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

• ClinicalTrials.gov Identifier: NCT01974687
• Recruitment Status: Completed
• First Posted: November 1, 2013
• Results First Posted: September 13, 2018
• Last Update Posted: September 13, 2018
• Sponsor: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): Merck Sharp & Dohme LLC

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Chronic Hepatitis C
• Interventions: Drug: Uprifosbuvir; Drug: Placebo; Drug: Itraconazole
• Enrollment: 178

Participant Flow

Recruitment Details	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.
Pre-assignment Details

Arm/Group Title	Group A: Uprifosbuvir 10 mg (Cohort 1a)	Group A: Uprifosbuvir 25 mg (Cohort 2a)	Group A: Uprifosbuvir 150 mg (Cohort 4a)	Group A: Uprifosbuvir 300 mg (Cohort 5a)	Group A: Placebo (Cohort 6a)	Group A: Uprifosbuvir 300 mg (Cohort 6a)	Group B: Uprifosbuvir 10 mg (Cohort 1b)	Group B: Uprifosbuvir 25 mg (Cohort 2b)	Group B: Uprifosbuvir 50 mg (Cohort 3b)	Group B: Uprifosbuvir 150 mg (Cohort 4b)	Group B: Uprifosbuvir 300 mg (Cohort 5b)	Groups C & D: Uprifosbuvir 50 mg (Capsule)	Groups C & D: Uprifosbuvir 150 mg (Capsule)	Groups C & D: Uprifosbuvir 250 mg (Capsule)	Groups C & D: Uprifosbuvir 300 mg (Capsule)	Groups C & D: Uprifosbuvir 400 mg (Capsule)	Groups C & D: Uprifosbuvir 300 mg (Tablet)	Groups C & D: Uprifosbuvir 450 mg (Tablet)	Groups C & D: Placebo (Pooled)	Group E: Uprifosbuvir 150 mg (Cohort 1e)	Group E: Uprifosbuvir 300 mg (Cohort 2e)	Group E: Uprifosbuvir 450 mg (Cohort 3e)	Group F: Uprifosbuvir 300 mg (Tablet)	Group A: Uprifosbuvir 50 mg (Cohort 3a)	Group A: Placebo (Cohorts 1a-5a - Pooled)
Arm/Group Description	Participants were administered a single dose of uprifosbuvir (MK-3682/IDX21437) 10 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 25 mg as oral capsules under fasted conditions.	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.	Participants were administered a single dose of uprifosbuvir 300 mg as oral capsules under fasted conditions.	Participants were administered single doses of uprifosbuvir-matching placebo oral capsules once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 300 mg as oral capsules once daily for 7 days under fasted conditions.	Participants were administered a single dose of uprifosbuvir 10 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 25 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 50 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 150 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 300 mg as oral capsules under fasted conditions.	Participants were administered single doses of uprifosbuvir 50 mg as oral capsules once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 150 mg as oral capsules once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 250 mg as oral capsules once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 300 mg as oral capsules once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 400 mg as oral capsules once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 300 mg as oral tablets once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 450 mg as oral tablets once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir-matching placebo as oral capsules once daily for 7 days under fasted conditions.	Participants were administered a single dose of uprifosbuvir 150 mg as oral capsules under fasted conditions.	Participants were administered single doses of uprifosbuvir 300 mg as oral capsules once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 450 mg as oral tablets once daily for 7 days under fasted conditions.	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.	Participants were administered a single dose of uprifosbuvir 50 mg as oral capsules under fasted conditions.	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).
Period Title: 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
Treated	6	6	6	6	2	6	3	3	3	3	3	11 [1]	10 [2]	8 [1]	18 [3]	8 [3]	8 [3]	8 [2]	9	3	3	8	8	6	10
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
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
[1] 2 participants discontinued prior to receiving study drug; [2] 3 participants discontinued prior to receiving study drug; [3] 1 participant discontinued prior to receiving study drug

Baseline Characteristics

Arm/Group Title		Group A: Placebo (Cohort 1a-Cohort 5a - Pooled)	Group A: Uprifosbuvir 10 mg (Cohort 1a)	Group A: Uprifosbuvir 25 mg (Cohort 2a)	Group A: Uprifosbuvir 150 mg (Cohort 4a)	Group A: Uprifosbuvir 300 mg (Cohort 5a)	Group A: Placebo (Cohort 6a)	Group A: Uprifosbuvir 300 mg (Cohort 6a)	Group B: Uprifosbuvir 10 mg (Cohort 1b)	Group B: Uprifosbuvir 25 mg (Cohort 2b)	Group B: Uprifosbuvir 50 mg (Cohort 3b)	Group B: Uprifosbuvir 150 mg (Cohort 4b)	Group B: Uprifosbuvir 300 mg (Cohort 5b)	Groups C & D: Uprifosbuvir 50 mg (Capsule)	Groups C & D: Uprifosbuvir 150 mg (Capsule)	Groups C & D: Uprifosbuvir 250 mg (Capsule)	Groups C & D: Uprifosbuvir 300 mg (Capsule)	Groups C & D: Uprifosbuvir 400 mg (Capsule)	Groups C & D: Uprifosbuvir 300 mg (Tablet)	Groups C & D: Uprifosbuvir 450 mg (Tablet)	Groups C & D: Placebo (Pooled)	Group E: Uprifosbuvir 150 mg (Cohort 1e)	Group E: Uprifosbuvir 300 mg (Cohort 2e)	Group E: Uprifosbuvir 450 mg (Cohort 3e)	Group F: Uprifosbuvir 300 mg (Tablet)	Group A: Uprifosbuvir 50 mg (Cohort 3a)	Total
Arm/Group Description		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).	Participants were administered a single dose of uprifosbuvir 10 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 25 mg as oral capsules under fasted conditions.	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.	Participants were administered a single dose of uprifosbuvir 300 mg as oral capsules under fasted conditions.	Participants were administered single doses of uprifosbuvir-matching placebo oral capsules once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 300 mg as oral capsules once daily for 7 days under fasted conditions.	Participants were administered a single dose of uprifosbuvir 10 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 25 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 50 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 150 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 300 mg as oral capsules under fasted conditions.	Participants were administered single doses of uprifosbuvir 50 mg as oral capsules once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 150 mg as oral capsules once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 250 mg as oral capsules once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 300 mg as oral capsules once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 400 mg as oral capsules once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 300 mg as oral tablets once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 450 mg as oral tablets once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir-matching placebo as oral capsules once daily for 7 days under fasted conditions.	Participants were administered a single dose of uprifosbuvir 150 mg as oral capsules under fasted conditions.	Participants were administered single doses of uprifosbuvir 300 mg as oral capsules once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 450 mg as oral tablets once daily for 7 days under fasted conditions.	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.	Participants were administered a single dose of uprifosbuvir 50 mg as oral capsules under fasted conditions.	Total of all reporting groups
Overall Number of Baseline Participants		10	6	6	6	6	2	6	3	3	3	3	3	11	10	8	18	8	8	8	9	3	3	8	8	6	165
Baseline Analysis Population Description		The baseline analysis population consisted of all participants who received at least one dose of study drug.
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	10 participants	6 participants	6 participants	6 participants	6 participants	2 participants	6 participants	3 participants	3 participants	3 participants	3 participants	3 participants	11 participants	10 participants	8 participants	18 participants	8 participants	8 participants	8 participants	9 participants	3 participants	3 participants	8 participants	8 participants	6 participants	165 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	10 100.0%	6 100.0%	6 100.0%	6 100.0%	6 100.0%	2 100.0%	6 100.0%	3 100.0%	3 100.0%	3 100.0%	3 100.0%	3 100.0%	11 100.0%	10 100.0%	8 100.0%	18 100.0%	8 100.0%	8 100.0%	8 100.0%	9 100.0%	3 100.0%	3 100.0%	8 100.0%	8 100.0%	6 100.0%	165 100.0%
	>=65 years	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	10 participants	6 participants	6 participants	6 participants	6 participants	2 participants	6 participants	3 participants	3 participants	3 participants	3 participants	3 participants	11 participants	10 participants	8 participants	18 participants	8 participants	8 participants	8 participants	9 participants	3 participants	3 participants	8 participants	8 participants	6 participants	165 participants
		35.3 (7.72)	29.2 (7.36)	33.3 (15.06)	35.5 (11.76)	35.2 (9.87)	36.0 (2.83)	35.3 (12.69)	37.0 (9.54)	42.3 (7.23)	46.7 (4.16)	43.3 (5.69)	41.3 (8.96)	41.2 (10.68)	42.7 (10.37)	44.3 (8.63)	40.1 (11.69)	43.3 (8.45)	40.5 (11.70)	40.5 (8.94)	43.7 (7.68)	57.0 (4.36)	56.3 (3.06)	49.1 (8.04)	43.1 (12.54)	31.3 (11.60)	40.47 (10.85)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	10 participants	6 participants	6 participants	6 participants	6 participants	2 participants	6 participants	3 participants	3 participants	3 participants	3 participants	3 participants	11 participants	10 participants	8 participants	18 participants	8 participants	8 participants	8 participants	9 participants	3 participants	3 participants	8 participants	8 participants	6 participants	165 participants
	Female	4 40.0%	4 66.7%	2 33.3%	5 83.3%	4 66.7%	0 0.0%	4 66.7%	0 0.0%	0 0.0%	1 33.3%	2 66.7%	1 33.3%	5 45.5%	0 0.0%	5 62.5%	5 27.8%	3 37.5%	5 62.5%	4 50.0%	3 33.3%	0 0.0%	0 0.0%	1 12.5%	6 75.0%	3 50.0%	67 40.6%
	Male	6 60.0%	2 33.3%	4 66.7%	1 16.7%	2 33.3%	2 100.0%	2 33.3%	3 100.0%	3 100.0%	2 66.7%	1 33.3%	2 66.7%	6 54.5%	10 100.0%	3 37.5%	13 72.2%	5 62.5%	3 37.5%	4 50.0%	6 66.7%	3 100.0%	3 100.0%	7 87.5%	2 25.0%	3 50.0%	98 59.4%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Who Experienced at Least One Treatment-emergent Adverse Event (AE)
Description	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.
Time Frame	Up to 42 days

