E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Non diabetic patients with Non-Alcoholic Steato-Hepatitis (NASH) |
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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 | LLT |
E.1.2 | Classification code | 10053219 |
E.1.2 | Term | Non-alcoholic steatohepatitis |
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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 objective of this study is to demonstrate in patients without co-morbid diabetes following a minimum of 24 months treatment, the superiority of rimonabant 20 mg OD over placebo for improving the severity of NASH as measured by histological features of liver injury. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are to demonstrate in patients without co-morbid diabetes following a minimum of 24 months treatment, the superiority of rimonabant 20 mg OD over placebo: 1) In severity of hepatic fibrosis as measured by hepatic fibrosis stage; 2) In level of circulating plasma adiponectin; 3) In level of circulating hyaluronate; 4) In degree of insulin sensitivity; and, 5) In AST/ALT level. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Non diabetic patients with Non-Alcoholic Steato-Hepatitis |
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E.4 | Principal exclusion criteria |
Exclusion criteria related to study methodology - Refusal or inability to give informed consent to participate in the study - Average alcohol ingestion > 21 units/wk (males) or > 14 units/wk (females) - No history of or presence of overt diabetes -Other cause of chronic liver disease and/or hepatic steatosis: −Wilsons Disease −Alpha-1-Antitrypsin deficiency −Viral hepatitis −Primary Biliary Cirrhosis −Autoimmune hepatitis −Genetic iron overload −History of sleep apnea −History of or current HIV infection −Hypo- or hyper-thyroidism -Any contraindication to liver biopsy based on local standard for pre-liver biopsy risk assessment -History of or planned gastrointestinal bypass surgery/intervention -Hepatic Cirrhosis with a Child-Pugh classification of B or C - Concomitant Hepatocellular Carcinoma (HCC) -Previous hepatic transplantation -Recent significant weight loss -ALT or AST > 10 x ULN at screening or within 3 months of screening -Recent or concomitant use of agent known to cause hepatic steatosis: −corticosteroids −amiodarone −methotrexate −tamoxifen −tetracycline −high dose estrogens −valproic acid - Use of insulin, biguanide, sufonylurea or thiazolidinedione within last 6 months before baseline liver biopsy and screening visit -Recent change in dose/ regimen or introduction of: −Vitamin E, Vitamin C −betaine, s-adenosyl methionine , ursodeoxycholate −silymarin −fibrate −statin −pentoxyfilline −angiotensin II inhibitor -Recent change in dose/ regimen or introduction of weight loss agent such as: −orlistat −sibutramine - rimonabant -Any situation that in the Investigators opinion, may interfere with optimal study participation -Participation in any clinical study of an investigational agent -Presence of clinically relevant cardiovascular, pulmonary, gastro-intestinal, hepatic, renal, metabolic, hematological, neurological, psychiatric, systemic, ocular, gynecologic (if female), or any acute infectious disease or signs of acute illness -Presence or history of multiple allergic reactions to drugs -Presence or history of cancer within past 5 years with exception of adequately treated localized basal cell carcinoma of the skin, in situ cervical cancer or solid malignancy surgically excised in toto without recurrence for five years -Women of childbearing potential not protected by effective contraceptive method of birth control or surgical sterilization and/or who are unwilling or unable to be tested for pregnancy. -Patient is the Investigator or any Sub-Investigator, research assistant, pharmacist, study coordinator, other staff or relative thereof directly involved in the conduct of the protocol Exclusion criteria related to the sanofi-aventis compound -Be pregnant or breastfeeding -Hypersensitivity to rimonabant or to any of the excipients. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is the mean change per year in NAS (NAFLD Activity Score) between baseline and end of study biopsy evaluation |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
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 | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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.8.5 | The trial involves multiple Member States | Yes |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |