Conditions: Chronic Hepatitis C
Keywords: Hepatitis C virus HCV
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 178
Healthy volunteers: yes

Brief summary:
This is a multi-part study to evaluate the safety, tolerability, and pharmacokinetics (PK) of uprifosbuvir (MK-3682/IDX21437) in healthy participants and in participants infected with Hepatitis C virus (HCV) genotype (GT)1-GT6. The effect of food on the PK of uprifosbuvir will be evaluated. The antiviral activity of uprifosbuvir will also be assessed in HCV-infected participants.

Detailed description:

Arms:
arm 1: Healthy participants will receive sequentially higher doses of uprifosbuvir (10 mg - 300 mg) capsules or matching placebo capsules once daily (QD) on Day 1 (Cohorts 1a-3a, 5a), Days 1 and 7 (Cohort 4a), or Day 1 - Day 7 (Cohort 6a). Dosing of next cohort will be based on review of available safety and PK data. Dosing will occur under fasted conditions with the exception of Cohort 4a, in which drug administration will occur under both fasted and fed conditions. arm 2: HCV GT1 participants with no prior direct-acting antiviral (DAA) exposure will receive a single dose of uprifosbuvir (10 mg - 300 mg) for 1 day across sequential dose cohorts. Dosing will commence following review of available safety and PK data from respective dose cohorts in Group A. All dosing will occur under fasted conditions. arm 3: HCV GT1 participants will receive uprifosbuvir (50 mg - 400 mg in capsules or 300 mg or 450 mg in tablets) or matching placebo capsules QD for 7 days. Dosing will commence following review of available safety and PK data of Group A. Fed vs. fasted dosing will be dependent on food effect results from Group A. arm 4: HCV GT2 - GT6 participants will receive uprifosbuvir (50 mg - 300 mg) capsules QD for 7 days. Dosing will commence following review of available safety and PK data from Group A. Fed vs. fasted dosing will be dependent on food effect results from Group A. arm 5: HCV GT1 participants with mildly impaired hepatic function will receive uprifosbuvir (150 mg - 450 mg) capsules QD for 1 or 7 days. Dosing of subsequent cohorts will be based on review of available safety and PK data. Fed vs. fasted dosing will be dependent on food effect results from Group A. arm 6: HCV GT1 participants will receive itraconazole 200 mg twice daily (BID) on Day -5 and itraconazole 200 mg QD from Day -4 to Day 11. Participants will also be co-administered uprifosbuvir 300 mg from Day 1 to Day 7.

Interventions: intervention 1: Uprifosbuvir intervention 2: Placebo intervention 3: Itraconazole
Intervention descriptions: intervention 1: Uprifosbuvir 5 mg, 25 mg, or 50 mg capsule, or 150 mg tablet, administered by mouth. intervention 2: Matching placebo to uprifosbuvir capsule administered by mouth. intervention 3: Itraconazole is supplied as 10 mg/mL oral solution or 100 mg capsules administered by mouth.

Protocol document: