Trial Outcomes & Findings for A Multiple Ascending Dose Study of Daclatasvir (BMS-790052) in Hepatitis C Virus Genotype 1 Infected Subjects (NCT NCT00663208)

NCT ID: NCT00663208

Last Updated: 2015-10-14

Results Overview

The Roche TaqMan HCV quantitative assay was used for analysis with detection limit of 10 IU/mL. Baseline was Day -1.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

167 participants

Primary outcome timeframe

Baseline, Day 7

Results posted on

2015-10-14

Participant Flow

167 enrolled; 30 entered treatment Period. Reasons for not entering: 1 lost to follow-up, 4 withdrew consent, 5 administrative reasons, 6 other, 121 did not meet study criteria.

A total of 30 participants received study treatment.

Participant milestones

Participant milestones
Measure	Daclatasvir (1 mg) QD Participants received once daily (QD) dose of daclatasvir 1 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (10 mg) QD Participants received QD dose of daclatasvir 10 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (30 mg) QD Participants received QD dose of daclatasvir 30 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (60 mg) QD Participants received QD dose of daclatasvir 60 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (30 mg) BID Participants received twice daily (BID) dose of daclatasvir 30 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (100 mg) QD Participants received QD dose of daclatasvir 100 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Placebo Participants received QD/BID dose of placebo matched to daclatasvir during 14 day treatment period. Participants who received placebo were discharged after Day 28 and after unblinding of the dose panel.
Treatment Period STARTED	4	4	4	4	4	4	6
Treatment Period COMPLETED	4	3	4	4	4	4	6
Treatment Period NOT COMPLETED	0	1	0	0	0	0	0
Follow-up Period STARTED	4	3	4	4	4	4	6
Follow-up Period COMPLETED	1	3	1	2	4	4	5
Follow-up Period NOT COMPLETED	3	0	3	2	0	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Daclatasvir (1 mg) QD Participants received once daily (QD) dose of daclatasvir 1 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (10 mg) QD Participants received QD dose of daclatasvir 10 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (30 mg) QD Participants received QD dose of daclatasvir 30 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (60 mg) QD Participants received QD dose of daclatasvir 60 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Placebo Participants received QD/BID dose of placebo matched to daclatasvir during 14 day treatment period. Participants who received placebo were discharged after Day 28 and after unblinding of the dose panel.
Treatment Period Lost to Follow-up	0	1	0	0	0
Follow-up Period Lost to Follow-up	2	0	3	2	0
Follow-up Period Other reason	1	0	0	0	1

Baseline Characteristics

A Multiple Ascending Dose Study of Daclatasvir (BMS-790052) in Hepatitis C Virus Genotype 1 Infected Subjects

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Daclatasvir (1 mg) QD n=4 Participants Participants received QD dose of daclatasvir 1 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (10 mg) QD n=4 Participants Participants received QD dose of daclatasvir 10 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (30 mg) QD n=4 Participants Participants received QD dose of daclatasvir 30 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (60 mg) QD n=4 Participants Participants received QD dose of daclatasvir 60 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (30 mg) BID n=4 Participants Participants received BID dose of daclatasvir 30 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (100 mg) QD n=4 Participants Participants received QD dose of daclatasvir 100 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Placebo n=6 Participants Participants received QD/BID dose of placebo matched to daclatasvir during 14 day treatment period. Participants who received placebo were discharged after Day 28 and after unblinding of the dose panel.	Total n=30 Participants Total of all reporting groups
Age, Continuous	39.5 years STANDARD_DEVIATION 9.95 • n=5 Participants	46.5 years STANDARD_DEVIATION 13.00 • n=7 Participants	47.5 years STANDARD_DEVIATION 3.70 • n=5 Participants	39.5 years STANDARD_DEVIATION 7.55 • n=4 Participants	44.8 years STANDARD_DEVIATION 6.40 • n=21 Participants	44.3 years STANDARD_DEVIATION 6.90 • n=10 Participants	48.0 years STANDARD_DEVIATION 4.20 • n=115 Participants	44.5 years STANDARD_DEVIATION 7.65 • n=6 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	0 Participants n=21 Participants	1 Participants n=10 Participants	1 Participants n=115 Participants	5 Participants n=6 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants	3 Participants n=4 Participants	4 Participants n=21 Participants	3 Participants n=10 Participants	5 Participants n=115 Participants	25 Participants n=6 Participants

PRIMARY outcome

Timeframe: Baseline, Day 7

Population: All randomized participants who took at least 1 dose of study medication.

The Roche TaqMan HCV quantitative assay was used for analysis with detection limit of 10 IU/mL. Baseline was Day -1.

Outcome measures

Outcome measures
Measure	Daclatasvir (1 mg) QD n=4 Participants Participants received QD dose of daclatasvir 1 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (10 mg) QD n=4 Participants Participants received QD dose of daclatasvir 10 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (30 mg) QD n=4 Participants Participants received QD dose of daclatasvir 30 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (60 mg) QD n=4 Participants Participants received QD dose of daclatasvir 60 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (30 mg) BID n=4 Participants Participants received BID dose of daclatasvir 30 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (100 mg) QD n=4 Participants Participants received QD dose of daclatasvir 100 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Placebo n=6 Participants Participants received QD/BID dose of placebo matched to daclatasvir during 14 day treatment period. Participants who received placebo were discharged after Day 28 and after unblinding of the dose panel.
Change From Baseline at Day 7 in log10 Hepatitis C Virus (HCV) RNA of All Participants	-2.13 log10 IU/mL Interval -3.1 to -1.16	-3.31 log10 IU/mL Interval -4.28 to -2.34	-2.91 log10 IU/mL Interval -3.88 to -1.94	-2.58 log10 IU/mL Interval -3.55 to -1.61	-3.03 log10 IU/mL Interval -4.0 to -2.07	-3.56 log10 IU/mL Interval -4.52 to -2.59	0.00 log10 IU/mL Interval -0.86 to 0.87

SECONDARY outcome

Timeframe: Baseline, Day 7

Population: All randomized participants who took at least 1 dose of study medication.

