E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with Coronary Heart Disease (CHD) or CHD Risk Equivalents |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | HLGT |
E.1.2 | Classification code | 10013317 |
E.1.2 | Term | Lipid metabolism disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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.
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E.2.2 | Secondary objectives of the trial |
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
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
1. Biomarker research samples / blood samples will be taken at visits 1 and 4, and at the end of treatment visit. The sampling is optional and subject to a separate signature on the informed consent. Biomarker research samples will be collected to promote, facilitate and improve individualized health care by better understanding/predicting: efficacy of RO4607381, dose responses, safety, mode of action, progression of cardiovascular and associated diseases. These samples will be stored for up to 15 years after database closure. Protocol Number BC21144, Protocol Version: A, 06-Sep-2007
2. Roche Sample Repository Research Project in association with protocol BC21144. To obtain a single blood sample from consenting patients enrolled in associated study BC21144 for pharmacogenetic and genetic research analysis. Protocol Number RSRBC21144RG, Protocol Version: A, 23-Aug-2007 |
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E.3 | Principal 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 <50 mg/dL (<1.3 mmol/L) at visit 1 •Triglycerides level 400 mg/dL (<4.5 mmol/L) at visit 1 •Appropriately treated with statin and/or other LDL lowering drug to a stable accepted LDL level (<100 mg/dL [<2.6 mmol/L] unless taking maximimum tolerated doses of therapy) based on their medical condition
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E.4 | Principal 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
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E.5 End points |
E.5.1 | 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. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Information not present in EudraCT |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Information not present in EudraCT |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 17 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of the study is defined as the date of the last patient visit of the last patient to complete the study, or the date at which the last data point, which is required for statistical analysis (i.e. key safety and efficacy results for decision making), is received, whichever is the later date. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 11 |