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)

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Coronary Heart Disease

Intervention / Treatment
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* Drug: darapladib
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Group 1: subjects from LPL100601<br>randomized subjects in study LPL100601 | Drug: darapladib<br>* darapladib enteric coated tablets 160 mg<br>Drug: placebo<br>* placebo<br>|
| Group 2: subjects from SB480848/033<br>randomized subjects in study SB480848/033 | Drug: darapladib<br>* darapladib enteric coated tablets 160 mg<br>Drug: placebo<br>* placebo<br>|

What is the study measuring?
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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. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CV Risk, Cardiovascular Disease, Atherosclerosis, Acute coronary syndrome