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Group A: Placebo (Cohort 1a-Cohort 5a - Pooled)	Group A: Uprifosbuvir 10 mg (Cohort 1a)	Group A: Uprifosbuvir 25 mg (Cohort 2a)	Group A: Uprifosbuvir 50 mg (Cohort 3a)	Group A: Uprifosbuvir 150 mg (Cohort 4a) (Fasted and Fed)	Group A: Uprifosbuvir 300 mg (Cohort 5a)	Group A: Uprifosbuvir 300 mg (Cohort 6a)	Group A: Placebo (Cohort 6a)	Group B: Uprifosbuvir 10 mg (Cohort 1b)	Group B: Uprifosbuvir 25 mg (Cohort 2b)	Group B: Uprifosbuvir 50 mg (Cohort 3b)	Group B: Uprifosbuvir 150 mg (Cohort 4b)	Group B: Uprifosbuvir 300 mg (Cohort 5b)	Groups C & D: Uprifosbuvir 50 mg (Capsule)	Groups C & D: Uprifosbuvir 150 mg (Capsule)	Groups C & D: Uprifosbuvir 250 mg (Capsule)	Groups C & D: Uprifosbuvir 300 mg (Capsule)	Groups C & D: Uprifosbuvir 400 mg (Capsule)	Groups C & D: Uprifosbuvir 300 mg (Tablet)	Groups C & D: Uprifosbuvir 450 mg (Tablet)	Groups C & D: Placebo (Pooled)	Group E: Uprifosbuvir 150 mg (Cohort 1e)	Group E: Uprifosbuvir 300 mg (Cohort 2e)	Group E: Uprifosbuvir 450 mg (Cohort 3e)	Group F: Uprifosbuvir 300 mg (Tablet)
Arm/Group Description:	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).	Participants were administered a single dose of uprifosbuvir 10 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 25 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 50 mg as oral capsules under fasted conditions.	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.	Participants were administered a single dose of uprifosbuvir 300 mg as oral capsules under fasted conditions.	Participants were administered single doses of uprifosbuvir 300 mg as oral capsules once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir-matching placebo oral capsules once daily for 7 days under fasted conditions.	Participants were administered a single dose of uprifosbuvir 10 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 25 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 50 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 150 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 300 mg as oral capsules under fasted conditions.	Participants were administered single doses of uprifosbuvir 50 mg as oral capsules once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 150 mg as oral capsules once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 250 mg as oral capsules once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 300 mg as oral capsules once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 400 mg as oral capsules once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 300 mg as oral tablets once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 450 mg as oral tablets once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir-matching placebo as oral capsules once daily for 7 days under fasted conditions.	Participants were administered a single dose of uprifosbuvir 150 mg as oral capsules under fasted conditions.	Participants were administered single doses of uprifosbuvir 300 mg as oral capsules once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 450 mg as oral tablets once daily for 7 days under fasted conditions.	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.
Overall Number of Participants Analyzed	10	6	6	6	6	6	6	2	3	3	3	3	3	11	10	8	18	8	8	8	9	3	3	8	8
Measure Type: Number; Unit of Measure: Percentage of Participants
	50.0	0.0	33.3	33.3	66.7	50.0	33.3	50.0	33.3	66.7	33.3	66.7	66.7	72.7	70.0	87.5	44.4	62.5	75.0	62.5	66.7	0.0	100.0	62.5	37.5

2. Primary Outcome

Title	Percentage of Participants Who Experienced at Least One Treatment-emergent Serious AE (SAE)
Description	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.
Time Frame	Up to 42 days

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Group A: Placebo (Cohort 1a-Cohort 5a - Pooled)	Group A: Uprifosbuvir 10 mg (Cohort 1a)	Group A: Uprifosbuvir 25 mg (Cohort 2a)	Group A: Uprifosbuvir 50 mg (Cohort 3a)	Group A: Uprifosbuvir 150 mg (Cohort 4a) (Fasted and Fed)	Group A: Uprifosbuvir 300 mg (Cohort 5a)	Group A: Uprifosbuvir 300 mg (Cohort 6a)	Group A: Placebo (Cohort 6a)	Group B: Uprifosbuvir 10 mg (Cohort 1b)	Group B: Uprifosbuvir 25 mg (Cohort 2b)	Group B: Uprifosbuvir 50 mg (Cohort 3b)	Group B: Uprifosbuvir 150 mg (Cohort 4b)	Group B: Uprifosbuvir 300 mg (Cohort 5b)	Groups C & D: Uprifosbuvir 50 mg (Capsule)	Groups C & D: Uprifosbuvir 150 mg (Capsule)	Groups C & D: Uprifosbuvir 250 mg (Capsule)	Groups C & D: Uprifosbuvir 300 mg (Capsule)	Groups C & D: Uprifosbuvir 400 mg (Capsule)	Groups C & D: Uprifosbuvir 300 mg (Tablet)	Groups C & D: Uprifosbuvir 450 mg (Tablet)	Groups C & D: Placebo (Pooled)	Group E: Uprifosbuvir 150 mg (Cohort 1e)	Group E: Uprifosbuvir 300 mg (Cohort 2e)	Group E: Uprifosbuvir 450 mg (Cohort 3e)	Group F: Uprifosbuvir 300 mg (Tablet)
Arm/Group Description:	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).	Participants were administered a single dose of uprifosbuvir 10 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 25 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 50 mg as oral capsules under fasted conditions.	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.	Participants were administered a single dose of uprifosbuvir 300 mg as oral capsules under fasted conditions.	Participants were administered single doses of uprifosbuvir 300 mg as oral capsules once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir-matching placebo oral capsules once daily for 7 days under fasted conditions.	Participants were administered a single dose of uprifosbuvir 10 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 25 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 50 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 150 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 300 mg as oral capsules under fasted conditions.	Participants were administered single doses of uprifosbuvir 50 mg as oral capsules once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 150 mg as oral capsules once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 250 mg as oral capsules once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 300 mg as oral capsules once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 400 mg as oral capsules once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 300 mg as oral tablets once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 450 mg as oral tablets once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir-matching placebo as oral capsules once daily for 7 days under fasted conditions.	Participants were administered a single dose of uprifosbuvir 150 mg as oral capsules under fasted conditions.	Participants were administered single doses of uprifosbuvir 300 mg as oral capsules once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 450 mg as oral tablets once daily for 7 days under fasted conditions.	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.
Overall Number of Participants Analyzed	10	6	6	6	6	6	6	2	3	3	3	3	3	11	10	8	18	8	8	8	9	3	3	8	8
Measure Type: Number; Unit of Measure: Percentage of Participants
	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0

3. Primary Outcome

Title	Percentage of Participants Who Experienced a Treatment-emergent Dose-limiting Toxicity (DLT)
Description	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.
Time Frame	Up to 13 days

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Group A: Placebo (Cohort 1a-Cohort 5a - Pooled)	Group A: Uprifosbuvir 10 mg (Cohort 1a)	Group A: Uprifosbuvir 25 mg (Cohort 2a)	Group A: Uprifosbuvir 50 mg (Cohort 3a)	Group A: Uprifosbuvir 150 mg (Cohort 4a) (Fasted and Fed)	Group A: Uprifosbuvir 300 mg (Cohort 5a)	Group A: Uprifosbuvir 300 mg (Cohort 6a)	Group A: Placebo (Cohort 6a)	Group B: Uprifosbuvir 10 mg (Cohort 1b)	Group B: Uprifosbuvir 25 mg (Cohort 2b)	Group B: Uprifosbuvir 50 mg (Cohort 3b)	Group B: Uprifosbuvir 150 mg (Cohort 4b)	Group B: Uprifosbuvir 300 mg (Cohort 5b)	Groups C & D: Uprifosbuvir 50 mg (Capsule)	Groups C & D: Uprifosbuvir 150 mg (Capsule)	Groups C & D: Uprifosbuvir 250 mg (Capsule)	Groups C & D: Uprifosbuvir 300 mg (Capsule)	Groups C & D: Uprifosbuvir 400 mg (Capsule)	Groups C & D: Uprifosbuvir 300 mg (Tablet)	Groups C & D: Uprifosbuvir 450 mg (Tablet)	Groups C & D: Placebo (Pooled)	Group E: Uprifosbuvir 150 mg (Cohort 1e)	Group E: Uprifosbuvir 300 mg (Cohort 2e)	Group E: Uprifosbuvir 450 mg (Cohort 3e)	Group F: Uprifosbuvir 300 mg (Tablet)
Arm/Group Description:	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).	Participants were administered a single dose of uprifosbuvir 10 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 25 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 50 mg as oral capsules under fasted conditions.	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.	Participants were administered a single dose of uprifosbuvir 300 mg as oral capsules under fasted conditions.	Participants were administered single doses of uprifosbuvir 300 mg as oral capsules once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir-matching placebo oral capsules once daily for 7 days under fasted conditions.	Participants were administered a single dose of uprifosbuvir 10 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 25 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 50 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 150 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 300 mg as oral capsules under fasted conditions.	Participants were administered single doses of uprifosbuvir 50 mg as oral capsules once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 150 mg as oral capsules once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 250 mg as oral capsules once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 300 mg as oral capsules once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 400 mg as oral capsules once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 300 mg as oral tablets once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 450 mg as oral tablets once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir-matching placebo as oral capsules once daily for 7 days under fasted conditions.	Participants were administered a single dose of uprifosbuvir 150 mg as oral capsules under fasted conditions.	Participants were administered single doses of uprifosbuvir 300 mg as oral capsules once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 450 mg as oral tablets once daily for 7 days under fasted conditions.	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.
Overall Number of Participants Analyzed	10	6	6	6	6	6	6	2	3	3	3	3	3	11	10	8	18	8	8	8	9	3	3	8	8
Measure Type: Number; Unit of Measure: Percentage of Participants
	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0

4. Primary Outcome

Title	Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality
Description	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.
Time Frame	Up to 42 days

