Please select the eligibility criteria that correspond to the clinical trial below.
Title: Safety, Antiviral Activity, and Pharmacokinetics of Multiple Rising Oral Doses of BI 201335 NA in Treatment-naïve Patients With Chronic Hepatitis C Infection for 14 Days Monotherapy Followed by Combination With Pegylated Interferon and Ribavirin for an Additional 14 Days (Double-blind, Placebo Controlled), and in Treatment-experienced Patients With Chronic Hepatitis C Infection for 28 Days as Combination Therapy With Pegylated Interferon and Ribavirin (Open-label)
Brief Summary: This study will investigate safety, antiviral activity, and pharmacokinetics of BI 201335 NA in HCV genotype 1 infected patients treated for 14 days monotherapy followed by BI 201335 NA combination therapy with PegIFN/RBV for an additional 14 days for treatment-naïve patients; or for 28 days as BI 201335 NA combination therapy with PegIFN/RBV for treatment-experienced patients.

A secondary objective is to investigate antiviral activity, potential drug-drug interactions and safety of combination therapy of BI 201335 NA and PegIFN/RBV up to 28 days for treatment-naïve patients.


Options:
A: Inclusion Criteria:

* Male or female subjects at least 18 years of age.
* HCV seropositive.
* HCV RNA \>10,000 IU/mL at screening.
* HCV Genotype 1. Subjects infected with a non-genotype 1 strain or mixed genotypes are not eligible.
* Treatment naïve (no prior treatment with IFN alfa +/ RBV regimens or investigational anti-HCV agents).
* Liver biopsy within two years (24 months) of Screening with non-cirrhotic fibrosis classification. For those subjects with liver biopsy outside of the time window or for those subjects with no history of liver biopsy, a biopsy must be performed prior to randomization.
* Ultrasound within 6 months of Screening for 1) those subjects with bridging fibrosis or 2) those subjects with AFP \>50 and \<100 ng/mL with no evidence of hepatocellular carcinoma. For those subjects with an ultrasound conducted outside the 6-month time window, an ultrasound must be performed prior to randomization.

Exclusion Criteria:

* Co-infection with either HIV or HBV.
* Evidence of severe or decompensated liver disease.
* Subjects with liver disease unrelated to HCV infection.
* Pre-existing medical condition that makes the subject unsuitable for treatment with pegIFN/RBV therapy per product labeling.
* Laboratory abnormality at Screening that makes the subject unsuitable for treatment with pegIFN/RBV therapy per product labeling.
* Abnormal ECG suggestive of clinically significant cardiac disease or QTc\>450msec.
* History of organ transplant.
* Contraindicated medications being taken by the subject at the time of randomization that must be continued during the study period, including potent CYP3A4 inhibitors, sensitive CYP3A4 substrates, CYP3A4 substrates with narrow therapeutic range and CYP3A4 inducers.
* Active alcohol or substance abuse sufficient, in the Investigator's judgment, to prevent adherence to study medication and/or follow up.
* Pregnant or nursing females.
* Males whose female partner is pregnant.
B: Inclusion criteria:

1a. For treatment-naïve patients: no prior therapy with interferon, peginterferon, or ribavirin for acute or chronic hepatitis C infection

1b. For treatment-experienced patients: confirmed virological failure during or after combination treatment with an approved dose of alfa-2a or alfa-2b peginterferon combined with ribavirin; such patients must have received at least 12 weeks of therapy with a 90 day washout period prior to screening and must have documentation of medical history prior to enrolment in 1220.2 2. Age 18 years or older 3. Signed informed consent form prior to trial participation 4. Male or female with documented hysterectomy or menopausal female with last menstrual period at least 6 months prior to screening 5. Chronic hepatitis C infection of genotype 1, diagnosed by positive HCV serology test (HCV Ab positive) or detectable HCV RNA at least 6 months prior to screening 6. HCV viral load \>= 100,000 IU/mL at screening 7. TSH and T4 within normal limits or adequately controlled thyroid function 8. Histological evidence within 36 months prior to study enrolment of any degree of chronic necroinflammatory activity or the presence of fibrosis (Ishak Grade 1-4 or Metavir Grade 1-3)

Exclusion criteria:

1. Patients who have been previously treated with at least one dose of any protease inhibitor for acute or chronic hepatitis C infection
2. Evidence of liver disease due to causes other than chronic HCV infection
3. Positive ELISA for HIV-1 or HIV-2
4. Hepatitis B virus (HBV) infection based on presence of Hbs Ag or HBV DNA
5. Any previous liver biopsy consistent with cirrhosis
6. Decompensated liver diseases as evidenced by ascites, portal hypertension, jaundice or hepatic encephalopathy
7. Haemophilia
8. Hemoglobinopathy (e.g., thalassemia major or sickle cell anemia)
9. Severe pre-existing psychiatric disease
10. Poorly controlled diabetes mellitus
11. Ischaemic heart disease
12. Chronic obstructive airway disease
13. Autoimmune disease; including autoimmune hepatitis
14. History of alcohol abuse within the past 12 months
15. Hyperbilirubinemia (conjugated bilirubin) \>1.5x ULN
16. Alkaline phosphatase \>1.5x ULN
17. ALT and AST levels \>= 5 x ULN
18. Hemoglobin \< 12.0 g/dL for women and \< 13.0 g/dL for men
19. White blood cell count \< 2000 cells/mm3
20. Absolute Neutrophil Count \< 1500 cells/mm3
21. Platelet count \< 100,000 cells/mm3
22. Prothrombin time INR (Institutional Normalized Ratio) prolonged to \> 1.5 x ULN
23. Usage of any investigational drug within 30 days prior to enrolment; or the planned usage of an investigational drug during the course of the current study
24. Known hypersensitivity to study drugs
C: Inclusion Criteria:

