Evaluation of IDX375 in healthy and hepatitis C-infected subjects

INTERVENTION: 1. Dose escalation in healthy subjects ‐ 8 subjects per dosing cohort, randomised 6:2 (active:placebo): 1.1. 200 mg IDX375 (or placebo) x 1 day 1.2. 400 mg IDX375 (or placebo) on days 1 and 8 1.3. 300 mg IDX375 (or placebo) x 1 day 1.4. 1200 mg IDX375 (or placebo) x 1 day 1.5. 800 mg IDX375 twice daily (BID) or (placebo BID) x 1 day 1.6. 800 mg IDX375 BID or (placebo BID) x 3 days 2. Proof‐of‐concept in HCV‐infected subjects ‐ 10 subjects per dosing cohort, randomised 8:2 (active:placebo): 2.1. 400 mg IDX375 BID or (placebo BID) x 3 days 2.2. 800 mg IDX375 BID or (placebo BID) x 3 days 2.3. 1200 mg IDX375 four times a day (QD) or (placebo QD) x 3 days Total duration of treatment: maximum 3 days dosing Total duration of follow‐up: maximum 25 days follow‐up CONDITION: Genotype 1 chronic hepatitis C virus ; Infections and Infestations ; Chronic viral hepatitis PRIMARY OUTCOME: 1. Adverse events, physical examination, vital signs, electrocardiograms (ECGs), standard safety laboratory tests; 2. Change in plasma HCV RNA, emergence of resistance mutations; ; Measured daily during research unit confinement up to 14 days maximum, with weekly visits for follow‐up. SECONDARY OUTCOME: Plasma concentrations of IDX375. Measured daily during research unit confinement up to 14 days maximum, with weekly visits for follow‐up. INCLUSION CRITERIA: All participants: 1. Aged 18 ‐ 65 years 2. Body mass index (BMI) 18 ‐ 35 kg/m^2 3. Must agree to use an acceptable double‐barrier method of birth control 4. Male subject must agree not to donate sperm for 90 days after the last dose of study drug 5. Subject has provided written informed consent to participate in the study Specific to healthy subjects: 6. Subject must be male 7. Subject must be a non‐smoker Specific to HCV‐infected subjects: 8. Female subjects must be of non‐childbearing potential 9. Documented clinical history compatible with chronic hepatitis C 10. Plasma HCV ribonucleic acid (RNA) greater than or equal to 5 log10 IU/mL at screening 11. HCV genotype 1 12. HCV treatment‐naive