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Vericiguat: A Randomized, Phase Ib, Placebo-Controlled, Double-Blind, QTc Interval Study in Patients with Chronic Coronary Syndromes
BACKGROUND: Vericiguat is indicated for the treatment of symptomatic chronic heart failure in adult patients with reduced ejection fraction who are stabilized after a recent decompensation event. OBJECTIVE: To investigate the effects of vericiguat on QT interval in patients with chronic coronary syn...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer International Publishing
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10006255/ https://www.ncbi.nlm.nih.gov/pubmed/36633816 http://dx.doi.org/10.1007/s40256-022-00557-2 |
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author | Böttcher, Michael Düngen, Hans-Dirk Corcea, Vasile Donath, Frank Fuhr, Rainard Gal, Pim Mikus, Gerd Trenk, Dietmar Coenen, Martin Pires, Philippe Vieira Maschke, Claudia Aliprantis, Antonios Othon Besche, Nina Becker, Corina |
author_facet | Böttcher, Michael Düngen, Hans-Dirk Corcea, Vasile Donath, Frank Fuhr, Rainard Gal, Pim Mikus, Gerd Trenk, Dietmar Coenen, Martin Pires, Philippe Vieira Maschke, Claudia Aliprantis, Antonios Othon Besche, Nina Becker, Corina |
author_sort | Böttcher, Michael |
collection | PubMed |
description | BACKGROUND: Vericiguat is indicated for the treatment of symptomatic chronic heart failure in adult patients with reduced ejection fraction who are stabilized after a recent decompensation event. OBJECTIVE: To investigate the effects of vericiguat on QT interval in patients with chronic coronary syndromes (CCS). METHODS: This was a randomized, phase Ib, placebo-controlled, double-blind, double-dummy, multicenter study. Vericiguat once daily was up-titrated from 2.5 mg to 5 mg and then to 10 mg (treatments A, B, and C) at 14-day intervals. Positive control was moxifloxacin 400 mg (single dose on day 8 or day 50; placebo on other days [treatment D]). We evaluated the placebo-adjusted change from baseline of the Frederica-corrected QTc interval (QTcF), pharmacokinetics, safety, and tolerability of vericiguat. RESULTS: In total, 74 patients with CCS, with mean (standard deviation) age 63.4 (8.0) years, were included and 72 patients completed the study. At each timepoint up to 7 h after administration, mean placebo-corrected change in QTcF from baseline was < 6 ms and the upper limit of the two-sided 90% confidence interval of the mean was below the 10-ms threshold for clinical relevance. Moxifloxacin confirmed the assay sensitivity. Median time of maximum concentration of vericiguat was 4.5 h post-dose. The adverse event profile of vericiguat was consistent with its mechanism of action, and the findings did not indicate any safety concerns. CONCLUSIONS: As part of an integrative risk assessment, this study demonstrated no clinically relevant corrected QT prolongation with vericiguat 10 mg once daily at steady state. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov number, NCT03504982. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40256-022-00557-2. |
format | Online Article Text |
id | pubmed-10006255 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Springer International Publishing |
record_format | MEDLINE/PubMed |
spelling | pubmed-100062552023-03-12 Vericiguat: A Randomized, Phase Ib, Placebo-Controlled, Double-Blind, QTc Interval Study in Patients with Chronic Coronary Syndromes Böttcher, Michael Düngen, Hans-Dirk Corcea, Vasile Donath, Frank Fuhr, Rainard Gal, Pim Mikus, Gerd Trenk, Dietmar Coenen, Martin Pires, Philippe Vieira Maschke, Claudia Aliprantis, Antonios Othon Besche, Nina Becker, Corina Am J Cardiovasc Drugs Original Research Article BACKGROUND: Vericiguat is indicated for the treatment of symptomatic chronic heart failure in adult patients with reduced ejection fraction who are stabilized after a recent decompensation event. OBJECTIVE: To investigate the effects of vericiguat on QT interval in patients with chronic coronary syndromes (CCS). METHODS: This was a randomized, phase Ib, placebo-controlled, double-blind, double-dummy, multicenter study. Vericiguat once daily was up-titrated from 2.5 mg to 5 mg and then to 10 mg (treatments A, B, and C) at 14-day intervals. Positive control was moxifloxacin 400 mg (single dose on day 8 or day 50; placebo on other days [treatment D]). We evaluated the placebo-adjusted change from baseline of the Frederica-corrected QTc interval (QTcF), pharmacokinetics, safety, and tolerability of vericiguat. RESULTS: In total, 74 patients with CCS, with mean (standard deviation) age 63.4 (8.0) years, were included and 72 patients completed the study. At each timepoint up to 7 h after administration, mean placebo-corrected change in QTcF from baseline was < 6 ms and the upper limit of the two-sided 90% confidence interval of the mean was below the 10-ms threshold for clinical relevance. Moxifloxacin confirmed the assay sensitivity. Median time of maximum concentration of vericiguat was 4.5 h post-dose. The adverse event profile of vericiguat was consistent with its mechanism of action, and the findings did not indicate any safety concerns. CONCLUSIONS: As part of an integrative risk assessment, this study demonstrated no clinically relevant corrected QT prolongation with vericiguat 10 mg once daily at steady state. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov number, NCT03504982. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40256-022-00557-2. Springer International Publishing 2023-01-12 2023 /pmc/articles/PMC10006255/ /pubmed/36633816 http://dx.doi.org/10.1007/s40256-022-00557-2 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by-nc/4.0/Open AccessThis article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) . |
spellingShingle | Original Research Article Böttcher, Michael Düngen, Hans-Dirk Corcea, Vasile Donath, Frank Fuhr, Rainard Gal, Pim Mikus, Gerd Trenk, Dietmar Coenen, Martin Pires, Philippe Vieira Maschke, Claudia Aliprantis, Antonios Othon Besche, Nina Becker, Corina Vericiguat: A Randomized, Phase Ib, Placebo-Controlled, Double-Blind, QTc Interval Study in Patients with Chronic Coronary Syndromes |
title | Vericiguat: A Randomized, Phase Ib, Placebo-Controlled, Double-Blind, QTc Interval Study in Patients with Chronic Coronary Syndromes |
title_full | Vericiguat: A Randomized, Phase Ib, Placebo-Controlled, Double-Blind, QTc Interval Study in Patients with Chronic Coronary Syndromes |
title_fullStr | Vericiguat: A Randomized, Phase Ib, Placebo-Controlled, Double-Blind, QTc Interval Study in Patients with Chronic Coronary Syndromes |
title_full_unstemmed | Vericiguat: A Randomized, Phase Ib, Placebo-Controlled, Double-Blind, QTc Interval Study in Patients with Chronic Coronary Syndromes |
title_short | Vericiguat: A Randomized, Phase Ib, Placebo-Controlled, Double-Blind, QTc Interval Study in Patients with Chronic Coronary Syndromes |
title_sort | vericiguat: a randomized, phase ib, placebo-controlled, double-blind, qtc interval study in patients with chronic coronary syndromes |
topic | Original Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10006255/ https://www.ncbi.nlm.nih.gov/pubmed/36633816 http://dx.doi.org/10.1007/s40256-022-00557-2 |
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