Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase 2a Study of BMS-790052 in Combination With Peginterferon Alfa-2a (Pegasys®) and Ribavirin (Copegus®) in Treatment Naive Subjects With Chronic Hepatitis C Virus Genotype 1
Brief Summary: The purpose of this study is to identify 1 or more doses of daclatasvir, which when used in combination with pegylated interferon alpha and ribavirin, are safe and demonstrate sufficient anti-hepatitis C virus activity.


Options:
A: Inclusion Criteria:

* Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and ECG, including no cardiac, pulmonary, hepatic, biliary (except Gilbert's disease, gastrointestinal, or renal (defined as serum creatinine \>1.5 mg/dL or a calculated creatinine clearance (CrCl)\<50 mL/min), disorders, or cancer within the past 5 years (except localized or in situ cancer of the skin). A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator and the GSK Medical Monitor agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. A single repeat laboratory evaluation is allowed for eligibility determination.
* Male or female between 18 and 65 years of age inclusive, at the time of signing the informed consent.
* A female is eligible to enter and participate in this study if she is of: Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation, bilateral oophorectomy, hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea.
* Male subjects must agree to use one of the contraception methods listed in the protocol.
* Body weight greater than or equal to 50 kg (110 lbs.) for men and greater than or equal to 45 kg (99 lbs.) for women. For Part 1, body mass index (BMI) between 18.5-32 kg/m2 inclusive will be allowed. For Part 3, BMI between 18.5-35.0 kg/m2 inclusive will be allowed.
* For healthy subjects in Part 1 and Part 2, Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), alkaline phosphatase, bilirubin, and creatinine less than the upper limits of normal (ULN) (isolated bilirubin \<2.0xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%).
* QTcB or QTcF \< 450 msec; or QTc \<480 msec in subjects with Bundle Branch Block.
* The subject's systolic blood pressure is inside the range of 90-140 mmHg, or diastolic blood pressure is inside the range of 45-90 mmHg or heart rate is inside the range of 50-100 beats per minute (bpm) for female subjects or 45-100 bpm for male subjects.
* Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
* The subject is able to understand and comply with protocol requirements, instructions and protocol-stated restrictions and is likely to complete the study as planned.
* The following are Supplemental inclusion criteria for Part 3: HCV positive subjects: Treatment naive chronically infected genotype 1 HCV patients, defined as infection for \>6 months and no prior HCV therapy.
* An HCV RNA viral load of greater than 100,000 IU/mL using a COBAS TaqMan HCV test and HCV genotype 1a or 1b as assessed by VERSANT HCV genotyping LiPA 2.0 (Bayer Healthcare, Berkeley, California), or by direct Deoxyribonucleic acid (DNA) sequencing of the NS5B gene Hepatitis C virus infection of mixed genotype excluded. HCV subjects with mixed genotypes are not eligible for the study.
* ALT greater than or equal to 3x ULN is allowed.
* Liver biopsy within two years prior to screening indicating the absence of cirrhosis.

Exclusion Criteria:

