GSK initiates second pivotal Phase III trial for investigational cardiovascular medication Darapladib

Issued:  Wednesday 9 December, London UK

GlaxoSmithKline today announced initiation of the second large-scale Phase III clinical trial to evaluate long-term treatment with the investigational Lp-PLA₂ inhibitor darapladib in men and women with acute coronary syndrome (ACS).  The study, called SOLID-TIMI 52 (The Stabilisation of pLaque Using darapladib -Thrombolysis In Myocardial Infarction 52), will include 11,500 patients from 40 countries.

SOLID-TIMI 52 is a randomised, placebo-controlled, double-blind trial in men and women with ACS.  The study will evaluate the clinical efficacy of long-term use of darapladib as compared with placebo when both are added to standard of care (which may include a statin, aspirin and blood pressure medications).  The study will test whether darapladib affects the chances of having a cardiovascular event, such as a heart attack or stroke, when treatment is started within 30 days after an acute coronary syndrome.

“Because cardiovascular disease remains the world’s number one killer, new approaches to treatment are needed. Targeting and inhibiting the Lp-PLA₂ enzyme may reduce the risk of cardiovascular events in patients with heart disease,” said Patrick Vallance, MD, Senior Vice President, Drug Discovery, GlaxoSmithKline.  “With more than 27,000 patients, the combined Phase III clinical programme for darapladib will be one of the largest ever conducted to evaluate the efficacy and safety of any cardiovascular medication”.

SOLID-TIMI 52 is the second pivotal Phase III trial to evaluate darapladib. The first large-scale trial, STABILITY, is studying darapladib in patients with chronic coronary artery disease.  STABILITY was initiated in late 2008 and has completed enrolment ahead of schedule with more than 15,000 patients recruited.¹

About SOLID-TIMI 52

In SOLID-TIMI 52, men and women with ACS and receiving standard of care will be randomised 1:1 to once-daily doses of darapladib 160 mg enteric-coated tablets or placebo.  The study will be stopped when approximately 1500 reports of first occurrence of a major adverse coronary event (MACE), including cardiovascular death, non-fatal heart attack or non-fatal stroke have occurred.  This is estimated to be in approximately three years, with interim independent analyses planned. It is anticipated that most subjects will be dosed for a minimum of 2 years and up to 3.5 years or more.

The secondary objectives of SOLID-TIMI 52 are to evaluate whether darapladib has an impact on the occurrence of major and total coronary events including coronary heart disease death, non-fatal heart attack, urgent and non-urgent coronary revascularisation, hospitalisation for unstable angina and all-cause mortality.  Additional safety data will also be collected.

About Darapladib and Lp-PLA₂

Darapladib is a selective and orally active inhibitor of LpPLA₂ currently in Phase III development as a potential anti-atherosclerosis agent.  Darapladib is being investigated to determine whether it can reduce the occurrence of major cardiovascular events in patients with coronary heart disease.

Lp-PLA₂ is an enzyme found in blood and atherosclerotic plaque. The underlying process in most heart attacks and strokes is atherosclerosis, which is an inflammatory disease characterised by the build-up of plaque within the walls of arteries. The rupture of unstable atherosclerotic plaque, regardless of the size of the plaque, causes most heart attacks and strokes. Elevated Lp-PLA₂ activity has been implicated in the development and progression of atherosclerosis. Large amounts of Lp-PLA₂ are present in the necrotic core of rupture-prone human coronary plaques.

About Acute Coronary Syndrome (ACS)

Acute Coronary Syndrome is a term used for any condition brought on by sudden reduced flow to the heart. It includes unstable angina (increasing unpredictable chest pain) and heart attack.²   ACS may develop slowly over time by the build-up of plaques in the arteries of the heart.^3,4

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 and more than 12 million die from a heart attack or stroke.⁵ 

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