A Phase 3b, Multi-Center, Double-Blind, Placebo-Controlled, Parallel Group, Study to Evaluate the Effect of Dalcetrapib 600 mg on Cardiovascular (CV) Events in Adult Patients with Stable Coronary Heart Disease (CHD), CHD Risk Equivalents or at Elevated Risk for Cardiovascular Disease (CVD).

Phase 3

Conditions: Cardiovascular disease
Coronary Heart Disease
10011082

Registration Number: NL-OMON37839

Lead Sponsor: Hoffmann-La Roche

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Pending

Sex: Not specified

Target Recruitment: 740

Inclusion Criteria

1. Male and female patients at least 45 years of age with stable CHD, CHD risk equivalents or at elevated risk for CVD defined as the documented presence of at least one criterion in the categories A to D or at least 3 criteria in category E:;Patients with established CVD:;A. Stable coronary heart disease (CHD):
• Prior myocardial infarction (> 3 months prior to randomization)
• Prior coronary revascularization (PCI or CABG) (> 3 months prior to randomization)
• Angiographic or CT-imaging (e.g., MDCT/CTA) evidence of coronary atherosclerosis (> 70% stenosis in at least one major epicardial coronary artery);B. Cerebrovascular disease:
• Prior ischemic stroke (> 3 months prior to randomization) confirmed by a brain imaging study -
CT or MRI; thought not to be caused by atrial fibrillation, valvular heart disease or mural thrombus
• Carotid artery stenosis > 70% on prior angiography or ultrasound
• History of prior percutaneous or surgical carotid artery revascularization (> 3 months prior to randomization);C. Peripheral arterial disease (PAD):
• Prior documentation of a resting ankle-brachial index <= 0.85
• History of prior percutaneous or surgical revascularization of an iliac, femoral, or popliteal artery
(> 3 months prior to randomization)
• Prior non-traumatic amputation of a lower extremity (> 3 months prior to randomization) due to peripheral artery disease;Patients without established CVD:;D. Patients with pharmacologically treated type 2 diabetes and one or more additional risk factor for
CVD:
• Age at least 70 years
• History of type 2 diabetes at least15 years
• eGFR at least 30 and max 60 ml/min/1.73m2 using the MDRD formula within 1 year prior to randomization
• Albuminuria defined as spot urine albumin to creatinine ratio (ACR) at least 30 µg albumin /mg creatinine within 1 year prior to randomization;E. Patients with 3 or more of the following risk factors for CVD but without T2D:
• HDL-C < 40 mg/dL (1.03 mmol/L) for men; < 50 mg/dL (1.29 mmol/L) for women within 1 year prior to randomization
• Waist circumference at least 94 cm (men) at least 80 cm (women); at least 90 cm (men) at least 80 cm (women) for Asians and patients of Asian descent within 1 year prior to randomization
• Hypertension: persistent elevated SBP at least 140 mmHG and/or DBP at least 90 mmHG despite treatment for hypertension
• Family history of premature CHD (symptomatic CHD in male first degree relative < 55 years or in female first degree relative < 65 years. Symptomatic CHD defined as myocardial infarction or coronary revascularization)
• Albuminuria defined as spot urine albumin to creatinine ratio (ACR) at least 30 µg albumin /mg creatinine within 1 year prior to randomization
• eGFR at least 30 and max 60 ml/min/1.73m2 using the MDRD formula within 1 year prior to randomization
• Current cigarette smoking;Appropriate documentation may include mention of the diagnosis in a discharge letter or in the patient*s file.;2. Within 6 months prior to randomization, evidence of guidelines-based management of LDL-C, at a minimum to include medical and dietary treatment to a level of LDL-C <100 mg/dL (2.6 mmol/L). Patients may be randomized if they cannot reach the goal of LDL-C < 100 mg/dL despite an
intensive statin / LDL-C lowering drug regimen (comprising of a maximum tolerated dose of statin as determined by the investigator) or are unable to tolerate stat

Exclusion Criteria

1. Occurrence of myocardial infarction, hospitalization for unstable angina, stroke or revascularization (coronary, carotid or peripheral) within three months prior to randomization.
2. Planned revascularization (coronary, carotid or peripheral) after randomization.
3. Sustained systolic blood pressure > 180 mmHg and/or diastolic blood pressure > 110 mmHg.
4. Symptomatic congestive heart failure (NYHA Class III or IV).
5. Known left ventricular ejection fraction < 25%.
6. Presence of any of the following laboratory abnormality assessed within 6 months prior to randomization:
a. Triglycerides at least 400 mg/dL (4.5 mmol/L),
b. Hepatic transaminase > 2 x ULN or alkaline phosphatase levels > 2 x ULN or total bilirubin level > 1.5 x ULN
c. Creatine phosphokinase levels > 3 x ULN
d. eGFR < 30 ml/min/1.73m2 using the MDRD formula
e. or any laboratory abnormality that is considered to be clinically important by the investigator.
7. Known HbA1c > 10%
8. Known Hb < 8 g/dL
9. Current or previous (within 3 months prior to randomization) treatment with niacin, fibrates, bile acid sequestrants or drugs other than dalcetrapib administered for increasing HDL-C (treatment with ezetimibe, fish oil derivatives and multivitamins containing nicotinic acid (vitamin B3) is permitted).
10. Previous treatment with compounds targeting CETP, e.g. torcetrapib, anacetrapib or dalcetrapib.
11. Known or suspected intolerance or hypersensitivity to lactose.
12. Patients with clinically apparent liver disease, eg, jaundice, cholestasis, or active hepatitis.
13. History of malignancy (except for curatively treated basal cell or squamous cell carcinoma of the skin) during the 3 years prior to randomization.
14. Any clinically significant medical condition that according to the investigator could interfere with the conduct of the study or life expectancy shorter than the duration of the trial.
15. Current alcohol or drug abuse or history thereof within 5 years prior to randomization.
16. Patients who have received any investigational drug or device within 1 month prior to randomization, or who are expected to participate in any other investigational drug or device study during the conduct of this trial.
17. Women who are pregnant or breast-feeding.
18. Women of childbearing potential who are not using a highly effective contraceptive method at randomization (see protocol section 4.2.2).
19. Unable or unwilling to comply with protocol requirements throughout the duration of the trial (approximately 4 to 5 years follow-up), or deemed by the investigator to be unfit for the study.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The primary endpoint of this study is the time to first occurrence of any<br /><br>component of the composite endpoint; including<br /><br>• Coronary heart disease death<br /><br>• Non-fatal MI<br /><br>• Fatal and non-fatal stroke of ischemic origin</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>The secondary endpoints of this study are listed below.<br /><br>Time to first occurrence of:<br /><br>• A composite including coronary heart disease death, nonfatal MI, fatal and<br /><br>non-fatal stroke of ischemic origin and coronary revascularization<br /><br>• A composite including coronary heart disease death, nonfatal MI, fatal and<br /><br>non-fatal stroke of ischemic origin and hospitalization for unstable angina<br /><br>• A composite including cardiovascular death, non-fatal MI and non-fatal stroke<br /><br>• All-cause mortality<br /><br>• A composite including all-cause mortality, non-fatal MI, non-fatal stroke<br /><br>• Individual components of the primary endpoint<br /><br>• Coronary revascularization, i.e. PCI or CABG; including separate analysis for<br /><br>PCI and CABG<br /><br>• Hospitalization for unstable angina<br /><br><br /><br>Percent change from baseline for:<br /><br>• Blood lipid markers (TC, TG, HDL-C, LDL-C, Apo A1, ApoB)<br /><br>• Biomarkers of CV risk</p><br>