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Group A: Placebo (Cohort 1a-Cohort 5a - Pooled)	Group A: Uprifosbuvir 10 mg (Cohort 1a)	Group A: Uprifosbuvir 25 mg (Cohort 2a)	Group A: Uprifosbuvir 50 mg (Cohort 3a)	Group A: Uprifosbuvir 150 mg (Cohort 4a) (Fasted and Fed)	Group A: Uprifosbuvir 300 mg (Cohort 5a)	Group A: Uprifosbuvir 300 mg (Cohort 6a)	Group A: Placebo (Cohort 6a)	Group B: Uprifosbuvir 10 mg (Cohort 1b)	Group B: Uprifosbuvir 25 mg (Cohort 2b)	Group B: Uprifosbuvir 50 mg (Cohort 3b)	Group B: Uprifosbuvir 150 mg (Cohort 4b)	Group B: Uprifosbuvir 300 mg (Cohort 5b)	Groups C & D: Uprifosbuvir 50 mg (Capsule)	Groups C & D: Uprifosbuvir 150 mg (Capsule)	Groups C & D: Uprifosbuvir 250 mg (Capsule)	Groups C & D: Uprifosbuvir 300 mg (Capsule)	Groups C & D: Uprifosbuvir 400 mg (Capsule)	Groups C & D: Uprifosbuvir 300 mg (Tablet)	Groups C & D: Uprifosbuvir 450 mg (Tablet)	Groups C & D: Placebo (Pooled)	Group E: Uprifosbuvir 150 mg (Cohort 1e)	Group E: Uprifosbuvir 300 mg (Cohort 2e)	Group E: Uprifosbuvir 450 mg (Cohort 3e)	Group F: Uprifosbuvir 300 mg (Tablet)
Arm/Group Description:	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).	Participants were administered a single dose of uprifosbuvir 10 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 25 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 50 mg as oral capsules under fasted conditions.	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.	Participants were administered a single dose of uprifosbuvir 300 mg as oral capsules under fasted conditions.	Participants were administered single doses of uprifosbuvir 300 mg as oral capsules once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir-matching placebo oral capsules once daily for 7 days under fasted conditions.	Participants were administered a single dose of uprifosbuvir 10 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 25 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 50 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 150 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 300 mg as oral capsules under fasted conditions.	Participants were administered single doses of uprifosbuvir 50 mg as oral capsules once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 150 mg as oral capsules once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 250 mg as oral capsules once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 300 mg as oral capsules once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 400 mg as oral capsules once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 300 mg as oral tablets once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 450 mg as oral tablets once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir-matching placebo as oral capsules once daily for 7 days under fasted conditions.	Participants were administered a single dose of uprifosbuvir 150 mg as oral capsules under fasted conditions.	Participants were administered single doses of uprifosbuvir 300 mg as oral capsules once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 450 mg as oral tablets once daily for 7 days under fasted conditions.	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.
Overall Number of Participants Analyzed	10	6	6	6	6	6	6	2	3	3	3	3	3	11	10	8	18	8	8	8	9	3	3	8	8
Measure Type: Number; Unit of Measure: Percentage of Participants
Grade 1	50.00	0.0	16.7	16.7	50.0	33.3	33.3	50.0	0.0	66.7	33.3	66.7	66.7	45.5	60.0	37.5	33.3	0.0	37.5	25.0	33.3	0.0	100.0	12.5	0.0
Grade 2	0.0	0.0	16.7	16.7	16.7	16.7	0.0	0.0	0.0	0.0	0.0	0.0	33.3	18.2	0.0	50.0	5.6	62.5	37.5	25.0	33.3	0.0	0.0	37.5	37.5
Grade 3	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	33.3	0.0	0.0	0.0	0.0	9.1	10.0	0.0	5.6	0.0	0.0	0.0	0.0	0.0	0.0	12.5	0.0
Grade 4	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	12.5	0.0	0.0	0.0	0.0	0.0
Grade 5	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0

5. Primary Outcome

Title	Percentage of Participants Who Discontinued Study Drug Due to a Treatment-emergent AE
Description	The percentage of participants who discontinued study drug due to an AE is presented.
Time Frame	Up to 14 days

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Group A: Placebo (Cohort 1a-Cohort 5a - Pooled)	Group A: Uprifosbuvir 10 mg (Cohort 1a)	Group A: Uprifosbuvir 25 mg (Cohort 2a)	Group A: Uprifosbuvir 50 mg (Cohort 3a)	Group A: Uprifosbuvir 150 mg (Cohort 4a) (Fasted and Fed)	Group A: Uprifosbuvir 300 mg (Cohort 5a)	Group A: Uprifosbuvir 300 mg (Cohort 6a)	Group A: Placebo (Cohort 6a)	Group B: Uprifosbuvir 10 mg (Cohort 1b)	Group B: Uprifosbuvir 25 mg (Cohort 2b)	Group B: Uprifosbuvir 50 mg (Cohort 3b)	Group B: Uprifosbuvir 150 mg (Cohort 4b)	Group B: Uprifosbuvir 300 mg (Cohort 5b)	Groups C & D: Uprifosbuvir 50 mg (Capsule)	Groups C & D: Uprifosbuvir 150 mg (Capsule)	Groups C & D: Uprifosbuvir 250 mg (Capsule)	Groups C & D: Uprifosbuvir 300 mg (Capsule)	Groups C & D: Uprifosbuvir 400 mg (Capsule)	Groups C & D: Uprifosbuvir 300 mg (Tablet)	Groups C & D: Uprifosbuvir 450 mg (Tablet)	Groups C & D: Placebo (Pooled)	Group E: Uprifosbuvir 150 mg (Cohort 1e)	Group E: Uprifosbuvir 300 mg (Cohort 2e)	Group E: Uprifosbuvir 450 mg (Cohort 3e)	Group F: Uprifosbuvir 300 mg (Tablet)
Arm/Group Description:	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).	Participants were administered a single dose of uprifosbuvir 10 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 25 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 50 mg as oral capsules under fasted conditions.	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.	Participants were administered a single dose of uprifosbuvir 300 mg as oral capsules under fasted conditions.	Participants were administered single doses of uprifosbuvir 300 mg as oral capsules once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir-matching placebo oral capsules once daily for 7 days under fasted conditions.	Participants were administered a single dose of uprifosbuvir 10 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 25 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 50 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 150 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 300 mg as oral capsules under fasted conditions.	Participants were administered single doses of uprifosbuvir 50 mg as oral capsules once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 150 mg as oral capsules once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 250 mg as oral capsules once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 300 mg as oral capsules once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 400 mg as oral capsules once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 300 mg as oral tablets once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 450 mg as oral tablets once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir-matching placebo as oral capsules once daily for 7 days under fasted conditions.	Participants were administered a single dose of uprifosbuvir 150 mg as oral capsules under fasted conditions.	Participants were administered single doses of uprifosbuvir 300 mg as oral capsules once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 450 mg as oral tablets once daily for 7 days under fasted conditions.	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.
Overall Number of Participants Analyzed	10	6	6	6	6	6	6	2	3	3	3	3	3	11	10	8	18	8	8	8	9	3	3	8	8
Measure Type: Number; Unit of Measure: Percentage of Participants
	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0

6. Primary Outcome

Title	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)
Description	AUC0-t was calculated using linear log trapezoidal summation from time zero to last measurable concentration. All participants were fasted.
Time Frame	Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Group A: Uprifosbuvir 10 mg (Cohort 1a)	Group A: Uprifosbuvir 25 mg (Cohort 2a)	Group A: Uprifosbuvir 150 mg (Cohort 4a Fasted)	Group A: Uprifosbuvir 300 mg (Cohort 5a)	Group A: Uprifosbuvir 50 mg (Cohort 3a)
Arm/Group Description:	Participants were administered a single dose of uprifosbuvir 10 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 25 mg as oral capsules under fasted conditions.	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.	Participants were administered a single dose of uprifosbuvir 300 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 50 mg as oral capsules under fasted conditions.
Overall Number of Participants Analyzed	6	6	6	6	6
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: h*umol/L
	0.0410; (32.7%)	0.0837; (27.9%)	1.67; (62.7%)	2.78; (37.7%)	0.246; (63.2%)

7. Primary Outcome

Title	AUC0-t of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Fed State in Healthy Participants (Group A - Cohort 4a)
Description	AUC0-t was calculated using linear log trapezoidal summation from time zero to last measurable concentration.
Time Frame	Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Group A: Uprifosbuvir 150 mg (Cohort 4a Fed)
Arm/Group Description:	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.
Overall Number of Participants Analyzed	6
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: h*umol/L
	1.05; (48.5%)

8. Primary Outcome

Title	AUC0-t of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Healthy Participants (Group A - Cohort 6a)
Description	AUC0-t was calculated using linear log trapezoidal summation from time zero to last measurable concentration.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Group A: Uprifosbuvir 300 mg (Cohort 6a)
Arm/Group Description:	Participants were administered single doses of uprifosbuvir 300 mg as oral capsules once daily for 7 days under fasted conditions.
Overall Number of Participants Analyzed	6
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: h*umol/L
Day 1	3.62; (34.0%)
Day 7	3.77; (21.7%)

9. Primary Outcome

Title	AUC0-t of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Genotype 1, HCV-Infected Participants (Group B)
Description	AUC0-t was calculated using linear log trapezoidal summation from time zero to last measurable concentration.
Time Frame	Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Group B: Uprifosbuvir 10 mg (Cohort 1b)	Group B: Uprifosbuvir 25 mg (Cohort 2b)	Group B: Uprifosbuvir 50 mg (Cohort 3b)	Group B: Uprifosbuvir 150 mg (Cohort 4b)	Group B: Uprifosbuvir 300 mg (Cohort 5b)
Arm/Group Description:	Participants were administered a single dose of uprifosbuvir 10 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 25 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 50 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 150 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 300 mg as oral capsules under fasted conditions.
Overall Number of Participants Analyzed	3	3	3	2	3
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: h*umol/L
	0.0640; (39.8%)	0.228; (49.1%)	0.341; (20.4%)	1.17 [1]; (NA%)	1.39; (35.4%)

[1]

Not calculated

10. Primary Outcome

Title	AUC0-t of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D)
Description	AUC0-t was calculated using linear log trapezoidal summation from time zero to last measurable concentration.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Groups C & D: Uprifosbuvir 50 mg (Capsule)	Groups C & D: Uprifosbuvir 150 mg (Capsule)	Groups C & D: Uprifosbuvir 300 mg (Capsule)	Groups C & D: Uprifosbuvir 400 mg (Capsule)
Arm/Group Description:	Participants were administered single doses of uprifosbuvir 50 mg as oral capsules once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 150 mg as oral capsules once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 300 mg as oral capsules once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 400 mg as oral capsules once daily for 7 days under fasted conditions.
Overall Number of Participants Analyzed	10	9	17	7
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: h*umol/L
Day 1	0.394; (51.4%)	1.01; (52.9%)	2.80; (45.4%)	5.54; (40.1%)
Day 7	0.347; (36.2%)	0.935; (36.7%)	2.42; (46.8%)	4.59; (22.1%)

11. Primary Outcome

Title	AUC0-t of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-Infected Participants (Group C)
Description	AUC0-t was calculated using linear log trapezoidal summation from time zero to last measurable concentration.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Group C: Uprifosbuvir 300 mg (Tablet)	Group C: Uprifosbuvir 450 mg (Tablet)
Arm/Group Description:	Participants were administered single doses of uprifosbuvir 300 mg as oral tablets once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 450 mg as oral tablets once daily for 7 days under fasted conditions.
Overall Number of Participants Analyzed	7	7
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: h*umol/L
Day 1	2.00; (51.7%)	3.11; (45.0%)
Day 7	1.82; (43.9%)	2.88; (30.4%)

12. Primary Outcome

Title	AUC0-t of Uprifosbuvir After Single Dose of Uprifosbuvir as Capsule Formulation in Genotype 1, HCV-Infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 1e)
Description	AUC0-t was calculated using linear log trapezoidal summation from time zero to last measurable concentration.
Time Frame	Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Group E: Uprifosbuvir 150 mg (Cohort 1e)
Arm/Group Description:	Participants were administered a single dose of uprifosbuvir 150 mg as oral capsules under fasted conditions.
Overall Number of Participants Analyzed	2
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: h*umol/L
	1.05 [1]; (NA%)

[1]

