GlaxoSmithKline (GSK) announced initiation of the first pivotal phase-III clinical trial to evaluate the efficacy of long-term treatment with the investigational Lp-PLA2 inhibitor darapladib in men and women with chronic coronary heart disease (CHD). The study, called STABILITY (STabilisation of Atherosclerotic plaque By Initiation of darapLadIb TherapY) will include more than 15,000 patients from 39 countries.

"Despite major advances in medical treatment, coronary heart disease remains the leading cause of death worldwide and new approaches are needed to help reduce this burden to patients and society," said Patrick Vallance, senior vice president, Drug Discovery, GlaxoSmithKline. "GSK is initiating the large STABILITY trial with darapladib as part of a phase-III programme to determine if this novel medication could improve people's lives by reducing the risk of cardiovascular events."

STABILITY is a randomised, placebo-controlled, double-blind, parallel group multi-center, event-driven trial in men and women with chronic CHD. The study will evaluate the clinical efficacy of long-term treatment with darapladib as compared with placebo (when both are added to standard of care which may include a statin, aspirin and blood pressure medications) on the incidence of first occurrence of major adverse cardiovascular events (MACE), including CV death, non-fatal heart attack and non-fatal stroke.

"The recently completed IBIS-2 study (Integrated Biomarker and Imaging Study-2) showed that use of darapladib dramatically reduced Lp-PLA2 activity in plasma and prevented expansion of the necrotic core - a region within coronary artery plaques associated with a high risk of rupture which is the major cause of heart attacks and cardiovascular death," said Harvey White, co-chair of the Steering Committee for STABILITY and director of Coronary Care and Cardiovascular Research Unit, Auckland City Hospital, Auckland, New Zealand. "STABILITY will help us to determine whether treatment with darapladib is in fact associated with favourable effects on these outcomes as well as stroke."

Coronary artery disease is the leading cause of death globally and the single largest killer of Americans. According to the World Health Organization (WHO), 7.2 million people worldwide die each year from CAD. Advances in science, clinical medicine, and public health over the past 50 years have resulted in significant reductions in the age-adjusted death rates from coronary heart disease and stroke, however, the clinical event rates associated with atherosclerosis have largely remained unchanged over the past 30 years.

Darapladib is a selective and orally active inhibitor of LpPLA2 currently in phase-III development as a potential anti-atherosclerosis agent for the reduction of major cardiovascular events in patients with coronary heart disease.