The Roche TaqMan HCV quantitative assay was used for analysis with detection limit of 10 international units/ millilitre (IU/mL). Baseline was Day -1

Outcome measures

Outcome measures
Measure	Daclatasvir (1 mg) QD n=4 Participants Participants received QD dose of daclatasvir 1 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (10 mg) QD n=4 Participants Participants received QD dose of daclatasvir 10 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (30 mg) QD n=4 Participants Participants received QD dose of daclatasvir 30 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (60 mg) QD n=3 Participants Participants received QD dose of daclatasvir 60 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (30 mg) BID n=3 Participants Participants received BID dose of daclatasvir 30 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (100 mg) QD n=3 Participants Participants received QD dose of daclatasvir 100 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Placebo n=6 Participants Participants received QD/BID dose of placebo matched to daclatasvir during 14 day treatment period. Participants who received placebo were discharged after Day 28 and after unblinding of the dose panel.
Change From Baseline at Day 7 in log10 Hepatitis C Virus (HCV) RNA Levels of Participants Without Baseline Drug Resistance	-2.13 log10 IU/mL Interval -3.1 to -1.16	-3.31 log10 IU/mL Interval -4.28 to -2.34	-2.91 log10 IU/mL Interval -3.88 to -1.94	-2.58 log10 IU/mL Interval -3.55 to -1.61	-3.03 log10 IU/mL Interval -4.0 to -2.07	-3.56 log10 IU/mL Interval -4.52 to -2.59	0.00 log10 IU/mL Interval -0.86 to 0.87

SECONDARY outcome

Timeframe: Baseline, 2, 4, 6, 8, 12, 16, 20, and 24 hours post dose on Day 1

Population: All randomized participants who took at least 1 dose of study medication and did not have baseline genotypic drug resistance mutations were summarized.

The Roche TaqMan HCV quantitative assay was used for analysis with detection limit of 10 IU/mL. Baseline was Day -1.

Outcome measures

Outcome measures
Measure	Daclatasvir (1 mg) QD n=4 Participants Participants received QD dose of daclatasvir 1 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (10 mg) QD n=4 Participants Participants received QD dose of daclatasvir 10 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (30 mg) QD n=4 Participants Participants received QD dose of daclatasvir 30 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (60 mg) QD n=3 Participants Participants received QD dose of daclatasvir 60 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (30 mg) BID n=3 Participants Participants received BID dose of daclatasvir 30 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (100 mg) QD n=3 Participants Participants received QD dose of daclatasvir 100 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Placebo n=6 Participants Participants received QD/BID dose of placebo matched to daclatasvir during 14 day treatment period. Participants who received placebo were discharged after Day 28 and after unblinding of the dose panel.
Change From Baseline at 24 h Post Dose on Day 1 in log10 Hepatitis C Virus (HCV) RNA of Participants Without Baseline Drug Resistance Change at Hour 2	0.02 log10 IU/mL Standard Deviation 0.137	-0.00 log10 IU/mL Standard Deviation 0.083	-0.21 log10 IU/mL Standard Deviation 0.244	-0.43 log10 IU/mL Standard Deviation 0.324	-0.35 log10 IU/mL Standard Deviation 0.284	0.04 log10 IU/mL Standard Deviation 0.107	-0.00 log10 IU/mL Standard Deviation 0.216
Change From Baseline at 24 h Post Dose on Day 1 in log10 Hepatitis C Virus (HCV) RNA of Participants Without Baseline Drug Resistance Change at Hour 4	-0.78 log10 IU/mL Standard Deviation 0.273	-0.91 log10 IU/mL Standard Deviation 0.206	-1.22 log10 IU/mL Standard Deviation 0.202	-1.24 log10 IU/mL Standard Deviation 0.711	-1.24 log10 IU/mL Standard Deviation 0.397	-1.01 log10 IU/mL Standard Deviation 0.345	0.07 log10 IU/mL Standard Deviation 0.248
Change From Baseline at 24 h Post Dose on Day 1 in log10 Hepatitis C Virus (HCV) RNA of Participants Without Baseline Drug Resistance Change at Hour 6	-1.47 log10 IU/mL Standard Deviation 0.466	-1.73 log10 IU/mL Standard Deviation 0.272	-2.05 log10 IU/mL Standard Deviation 0.237	-1.96 log10 IU/mL Standard Deviation 0.717	-1.99 log10 IU/mL Standard Deviation 0.552	-1.36 log10 IU/mL Standard Deviation 0.473	0.00 log10 IU/mL Standard Deviation 0.209
Change From Baseline at 24 h Post Dose on Day 1 in log10 Hepatitis C Virus (HCV) RNA of Participants Without Baseline Drug Resistance Change at Hour 20	-1.92 log10 IU/mL Standard Deviation 0.447	-2.80 log10 IU/mL Standard Deviation 0.095	-3.02 log10 IU/mL Standard Deviation 0.086	-3.50 log10 IU/mL Standard Deviation 0.312	-3.38 log10 IU/mL Standard Deviation 0.477	-2.29 log10 IU/mL Standard Deviation 1.240	0.01 log10 IU/mL Standard Deviation 0.155
Change From Baseline at 24 h Post Dose on Day 1 in log10 Hepatitis C Virus (HCV) RNA of Participants Without Baseline Drug Resistance Change at Hour 24	-1.82 log10 IU/mL Standard Deviation 0.480	-2.97 log10 IU/mL Standard Deviation 0.216	-3.24 log10 IU/mL Standard Deviation 0.103	-3.60 log10 IU/mL Standard Deviation 0.204	-3.53 log10 IU/mL Standard Deviation 0.624	-2.58 log10 IU/mL Standard Deviation 1.292	0.02 log10 IU/mL Standard Deviation 0.246
Change From Baseline at 24 h Post Dose on Day 1 in log10 Hepatitis C Virus (HCV) RNA of Participants Without Baseline Drug Resistance Change at Hour 8	-1.92 log10 IU/mL Standard Deviation 0.516	-2.12 log10 IU/mL Standard Deviation 0.216	-2.62 log10 IU/mL Standard Deviation 0.195	-2.47 log10 IU/mL Standard Deviation 0.733	-2.59 log10 IU/mL Standard Deviation 0.509	-1.74 log10 IU/mL Standard Deviation 0.917	-0.01 log10 IU/mL Standard Deviation 0.251
Change From Baseline at 24 h Post Dose on Day 1 in log10 Hepatitis C Virus (HCV) RNA of Participants Without Baseline Drug Resistance Change at Hour 12	-2.18 log10 IU/mL Standard Deviation 0.439	-2.44 log10 IU/mL Standard Deviation 0.092	-2.91 log10 IU/mL Standard Deviation 0.083	-3.08 log10 IU/mL Standard Deviation 0.562	-2.92 log10 IU/mL Standard Deviation 0.511	-2.00 log10 IU/mL Standard Deviation 1.158	-0.01 log10 IU/mL Standard Deviation 0.284
Change From Baseline at 24 h Post Dose on Day 1 in log10 Hepatitis C Virus (HCV) RNA of Participants Without Baseline Drug Resistance Change at Hour 16	-2.09 log10 IU/mL Standard Deviation 0.420	-2.76 log10 IU/mL Standard Deviation 0.183	-2.95 log10 IU/mL Standard Deviation 0.250	-3.38 log10 IU/mL Standard Deviation 0.521	-3.04 log10 IU/mL Standard Deviation 0.535	-2.03 log10 IU/mL Standard Deviation 1.009	-0.00 log10 IU/mL Standard Deviation 0.246

SECONDARY outcome

Timeframe: Baseline to Day 4

Population: All randomized participants who took at least 1 dose of study medication and did not have baseline genotypic drug resistance mutations.