* Unwillingness or inability to follow the procedures outlined in the protocol.
* A positive pre-study test for Human Immunodeficiency Virus (HIV) antibody or Hepatitis B surface antigen.
* For healthy subjects in Parts 1 and 2, a positive Hepatitis C antibody result within 3 months of screening. Chronic HCV infected subjects in Part 3 will have a positive HCV antibody and a positive HCV RNA.
* Pregnant females as determined by positive serum or urine Human chorionic gonadotropin (hCG) test at screening or prior to dosing.
* Subject is mentally or legally incapacitated.
* Has a history of regular alcohol consumption averaging: \>7 drinks/week for women or \>14 drinks/week for men within 6 months of the screening visit.
* Unwilling to abstain from alcohol for 48 hours prior to the start of dosing until collection of the final pharmacokinetic sample during each treatment period.
* For healthy subjects in Parts 1 and 2, history of regular use of tobacco- or nicotine-containing products within 3 months of the screening visit or indication of tobacco use as evidenced by a positive urine cotinine test at screening. For chronic HCV infected subjects in Part 3, history of regular use of tobacco- or nicotine-containing products is allowed; however, use of tobacco is not allowed on days of PK draws nor at the study site.
* Consumption of red wine, seville oranges, grapefruit or grapefruit juice, pummelos, satsuma, ugli, tangerine, and tangelo, exotic citrus fruits, grapefruit hybrids or fruit juices from 5 days prior to the first dose of study medication.
* The subject has a positive pre-study drug screen. A minimum list of drugs that will be screened for include amphetamines, barbiturates, cocaine, opiates, cannabinoids, phencyclidine (PCP), and benzodiazepines. Unwilling to refrain from the use of illicit drugs and adhere to other protocol-stated restrictions while participating in the study.
* Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
* The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
* Exposure to more than four new investigational entities within 12 months prior to the first dosing day.
* History or presence of allergy or intolerance to the study drugs or their components or drugs of their class, or a history of drug or other allergy that, in the opinion of the physician responsible, contraindicates their participation. In addition, if heparin is used during PK sampling, subjects with a history of sensitivity to heparin or heparin-induced thrombocytopenia should not be enrolled.
* Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
* Holter monitoring shows one or more of the following: Any symptomatic arrhythmia (except isolated extra systoles); Sustained cardiac arrhythmias (such as atrial fibrillation or flutter, sustained ventricular tachycardia (SVT) (\>10 consecutive beats)); Non-sustained or sustained ventricular tachycardia (defined as \>3 consecutive ventricular ectopic beats); Any conduction abnormality (including but not specific to left or right complete bundle branch block, atrioventricular (AV) block \[2nd degree or higher in an awake subject\], Wolff-Parkinson-White syndrome (WPW) syndrome, other pre-excitation syndromes); Symptomatic sinus pause or sinus pause \>3 seconds - unless patient is straining, vomiting, or having some other type of hypervagal response; 300 or more supraventricular ectopic beats in 24 hours; 250 or more ventricular ectopic beats in 24 hours; Ischemia, diagnosed by a sequence of EKG changes that include flat or down sloping ST-segment depression \>0.1 mV, with a gradual onset and offset that lasts for a minimum period of 1 minute. Each episode of ischemia must be separated by a minimum duration of at least 1 minute, during which the ST segment returns back to baseline (1x1x1 rule)
B: For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

* Males and females, ≥ 18 years of age
* HCV Genotype 1b who previously failed treatment with peginterferon alfa and ribavirin, classified as previous null or partial responders based on previous therapy, OR intolerant or ineligible to P/R due to neutropenia, anemia, depression or thrombocytopenia with fibrosis/cirrhosis, OR treatment naive
* HCV RNA ≥ 10,000 IU/mL
* Seronegative for Human immunodeficiency virus (HIV) and Hepatitis B surface antigen (HBsAg)
* Subjects with compensated cirrhosis are permitted (compensated cirrhotics are capped at approximately 25% of treated population)

Exclusion Criteria:

* Prior treatment of HCV with HCV direct acting antiviral (DAA)
* Evidence of a medical condition contributing to chronic liver disease other than HCV
* Evidence of decompensated liver disease including, but not limited to, a history or presence of ascites, bleeding varices, or hepatic encephalopathy
* Diagnosed or suspected hepatocellular carcinoma or other malignancies
* Uncontrolled diabetes or hypertension
C: 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.
D: Key Inclusion Criteria:

* Patients chronically infected with hepatitis C virus (HCV) genotype 1
* HCV RNA viral load of ≥10\*5\* IU/mL (100,000 IU/mL) at screening
* Treatment naive

Key Exclusion Criteria:

* Women of child-bearing potential
* Cirrhosis
* Coinfection with HIV or hepatitis B virus

Answer: D