To Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of MYK-224 in Healthy Volunteers

Study consists of single-ascending doses (SAD) and multiple ascending doses (MAD) of MYK-224 to healthy participants aged 18-45 years. This is a first in human (FIH) study, a sentinel dosing plan will be employed at each dose level. The first 2 healthy participants of each cohort will be dosed as sentinels. One of the sentinel healthy participants will be randomized to receive MYK-224 and the other will be randomized to receive placebo. Part A – SAD Cohorts This part will consist of a SAD design, where up to 6 cohorts of 8 healthy men or women will be randomized to MYK-224 or matching placebo in a 6:2 ratio. The starting dose of MYK-224 will be 1.5 mg and subsequent dose levels will be based on a review of the safety, PK and PD (including left ventricular ejection fraction, global longitudinal strain, and left ventricular fractional shortening) data from the previous dose level. The SRC will determine which cohort will participate in the FE portion of the study. That cohort will receive their dose twice in a cross-over fashion (once fasted, once fed); the 2 periods will be separated by a washout period of 35 days (or, after consultation with the Investigator, up to 42 days). Part B – MAD Cohorts This part will consist of a MAD design, where up to 6 cohorts of 8 healthy men or women will be randomized to MYK-224 or its placebo in a 6:2 ratio. This part will be initiated after satisfactory SRC review of safety data from at least 2 cohorts of healthy participants in Part A and SRC approval to initiate the MAD portion. The starting dose will be determined based on data obtained in Part A. Route of administration: Oral suspension Frequency/duration of dosing: SAD cohort: Single dose only; Food Effect -cohort Part 1: 1 Single dose, Part 2: 1 Single dose; MAD cohort: once daily Dose is being conducted under close supervision in a Phase I unit. Syringes containing MYK224 suspension are retained for drug accountability. fasting and fed conditions: In the fasting condition, participants are required to not consume food or liquid (except water) overnight for at least 8 hours prior to drug administration (i.e. pre-dose fast). Participants are then required to fast another four hours after the drug administration (i.e. post-dose fast). In the fed condition, participants are required to consume a high fat, high caloric breakfast containing 800 to 1,000 calories, with about 50% of calories from fat, prior to drug administration. Duration of the wash-out period between the fasted and fed conditions: 35 days after discharge from the CRU (or up to 42 days with approval from the PI) Part A (SAD): up to 64 days; Part A (FE): up to 121 days; Part B (MAD): up to 84 days Overall duration of treatment for part B: One administration of MYK-224 or placebo each day for 28 days; overall confinement period is 35 days with a follow-up visit between days 45 and 56. The starting dose of the MAD cohort is dependent on the data from the SAD cohorts.