A study of RO4607381 in stable coronary heart disease patients with recent acute coronary syndrome

• Conditions: Stable CHD patients, with a documented recent Acute Coronary Syndrome (ACS); Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]; MedDRA version: 14.1Level: PTClassification code 10007649Term: Cardiovascular disorderSystem Organ Class: 10007541 - Cardiac disorders

• Registration Number: EUCTR2007-005103-18-NL
• Lead Sponsor: F.Hoffmann-La Roche Ltd.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-03-18
• Last Update Posted: 28 August 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 15600

Inclusion Criteria

Patients recently hospitalized for ACS (between 4 and 12 weeks after the index event), and whose residual cardiovascular risk may benefit from an increase in HDL-C as assessed by the investigator, will be enrolled in this trial. ACS is defined as the occurrence of at least one of the following events:
Myocardial Infarction
- Spontaneous Myocardial Infarction
• A diagnosis of a qualifying MI event will be defined by abnormal levels of cardiac biomarkers (troponin I or T or CK-MB mass) with at least one determination > the 99th percentile or upper limits of normal for the laboratory. and at least one of the following described below. Symptoms of myocardial ischemia within 48 hours prior to the MI
• New ECG findings (or presumed new if no prior ECG available) as described below
• Loss of viable myocardium based on imaging evidence of new or presumed new wall motion or perfusion deficit (eg, echocardiography, left ventriculography during cardiac catheterization radionuclide angiography, single-photon emission tomography, MRI)
Procedure-Related Myocardial Infarction after PCI
Patients experiencing a myocardial infarction after a PCI will also be included in this study. A procedure-related MI after PCI is defined as follows:
Normal biomarkers (eg, CK-MB or troponin I or T) before the procedure and biomarkers after procedure elevated to >3 times the 99th percentile or upper limits of normal for the laboratory.
Hospitalization for ACS (ECG Abnormalities without Biomarkers):
A diagnosis of a qualifying ACS event without increases in cardiac biomarkers will require admission to hospital or emergency room (exceeding 23 hrs) with symptoms presumed to be caused by myocardial ischemia with an accelerating tempo in the prior 48 hrs and/or prolonged (at least 20 min) rest chest discomfort and new ECG findings (or presumed new if no prior ECG available) as described below and at least one of the following:
• 50% stenosis of an epicardial coronary artery;
• positive exercise or pharmacologic stress indicating reversible ischemia; or
• presence of pathologic Q-waves on ECG
Examples of New ECG findings include:
• New or presumed new ST depression > 0.5mm in 2 contiguous leads or T wave inversion > 1mm in leads with predominant R wave or R/S >1 in 2 contiguous leads.
• New or presumed new ST elevation at the J point in = 2 contiguous leads with the cut-off points: = 0.2mV in men or = 0.15mV in women in leads V2-V3 and/or =0.1 mV in other leads or new or presumed new LBBB
• New tall R wave > 40ms in V1,V2 and R/S = 1 in V1 with concordant positive T-wave in the absence of a conduction defect.
• New Q waves = 30 ms wide and > 1mm deep in any 2 leads of a contiguous lead grouping or Q wave >20ms or QS complex in leads V2 and V3 (These criteria also apply to silent MI detected during a routine follow-up visit)
In addition, the following inclusion criteria apply:
1. Both male and female patients able and willing to give written informed consent.
2. Age 45 and over at Visit 1
3. Signed informed consent (approved by Institutional Review Board [IRB]/Independent Ethics Committee [IEC]) obtained prior to any study specific screening procedures
4. Clinically stable, ie, free of ischemic symptoms at rest or with minimal exertion for at least 1 week prior to randomization
5. Triglycerides < 400 mg/dL (<4.5 mmol/L) at Visit 2
6. Evidence-based management of LDL-C cholesterol, at a minimum to include medical and dietary treatment to a t

Exclusion Criteria

1. Females who are pregnant or breast-feeding
2. Women of childbearing potential (women who are not surgically sterile or postmenopausal defined as amenorrhea for >12 months) who are not using a highly effective contraceptive method (failure rate less than 1% per year) such as implants, injectibles, combined oral contraceptives or hormonal intrauterine devices (IUDs). In addition, a negative serum pregnancy test must be available before starting the run-in period.
3. Symptomatic (NYHA Class II or greater) congestive heart failure requiring appropriate medical treatment and persisting despite such treatment at the end of the run-in period. Patients with NYHA Class II heart failure symptoms may be included if a measurement of left ventricular function is performed and ejection fraction is shown to be >40%.
4. Severe anemia defined as hemoglobin =10 g/dL at the end of the run-in period.
5. Index ACS event presumed due to uncontrolled hypertension and/or systolic blood pressure =180 mmHg and/or diastolic blood pressure =110 mmHg by the end of the placebo run-in period despite anti-hypertensive therapy
6. Hemoglobin A1c >10% at Visit 2
7. Patients with clinically apparent liver disease, eg, jaundice, choleastasis, hepatic synthetic impairment, or active hepatitis
8. Hepatic transaminase, alkaline phosphatase or total bilirubin levels >1.5 times the ULN at the end of the run-in period
9. Unexplained creatine phosphokinase levels >3 times the ULN at visit 2
10. Serum creatinine > 2.2 mg/dL (194.5 µmol/l) at the end of the run-in period
11. Concomitant treatment with niacin, fibrates, bile acid sequestrants, or rimonabant. Treatment with ezetimibe or fish oil derivatives is permitted.
12. Concomitant treatment with any drug other than dalcetrapib administered for the purpose of increasing levels of HDL C.
13. Previous exposure to torcetrapib or any other CETP inhibitor as for example MK-859
14. History of malignancy (except for curatively treated basal cell or squamous cell carcinoma of the skin) during the 3 years prior to the screening.
15. Any clinically significant medical condition that according to the investigator could interfere with the conduct of the study.
16. Patients whose life expectancy is shorter than duration of the trial
17. Presence of any laboratory abnormality performed prior to randomization that is considered by the investigator to be clinically important.
18. Current alcohol or drug abuse or history thereof within 5 years prior to screening.
19. Patients exposed to dalcetrapib within the last 12 months before the start of this study and/or have a known or suspected hypersensitivity to excipients of trial medication, including placebo (which contains lactose)
20. Subjects who have received any investigational drug or device within 1 month of visit 1, or who expect to participate in any other investigational drug or device study during the conduct of this trial
21. Unable or unwilling to comply with protocol requirements, or deemed by the investigator to be unfit for the study

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified