Phase 1 Evaluation of the Pharmacokinetics of Sevasemten ( EDG ‐5506) for Potential Food Effect and Drug–Drug Interaction With a CYP3A4 Moderate Inh

ABSTRACT

Sevasemten (EDG‐5506) is an investigational, small molecule, in development for the treatment of Becker and Duchenne muscular dystrophy. In vitro data suggest sevasemten is a substrate for cytochrome P450 (CYP)3A4. Here, we investigate whether the pharmacokinetics (PK) of sevasemten are affected when co‐administered with a moderate CYP3A4 inhibitor, verapamil. The impact of a high‐fat meal on the PK of sevasemten was also investigated. This Phase 1, open‐label, parallel study of healthy subjects dosed three unique cohorts (sevasemten alone, sevasemten co‐administered with verapamil, and sevasemten under fed conditions). Administration of a single dose of sevasemten with daily dosing of verapamil had no significant effect on the maximum concentration (C _max ) or area under the plasma concentration‐time curve (AUC) of sevasemten compared to a single dose of sevasemten under fasted conditions (Geometric mean ratios of 101.6% and 97.5%, respectively), indicating that the PK of sevasemten may not be influenced by verapamil, a moderate CYP3A4 inhibitor. Administration of a single dose of sevasemten under fed conditions increased the AUCs of sevasemten by 20% to 38%, while the C _max remained comparable to that under fasted conditions. Together, these data support allowing patients who benefit from sevasemten to also use a moderate CYP3A inhibitor without dose modification and support administration of sevasemten without regard to food intake.