Trial Outcomes & Findings for Single and Multiple Dose Study of Uprifosbuvir (MK-3682/IDX21437) in Healthy and Hepatitis C Virus (HCV)-Infected Participants (MK-3682-001) (NCT NCT01974687)

Results Overview

Maximum observed plasma drug concentration was obtained.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

178 participants

Primary outcome timeframe

Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose

Results posted on

2018-09-13

Participant Flow

Per protocol, the Group D part of the study allowed to randomize Genotype 2, 3, 4, 5 and 6 Hepatitis C Virus (HCV)-infected participants, however, only Genotype 2 and 3 HCV-infected participants were enrolled.

Participant milestones

Participant milestones
Measure	Group A: Uprifosbuvir 10 mg (Cohort 1a) Participants were administered a single dose of uprifosbuvir (MK-3682/IDX21437) 10 mg as oral capsules under fasted conditions.	Group A: Uprifosbuvir 25 mg (Cohort 2a) Participants were administered a single dose of uprifosbuvir 25 mg as oral capsules under fasted conditions.	Group A: Uprifosbuvir 150 mg (Cohort 4a) Participants were administered single doses of uprifosbuvir 150 mg as oral capsules on Days 1 and 7 in a 2-period crossover design (fasted/fed) with a 6 day washout between dosing periods.	Group A: Uprifosbuvir 300 mg (Cohort 5a) Participants were administered a single dose of uprifosbuvir 300 mg as oral capsules under fasted conditions.	Group A: Placebo (Cohort 6a) Participants were administered single doses of uprifosbuvir-matching placebo oral capsules once daily for 7 days under fasted conditions.	Group A: Uprifosbuvir 300 mg (Cohort 6a) Participants were administered single doses of uprifosbuvir 300 mg as oral capsules once daily for 7 days under fasted conditions.	Group B: Uprifosbuvir 10 mg (Cohort 1b) Participants were administered a single dose of uprifosbuvir 10 mg as oral capsules under fasted conditions.	Group B: Uprifosbuvir 25 mg (Cohort 2b) Participants were administered a single dose of uprifosbuvir 25 mg as oral capsules under fasted conditions.	Group B: Uprifosbuvir 50 mg (Cohort 3b) Participants were administered a single dose of uprifosbuvir 50 mg as oral capsules under fasted conditions.	Group B: Uprifosbuvir 150 mg (Cohort 4b) Participants were administered a single dose of uprifosbuvir 150 mg as oral capsules under fasted conditions.	Group B: Uprifosbuvir 300 mg (Cohort 5b) Participants were administered a single dose of uprifosbuvir 300 mg as oral capsules under fasted conditions.	Groups C & D: Uprifosbuvir 50 mg (Capsule) Participants were administered single doses of uprifosbuvir 50 mg as oral capsules once daily for 7 days under fasted conditions.	Groups C & D: Uprifosbuvir 150 mg (Capsule) Participants were administered single doses of uprifosbuvir 150 mg as oral capsules once daily for 7 days under fasted conditions.	Groups C & D: Uprifosbuvir 250 mg (Capsule) Participants were administered single doses of uprifosbuvir 250 mg as oral capsules once daily for 7 days under fasted conditions.	Groups C & D: Uprifosbuvir 300 mg (Capsule) Participants were administered single doses of uprifosbuvir 300 mg as oral capsules once daily for 7 days under fasted conditions.	Groups C & D: Uprifosbuvir 400 mg (Capsule) Participants were administered single doses of uprifosbuvir 400 mg as oral capsules once daily for 7 days under fasted conditions.	Groups C & D: Uprifosbuvir 300 mg (Tablet) Participants were administered single doses of uprifosbuvir 300 mg as oral tablets once daily for 7 days under fasted conditions.	Groups C & D: Uprifosbuvir 450 mg (Tablet) Participants were administered single doses of uprifosbuvir 450 mg as oral tablets once daily for 7 days under fasted conditions.	Groups C & D: Placebo (Pooled) Participants were administered single doses of uprifosbuvir-matching placebo as oral capsules once daily for 7 days under fasted conditions.	Group E: Uprifosbuvir 150 mg (Cohort 1e) Participants were administered a single dose of uprifosbuvir 150 mg as oral capsules under fasted conditions.	Group E: Uprifosbuvir 300 mg (Cohort 2e) Participants were administered single doses of uprifosbuvir 300 mg as oral capsules once daily for 7 days under fasted conditions.	Group E: Uprifosbuvir 450 mg (Cohort 3e) Participants were administered single doses of uprifosbuvir 450 mg as oral tablets once daily for 7 days under fasted conditions.	Group F: Uprifosbuvir 300 mg (Tablet) Participants were administered single doses of uprifosbuvir 300 mg as oral tablets once daily for 7 days under fasted conditions. Participants were also administered itraconazole 200 mg twice daily as oral solution on Day -5 and 200 mg once daily from Day -4 to Day 11.	Group A: Uprifosbuvir 50 mg (Cohort 3a) Participants were administered a single dose of uprifosbuvir 50 mg as oral capsules under fasted conditions.	Group A: Placebo (Cohorts 1a-5a - Pooled) Participants were administered a single dose of uprifosbuvir-matching placebo as oral capsules under fasted conditions (Cohorts 1a, 2a, 3a, 5a); Participants were administered single doses of uprifosbuvir-matching placebo as oral capsules on Days 1 and 7 in a 2-period crossover design (fasted/fed) with a 6 day washout between dosing periods (Cohort 4a).
Overall Study Treated	6	6	6	6	2	6	3	3	3	3	3	11	10	8	18	8	8	8	9	3	3	8	8	6	10
Overall Study STARTED	6	6	6	6	2	6	3	3	3	3	3	13	13	10	19	9	9	11	9	3	3	8	8	6	10
Overall Study COMPLETED	6	6	6	6	2	6	3	3	3	3	3	11	10	8	18	8	8	8	9	3	3	8	8	6	10
Overall Study NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	0	2	3	2	1	1	1	3	0	0	0	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Single and Multiple Dose Study of Uprifosbuvir (MK-3682/IDX21437) in Healthy and Hepatitis C Virus (HCV)-Infected Participants (MK-3682-001)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Groups C & D: Uprifosbuvir 50 mg (Capsule) n=11 Participants Participants were administered single doses of uprifosbuvir 50 mg as oral capsules once daily for 7 days under fasted conditions.	Groups C & D: Uprifosbuvir 150 mg (Capsule) n=10 Participants Participants were administered single doses of uprifosbuvir 150 mg as oral capsules once daily for 7 days under fasted conditions.	Groups C & D: Uprifosbuvir 250 mg (Capsule) n=8 Participants Participants were administered single doses of uprifosbuvir 250 mg as oral capsules once daily for 7 days under fasted conditions.	Groups C & D: Uprifosbuvir 300 mg (Capsule) n=18 Participants Participants were administered single doses of uprifosbuvir 300 mg as oral capsules once daily for 7 days under fasted conditions.	Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) n=10 Participants Participants were administered a single dose of uprifosbuvir-matching placebo as oral capsules under fasted conditions (Cohorts 1a, 2a, 3a, 5a); Participants were administered single doses of uprifosbuvir-matching placebo as oral capsules on Days 1 and 7 in a 2-period crossover design (fasted/fed) with a 6 day washout between dosing periods (Cohort 4a).	Group A: Uprifosbuvir 10 mg (Cohort 1a) n=6 Participants Participants were administered a single dose of uprifosbuvir 10 mg as oral capsules under fasted conditions.	Group A: Uprifosbuvir 25 mg (Cohort 2a) n=6 Participants Participants were administered a single dose of uprifosbuvir 25 mg as oral capsules under fasted conditions.	Group A: Uprifosbuvir 150 mg (Cohort 4a) n=6 Participants Participants were administered single doses of uprifosbuvir 150 mg as oral capsules on Days 1 and 7 in a 2-period crossover design (fasted/fed) with a 6 day washout between dosing periods.	Group A: Uprifosbuvir 300 mg (Cohort 5a) n=6 Participants Participants were administered a single dose of uprifosbuvir 300 mg as oral capsules under fasted conditions.	Group A: Placebo (Cohort 6a) n=2 Participants Participants were administered single doses of uprifosbuvir-matching placebo oral capsules once daily for 7 days under fasted conditions.	