Clinical Trials

STABILITY (STtabilisation of Atherosclerotic plaque By Initiation of darapLadIb TherapY) is the first of two Phase III studies with darapladib. It was a randomised, placebo-controlled, double-blind event-driven study in adults with chronic coronary heart disease. Patients were randomised to receive either 160mg darapladib or placebo in addition to standard of care. Standard of care could include a statin, aspirin and blood pressure medications. The study enrolled more than 15,000 patients across 39 countries and continued until 1,500 major adverse cardiovascular events had occurred. The study design of STABILITY was published in the October 2010 edition of the American Heart Journal (H. White et al).
The second Phase III study, SOLID-TIMI 52 will evaluate the effects of darapladib in patients with acute coronary syndrome. The trial has enrolled over 13,000 patients across 36 countries. SOLID-TIMI 52 is ongoing and remains blinded. Results are expected in the second quarter of 2014. The study design of SOLID-TIMI 52 was published in the October 2011 edition of the American Heart Journal (M.L. O’Donoghue et al).

* On March 30, 2014, GSK has presented data from the pivotal Phase III STABILITY study of darapladib at the American College of Cardiology 63rd Annual Scientific Session in Washington, DC. The data have also been published in the New England Journal of Medicine. This global, double-blind, event-driven trial randomized 15,828 patients with chronic coronary heart disease (CHD) to receive 160mg of darapladib or placebo once daily on a background of standard of care. The primary endpoint was time to first occurrence of any major adverse cardiovascular event  comprising cardiovascular death, myocardial infarction (MI) and stroke. Secondary endpoints included major coronary events 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.No difference was seen 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. 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; HR 0.90 (0.82 - 1.00), p=0.045 (nominal significance). 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.The safety profile was well-characterised in this large outcome study.  The frequency of serious adverse events was 43% in the darapladib group and 44% in the placebo group. Adverse events leading to study drug discontinuation occurred in 20% of patients on darapladib and 14% on placebo.

* On November 12, 2013, GSK has announced top-line results from the Phase III STABILITY trial (STabilisation of Atherosclerotic plaque By Initiation of darapLadIb TherapY), evaluating the efficacy of its investigational Lp-PLA2 inhibitor darapladib in adults with chronic coronary heart disease (CHD).  
The study did not meet the primary endpoint measure, which was time to first occurrence of any major adverse cardiovascular event (MACE) from the composite of myocardial infarction (heart attack), stroke, and cardiovascular death (relative risk reduction of 6%; p=0.199). There were greater reductions (nominal p<=0.05) in some of the pre-defined secondary endpoints that require further analysis. Additional data will be forthcoming from the second Phase III study, SOLID-TIMI 52.
In STABILITY, the overall safety profile showed no major imbalance in serious adverse events between the active and placebo groups. Frequently reported adverse events included diarrhoea and odour which occurred at a similar frequency to that seen in Phase II.  Further analysis of the data is ongoing. Full results of the STABILITY study will be submitted for presentation at a scientific meeting in 2014.  The data from this study will contribute to any future regulatory submissions for darapladib.