Not calculated

13. Primary Outcome

Title	AUC0-t of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as Capsule or Tablet Formulation in Genotype 1, HCV-Infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 2e and Cohort 3e)
Description	AUC0-t was calculated using linear log trapezoidal summation from time zero to last measurable concentration.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Group E: Uprifosbuvir 300 mg (Cohort 2e)	Group E: Uprifosbuvir 450 mg (Cohort 3e)
Arm/Group Description:	Participants were administered single doses of uprifosbuvir 300 mg as oral capsules once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 450 mg as oral tablets once daily for 7 days under fasted conditions.
Overall Number of Participants Analyzed	3	7
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: h*umol/L
Day 1	3.19; (32.8%)	4.21; (35.2%)
Day 7	2.31; (31.8%)	3.51; (23.2%)

14. Primary Outcome

Title	AUC0-t of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as Tablet Formulation in Genotype 1, HCV-Infected Participants, With Itraconazole (Group F)
Description	AUC0-t was calculated using linear log trapezoidal summation from time zero to last measurable concentration.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Group F: Uprifosbuvir 300 mg (Tablet)
Arm/Group Description:	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.
Overall Number of Participants Analyzed	8
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: h*umol/L
Day 1	10.6; (44.0%)
Day 7	9.39; (46.1%)

15. Primary Outcome

Title	Maximum (Peak) Observed Plasma Drug Concentration (Cmax) of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Healthy Participants (Group A)
Description	Maximum observed plasma drug concentration was obtained. All participants were fasted.
Time Frame	Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Group A: Uprifosbuvir 10 mg (Cohort 1a)	Group A: Uprifosbuvir 25 mg (Cohort 2a)	Group A: Uprifosbuvir 150 mg (Cohort 4a Fasted)	Group A: Uprifosbuvir 300 mg (Cohort 5a)	Group A: Uprifosbuvir 50 mg (Cohort 3a)
Arm/Group Description:	Participants were administered a single dose of uprifosbuvir 10 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 25 mg as oral capsules under fasted conditions.	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.	Participants were administered a single dose of uprifosbuvir 300 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 50 mg as oral capsules under fasted conditions.
Overall Number of Participants Analyzed	6	6	6	6	6
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: nmol/L
	29.6; (45.3%)	47.7; (54.4%)	1120; (47.8%)	1530; (53.6%)	119; (89.2%)

16. Primary Outcome

Title	Cmax of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Fed State in Healthy Participants (Group A - Cohort 4a)
Description	Maximum observed plasma drug concentration was obtained.
Time Frame	Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Group A: Uprifosbuvir 150 mg (Cohort 4a Fed)
Arm/Group Description:	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.
Overall Number of Participants Analyzed	6
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: nmol/L
	293; (63.0%)

17. Primary Outcome

Title	Cmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Healthy Participants (Group A - Cohort 6a)
Description	Maximum observed plasma drug concentration was obtained.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Group A: Uprifosbuvir 300 mg (Cohort 6a)
Arm/Group Description:	Participants were administered single doses of uprifosbuvir 300 mg as oral capsules once daily for 7 days under fasted conditions.
Overall Number of Participants Analyzed	6
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: nmol/L
Day 1	2300; (26.6%)
Day 7	2320; (19.9%)

18. Primary Outcome

Title	Cmax of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Genotype 1, HCV-Infected Participants (Group B)
Description	Maximum observed plasma drug concentration was obtained.
Time Frame	Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Group B: Uprifosbuvir 10 mg (Cohort 1b)	Group B: Uprifosbuvir 25 mg (Cohort 2b)	Group B: Uprifosbuvir 50 mg (Cohort 3b)	Group B: Uprifosbuvir 150 mg (Cohort 4b)	Group B: Uprifosbuvir 300 mg (Cohort 5b)
Arm/Group Description:	Participants were administered a single dose of uprifosbuvir 10 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 25 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 50 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 150 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 300 mg as oral capsules under fasted conditions.
Overall Number of Participants Analyzed	3	3	3	2	3
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: nmol/L
	43.6; (60.7%)	122; (26.4%)	168; (11.4%)	510 [1]; (NA%)	667; (15.3%)

[1]

Not calculated

19. Primary Outcome

Title	Cmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D)
Description	Maximum observed plasma drug concentration was obtained. All participants were fasted.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Groups C & D: Uprifosbuvir 50 mg (Capsule)	Groups C & D: Uprifosbuvir 150 mg (Capsule)	Groups C & D: Uprifosbuvir 300 mg (Capsule)	Groups C & D: Uprifosbuvir 400 mg (Capsule)
Arm/Group Description:	Participants were administered single doses of uprifosbuvir 50 mg as oral capsules once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 150 mg as oral capsules once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 300 mg as oral capsules once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 400 mg as oral capsules once daily for 7 days under fasted conditions.
Overall Number of Participants Analyzed	10	9	17	7
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: nmol/L
Day 1	286; (77.1%)	524; (80.1%)	1360; (55.5%)	2320; (50.2%)
Day 7	199; (45.6%)	587; (34.9%)	1200; (59.4%)	2490; (25.7%)

20. Primary Outcome

Title	Cmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-Infected Participants (Group C)
Description	Maximum observed plasma drug concentration was obtained.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Group C: Uprifosbuvir 300 mg (Tablet)	Group C: Uprifosbuvir 450 mg (Tablet)
Arm/Group Description:	Participants were administered single doses of uprifosbuvir 300 mg as oral tablets once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 450 mg as oral tablets once daily for 7 days under fasted conditions.
Overall Number of Participants Analyzed	7	7
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: nmol/L
Day 1	618; (45.2%)	778; (29.7%)
Day 7	537; (56.4%)	717; (47.2%)

21. Primary Outcome

Title	Cmax of Uprifosbuvir After Single Dose of Uprifosbuvir as Capsule Formulation in Genotype 1, HCV-Infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 1e)
Description	Maximum observed plasma drug concentration was obtained.
Time Frame	Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Group E: Uprifosbuvir 150 mg (Cohort 1e)
Arm/Group Description:	Participants were administered a single dose of uprifosbuvir 150 mg as oral capsules under fasted conditions.
Overall Number of Participants Analyzed	2
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: nmol/L
	613 [1]; (NA%)

[1]

Not calculated

22. Primary Outcome

Title	Cmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as Capsule or Tablet Formulation in Genotype 1, HCV-Infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 2e and Cohort 3e)
Description	Maximum observed plasma drug concentration was obtained.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Group E: Uprifosbuvir 300 mg (Cohort 2e)	Group E: Uprifosbuvir 450 mg (Cohort 3e)
Arm/Group Description:	Participants were administered single doses of uprifosbuvir 300 mg as oral capsules once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 450 mg as oral tablets once daily for 7 days under fasted conditions.
Overall Number of Participants Analyzed	3	7
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: nmol/L
Day 1	1440; (35.9%)	1090; (34.4%)
Day 7	1550; (47.5%)	929; (26.6%)

23. Primary Outcome

Title	Cmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as Tablet Formulation in Genotype 1, HCV-Infected Participants, With Itraconazole (Group F)
Description	Maximum observed plasma drug concentration was obtained.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Group F: Uprifosbuvir 300 mg (Tablet)
Arm/Group Description:	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.
Overall Number of Participants Analyzed	8
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: nmol/L
Day 1	2140; (39.4%)
Day 7	1910; (42.6%)

24. Primary Outcome

Title	Time to Maximum Plasma Concentration (Tmax) of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Healthy Participants (Group A)
Description	Time to maximum plasma concentration was obtained. All participants were fasted.
Time Frame	Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Group A: Uprifosbuvir 10 mg (Cohort 1a)	Group A: Uprifosbuvir 25 mg (Cohort 2a)	Group A: Uprifosbuvir 150 mg (Cohort 4a Fasted)	Group A: Uprifosbuvir 300 mg (Cohort 5a)	Group A: Uprifosbuvir 50 mg (Cohort 3a)
Arm/Group Description:	Participants were administered a single dose of uprifosbuvir 10 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 25 mg as oral capsules under fasted conditions.	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.	Participants were administered a single dose of uprifosbuvir 300 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 50 mg as oral capsules under fasted conditions.
Overall Number of Participants Analyzed	6	6	6	6	6
Median (Full Range); Unit of Measure: hours
	0.80; (0.50 to 1.05)	1.00; (0.50 to 3.00)	0.76; (0.50 to 2.00)	0.50; (0.50 to 2.00)	1.00; (0.50 to 1.00)

25. Primary Outcome

Title	Tmax of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Fed State in Healthy Participants (Group A - Cohort 4a)
Description	Time to maximum plasma concentration was obtained.
Time Frame	Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Group A: Uprifosbuvir 150 mg (Cohort 4a Fed)
Arm/Group Description:	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.
Overall Number of Participants Analyzed	6
Median (Full Range); Unit of Measure: hours
	3.04; (3.00 to 4.05)

26. Primary Outcome

Title	Tmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Healthy Participants (Group A - Cohort 6a)
Description	Maximum observed plasma drug concentration was obtained.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Group A: Uprifosbuvir 300 mg (Cohort 6a)
Arm/Group Description:	Participants were administered single doses of uprifosbuvir 300 mg as oral capsules once daily for 7 days under fasted conditions.
Overall Number of Participants Analyzed	6
Median (Full Range); Unit of Measure: hours
Day 1	0.75; (0.50 to 1.00)
Day 7	0.50; (0.50 to 2.03)

27. Primary Outcome

Title	Tmax of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Genotype 1, HCV-infected Participants (Group B)
Description	Time to maximum plasma concentration was obtained.
Time Frame	Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Group B: Uprifosbuvir 10 mg (Cohort 1b)	Group B: Uprifosbuvir 25 mg (Cohort 2b)	Group B: Uprifosbuvir 50 mg (Cohort 3b)	Group B: Uprifosbuvir 150 mg (Cohort 4b)	Group B: Uprifosbuvir 300 mg (Cohort 5b)
Arm/Group Description:	Participants were administered a single dose of uprifosbuvir 10 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 25 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 50 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 150 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 300 mg as oral capsules under fasted conditions.
Overall Number of Participants Analyzed	3	3	3	2	3
Median (Full Range); Unit of Measure: hours
	0.50; (0.50 to 1.00)	1.00; (0.53 to 1.00)	1.00; (0.68 to 1.00)	0.76; (0.52 to 1.00)	1.00; (0.50 to 1.08)

28. Primary Outcome

Title	Tmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-infected Participants (Groups C and D)
Description	Time to maximum plasma concentration was obtained.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Groups C & D: Uprifosbuvir 50 mg (Capsule)	Groups C & D: Uprifosbuvir 150 mg (Capsule)	Groups C & D: Uprifosbuvir 300 mg (Capsule)	Groups C & D: Uprifosbuvir 400 mg (Capsule)
Arm/Group Description:	Participants were administered single doses of uprifosbuvir 50 mg as oral capsules once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 150 mg as oral capsules once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 300 mg as oral capsules once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 400 mg as oral capsules once daily for 7 days under fasted conditions.
Overall Number of Participants Analyzed	10	9	17	7
Median (Full Range); Unit of Measure: hours
Day 1	0.85; (0.50 to 2.03)	0.50; (0.50 to 2.00)	1.00; (0.50 to 4.00)	0.50; (0.50 to 2.00)
Day 7	0.97; (0.50 to 1.00)	0.50; (0.50 to 1.00)	0.50; (0.48 to 3.00)	0.50; (0.50 to 3.00)

