Effect of Dalcetrapib vs Placebo on CV Risk in a Genetically Defined Population With a Recent ACS

Study Overview
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Brief Summary
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A placebo-controlled, randomized, double-blind, parallel group, phase III multicenter study in subjects recently hospitalized for ACS and with the appropriate genetic profile. Subjects will provide informed consent before any study-specific procedures are performed. Subject enrollment may begin in the hospital and will continue following release from the hospital. Screening procedures may be performed at the time of the index ACS event or anytime thereafter, with the condition that randomization must occur within the mandated window (4-12 weeks after the index event). Subjects will be assessed based on their medical history. Those who are likely to qualify will undergo Genotype Assay testing to evaluate genetic determination for the presence of AA genotype.

Detailed Description
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This is an event driven study to reach statistical power given all other assumptions. Subjects will visit the clinic 1 month after randomization and at regular intervals thereafter. Additionally, for any subject prematurely discontinuing study medication, assessments will be conducted every 6 months for the collection of study endpoints. Those who are likely to qualify will undergo Genotype Assay Testing to evaluate genetic determination or the presence of the AA genotype. The test is investigational and test procedures are Roche Molecular Diagnostics protocol ADCY9-COB-389.

Official Title
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A Phase III, Double-blind, Randomized Placebo-controlled Study to Evaluate the Effects of Dalcetrapib on Cardiovascular (CV) Risk in a Genetically Defined Population With a Recent Acute Coronary Syndrome (ACS): The Dal-GenE Trial

Conditions
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Acute Coronary Syndrome

Intervention / Treatment
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* Drug: dalcetrapib
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects with the appropriate genetic background and recently hospitalized for ACS (between 4 and 12 weeks following the index event), will be enrolled in this trial. AA genotype at variant gene as determined by Genotype Assay testing, conducted at a designated investigational testing site (ITS) Clinically stable, ie, free of ischemic symptoms at rest or with minimal exertion for at least 1 week prior to randomization Prior to randomization, subject must have evidence of guidelines-based management of LDL-C, at a minimum to include medical and dietary treatment to a target level of LDL-C <100 mg/dl (<2.6 mmol/L). Exclusion Criteria: Females who are pregnant (negative pregnancy test required for all women of child-bearing potential at Visit 2, Day 0) or breast-feeding Women of childbearing potential (women who are not surgically sterile or postmenopausal defined as amenorrhea for >12 months) who are not using at least one method of contraception* New York Heart Association (NYHA) Class III or IV heart failure Last known hemoglobin <10 g/dL Index ACS event presumed due to uncontrolled hypertension (*) Varies by region

Ages Eligible for Study
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Minimum Age: 45 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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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Dalcetrapib<br>Participants received dalcetrapib 600 mg (two 300 mg tablets) orally once daily. dalcetrapib: Cholesterol Ester Transfer Protein inhibitor, 300 mg tablets | Drug: dalcetrapib<br>* Cholesterol Ester Transfer Protein inhibitor<br>|
| Placebo Comparator: Placebo<br>Participants received dalcetrapib placebo tablets matching dalcetrapib orally once daily. Placebo: dalcetrapib matching placebo tablets | Drug: Placebo<br>* matching placebo tablets<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite of Cardiovascular Death, Resuscitated Cardiac Arrest, Non-Fatal Myocardial Infarction, and Non-Fatal Stroke | All efficacy endpoints were adjudicated by an independent clinical endpoint committee (CEC). The primary efficacy endpoint was the time from randomization to the first occurrence of any component of the composite endpoint, which included death from cardiovascular causes, resuscitated cardiac arrest, non-fatal myocardial infarction, or non-fatal stroke, as positively adjudicated by the CEC. | From randomization to the first occurrence of any component of the composite primary endpoint (median duration of follow-up was 39.9 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite Endpoint of Cardiovascular Death, Resuscitated Cardiac Arrest, Non-Fatal Myocardial Infarction, Non-Fatal Stroke, Hospitalization for ACS (With Electrocardiogram Abnormalities) or Unanticipated Coronary Revascularization | All efficacy endpoints were adjudicated by an independent clinical endpoint committee (CEC). The primary efficacy endpoint was the time from randomization to the first occurrence of any component of the composite endpoint, which included death from cardiovascular causes, resuscitated cardiac arrest, non-fatal myocardial infarction, non-fatal stroke, hospitalization for acute coronary syndrome (with electrocardiogram abnormalities) or unanticipated coronary revascularization, as positively adjudicated by the CEC. | From randomization to the first occurrence of any component of the composite secondary endpoint (median duration of follow-up was 39.9 months) | 
| Composite Endpoint of Cardiovascular Death, Resuscitated Cardiac Arrest, Non-Fatal Myocardial Infarction, Non-Fatal Stroke or Hospitalization for New or Worsening Heart Failure | All efficacy endpoints were adjudicated by an independent clinical endpoint committee (CEC). The secondary efficacy endpoint was the time from randomization to the first occurrence of any component of the composite secondary endpoint, which included death from cardiovascular causes, cardiovascular death, resuscitated cardiac arrest, non-fatal myocardial infarction, non-fatal stroke, or hospitalization for new or worsening heart failure, as positively adjudicated by the CEC. | From randomization to the first occurrence of any component of the composite secondary endpoint (median duration of follow-up was 39.9 months) |