Open Label Single Dose Phase I Trial of BI 201335 to Study Pharmacokinetics and Safety in Patients With Compensated Liver Cirrhosis

An Open Label Single Dose Phase I Trial of 120 mg and 240 mg BI 201335 Soft Gel Capsules to Study Pharmacokinetic Properties and Safety in Patients With Compensated Liver Cirrhosis in Historical Comparison With 1220.2

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).

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)