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Usefulness of ambulatory blood pressure monitoring to assess the melanocortin receptor agonist bremelanotide
BACKGROUND: Melanocortin receptor agonists that bind to the melanocortin receptor 4 may cause increases in blood pressure (BP). Bremelanotide is an on-demand, subcutaneous melanocortin-receptor agonist that binds to the melanocortin receptor 4 and is being developed for the treatment of female sexua...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Lippincott Williams & Wilkins
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5338879/ https://www.ncbi.nlm.nih.gov/pubmed/27977473 http://dx.doi.org/10.1097/HJH.0000000000001221 |
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author | White, William B. Myers, Martin G. Jordan, Robert Lucas, Johna |
author_facet | White, William B. Myers, Martin G. Jordan, Robert Lucas, Johna |
author_sort | White, William B. |
collection | PubMed |
description | BACKGROUND: Melanocortin receptor agonists that bind to the melanocortin receptor 4 may cause increases in blood pressure (BP). Bremelanotide is an on-demand, subcutaneous melanocortin-receptor agonist that binds to the melanocortin receptor 4 and is being developed for the treatment of female sexual dysfunction. METHODS: We studied the effects of bremelanotide administration on ambulatory BP and heart rate (HR), in a randomized, double-blind, placebo-controlled, and parallel-arm trial of three doses of bremelanotide (0.75, 1.25, and 1.75 mg) in 397 premenopausal women with female sexual dysfunction with normotension or controlled hypertension. Pharmacokinetic exposure was assessed in conjunction with ambulatory BP measurements. RESULTS: Increases in ambulatory SBP relative to placebo of 2.4 and 3.0 mmHg (1.25 mg; P values: 0.029 and 0.076) and 3.1 and 3.2 mmHg (1.75 mg; P values: 0.006 and 0.027), respectively, occurred following two doses, separated by 24 h at the 0 to 4-h postdose interval; peak increases typically lasted less than 15 min. Similar increases in the DBP were observed. Increases in BP were accompanied by reductions in HR during the 0–4-h interval for the 1.75-mg dose (−4.6 to −4.7 bpm; P < 0.001). Twenty-six participants discontinued after randomization due to prespecified increases in BP but the proportions were similar among the four treatment groups. CONCLUSION: These data show that ambulatory monitoring was a useful methodology to detect small, transient increases in ambulatory BP accompanied by reductions in HR following bremelanotide. Results of this trial led to appropriate in-clinic BP monitoring during the larger clinical development trials of this agent for female sexual dysfunction. |
format | Online Article Text |
id | pubmed-5338879 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Lippincott Williams & Wilkins |
record_format | MEDLINE/PubMed |
spelling | pubmed-53388792017-03-22 Usefulness of ambulatory blood pressure monitoring to assess the melanocortin receptor agonist bremelanotide White, William B. Myers, Martin G. Jordan, Robert Lucas, Johna J Hypertens ORIGINAL PAPERS: BP measurement BACKGROUND: Melanocortin receptor agonists that bind to the melanocortin receptor 4 may cause increases in blood pressure (BP). Bremelanotide is an on-demand, subcutaneous melanocortin-receptor agonist that binds to the melanocortin receptor 4 and is being developed for the treatment of female sexual dysfunction. METHODS: We studied the effects of bremelanotide administration on ambulatory BP and heart rate (HR), in a randomized, double-blind, placebo-controlled, and parallel-arm trial of three doses of bremelanotide (0.75, 1.25, and 1.75 mg) in 397 premenopausal women with female sexual dysfunction with normotension or controlled hypertension. Pharmacokinetic exposure was assessed in conjunction with ambulatory BP measurements. RESULTS: Increases in ambulatory SBP relative to placebo of 2.4 and 3.0 mmHg (1.25 mg; P values: 0.029 and 0.076) and 3.1 and 3.2 mmHg (1.75 mg; P values: 0.006 and 0.027), respectively, occurred following two doses, separated by 24 h at the 0 to 4-h postdose interval; peak increases typically lasted less than 15 min. Similar increases in the DBP were observed. Increases in BP were accompanied by reductions in HR during the 0–4-h interval for the 1.75-mg dose (−4.6 to −4.7 bpm; P < 0.001). Twenty-six participants discontinued after randomization due to prespecified increases in BP but the proportions were similar among the four treatment groups. CONCLUSION: These data show that ambulatory monitoring was a useful methodology to detect small, transient increases in ambulatory BP accompanied by reductions in HR following bremelanotide. Results of this trial led to appropriate in-clinic BP monitoring during the larger clinical development trials of this agent for female sexual dysfunction. Lippincott Williams & Wilkins 2017-04 2016-12-12 /pmc/articles/PMC5338879/ /pubmed/27977473 http://dx.doi.org/10.1097/HJH.0000000000001221 Text en Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. http://creativecommons.org/licenses/by-nc-nd/4.0 This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBYNC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0 |
spellingShingle | ORIGINAL PAPERS: BP measurement White, William B. Myers, Martin G. Jordan, Robert Lucas, Johna Usefulness of ambulatory blood pressure monitoring to assess the melanocortin receptor agonist bremelanotide |
title | Usefulness of ambulatory blood pressure monitoring to assess the melanocortin receptor agonist bremelanotide |
title_full | Usefulness of ambulatory blood pressure monitoring to assess the melanocortin receptor agonist bremelanotide |
title_fullStr | Usefulness of ambulatory blood pressure monitoring to assess the melanocortin receptor agonist bremelanotide |
title_full_unstemmed | Usefulness of ambulatory blood pressure monitoring to assess the melanocortin receptor agonist bremelanotide |
title_short | Usefulness of ambulatory blood pressure monitoring to assess the melanocortin receptor agonist bremelanotide |
title_sort | usefulness of ambulatory blood pressure monitoring to assess the melanocortin receptor agonist bremelanotide |
topic | ORIGINAL PAPERS: BP measurement |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5338879/ https://www.ncbi.nlm.nih.gov/pubmed/27977473 http://dx.doi.org/10.1097/HJH.0000000000001221 |
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