24.0)35.931.4 (23.8)75.8
AUClast (h*ng/mL)1790.0 (1360.0)76.1839.0 (397.0)47.3
t1/2 (d)5.7 (2.8)49.75.9 (3.0)50.9

Funding

  • Commercial Support