Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase IIb, Randomized, Double-Blind, Placebo-Controlled Trial to Investigate the Efficacy, Tolerability, Safety and Pharmacokinetics of TMC435 as Part of a Treatment Regimen Including Peginterferon Alfa-2a and Ribavirin In Treatment-Naive Genotype 1 Hepatitis C-Infected Subjects
Brief Summary: The purpose of this study is to evaluate the efficacy of 4 different regimens of TMC435 in combination with peginterferon alfa-2a (PegIFNα-2a) and ribavirin (RBV), defined as the proportion of patients with sustained virologic response at Week 72 (patients with undetectable plasma HCV RNA \[less than 25 IU per mL undetectable\] at the end of treatment and at Week 72), compared to the control group receiving PegIFN and RBV in combination with TMC435-matched placebo.


Options:
A: Inclusion Criteria:

* Infection with HCV genotype 2 or 3
* Had cirrhosis determination
* Prior treatment failure
* Screening laboratory values within defined thresholds
* Subject had not been treated with any investigational drug or device within 30 days of the screening visit
* Use of highly effective contraception methods if female of childbearing potential or sexually active male

Exclusion Criteria:

* Prior exposure to an direct-acting antiviral targeting the HCV nonstructural protein (NS)5B polymerase
* Pregnant or nursing female or male with pregnant female partner
* Current or prior history of clinical hepatic decompensation
* History of clinically significant illness or any other major medical disorder that may have interfered with subject treatment, assessment or compliance with the protocol
* Excessive alcohol ingestion or significant drug abuse
B: Inclusion Criteria:

* Patients with documented chronic genotype-1 hepatitis C infection and with plasma HCV RNA of \> 100,000 IU/mL at screening
* Patients that have not been treated before for HCV
* Patients that are of childbearing potential or have a partner of childbearing potential should agree to use 2 effective methods of contraception

Exclusion Criteria:

* Patients with cirrhosis or evidence of hepatic decompensation
* Co-infection with the human immunodeficiency virus (HIV)
* Any contraindication to Pegasys or Copegus therapy
* History of, or any current medical condition which could impact the safety of the patient in the study
C: Inclusion Criteria:

For Arms A, B and C:

- Participants must meet one of the following:

* Treatment-naive: Participant has never received antiviral treatment for hepatitis C infection OR
* Treatment Experienced (Prior null responders, Partial responders or Relapsers to IFN/RBV);

For Arm D:

- Participant must have prior treatment experience with SOF/pegIFN/RBV or SOF/RBV and meet one of the following categories:

* Prior SOF breakthrough/non-responder: HCV RNA detectable at the end of treatment with SOF/pegIFN/RBV or SOF/RBV;
* Prior SOF relapser: achieved HCV RNA undetectable at end of a prior treatment course SOF/pegIFN/RBV or SOF/RBV, but HCV RNA was detectable within 52 weeks following completion of therapy.

For Arms A, B, C and D:

* Chronic HCV genotype 4 infection with cirrhosis.
* Participant has plasma HCV RNA level \> 1,000 IU/mL at Screening

Exclusion Criteria:

* Positive test result at Screening for Hepatitis B surface antigen (HBsAg) or anti-human immunodeficiency virus antibody (HIV Ab).
* Current enrollment in another interventional clinical study, previous enrollment in this study, or previous use of any protease inhibitor, non-nucleoside polymerase inhibitor, or Nonstructural viral protein (NS) 5A inhibitor, either investigational or commercially available (including previous exposure to paritaprevir or ombitasvir), or receipt of any investigational product within 6 weeks prior to study drug administration. Prior use of any direct-acting antiviral will not be allowed, except for Arm D where prior experience with the nucleoside polymerase inhibitor, sofosbuvir with pegIFN/RBV or SOF with RBV is required.
* Any current or past clinical evidence of Child-Pugh B or C classification or clinical history of liver decompensation including ascites, variceal bleeding, or hepatic encephalopathy.
* Confirmed presence of hepatocellular carcinoma.
* Any cause of liver disease other than chronic HCV infection.
* Abnormal laboratory tests.
D: 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)

Answer: B