Diabetic patients with Non-Alcoholic Steato-Hepatitis MedDRA version: 9.1 Level: LLT Classification code 10053219 Term: Non-alcoholic steatohepatitis
Conditions
Interventions
Trade Name: ACOMPLIA
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: rimonabant
CAS Number: 168273-06-01
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number
Sponsors
sanofi-aventis recherche & development
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients who are at least 18 years of age and with a diagnosis of NASH by liver biopsy performed within last 6 months (based on pre-defined histological criteria as confirmed by a central pathologist) 2. Confirmed Type 2 DM diagnosed by fasting plasma glucose = 126 mg/dl or 2-hour post load glucose = 200 mg/dl during an OGTT (equivalent of 75 g anhydrous glucose in water) of at least 6 months duration. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range ;Inclusion criteria: 1. Patients who are at least 18 years of age and with a diagnosis of NASH by liver biopsy performed within last 6 months (based on pre-defined histological criteria as confirmed by a central pathologist) 2. Confirmed Type 2 DM diagnosed by fasting plasma glucose = 126 mg/dl or 2-hour post load glucose = 200 mg/dl during an OGTT (equivalent of 75 g anhydrous glucose in water) of at least 6 months duration. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Exclusion criteria related to study methodology 1. Refusal or inability to give informed consent to participate in the study 2. Average alcohol ingestion > 21 units/wk (males) or > 14 units/wk (females) [self-administered quantity-frequency and 7-day recall tests and confirmed by a family member] 3. History of or presence of Type 1 diabetes mellitus (requirement for insulin replacement and presence of autoantibodies, e.g., antipancreatic islet cell, insulin autoantibodies, tyrosine phosphate autoantibodies or GADAb) 4. Hemoglobin A1C > 8.5. 5. Other cause of chronic liver disease and/or hepatic steatosis: - Wilson’s Disease - Alpha-1-Antitrypsin deficiency - Viral hepatitis - Primary Biliary Cirrhosis - Autoimmune hepatitis - Genetic iron overload - History of sleep apnea (unless on Constant Positive Airway Pressure therapy) - History of or current HIV infection - Hypo- or hyper-thyroidism 6. Any contraindication to liver biopsy based on local standard for pre-liver biopsy risk assessment (as examples,: presence of a bleeding dyscrasia, platelets 3 sec above control as measured locally during pre-biopsy evaluation of coagulation parameters) 7. History of or planned gastrointestinal bypass surgery/intervention (i.e., bariatric surgery) 8. Hepatic Cirrhosis with a Child-Pugh classification of B or C (score > 6) 9. Concomitant Hepatocellular Carcinoma (HCC) (i.e., AFP > 100 ng/mL on screening Liver Disease Panel or otherwise unexplained liver mass visualized on ultrasound or computed tomography examination of the liver) 10. Previous hepatic transplantation 11. Recent significant weight loss (> 5% TBW within previous 6 months) 12. ALT or AST > 10 x ULN at screening or within 3 months of screening 13. Recent (within 6 months of baseline liver biopsy and screening visit) or concomitant use of agent known to cause hepatic steatosis: - corticosteroids - amiodarone - methotrexate - tamoxifen - tetracycline - high dose estrogens (standard HRT and oral contraceptive doses allowed) - valproic acid 14. Recent (within 3 months of baseline liver biopsy and screening visit) change in anti-diabetes treatment, such as a change in dose-regimen of anti-diabetes agent or introduction of new- antidiabetes agent (a specific diabetes medication /treatment page will be included in the CRF). 15. Recent (within 3 months of baseline liver biopsy and screening visit) change in dose/ regimen or introduction of: - Vitamin E, Vitamin C - betaine, s-adenosyl methionine (SAM), ursodeoxycholate (UDCA) - silymarin (silybin) - fibrate - statin - pentoxyfilline - angiotensin II inhibitor 16. Recent (within 3 months of baseline liver biopsy and screening visit) change in dose/ regimen or introduction of weight loss agent such as: - orlistat - sibutramine - rimonabant 17. Any situation that in the Investigator’s opinion, may interfere with optimal study participation such as alcohol or drug abuse, domicile too distant from study site, potential non-compliance during the study or inability to cooperate because of a language problem or poor mental development 18. Participation in any clinical study of an investigational agent within 30 days or five half-lives of the investigational agent, whichever is longer 19. Presence of clinically relevant