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

NCT02200029 | Completed Phase 3

• 1 other identifier: M14-168
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 12

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

Keywords

Intrahepatic Cholestasis

Outcome Measures

Primary Outcomes (1)

• Concentrations (Units per liter) of Alkaline phosphatase (ALP) or gamma-glutamyltransferase (γGT)

  Improvement of ALP or γGT after 8 weeks of treatment with ademetionine compared to baseline

  from baseline up to the end of treatment visit (56-60 days)

Secondary Outcomes (3)

• Concentrations of ALP, γGT, Alanine Transaminase (ALT) and Aspartate aminotransferase (AST) (Units per liter) and of serum total and conjugated bilirubin (µmol per liter)

  At baseline and after 2 weeks intravenously (IV) treatment or after 4 weeks oral treatment and after 2 months treatment

• 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).

  At baseline and after 2 weeks IV treatment or after 4 weeks oral treatment and after 2 months treatment

• Evaluation of the responder rate by comparing concentrations at certain time points (units per liter) to baseline concentrations

  At baseline and after 2 weeks IV treatment or after 4 weeks oral treatment and after 2 months treatment

Study Arms (2)

Ademetionine IV

EXPERIMENTAL

Drug: Ademetionine IV+tablet

Ademetionine oral

EXPERIMENTAL

Drug: Ademetionine tablet

Interventions

Ademetionine IV+tablet 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 IV

Ademetionine tablet DRUG

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

Ademetionine oral

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Abbott: lead
• Ascent: collaborator
• Datamap: collaborator
• ClinIntel: collaborator
• Catalent: collaborator

Study Sites (12)

Research facility ORG-000962

Moscow, 107014, Russia

Location

Research facility ORG-000957

Moscow, 117292, Russia

Location

Research facility ORG-000961

Moscow, 119435, Russia

Location

Research facility ID ORG-000960

Moscow, 119992, Russia

Location

Research facility ID ORG-000726

Moscow, 125284, Russia

Location

Research facility ORG-000967

Saint Petersburg, 117630, Russia

Location

Research facility ORG-000966

Saint Petersburg, 191015, Russia

Location

Research facility ORG-000968

Saint Petersburg, 195257, Russia

Location

Research facility ORG-000965

Saint Petersburg, 197022, Russia

Location

Research facility ORG-000970

Saint Petersburg, 198216, Russia

Location

Research facility ORG-000958

Troitsk, 142190, Russia

Location

Research facility ORG-000969

Yaroslavl, 150003, Russia

Location

MeSH Terms

Conditions

Cholestasis, Intrahepatic

Interventions

S-Adenosylmethionine

Condition Hierarchy (Ancestors)

Cholestasis; Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Methionine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Adenosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Amino Acids; Amino Acids, Peptides, and Proteins; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Suntje Sander-Struckmeier, PhD

  Abbott

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 21, 2014
• First Posted: July 25, 2014
• Study Start: June 1, 2014
• Primary Completion: February 1, 2015
• Study Completion: February 1, 2015
• Last Updated: June 16, 2015

Record last verified: 2015-06

Locations

RU (12)