Vol 29: Velcalcetide AMG 416, a novel peptide agonist of the calcium-sensing receptor, reduces serum parathyroid hormone and FGF23 levels in healthy male subjects.Report as inadecuate



 Vol 29: Velcalcetide AMG 416, a novel peptide agonist of the calcium-sensing receptor, reduces serum parathyroid hormone and FGF23 levels in healthy male subjects.


Vol 29: Velcalcetide AMG 416, a novel peptide agonist of the calcium-sensing receptor, reduces serum parathyroid hormone and FGF23 levels in healthy male subjects. - Download this document for free, or read online. Document in PDF available to download.

Download or read this book online for free in PDF: Vol 29: Velcalcetide AMG 416, a novel peptide agonist of the calcium-sensing receptor, reduces serum parathyroid hormone and FGF23 levels in healthy male subjects.
This article is from Nephrology Dialysis Transplantation, volume 29.AbstractContext: Velcalcetide, also known as AMG 416, is a novel, long-acting selective peptide agonist of the calcium sensing receptor. It is being developed as an intravenous treatment of secondary hyperparathyroidism SHPT in hemodialysis patients with chronic kidney disease—mineral and bone disorder. Objective: To assess the safety, tolerability, pharmacokinetics and pharmacodynamics of velcalcetide in healthy male volunteers. Methods: The study was a double-blind, randomized, placebo-controlled, single-dose, dose-escalation study in healthy males aged 18–45 years conducted at a single center. Each cohort included eight subjects randomized 6:2 to velcalcetide or placebo. Intervention: Velcalcetide at 0.5, 2, 5 and 10 mg or placebo was administered intravenously. Outcomes: Measurements included plasma ionized calcium iCa, serum total calcium, intact parathyroid hormone iPTH, phosphorus and fibroblast growth factor-23 FGF23, 1,25-dihydroxyvitamin D, calcitonin and urine creatinine, calcium and phosphorus and plasma pharmacokinetics for velcalcetide. Vital signs, safety biochemical and hematological indices, and adverse events were monitored throughout the study. Results: Intravenous administration of velcalcetide was well tolerated with no adverse reaction of nausea, vomiting or diarrhea reported. Velcalcetide mediated dose-dependent decreases in serum iPTH at 30 min, FGF23 at 24 h and iCa at 12 h post dose P 0.05 and in urine fractional excretion of phosphorus and increases in tubular reabsorption of phosphorus. Velcalcetide plasma exposure increased in a dose-related manner and the terminal elimination of half-life was comparable across the dose range evaluated and ranged from 18.4 to 20.0 h. Conclusion: Single IV doses of velcalcetide were well tolerated and associated with rapid, sustained, dose-dependent reductions in serum PTH. The results support further evaluation of velcalcetide as a treatment for SHPT in hemodialysis patients.



Author: Martin, Kevin J.; Bell, Gregory; Pickthorn, Karen; Huang, Saling; Vick, Andrew; Hodsman, Peter; Peacock, Munro

Source: https://archive.org/







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