E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
CHD or CHD Risk Equivalent |
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MedDRA Classification |
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 |
• To evaluate the effect of RO4607381 (900 mg daily) on HDL C in patients with CHD or a CHD risk equivalent. • To evaluate the 24-week safety profile of RO4607381. In addition to assessing the general safety profile of RO4607381, MRI imaging will be performed to evaluate potential changes in mesenteric lymph nodes.
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E.2.2 | Secondary objectives of the trial |
• To assess the effects of RO4607381 on lipoprotein metabolism through determinations of change in blood lipid, lipoprotein and apoprotein levels during the 24 week period of double-blind treatment. • To explore the effect in other tissues using MRI, including small bowel mucosa, liver and abdominal aorta • To investigate the relationship between RO4607381 plasma concentrations and efficacy parameters • To explore a potential relationship between RO4607381 plasma concentrations and changes in mesenteric lymph nodes. • To evaluate the effects of RO4607381 on blood lymphocyte and lymphocyte subtype counts and hsCRP levels |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male and female patients aged 18 – 75 years. 2. Patients must have CHD or CHD risk equivalent based on NCEP ATPIII, eg, atherosclerosis, diabetes or >20% 10 year risk of CHD events >20% 3. Female patients must be post-menopausal (defined as amenorrhoea for 6 – 12 months with FSH > 45 U/L or amenorrhoea for ≥ 12 months) or surgically sterile if pre-menopausal. 4. Body weight < 125 kg at Visit 1. 5. TG < 600 mg/dL at each pre-randomization visit. 6. LDL-C < 100 mg/dL prior to randomization to RO4607381 or placebo. 7. Written informed consent (approved by the Institutional Review Board [IRB]/Independent Ethics Committee [IEC]) obtained prior to any study specific screening procedures.
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E.4 | Principal exclusion criteria |
1. Females who are pregnant or breast-feeding, and female of child-bearing potential. 2. Concomitant use of the following drugs: • Systemic corticosteroids • Anti-epileptics • Immunosuppressive drugs • Macrolide antibiotics • Antiviral drugs including HIV protease inhibitors • Systemic azole antifungal drugs • Oestrogen in doses > 30 μg/day 3. History of alcohol or drug abuse within 5 years prior to screening. 4. Patient exposed to RO4607381 within the last 12 months before the start of this study. 5. Excessive alcohol intake, defined as > 21 units/week for males and > 14 units/week for females. An alcohol unit is defined as 10 mL (0.33 oz) of absolute alcohol, 300 mL (10 oz) of beer, 25 mL (0.83 oz) of a single spirit, or 100 mL (3.3 oz) of wine. 6. Use of an investigational drug within 3 months prior to screening. 7. A history of clinically significant gastro-intestinal, cardiovascular, musculoskeletal, endocrine, hematological, psychiatric, renal, hepatic, bronchopulmonary, neurological or allergic disease 8. Any clinically significant medical condition that could interfere with the conduct of the study. 9. Systolic blood pressure ≥180 mmHg and/or diastolic blood pressure ≥100 mmHg at screening or any other pre-randomization visit. 10. Poorly controlled diabetes mellitus with HbA1c > 10% at screening. 11. Untreated or inadequately treated hypothyroidism, defined as the presence of an elevated TSH at screening. 12. History of obstructive biliary disorders, pancreatitis, collagen diseases, or auto-immune diseases. 13. History of malignancy (except for curatively treated basal cell or squamous cell carcinoma of the skin) during the 3 years prior to the screening. 14. Known or suspected diagnosis of hepatitis or human immunodeficiency virus (HIV) infection. 15. Recent (within 3 months of screening) clinically significant coronary events including unstable angina, myocardial infarction, angioplasty, or coronary artery bypass graft, and transient ischemic attacks or cerebrovascular accident. 16. History of a statin-associated myopathy or intolerance to statin 17. ALT, AST alkaline phoshatase, or total bilirubin > 1.5 x ULN or unexplained, ie, not explained by exercise, creatinine phosphokinase levels >3 times the upper limit of normal (ULN) at any visit prior to randomisation. 18. Serum creatinine > 2.2 mg/dL at any visit prior to randomisation. 19. Presence of any laboratory abnormality performed prior to randomization that is considered by the investigator to be clinically important. 20. Unable or unwilling to comply with protocol requirements, or deemed by the investigator to be unfit for the study. 21. Recent history (within 1 month of V1) of acute gastro-intestinal illness or investigation for GI symptoms/illness. 22. Active gastro-intestinal disease e.g. inflammatory bowel disease. 23. Patients contra-indicated to receive MRI scanning e.g. surgical prostheses, ferromagnetic implants or foreign bodies, pacemakers. 24. Patients with enlarged lymph nodes if an underlying pathology has been identified or is suspected. Enlarged lymph nodes are defined as follows: • first pre-randomization scan: mesenteric lymph node ≥10 mm • second pre-randomization scan : appearance of a new lymph node that is ≥ 10 mm, increase of a node seen at the first scan by more than 50% to a size ≥ 10 mm, or increase by more than 50% of a node that is ≥10 mm on the first scan |
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E.5 End points |
E.5.1 | Primary end point(s) |
Percentage and absolute change from baseline to week 24 in HDL-C level |
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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 | Yes |
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
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.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
E.8.5 | The trial involves multiple Member States | No |
E.8.5.1 | Number of sites anticipated in the EEA | 7 |
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 | Information not present in EudraCT |
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 clinical trial is defined as the date of the last subject's last observation. |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 1 |