Key result
A single 50-mg dose of omecamtiv mecarbil did not prolong the QTc interval in healthy subjects, with the highest upper bound of the 1-sided 95% CI for placebo-corrected change being 0.7 ms.
Why the study?
Omecamtiv mecarbil is under investigation for heart failure, but its effect at therapeutic concentrations on ECG parameters and the QTc interval needed to be evaluated.
Does a single 50 mg oral dose of omecamtiv mecarbil prolong the QTc interval in healthy subjects compared to placebo?
RCT (n=60)
crossover
Does a single 50 mg oral dose of omecamtiv mecarbil prolong the QTc interval in healthy subjects compared to placebo?
Omecamtiv mecarbil does not cause clinically relevant QTc prolongation at therapeutic concentrations, supporting its cardiac safety profile.
Answers are grounded in this paper and cite their sources.
Supports OM use in HF without QTc monitoring; confirms no clinically relevant repolarization effects at therapeutic concentrations.
AIMS: Omecamtiv mecarbil (OM) is a novel selective cardiac myosin activator under investigation for the treatment of heart failure. This study aimed to evaluate the effect of therapeutic concentrations of OM on electrocardiogram (ECG) parameters and exclude a clinically concerning effect on the rate-corrected QT (QTc) interval. METHODS: In part A, 70 healthy subjects received a 25 mg oral dose of OM, and pharmacokinetics were assessed. Only subjects with maximum observed plasma concentration ≤ 350 ng/mL (n = 60) were randomized into part B, where they received a single oral dose of placebo, 50 mg OM and 400 mg moxifloxacin in a 3-period, 3-treatment, 6-sequence crossover study with continuous ECG collection. RESULTS: After a 50-mg dose of OM, mean placebo-corrected change from baseline QTcF (∆∆QTcF; Fridericia correction) ranged from -6.7 ms at 1 hour postdose to -0.8 ms at 4 hours postdose. The highest upper bound of the 1-sided 95% confidence interval (CI) was 0.7 ms (4 h postdose). Moxifloxacin resulted in a clear increase in mean ∆∆QTcF, with a peak value of 13.1 ms (90% CI: 11.71-14.57) at 3 hours; lower bound of the 1-sided 95% CI was > 5 ms at all of the 3 prespecified time points. Based on a concentration-QTc analysis, an effect on ∆∆QTcF exceeding 10 ms can be excluded up to OM plasma concentrations of ~800 ng/mL. There were no serious or treatment-emergent adverse events leading to discontinuation from the study. CONCLUSION: OM does not have a clinically relevant effect on the studied ECG parameters.
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Trivedi et al. (2021) conducted an RCT in Healthy subjects (n=60). Omecamtiv mecarbil vs. Placebo was evaluated on Placebo-corrected change from baseline QTcF (∆∆QTcF) (MD -0.8 ms). A single 50-mg dose of omecamtiv mecarbil did not prolong the QTc interval in healthy subjects, with the highest upper bound of the 1-sided 95% CI for placebo-corrected change being 0.7 ms.
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