Vericiguat: a randomized, phase Ib, placebo-controlled, double-blind, QTc interval study in patients with chronic coronary syndromes

Abstract: 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

Object Details

• Location: Deutsche Nationalbibliothek Frankfurt am Main
• Extent: Online-Ressource
• Language: Englisch
• Notes: American journal of cardiovascular drugs. - 23, 2 (2023) , 145-155, ISSN: 1179-187X

Contributors, Places and Time

• Event: Veröffentlichung
• (where): Freiburg
• (who): Universität
• (when): 2023
• Creator: 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

Further information

• DOI: 10.1007/s40256-022-00557-2
• URN: urn:nbn:de:bsz:25-freidok-2332482
• Rights: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Last update: 25.03.2025, 1:51 PM CET