MyoKardia presented data at the European Society of Cardiology from its Phase 1a single-ascending dose study of MYK-491 in healthy volunteers. MYK-491 is MyoKardia’s most advanced activator molecule, designed to increase contractility of the heart with minimal effects on myocardial relaxation. First-in-human data from the Phase 1a clinical trial of MYK-491 in healthy volunteers showed the drug to be well tolerated. MYK-491 increased cardiac contractility by 5%-20% across multiple echocardiographic parameters at higher drug concentrations, with minimal impact on diastolic function. MYK-491 is currently being studied in a Phase 2a multiple-ascending dose clinical trial for the treatment of patients with systolic heart failure, in which the heart is unable to contract sufficiently to meet the demands of the body. The Phase 1 randomized, double-blind placebo-controlled study was designed to assess safety, tolerability, pharmacokinetics and pharmacodynamics of single-ascending oral doses of MYK-491. Sixty-four healthy adult volunteers were enrolled and randomized to receive placebo or single-ascending doses of MYK-491 ranging from 3mg-550mg. MYK-491 was generally well tolerated with no dose-limiting toxicities observed. Transient and spontaneously resolving arrhythmias were reported. The most common adverse event reported was headache, and there was no trend for increased AE frequency associated with higher dose concentrations. Pharmacokinetic results indicated MYK-491 may be amenable to once- or twice-daily dosing. Dose- and concentration-dependent increases in stroke volume and other indicators of enhanced systolic function were observed, including increases in left ventricular fractional shortening and ejection fraction as well as decreases in end-systolic left ventricular dimensions. At the highest dose cohort, a modest prolongation of systolic ejection time and no discernible impact on relaxation and diastolic function were observed.
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