Hypertrophic cardiomyopathy is the most common inherited cardiovascular disorder. Credit: Patrick J. Lynch, medical illustrator.

Cytokinetics has dosed the first subject in a Phase I trial evaluating the safety and tolerability of CK-3773274 (CK-274) to treat hypertrophic cardiomyopathy (HCM).

HCM is the most common inherited cardiovascular disorder that is estimated to affect around one in 500 individuals globally.

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Cytokinetics aims to assess single and multiple oral doses of CK-274 in healthy subjects as part of the double-blind, randomised, placebo-controlled trial.

The multi-part trial comprises eight single and three multiple ascending dose cohorts consisting of eight subjects each.

Key endpoints include explaining the pharmacokinetics (PK) of CK-274 and its pharmacodynamic effects (PD) as measured by echocardiography.

“This first trial will elaborate on CK-274 and its potential to be best-in-class and we look forward to reporting data in 2019.”

It will also characterise the relationship between the PK and PD of CK-274 for cardiac function.

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Cytokinetics Research and Development executive vice-president of Fady Malik said: “The start of clinical trials for CK-274 marks an important milestone in our continuing innovation of potential sarcomere-directed medicines.

“Our scientists pioneered this emerging area of muscle pharmacology and have now advanced a next-generation drug candidate that was optimized for pharmacokinetic properties and therapeutic index.

“This first trial will elaborate on CK-274 and its potential to be best-in-class and we look forward to reporting data in 2019.”

CK-274 is a new, oral, small molecule cardiac myosin inhibitor designed to reduce the hypercontractility associated with HCM.

The drug has previously been able to minimise myocardial contractility by binding directly to cardiac myosin at a separate and selective allosteric binding site.