A phase III, double-blind, randomized placebo-controlled study, to evaluate the effects of RO4607381 on cardiovascular (CV) risk in stable CHD patients, with a documented recent Acute Coronary Syndrome (ACS). - ND

• Register: EUCTR
• Last refreshed on: 28 August 2012
• Main ID: EUCTR2007-005103-18-IT
• Date of registration: 21/05/2008
• Prospective Registration: Yes
• Primary sponsor: ROCHE
• Public title: A phase III, double-blind, randomized placebo-controlled study, to evaluate the effects of RO4607381 on cardiovascular (CV) risk in stable CHD patients, with a documented recent Acute Coronary Syndrome (ACS). - ND
• Scientific title: A phase III, double-blind, randomized placebo-controlled study, to evaluate the effects of RO4607381 on cardiovascular (CV) risk in stable CHD patients, with a documented recent Acute Coronary Syndrome (ACS). - ND
• Date of first enrolment: 26/05/2008
• Target sample size: 15600
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-005103-18
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Austria, Belgium, Czech Republic, Denmark, Finland, France, Germany, Hungary, Ireland, Italy, Netherlands, Spain, Sweden, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
Patients recently hospitalized for ACS, and whose residual cardiovascular risk ay benefit from an increase in HDL-C, will be enrolled in this trial. ACS is defined as the occurrence of at least one of the following events: Myocardial Infarction A diagnosis of a qualifying MI event will be defined by abnormal levels of troponin (at least one determination >2x ULN or a set of at least two troponin determinations, drawn at least 6 hours apart, with at least one value elevated between 1 and 2 x ULN and demonstrating a rising or falling pattern) and at least one of the following: 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 Imaging evidence (eg, echocardiography, radionuclide angiography, singlephoton emission tomography, MRI) of new or presumed new wall motion or perfusion deficit Please note: The preferred biomarker for myocardial necrosis is troponin (I or T). If troponin assays are not available the preferred alternative is CKMB measured by mass assay. When measuring cardiac troponin or CK-MB the ULN should reflect the 99th percentile of distribution in a normal healthy population. 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) Etc.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Females who are pregnant or breast-feeding 2. Women of child bearing potential (women who are not surgically sterile or post-menopausal defined as amenorrhea for > 12 months or amenorrhea for 6 ? 12 months and FSH ≥ 45U/L) 3. Symptomatic (NYHA Class II or greater) congestive heart failure requiring and persisting despite appropriate medical treatment at randomization 4. Severe anemia defined as hemoglobin ≤ 10 g/L at Visit 2 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 Visit 2 9. Unexplained creatine phosphokinase levels >3 times the ULN at visit 2 10. Serum creatinine > 2.2 mg/dL at Visit 2 11. Concomitant treatment with niacin, fibrates, bile acid sequestrants, or riminabant. Treatment with ezetimibe or fish oil derivatives is permitted. 12. Concomitant treatment with any drug other than RO4607381 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 RO4607381 within the last 12 months before the start of his study 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


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Patients with a documented recent Acute Coronary Syndrome (ACS)
MedDRA version: 9.1 Level: LLT Classification code 10051592 Term: Acute coronary syndrome

Intervention(s)

Product Code: RO4607381
Pharmaceutical Form: Film-coated tablet
CAS Number: 211513-37-0
Current Sponsor code: RO4607381
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 300-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: The primary objective of this trial is to evaluate the potential of RO4607381 to reduce cardiovascular morbidity and mortality in stable CHD patients, with a documented recent ACS.

Primary end point(s): The primary endpoint of this study is the time to first occurrence of any component of the composite event; as adjudicated by the Clinical Event Committee (CEC). Components of the event are: Coronary heart disease death Major coronary events (nonfatal MI, ,hospitalization for ACS [ECG abnormalities without biomarkers] and resuscitated cardiac arrest:) Stroke, fatal or non-fatal, of presumed atherothrombotic etiology

Secondary Objective: Assessment of the long-term safety profile of RO4607381
Evaluation of the effect of RO4607381 on lipid metabolism and markers of inflammation and oxidation

Secondary ID(s)

2007-005103-18-FR

NC20971