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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00666016
Recruitment Status : Completed
First Posted : April 24, 2008
Last Update Posted : November 22, 2016
Information provided by (Responsible Party):
Hoffmann-La Roche

Brief Summary:
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 or disease Intervention/treatment Phase
Non-Alcoholic Steatohepatitis (NASH) Drug: TRO19622 Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 35 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
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)
Study Start Date : April 2008
Actual Primary Completion Date : February 2009
Actual Study Completion Date : April 2009

Arm Intervention/treatment
Experimental: 1
TRO19622 500 mg
Drug: TRO19622
TRO19622 500 mg once a day before noon meal during 6 weeks

Primary Outcome Measures :
  1. 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) ]

Secondary Outcome Measures :
  1. 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) ]

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00666016

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
Hoffmann-La Roche
Principal Investigator: Vlad Ratziu, MD GH PITIE-SALPETRIERE

Responsible Party: Hoffmann-La Roche Identifier: NCT00666016     History of Changes
Other Study ID Numbers: WN29850
TRO19622 CL E Q 1159-1 ( Other Identifier: trophos id )
First Posted: April 24, 2008    Key Record Dates
Last Update Posted: November 22, 2016
Last Verified: November 2016

Keywords provided by Hoffmann-La Roche:
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
Non-alcoholic Fatty Liver Disease
Liver Diseases
Digestive System Diseases