29. Primary Outcome

Title	Tmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-infected Participants (Group C)
Description	Time to maximum plasma concentration was obtained.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Group C: Uprifosbuvir 300 mg (Tablet)	Group C: Uprifosbuvir 450 mg (Tablet)
Arm/Group Description:	Participants were administered single doses of uprifosbuvir 300 mg as oral tablets once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 450 mg as oral tablets once daily for 7 days under fasted conditions.
Overall Number of Participants Analyzed	7	7
Median (Full Range); Unit of Measure: hours
Day 1	1.00; (0.50 to 4.00)	2.00; (0.50 to 3.00)
Day 7	0.50; (0.50 to 3.00)	0.50; (0.50 to 3.00)

30. Primary Outcome

Title	Tmax of Uprifosbuvir After Singe Dose of Uprifosbuvir as Capsule Formulation in Genotype 1, HCV-infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 1e)
Description	Time to maximum plasma concentration was obtained.
Time Frame	Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Group E: Uprifosbuvir 150 mg (Cohort 1e)
Arm/Group Description:	Participants were administered a single dose of uprifosbuvir 150 mg as oral capsules under fasted conditions.
Overall Number of Participants Analyzed	2
Median (Full Range); Unit of Measure: hours
	0.75; (0.50 to 1.00)

31. Primary Outcome

Title	Tmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as Capsule or Tablet Formulation in Genotype 1, HCV-infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 2e and Cohort 3e)
Description	AUC0-t was calculated using linear log trapezoidal summation from time zero to last measurable concentration.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Group E: Uprifosbuvir 300 mg (Cohort 2e)	Group E: Uprifosbuvir 450 mg (Cohort 3e)
Arm/Group Description:	Participants were administered single doses of uprifosbuvir 300 mg as oral capsules once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 450 mg as oral tablets once daily for 7 days under fasted conditions.
Overall Number of Participants Analyzed	3	7
Median (Full Range); Unit of Measure: hours
Day 1	1.00; (0.50 to 3.00)	1.00; (0.50 to 2.00)
Day 7	1.00; (0.50 to 1.00)	1.00; (0.50 to 2.00)

32. Primary Outcome

Title	Tmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-infected Participants, With Itraconazole (Group F)
Description	Time to maximum plasma concentration was obtained.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Group F: Uprifosbuvir 300 mg (Tablet)
Arm/Group Description:	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.
Overall Number of Participants Analyzed	8
Median (Full Range); Unit of Measure: hours
Day 1	2.00; (1.00 to 3.00)
Day 7	1.00; (1.00 to 3.00)

33. Primary Outcome

Title	Observed Terminal Half-Life (t1/2) of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Healthy Participants (Group A)
Description	The time measured for the plasma concentration to decrease by one half (t1/2) was obtained. All participants were fasted.
Time Frame	Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Group A: Uprifosbuvir 10 mg (Cohort 1a)	Group A: Uprifosbuvir 25 mg (Cohort 2a)	Group A: Uprifosbuvir 150 mg (Cohort 4a Fasted)	Group A: Uprifosbuvir 300 mg (Cohort 5a)	Group A: Uprifosbuvir 50 mg (Cohort 3a)
Arm/Group Description:	Participants were administered a single dose of uprifosbuvir 10 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 25 mg as oral capsules under fasted conditions.	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.	Participants were administered a single dose of uprifosbuvir 300 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 50 mg as oral capsules under fasted conditions.
Overall Number of Participants Analyzed	6	6	6	6	6
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: hours
	0.839; (27.3%)	0.872; (33.7%)	1.05; (25.0%)	1.13; (31.6%)	0.979; (36.6%)

34. Primary Outcome

Title	t1/2 of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Fed State in Healthy Participants (Group A - Cohort 4a)
Description	The time measured for the plasma concentration to decrease by one half (t1/2) was obtained.
Time Frame	Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Group A: Uprifosbuvir 150 mg (Cohort 4a Fed)
Arm/Group Description:	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.
Overall Number of Participants Analyzed	6
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: hours
	1.63; (31.9%)

35. Primary Outcome

Title	t1/2 of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Genotype 1, HCV-infected Participants (Group B)
Description	The time measured for the plasma concentration to decrease by one half (t1/2) was obtained.
Time Frame	Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Group B: Uprifosbuvir 10 mg (Cohort 1b)	Group B: Uprifosbuvir 25 mg (Cohort 2b)	Group B: Uprifosbuvir 50 mg (Cohort 3b)	Group B: Uprifosbuvir 150 mg (Cohort 4b)	Group B: Uprifosbuvir 300 mg (Cohort 5b)
Arm/Group Description:	Participants were administered a single dose of uprifosbuvir 10 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 25 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 50 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 150 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 300 mg as oral capsules under fasted conditions.
Overall Number of Participants Analyzed	3	3	3	2	3
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: hours
	1.36; (52.7%)	0.926; (34.5%)	1.09; (32.5%)	1.11 [1]; (NA%)	1.59; (1.7%)

[1]

Not calculated

36. Primary Outcome

Title	t1/2 of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-infected Participants (Groups C and D)
Description	The time measured for the plasma concentration to decrease by one half (t1/2) was obtained.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Groups C & D: Uprifosbuvir 50 mg (Capsule)	Groups C & D: Uprifosbuvir 150 mg (Capsule)	Groups C & D: Uprifosbuvir 300 mg (Capsule)	Groups C & D: Uprifosbuvir 400 mg (Capsule)
Arm/Group Description:	Participants were administered single doses of uprifosbuvir 50 mg as oral capsules once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 150 mg as oral capsules once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 300 mg as oral capsules once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 400 mg as oral capsules once daily for 7 days under fasted conditions.
Overall Number of Participants Analyzed	10	9	17	7
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: hours
	1.04; (25.1%)	1.11; (22.5%)	154.; (34.0%)	2.58; (40.3%)

37. Primary Outcome

Title	t1/2 of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-infected Participants (Group C)
Description	The time measured for the plasma concentration to decrease by one half (t1/2) was obtained.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Group C: Uprifosbuvir 300 mg (Tablet)	Group C: Uprifosbuvir 450 mg (Tablet)
Arm/Group Description:	Participants were administered single doses of uprifosbuvir 300 mg as oral tablets once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 450 mg as oral tablets once daily for 7 days under fasted conditions.
Overall Number of Participants Analyzed	7	7
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: hours
	2.50; (55.9%)	3.64; (54.8%)

38. Primary Outcome

Title	t1/2 of Uprifosbuvir After Single Dose of Uprifosbuvir as Capsule Formulation in Genotype 1, HCV-infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 1e)
Description	The time measured for the plasma concentration to decrease by one half (t1/2) was obtained.
Time Frame	Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Group E: Uprifosbuvir 150 mg (Cohort 1e)
Arm/Group Description:	Participants were administered a single dose of uprifosbuvir 150 mg as oral capsules under fasted conditions.
Overall Number of Participants Analyzed	2
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: hours
	1.16 [1]; (NA%)

[1]

Not calculated

39. Primary Outcome

Title	t1/2 of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as Capsule or Tablet Formulation in Genotype 1, HCV-infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 2e and Cohort 3e)
Description	The time measured for the plasma concentration to decrease by one half (t1/2) was obtained.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Group E: Uprifosbuvir 300 mg (Cohort 2e)	Group E: Uprifosbuvir 450 mg (Cohort 3e)
Arm/Group Description:	Participants were administered single doses of uprifosbuvir 300 mg as oral capsules once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 450 mg as oral tablets once daily for 7 days under fasted conditions.
Overall Number of Participants Analyzed	3	7
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: hours
	1.18; (27.2%)	2.38; (34.3%)

40. Primary Outcome

Title	t1/2 of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-infected Participants, With Itraconazole (Group F)
Description	The time measured for the plasma concentration to decrease by one half (t1/2) was obtained.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Group F: Uprifosbuvir 300 mg (Tablet)
Arm/Group Description:	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.
Overall Number of Participants Analyzed	8
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: hours
	4.30; (52.8%)

41. Primary Outcome

Title	AUC0-inf of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Healthy Participants (Group A)
Description	Area under the drug concentration-time curve from time zero to infinity for M6, a metabolite of uprifosbuvir, estimated as AUC0-t + Cest/λz, where λz is the terminal elimination rate constant, calculated for the first dose only. All participants were fasted.
Time Frame	Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Group A: Uprifosbuvir 10 mg (Cohort 1a)	Group A: Uprifosbuvir 25 mg (Cohort 2a)	Group A: Uprifosbuvir 150 mg (Cohort 4a Fasted)	Group A: Uprifosbuvir 300 mg (Cohort 5a)	Group A: Uprifosbuvir 50 mg (Cohort 3a)
Arm/Group Description:	Participants were administered a single dose of uprifosbuvir 10 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 25 mg as oral capsules under fasted conditions.	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.	Participants were administered a single dose of uprifosbuvir 300 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 50 mg as oral capsules under fasted conditions.
Overall Number of Participants Analyzed	6	6	6	6	6
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: h*umol/L
	1.68; (47.4%)	5.01; (27.2%)	19.8; (12.7%)	29.7; (32.1%)	8.77; (8.4%)

42. Primary Outcome

Title	AUC0-inf of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Fed State in Healthy Participants (Group A - Cohort 4a)
Description	Area under the drug concentration-time curve from time zero to infinity estimated as AUC0-t + Cest/λz, where λz is the terminal elimination rate constant, calculated for the first dose only.
Time Frame	Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Group A: Uprifosbuvir 150 mg (Cohort 4a Fed)
Arm/Group Description:	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.
Overall Number of Participants Analyzed	6
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: h*umol/L
	17.9; (13.4%)

43. Primary Outcome

Title	AUC0-inf of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Healthy Participants (Group A - Cohort 6a)
Description	Area under the drug concentration-time curve from time zero to infinity estimated as AUC0-t + Cest/λz, where λz is the terminal elimination rate constant, calculated for the first dose only.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Group A: Uprifosbuvir 300 mg (Cohort 6a)
Arm/Group Description:	Participants were administered single doses of uprifosbuvir 300 mg as oral capsules once daily for 7 days under fasted conditions.
Overall Number of Participants Analyzed	6
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: h*umol/L
Day 1	15.1; (16.5%)
Day 7	20.6; (17.9%)

