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

Overview[ - collapse ][ - ]

Purpose 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.
ConditionIntrahepatic Cholestasis Associated With Alcoholic Liver Disease
InterventionDrug: Ademetionine IV+tablet
Drug: Ademetionine tablet
PhasePhase 3
SponsorAbbott
Responsible PartyAbbott
ClinicalTrials.gov IdentifierNCT02200029
First ReceivedJuly 21, 2014
Last UpdatedAugust 13, 2014
Last verifiedJuly 2014

Tracking Information[ + expand ][ + ]

First Received DateJuly 21, 2014
Last Updated DateAugust 13, 2014
Start DateAugust 2014
Estimated Primary Completion DateDecember 2014
Current Primary Outcome MeasuresConcentrations (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)] [Designated as safety issue: No]Improvement of ALP or γGT after 8 weeks of treatment with ademetionine compared to baseline
Current Secondary Outcome Measures
  • 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] [Designated as safety issue: No]Improvement of ALP, γGT and serum total and conjugated bilirubin, ALT and AST compared to baseline
  • 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] [Designated as safety issue: No]Record of intensity of jaundice, pruritus, fatigue and depressed mood compared to baseline
  • 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] [Designated as safety issue: No]>20% reduction of ALP or γGT or normalization of ALP or γGT compared to baseline

Descriptive Information[ + expand ][ + ]

Brief TitleStudy With Heptral in Subjects With Liver Disease Due to Alcohol Consumption
Official TitleOpen-Label Study With Ademetionine (Heptral®) in Subjects With Intrahepatic Cholestasis (IHC) Associated With Alcoholic Liver Disease (ALD)
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.
Detailed DescriptionNot Provided
Study TypeInterventional
Study PhasePhase 3
Study DesignAllocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
ConditionIntrahepatic Cholestasis Associated With Alcoholic Liver Disease
InterventionDrug: 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
Drug: Ademetionine tablet
oral ademetionine (500 mg/tablet, 2 in the morning and 1 before dinner) for 8 weeks
Study Arm (s)
  • Experimental: Ademetionine IV
  • Experimental: Ademetionine oral

Recruitment Information[ + expand ][ + ]

Recruitment StatusRecruiting
Estimated Enrollment50
Estimated Completion DateDecember 2014
Estimated Primary Completion DateDecember 2014
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
GenderBoth
Ages18 Years
Accepts Healthy VolunteersNo
ContactsContact: van Assche
+31 (0)294 477367
hanneke.vanassche@abbott.com
Location CountriesRussian Federation

Administrative Information[ + expand ][ + ]

NCT Number NCT02200029
Other Study ID NumbersM14-168
Has Data Monitoring CommitteeNo
Information Provided ByAbbott
Study SponsorAbbott
CollaboratorsAscent
Datamap
ClinIntel
Catalent
Investigators Study Director: Suntje Sander-Struckmeier, PhD Abbott
Verification DateJuly 2014

Locations[ + expand ][ + ]

Research facility ORG-000957
Moscow, Russian Federation, 117292
Recruiting
Research facility ORG-000963
Moscow, Russian Federation, 129110
Not yet recruiting
Research facility ID ORG-000726
Moscow, Russian Federation, 125284
Not yet recruiting
Research facility ID ORG-000959
Moscow, Russian Federation, 111539
Withdrawn
Research facility ID ORG-000960
Moscow, Russian Federation, 119992
Not yet recruiting
Research facility ORG-000961
Moscow, Russian Federation, 119435
Not yet recruiting
Research facility ORG-000962
Moscow, Russian Federation, 107014
Recruiting
Research facility ORG-000964
Moscow, Russian Federation, 129128
Not yet recruiting
Research facility ORG-000970
St. Petersburg, Russian Federation, 198216
Not yet recruiting
Research facility ORG-000965
St. Petersburg, Russian Federation, 197022
Not yet recruiting
Research facility ORG-000966
St. Petersburg, Russian Federation, 191015
Not yet recruiting
Research facility ORG-000967
St. Petersburg, Russian Federation, 117630
Not yet recruiting
Research facility ORG-000968
St. Petersburg, Russian Federation, 195257
Not yet recruiting
Research facility ORG-000958
Troitsk, Russian Federation, 142190
Recruiting
Research facility ORG-000969
Yaroslavl, Russian Federation, 150003
Not yet recruiting