The Roche TaqMan HCV quantitative assay was used for analysis with detection limit of 10 IU/mL. Baseline was Day -1.

Outcome measures

Outcome measures
Measure	Daclatasvir (1 mg) QD n=4 Participants Participants received QD dose of daclatasvir 1 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (10 mg) QD n=4 Participants Participants received QD dose of daclatasvir 10 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (30 mg) QD n=4 Participants Participants received QD dose of daclatasvir 30 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (60 mg) QD n=3 Participants Participants received QD dose of daclatasvir 60 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (30 mg) BID n=3 Participants Participants received BID dose of daclatasvir 30 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (100 mg) QD n=3 Participants Participants received QD dose of daclatasvir 100 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Placebo n=6 Participants Participants received QD/BID dose of placebo matched to daclatasvir during 14 day treatment period. Participants who received placebo were discharged after Day 28 and after unblinding of the dose panel.
Change From Baseline to Day 4 in log10 Hepatitis C Virus (HCV) RNA in Participants Without Baseline Drug Resistance	-2.16 log10 IU/mL Interval -2.68 to -1.64	-3.29 log10 IU/mL Interval -3.81 to -2.77	-3.04 log10 IU/mL Interval -3.56 to -2.52	-3.85 log10 IU/mL Interval -4.45 to -3.25	-3.82 log10 IU/mL Interval -4.42 to -3.22	-3.14 log10 IU/mL Interval -3.74 to -2.54	-0.07 log10 IU/mL Interval -0.49 to 0.36

SECONDARY outcome

Timeframe: Baseline to Day 14

Population: All randomized participants who took at least 1 dose of study medication and did not have baseline genotypic drug resistance mutations.

The Roche TaqMan HCV quantitative assay was used for analysis with detection limit of 10 IU/mL. Baseline was Day -1.

Outcome measures

Outcome measures
Measure	Daclatasvir (1 mg) QD n=4 Participants Participants received QD dose of daclatasvir 1 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (10 mg) QD n=4 Participants Participants received QD dose of daclatasvir 10 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (30 mg) QD n=4 Participants Participants received QD dose of daclatasvir 30 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (60 mg) QD n=3 Participants Participants received QD dose of daclatasvir 60 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (30 mg) BID n=3 Participants Participants received BID dose of daclatasvir 30 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (100 mg) QD n=3 Participants Participants received QD dose of daclatasvir 100 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Placebo n=6 Participants Participants received QD/BID dose of placebo matched to daclatasvir during 14 day treatment period. Participants who received placebo were discharged after Day 28 and after unblinding of the dose panel.
Change From Baseline to Day 14 in Log10 Hepatitis C Virus (HCV) RNA in Participants Without Baseline Drug Resistance	-1.89 log10 IU/mL Interval -3.38 to -0.39	-2.32 log10 IU/mL Interval -3.81 to -0.82	-1.68 log10 IU/mL Interval -3.17 to -0.18	-1.34 log10 IU/mL Interval -3.07 to 0.39	-3.55 log10 IU/mL Interval -5.27 to -1.82	-1.35 log10 IU/mL Interval -3.07 to 0.38	-0.59 log10 IU/mL Interval -1.81 to 0.63

SECONDARY outcome

Timeframe: Day 1 up to Day 14

Population: All randomized participants who took at least 1 dose of study medication and did not have baseline genotypic drug resistance mutations.

Participants without baseline drug resistance were assessed for time to reach maximum decrease in log10 HCV RNA level.

Outcome measures

Outcome measures
Measure	Daclatasvir (1 mg) QD n=4 Participants Participants received QD dose of daclatasvir 1 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (10 mg) QD n=4 Participants Participants received QD dose of daclatasvir 10 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (30 mg) QD n=4 Participants Participants received QD dose of daclatasvir 30 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (60 mg) QD n=3 Participants Participants received QD dose of daclatasvir 60 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (30 mg) BID n=3 Participants Participants received BID dose of daclatasvir 30 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (100 mg) QD n=3 Participants Participants received QD dose of daclatasvir 100 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Placebo n=6 Participants Participants received QD/BID dose of placebo matched to daclatasvir during 14 day treatment period. Participants who received placebo were discharged after Day 28 and after unblinding of the dose panel.
Time to Maximum Decline From Baseline in Hepatitis C Virus (HCV) RNA in Participants Without Baseline Drug Resistance	4.50 Days Standard Deviation 4.726	5.25 Days Standard Deviation 2.363	3.50 Days Standard Deviation 2.380	3.33 Days Standard Deviation 1.528	10.33 Days Standard Deviation 6.028	7.67 Days Standard Deviation 6.429	10.17 Days Standard Deviation 6.524

SECONDARY outcome

Timeframe: Day 1 up to Day 14

Population: All randomized participants who took at least 1 dose of study medication and did not have baseline genotypic drug resistance mutations.

The Roche TaqMan HCV quantitative assay was used for analysis with detection limit of 10 IU/mL.

Outcome measures

Outcome measures
Measure	Daclatasvir (1 mg) QD n=4 Participants Participants received QD dose of daclatasvir 1 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (10 mg) QD n=4 Participants Participants received QD dose of daclatasvir 10 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (30 mg) QD n=4 Participants Participants received QD dose of daclatasvir 30 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (60 mg) QD n=3 Participants Participants received QD dose of daclatasvir 60 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (30 mg) BID n=3 Participants Participants received BID dose of daclatasvir 30 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (100 mg) QD n=3 Participants Participants received QD dose of daclatasvir 100 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Placebo n=6 Participants Participants received QD/BID dose of placebo matched to daclatasvir during 14 day treatment period. Participants who received placebo were discharged after Day 28 and after unblinding of the dose panel.
Maximum Decline From Baseline in Log10 Hepatitis C Virus (HCV) RNA in Participants Without Baseline Drug Resistance	-2.81 log10 IU/mL Standard Deviation 0.700	-3.63 log10 IU/mL Standard Deviation 0.776	-3.31 log10 IU/mL Standard Deviation 0.050	-4.03 log10 IU/mL Standard Deviation 0.626	-4.88 log10 IU/mL Standard Deviation 1.335	-3.62 log10 IU/mL Standard Deviation 0.170	-1.32 log10 IU/mL Standard Deviation 1.629

SECONDARY outcome

Timeframe: 0 hour (pre-dose) 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hours (post morning dose) at Day1 and Day 14, 0 hour (pre-dose) at Days 2, 3, 4, 5, 7, 9, 11, 13 and 24, 48 and 72 hours (post morning dose) at Day 14

Population: All participants who received at least 1 dose of study medication and with available Pharmacokinetic (PK) data were summarized.

