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

This is an interventional treatment trial for Hepatitis C Read More

Inclusion Criteria for Healthy Volunteers (SAD and MAD Phases):

• Healthy male and female subjects of any ethnic origin between the ages of 18 and 55 years, inclusive.
• Female subjects must be of non-childbearing potential.
• All male participants who have not had a vasectomy must use effective contraception from Day -1 to 90 days after their last dose of study drug.
• Body mass index of 18 to 30 kg/m2 with a minimum body weight of 50 kg.
• An informed consent document signed and dated by the subject.

Exclusion Criteria for Healthy Volunteers (SAD and MAD Phases):

• 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

Inclusion Criteria for HCV-Infected Subjects (POC Phase):

• Males and females aged 18 years and less than 70 years.
• Female subjects must be of non-childbearing potential.
• All male participants who have not had a vasectomy must use effective contraception from Day -1 to 90 days after their last dose of study drug.
• Body mass index of 18 to 36 kg/m2 with a minimum body weight of 50 kg.
• Treatment naïve subjects with chronic HCV infection,
• HCV GT1 (including 1a, 1b, or mixed subtypes of GT1) or GT3.
• HCV RNA ≥100,000 IU/mL at screening.
• An informed consent document signed and dated by the subject.

Exclusion Criteria for HCV-Infected Subjects (POC Phase):

• 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