Group A: Uprifosbuvir 300 mg (Cohort 6a) n=6 Participants Participants were administered single doses of uprifosbuvir 300 mg as oral capsules once daily for 7 days under fasted conditions.	Group B: Uprifosbuvir 10 mg (Cohort 1b) n=3 Participants Participants were administered a single dose of uprifosbuvir 10 mg as oral capsules under fasted conditions.	Group B: Uprifosbuvir 25 mg (Cohort 2b) n=3 Participants Participants were administered a single dose of uprifosbuvir 25 mg as oral capsules under fasted conditions.	Group B: Uprifosbuvir 50 mg (Cohort 3b) n=3 Participants Participants were administered a single dose of uprifosbuvir 50 mg as oral capsules under fasted conditions.	Group B: Uprifosbuvir 150 mg (Cohort 4b) n=3 Participants Participants were administered a single dose of uprifosbuvir 150 mg as oral capsules under fasted conditions.	Group B: Uprifosbuvir 300 mg (Cohort 5b) n=3 Participants Participants were administered a single dose of uprifosbuvir 300 mg as oral capsules under fasted conditions.	Groups C & D: Uprifosbuvir 400 mg (Capsule) n=8 Participants Participants were administered single doses of uprifosbuvir 400 mg as oral capsules once daily for 7 days under fasted conditions.	Groups C & D: Uprifosbuvir 300 mg (Tablet) n=8 Participants Participants were administered single doses of uprifosbuvir 300 mg as oral tablets once daily for 7 days under fasted conditions.	Groups C & D: Uprifosbuvir 450 mg (Tablet) n=8 Participants Participants were administered single doses of uprifosbuvir 450 mg as oral tablets once daily for 7 days under fasted conditions.	Groups C & D: Placebo (Pooled) n=9 Participants Participants were administered single doses of uprifosbuvir-matching placebo as oral capsules once daily for 7 days under fasted conditions.	Group E: Uprifosbuvir 150 mg (Cohort 1e) n=3 Participants Participants were administered a single dose of uprifosbuvir 150 mg as oral capsules under fasted conditions.	Group E: Uprifosbuvir 300 mg (Cohort 2e) n=3 Participants Participants were administered single doses of uprifosbuvir 300 mg as oral capsules once daily for 7 days under fasted conditions.	Group E: Uprifosbuvir 450 mg (Cohort 3e) n=8 Participants Participants were administered single doses of uprifosbuvir 450 mg as oral tablets once daily for 7 days under fasted conditions.	Group F: Uprifosbuvir 300 mg (Tablet) n=8 Participants Participants were administered single doses of uprifosbuvir 300 mg as oral tablets once daily for 7 days under fasted conditions. Participants were also administered itraconazole 200 mg twice daily as oral solution on Day -5 and 200 mg once daily from Day -4 to Day 11.	Group A: Uprifosbuvir 50 mg (Cohort 3a) n=6 Participants Participants were administered a single dose of uprifosbuvir 50 mg as oral capsules under fasted conditions.	Total n=165 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=36 Participants	0 Participants n=36 Participants	0 Participants n=24 Participants	0 Participants n=135 Participants	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=136 Participants	0 Participants n=44 Participants	0 Participants n=667 Participants	0 Participants n=12 Participants	0 Participants n=12 Participants	0 Participants n=12 Participants	0 Participants n=12 Participants	0 Participants n=11 Participants	0 Participants n=6 Participants	0 Participants n=7 Participants
Age, Categorical Between 18 and 65 years	11 Participants n=36 Participants	10 Participants n=36 Participants	8 Participants n=24 Participants	18 Participants n=135 Participants	10 Participants n=5 Participants	6 Participants n=7 Participants	6 Participants n=5 Participants	6 Participants n=4 Participants	6 Participants n=21 Participants	2 Participants n=8 Participants	6 Participants n=8 Participants	3 Participants n=24 Participants	3 Participants n=42 Participants	3 Participants n=42 Participants	3 Participants n=42 Participants	3 Participants n=42 Participants	8 Participants n=136 Participants	8 Participants n=44 Participants	8 Participants n=667 Participants	9 Participants n=12 Participants	3 Participants n=12 Participants	3 Participants n=12 Participants	8 Participants n=12 Participants	8 Participants n=11 Participants	6 Participants n=6 Participants	165 Participants n=7 Participants
Age, Categorical >=65 years	0 Participants n=36 Participants	0 Participants n=36 Participants	0 Participants n=24 Participants	0 Participants n=135 Participants	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=136 Participants	0 Participants n=44 Participants	0 Participants n=667 Participants	0 Participants n=12 Participants	0 Participants n=12 Participants	0 Participants n=12 Participants	0 Participants n=12 Participants	0 Participants n=11 Participants	0 Participants n=6 Participants	0 Participants n=7 Participants
Age, Continuous	41.2 Years STANDARD_DEVIATION 10.68 • n=36 Participants	42.7 Years STANDARD_DEVIATION 10.37 • n=36 Participants	44.3 Years STANDARD_DEVIATION 8.63 • n=24 Participants	40.1 Years STANDARD_DEVIATION 11.69 • n=135 Participants	35.3 Years STANDARD_DEVIATION 7.72 • n=5 Participants	29.2 Years STANDARD_DEVIATION 7.36 • n=7 Participants	33.3 Years STANDARD_DEVIATION 15.06 • n=5 Participants	35.5 Years STANDARD_DEVIATION 11.76 • n=4 Participants	35.2 Years STANDARD_DEVIATION 9.87 • n=21 Participants	36.0 Years STANDARD_DEVIATION 2.83 • n=8 Participants	35.3 Years STANDARD_DEVIATION 12.69 • n=8 Participants	37.0 Years STANDARD_DEVIATION 9.54 • n=24 Participants	42.3 Years STANDARD_DEVIATION 7.23 • n=42 Participants	46.7 Years STANDARD_DEVIATION 4.16 • n=42 Participants	43.3 Years STANDARD_DEVIATION 5.69 • n=42 Participants	41.3 Years STANDARD_DEVIATION 8.96 • n=42 Participants	43.3 Years STANDARD_DEVIATION 8.45 • n=136 Participants	40.5 Years STANDARD_DEVIATION 11.70 • n=44 Participants	40.5 Years STANDARD_DEVIATION 8.94 • n=667 Participants	43.7 Years STANDARD_DEVIATION 7.68 • n=12 Participants	57.0 Years STANDARD_DEVIATION 4.36 • n=12 Participants	56.3 Years STANDARD_DEVIATION 3.06 • n=12 Participants	49.1 Years STANDARD_DEVIATION 8.04 • n=12 Participants	43.1 Years STANDARD_DEVIATION 12.54 • n=11 Participants	31.3 Years STANDARD_DEVIATION 11.60 • n=6 Participants	40.47 Years STANDARD_DEVIATION 10.85 • n=7 Participants
Sex: Female, Male Female	5 Participants n=36 Participants	0 Participants n=36 Participants	5 Participants n=24 Participants	5 Participants n=135 Participants	4 Participants n=5 Participants	4 Participants n=7 Participants	2 Participants n=5 Participants	5 Participants n=4 Participants	4 Participants n=21 Participants	0 Participants n=8 Participants	4 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	1 Participants n=42 Participants	2 Participants n=42 Participants	1 Participants n=42 Participants	3 Participants n=136 Participants	5 Participants n=44 Participants	4 Participants n=667 Participants	3 Participants n=12 Participants	0 Participants n=12 Participants	0 Participants n=12 Participants	1 Participants n=12 Participants	6 Participants n=11 Participants	3 Participants n=6 Participants	67 Participants n=7 Participants
Sex: Female, Male Male	6 Participants n=36 Participants	10 Participants n=36 Participants	3 Participants n=24 Participants	13 Participants n=135 Participants	6 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants	1 Participants n=4 Participants	2 Participants n=21 Participants	2 Participants n=8 Participants	2 Participants n=8 Participants	3 Participants n=24 Participants	3 Participants n=42 Participants	2 Participants n=42 Participants	1 Participants n=42 Participants	2 Participants n=42 Participants	5 Participants n=136 Participants	3 Participants n=44 Participants	4 Participants n=667 Participants	6 Participants n=12 Participants	3 Participants n=12 Participants	3 Participants n=12 Participants	7 Participants n=12 Participants	2 Participants n=11 Participants	3 Participants n=6 Participants	98 Participants n=7 Participants

PRIMARY outcome

Timeframe: Up to 42 days

Population: Safety Population: all participants who received at least one dose of the study drug

An AE was defined as any untoward medical occurrence in a participant administered study drug, and that does not necessarily have a causal relationship with the study drug(s). An AE can be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug(s), whether or not related to study drug(s). The percentage of participants who experienced at least one AE is presented.

Outcome measures

Outcome measures
Measure	Group B: Uprifosbuvir 10 mg (Cohort 1b) n=10 Participants Participants were administered a single dose of uprifosbuvir 10 mg as oral capsules under fasted conditions.	Group B: Uprifosbuvir 25 mg (Cohort 2b) n=6 Participants Participants were administered a single dose of uprifosbuvir 25 mg as oral capsules under fasted conditions.	Groups C & D: Placebo (Pooled) n=9 Participants Participants were administered single doses of uprifosbuvir-matching placebo as oral capsules once daily for 7 days under fasted conditions.	Group E: Uprifosbuvir 150 mg (Cohort 1e) n=3 Participants Participants were administered a single dose of uprifosbuvir 150 mg as oral capsules under fasted conditions.	Group E: Uprifosbuvir 300 mg (Cohort 2e) n=3 Participants Participants were administered single doses of uprifosbuvir 300 mg as oral capsules once daily for 7 days under fasted conditions.	Group A: Uprifosbuvir 50 mg (Cohort 3a) n=6 Participants Participants were administered a single dose of uprifosbuvir 50 mg as oral capsules under fasted conditions.	Group E: Uprifosbuvir 450 mg (Cohort 3e) n=8 Participants Participants were administered single doses of uprifosbuvir 450 mg as oral tablets once daily for 7 days under fasted conditions.	Group F: Uprifosbuvir 300 mg (Tablet) n=8 Participants Participants were administered single doses of uprifosbuvir 300 mg as oral tablets once daily for 7 days under fasted conditions. Participants were also administered itraconazole 200 mg twice daily as oral solution on Day -5 and 200 mg once daily from Day -4 to Day 11.	Group A: Uprifosbuvir 25 mg (Cohort 2a) n=6 Participants Participants were administered a single dose of uprifosbuvir 25 mg as oral capsules under fasted conditions.	Group A: Uprifosbuvir 50 mg (Cohort 3a) n=6 Participants Participants were administered a single dose of uprifosbuvir 50 mg as oral capsules under fasted conditions.	Group A: Uprifosbuvir 300 mg (Cohort 5a) n=6 Participants Participants were administered a single dose of uprifosbuvir 300 mg as oral capsules under fasted conditions.	Group A: Uprifosbuvir 300 mg (Cohort 6a) n=6 Participants Participants were administered single doses of uprifosbuvir 300 mg as oral capsules once daily for 7 days under fasted conditions.	Group A: Placebo (Cohort 6a) n=2 Participants Participants were administered single doses of uprifosbuvir-matching placebo oral capsules once daily for 7 days under fasted conditions.	Group B: Uprifosbuvir 10 mg (Cohort 1b) n=3 Participants Participants were administered a single dose of uprifosbuvir 10 mg as oral capsules under fasted conditions.	Group B: Uprifosbuvir 25 mg (Cohort 2b) n=3 Participants Participants were administered a single dose of uprifosbuvir 25 mg as oral capsules under fasted conditions.	Group B: Uprifosbuvir 50 mg (Cohort 3b) n=3 Participants Participants were administered a single dose of uprifosbuvir 50 mg as oral capsules under fasted conditions.	Group B: Uprifosbuvir 150 mg (Cohort 4b) n=3 Participants Participants were administered a single dose of uprifosbuvir 150 mg as oral capsules under fasted conditions.	Group B: Uprifosbuvir 300 mg (Cohort 5b) n=3 Participants Participants were administered a single dose of uprifosbuvir 300 mg as oral capsules under fasted conditions.	Groups C & D: Uprifosbuvir 50 mg (Capsule) n=11 Participants Participants were administered single doses of uprifosbuvir 50 mg as oral capsules once daily for 7 days under fasted conditions.	Groups C & D: Uprifosbuvir 150 mg (Capsule) n=10 Participants Participants were administered single doses of uprifosbuvir 150 mg as oral capsules once daily for 7 days under fasted conditions.	Groups C & D: Uprifosbuvir 250 mg (Capsule) n=8 Participants Participants were administered single doses of uprifosbuvir 250 mg as oral capsules once daily for 7 days under fasted conditions.	Groups C & D: Uprifosbuvir 300 mg (Capsule) n=18 Participants Participants were administered single doses of uprifosbuvir 300 mg as oral capsules once daily for 7 days under fasted conditions.	Groups C & D: Uprifosbuvir 400 mg (Capsule) n=8 Participants Participants were administered single doses of uprifosbuvir 400 mg as oral capsules once daily for 7 days under fasted conditions.	Groups C & D: Uprifosbuvir 300 mg (Tablet) n=8 Participants Participants were administered single doses of uprifosbuvir 300 mg as oral tablets once daily for 7 days under fasted conditions.	Groups C & D: Uprifosbuvir 450 mg (Tablet) n=8 Participants Participants were administered single doses of uprifosbuvir 450 mg as oral tablets once daily for 7 days under fasted conditions.
Percentage of Participants Who Experienced at Least One Treatment-emergent Adverse Event (AE)	50.0 Percentage of Participants	0.0 Percentage of Participants	66.7 Percentage of Participants	0.0 Percentage of Participants	100.0 Percentage of Participants	66.7 Percentage of Participants	62.5 Percentage of Participants	37.5 Percentage of Participants	33.3 Percentage of Participants	33.3 Percentage of Participants	50.0 Percentage of Participants	33.3 Percentage of Participants	50.0 Percentage of Participants	33.3 Percentage of Participants	66.7 Percentage of Participants	33.3 Percentage of Participants	66.7 Percentage of Participants	66.7 Percentage of Participants	72.7 Percentage of Participants	70.0 Percentage of Participants	87.5 Percentage of Participants	44.4 Percentage of Participants	62.5 Percentage of Participants	75.0 Percentage of Participants	62.5 Percentage of Participants

