Patients with Coronary Heart Disease (CHD) or CHD Risk Equivalents MedDRA version: 9.1 Level: HLGT Classification code 10013317 Term: Lipid metabolism disorders
Conditions
Interventions
Product Code: RO4607381/F51
Pharmaceutical Form: Film-coated tablet
Current Sponsor code: RO4607381
Concentration unit: mg milligram(s)
Concentration number: 300-
Pharmaceutical form of the placebo: F
Sponsors
F.Hoffmann-La Roche Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: •Both male and female patients able and willing to provide written informed consent •Age 18-75 years (inclusive) at visit 1 •Signed informed consent (approved by Institutional Review Board [IRB]/Independent Ethics Committee [IEC]) obtained prior to any study specific screening procedures •Patients with CHD or CHD risk equivalent based on NCEP ATPIII, eg. atherosclerosis, diabetes or >20% 10 year risk of CHD events •HDL-C =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: •Females who are pregnant or breast feeding •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) •Concomitant treatment with niacin, fibrates, bile acid sequestrants, rimonabant or CETP therapy. Treatment with ezetimibe and fish oil derivatives will be permitted. •Concomitant treatment with any drug other than RO4607381 administered for the purpose of increasing levels of HDL C. •Patients with clinically apparent liver disease, eg, jaundice, choleastasis, hepatic synthetic impairment, or active hepatitis •Hepatic transaminase, alkaline phosphatase or total bilirubin levels >1.5 times the ULN at Visit 1 •Unexplained creatine phosphokinase levels >3 times the ULN at visit 1 •Uncontrolled blood pressure: Systolic blood pressure =160 mmHg and/or diastolic blood pressure =100 mmHg at screening or any other pre-randomization visit •Serum creatinine > 2.2 mg/dL at Visit 1. •Recent (within 3 months before Visit 1) clinically significant coronary events, including unstable angina, myocardial infarction, angioplasty, or coronary artery bypass graft. •Recent (within 3 months before Visit 1) transient ischemic attacks or cerebrovascular accident •Poorly controlled diabetes mellitus (HbA1c >10%) due to inability to comply with recommended diabetes management •Severe anemia defined as hemoglobin (Hb)< 10g/dL •Patients with homozygous familial hypercholesterolemia •Current or history of drug or alcohol abuse within 5 years of Visit 1 •History of malignancy (except for curatively treated basal cell or squamous cell carcinoma of the skin) during the 3 years prior to Visit 1 •Any clinically significant medical condition that could interfere with the conduct of the study •Presence of any abnormality on a laboratory evaluation performed prior to randomization that is considered by the investigator to be clinically important. •History of receiving R04607381 in a clinical trial in the previous 12 months •Subjects previously exposed to torcetrapib •Use of any investigational drug within 1 month before Visit 1 •Subjects who have received an 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 •Inability or unwillingness to comply with the protocol requirements, or deemed by the investigator to be unfit for the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary efficacy objective of this study is to evaluate the effect of RO4607381 on endothelial function as measured by flow mediated dilatation (FMD) of the brachial artery in patients with CHD or CHD risk equivalents at 12 weeks. The primary safety objective of this study is to evaluate the effect of RO4607381 on blood pressure as measured by 24 hour ambulatory blood pressure monitoring (ABPM) at 4 weeks. ;Secondary Objective: Secondary efficacy and safety Objectives The secondary objectives of this study are: • To evaluate the effect of RO4607381 on endothelial function as measured by flow mediated dilatation (FMD) of the brachial artery in patients with CHD or CHD risk equivalents at 36 weeks • To evaluate the effect of RO4607381 on blood pressure as measured by 24 hour ambulatory blood pressure monitoring (ABPM) at 12 and 26 weeks • To explore the effect of RO4607381 on biomarkers of inflammation, oxidation and CV risk (hsCRP, IL6, sP Selectin, sE-Selectin, sICAM, sVCAM, PLA2, MMP-3, MMP-9, Adiponectin, MPO, TPA, PAI-1) • To explore the effect of RO4607381 on clinical and laboratory parameters including blood lipid, lipoprotein and apolipoprotein levels, CETP mass and activity, and insulin sensitivity • To evaluate the safety profile of RO4607381 • To assess the effect of RO4607381 on clinical outcomes as part of an outcome analysis across the entire phase program ;Primary end point(s): Primary Efficacy Endpoint: change from baseline in %FMD as measured in the right brachial artery 5 to 10 cm proximal to the antecubital fossa with a high resolution ultrasound probe after 12 weeks of treatment. Primary Safety Endpoint: change from baseline in mean blood pressure at 4 weeks as measured by 24 hour ambulatory blood pressure monitoring. | — |
Countries
Austria, France, Germany, Italy, Netherlands
Outcome results
None listed