* Subjects must have a qualifying regimen defined as peginterferon alfa-2a/ribavirin or peginterferon alfa-2b/ribavirin for a minimum of 12 weeks.
* During the qualifying regimen, subjects must have either:

  * A documented undetectable Hepatitis C Virus-Ribonucleic Acid (HCV-RNA) within 30 days of the end-of-treatment and a subsequent detectable HCV-RNA during follow-up OR
  * A documented decline in HCV-RNA by \>=2 log10 after 12 weeks of treatment.
* Subject must have previously documented chronic hepatitis C genotype 1 infection.
* Subject must have a liver biopsy with histology consistent with chronic hepatitis C infection and no other etiology.
* Subjects with bridging fibrosis or cirrhosis must have an ultrasound within 6 months with no findings suspicious for hepatocellular carcinoma (HCC).
* Subject must be \>=18 years of age.
* Subject must weigh between 40 kg and 125 kg.
* Subject and subject's partner(s) must each agree to use acceptable methods of contraception.
* Subjects must be willing to give written informed consent.

Exclusion Criteria:

Subject will be excluded from entry if ANY of the criteria listed below are

met:

* Subjects known to be coinfected with the human immunodeficiency virus (HIV) or hepatitis B virus (hepatitis B surface antigen \[HBsAg\] positive) and/or demonstrating signs and symptoms consistent with co-infection.
* Subjects who required discontinuation of previous interferon or ribavirin regimen for an adverse event considered by the investigator to be possibly or probably related to ribavirin and/or interferon.
* Treatment with ribavirin within 90 days and any interferon alfa within 1 month of Screening.
* Treatment for hepatitis C with any investigational medication. Prior treatment with herbal remedies with known hepatotoxicity is exclusionary.
* Treatment with any investigational drug within 30 days of the randomization visit in this study.
* Participation in any other clinical trial within 30 days of randomization or intention to participate in another clinical trial during participation in this study.
* Evidence of decompensated liver disease.
* Diabetic and/or hypertensive subjects with clinically significant ocular examination findings.
* Pre-existing psychiatric condition(s).
* Clinical diagnosis of substance abuse.
* Any known pre-existing medical condition that could interfere with the subject's participation in and completion of the study.
* Evidence of active or suspected malignancy, or a history of malignancy, within the last 5 years (except adequately treated carcinoma in situ and basal cell carcinoma of the skin).
* Subjects who are pregnant or nursing. Subjects who intend to become pregnant during the study period. Male subjects with partners who are or who intend to become pregnant during the study period.
* Any other condition which, in the opinion of a physician, would make the subject unsuitable for enrollment or could interfere with the subject participating in and completing the study.
* Subjects who are part of the site personnel directly involved with this study.
* Subjects who are family members of the investigational study staff.
* Subjects who had a life-threatening serious adverse event (SAE) during the screening period.
* Subjects with a history of pancreatitis, except for one episode clearly secondary to gallstone.

Laboratory Exclusion Criteria:

* Hematologic, biochemical, and serologic criteria (growth factors may not be used to achieve study entry requirements):

  * Hemoglobin (Hgb) \<12 g/dL for females and \<13 g/dL for males
  * Neutrophils \<1500/mm3 (blacks: \<1200/mm3)
  * Platelets \<100,000/mm3
  * Direct bilirubin \>1.5 x upper limit of normal (ULN) of the laboratory reference range. Total bilirubin \>1.6 mg/dL unless the subject has a history of Gilbert's disease. If Gilbert's disease is the proposed etiology, this must be documented in the subject's chart.
* Serum albumin \< lower limit of normal (LLN) of laboratory reference range.
* Thyroid-stimulating hormone (TSH) \>1.2 x ULN or \<0.8 x LLN of laboratory reference range.
* Serum creatinine \>ULN of the laboratory reference range.
* Serum glucose:

  * For subjects not previously diagnosed with diabetes mellitus:

    * \>=140 mg/dL (nonfasting) unless hemoglobin A1c subtype (HbA1c) \<=7% OR
    * \>=100 mg/dL (fasting) unless HbA1c \<=7%.
  * For subjects previously diagnosed with diabetes mellitus: HbA1c \>8.5%.
* Prothrombin time/partial thromboplastin time (PT/PTT) values \>10% above laboratory reference range.
* Anti-nuclear antibodies (ANA) \>1:320.
* Alpha fetoprotein (AFP):

  * AFP \>100 ng/mL OR
  * AFP 50 to 100 ng/mL requires a liver ultrasound and subjects with findings suspicious for HCC are excluded.
D: Inclusion criteria:

* Has chronic HCV genotype 1 infection
* Is treatment-experienced
* For the non-cirrhotic population, has had a liver biopsy without evidence of cirrhosis and hepatocellular carcinoma; for the cirrhotic population, has had a liver biopsy with evidence of cirrhosis and without evidence of hepatocellular carcinoma.

Exclusion criteria:

* Has not tolerated previous course peg-IFN and RBV
* Is unlikely to tolerate at least 24 weeks of continuous therapy with Peg-IFN and RBV
* Is co-infected with Human Immunodeficiency Virus (HIV) and/or hepatitis B
* Consumes excessive amounts of alcohol
* Has a history of drug or alcohol abuse
* If female, participant is pregnant or breastfeeding
* Has been in a clinical trail with an investigational drug in the last 30 days
* Has used IFN/Peg-IFN and RBV in the last 3 months

Answer: B