Impact of HCV Treatment on Neurocognitive Functions and Brain Metabolism

Exclusion Criteria

• •Target disease
• •Infected with HCV other than genotype 1
• •Medical history and concurrent diseases
• •Current hazardous consumption of alcohol, defined by an AUDIT-C score ≥4 for men and ≥3 for women
• •Illicit substance use, identified by urinary drug test at screening
• •Past history of non HCV-related CNS disorder, including seizures and traumatic brain injury
• •Currently on an SSRI or other neuropsychiatric therapy
• •Liver or any other organ transplant other than cornea and hair
• •Current or known history of cancer (except in situ carcinoma of the cervix or adequately treated basal or squamous cell carcinoma of the skin) within 5 years prior to enrolment
• •Evidence of a medical condition contributing to chronic liver disease other than HCV (such, but not limited to: hemochromatosis, autoimmune hepatitis, metabolic liver disease, alcohol liver disease)
• •Any gastrointestinal disease or surgical procedure that may impact the absorption of study drug (subjects who have cholecystectomy are permitted to enter the study)
• •Known history of coagulopathy including, but not limited to, hemophilia
• •Uncontrolled diabetes defined as HbA1c \>7% at screening
• •Confirmed, uncontrolled hypertension (any screening systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥100 mmHg should be excluded unless discussed with the study medical monitor)
• •Inability to tolerate oral medication
• •Poor venous access
• •Any other medical, psychiatric and/or social reason which, in the opinion of the investigator would make the subject inappropriate for the study
• •Physical and Laboratory Test Findings
• •ALT ≥ 5 x ULN
• •Total Bilirubin ≥ 34 µmol/L (≥ 2 mg/dl), unless subject has documented history of Gilbert's disease
• •INR ≥ 1.3
• •Albumin \< 3.5 g/dL (35g/L)
• •Platelets \< 100 x 109 cells/L
• •ANC \< 0.75 x 109 cells/L
• •Hemoglobin \< 10 g/dL (100g/L)
• •Creatinine clearance (CrCL) ≤ 50 mL/min
• •Alpha fetoprotein (AFP) \> 50ng/mL
• •QTcF or QTcB \> 580mSec
• •Positive HBsAg, HIV-1 or HIV-2 Ab
• •Allergies and Adverse Drug Reaction
• •History of hypersensitivity to drugs with a similar biochemical structure to DCV, ASV or BCV
• •Any other criteria or know contraindication that would exclude the subject from receiving DCV, ASV or BCV Prohibited treatments and/or Therapies
• •Exposure to any investigational drug or placebo within 4 weeks of study drug administration
• •Refer to 5.5 for prohibited and/or restricted treatments during and post-treatment Sex and reproductive status
• •Prisoners or subjects who are involuntarily incarcerated
• •Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g. infection disease) illness