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

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

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

ContextVelcalcetide, 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.ObjectiveTo 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.InterventionVelcalcetide at 0.5, 2, 5 and 10 mg or placebo was administered intravenously.OutcomesMeasurements 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. Conclusions. ingle 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.

Original languageEnglish
Pages (from-to)385-392
Number of pages8
JournalNephrology Dialysis Transplantation
Volume29
Issue number2
DOIs
StatePublished - Feb 2014

Fingerprint

Calcium-Sensing Receptors
Parathyroid Hormone
Healthy Volunteers
Peptides
Serum
Phosphorus
Calcium
Secondary Hyperparathyroidism
Placebos
Renal Dialysis
Pharmacokinetics
Urine
Chronic Kidney Disease-Mineral and Bone Disorder
Safety
fibroblast growth factor 23
AMG-416
Fibroblast Growth Factor 1
Dihydroxycholecalciferols
Vital Signs
Calcitonin

Keywords

  • AMG 416
  • calcimimetic
  • FGF23
  • parathyroid hormone
  • velcalcetide

ASJC Scopus subject areas

  • Nephrology
  • Transplantation

Cite this

Velcalcetide (AMG 416), a novel peptide agonist of the calcium-sensing receptor, reduces serum parathyroid hormone and FGF23 levels in healthy male subjects. / Martin, Kevin J.; Bell, Gregory; Pickthorn, Karen; Huang, Saling; Vick, Andrew; Hodsman, Peter; Peacock, Munro.

In: Nephrology Dialysis Transplantation, Vol. 29, No. 2, 02.2014, p. 385-392.

Research output: Contribution to journalArticle

Martin, Kevin J. ; Bell, Gregory ; Pickthorn, Karen ; Huang, Saling ; Vick, Andrew ; Hodsman, Peter ; Peacock, Munro. / Velcalcetide (AMG 416), a novel peptide agonist of the calcium-sensing receptor, reduces serum parathyroid hormone and FGF23 levels in healthy male subjects. In: Nephrology Dialysis Transplantation. 2014 ; Vol. 29, No. 2. pp. 385-392.
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T1 - Velcalcetide (AMG 416), a novel peptide agonist of the calcium-sensing receptor, reduces serum parathyroid hormone and FGF23 levels in healthy male subjects

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AU - Huang, Saling

AU - Vick, Andrew

AU - Hodsman, Peter

AU - Peacock, Munro

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N2 - ContextVelcalcetide, 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.ObjectiveTo 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.InterventionVelcalcetide at 0.5, 2, 5 and 10 mg or placebo was administered intravenously.OutcomesMeasurements 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. Conclusions. ingle 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.

AB - ContextVelcalcetide, 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.ObjectiveTo 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.InterventionVelcalcetide at 0.5, 2, 5 and 10 mg or placebo was administered intravenously.OutcomesMeasurements 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. Conclusions. ingle 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.

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