cardiovascular, pulmonary, gastro-intestinal, hepatic, renal, metabolic, hematological, neurological, psychiatric, systemic, ocular, gynecologic (if female), or any acute infectious;Exclusion criteria: Exclusion criteria related to study methodology 1. Refusal or inability to give informed consent to participate in the study 2. Average alcohol ingestion > 21 units/wk (males) or > 14 units/wk (females) [self-administered quantity-frequency and 7-day recall tests and confirmed by a family member] 3. History of or presence of Type 1 diabetes mellitus (requirement for insulin replacement and presence of autoantibodies, e.g., antipancreatic islet cell, insulin autoantibodies, tyrosine phosphate autoantibodies or GADAb) 4. Hemoglobin A1C > 8.5. 5. Other cause of chronic liver disease and/or hepatic steatosis: - Wilson’s Disease - Alpha-1-Antitrypsin deficiency - Viral hepatitis - Primary Biliary Cirrhosis - Autoimmune hepatitis - Genetic iron overload - History of sleep apnea (unless on Constant Positive Airway Pressure therapy) - History of or current HIV infection - Hypo- or hyper-thyroidism 6. Any contraindication to liver biopsy based on local standard for pre-liver biopsy risk assessment (as examples,: presence of a bleeding dyscrasia, platelets 3 sec above control as measured locally during pre-biopsy evaluation of coagulation parameters) 7. History of or planned gastrointestinal bypass surgery/intervention (i.e., bariatric surgery) 8. Hepatic Cirrhosis with a Child-Pugh classification of B or C (score > 6) 9. Concomitant Hepatocellular Carcinoma (HCC) (i.e., AFP > 100 ng/mL on screening Liver Disease Panel or otherwise unexplained liver mass visualized on ultrasound or computed tomography examination of the liver) 10. Previous hepatic transplantation 11. Recent significant weight loss (> 5% TBW within previous 6 months) 12. ALT or AST > 10 x ULN at screening or within 3 months of screening 13. Recent (within 6 months of baseline liver biopsy and screening visit) or concomitant use of agent known to cause hepatic steatosis: - corticosteroids - amiodarone - methotrexate - tamoxifen - tetracycline - high dose estrogens (standard HRT and oral contraceptive doses allowed) - valproic acid 14. Recent (within 3 months of baseline liver biopsy and screening visit) change in anti-diabetes treatment, such as a change in dose-regimen of anti-diabetes agent or introduction of new- antidiabetes agent (a specific diabetes medication /treatment page will be included in the CRF). 15. Recent (within 3 months of baseline liver biopsy and screening visit) change in dose/ regimen or introduction of: - Vitamin E, Vitamin C - betaine, s-adenosyl methionine (SAM), ursodeoxycholate (UDCA) - silymarin (silybin) - fibrate - statin - pentoxyfilline - angiotensin II inhibitor 16. Recent (within 3 months of baseline liver biopsy and screening visit) change in dose/ regimen or introduction of weight loss agent such as: - orlistat - sibutramine - rimonabant 17. Any situation that in the Investigator’s opinion, may interfere with optimal study participation such as alcohol or drug abuse, domicile too distant from study site, potential non-compliance during the study or inability to cooperate because of a language problem or poor mental development 18. Participation in any clinical study of an investigational agent within 30 days or five half-lives of the investigational agent, whichever is longer 19. Presence of clinically relevant cardiovascular, pulmonary, gastro-intestinal, hepatic, renal, metabolic, hematological, neurological, psychiatric, systemic, ocular, gynecologic (if female), or any acute infectious
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to demonstrate in patients with co-morbid Type 2 diabetes following 18 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.;Secondary Objective: The secondary objectives of this study are to demonstrate in patients with co-morbid diabetes following 18 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. ;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. ;Main Objective: The primary objective of this study is to demonstrate in patients with co-morbid Type 2 diabetes following 18 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.;Secondary Objective: The secondary objectives of this study are to demonstrate in patients with co-morbid diabetes following 18 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. ;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. | — |
Countries
Belgium, France, Germany, Hungary, Italy, Portugal, Spain, United Kingdom
Contacts
Public Contact; ;
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Outcome results
None listed