44. Primary Outcome

Title	AUC0-inf of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Genotype 1, HCV-Infected Participants (Group B)
Description	Area under the drug concentration-time curve from time zero to infinity estimated as AUC0-t + Cest/λz, where λz is the terminal elimination rate constant, calculated for the first dose only.
Time Frame	Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Group B: Uprifosbuvir 10 mg (Cohort 1b)	Group B: Uprifosbuvir 25 mg (Cohort 2b)	Group B: Uprifosbuvir 50 mg (Cohort 3b)	Group B: Uprifosbuvir 150 mg (Cohort 4b)	Group B: Uprifosbuvir 300 mg (Cohort 5b)
Arm/Group Description:	Participants were administered a single dose of uprifosbuvir 10 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 25 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 50 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 150 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 300 mg as oral capsules under fasted conditions.
Overall Number of Participants Analyzed	3	3	3	2	3
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: h*umol/L
	2.26; (22.3%)	5.78; (4.7%)	7.31; (11.1%)	17.5 [1]; (NA%)	33.4; (37.0%)

[1]

Not calculated

45. Primary Outcome

Title	AUC0-inf of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D)
Description	Area under the drug concentration-time curve from time zero to infinity estimated as AUC0-t + Cest/λz, where λz is the terminal elimination rate constant, calculated for the first dose only.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Groups C & D: Uprifosbuvir 50 mg (Capsule)	Groups C & D: Uprifosbuvir 150 mg (Capsule)	Groups C & D: Uprifosbuvir 300 mg (Capsule)	Groups C & D: Uprifosbuvir 400 mg (Capsule)
Arm/Group Description:	Participants were administered single doses of uprifosbuvir 50 mg as oral capsules once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 150 mg as oral capsules once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 300 mg as oral capsules once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 400 mg as oral capsules once daily for 7 days under fasted conditions.
Overall Number of Participants Analyzed	10	9	17	7
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: h*umol/L
Day 1	4.74; (37.6%)	8.94; (20.2%)	14.4; (20.8%)	19.4; (11.1%)
Day 7	7.12; (37.6%)	12.2; (18.9%)	19.0; (16.3%)	24.4; (7.2%)

46. Primary Outcome

Title	AUC0-inf of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-Infected Participants (Group C)
Description	Area under the drug concentration-time curve from time zero to infinity estimated as AUC0-t + Cest/λz, where λz is the terminal elimination rate constant, calculated for the first dose only.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Group C: Uprifosbuvir 300 mg (Tablet)	Group C: Uprifosbuvir 450 mg (Tablet)
Arm/Group Description:	Participants were administered single doses of uprifosbuvir 300 mg as oral tablets once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 450 mg as oral tablets once daily for 7 days under fasted conditions.
Overall Number of Participants Analyzed	7	7
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: h*umol/L
Day 1	14.7; (36.6%)	16.1; (23.5%)
Day 7	21.4; (26.7%)	24.7; (22.5%)

47. Primary Outcome

Title	AUC0-inf of M6 After Single Dose of Uprifosbuvir as Capsule Formulation in Genotype 1, HCV-Infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 1e)
Description	Area under the drug concentration-time curve from time zero to infinity estimated as AUC0-t + Cest/λz, where λz is the terminal elimination rate constant, calculated for the first dose only.
Time Frame	Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Group E: Uprifosbuvir 150 mg (Cohort 1e)
Arm/Group Description:	Participants were administered a single dose of uprifosbuvir 150 mg as oral capsules under fasted conditions.
Overall Number of Participants Analyzed	2
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: h*umol/L
	1.05 [1]; (NA%)

[1]

Not calculated

48. Primary Outcome

Title	AUC0-inf of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as Capsule or Tablet Formulation in Genotype 1, HCV-Infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 2e and Cohort 3e)
Description	Area under the drug concentration-time curve from time zero to infinity estimated as AUC0-t + Cest/λz, where λz is the terminal elimination rate constant, calculated for the first dose only.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Group E: Uprifosbuvir 300 mg (Cohort 2e)	Group E: Uprifosbuvir 450 mg (Cohort 3e)
Arm/Group Description:	Participants were administered single doses of uprifosbuvir 300 mg as oral capsules once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 450 mg as oral tablets once daily for 7 days under fasted conditions.
Overall Number of Participants Analyzed	3	7
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: h*umol/L
Day 1	13.4; (22.3%)	18.4; (17.0%)
Day 7	17.5; (23.5%)	26.1; (26.5%)

49. Primary Outcome

Title	AUC0-inf of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-Infected Participants, With Itraconazole (Group F)
Description	Area under the drug concentration-time curve from time zero to infinity estimated as AUC0-t + Cest/λz, where λz is the terminal elimination rate constant, calculated for the first dose only.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Group F: Uprifosbuvir 300 mg (Tablet)
Arm/Group Description:	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.
Overall Number of Participants Analyzed	8
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: h*umol/L
Day 1	13.2; (32.0%)
Day 7	23.8; (37.0%)

50. Primary Outcome

Title	Cmax of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Healthy Participants (Group A)
Description	Maximum observed plasma drug concentration was obtained. All participants were fasted.
Time Frame	Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Group A: Uprifosbuvir 10 mg (Cohort 1a)	Group A: Uprifosbuvir 25 mg (Cohort 2a)	Group A: Uprifosbuvir 150 mg (Cohort 4a Fasted)	Group A: Uprifosbuvir 300 mg (Cohort 5a)	Group A: Uprifosbuvir 50 mg (Cohort 3a)
Arm/Group Description:	Participants were administered a single dose of uprifosbuvir 10 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 25 mg as oral capsules under fasted conditions.	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.	Participants were administered a single dose of uprifosbuvir 300 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 50 mg as oral capsules under fasted conditions.
Overall Number of Participants Analyzed	6	6	6	6	6
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: nmol/L
	63.2; (19.8%)	146; (13.6%)	758; (28.2%)	1190; (16.6%)	283; (14.7%)

51. Primary Outcome

Title	Cmax of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Fed State in Healthy Participants (Group A - Cohort 4a)
Description	Maximum observed plasma drug concentration was obtained.
Time Frame	Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Group A: Uprifosbuvir 150 mg (Cohort 4a Fed)
Arm/Group Description:	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.
Overall Number of Participants Analyzed	6
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: nmol/L
	509; (8.4%)

52. Primary Outcome

Title	Cmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Healthy Participants (Group A - Cohort 6a)
Description	Maximum observed plasma drug concentration was obtained.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Group A: Uprifosbuvir 300 mg (Cohort 6a)
Arm/Group Description:	Participants were administered single doses of uprifosbuvir 300 mg as oral capsules once daily for 7 days under fasted conditions.
Overall Number of Participants Analyzed	6
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: nmol/L
Day 1	1310; (7.5%)
Day 7	1630; (14.9%)

53. Primary Outcome

Title	Cmax of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Genotype 1, HCV-Infected Participants (Group B)
Description	Maximum observed plasma drug concentration was obtained.
Time Frame	Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Group B: Uprifosbuvir 10 mg (Cohort 1b)	Group B: Uprifosbuvir 25 mg (Cohort 2b)	Group B: Uprifosbuvir 50 mg (Cohort 3b)	Group B: Uprifosbuvir 150 mg (Cohort 4b)	Group B: Uprifosbuvir 300 mg (Cohort 5b)
Arm/Group Description:	Participants were administered a single dose of uprifosbuvir 10 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 25 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 50 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 150 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 300 mg as oral capsules under fasted conditions.
Overall Number of Participants Analyzed	3	3	3	2	3
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: nmol/L
	55.0; (15.0%)	170; (7.2%)	279; (5.2%)	710 [1]; (NA%)	1210; (33.8%)

[1]

Not calculated

54. Primary Outcome

Title	Cmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D)
Description	Maximum observed plasma drug concentration was obtained.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Groups C & D: Uprifosbuvir 50 mg (Capsule)	Groups C & D: Uprifosbuvir 150 mg (Capsule)	Groups C & D: Uprifosbuvir 300 mg (Capsule)	Groups C & D: Uprifosbuvir 400 mg (Capsule)
Arm/Group Description:	Participants were administered single doses of uprifosbuvir 50 mg as oral capsules once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 150 mg as oral capsules once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 300 mg as oral capsules once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 400 mg as oral capsules once daily for 7 days under fasted conditions.
Overall Number of Participants Analyzed	10	9	17	7
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: nmol/L
Day 1	298; (34.2%)	641; (7.6%)	1130; (22.7%)	1560; (18.9%)
Day 7	471; (33.7%)	931; (14.4%)	1420; (15.3%)	1760; (10.4%)

55. Primary Outcome

Title	Cmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-Infected Participants (Group C)
Description	Maximum observed plasma drug concentration was obtained.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Group C: Uprifosbuvir 300 mg (Tablet)	Group C: Uprifosbuvir 450 mg (Tablet)
Arm/Group Description:	Participants were administered single doses of uprifosbuvir 300 mg as oral tablets once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 450 mg as oral tablets once daily for 7 days under fasted conditions.
Overall Number of Participants Analyzed	7	7
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: nmol/L
Day 1	1010; (31.5%)	1210; (21.9%)
Day 7	1420; (23.2%)	1680; (21.5%)

56. Primary Outcome

Title	Cmax of M6 After Single Dose of Uprifosbuvir as Capsule Formulation in Genotype 1, HCV-Infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 1e)
Description	Maximum observed plasma drug concentration was obtained.
Time Frame	Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Group E: Uprifosbuvir 150 mg (Cohort 1e)
Arm/Group Description:	Participants were administered a single dose of uprifosbuvir 150 mg as oral capsules under fasted conditions.
Overall Number of Participants Analyzed	2
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: nmol/L
	597 [1]; (NA%)

[1]

Not calculated

57. Primary Outcome

Title	Cmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as Capsule or Tablet Formulation in Genotype 1, HCV-Infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 2e and Cohort 3e)
Description	Maximum observed plasma drug concentration was obtained.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Group E: Uprifosbuvir 300 mg (Cohort 2e)	Group E: Uprifosbuvir 450 mg (Cohort 3e)
Arm/Group Description:	Participants were administered single doses of uprifosbuvir 300 mg as oral capsules once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 450 mg as oral tablets once daily for 7 days under fasted conditions.
Overall Number of Participants Analyzed	3	7
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: nmol/L
Day 1	1100; (11.5%)	1180; (11.9%)
Day 7	1550; (11.4%)	1740; (19.7%)

58. Primary Outcome

Title	Cmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-Infected Participants, With Itraconazole (Group F)
Description	Maximum observed plasma drug concentration was obtained.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Group F: Uprifosbuvir 300 mg (Tablet)
Arm/Group Description:	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.
Overall Number of Participants Analyzed	8
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: nmol/L
Day 1	738; (31.7%)
Day 7	1180; (33.2%)

59. Primary Outcome

Title	Tmax of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Healthy Participants (Group A)
Description	Time to maximum plasma concentration was obtained. All participants were fasted.
Time Frame	Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Group A: Uprifosbuvir 10 mg (Cohort 1a)	Group A: Uprifosbuvir 25 mg (Cohort 2a)	Group A: Uprifosbuvir 150 mg (Cohort 4a Fasted)	Group A: Uprifosbuvir 300 mg (Cohort 5a)	Group A: Uprifosbuvir 50 mg (Cohort 3a)
Arm/Group Description:	Participants were administered a single dose of uprifosbuvir 10 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 25 mg as oral capsules under fasted conditions.	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.	Participants were administered a single dose of uprifosbuvir 300 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 50 mg as oral capsules under fasted conditions.
Overall Number of Participants Analyzed	6	6	6	6	6
Median (Full Range); Unit of Measure: hours
	3.01; (2.00 to 6.00)	3.50; (2.00 to 4.05)	2.53; (2.00 to 6.05)	3.50; (3.00 to 4.00)	4.00; (2.00 to 6.00)

60. Primary Outcome

Title	Tmax of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Fed State in Healthy Participants (Group A - Cohort 4a)
Description	Time to maximum plasma concentration was obtained.
Time Frame	Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Group A: Uprifosbuvir 150 mg (Cohort 4a Fed)
Arm/Group Description:	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.
Overall Number of Participants Analyzed	6
Median (Full Range); Unit of Measure: hours
	6.00; (6.00 to 8.00)

61. Primary Outcome

Title	Tmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Healthy Participants (Group A - Cohort 6a)
Description	Time to maximum plasma concentration was obtained.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Group A: Uprifosbuvir 300 mg (Cohort 6a)
Arm/Group Description:	Participants were administered single doses of uprifosbuvir 300 mg as oral capsules once daily for 7 days under fasted conditions.
Overall Number of Participants Analyzed	6
Median (Full Range); Unit of Measure: hours
Day 1	3.00; (2.00 to 3.05)
Day 7	2.50; (1.00 to 4.00)

62. Primary Outcome

Title	Tmax of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Genotype 1, HCV-Infected Participants (Group B)
Description	Time to maximum plasma concentration was obtained.
Time Frame	Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Group B: Uprifosbuvir 10 mg (Cohort 1b)	Group B: Uprifosbuvir 25 mg (Cohort 2b)	Group B: Uprifosbuvir 50 mg (Cohort 3b)	Group B: Uprifosbuvir 150 mg (Cohort 4b)	Group B: Uprifosbuvir 300 mg (Cohort 5b)
Arm/Group Description:	Participants were administered a single dose of uprifosbuvir 10 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 25 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 50 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 150 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 300 mg as oral capsules under fasted conditions.
Overall Number of Participants Analyzed	3	3	3	2	3
Median (Full Range); Unit of Measure: hours
	4.00; (4.00 to 6.00)	4.00; (3.03 to 4.00)	2.05; (2.00 to 4.00)	3.52; (3.03 to 4.00)	4.00; (1.00 to 6.00)

63. Primary Outcome

Title	Tmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D)
Description	Time to maximum plasma concentration was obtained.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Groups C & D: Uprifosbuvir 50 mg (Capsule)	Groups C & D: Uprifosbuvir 150 mg (Capsule)	Groups C & D: Uprifosbuvir 300 mg (Capsule)	Groups C & D: Uprifosbuvir 400 mg (Capsule)
Arm/Group Description:	Participants were administered single doses of uprifosbuvir 50 mg as oral capsules once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 150 mg as oral capsules once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 300 mg as oral capsules once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 400 mg as oral capsules once daily for 7 days under fasted conditions.
Overall Number of Participants Analyzed	10	9	17	7
Median (Full Range); Unit of Measure: hours
Day 1	4.00; (1.00 to 8.00)	3.00; (0.98 to 4.00)	3.00; (2.00 to 6.00)	4.00; (3.00 to 6.00)
Day 7	2.00; (1.92 to 6.00)	2.00; (1.00 to 3.00)	3.00; (1.00 to 4.00)	4.00; (2.00 to 4.00)

64. Primary Outcome

Title	Tmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-Infected Participants (Group C)
Description	Time to maximum plasma concentration was obtained.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Group C: Uprifosbuvir 300 mg (Tablet)	Group C: Uprifosbuvir 450 mg (Tablet)
Arm/Group Description:	Participants were administered single doses of uprifosbuvir 300 mg as oral tablets once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 450 mg as oral tablets once daily for 7 days under fasted conditions.
Overall Number of Participants Analyzed	7	7
Median (Full Range); Unit of Measure: hours
Day 1	4.00; (2.00 to 6.00)	4.00; (3.00 to 6.03)
Day 7	4.00; (2.00 to 4.00)	4.00; (3.00 to 6.00)

65. Primary Outcome

Title	Tmax of M6 After Single Dose of Uprifosbuvir as Capsule Formulation in Genotype 1, HCV-Infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 1e)
Description	Time to maximum plasma concentration was obtained.
Time Frame	Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Group E: Uprifosbuvir 150 mg (Cohort 1e)
Arm/Group Description:	Participants were administered a single dose of uprifosbuvir 150 mg as oral capsules under fasted conditions.
Overall Number of Participants Analyzed	2
Median (Full Range); Unit of Measure: hours
	4.00; (4.00 to 4.00)

66. Primary Outcome

Title	Tmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as Capsule or Tablet Formulation in Genotype 1,HCV-Infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 2e and Cohort 3e)
Description	Time to maximum plasma concentration was obtained.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Group E: Uprifosbuvir 300 mg (Cohort 2e)	Group E: Uprifosbuvir 450 mg (Cohort 3e)
Arm/Group Description:	Participants were administered single doses of uprifosbuvir 300 mg as oral capsules once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 450 mg as oral tablets once daily for 7 days under fasted conditions.
Overall Number of Participants Analyzed	3	7
Median (Full Range); Unit of Measure: hours
Day 1	3.00; (2.00 to 4.00)	4.00; (3.00 to 4.00)
Day 7	2.00; (2.00 to 4.00)	4.00; (2.00 to 4.00)

67. Primary Outcome

Title	Tmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-Infected Participants, With Itraconazole (Group F)
Description	Time to maximum plasma concentration was obtained.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Group F: Uprifosbuvir 300 mg (Tablet)
Arm/Group Description:	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.
Overall Number of Participants Analyzed	8
Median (Full Range); Unit of Measure: hours
Day 1	10.00; (6.00 to 23.5)
Day 7	4.00; (3.00 to 8.00)

68. Primary Outcome

Title	t1/2 of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Healthy Participants (Group A)
Description	The time measured for the plasma concentration to decrease by one half (t1/2) was obtained. All participants were fasted.
Time Frame	Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Group A: Uprifosbuvir 10 mg (Cohort 1a)	Group A: Uprifosbuvir 25 mg (Cohort 2a)	Group A: Uprifosbuvir 150 mg (Cohort 4a Fasted)	Group A: Uprifosbuvir 300 mg (Cohort 5a)	Group A: Uprifosbuvir 50 mg (Cohort 3a)
Arm/Group Description:	Participants were administered a single dose of uprifosbuvir 10 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 25 mg as oral capsules under fasted conditions.	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.	Participants were administered a single dose of uprifosbuvir 300 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 50 mg as oral capsules under fasted conditions.
Overall Number of Participants Analyzed	6	6	6	6	6
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: hours
	22.5; (6.2%)	24.6; (12.8%)	29.1; (15.5%)	28.8; (14.2%)	22.9; (14.0%)

69. Primary Outcome

Title	t1/2 of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Fed State in Healthy Participants (Group A - Cohort 4a)
Description	The time measured for the plasma concentration to decrease by one half (t1/2) was obtained.
Time Frame	Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Group A: Uprifosbuvir 150 mg (Cohort 4a Fed)
Arm/Group Description:	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.
Overall Number of Participants Analyzed	6
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: hours
	27.1; (9.1%)

70. Primary Outcome

Title	t1/2 of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Healthy Participants (Group A - Cohort 6a)
Description	The time measured for the plasma concentration to decrease by one half (t1/2) was obtained.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Group A: Uprifosbuvir 300 mg (Cohort 6a)
Arm/Group Description:	Participants were administered single doses of uprifosbuvir 300 mg as oral capsules once daily for 7 days under fasted conditions.
Overall Number of Participants Analyzed	6
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: hours
	32.2; (10.3%)

71. Primary Outcome

Title	t1/2 of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Genotype 1, HCV-Infected Participants (Group B)
Description	The time measured for the plasma concentration to decrease by one half (t1/2) was obtained.
Time Frame	Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Group B: Uprifosbuvir 10 mg (Cohort 1b)	Group B: Uprifosbuvir 25 mg (Cohort 2b)	Group B: Uprifosbuvir 50 mg (Cohort 3b)	Group B: Uprifosbuvir 150 mg (Cohort 4b)	Group B: Uprifosbuvir 300 mg (Cohort 5b)
Arm/Group Description:	Participants were administered a single dose of uprifosbuvir 10 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 25 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 50 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 150 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 300 mg as oral capsules under fasted conditions.
Overall Number of Participants Analyzed	3	3	3	2	3
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: hours
	20.1; (3.4%)	21.2; (4.8%)	21.7; (19.8%)	26.9 [1]; (NA%)	28.0; (12.1%)

[1]

Not calculated

72. Primary Outcome

Title	t1/2 of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D)
Description	The time measured for the plasma concentration to decrease by one half (t1/2) was obtained.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Groups C & D: Uprifosbuvir 50 mg (Capsule)	Groups C & D: Uprifosbuvir 150 mg (Capsule)	Groups C & D: Uprifosbuvir 300 mg (Capsule)	Groups C & D: Uprifosbuvir 400 mg (Capsule)
Arm/Group Description:	Participants were administered single doses of uprifosbuvir 50 mg as oral capsules once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 150 mg as oral capsules once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 300 mg as oral capsules once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 400 mg as oral capsules once daily for 7 days under fasted conditions.
Overall Number of Participants Analyzed	10	9	17	7
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: hours
	25.5; (16.8%)	28.9; (15.2%)	32.6; (12.7%)	35.8; (17.8%)

73. Primary Outcome

Title	t1/2 of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-Infected Participants (Group C)
Description	The time measured for the plasma concentration to decrease by one half (t1/2) was obtained.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Group C: Uprifosbuvir 300 mg (Tablet)	Group C: Uprifosbuvir 450 mg (Tablet)
Arm/Group Description:	Participants were administered single doses of uprifosbuvir 300 mg as oral tablets once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 450 mg as oral tablets once daily for 7 days under fasted conditions.
Overall Number of Participants Analyzed	7	7
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: hours
	32.4; (7.7%)	30.8; (26.8%)

74. Primary Outcome

Title	t1/2 of M6 After Single Dose of Uprifosbuvir as Capsule Formulation in Genotype 1, HCV-Infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 1e)
Description	The time measured for the plasma concentration to decrease by one half (t1/2) was obtained.
Time Frame	Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Group E: Uprifosbuvir 150 mg (Cohort 1e)
Arm/Group Description:	Participants were administered a single dose of uprifosbuvir 150 mg as oral capsules under fasted conditions.
Overall Number of Participants Analyzed	2
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: hours
	24.0 [1]; (NA%)

