Clinical trial NCT02200029: Study With Heptral in Subjects With Liver Disease Due to Alcohol Consumption
Official title: Open-Label Study With Ademetionine (Heptral®) in Subjects With Intrahepatic Cholestasis (IHC) Associated With Alcoholic Liver Disease (ALD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Intrahepatic Cholestasis Associated With Alcoholic Liver Disease
Keywords: Intrahepatic Cholestasis
Lead sponsor: Abbott
Sponsor class: INDUSTRY
Collaborators: name: Ascent
name: Datamap
name: ClinIntel
name: Catalent
First posted: 2014-07-25
Enrollment: 75
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Concentrations (Units per liter) of Alkaline phosphatase (ALP) or gamma-glutamyltransferase (γGT)
timeFrame: from baseline up to the end of treatment visit (56-60 days)
Secondary outcomes:
measure: Concentrations of ALP, γGT, Alanine Transaminase (ALT) and Aspartate aminotransferase (AST) (Units per liter) and of serum total and conjugated bilirubin (µmol per liter)
timeFrame: At baseline and after 2 weeks intravenously (IV) treatment or after 4 weeks oral treatment and after 2 months treatment
measure: 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).
timeFrame: At baseline and after 2 weeks IV treatment or after 4 weeks oral treatment and after 2 months treatment
measure: Evaluation of the responder rate by comparing concentrations at certain time points (units per liter) to baseline concentrations
timeFrame: At baseline and after 2 weeks IV treatment or after 4 weeks oral treatment and after 2 months treatment
Other outcomes:
Locations:
city: Moscow
country: Russian Federation
facility: Research facility ORG-000962
city: Moscow
country: Russian Federation
facility: Research facility ORG-000957
city: Moscow
country: Russian Federation
facility: Research facility ORG-000961
city: Moscow
country: Russian Federation
facility: Research facility ID ORG-000960
city: Moscow
country: Russian Federation
facility: Research facility ID ORG-000726
city: St. Petersburg
country: Russian Federation
facility: Research facility ORG-000967
city: St. Petersburg
country: Russian Federation
facility: Research facility ORG-000966
city: St. Petersburg
country: Russian Federation
facility: Research facility ORG-000968
city: St. Petersburg
country: Russian Federation
facility: Research facility ORG-000965
city: St. Petersburg
country: Russian Federation
facility: Research facility ORG-000970
city: Troitsk
country: Russian Federation
facility: Research facility ORG-000958
city: Yaroslavl
country: Russian Federation
facility: Research facility ORG-000969
Study officials:
affiliation: Abbott
name: Suntje Sander-Struckmeier, PhD
role: STUDY_DIRECTOR
References: