Study With Heptral in Subjects With Liver Disease Due to Alcohol Consumption

NCT ID: NCT02200029

Last Updated: 2015-06-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 75 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-06-30
• Study Completion Date: 2015-02-28

Brief Summary

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.

Conditions

Intrahepatic Cholestasis Associated With Alcoholic Liver Disease

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Ademetionine IV

Group Type: EXPERIMENTAL

Ademetionine IV+tablet

Intervention Type: DRUG

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

Ademetionine oral

Group Type: EXPERIMENTAL

Ademetionine tablet

Intervention Type: DRUG

oral ademetionine (500 mg/tablet, 2 in the morning and 1 before dinner) for 8 weeks

Interventions

Ademetionine IV+tablet

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

Intervention Type: DRUG

Ademetionine tablet

oral ademetionine (500 mg/tablet, 2 in the morning and 1 before dinner) for 8 weeks

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ascent

UNKNOWN

Sponsor Role: collaborator

Datamap

INDUSTRY

Sponsor Role: collaborator

ClinIntel

INDUSTRY

Sponsor Role: collaborator

Catalent

INDUSTRY

Sponsor Role: collaborator

Abbott

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Suntje Sander-Struckmeier, PhD

Role: STUDY_DIRECTOR

Abbott

Locations

Research facility ORG-000962

Moscow, , Russia

Research facility ORG-000957

Moscow, , Russia

Research facility ORG-000961

Moscow, , Russia

Research facility ID ORG-000960

Moscow, , Russia

Research facility ID ORG-000726

Moscow, , Russia

Research facility ORG-000967

Saint Petersburg, , Russia

Research facility ORG-000966

Saint Petersburg, , Russia

Research facility ORG-000968

Saint Petersburg, , Russia

Research facility ORG-000965

Saint Petersburg, , Russia

Research facility ORG-000970

Saint Petersburg, , Russia

Research facility ORG-000958

Troitsk, , Russia

Research facility ORG-000969

Yaroslavl, , Russia

Countries

Russia

Other Identifiers

M14-168

Identifier Type: -

Identifier Source: org_study_id