Etelcalcetide (AMG 416), a novel calcimimetic agent for the treatment of secondary hyperparathyroidism (SHPT), is mostly cleared during hemodialysis (HD) finds a new study investigating its pharmacokinetics, biotransformation, and excretion.
The results add information on the intravenous (IV) drug under clinical development by Amgen. Notably, no new safety signals or anti-etelcalcetide antibodies were detected.
For the study, Raju Subramanian, PhD, director at Gilead Sciences in San Francisco, and colleagues, reviewed data on 6 HD patients with parathyroid hormone levels of 300 to 1200 pg/mL who were administered a single IV dose of radiolabeled etelcalcetide (10 mg). Blood, dialysate, urine, feces, and emesis were collected from each patient and analyzed.
According to results published in Clinical Pharmacokinetics, about 67% of the radioactive etelcalcetide dose was recovered in dialysate, urine, and feces within 176 days. The vast majority (60%) was eliminated in dialysate with minor excretions in urine and feces.
“Biotransformation resulted from reversible disulfide exchange with endogenous thiols, and the etelcalcetide D-amino acid backbone was preserved,” Dr Subramanian and colleagues wrote. “The majority of circulating etelcalcetide-related biotransformed moieties existed as serum albumin peptide conjugate (SAPC).”
After removal of plasma etelcalcetide by dialysis, reequilibration between SAPC and L-cysteine in blood partially restored predialysis concentrations of etelcalcetide, they added.
Mild adverse events occurred in 5 of the 6 patients, including constipation, contact dermatitis, flatulence, nausea, pneumonia, upper respiratory tract infection, and vomiting. One serious adverse event of severe pneumonia also occurred. Of these, only constipation and flatulence were considered treatment-related.
The study was funded by Amgen, the maker of IV etelcalcetide (Parsabiv™). Several of the study authors are shareholders or employees of the company.
1. Subramanian R, Zhu X, Hock B, et al. Pharmacokinetics, Biotransformation, and Excretion of [14C]Etelcalcetide (AMG 416) Following a Single Microtracer Intravenous Dose in Patients with Chronic Kidney Disease on Hemodialysis. Clin Pharmacokinet. doi 10.1007/s40262-016-0433-0.