Multiple Oral Doses of BI 207127 NA in Treatment naïve and Treatment-experienced Hepatitis C Virus (HCV)-Infected Patients
Condition: Hepatitis C, Chronic
MeSH terms: Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Hepatitis
Intervention: BI 207127 NA; Placebo
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double
Enrollment: 75.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No

Summary:

      The purpose of this study was to investigate antiviral activity, safety and pharmacokinetics
      of 5 days of monotherapy with BI 207127 in HCV genotype 1 (GT1) infected patients. Both
      treatment-naïve patients and patients previously treated with peginterferon and ribavirin
      were included. In addition, the effect of study medication was examined in a group of
      patients with liver cirrhosis.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Adults from 18 - 70 years

          -  Male OR female with documented hysterectomy OR menopausal female with last menstrual
             period at least 12 months prior to screening

          -  Written informed consent consistent with International Conference on
             Harmonization/Good Clinical Practice and local legislation given prior to any study
             procedures

          -  Chronic HCV infection demonstrated by positive HCV immunoglobulin G Antibody

          -  HCV genotype 1 which has to be confirmed by central laboratory test before Visit 2

          -  For non-cirrhotic cohorts: Liver biopsy obtained within the last 36 months consistent
             with HCV infection showing minimal to mild liver fibrosis and without cirrhosis (Ishak
             or Metavir grade ≤ 2). For cirrhotic cohorts, previous liver biopsy or Fibroscan
             consistent with liver cirrhosis performed at any time before screening

          -  HCV RNA load > 100,000 IU RNA per ml serum at screening

        Exclusion Criteria:

          -  All fertile males not willing to use an adequate form of contraception (condom,
             sterilisation at least 6 months post operation) in case their partner is of
             childbearing potential and is not using an adequate form of contraception (hormonal
             contraceptives, oral or injectable/ implantable, intra-uterine device)

          -  Patients who have been treated with at least one dose of any HCV-polymerase inhibitor
             for acute or chronic hepatitis C infection

          -  Any other or additional plausible cause for chronic liver disease, including the
             presence of other viruses known or suspected to cause hepatitis

          -  Decompensated liver disease within past 12 months, as indicated by variceal bleeding,
             ascites, encephalopathy, Prothrombin or International Normalized Ratio (INR) prolonged
             to >1.7 x upper limit of normal (ULN), serum bilirubin > 2 mg/dl or albumin < 3.5 g/dl
             (i.e. Child-Pugh grade B, score > 7)

          -  For non-cirrhotic cohorts: Any previous liver biopsy consistent with cirrhosis. For
             cirrhotic cohorts: Any liver biopsy or fibroscan result from last 2 years excluding
             liver cirrhosis.

          -  Positive test for human immunodeficiency virus (HIV) or hepatitis B antigen at
             screening

          -  Current alcohol or drug abuse, or history of the same, within the past six (6) months.
             Exception: Occasional use of cannabis is not an exclusion criterion. The investigator
             must however instruct the patient that consumption of cannabis is not allowed during
             the treatment period.

          -  Any concurrent disease (cardiovascular, pulmonary, renal, haematological,
             neurological, psychiatric, immunologic, metabolic or endocrine dysfunction) if
             clinically significant based on the investigator's medical assessment at screening. A
             clinically significant disease is defined as one which in the opinion of the
             investigator may either put the patient at risk because of participation in the study
             or may influence the results of the study or the patient's ability to participate in
             the study. Exclusion is also necessary for any pre-existing cardiac abnormality by
             history.

          -  Clinically significant abnormalities at screening ECG, including but not limited to a
             QTc longer than 435 msec, Pulse Rate > 240 msec at baseline and any bundle branch
             block pattern, but not necessarily non-specific T wave abnormalities

          -  History of malignancy (except for previously cured squamous cell or basal cell
             carcinoma)

          -  Patients treated with any interferon (IFN) (approved or investigational) or Peg-IFN
             and/or Ribavirin within 3 months prior to screening

          -  Planned or concurrent usage of any other pharmacological therapy including any
             antiviral therapy or vaccination from 7 days before treatment and during treatment

          -  Usage of any investigational drug within thirty (30) days prior to enrolment or 5
             halflives, whichever is longer; or the planned usage of an investigational drug during
             the course of the current study

          -  Known hypersensitivity to drugs or excipients

          -  Patients with any one of the following laboratory values at screening:

               -  Alanine transaminase (ALT) > 3x ULN, local lab

               -  Aspartate aminotransferase (AST) > 3x ULN, local lab

               -  Total bilirubin > 1.5x ULN, local lab, unless predominantly conjugated and
                  reflecting Gilbert's disease

               -  Alkaline phosphatase > 1.5x ULN, local lab

               -  Prothrombin time (INR) > 1.5x ULN, central lab

               -  Creatinine > 1x ULN, local lab

               -  Urine protein / creatinine ratio > 0.3 g protein / g creatinine, central lab

               -  Alpha-1-microglobulin / creatinine in urine > 1x ULN, central lab

               -  Platelet count < 100,000 / mm3, central lab

               -  White Blood cell count < 2000 cells/mm3, central lab

               -  Absolute neutrophile count < 1500 cells, central lab

               -  Hemoglobin < 12 g/dL, central lab

               -  For patients with liver cirrhosis:

                    -  ALT > 5x ULN, local lab

                    -  AST > 5x ULN, local lab

                    -  Platelet count < 70,000 / mm3, central lab

          -  Patients with any clinically significant laboratory abnormalities based on the
             investigator's medical assessment at screening

          -  Positive urine test for drug abuse at screening

          -  Prior randomisation into this trial

          -  Inability to comply with the protocol

          -  Patients with ongoing or historical photosensitivity or recurrent rash

          -  Alpha fetoprotein value (AFP) > 100 ng/ml; if AFP is > 20 and ≤ 100 ng/ml, patients
             can be included if liver cancer is excluded by a current imaging study (i.e.
             ultrasound, computer tomography scan or magnetic resonance imaging)