Hepatitis C
Conditions
Brief summary
This randomized, double-blind study will assess the safety, pharmacokinetics and efficacy of a single and multiple dose(s) of orally QD administered EDP-494 in healthy volunteers (HV) and in treatment-naive subjects with GT1/3 chronic hepatitis C (CHC) infection.
Detailed description
The first phase explores single ascending doses of EDP-494 (active drug or placebo) in healthy subjects. A 'fasted' vs 'fed' two-part cohort will also assess food effect. The second phase involves multiple ascending doses (active drug or placebo) for 14 days in healthy subjects. The third, proof of concept, phase will assess two different doses for 14 days each in Hepatitis C patients. Each cohort within each phase will consist of 8 subjects randomized to either EDP-494 or placebo in a 3 to 1 ratio, with the exception of the food effect cohort, which will consist of 10 subjects randomised in a 4 to 1 ratio.
Interventions
DRUGEDP-494
10, 100 and 200 mg capsules
DRUGPlacebo
placebo to match EDP-494
Sponsors
Novotech (Australia) Pty Limited
Enanta Pharmaceuticals, Inc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Composite number and frequency of treatment emergent adverse events, physical examination findings, abnormal vital signs, 12 lead ECG, and abnormal clinical laboratory results administered to healthy volunteers and multiple doses of EDP-494 | From screening and baseline to the 4 week follow-up visit | Tabulation of the number and frequency of treatment emergent adverse events, physical examination findings, abnormal vital signs, 12 lead ECG, echo and abnormal clinical laboratory results (including chemistry, hematology, and urine). Administered to healthy volunteers and multiple doses of EDP-494 administered to healthy volunteers and subjects with Chronic Hepatitis C (CHC) genotype 1 and 3 infection |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cmax | 0 (predose), 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 15, 24, 30, 36, 48, 60, 72 (Day 4), 96 (Day 5), 120 (Day 6)*, 144 (Day 7) and 168 (Day 8) hrs postdose | EDP-494 and metabolites |
| AUC | 0 (predose), 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 15, 24, 30, 36, 48, 60, 72, 96, 120*, 144, and 168 hrs postdose | EDP-494 and metabolites |
| Change from baseline in plasma HCV RNA (log10 IU/mL) | Baseline up to 14 days | — |
| Amino Acid Changes in HCV polymerase NS5b | Baseline up to 3 months | — |
Countries
New Zealand
Outcome results
None listed