- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02200029
Study With Heptral in Subjects With Liver Disease Due to Alcohol Consumption
June 15, 2015 updated by: Abbott
Open-Label Study With Ademetionine (Heptral®) in Subjects With Intrahepatic Cholestasis (IHC) Associated With Alcoholic Liver Disease (ALD)
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.
Study Overview
Status
Completed
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
75
Phase
- Phase 3
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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-
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Moscow, Russian Federation, 107014
- Research facility ORG-000962
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Moscow, Russian Federation, 117292
- Research facility ORG-000957
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Moscow, Russian Federation, 119435
- Research facility ORG-000961
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Moscow, Russian Federation, 119992
- Research facility ID ORG-000960
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Moscow, Russian Federation, 125284
- Research facility ID ORG-000726
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St. Petersburg, Russian Federation, 117630
- Research facility ORG-000967
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St. Petersburg, Russian Federation, 191015
- Research facility ORG-000966
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St. Petersburg, Russian Federation, 195257
- Research facility ORG-000968
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St. Petersburg, Russian Federation, 197022
- Research facility ORG-000965
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St. Petersburg, Russian Federation, 198216
- Research facility ORG-000970
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Troitsk, Russian Federation, 142190
- Research facility ORG-000958
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Yaroslavl, Russian Federation, 150003
- Research facility ORG-000969
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 75 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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
- γGT: 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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Ademetionine IV
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IV ademetionine (500 mg/vial) for 2 weeks followed by oral ademetionine (500 mg/tablet, 2 in the morning and 1 before dinner) for 6 weeks
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Experimental: Ademetionine oral
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oral ademetionine (500 mg/tablet, 2 in the morning and 1 before dinner) for 8 weeks
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Concentrations (Units per liter) of Alkaline phosphatase (ALP) or gamma-glutamyltransferase (γGT)
Time Frame: from baseline up to the end of treatment visit (56-60 days)
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Improvement of ALP or γGT after 8 weeks of treatment with ademetionine compared to baseline
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from baseline up to the end of treatment visit (56-60 days)
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Concentrations of ALP, γGT, Alanine Transaminase (ALT) and Aspartate aminotransferase (AST) (Units per liter) and of serum total and conjugated bilirubin (µmol per liter)
Time Frame: At baseline and after 2 weeks intravenously (IV) treatment or after 4 weeks oral treatment and after 2 months treatment
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Improvement of ALP, γGT and serum total and conjugated bilirubin, ALT and AST compared to baseline
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At baseline and after 2 weeks intravenously (IV) treatment or after 4 weeks oral treatment and after 2 months treatment
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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).
Time Frame: At baseline and after 2 weeks IV treatment or after 4 weeks oral treatment and after 2 months treatment
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Record of intensity of jaundice, pruritus, fatigue and depressed mood compared to baseline
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At baseline and after 2 weeks IV treatment or after 4 weeks oral treatment and after 2 months treatment
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Evaluation of the responder rate by comparing concentrations at certain time points (units per liter) to baseline concentrations
Time Frame: At baseline and after 2 weeks IV treatment or after 4 weeks oral treatment and after 2 months treatment
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>20% reduction of ALP or γGT or normalization of ALP or γGT compared to baseline
|
At baseline and after 2 weeks IV treatment or after 4 weeks oral treatment and after 2 months treatment
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
June 1, 2014
Primary Completion (Actual)
February 1, 2015
Study Completion (Actual)
February 1, 2015
Study Registration Dates
First Submitted
July 21, 2014
First Submitted That Met QC Criteria
July 24, 2014
First Posted (Estimate)
July 25, 2014
Study Record Updates
Last Update Posted (Estimate)
June 16, 2015
Last Update Submitted That Met QC Criteria
June 15, 2015
Last Verified
June 1, 2015
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- M14-168
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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