The peak concentrations in plasma (Cmax) and minimum observed plasma concentration (Cmin) were defined as the peak maximum and minimum plasma level of daclatasvir, derived from plasma concentration-time data analyzed by non-compartmental methods. Cmax and Cmin of daclatasvir in plasma was assayed using a validated liquid chromatography tandem mass spectrometry method.

Outcome measures

Outcome measures
Measure	Daclatasvir (1 mg) QD n=4 Participants Participants received QD dose of daclatasvir 1 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (10 mg) QD n=4 Participants Participants received QD dose of daclatasvir 10 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (30 mg) QD n=4 Participants Participants received QD dose of daclatasvir 30 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (60 mg) QD n=4 Participants Participants received QD dose of daclatasvir 60 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (30 mg) BID n=4 Participants Participants received BID dose of daclatasvir 30 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (100 mg) QD n=4 Participants Participants received QD dose of daclatasvir 100 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Placebo Participants received QD/BID dose of placebo matched to daclatasvir during 14 day treatment period. Participants who received placebo were discharged after Day 28 and after unblinding of the dose panel.
Maximum Observed Plasma Concentration (Cmax) and Minimum Observed Plasma Concentration (Cmin) of Daclatasvir on Days 1 and 14 Cmin at Day 14	1.234 nanograms/milliliters(ng/mL) Geometric Coefficient of Variation 95	23.674 nanograms/milliliters(ng/mL) Geometric Coefficient of Variation 53	61.635 nanograms/milliliters(ng/mL) Geometric Coefficient of Variation 42	254.602 nanograms/milliliters(ng/mL) Geometric Coefficient of Variation 42	206.941 nanograms/milliliters(ng/mL) Geometric Coefficient of Variation 74	287.852 nanograms/milliliters(ng/mL) Geometric Coefficient of Variation 37	—
Maximum Observed Plasma Concentration (Cmax) and Minimum Observed Plasma Concentration (Cmin) of Daclatasvir on Days 1 and 14 Cmax at Day 14	10.430 nanograms/milliliters(ng/mL) Geometric Coefficient of Variation 76	154.196 nanograms/milliliters(ng/mL) Geometric Coefficient of Variation 49	555.878 nanograms/milliliters(ng/mL) Geometric Coefficient of Variation 38	1726.383 nanograms/milliliters(ng/mL) Geometric Coefficient of Variation 21	831.792 nanograms/milliliters(ng/mL) Geometric Coefficient of Variation 37	1853.925 nanograms/milliliters(ng/mL) Geometric Coefficient of Variation 26	—
Maximum Observed Plasma Concentration (Cmax) and Minimum Observed Plasma Concentration (Cmin) of Daclatasvir on Days 1 and 14 Cmin at Day 1	1.212 nanograms/milliliters(ng/mL) Geometric Coefficient of Variation 105	15.141 nanograms/milliliters(ng/mL) Geometric Coefficient of Variation 49	41.114 nanograms/milliliters(ng/mL) Geometric Coefficient of Variation 34	129.822 nanograms/milliliters(ng/mL) Geometric Coefficient of Variation 25	171.330 nanograms/milliliters(ng/mL) Geometric Coefficient of Variation 53	174.642 nanograms/milliliters(ng/mL) Geometric Coefficient of Variation 21	—
Maximum Observed Plasma Concentration (Cmax) and Minimum Observed Plasma Concentration (Cmin) of Daclatasvir on Days 1 and 14 Cmax at Day 1	15.731 nanograms/milliliters(ng/mL) Geometric Coefficient of Variation 48	159.665 nanograms/milliliters(ng/mL) Geometric Coefficient of Variation 41	483.365 nanograms/milliliters(ng/mL) Geometric Coefficient of Variation 25	1409.202 nanograms/milliliters(ng/mL) Geometric Coefficient of Variation 13	563.569 nanograms/milliliters(ng/mL) Geometric Coefficient of Variation 26	1960.732 nanograms/milliliters(ng/mL) Geometric Coefficient of Variation 21	—

SECONDARY outcome

Timeframe: 0 hour (pre-dose) 0.5, 1,1.5, 2, 3, 4, 6, 8 and 12 hours (post morning dose) at Day1 and Day 14, 0 hr (pre-dose) at Days 2, 3, 4, 5, 7, 9, 11, 13, and 24, 48 and 72 hours (post morning dose) at Day 14

Population: All participants who received at least 1 dose of study medication and with available PK data were summarized.

The area under the concentration-time curve in 1 Dosing Interval AUC(TAU) was used to measure the drug exposure over 1 dosing interval., derived from plasma concentration-time data analyzed by non-compartmental methods. AUC(TAU) of daclatasvir in plasma was assayed using a validated liquid chromatography tandem mass spectrometry method.

Outcome measures

Outcome measures
Measure	Daclatasvir (1 mg) QD n=4 Participants Participants received QD dose of daclatasvir 1 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (10 mg) QD n=4 Participants Participants received QD dose of daclatasvir 10 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (30 mg) QD n=4 Participants Participants received QD dose of daclatasvir 30 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (60 mg) QD n=4 Participants Participants received QD dose of daclatasvir 60 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (30 mg) BID n=4 Participants Participants received BID dose of daclatasvir 30 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (100 mg) QD n=4 Participants Participants received QD dose of daclatasvir 100 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Placebo Participants received QD/BID dose of placebo matched to daclatasvir during 14 day treatment period. Participants who received placebo were discharged after Day 28 and after unblinding of the dose panel.
Area Under the Concentration-time Curve (AUC) in 1 Dosing Interval of Daclatasvir at Days 1 and 14 Day 14	92.0 ng*h/mL Geometric Coefficient of Variation 80	1332.1 ng*h/mL Geometric Coefficient of Variation 46	4391.3 ng*h/mL Geometric Coefficient of Variation 27	15120.9 ng*h/mL Geometric Coefficient of Variation 35	5431.6 ng*h/mL Geometric Coefficient of Variation 35	17592.8 ng*h/mL Geometric Coefficient of Variation 15	—
Area Under the Concentration-time Curve (AUC) in 1 Dosing Interval of Daclatasvir at Days 1 and 14 Day 1	111.8 ng*h/mL Geometric Coefficient of Variation 54	1113.6 ng*h/mL Geometric Coefficient of Variation 38	3528.6 ng*h/mL Geometric Coefficient of Variation 19	10691.5 ng*h/mL Geometric Coefficient of Variation 20	3307.2 ng*h/mL Geometric Coefficient of Variation 36	15136.1 ng*h/mL Geometric Coefficient of Variation 19	—

SECONDARY outcome

Population: All participants who received at least 1 dose of study medication and with available PK data were summarized.

The absolute values of lamda (λ) were used to evaluate apparent terminal half-life (T-half) was defined as T-half= ln 2/λ. T-half was derived from plasma concentration-time data analyzed by non-compartmental methods. T-half of daclatasvir in plasma was assayed using a validated liquid chromatography tandem mass spectrometry method.

Outcome measures

Outcome measures
Measure	Daclatasvir (1 mg) QD n=4 Participants Participants received QD dose of daclatasvir 1 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (10 mg) QD n=4 Participants Participants received QD dose of daclatasvir 10 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (30 mg) QD n=4 Participants Participants received QD dose of daclatasvir 30 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (60 mg) QD n=4 Participants Participants received QD dose of daclatasvir 60 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (30 mg) BID n=4 Participants Participants received BID dose of daclatasvir 30 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (100 mg) QD n=4 Participants Participants received QD dose of daclatasvir 100 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Placebo Participants received QD/BID dose of placebo matched to daclatasvir during 14 day treatment period. Participants who received placebo were discharged after Day 28 and after unblinding of the dose panel.
Plasma Half-life (T-half) of Daclatasvir at Day 14	11.68 h Standard Deviation 2.214	14.31 h Standard Deviation 3.848	12.99 h Standard Deviation 2.039	12.81 h Standard Deviation 1.233	13.04 h Standard Deviation 3.654	15.19 h Standard Deviation 3.411	—

SECONDARY outcome

Timeframe: 0 hour (pre-dose) 0.5, 1,1.5, 2, 3, 4, 6, 8 and 12 hours (post morning dose) at Day1 and Day 14, 0 hour (pre-dose) at Days 2, 3, 4, 5, 7, 9, 11, 13, and 24, 48 and 72 hours (post morning dose) at Day 14

Population: All participants who received at least 1 dose of study medication and with available PK data were summarized.

The apparent total body clearance at steady state (CLT/F) was defined as the apparent body clearance of canakinumab from the serum when the systemic availability was unknown. CLT/F was derived from plasma concentration-time data analyzed by non-compartmental methods. CLT/F of daclatasvir in plasma was assayed using a validated liquid chromatography tandem mass spectrometry method.

Outcome measures

Outcome measures
Measure	Daclatasvir (1 mg) QD n=4 Participants Participants received QD dose of daclatasvir 1 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (10 mg) QD n=4 Participants Participants received QD dose of daclatasvir 10 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (30 mg) QD n=4 Participants Participants received QD dose of daclatasvir 30 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (60 mg) QD n=4 Participants Participants received QD dose of daclatasvir 60 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (30 mg) BID n=4 Participants Participants received BID dose of daclatasvir 30 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (100 mg) QD n=4 Participants Participants received QD dose of daclatasvir 100 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Placebo Participants received QD/BID dose of placebo matched to daclatasvir during 14 day treatment period. Participants who received placebo were discharged after Day 28 and after unblinding of the dose panel.
Apparent Total Body Clearance (CLT/F) of Daclatasvir on Day 14	181.118 mL/min Geometric Coefficient of Variation 52	125.119 mL/min Geometric Coefficient of Variation 52	113.861 mL/min Geometric Coefficient of Variation 25	66.133 mL/min Geometric Coefficient of Variation 29	92.054 mL/min Geometric Coefficient of Variation 35	94.736 mL/min Geometric Coefficient of Variation 15	—

SECONDARY outcome

Timeframe: 0 hour (pre-dose) 0.5, 1,1.5, 2, 3, 4, 6, 8 and 12 hours (post morning dose) at Day1 and Day 14, 0 hr (pre-dose) at Days 2, 3, 4, 5, 7, 9, 11,13, and 24, 48 and 72 hours (post morning dose) at Day 14

Population: All participants who received at least 1 dose of study medication and with available PK data were summarized.

The average observed plasma concentration at steady state (Css-av) was calculated as ratio of AUC(TAU) by TAU, where TAU = 24 h for QD dosing and 12 h for BID dosing. Css-av was derived from plasma concentration-time data analyzed by non-compartmental methods. Css-av of daclatasvir in plasma was assayed using a validated liquid chromatography tandem mass spectrometry method.

Outcome measures

Outcome measures
Measure	Daclatasvir (1 mg) QD n=4 Participants Participants received QD dose of daclatasvir 1 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (10 mg) QD n=4 Participants Participants received QD dose of daclatasvir 10 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (30 mg) QD n=4 Participants Participants received QD dose of daclatasvir 30 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (60 mg) QD n=4 Participants Participants received QD dose of daclatasvir 60 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (30 mg) BID n=4 Participants Participants received BID dose of daclatasvir 30 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (100 mg) QD n=4 Participants Participants received QD dose of daclatasvir 100 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Placebo Participants received QD/BID dose of placebo matched to daclatasvir during 14 day treatment period. Participants who received placebo were discharged after Day 28 and after unblinding of the dose panel.
Average Observed Plasma Concentration (Css-av) at Steady State of Daclatasvir at Days 1 and 14 Day 1	4.659 ng/mL Geometric Coefficient of Variation 54	46.401 ng/mL Geometric Coefficient of Variation 38	147.024 ng/mL Geometric Coefficient of Variation 19	445.478 ng/mL Geometric Coefficient of Variation 20	275.596 ng/mL Geometric Coefficient of Variation 36	630.673 ng/mL Geometric Coefficient of Variation 19	—
Average Observed Plasma Concentration (Css-av) at Steady State of Daclatasvir at Days 1 and 14 Day 14	3.834 ng/mL Geometric Coefficient of Variation 80	55.503 ng/mL Geometric Coefficient of Variation 46	182.972 ng/mL Geometric Coefficient of Variation 27	630.039 ng/mL Geometric Coefficient of Variation 35	452.634 ng/mL Geometric Coefficient of Variation 35	733.035 ng/mL Geometric Coefficient of Variation 15	—

SECONDARY outcome

Population: All participants who received at least 1 dose of study medication and with available PK data were summarized.

Accumulation index area under the concentration-time curve of daclatasvir to the end of the dosing period \[AI AUC(TAU)\] was defined as the ratio of AUC(TAU) at steady-state to AUC(TAU) after the first dose.Accumulation index maximum observed concentration of daclatasvir in plasma (AI Cmax) was defined as the ratio of Cmax at steady-state to Cmax after the first dose. Degree of Fluctuation (DF) was defined as the ratio of difference between Cmax and Cmin at steady state by Css-av. The parameters were analyzed using non-compartmental methods, assayed by validated liquid chromatography tandem mass spectrometry (LC-MS/MS).

