Search

Obstructive hypertrophic cardiomyopathy (oHCM) is a subtype of HCM characterized by left ventricular outflow tract obstruction resulting from cardiac muscle hypertrophy and anatomic alterations in the mitral valve and apparatus. Mavacamten, a cardiac myosin inhibitor metabolized primarily by CYP2C19 in the liver, is the first and only targeted medication approved for the treatment of symptomatic New York Heart Association (NYHA) class II–III oHCM. Previous pharmacokinetic (PK) results of mavacamten in healthy Caucasian, Japanese, and Asian participants demonstrated that mavacamten exposure was affected by CYP2C19 metabolism status. This open‐label, parallel‐group, phase I trial aimed to determine the PK and safety of mavacamten in healthy Chinese participants with different CYP2C19 genotypes. The primary outcome was to define the PK of mavacamten in healthy Chinese participants; the secondary outcome was to examine safety and tolerability. After a single oral dose of 15 or 25 mg mavacamten in fasted healthy adult Chinese individuals, Cmax was reached within a median Tmax of 0.6–1.5 h, indicating rapid absorption. Inter‐individual variability was moderate, and individuals carrying non‐functional CYP2C19 alleles (*2/*2, *3/*3, or *2/*3) exhibited longer half‐life and increased total exposure. After stratification of CYP2C19 genotypes, total mavacamten exposures were similar among different ethnic groups when compared with prior PK studies. No significant adverse events were observed in this study. Single oral administration of mavacamten at 15 mg was well tolerated across all CYP2C19 genotypes, and 25 mg dose was well tolerated in healthy participants with CYP2C19 genotypes UM/RM/NM. The PK profile of mavacamten in the healthy Chinese population was consistent with that in other healthy populations. [ABSTRACT FROM AUTHOR]

The objectives of this phase I study are to assess the safety, tolerability, and pharmacokinetics (PKs) of RO7049389 in healthy Chinese volunteers (HVs) and evaluate potential ethnic differences in the safety and PKs using data from this study and the first‐in‐human study (in which most of the HVs were non‐Asian). HVs randomly received a single dose of 200–600 mg of RO7049389 or a placebo in a single ascending dose (n = 28) or multiple doses of 200–400 mg of RO7049389 or a placebo in multiple ascending doses (n = 24). Safety and tolerability were monitored throughout the study. Serial blood samples were collected for PK analysis. RO7049389 was safe and well‐tolerated in the HVs. The time to maximum concentration ranged from 1.5 to 3.0 h, and terminal half‐life ranged from 3.66 to 14.6 h. A single dose of 200–600 mg and multiple doses of 200–400 mg exhibited nonlinear PKs. In general, the safety profiles were comparable between non‐Asian and Asian HVs, but the plasma exposure of RO7049389 in Chinese HVs was higher than that in non‐Asian HVs. The data generated from this study will provide guidance for future clinical studies on RO7049389 in Chinese/Asian patients with hepatitis B virus. [ABSTRACT FROM AUTHOR]