CHD or CHD Risk Equivalent
Conditions
Interventions
Product Name: RO4607381
Product Code: RO4607381
Pharmaceutical Form: Film-coated tablet
Current Sponsor code: RO4607381
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration numb
Sponsors
F. Hoffmann-La Roche Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
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 =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • 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. ;Secondary Objective: • 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;Primary end point(s): Percentage and absolute change from baseline to week 24 in HDL-C level | — |
Countries
Germany
Outcome results
None listed