BioCentury
ARTICLE | Clinical News

Dalcetrapib: Additional Phase III data

November 12, 2012 8:00 AM UTC

Detailed data from the double-blind, international Phase III dal-OUTCOMES trial in 15,871 patients with stable CHD following a recent acute coronary syndrome (ACS) showed that once-daily 600 mg oral dalcetrapib plus standard of care (SOC) missed the primary endpoint of reducing a composite of time to first occurrence of CHD death, non-fatal acute MI, hospitalization for unstable angina, resuscitated cardiac arrest or stroke vs. placebo plus SOC (8.3% vs. 8%, p=0.52). The analysis, which was conducted at a median follow-up of 31 months, included 1,135 primary endpoint events (71% of the projected total number). In May, Roche discontinued development of dalcetrapib due a "lack of clinically meaningful efficacy." The pharma made the decision based on a recommendation from the study's DSMB, which said that dalcetrapib plus SOC would not show a 15% reduction on the composite primary endpoint vs. placebo plus SOC (see BioCentury, May 14).

Dalcetrapib did increase HDL-C by 31-40% from baseline vs. 4-11% for placebo. Dalcetrapib had a "minimal effect" on LDL-C. Additionally, dalcetrapib did not significantly reduce the incidence of any component of the primary endpoint vs. placebo - CHD death (1.5% vs. 1.6%, p=0.66), non-fatal acute MI (5.2% vs. 5.1%, p=0.8), hospitalization for unstable angina (1.1% vs. 1.2%, p=0.54), resuscitated cardiac arrest (0.2% vs. 0.1%, p=0.4) or stroke (1.1% vs. 0.9%, p=0.16). Dalcetrapib also did not significantly reduce the incidence of unanticipated coronary revascularization (8.5% for both, p=0.97) or death from any cause (2.8% vs. 2.9%, p=0.9) vs. placebo. Dalcetrapib also significantly increased mean systolic blood pressure (SBP) and median C-reactive protein (CRP) levels vs. placebo (p<0.001). ...