Open Label Single Dose Phase I Trial of BI 201335 to Study Pharmacokinetics and Safety in Patients With Compensated Liver Cirrhosis
Condition: Hepatitis C; Liver Cirrhosis
MeSH terms: Hepatitis C; Liver Cirrhosis; Fibrosis
Intervention: BI 201335
Intervention description: single oral doses
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 2.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This trial was intended to investigate the pharmacokinetics, safety and tolerability of BI
      201335 NA soft-gel capsules in patients with compensated liver cirrhosis, i.e. grade A
      according to Child-Pugh classification (< 7 points).
    

Eligibility criteria:

        Inclusion criteria:

          1. Patients with liver cirrhosis, that is histologically proven in a previous liver
             biopsy; possible aetiologies are: cured HCV infection, former alcohol abuse, genetic
             haemochromatosis, non-alcoholic steatohepatitis or others.

          2. Compensated liver disease, as indicated by Prothrombin time or INR prolonged to <1.7 x
             ULN, serum bilirubin < 2 mg/dl, albumin > 3.5 g/dl, no ascites or encephalopathy
             (Child-Pugh grade A, score < 7)

          3. Age 18 years or older

          4. Male patients, or female with documented hysterectomy, ovariectomy or tubal ligation
             OR menopausal female with last menstrual period at least 12 months prior to screening
             OR female of childbearing potential with a negative serum pregnancy test at screening
             and day 1 and willing to ensure consistent and correct contraception

          5. Written informed consent prior to study enrolment which must be consistent with
             international conference on harmonisation ¿ good clinical practice (ICH-GCP) and local
             legislation.

        Exclusion criteria:

          1. Serological evidence of active HBV, HCV or HIV infection (i.e. seropositivity for HBs
             antigen, anti-HIV-1 or -2 antibodies; if anti-HCV antibody positive, patients must
             have documented negative HCV RNA for at least 12 months)

          2. Usage of any drug within 7 days or 5 halftimes, whichever is longer, prior to
             treatment; or the planned usage of a drug during the course of the current study

          3. Usage of any investigational drug within 30 days prior to treatment; or the planned
             usage of an investigational drug during the course of the current study

          4. Decompensated liver disease within past 12 months, as indicated by variceal bleeding,
             ascites, encephalopathy, Prothrombin time or INR prolonged to > 1,7 x ULN, serum
             bilirubin > 2 mg/dl or albumin < 3,5 g/dl (i.e. Child-Pugh grade B)

          5. ALT or AST levels > 5xULN, Alkaline Phosphatase > 2xULN

          6. Liver cirrhosis due to primary or secondary biliary cirrhosis, sclerosing cholangitis,
             vanishing bile duct disease

          7. History of alcohol abuse within the past 3 months

          8. Known hypersensitivity to any content of the study drug

          9. Pregnant or breast feeding females

         10. Females of childbearing potential who are not willing to ensure consistent and correct
             use of condoms and at least one additional medically accepted method of contraception
             (diaphragm with spermicidal substance, cervical caps) or who are unwilling to comply
             to complete abstinence, from the date of screening until 6 months after the last dose
             of study drug

         11. AFP value > 100 ng/ml; if AFP is > 20 and <= 100 ng/ml, patients can be included if
             liver cancer is excluded by two congruent imaging studies (i.e. ultrasound plus CT
             scan or MRI)

         12. Evidence of chronic kidney failure (i.e. serum creatinine > ULN)

         13. Haemoglobinopathy (e.g., thalassaemia major or sickle cell anaemia)

         14. Concomitant intercurrent illnesses including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness or social situation that would limit compliance
             with trial requirement or which are considered relevant for the evaluation of the
             pharmacokinetic parameters or safety of the trial drug.

         15. Active or suspected malignancy or history of malignancy within the last 2 years (with
             the exception of appropriately treated basal cell carcinoma or in situ carcinoma of
             the uterine cervix)