Clinical Evaluation of the Effect of Aficamten on QT/QTc Interval in Healthy Participants
Abstract
Aficamten is a next-in-class, small-molecule, cardiac myosin inhibitor in development for treating hypertrophic cardiomyopathy (HCM). This 2-part study evaluated aficamten's impact on QTc interval in healthy participants. Part A (n = 10) was an open-label study to find the appropriate dose for thorough QT (TQT) evaluation in Part B. Part B (n = 34) was a double-blind, 3-way crossover TQT study conducted as per ICH E14 guidance using negative (placebo) and positive (moxifloxacin) controls. A single 50 mg aficamten dose achieved exposures (Cmax range: 124-1660 ng/mL) comparable to the highest clinical dose (20 mg QD) in obstructive HCM patients (NCT05186818; [Cmax range: 131-1230 ng/mL]) and was chosen for TQT evaluation. Using concentration-QT (C-QT) modeling, the placebo- and baseline-corrected QT interval using Fridericia's correction (ΔΔQTcF) was -1.82 msec (90% CI: -3.43, -0.214) at peak aficamten concentrations (298.3 ng/mL) following the 50 mg dose. The 90% CI upper bound of ΔΔQTcF for aficamten was < 10 msec at all post-dose time points. Assay sensitivity was established by the 90% CI lower bound for moxifloxacin (ΔΔQTcF) exceeding 5 msec. Aficamten did not cause QTc prolongation (using C-QT and by time point analyses) within observed plasma concentrations up to 1660 ng/mL (aficamten), 213 ng/mL (metabolite CK-3834282), and 343 ng/mL (metabolite CK-3834283). No clinically meaningful effect on electrocardiogram parameters, including absolute QTcF (≤ 450 msec) and change…
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design. Reported size: 34 participants or records.
Read the paper
Related studies
- Synthesis, In Vitro and In Silico Molecular Docking Studies of Novel Phthalimide–Pyrimidine Hybrid Analogues to Thalidomide as Potent Antitubercular Agents
- Exploring the inhibitory performance of expired moxifloxacin and norfloxacin on copper corrosion in saline environment
- Molecular investigation of antimicrobial peptides against Helicobacter pylori proteins using a peptide-protein docking approach
- Screening of novel narrow-spectrum benzofuroxan derivatives for the treatment of multidrug-resistant tuberculosis through in silico, in vitro, and in vivo approaches
- Synthesis, Characterization, Anticancer, Antioxidant, and In Silico Evaluation of Semicarbazides and Thiosemicarbazides
- Fast and accurate prediction of drug induced proarrhythmic risk with sex specific cardiac emulators
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.