GlaxoSmithKline (GSK) has reported the results of a Phase III STABILITY trial of darapladib for the treatment of patients with chronic coronary heart disease (CHD).
In the double-blind, event-driven Phase III trial, 15,828 CHD patients were given 160mg of darapladib or placebo once-daily on a background of standard of care.
The trial’s primary endpoint was time to first occurrence of any major adverse cardiovascular event (MACE) comprising cardiovascular death, myocardial infarction (MI) and stroke.
The trial’s secondary endpoints included major coronary events (MCE) comprising CHD death, MI or urgent coronary revascularisation for myocardial ischemia; total coronary events comprising CHD death, MI, hospitalisation for unstable angina or any coronary revascularisation procedure; the individual components of MACE; and all-cause mortality.
The company said that no difference was observed in the treatment groups in the time to first occurrence of MACE.
During 3.7 years median follow-up, the primary endpoint of MACE occurred in 9.7% of patients in the darapladib group and 10.4% of patients in the placebo group; hazard ratio (HR) 0.94, 95% confidence interval (0.85 – 1.03), p=0.199.
Hazard ratios (HRs) for individual components were cardiovascular death 0.96 (0.83 – 1.11), MI 0.89 (0.77 – 1.03) and stroke 1.01 (0.81 – 1.27).
Among the secondary endpoints, major coronary events occurred in 9.3% of patients taking darapladib versus 10.3% in the placebo group.
Similar effects were observed for the composite of total coronary events, which occurred in 14.9% of patients on darapladib versus 16.1% on placebo; HR 0.91 (0.84, 0.98), p=0.019 (nominal significance).
There was no difference in all-cause mortality, which occurred in 7.3% of patients in both groups.
Auckland City Hospital director of Coronary Care Unit, Green Lane Cardiovascular Unit and the co-chair of the STABILTY study Harvey White said in the STABILITY study, the lack of effect on stroke was disappointing but not unexpected given the emerging epidemiology data.
"While the study didn’t meet its primary endpoint, the effects of darapladib on the reduction of coronary events are of potential interest," White added.
"These findings take us a step further towards defining which patients may benefit from treatment with darapladib."
Darapladib is a selective and orally active inhibitor of Lp-PLA2, an enzyme that is found in blood and in atherosclerotic plaques, currently being investigated as a potential agent for the reduction of cardiovascular events in patients with CHD.
STABILITY (‘STtabilisation of Atherosclerotic plaque By Initiation of darapLadIbTherapY’) is the first of two Phase III studies with darapladib.
The second Phase III trial, SOLID-TIMI 52 will evaluate the effects of darapladib in patients with acute coronary syndrome.
More than 13,000 patients across 36 countries are enrolled in the Phase III SOLID-TIMI 52 trial.
Darapladib is not currently approved for use anywhere in the world.
Image: Micrograph of a coronary artery with the most common form of coronary artery disease (atherosclerosis) and marked luminal narrowing. Photo: courtesy of Nephron.