Outcome measures

Outcome measures
Measure	Daclatasvir (1 mg) QD n=4 Participants Participants received QD dose of daclatasvir 1 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (10 mg) QD n=4 Participants Participants received QD dose of daclatasvir 10 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (30 mg) QD n=4 Participants Participants received QD dose of daclatasvir 30 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (60 mg) QD n=4 Participants Participants received QD dose of daclatasvir 60 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (30 mg) BID n=4 Participants Participants received BID dose of daclatasvir 30 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (100 mg) QD n=4 Participants Participants received QD dose of daclatasvir 100 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Placebo Participants received QD/BID dose of placebo matched to daclatasvir during 14 day treatment period. Participants who received placebo were discharged after Day 28 and after unblinding of the dose panel.
Accumulation Index (AI) AUC(TAU), AI Cmax, and Degree of Fluctuation (DF) of Daclatasvir on Day 14 AI Cmax	0.663 ratio Geometric Coefficient of Variation 57	0.966 ratio Geometric Coefficient of Variation 26	1.150 ratio Geometric Coefficient of Variation 28	1.225 ratio Geometric Coefficient of Variation 10	1.476 ratio Geometric Coefficient of Variation 32	0.946 ratio Geometric Coefficient of Variation 42	—
Accumulation Index (AI) AUC(TAU), AI Cmax, and Degree of Fluctuation (DF) of Daclatasvir on Day 14 Degree of Fluctuation	2.389 ratio Geometric Coefficient of Variation 13	2.335 ratio Geometric Coefficient of Variation 18	2.659 ratio Geometric Coefficient of Variation 25	2.321 ratio Geometric Coefficient of Variation 24	1.251 ratio Geometric Coefficient of Variation 18	2.133 ratio Geometric Coefficient of Variation 12	—
Accumulation Index (AI) AUC(TAU), AI Cmax, and Degree of Fluctuation (DF) of Daclatasvir on Day 14 AI AUC(TAU)	0.823 ratio Geometric Coefficient of Variation 29	1.196 ratio Geometric Coefficient of Variation 16	1.245 ratio Geometric Coefficient of Variation 20	1.414 ratio Geometric Coefficient of Variation 17	1.642 ratio Geometric Coefficient of Variation 16	1.162 ratio Geometric Coefficient of Variation 25	—

SECONDARY outcome

Population: All participants who received at least 1 dose of study medication and with available PK data were summarized.

Tmax was defined as the time to reach maximum observed plasma concentration of daclatasvir in plasma. Tmax was derived from plasma concentration-time data analyzed by non-compartmental methods. Tmax of daclatasvir in plasma was assayed using a validated liquid chromatography tandem mass spectrometry method.

Outcome measures

Outcome measures
Measure	Daclatasvir (1 mg) QD n=4 Participants Participants received QD dose of daclatasvir 1 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (10 mg) QD n=4 Participants Participants received QD dose of daclatasvir 10 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (30 mg) QD n=4 Participants Participants received QD dose of daclatasvir 30 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (60 mg) QD n=4 Participants Participants received QD dose of daclatasvir 60 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (30 mg) BID n=4 Participants Participants received BID dose of daclatasvir 30 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (100 mg) QD n=4 Participants Participants received QD dose of daclatasvir 100 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Placebo Participants received QD/BID dose of placebo matched to daclatasvir during 14 day treatment period. Participants who received placebo were discharged after Day 28 and after unblinding of the dose panel.
Time of Maximum Observed Plasma Concentration (Tmax) of Daclatasvir on Days 1 and 14 Day 1	2.000 h Interval 1.0 to 3.0	1.000 h Interval 1.0 to 2.0	1.000 h Interval 0.5 to 1.0	1.500 h Interval 1.5 to 3.0	2.500 h Interval 1.5 to 3.0	1.500 h Interval 1.0 to 1.5	—
Time of Maximum Observed Plasma Concentration (Tmax) of Daclatasvir on Days 1 and 14 Day 14	1.250 h Interval 1.0 to 2.0	1.250 h Interval 1.0 to 1.5	1.000 h Interval 1.0 to 1.5	1.000 h Interval 1.0 to 2.0	1.750 h Interval 1.0 to 2.0	1.750 h Interval 1.0 to 2.0	—

SECONDARY outcome

Timeframe: Day 4, Day 14

Population: All participants who received at least 1 dose of daclatasvir and who had no baseline genotype resistance were analyzed. Placebo participants were excluded from this analysis.

Correlation between decline of log10 hepatitis C virus (HCV) RNA and exposure to study drug was measured by Pearson Correlation Coefficients. The change from baseline at Day 4 in log10 HCV RNA and the maximum decline in log10 HCV RNA were evaluated against the PK parameters Cmax, Cmin and AUC(TAU).

Outcome measures

Outcome measures
Measure	Daclatasvir (1 mg) QD n=21 Participants Participants received QD dose of daclatasvir 1 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (10 mg) QD Participants received QD dose of daclatasvir 10 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (30 mg) QD Participants received QD dose of daclatasvir 30 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (60 mg) QD Participants received QD dose of daclatasvir 60 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (30 mg) BID Participants received BID dose of daclatasvir 30 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (100 mg) QD Participants received QD dose of daclatasvir 100 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Placebo Participants received QD/BID dose of placebo matched to daclatasvir during 14 day treatment period. Participants who received placebo were discharged after Day 28 and after unblinding of the dose panel.
Correlation Coefficients Between Measures of Decline in log10 Hepatitis C Virus (HCV) RNA and Daclatasvir PK Parameters Cmax, AUC(TAU), and Cmin on Day 14 in Participants Without Baseline Drug Resistance Cmax and Delta log10 HCV RNA at Day 4	-0.61 Correlation Coefficient	—	—	—	—	—	—
Correlation Coefficients Between Measures of Decline in log10 Hepatitis C Virus (HCV) RNA and Daclatasvir PK Parameters Cmax, AUC(TAU), and Cmin on Day 14 in Participants Without Baseline Drug Resistance AUC(Tau) and Delta log10 HCV RNA at Day 4	-0.61 Correlation Coefficient	—	—	—	—	—	—
Correlation Coefficients Between Measures of Decline in log10 Hepatitis C Virus (HCV) RNA and Daclatasvir PK Parameters Cmax, AUC(TAU), and Cmin on Day 14 in Participants Without Baseline Drug Resistance Cmin and Delta log10 HCV RNA at Day 4	-0.63 Correlation Coefficient	—	—	—	—	—	—
Correlation Coefficients Between Measures of Decline in log10 Hepatitis C Virus (HCV) RNA and Daclatasvir PK Parameters Cmax, AUC(TAU), and Cmin on Day 14 in Participants Without Baseline Drug Resistance Cmax and Maximum Decline in log10 HCV RNA	-0.51 Correlation Coefficient	—	—	—	—	—	—
Correlation Coefficients Between Measures of Decline in log10 Hepatitis C Virus (HCV) RNA and Daclatasvir PK Parameters Cmax, AUC(TAU), and Cmin on Day 14 in Participants Without Baseline Drug Resistance AUC(Tau) and Maximum Decline in log10 HCV RNA	-0.50 Correlation Coefficient	—	—	—	—	—	—
Correlation Coefficients Between Measures of Decline in log10 Hepatitis C Virus (HCV) RNA and Daclatasvir PK Parameters Cmax, AUC(TAU), and Cmin on Day 14 in Participants Without Baseline Drug Resistance Cmin and Maximum Decline in log10 HCV RNA	-0.59 Correlation Coefficient	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Day 1 to Day 182 or Day of Discharge

Population: All participants who received study drug were summarized.

AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization.

Outcome measures

Outcome measures
Measure	Daclatasvir (1 mg) QD n=4 Participants Participants received QD dose of daclatasvir 1 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (10 mg) QD n=4 Participants Participants received QD dose of daclatasvir 10 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (30 mg) QD n=4 Participants Participants received QD dose of daclatasvir 30 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (60 mg) QD n=4 Participants Participants received QD dose of daclatasvir 60 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (30 mg) BID n=4 Participants Participants received BID dose of daclatasvir 30 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (100 mg) QD n=4 Participants Participants received QD dose of daclatasvir 100 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Placebo n=6 Participants Participants received QD/BID dose of placebo matched to daclatasvir during 14 day treatment period. Participants who received placebo were discharged after Day 28 and after unblinding of the dose panel.
Number of Participants With Serious Adverse Events (SAEs), Discontinuation Due to Adverse Events (AEs), and Who Died Death	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants
Number of Participants With Serious Adverse Events (SAEs), Discontinuation Due to Adverse Events (AEs), and Who Died SAEs	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants
Number of Participants With Serious Adverse Events (SAEs), Discontinuation Due to Adverse Events (AEs), and Who Died Discontinuation Due to AEs	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants

SECONDARY outcome

Timeframe: Screening, Day 3, Day 7, Day 11, Day 14, and Day 28

Population: All participants treated with study drug were summarized.

Hematology marked laboratory abnormalities were defined as Hemoglobin (g/dL) Low as \< 0.85\*Pre-therapy (PreRx), Hematocrit (%) Low as \< 0.85\*PreRx, Platelet Count \*10\^9 c/L Low as \< 0.85\*Lower Limits of Normal (LLN) if PreRx = Missing/\< 0.85\*LLN if PreRx \>= LLN/\< 0.85\*PreRx if PreRx \< LLN, Eosinophils (absolute) \*10\^3 c/µL High as \> 0.75\*count, Leukocytes White Blood Cell (WBC) \*10\^3 c/µL High as \> 1.2\*ULN if LLN \<= PreRx \<= Upper Limits of Normal (ULN) \> 1.2\*ULN if PreRx = Missing/\> 1.5\*PreRx if PreRx \> ULN/\> ULN if PreRx \< LLN.

Outcome measures

Outcome measures
Measure	Daclatasvir (1 mg) QD n=4 Participants Participants received QD dose of daclatasvir 1 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (10 mg) QD n=4 Participants Participants received QD dose of daclatasvir 10 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (30 mg) QD n=4 Participants Participants received QD dose of daclatasvir 30 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (60 mg) QD n=4 Participants Participants received QD dose of daclatasvir 60 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (30 mg) BID n=4 Participants Participants received BID dose of daclatasvir 30 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (100 mg) QD n=4 Participants Participants received QD dose of daclatasvir 100 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Placebo n=6 Participants Participants received QD/BID dose of placebo matched to daclatasvir during 14 day treatment period. Participants who received placebo were discharged after Day 28 and after unblinding of the dose panel.
Number of Participants With Marked Laboratory Abnormalities in Hematology Low Hematocrit	0 participants	0 participants	0 participants	1 participants	0 participants	0 participants	0 participants
Number of Participants With Marked Laboratory Abnormalities in Hematology Low Hemoglobin	1 participants	0 participants	0 participants	1 participants	0 participants	0 participants	1 participants
Number of Participants With Marked Laboratory Abnormalities in Hematology High Leukocytes	0 participants	0 participants	0 participants	0 participants	0 participants	1 participants	0 participants
Number of Participants With Marked Laboratory Abnormalities in Hematology Low Platelet	0 participants	0 participants	0 participants	0 participants	0 participants	1 participants	0 participants
Number of Participants With Marked Laboratory Abnormalities in Hematology High Eosinophils	0 participants	0 participants	0 participants	0 participants	0 participants	1 participants	0 participants

SECONDARY outcome

Timeframe: Screening, Day 3, Day 7, Day 11, Day 14, and Day 28

Population: All participants who were treated with study drug were summarized.

Liver and kidney function marked laboratory abnormalities were defined as Alanine Aminotransferase (ALT) units per liter (U/L) High as \> 1.25\*PreRx if PreRx \> ULN/\> 1.25\*ULN if PreRx \<= ULN/\> 1.25\*ULN if PreRx = Missing, Aspartate Aminotransferase (AST) U/L High as \> 1.25\* PreRx if PreRx \> ULN/\> 1.25\*ULN if PreRx \<= ULN/\> 1.25\*ULN if PreRx = Missing, Alkaline Phosphatase(ALP)U/L High as \> 1.25\*PreRx if PreRx \> ULN/\> 1.25\*ULN if PreRx \<= ULN/\> 1.25\*ULN if PreRx = Missing, G-Glutamyl Transferase (GGT) in U/L High as \>1.15\*ULN if PreRx\<=ULN/\>1.15\* if PreRx missing/\>1.2\* PreRx if PreRx\>ULN, Phosphorus Inorganic (mg/dL) Low as \< 0.85\*LLN if LLN \<= PreRx \<= ULN/\< 0.85\*LLN if PreRx = Missing/\< 0.85\*PreRx if PreRx \< LLN/\< LLN if PreRx \> ULN, and Potassium serum milliequivalents per liter (mEq/L) High as \> 1.1\*PreRx if PreRx \> ULN/\> 1.1\*ULN if LLN \<= PreRx \<= ULN/\> 1.1\*ULN if PreRx = Missing/\> ULN if PreRx \< LLN.