PRIMARY outcome

Timeframe: Up to 42 days

Population: Safety Population: all participants who received at least one dose of the study drug

An SAE was defined as any untoward medical occurrence that at any dose that: resulted in death, was life threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was an important medical event. The percentage of participants who experienced at least one SAE is presented.

Outcome measures

Outcome measures
Measure	Group B: Uprifosbuvir 10 mg (Cohort 1b) n=10 Participants Participants were administered a single dose of uprifosbuvir 10 mg as oral capsules under fasted conditions.	Group B: Uprifosbuvir 25 mg (Cohort 2b) n=6 Participants Participants were administered a single dose of uprifosbuvir 25 mg as oral capsules under fasted conditions.	Groups C & D: Placebo (Pooled) n=9 Participants Participants were administered single doses of uprifosbuvir-matching placebo as oral capsules once daily for 7 days under fasted conditions.	Group E: Uprifosbuvir 150 mg (Cohort 1e) n=3 Participants Participants were administered a single dose of uprifosbuvir 150 mg as oral capsules under fasted conditions.	Group E: Uprifosbuvir 300 mg (Cohort 2e) n=3 Participants Participants were administered single doses of uprifosbuvir 300 mg as oral capsules once daily for 7 days under fasted conditions.	Group A: Uprifosbuvir 50 mg (Cohort 3a) n=6 Participants Participants were administered a single dose of uprifosbuvir 50 mg as oral capsules under fasted conditions.	Group E: Uprifosbuvir 450 mg (Cohort 3e) n=8 Participants Participants were administered single doses of uprifosbuvir 450 mg as oral tablets once daily for 7 days under fasted conditions.	Group F: Uprifosbuvir 300 mg (Tablet) n=8 Participants Participants were administered single doses of uprifosbuvir 300 mg as oral tablets once daily for 7 days under fasted conditions. Participants were also administered itraconazole 200 mg twice daily as oral solution on Day -5 and 200 mg once daily from Day -4 to Day 11.	Group A: Uprifosbuvir 25 mg (Cohort 2a) n=6 Participants Participants were administered a single dose of uprifosbuvir 25 mg as oral capsules under fasted conditions.	Group A: Uprifosbuvir 50 mg (Cohort 3a) n=6 Participants Participants were administered a single dose of uprifosbuvir 50 mg as oral capsules under fasted conditions.	Group A: Uprifosbuvir 300 mg (Cohort 5a) n=6 Participants Participants were administered a single dose of uprifosbuvir 300 mg as oral capsules under fasted conditions.	Group A: Uprifosbuvir 300 mg (Cohort 6a) n=6 Participants Participants were administered single doses of uprifosbuvir 300 mg as oral capsules once daily for 7 days under fasted conditions.	Group A: Placebo (Cohort 6a) n=2 Participants Participants were administered single doses of uprifosbuvir-matching placebo oral capsules once daily for 7 days under fasted conditions.	Group B: Uprifosbuvir 10 mg (Cohort 1b) n=3 Participants Participants were administered a single dose of uprifosbuvir 10 mg as oral capsules under fasted conditions.	Group B: Uprifosbuvir 25 mg (Cohort 2b) n=3 Participants Participants were administered a single dose of uprifosbuvir 25 mg as oral capsules under fasted conditions.	Group B: Uprifosbuvir 50 mg (Cohort 3b) n=3 Participants Participants were administered a single dose of uprifosbuvir 50 mg as oral capsules under fasted conditions.	Group B: Uprifosbuvir 150 mg (Cohort 4b) n=3 Participants Participants were administered a single dose of uprifosbuvir 150 mg as oral capsules under fasted conditions.	Group B: Uprifosbuvir 300 mg (Cohort 5b) n=3 Participants Participants were administered a single dose of uprifosbuvir 300 mg as oral capsules under fasted conditions.	Groups C & D: Uprifosbuvir 50 mg (Capsule) n=11 Participants Participants were administered single doses of uprifosbuvir 50 mg as oral capsules once daily for 7 days under fasted conditions.	Groups C & D: Uprifosbuvir 150 mg (Capsule) n=10 Participants Participants were administered single doses of uprifosbuvir 150 mg as oral capsules once daily for 7 days under fasted conditions.	Groups C & D: Uprifosbuvir 250 mg (Capsule) n=8 Participants Participants were administered single doses of uprifosbuvir 250 mg as oral capsules once daily for 7 days under fasted conditions.	Groups C & D: Uprifosbuvir 300 mg (Capsule) n=18 Participants Participants were administered single doses of uprifosbuvir 300 mg as oral capsules once daily for 7 days under fasted conditions.	Groups C & D: Uprifosbuvir 400 mg (Capsule) n=8 Participants Participants were administered single doses of uprifosbuvir 400 mg as oral capsules once daily for 7 days under fasted conditions.	Groups C & D: Uprifosbuvir 300 mg (Tablet) n=8 Participants Participants were administered single doses of uprifosbuvir 300 mg as oral tablets once daily for 7 days under fasted conditions.	Groups C & D: Uprifosbuvir 450 mg (Tablet) n=8 Participants Participants were administered single doses of uprifosbuvir 450 mg as oral tablets once daily for 7 days under fasted conditions.
Percentage of Participants Who Experienced at Least One Treatment-emergent Serious AE (SAE)	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants

PRIMARY outcome

Timeframe: Up to 13 days

Population: Safety Population: all participants who received at least one dose of the study drug

A DLT was defined as any of the following events: Any SAE considered by the investigator to be at least reasonably or possibly related to study drug; Any Grade 3 clinical AE considered by the investigator to be at least reasonably or possibly related to study drug; Any Grade 3 confirmed laboratory abnormalities considered by the investigator to be at least reasonably or possibly related to study drug, except for asymptomatic Grade ¾ cholesterol and triglyceride; Any clinical or laboratory AE of any intensity that is considered by the investigator to be at least reasonably or possibly related to study drug that necessitates permanent discontinuation of study drug; Confirmed increase in QT interval corrected for heart rate using Fridericia's (QTcF) formula ≥60 msec over Baseline or an absolute QTcF ≥500 msec.

Outcome measures

Outcome measures
Measure	Group B: Uprifosbuvir 10 mg (Cohort 1b) n=10 Participants Participants were administered a single dose of uprifosbuvir 10 mg as oral capsules under fasted conditions.	Group B: Uprifosbuvir 25 mg (Cohort 2b) n=6 Participants Participants were administered a single dose of uprifosbuvir 25 mg as oral capsules under fasted conditions.	Groups C & D: Placebo (Pooled) n=9 Participants Participants were administered single doses of uprifosbuvir-matching placebo as oral capsules once daily for 7 days under fasted conditions.	Group E: Uprifosbuvir 150 mg (Cohort 1e) n=3 Participants Participants were administered a single dose of uprifosbuvir 150 mg as oral capsules under fasted conditions.	Group E: Uprifosbuvir 300 mg (Cohort 2e) n=3 Participants Participants were administered single doses of uprifosbuvir 300 mg as oral capsules once daily for 7 days under fasted conditions.	Group A: Uprifosbuvir 50 mg (Cohort 3a) n=6 Participants Participants were administered a single dose of uprifosbuvir 50 mg as oral capsules under fasted conditions.	Group E: Uprifosbuvir 450 mg (Cohort 3e) n=8 Participants Participants were administered single doses of uprifosbuvir 450 mg as oral tablets once daily for 7 days under fasted conditions.	Group F: Uprifosbuvir 300 mg (Tablet) n=8 Participants Participants were administered single doses of uprifosbuvir 300 mg as oral tablets once daily for 7 days under fasted conditions. Participants were also administered itraconazole 200 mg twice daily as oral solution on Day -5 and 200 mg once daily from Day -4 to Day 11.	Group A: Uprifosbuvir 25 mg (Cohort 2a) n=6 Participants Participants were administered a single dose of uprifosbuvir 25 mg as oral capsules under fasted conditions.	Group A: Uprifosbuvir 50 mg (Cohort 3a) n=6 Participants Participants were administered a single dose of uprifosbuvir 50 mg as oral capsules under fasted conditions.	Group A: Uprifosbuvir 300 mg (Cohort 5a) n=6 Participants Participants were administered a single dose of uprifosbuvir 300 mg as oral capsules under fasted conditions.	Group A: Uprifosbuvir 300 mg (Cohort 6a) n=6 Participants Participants were administered single doses of uprifosbuvir 300 mg as oral capsules once daily for 7 days under fasted conditions.	Group A: Placebo (Cohort 6a) n=2 Participants Participants were administered single doses of uprifosbuvir-matching placebo oral capsules once daily for 7 days under fasted conditions.	Group B: Uprifosbuvir 10 mg (Cohort 1b) n=3 Participants Participants were administered a single dose of uprifosbuvir 10 mg as oral capsules under fasted conditions.	Group B: Uprifosbuvir 25 mg (Cohort 2b) n=3 Participants Participants were administered a single dose of uprifosbuvir 25 mg as oral capsules under fasted conditions.	Group B: Uprifosbuvir 50 mg (Cohort 3b) n=3 Participants Participants were administered a single dose of uprifosbuvir 50 mg as oral capsules under fasted conditions.	Group B: Uprifosbuvir 150 mg (Cohort 4b) n=3 Participants Participants were administered a single dose of uprifosbuvir 150 mg as oral capsules under fasted conditions.	Group B: Uprifosbuvir 300 mg (Cohort 5b) n=3 Participants Participants were administered a single dose of uprifosbuvir 300 mg as oral capsules under fasted conditions.	Groups C & D: Uprifosbuvir 50 mg (Capsule) n=11 Participants Participants were administered single doses of uprifosbuvir 50 mg as oral capsules once daily for 7 days under fasted conditions.	Groups C & D: Uprifosbuvir 150 mg (Capsule) n=10 Participants Participants were administered single doses of uprifosbuvir 150 mg as oral capsules once daily for 7 days under fasted conditions.	Groups C & D: Uprifosbuvir 250 mg (Capsule) n=8 Participants Participants were administered single doses of uprifosbuvir 250 mg as oral capsules once daily for 7 days under fasted conditions.	Groups C & D: Uprifosbuvir 300 mg (Capsule) n=18 Participants Participants were administered single doses of uprifosbuvir 300 mg as oral capsules once daily for 7 days under fasted conditions.	Groups C & D: Uprifosbuvir 400 mg (Capsule) n=8 Participants Participants were administered single doses of uprifosbuvir 400 mg as oral capsules once daily for 7 days under fasted conditions.	Groups C & D: Uprifosbuvir 300 mg (Tablet) n=8 Participants Participants were administered single doses of uprifosbuvir 300 mg as oral tablets once daily for 7 days under fasted conditions.	Groups C & D: Uprifosbuvir 450 mg (Tablet) n=8 Participants Participants were administered single doses of uprifosbuvir 450 mg as oral tablets once daily for 7 days under fasted conditions.
Percentage of Participants Who Experienced a Treatment-emergent Dose-limiting Toxicity (DLT)	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants

PRIMARY outcome

Timeframe: Up to 42 days

Population: Safety Population: all participants who received at least one dose of the study drug

Laboratory abnormalities were graded using the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events. Treatment-emergent AEs (TEAEs)were graded as: Grade 1: Mild TEAE as Worst Severity; Grade 2: Moderate TEAE as Worst Severity; Grade 3: Severe TEAE as Worst Severity; Grade 4: Potentially Life-Threatening TEAE as Worst Severity; Grade 5: TEAE Leading to Death. The percentage of participants who experienced at least one Grade 1, 2, 3, 4 or 5 laboratory abnormality is presented.

Outcome measures

Outcome measures
Measure	Group B: Uprifosbuvir 10 mg (Cohort 1b) n=10 Participants Participants were administered a single dose of uprifosbuvir 10 mg as oral capsules under fasted conditions.	Group B: Uprifosbuvir 25 mg (Cohort 2b) n=6 Participants Participants were administered a single dose of uprifosbuvir 25 mg as oral capsules under fasted conditions.	Groups C & D: Placebo (Pooled) n=9 Participants Participants were administered single doses of uprifosbuvir-matching placebo as oral capsules once daily for 7 days under fasted conditions.	Group E: Uprifosbuvir 150 mg (Cohort 1e) n=3 Participants Participants were administered a single dose of uprifosbuvir 150 mg as oral capsules under fasted conditions.	Group E: Uprifosbuvir 300 mg (Cohort 2e) n=3 Participants Participants were administered single doses of uprifosbuvir 300 mg as oral capsules once daily for 7 days under fasted conditions.	Group A: Uprifosbuvir 50 mg (Cohort 3a) n=6 Participants Participants were administered a single dose of uprifosbuvir 50 mg as oral capsules under fasted conditions.	Group E: Uprifosbuvir 450 mg (Cohort 3e) n=8 Participants Participants were administered single doses of uprifosbuvir 450 mg as oral tablets once daily for 7 days under fasted conditions.	Group F: Uprifosbuvir 300 mg (Tablet) n=8 Participants Participants were administered single doses of uprifosbuvir 300 mg as oral tablets once daily for 7 days under fasted conditions. Participants were also administered itraconazole 200 mg twice daily as oral solution on Day -5 and 200 mg once daily from Day -4 to Day 11.	Group A: Uprifosbuvir 25 mg (Cohort 2a) n=6 Participants Participants were administered a single dose of uprifosbuvir 25 mg as oral capsules under fasted conditions.	Group A: Uprifosbuvir 50 mg (Cohort 3a) n=6 Participants Participants were administered a single dose of uprifosbuvir 50 mg as oral capsules under fasted conditions.	Group A: Uprifosbuvir 300 mg (Cohort 5a) n=6 Participants Participants were administered a single dose of uprifosbuvir 300 mg as oral capsules under fasted conditions.	Group A: Uprifosbuvir 300 mg (Cohort 6a) n=6 Participants Participants were administered single doses of uprifosbuvir 300 mg as oral capsules once daily for 7 days under fasted conditions.	Group A: Placebo (Cohort 6a) n=2 Participants Participants were administered single doses of uprifosbuvir-matching placebo oral capsules once daily for 7 days under fasted conditions.	Group B: Uprifosbuvir 10 mg (Cohort 1b) n=3 Participants Participants were administered a single dose of uprifosbuvir 10 mg as oral capsules under fasted conditions.	Group B: Uprifosbuvir 25 mg (Cohort 2b) n=3 Participants Participants were administered a single dose of uprifosbuvir 25 mg as oral capsules under fasted conditions.	Group B: Uprifosbuvir 50 mg (Cohort 3b) n=3 Participants Participants were administered a single dose of uprifosbuvir 50 mg as oral capsules under fasted conditions.	Group B: Uprifosbuvir 150 mg (Cohort 4b) n=3 Participants Participants were administered a single dose of uprifosbuvir 150 mg as oral capsules under fasted conditions.	Group B: Uprifosbuvir 300 mg (Cohort 5b) n=3 Participants Participants were administered a single dose of uprifosbuvir 300 mg as oral capsules under fasted conditions.	Groups C & D: Uprifosbuvir 50 mg (Capsule) n=11 Participants Participants were administered single doses of uprifosbuvir 50 mg as oral capsules once daily for 7 days under fasted conditions.	Groups C & D: Uprifosbuvir 150 mg (Capsule) n=10 Participants Participants were administered single doses of uprifosbuvir 150 mg as oral capsules once daily for 7 days under fasted conditions.	Groups C & D: Uprifosbuvir 250 mg (Capsule) n=8 Participants Participants were administered single doses of uprifosbuvir 250 mg as oral capsules once daily for 7 days under fasted conditions.	Groups C & D: Uprifosbuvir 300 mg (Capsule) n=18 Participants Participants were administered single doses of uprifosbuvir 300 mg as oral capsules once daily for 7 days under fasted conditions.	Groups C & D: Uprifosbuvir 400 mg (Capsule) n=8 Participants Participants were administered single doses of uprifosbuvir 400 mg as oral capsules once daily for 7 days under fasted conditions.	Groups C & D: Uprifosbuvir 300 mg (Tablet) n=8 Participants Participants were administered single doses of uprifosbuvir 300 mg as oral tablets once daily for 7 days under fasted conditions.	Groups C & D: Uprifosbuvir 450 mg (Tablet) n=8 Participants Participants were administered single doses of uprifosbuvir 450 mg as oral tablets once daily for 7 days under fasted conditions.
Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality Grade 1	50.00 Percentage of Participants	0.0 Percentage of Participants	33.3 Percentage of Participants	0.0 Percentage of Participants	100.0 Percentage of Participants	50.0 Percentage of Participants	12.5 Percentage of Participants	0.0 Percentage of Participants	16.7 Percentage of Participants	16.7 Percentage of Participants	33.3 Percentage of Participants	33.3 Percentage of Participants	50.0 Percentage of Participants	0.0 Percentage of Participants	66.7 Percentage of Participants	33.3 Percentage of Participants	66.7 Percentage of Participants	66.7 Percentage of Participants	45.5 Percentage of Participants	60.0 Percentage of Participants	37.5 Percentage of Participants	33.3 Percentage of Participants	0.0 Percentage of Participants	37.5 Percentage of Participants	25.0 Percentage of Participants
Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality Grade 2	0.0 Percentage of Participants	0.0 Percentage of Participants	33.3 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	16.7 Percentage of Participants	37.5 Percentage of Participants	37.5 Percentage of Participants	16.7 Percentage of Participants	16.7 Percentage of Participants	16.7 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	33.3 Percentage of Participants	18.2 Percentage of Participants	0.0 Percentage of Participants	50.0 Percentage of Participants	5.6 Percentage of Participants	62.5 Percentage of Participants	37.5 Percentage of Participants	25.0 Percentage of Participants
Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality Grade 3	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	12.5 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	33.3 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	9.1 Percentage of Participants	10.0 Percentage of Participants	0.0 Percentage of Participants	5.6 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants
Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality Grade 4	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	12.5 Percentage of Participants
Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality Grade 5	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants

PRIMARY outcome

Timeframe: Up to 14 days

Population: Safety Population: all participants who received at least one dose of the study drug

The percentage of participants who discontinued study drug due to an AE is presented.

Outcome measures

Outcome measures
Measure	Group B: Uprifosbuvir 10 mg (Cohort 1b) n=10 Participants Participants were administered a single dose of uprifosbuvir 10 mg as oral capsules under fasted conditions.	Group B: Uprifosbuvir 25 mg (Cohort 2b) n=6 Participants Participants were administered a single dose of uprifosbuvir 25 mg as oral capsules under fasted conditions.	Groups C & D: Placebo (Pooled) n=9 Participants Participants were administered single doses of uprifosbuvir-matching placebo as oral capsules once daily for 7 days under fasted conditions.	Group E: Uprifosbuvir 150 mg (Cohort 1e) n=3 Participants Participants were administered a single dose of uprifosbuvir 150 mg as oral capsules under fasted conditions.	Group E: Uprifosbuvir 300 mg (Cohort 2e) n=3 Participants Participants were administered single doses of uprifosbuvir 300 mg as oral capsules once daily for 7 days under fasted conditions.	Group A: Uprifosbuvir 50 mg (Cohort 3a) n=6 Participants Participants were administered a single dose of uprifosbuvir 50 mg as oral capsules under fasted conditions.	Group E: Uprifosbuvir 450 mg (Cohort 3e) n=8 Participants Participants were administered single doses of uprifosbuvir 450 mg as oral tablets once daily for 7 days under fasted conditions.	Group F: Uprifosbuvir 300 mg (Tablet) n=8 Participants Participants were administered single doses of uprifosbuvir 300 mg as oral tablets once daily for 7 days under fasted conditions. Participants were also administered itraconazole 200 mg twice daily as oral solution on Day -5 and 200 mg once daily from Day -4 to Day 11.	Group A: Uprifosbuvir 25 mg (Cohort 2a) n=6 Participants Participants were administered a single dose of uprifosbuvir 25 mg as oral capsules under fasted conditions.	Group A: Uprifosbuvir 50 mg (Cohort 3a) n=6 Participants Participants were administered a single dose of uprifosbuvir 50 mg as oral capsules under fasted conditions.	Group A: Uprifosbuvir 300 mg (Cohort 5a) n=6 Participants Participants were administered a single dose of uprifosbuvir 300 mg as oral capsules under fasted conditions.	Group A: Uprifosbuvir 300 mg (Cohort 6a) n=6 Participants Participants were administered single doses of uprifosbuvir 300 mg as oral capsules once daily for 7 days under fasted conditions.	Group A: Placebo (Cohort 6a) n=2 Participants Participants were administered single doses of uprifosbuvir-matching placebo oral capsules once daily for 7 days under fasted conditions.	Group B: Uprifosbuvir 10 mg (Cohort 1b) n=3 Participants Participants were administered a single dose of uprifosbuvir 10 mg as oral capsules under fasted conditions.	Group B: Uprifosbuvir 25 mg (Cohort 2b) n=3 Participants Participants were administered a single dose of uprifosbuvir 25 mg as oral capsules under fasted conditions.	Group B: Uprifosbuvir 50 mg (Cohort 3b) n=3 Participants Participants were administered a single dose of uprifosbuvir 50 mg as oral capsules under fasted conditions.	Group B: Uprifosbuvir 150 mg (Cohort 4b) n=3 Participants Participants were administered a single dose of uprifosbuvir 150 mg as oral capsules under fasted conditions.	Group B: Uprifosbuvir 300 mg (Cohort 5b) n=3 Participants Participants were administered a single dose of uprifosbuvir 300 mg as oral capsules under fasted conditions.	Groups C & D: Uprifosbuvir 50 mg (Capsule) n=11 Participants Participants were administered single doses of uprifosbuvir 50 mg as oral capsules once daily for 7 days under fasted conditions.	Groups C & D: Uprifosbuvir 150 mg (Capsule) n=10 Participants Participants were administered single doses of uprifosbuvir 150 mg as oral capsules once daily for 7 days under fasted conditions.	Groups C & D: Uprifosbuvir 250 mg (Capsule) n=8 Participants Participants were administered single doses of uprifosbuvir 250 mg as oral capsules once daily for 7 days under fasted conditions.	Groups C & D: Uprifosbuvir 300 mg (Capsule) n=18 Participants Participants were administered single doses of uprifosbuvir 300 mg as oral capsules once daily for 7 days under fasted conditions.	Groups C & D: Uprifosbuvir 400 mg (Capsule) n=8 Participants Participants were administered single doses of uprifosbuvir 400 mg as oral capsules once daily for 7 days under fasted conditions.	Groups C & D: Uprifosbuvir 300 mg (Tablet) n=8 Participants Participants were administered single doses of uprifosbuvir 300 mg as oral tablets once daily for 7 days under fasted conditions.	Groups C & D: Uprifosbuvir 450 mg (Tablet) n=8 Participants Participants were administered single doses of uprifosbuvir 450 mg as oral tablets once daily for 7 days under fasted conditions.
Percentage of Participants Who Discontinued Study Drug Due to a Treatment-emergent AE	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants

PRIMARY outcome

Timeframe: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose

Population: Pharmacokinetics (PK) Population: a subpopulation of the per-protocol population, selecting all participants exposed to uprifosbuvir who had available and evaluable data (e.g., excluding deviations and/or other events that could have an impact on the PK analysis).

AUC0-t was calculated using linear log trapezoidal summation from time zero to last measurable concentration. All participants were fasted.

Outcome measures

Outcome measures
Measure	Group B: Uprifosbuvir 10 mg (Cohort 1b) n=6 Participants Participants were administered a single dose of uprifosbuvir 10 mg as oral capsules under fasted conditions.	Group B: Uprifosbuvir 25 mg (Cohort 2b) n=6 Participants Participants were administered a single dose of uprifosbuvir 25 mg as oral capsules under fasted conditions.	Groups C & D: Placebo (Pooled) Participants were administered single doses of uprifosbuvir-matching placebo as oral capsules once daily for 7 days under fasted conditions.	Group E: Uprifosbuvir 150 mg (Cohort 1e) Participants were administered a single dose of uprifosbuvir 150 mg as oral capsules under fasted conditions.	Group E: Uprifosbuvir 300 mg (Cohort 2e) Participants were administered single doses of uprifosbuvir 300 mg as oral capsules once daily for 7 days under fasted conditions.	Group A: Uprifosbuvir 50 mg (Cohort 3a) n=6 Participants Participants were administered a single dose of uprifosbuvir 50 mg as oral capsules under fasted conditions.	Group E: Uprifosbuvir 450 mg (Cohort 3e) Participants were administered single doses of uprifosbuvir 450 mg as oral tablets once daily for 7 days under fasted conditions.	Group F: Uprifosbuvir 300 mg (Tablet) Participants were administered single doses of uprifosbuvir 300 mg as oral tablets once daily for 7 days under fasted conditions. Participants were also administered itraconazole 200 mg twice daily as oral solution on Day -5 and 200 mg once daily from Day -4 to Day 11.	Group A: Uprifosbuvir 25 mg (Cohort 2a) n=6 Participants Participants were administered a single dose of uprifosbuvir 25 mg as oral capsules under fasted conditions.	Group A: Uprifosbuvir 50 mg (Cohort 3a) n=6 Participants Participants were administered a single dose of uprifosbuvir 50 mg as oral capsules under fasted conditions.	Group A: Uprifosbuvir 300 mg (Cohort 5a) Participants were administered a single dose of uprifosbuvir 300 mg as oral capsules under fasted conditions.	Group A: Uprifosbuvir 300 mg (Cohort 6a) Participants were administered single doses of uprifosbuvir 300 mg as oral capsules once daily for 7 days under fasted conditions.	Group A: Placebo (Cohort 6a) Participants were administered single doses of uprifosbuvir-matching placebo oral capsules once daily for 7 days under fasted conditions.	Group B: Uprifosbuvir 10 mg (Cohort 1b) Participants were administered a single dose of uprifosbuvir 10 mg as oral capsules under fasted conditions.	Group B: Uprifosbuvir 25 mg (Cohort 2b) Participants were administered a single dose of uprifosbuvir 25 mg as oral capsules under fasted conditions.	Group B: Uprifosbuvir 50 mg (Cohort 3b) Participants were administered a single dose of uprifosbuvir 50 mg as oral capsules under fasted conditions.	Group B: Uprifosbuvir 150 mg (Cohort 4b) Participants were administered a single dose of uprifosbuvir 150 mg as oral capsules under fasted conditions.	Group B: Uprifosbuvir 300 mg (Cohort 5b) Participants were administered a single dose of uprifosbuvir 300 mg as oral capsules under fasted conditions.	Groups C & D: Uprifosbuvir 50 mg (Capsule) Participants were administered single doses of uprifosbuvir 50 mg as oral capsules once daily for 7 days under fasted conditions.	Groups C & D: Uprifosbuvir 150 mg (Capsule) Participants were administered single doses of uprifosbuvir 150 mg as oral capsules once daily for 7 days under fasted conditions.	Groups C & D: Uprifosbuvir 250 mg (Capsule) Participants were administered single doses of uprifosbuvir 250 mg as oral capsules once daily for 7 days under fasted conditions.	Groups C & D: Uprifosbuvir 300 mg (Capsule) Participants were administered single doses of uprifosbuvir 300 mg as oral capsules once daily for 7 days under fasted conditions.	Groups C & D: Uprifosbuvir 400 mg (Capsule) Participants were administered single doses of uprifosbuvir 400 mg as oral capsules once daily for 7 days under fasted conditions.	Groups C & D: Uprifosbuvir 300 mg (Tablet) Participants were administered single doses of uprifosbuvir 300 mg as oral tablets once daily for 7 days under fasted conditions.	Groups C & D: Uprifosbuvir 450 mg (Tablet) Participants were administered single doses of uprifosbuvir 450 mg as oral tablets once daily for 7 days under fasted conditions.
Area Under the Plasma Drug Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Healthy Participants (Group A)	0.0410 h*umol/L Geometric Coefficient of Variation 32.7	0.0837 h*umol/L Geometric Coefficient of Variation 27.9	—	—	—	0.246 h*umol/L Geometric Coefficient of Variation 63.2	—	—	1.67 h*umol/L Geometric Coefficient of Variation 62.7	2.78 h*umol/L Geometric Coefficient of Variation 37.7	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose