Intrahepatic Cholestasis Associated With Alcoholic Liver Disease Clinical Trial
Official title:
Open-Label Study With Ademetionine (Heptral®) in Subjects With Intrahepatic Cholestasis (IHC) Associated With Alcoholic Liver Disease (ALD)
| Verified date | June 2015 |
| Source | Abbott |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | Russia: Ministry of Health of the Russian Federation |
| Study type | Interventional |
A research study of an approved drug called Heptral®, ademetionine, to treat adults with intrahepatic cholestasis (a condition where bile cannot flow from the liver to the duodenum) in pre-cirrhotic and cirrhotic states. Experience from clinical studies in subjects with liver disease has shown that ademetionine is effective.
| Status | Completed |
| Enrollment | 75 |
| Est. completion date | February 2015 |
| Est. primary completion date | February 2015 |
| Accepts healthy volunteers | No |
| Gender | Both |
| Age group | 18 Years to 75 Years |
| Eligibility |
Inclusion criteria: - Signed informed consent given by the subject - Age = 18 years to 75 years - Chronic liver disease due to alcoholic liver disease - Compensated alcoholic liver disease, defined as having a Maddrey Score < 32 and not being treated with pentoxifylline or prednisolone within 6 months prior to the study - History of chronic alcohol use, defined as, history of consumption of > 40 g of alcohol per day for females and > 80 g alcohol per day for males for more than 5 years prior to enrolment - Subjects who abstain from alcohol for more than 2 weeks and will not consume alcohol during the study - Subjects with Intrahepatic Cholestasis (IHC): - ALP: more than 1.5 x upper normal limit and - ?GT: more than 3 x upper normal limit - Subjects with additional serum conjugated bilirubin (SCB) > Upper Limit of Normal (ULN) will be selected for initial IV treatment Exclusion Criteria: - Subjects with a known hypersensitivity to the active substance of ademetionine or to any of the inactive ingredients - Subjects with extrahepatic cause of cholestasis (proven by ultrasound or described in medical history) - Diagnosis of human immunodeficiency virus (HIV) in medical history - Subjects with chronic liver disease Child-Pugh class C - Subjects in the decompensation stage of ALD (such as Maddrey Score >32) - Subjects with primary sclerosing cholangitis (PSC) - Subjects with primary biliary cirrhosis (PBC) - Any form of malignancy within the past 5 years and/or basal cell carcinoma and squamous cell carcinoma of the skin within the past two years - Subjects with drug-induced liver disease - History of active substance abuse (oral, inhaled or injected) within one year prior to the study - Subjects with renal impairment (creatinine level of >2.0 mg/dL or > 150 µmol/l) - Subjects with known genetic defects affecting the methionine cycle and/or causing homocystinuria and/or hyperhomocysteinemia (e.g., cystathionine beta-synthase deficiency, Vitamin B12 metabolism defect) or known folate, Vitamin B6 or B12 deficiency - Subjects on total parenteral nutrition in the year prior to screening - Subjects after or planned for bariatric surgery (jejunoileal bypass or gastric weight loss surgery) - Subjects after liver transplantation and subjects on the waiting list for liver transplantation - Subjects with any of the following disease in medical history: - Viral hepatitis (serum positive HBcAb or Hepatitis C Virus (HCV) RNA) - Evidence of autoimmune liver disease - Wilson´s disease - Hemochromatosis - Alpha-1-antitrypsin deficiency - Subjects with history of biliary diversion - History of major depression or bipolar disease - Women of childbearing potential: positive urine pregnancy test during screening or unwillingness to use an effective form of birth control during the study. - Breastfeeding women - Any condition that, in the opinion of the investigator, does not justify the patient's inclusion into the study - Investigational drug intake within one month prior to the study - Active, serious medical disease other than ALD with likely life-expectancy less than five years |
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
| Country | Name | City | State |
|---|---|---|---|
| Russian Federation | Research facility ID ORG-000726 | Moscow | |
| Russian Federation | Research facility ID ORG-000960 | Moscow | |
| Russian Federation | Research facility ORG-000957 | Moscow | |
| Russian Federation | Research facility ORG-000961 | Moscow | |
| Russian Federation | Research facility ORG-000962 | Moscow | |
| Russian Federation | Research facility ORG-000965 | St. Petersburg | |
| Russian Federation | Research facility ORG-000966 | St. Petersburg | |
| Russian Federation | Research facility ORG-000967 | St. Petersburg | |
| Russian Federation | Research facility ORG-000968 | St. Petersburg | |
| Russian Federation | Research facility ORG-000970 | St. Petersburg | |
| Russian Federation | Research facility ORG-000958 | Troitsk | |
| Russian Federation | Research facility ORG-000969 | Yaroslavl |
| Lead Sponsor | Collaborator |
|---|---|
| Abbott | Ascent, Catalent, ClinIntel, Datamap |
Russian Federation,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Concentrations (Units per liter) of Alkaline phosphatase (ALP) or gamma-glutamyltransferase (?GT) | Improvement of ALP or ?GT after 8 weeks of treatment with ademetionine compared to baseline | from baseline up to the end of treatment visit (56-60 days) | No |
| Secondary | Concentrations of ALP, ?GT, Alanine Transaminase (ALT) and Aspartate aminotransferase (AST) (Units per liter) and of serum total and conjugated bilirubin (µmol per liter) | Improvement of ALP, ?GT and serum total and conjugated bilirubin, ALT and AST compared to baseline | At baseline and after 2 weeks intravenously (IV) treatment or after 4 weeks oral treatment and after 2 months treatment | No |
| Secondary | The intensity of clinical symptoms (jaundice, pruritus, fatigue and depressed mood) will be recorded for each symptom separately using six categories: No symptoms (0), minimum (1) to maximum (5). | Record of intensity of jaundice, pruritus, fatigue and depressed mood compared to baseline | At baseline and after 2 weeks IV treatment or after 4 weeks oral treatment and after 2 months treatment | No |
| Secondary | Evaluation of the responder rate by comparing concentrations at certain time points (units per liter) to baseline concentrations | >20% reduction of ALP or ?GT or normalization of ALP or ?GT compared to baseline | At baseline and after 2 weeks IV treatment or after 4 weeks oral treatment and after 2 months treatment | No |