Outcome measures

Outcome measures
Measure	Daclatasvir (1 mg) QD n=4 Participants Participants received QD dose of daclatasvir 1 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (10 mg) QD n=4 Participants Participants received QD dose of daclatasvir 10 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (30 mg) QD n=4 Participants Participants received QD dose of daclatasvir 30 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (60 mg) QD n=4 Participants Participants received QD dose of daclatasvir 60 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (30 mg) BID n=4 Participants Participants received BID dose of daclatasvir 30 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (100 mg) QD n=4 Participants Participants received QD dose of daclatasvir 100 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Placebo n=6 Participants Participants received QD/BID dose of placebo matched to daclatasvir during 14 day treatment period. Participants who received placebo were discharged after Day 28 and after unblinding of the dose panel.
Number of Participants With Marked Abnormalities in Liver and Kidney Function Laboratory Tests and Electrolytes ALT High	0 participants	1 participants	0 participants	1 participants	2 participants	2 participants	0 participants
Number of Participants With Marked Abnormalities in Liver and Kidney Function Laboratory Tests and Electrolytes AST High	0 participants	1 participants	0 participants	0 participants	2 participants	2 participants	1 participants
Number of Participants With Marked Abnormalities in Liver and Kidney Function Laboratory Tests and Electrolytes ALP High	0 participants	0 participants	0 participants	0 participants	0 participants	1 participants	0 participants
Number of Participants With Marked Abnormalities in Liver and Kidney Function Laboratory Tests and Electrolytes Phosporus Low	1 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants
Number of Participants With Marked Abnormalities in Liver and Kidney Function Laboratory Tests and Electrolytes GGT	0 participants	0 participants	2 participants	0 participants	2 participants	1 participants	2 participants
Number of Participants With Marked Abnormalities in Liver and Kidney Function Laboratory Tests and Electrolytes Potassium High	0 participants	0 participants	1 participants	0 participants	0 participants	0 participants	1 participants

SECONDARY outcome

Timeframe: Screening, Day 3, Day 7, Day 11, Day 14, and Day 28

Population: All participants treated with study drug were summarized.

Marked abnormalities were defined as Lipase (U/L) High as \>1.5\*ULN, Glucose fasting serum (mg/dL) High as \> 1.3\*ULN if LLN \<= PreRx \<= ULN/\> 1.3\*ULN if PreRx = Missing/\>2\*PreRx; if PreRx \> ULN/\> ULN if PreRx \< LLN.

Outcome measures

Outcome measures
Measure	Daclatasvir (1 mg) QD n=4 Participants Participants received QD dose of daclatasvir 1 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (10 mg) QD n=4 Participants Participants received QD dose of daclatasvir 10 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (30 mg) QD n=4 Participants Participants received QD dose of daclatasvir 30 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (60 mg) QD n=4 Participants Participants received QD dose of daclatasvir 60 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (30 mg) BID n=4 Participants Participants received BID dose of daclatasvir 30 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (100 mg) QD n=4 Participants Participants received QD dose of daclatasvir 100 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Placebo n=6 Participants Participants received QD/BID dose of placebo matched to daclatasvir during 14 day treatment period. Participants who received placebo were discharged after Day 28 and after unblinding of the dose panel.
Number of Participants With Marked Laboratory Abnormalities in Lipase and Glucose Lipase High	0 participants	1 participants	0 participants	0 participants	1 participants	0 participants	0 participants
Number of Participants With Marked Laboratory Abnormalities in Lipase and Glucose Glucose Fasting High	0 participants	0 participants	0 participants	0 participants	0 participants	1 participants	1 participants

SECONDARY outcome

Timeframe: Screening, Day 3, Day 7, Day 11, Day 14, and Day 28

Population: All participants treated with study drug were summarized.

Marked laboratory abnormalities in urinalysis were defined as, Blood Urine High as \>= 2\*PreRx if PreRx \>= 1/\>= 2 if PreRx \< 1/\>= 2 if PreRx = Missing. Glucose Urine High as \>= 1 if PreRx \< 1/\>= 1 if PreRx = Missing/\>= 2\*PreRx if PreRx \>= 1.

Outcome measures

Outcome measures
Measure	Daclatasvir (1 mg) QD n=4 Participants Participants received QD dose of daclatasvir 1 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (10 mg) QD n=4 Participants Participants received QD dose of daclatasvir 10 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (30 mg) QD n=4 Participants Participants received QD dose of daclatasvir 30 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (60 mg) QD n=4 Participants Participants received QD dose of daclatasvir 60 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (30 mg) BID n=4 Participants Participants received BID dose of daclatasvir 30 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (100 mg) QD n=4 Participants Participants received QD dose of daclatasvir 100 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Placebo n=6 Participants Participants received QD/BID dose of placebo matched to daclatasvir during 14 day treatment period. Participants who received placebo were discharged after Day 28 and after unblinding of the dose panel.
Number of Participants With Marked Laboratory Abnormalities in Urinalysis Urine Blood High	1 participants	1 participants	0 participants	1 participants	0 participants	0 participants	1 participants
Number of Participants With Marked Laboratory Abnormalities in Urinalysis Urine Glucose High	1 participants	0 participants	0 participants	0 participants	0 participants	0 participants	2 participants

SECONDARY outcome

Timeframe: Screening, Day -1 and prior to morning dose on Day 1, 2, 14, and 28

Population: All participants treated with study drug were summarized.

Vital signs included: body temperature, respiratory rate, blood pressure (systolic and diastolic) and heart rate. Blood pressure and heart rate were measured after the participant had been supine, semi-supine, or seated quietly for at least 5 minutes. Baseline was defined as the last observation prior to dosing on Day 1.

Outcome measures

Outcome measures
Measure	Daclatasvir (1 mg) QD n=4 Participants Participants received QD dose of daclatasvir 1 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (10 mg) QD n=4 Participants Participants received QD dose of daclatasvir 10 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (30 mg) QD n=4 Participants Participants received QD dose of daclatasvir 30 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (60 mg) QD n=4 Participants Participants received QD dose of daclatasvir 60 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (30 mg) BID n=4 Participants Participants received BID dose of daclatasvir 30 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Daclatasvir (100 mg) QD n=4 Participants Participants received QD dose of daclatasvir 100 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	Placebo n=6 Participants Participants received QD/BID dose of placebo matched to daclatasvir during 14 day treatment period. Participants who received placebo were discharged after Day 28 and after unblinding of the dose panel.
Number of Participants With Clinically Relevant Change From Baseline in Vital Signs	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants

SECONDARY outcome

Timeframe: Screening, Day 2, 3, 5, 7, 9, 11, 13, 15, 21 and 28

Population: All participants treated with study drug were summarized.

Pre-specified criteria were defined as, Heart rate (HR) minimum as \<=50 bpm/change from baseline \<-20 bpm/maximum HR \>100 bpm, QT interval corrected using Fridericia's formula (QTcF) maximum as QTcF\<=450 msec/450 msec \<maximum QTcF and \<=480 msec/480 msec \<maximum QTcF \<= 500 msec/maximum QTcF\>500 msec, QRS interval as \<=120 msec/\>120 msec, and PR interval maximum as \<= 200 msec/\>200 msec.