EDP-494-001: A Study of EDP-494 in Healthy Subjects and Hepatitis C Patients

Exclusion Criteria

• •Clinically relevant evidence or history of illness or disease
• •Pregnant or nursing females.
• •History of febrile illness within 7 days prior to the first dose of study drug or subjects with evidence of active infection.
• •A positive urine drug screen at screening or Day -1.
• •Any condition possibly affecting drug absorption (e.g., gastrectomy).
• •History of regular alcohol consumption
• •Participation in a clinical trial within 30 days prior to study drug administration.
• •Use of prescription drugs, non-prescription drugs, dietary supplements, herbal supplements, hormonal therapy/replacement or CYP3A4 substrates, inducers and inhibitors within 14 days prior to the first dose of study medication
• •Women of childbearing potential (WOCBP).
• •Pregnant or nursing females.
• •History of febrile illness within 7 days prior to the first dose of study drug.
• •A positive urine drug screen at screening unless on an approved prescription.
• •History of participation in a clinical trial with a polymerase inhibitor or previous treatment with a polymerase inhibitor, where at least one dose of the polymerase inhibitor was consumed. Subjects who were dosed with placebo on a clinical trial may be enrolled in this study.
• •Clinically significant electrocardiogram abnormalities or QTcF greater than 450 msec for males and 470 msec for females at either screening or baseline, or any prior history of QT abnormality.
• •Co-infection with HIV-1, HIV-2 or HBV.
• •Have clinically significant laboratory abnormalities at screening:
• •* Absolute neutrophil count (ANC) \< 1500/mm2 (1.5 x 109L)
• •* Platelets \<90,000/mm2 (90 x 109L)
• •* Hemoglobin \< 13g/dL for males and \< 12g/dL for females
• •* Serum creatinine \>1.5 x upper limit of normal (ULN) or creatinine clearance \< 50 mL/min; estimated by the cockcroft -Gault formula \[(140-age) x weight (kg)/72 x serum creatinine (mg/dL), if female multiply by 0.85\]
• •* Total bilirubin greater than the ULN
• •* Serum alanine transaminase (ALT) \> 5 x ULN
• •* Serum aspartate aminotransferase (AST) \> 5 x ULN
• •* Alkaline phosphatase \> 1.25 x ULN
• •* Pancreatic Amylase \> 1.1 x ULN
• •* Alpha fetoprotein (AFP) \> 50 ng/mL unless a liver imaging study (CT, MRI) shows no clinically significant lesions within 6 months prior to the first dose of study drug.
• •Patients with evidence of cirrhosis; cirrhosis is defined as any one of the following: a) any biopsy showing cirrhosis (Knodell score \<3, Metavir score \<3, Ishak score \<4); b) Fibroscan evaluation within 6 months prior to screening with a liver stiffness score of \>\<12.5 kPa.
• •Other significant, unstable or uncontrolled medical history, such as neurological, endocrine, malignancy, renal, psychiatric, respiratory, cardiac, gastrointestinal, allergic, immunological, etc. disease.
• •Use of concomitant medications, including vitamins or herbal and dietary supplements within 7 days or 5 half-lives (whichever is longer) prior to the first dose of study medication