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

CONTEXT: 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. O...

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Autores principales: Martin, Kevin J., Bell, Gregory, Pickthorn, Karen, Huang, Saling, Vick, Andrew, Hodsman, Peter, Peacock, Munro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3910343/
https://www.ncbi.nlm.nih.gov/pubmed/24235081
http://dx.doi.org/10.1093/ndt/gft417
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author Martin, Kevin J.
Bell, Gregory
Pickthorn, Karen
Huang, Saling
Vick, Andrew
Hodsman, Peter
Peacock, Munro
author_facet Martin, Kevin J.
Bell, Gregory
Pickthorn, Karen
Huang, Saling
Vick, Andrew
Hodsman, Peter
Peacock, Munro
author_sort Martin, Kevin J.
collection PubMed
description CONTEXT: 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.
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spelling pubmed-39103432014-02-03 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 Nephrol Dial Transplant Clinical Science CONTEXT: 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. Oxford University Press 2014-02 2013-11-13 /pmc/articles/PMC3910343/ /pubmed/24235081 http://dx.doi.org/10.1093/ndt/gft417 Text en © The Author 2013. Published by Oxford University Press on behalf of ERA-EDTA. http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits noncommercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Clinical Science
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
title Velcalcetide (AMG 416), a novel peptide agonist of the calcium-sensing receptor, reduces serum parathyroid hormone and FGF23 levels in healthy male subjects
title_full Velcalcetide (AMG 416), a novel peptide agonist of the calcium-sensing receptor, reduces serum parathyroid hormone and FGF23 levels in healthy male subjects
title_fullStr Velcalcetide (AMG 416), a novel peptide agonist of the calcium-sensing receptor, reduces serum parathyroid hormone and FGF23 levels in healthy male subjects
title_full_unstemmed Velcalcetide (AMG 416), a novel peptide agonist of the calcium-sensing receptor, reduces serum parathyroid hormone and FGF23 levels in healthy male subjects
title_short Velcalcetide (AMG 416), a novel peptide agonist of the calcium-sensing receptor, reduces serum parathyroid hormone and FGF23 levels in healthy male subjects
title_sort velcalcetide (amg 416), a novel peptide agonist of the calcium-sensing receptor, reduces serum parathyroid hormone and fgf23 levels in healthy male subjects
topic Clinical Science
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3910343/
https://www.ncbi.nlm.nih.gov/pubmed/24235081
http://dx.doi.org/10.1093/ndt/gft417
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