SB-480848 in Major Adverse Cardiovascular Events - Integrated Summary of Efficacy and Safety From the STABILITY Trial (LPL100601) and the SOLID-TIMI-52 Trial (SB-480848/033)

SB-480848 in Major Adverse Cardiovascular Events - Integrated Phase III Summary of Efficacy and Safety

The overall objective of this integrated analysis is to evaluate the clinical safety and efficacy of long-term treatment with darapladib enteric coated tablets, 160mg, as compared to placebo when added to standard of care in subjects with clinical manifestations of cardiovascular disease (chronic coronary heart disease (CHD) and post Acute Coronary Syndrome (ACS)). With respect to efficacy, the key purpose of this integrated analysis is to evaluate the effects of darapladib on the following endpoints: urgent coronary revascularization for myoacrdial ischemia, fatal/non-fatal stroke, time to subsequent Major Adverse Cardiovascular Event (MACE), and heart failure requiring hospitalization. The first occurrent of MACE, Major and total coronary events as well as the individual components of MACE will also be evaluated descriptively.

Study Overview

• Status: Completed
• Conditions: Coronary Heart Disease
• Intervention / Treatment: Drug: placebo; Drug: darapladib

Detailed Description

The objective of the integrated safety analysis is to characterize the safety profile of darapladib in subjects with clinical manifestations of cardiovascular disease (chronic coronary heart disease (CHD) and post Acute Coronary Syndrome (ACS)).

The purpose of the integrated efficacy analysis is to test the effects of darapladib on select endpoints which are not part of the testing hierarchies associated with the individual studies, namely: urgent coronary revascularization for myocardial ischemia, stroke, subsequent MACE, and heart failure requiring hospitalization, For all other endpoints, the intent of the integrated analysis is to provide increased precision of the estimated effects of darapladib.

• Study Type: Observational
• Enrollment (Actual): 28855

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Subjects with clinical manifestations of cardiovascular disease (chronic coronary heart disease (CHD) or post Acute Coronary Syndrome (ACS)) randomized into the STABILITY trial (LPL100601) or the SOLID-TIMI 52 trial (SB-480848/033).

Description

Inclusion Criteria:

• This is an integrated analysis therefore inclusion criteria are not applicable.

Exclusion Criteria:

• This is an integrated analysis therefore exclusion criteria are not applicable.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Group 1: subjects from LPL100601; randomized subjects in study LPL100601	Drug: placebo; placebo; Drug: darapladib; darapladib enteric coated tablets 160 mg
Group 2: subjects from SB480848/033; randomized subjects in study SB480848/033	Drug: placebo; placebo; Drug: darapladib; darapladib enteric coated tablets 160 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The time to first occurrence of urgent coronary revascularization for myocardial ischemia	time to the first occurrence of any urgent coronary revascularization for myocardial ischemia	visits occur at month 1,3,6, and every 6 months thereafter until 1500 first occurrence MACE events have occurred in each study. It is anticipated that the median follow-up time will be approximately 3 years in each study.
The time to first occurrence of stroke (fatal/non-fatal)	time to the first occurrence of stroke (fatal or non-fatal)	visits occur at month 1,3,6, and every 6 months thereafter until 1500 first occurrence MACE events have occurred in each study. It is anticipated that the median follow-up time will be approximately 3 years in each study.
The time to subsequent Major Adverse Cardiovascular Events (MACE)	time to subsequent composite of MACE (CV death, non-fatal MI or non-fatal stroke)	visits occur at month 1,3,6, and every 6 months thereafter until 1500 first occurrence MACE events have occurred in each study. It is anticipated that the median follow-up time will be approximately 3 years in each study.
The time to first occurrence of heart failure requiring hospitalization	time to the first occurrence of heart failure requiring hospitalization	visits occur at month 1,3,6, and every 6 months thereafter until 1500 first occurrence MACE events have occurred in each study. It is anticipated that the median follow-up time will be approximately 3 years in each study.

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start: October 1, 2011
• Primary Completion (Actual): April 1, 2014
• Study Completion (Actual): April 1, 2014

Study Registration Dates

• First Submitted: May 31, 2012
• First Submitted That Met QC Criteria: July 5, 2012
• First Posted (Estimate): July 10, 2012

Study Record Updates

• Last Update Posted (Estimate): November 2, 2014
• Last Update Submitted That Met QC Criteria: October 30, 2014
• Last Verified: October 1, 2014

More Information

Terms related to this study

• Keywords: CV Risk; Cardiovascular Disease; Atherosclerosis; Acute coronary syndrome
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Heart Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Phospholipase A2 Inhibitors; Darapladib
• Other Study ID Numbers: 116740

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No