Ulacamten

Purpose-bred cats (1-10 years old; naturally occurring obstructive hypertrophic cardiomyopathy with subclinical LV hypertrophy without left atrial enlargement and left ventricular outflow tract obstruction)^[1]

2 mg/kg; 5 mg/kg; 10 mg/kg; 15 mg/kg

p.o.; single dose

Showed no significant differences in heart rate from vehicle at any timepoint across all doses.
Increased systolic LV internal diameter (LVIDs Sx) significantly from baseline at 6 hours post-dose at 15 mg/kg; produced significantly greater LVIDs Sx than vehicle in 2 mg/kg and 15 mg/kg groups at 6-hour dobutamine challenge.
Resolved dobutamine-induced increases in LV fractional shortening (LV FS%) seen in vehicle-treated cats at all tested doses; reduced LV FS% significantly from baseline at 6 hours post-dose at 15 mg/kg; produced significantly lower LV FS% than vehicle in 15 mg/kg group at 6 hours post-dose and 6-hour challenge, and in 10 mg/kg group at 24 hours post-dose.
Resolved dobutamine-induced increases in LV ejection fraction (LV EF%) seen in vehicle-treated cats at all tested doses; reduced LV EF% significantly from baseline at 6 hours post-dose at 15 mg/kg; produced significantly lower LV EF% than vehicle in 15 mg/kg group at 6 hours post-dose and 6-hour challenge, and in 10 mg/kg group at 24 hours post-dose.
Blunted dobutamine-induced increases in LVOT maximum pressure gradient (LVOTmaxPG) at 10 mg/kg and 15 mg/kg; reduced LVOTmaxPG significantly from baseline at 6 hours post-dose at 15 mg/kg; maintained median LVOTmaxPG values below the 14.5 mmHg obstruction threshold up to 48 hours post-dose in 5, 10, and 15 mg/kg groups.
Caused a dose-dependent decrease in the incidence of LVOTO (LVOTmaxPG ≥14.5 mmHg) at each timepoint; provided protection against dobutamine-induced obstruction in 10 and 15 mg/kg groups.