Exploratory Study to Assess the Short Term Effect on Liver Enzymes and the Safety of TRO19622 in Patients With Non-Alcoholic Steatohepatitis (NASH)

This study has been completed.
Sponsor:
Information provided by:
Trophos
ClinicalTrials.gov Identifier:
NCT00666016
First received: April 22, 2008
Last updated: January 26, 2011
Last verified: April 2008
  Purpose

The purpose of this study is to assess the safety, the tolerability and the short term effect on liver enzymes of TRO19622 500 mg for one month in patients with Non-Alcoholic Steatohepatitis (NASH).


Condition Intervention Phase
Non-Alcoholic Steatohepatitis (NASH)
Drug: TRO19622
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Double-Blind vs Placebo, Randomized, Exploratory Study to Assess the Short Term Effect on Liver Enzymes and the Safety of TRO19622 500 mg QD for One Month in Patients With Non-Alcoholic Steatohepatitis (NASH)

Resource links provided by NLM:


Further study details as provided by Trophos:

Primary Outcome Measures:
  • Mean change in ALT as assessed by an ANCOVA with the following covariates: treatment, gender, subject and time and a non parametric test (Conover-Salsburg). [ Time Frame: Mean change in ALT at V1 (Day15) and V2 (Day 30) ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Sustained reduction in ALT to either 50% of baseline or value < or equal to ULN. Sustained reduction serum AST and GGT.Clinical and laboratory safety. [ Time Frame: V1 (Day 15), V2 (Day 30) and V3 (Day 60) ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 30
Study Start Date: April 2008
Study Completion Date: April 2009
Primary Completion Date: February 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
TRO19622 500 mg
Drug: TRO19622
TRO19622 500 mg once a day before noon meal during 6 weeks

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adult subjects older than 18 years.
  • Persistent ALT elevation (> 2 times the ULN of the local laboratory of the investigating site) over 6 months prior to entry into study.

    • No more than one ALT value within the normal range in the past year.
    • Patients must have had an ALT measurement at least once every 6 months within the year before inclusion.
  • Histologically confirmed diagnosis of steatohepatitis on biopsy within 2 years prior to entry into protocol.
  • Compensated liver disease with the following hematologic, biochemical, and serological criteria on entry into protocol:

    • Hemoglobin > 11 gm/dL for females and > 12 gm/dL for males
    • White blood cell (WBC) > 2.5 K/UL
    • Neutrophil count > 1.5 K/UL
    • Platelets > 100 K/UL
    • Total bilirubin < 35 µmol/L)
    • Albumin > 36 g/L
    • TP > 80% .
    • Serum creatinine within normal limits
  • No other cause of chronic liver disease (autoimmune,primary biliary cirrhosis, HBV, Wilson, alpha-1-antitrypsin deficit, hemochromatosis etc\dots )
  • If applicable, have a stable diabetes, defined as HbA1c < 9% and fasting glycemia < 10 mmol/L,no changes in medication in the previous 6 months, and no new symptoms associated with diabetes in the previous 3 months.
  • If applicable have a stable metabolic condition (diagnosis made at least 6 months before inclusion), without major weight or laboratory tests changes.
  • Negative pregnancy test or post menopausal.
  • Have an electrocardiogram (ECG) without any clinically significant abnormality.
  • Subjects must be willing to give written informed consent.

Exclusion Criteria:

  • Evidence of another form of liver disease.
  • History of excess alcohol ingestion: daily alcohol consumption >30 g/day (3 drinks per day) for males and >20 g/day (2 drinks/day) for females.
  • Unstable metabolic condition: Weight change > +/- 10% in the previous year, diabetes with poor glycemic control (HbA1c >9%),introduction of an antidiabetic or of an anti-obesity drug in the past 6 months prior to screening.
  • History of gastrointestinal bypass surgery or ingestion of drugs known to produce hepatic steatosis including corticosteroids,high-dose estrogens, methotrexate, tetracycline or amiodarone in the previous 6 months.
  • Significant systemic or major illnesses other than liver disease,including congestive heart failure, coronary artery disease, cerebrovascular disease, pulmonary disease, renal failure, organ transplantation, serious psychiatric disease,malignancy that, in the opinion of the investigator would preclude treatment with TRO19622 and/or adequate follow up.
  • HIV infection.
  • Active substance abuse, such as inhaled or injection drugs within the previous year.
  • Pregnancy or inability to practice adequate contraception in women of child-bearing potential.
  • Active malignancy except cutaneous basocellular carcinoma.
  • Any other condition which, in the opinion of the investigator would impede competence or compliance or possibly hinder completion of the study.
  • Body mass index (BMI) >40 kg/m2 (obesity Grade III).
  • Type 1 diabetes or Insulin-treated type 2 diabetes.
  • Hemostasis disorders or current treatment with anticoagulants.
  • History of, or current cardiac dysrhythmias and / or a history of cardiovascular disease, including myocardial infarction, except patients with only well controlled hypertension.
  • Participation in any other investigational drug or therapy study within the previous 3 months.
  • Be possibly dependent on the Investigator or the Sponsor (eg, including, but not limited to, affiliated employee).
  • Medications that could interfere with TRO19622 absorption
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00666016

Locations
France
Hôpital Archet 2 - Pôle de Référence Hépatite C (Niveau -2) - 151, route Saint Antoine de Ginestière
Nice, France, 06200
Groupe Hospitalier Pitié-Salpétrière - Sce Hépato-Gastroentérologie - 47-83 Bd de l'Hôpital
Paris, France, 75651
Sponsors and Collaborators
Trophos
Investigators
Principal Investigator: Vlad Ratziu, MD GH PITIE-SALPETRIERE
  More Information

No publications provided

Responsible Party: Nathalie Strub Wourgaft, Trophos
ClinicalTrials.gov Identifier: NCT00666016     History of Changes
Other Study ID Numbers: TRO19622 CL E Q 1159-1
Study First Received: April 22, 2008
Last Updated: January 26, 2011
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Trophos:
non alcoholic steatohepatitis nash hepatoprotective hepatoprotection ALT AST new drug candidate interventional study TRO19622 Trophos cholest-4-en-3-one oxime

Additional relevant MeSH terms:
Fatty Liver
Liver Diseases
Digestive System Diseases

ClinicalTrials.gov processed this record on April 16, 2014