[1]

Not calculated

75. Primary Outcome

Title	t1/2 of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as Capsule or Tablet Formulation in Genotype 1, HCV-Infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 2e and Cohort 3e)
Description	The time measured for the plasma concentration to decrease by one half (t1/2) was obtained.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Group E: Uprifosbuvir 300 mg (Cohort 2e)	Group E: Uprifosbuvir 450 mg (Cohort 3e)
Arm/Group Description:	Participants were administered single doses of uprifosbuvir 300 mg as oral capsules once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 450 mg as oral tablets once daily for 7 days under fasted conditions.
Overall Number of Participants Analyzed	3	7
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: hours
	27.5; (9.3%)	26.2; (24.8%)

76. Primary Outcome

Title	t1/2 of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-Infected Participants, With Itraconazole (Group F)
Description	The time measured for the plasma concentration to decrease by one half (t1/2) was obtained.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Group F: Uprifosbuvir 300 mg (Tablet)
Arm/Group Description:	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.
Overall Number of Participants Analyzed	8
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: hours
	38.9; (17.7%)

77. Primary Outcome

Title	Cumulative Urine Excretion of Unchanged Uprifosbuvir in Healthy Participants (Group A)
Description	Cumulative urine excretion of unchanged MK-3682 in healthy participants was obtained. All participants were fasted.
Time Frame	Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Group A: Uprifosbuvir 10 mg (Cohort 1a)	Group A: Uprifosbuvir 25 mg (Cohort 2a)	Group A: Uprifosbuvir 150 mg (Cohort 4a Fasted)	Group A: Uprifosbuvir 300 mg (Cohort 5a)	Group A: Uprifosbuvir 50 mg (Cohort 3a)
Arm/Group Description:	Participants were administered a single dose of uprifosbuvir 10 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 25 mg as oral capsules under fasted conditions.	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.	Participants were administered a single dose of uprifosbuvir 300 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 50 mg as oral capsules under fasted conditions.
Overall Number of Participants Analyzed	6	6	6	6	6
Mean (Standard Deviation); Unit of Measure: umol
	0.280 (0.0800)	0.586 (0.164)	7.73 (4.67)	13.1 (4.16)	1.56 (0.397)

78. Primary Outcome

Title	Cumulative Urine Excretion of Unchanged M6 in Healthy Participants (Group A)
Description	Cumulative urine excretion of unchanged M6 in healthy participants was obtained. All participants were fasted.
Time Frame	Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Group A: Uprifosbuvir 10 mg (Cohort 1a)	Group A: Uprifosbuvir 25 mg (Cohort 2a)	Group A: Uprifosbuvir 150 mg (Cohort 4a Fasted)	Group A: Uprifosbuvir 300 mg (Cohort 5a)	Group A: Uprifosbuvir 50 mg (Cohort 3a)
Arm/Group Description:	Participants were administered a single dose of uprifosbuvir 10 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 25 mg as oral capsules under fasted conditions.	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.	Participants were administered a single dose of uprifosbuvir 300 mg as oral capsules under fasted conditions.	Participants were administered a single dose of uprifosbuvir 50 mg as oral capsules under fasted conditions.
Overall Number of Participants Analyzed	6	6	6	6	6
Mean (Standard Deviation); Unit of Measure: umol
	5.93 (1.42)	15.2 (2.50)	101 (6.86)	200 (37.9)	31.8 (5.69)

79. Primary Outcome

Title	Reduction in HCV RNA From Baseline on Day 8 Following Uprifosbuvir 50-450 mg for 7 Days in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D)
Description	Reduction in HCV RNA from baseline on Day 8 following uprifosbuvir 50-450 mg for 7 Days in Genotype 1, 2 and 3, HCV-infected participants was obtained.
Time Frame	Baseline and Day 8

Outcome Measure Data

Analysis Population Description

Per-Protocol Population: participants who complied with the protocol sufficiently to ensure that these data were likely to exhibit the effects of treatment, according to the underlying scientific model.

Arm/Group Title	Groups C & D: Uprifosbuvir 50 mg (Capsule)	Groups C & D: Uprifosbuvir 150 mg (Capsule)	Groups C & D: Uprifosbuvir 300 mg (Capsule)	Groups C & D: Uprifosbuvir 400 mg (Capsule)	Groups C & D: Placebo (Pooled)	Groups C & D: Uprifosbuvir 300 mg (Tablet)	Groups C & D: Uprifosbuvir 450 mg (Tablet)
Arm/Group Description:	Participants were administered single doses of uprifosbuvir 50 mg as oral capsules once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 150 mg as oral capsules once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 300 mg as oral capsules once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 400 mg as oral capsules once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir-matching placebo as oral capsules once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 300 mg as oral tablets once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 450 mg as oral tablets once daily for 7 days under fasted conditions.
Overall Number of Participants Analyzed	10	9	17	7	8	7	7
Mean (Standard Deviation); Unit of Measure: log10 IU/mL
Baseline	5.82 (0.879)	6.00 (0.630)	6.16 (0.633)	6.11 (0.540)	6.27 (0.485)	5.92 (0.838)	5.97 (0.739)
Day 8	0.78 (0.440)	2.49 (0.733)	4.22 (0.614)	4.39 (0.433)	0.42 (0.229)	3.34 (0.643)	4.50 (0.644)

80. Primary Outcome

Title	Maximum Reduction in log10 HCV RNA From Baseline - Normal Participants (From Groups B and C) vs. Mild Hepatic Impairment Participants (Group E)
Description	Reduction in HCV RNA from baseline on Day 8 following uprifosbuvir 50-450 mg for 7 Days in Genotype (Gt) 1, HCV-infected participants was obtained.
Time Frame	Baseline and 28 days after last dose of study drug (Up to 42 days)

Outcome Measure Data

Analysis Population Description

Per-Protocol Population: participants who complied with the protocol sufficiently to ensure that these data were likely to exhibit the effects of treatment, according to the underlying scientific model.

Arm/Group Title		Group B: Uprifosbuvir 150 mg (Cohort 4b)	Group C: Uprifosbuvir 300 mg (Capsule)	Group E: Uprifosbuvir 450 mg
Arm/Group Description:		Participants were administered a single dose of uprifosbuvir 150 mg as oral capsules under fasted conditions.	Participants were administered single doses of uprifosbuvir 300 mg as oral capsules once daily for 7 days under fasted conditions.	Participants were administered single doses of uprifosbuvir 450 mg as oral tablets once daily for 7 days under fasted conditions.
Overall Number of Participants Analyzed		2	8	7
Mean (Standard Deviation); Unit of Measure: log10 IU/mL
Baseline	Number Analyzed	2 participants	8 participants	7 participants
		5.91 (0.347)	6.16 (0.633)	6.14 (0.356)
Normal hepatic fcn: Gt1a	Number Analyzed	1 participants	3 participants	2 participants
		0.96 (NA)	4.82 (0.504)	5.06 (0.489)
Mild hepatic impairment: Gt1a	Number Analyzed	0 participants	2 participants	1 participants
			2.92 (0.239)	3.60 (NA)
Normal hepatic fcn: Gt1b	Number Analyzed	1 participants	5 participants	5 participants
		1.35 (NA)	3.82 (0.636)	4.28 (0.584)
Mild hepatic impairment: Gt1b	Number Analyzed	2 participants	1 participants	6 participants
		1.36 (0.774)	3.59 (NA)	3.08 (1.06)
Normal hepatic fcn: Gt1 (pooled 1a+1b)	Number Analyzed	2 participants	8 participants	7 participants
		1.15 (0.274)	4.19 (0.754)	4.50 (0.644)
Mild hepatic impairment;Gt1 (pooled 1a+1b)	Number Analyzed	2 participants	3 participants	7 participants
		1.36 (0.774)	3.15 (0.420)	3.16 (0.989)

Adverse Events

Time Frame

Up to 42 days (28 days after last study drug administration)

Adverse Event Reporting Description

Safety Population: participants who received at least one dose of the study drug. For Cohort 4a, serious AEs and nonserious AEs are presented for participants on the fasted regimen.

Arm/Group Title

Group A: Placebo (Cohort 1a - Cohort 5a - Pooled)

Group A: Uprifosbuvir 10 mg (Cohort 1a)

Group A: Uprifosbuvir 25 mg (Cohort 2a)

Group A: Uprifosbuvir 50 mg (Cohort 3a)

Group A: Uprifosbuvir 150 mg (Cohort 4a)

Group A: Uprifosbuvir 300 mg (Cohort 5a)

Group A: Placebo (Cohort 6a)

Group A: Uprifosbuvir 300 mg (Cohort 6a)

Group B: Uprifosbuvir 10 mg (Cohort 1b)

Group B: Uprifosbuvir 25 mg (Cohort 2b)

Group B: Uprifosbuvir 50 mg (Cohort 3b)

Group B: Uprifosbuvir 150 mg (Cohort 4b)

Group B: Uprifosbuvir 300 mg (Cohort 5b)

Groups C & D: Uprifosbuvir 50 mg (Capsule)

Groups C & D: Uprifosbuvir 150 mg (Capsule)

Groups C & D: Uprifosbuvir 250 mg (Capsule)

Groups C & D: Uprifosbuvir 300 mg (Capsule)

Groups C & D: Uprifosbuvir 400 mg (Capsule)

Groups C & D: Uprifosbuvir 300 mg (Tablet)

Groups C & D: Uprifosbuvir 450 mg (Tablet)

Groups C & D: Placebo (Pooled)

Group E: Uprifosbuvir 150 mg (Cohort 1e)

Group E: Uprifosbuvir 300 mg (Cohort 2e)

Group E: Uprifosbuvir 450 mg (Cohort 3e)

Group F: Uprifosbuvir 300 mg (Tablet)

Arm/Group Description

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).

Participants were administered a single dose of uprifosbuvir 10 mg as oral capsules under fasted conditions.

Participants were administered a single dose of uprifosbuvir 25 mg as oral capsules under fasted conditions.

Participants were administered a single dose of uprifosbuvir 50 mg as oral capsules under fasted conditions.

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.

Participants were administered a single dose of uprifosbuvir 300 mg as oral capsules under fasted conditions.

Participants were administered single doses of uprifosbuvir-matching placebo oral capsules once daily for 7 days under fasted conditions.

Participants were administered single doses of uprifosbuvir 300 mg as oral capsules once daily for 7 days under fasted conditions.

Participants were administered a single dose of uprifosbuvir 10 mg as oral capsules under fasted conditions.

Participants were administered a single dose of uprifosbuvir 25 mg as oral capsules under fasted conditions.

Participants were administered a single dose of uprifosbuvir 50 mg as oral capsules under fasted conditions.

Participants were administered a single dose of uprifosbuvir 150 mg as oral capsules under fasted conditions.

Participants were administered a single dose of uprifosbuvir 300 mg as oral capsules under fasted conditions.