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

Double-Blind, Placebo-Controlled, Multiple Ascending Dose Study to Evaluate the Antiviral Activity and Safety, Tolerability, and Pharmacokinetics of Daclatasvir in Subjects Infected With Hepatitis C Virus Genotype 1

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00663208

Enrollment

167

Registered

2008-04-22

Start date

2008-05-31

Completion date

2009-06-30

Last updated

2015-10-14

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Chronic Hepatitis C

Brief summary

The primary purpose of this study is to assess the change in Hepatitis C Virus RNA during dosing with daclatasvir and during the follow-up period in subjects with chronic hepatitis C infection

Interventions

DRUGDaclatasvir

Capsule, Oral, Approximately 182 days from initial dosing

DRUGPlacebo

Capsule, Oral, After 28 days from initial dosing and unblinding of the dose panel

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to 60 Years

Healthy volunteers

Inclusion criteria

* Chronically infected with Hepatitis C Virus (HCV) genotype 1 * Treatment naive or treatment non-responders or treatment intolerant; and not co-infected with HIV or Hepatitis B Virus * HCV RNA viral load of ≥10\*5 IU/mL * BMI 18 to 35kg/m²

Exclusion criteria

* Any significant acute or chronic medical illness which is not stable or is not controlled with medication and not consistent with Hepatitis C Virus infection * HIV and/or HBV positive * Major surgery within 4 weeks of study drug administration and any gastrointestinal surgery that could impact the absorption of study drug WOCBP will be enrolled as in-patient for 16 days

Design outcomes

Primary

Measure	Time frame	Description
Change From Baseline at Day 7 in log10 Hepatitis C Virus (HCV) RNA of All Participants	Baseline, Day 7	The Roche TaqMan HCV quantitative assay was used for analysis with detection limit of 10 IU/mL. Baseline was Day -1.

Secondary

Measure	Time frame	Description
Change From Baseline at 24 h Post Dose on Day 1 in log10 Hepatitis C Virus (HCV) RNA of Participants Without Baseline Drug Resistance	Baseline, 2, 4, 6, 8, 12, 16, 20, and 24 hours post dose on Day 1	The Roche TaqMan HCV quantitative assay was used for analysis with detection limit of 10 IU/mL. Baseline was Day -1.
Change From Baseline to Day 4 in log10 Hepatitis C Virus (HCV) RNA in Participants Without Baseline Drug Resistance	Baseline to Day 4	The Roche TaqMan HCV quantitative assay was used for analysis with detection limit of 10 IU/mL. Baseline was Day -1.
Change From Baseline to Day 14 in Log10 Hepatitis C Virus (HCV) RNA in Participants Without Baseline Drug Resistance	Baseline to Day 14	The Roche TaqMan HCV quantitative assay was used for analysis with detection limit of 10 IU/mL. Baseline was Day -1.
Time to Maximum Decline From Baseline in Hepatitis C Virus (HCV) RNA in Participants Without Baseline Drug Resistance	Day 1 up to Day 14	Participants without baseline drug resistance were assessed for time to reach maximum decrease in log10 HCV RNA level.
Maximum Decline From Baseline in Log10 Hepatitis C Virus (HCV) RNA in Participants Without Baseline Drug Resistance	Day 1 up to Day 14	The Roche TaqMan HCV quantitative assay was used for analysis with detection limit of 10 IU/mL.
Maximum Observed Plasma Concentration (Cmax) and Minimum Observed Plasma Concentration (Cmin) of Daclatasvir on Days 1 and 14	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	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.
Area Under the Concentration-time Curve (AUC) in 1 Dosing Interval of Daclatasvir at Days 1 and 14	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	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.
Plasma Half-life (T-half) of Daclatasvir at Day 14	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	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.
Apparent Total Body Clearance (CLT/F) of Daclatasvir on Day 14	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	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.
Average Observed Plasma Concentration (Css-av) at Steady State of Daclatasvir at Days 1 and 14	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	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.
Change From Baseline at Day 7 in log10 Hepatitis C Virus (HCV) RNA Levels of Participants Without Baseline Drug Resistance	Baseline, Day 7	The Roche TaqMan HCV quantitative assay was used for analysis with detection limit of 10 international units/ millilitre (IU/mL). Baseline was Day -1
Time of Maximum Observed Plasma Concentration (Tmax) of Daclatasvir on Days 1 and 14	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	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.
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	Day 4, Day 14	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).
Number of Participants With Serious Adverse Events (SAEs), Discontinuation Due to Adverse Events (AEs), and Who Died	Day 1 to Day 182 or Day of Discharge	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.
Number of Participants With Marked Laboratory Abnormalities in Hematology	Screening, Day 3, Day 7, Day 11, Day 14, and Day 28	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.
Number of Participants With Marked Abnormalities in Liver and Kidney Function Laboratory Tests and Electrolytes	Screening, Day 3, Day 7, Day 11, Day 14, and Day 28	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.
Number of Participants With Marked Laboratory Abnormalities in Lipase and Glucose	Screening, Day 3, Day 7, Day 11, Day 14, and Day 28	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.
Number of Participants With Marked Laboratory Abnormalities in Urinalysis	Screening, Day 3, Day 7, Day 11, Day 14, and Day 28	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.
Number of Participants With Clinically Relevant Change From Baseline in Vital Signs	Screening, Day -1 and prior to morning dose on Day 1, 2, 14, and 28	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.
Number of Participants Meeting Pre-Specified Criteria in Electrocardiogram Parameters	Screening, Day 2, 3, 5, 7, 9, 11, 13, 15, 21 and 28	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.
Accumulation Index (AI) AUC(TAU), AI Cmax, and Degree of Fluctuation (DF) of Daclatasvir on Day 14	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	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).

Countries

Puerto Rico, United States

Participant flow

Recruitment details

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.

Pre-assignment details

A total of 30 participants received study treatment.

Participants by arm

Arm	Count
Daclatasvir (1 mg) QD 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.	4
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.	4
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.	4
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.	4
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.	4
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.	4
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.	6
Total	30

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003	FG006
Follow-up Period	Lost to Follow-up	2	0	3	2	0
Follow-up Period	Other reason	1	0	0	0	1
Treatment Period	Lost to Follow-up	0	1	0	0	0

Baseline characteristics

Characteristic	Daclatasvir (10 mg) QD	Daclatasvir (1 mg) QD	Daclatasvir (30 mg) QD	Daclatasvir (60 mg) QD	Daclatasvir (30 mg) BID	Daclatasvir (100 mg) QD	Placebo	Total
Age, Continuous	46.5 years STANDARD_DEVIATION 13	39.5 years STANDARD_DEVIATION 9.95	47.5 years STANDARD_DEVIATION 3.7	39.5 years STANDARD_DEVIATION 7.55	44.8 years STANDARD_DEVIATION 6.4	44.3 years STANDARD_DEVIATION 6.9	48.0 years STANDARD_DEVIATION 4.2	44.5 years STANDARD_DEVIATION 7.65
Sex: Female, Male Female	1 Participants	1 Participants	0 Participants	1 Participants	0 Participants	1 Participants	1 Participants	5 Participants
Sex: Female, Male Male	3 Participants	3 Participants	4 Participants	3 Participants	4 Participants	3 Participants	5 Participants	25 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk	EG005 affected / at risk	EG006 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —	— / —	— / —	— / —	— / —
other Total, other adverse events	1 / 4	4 / 4	2 / 4	2 / 4	3 / 4	4 / 4	4 / 6
serious Total, serious adverse events	0 / 4	0 / 4	0 / 4	0 / 4	0 / 4	0 / 4	0 / 6

Outcome results

Primary

Change From Baseline at Day 7 in log10 Hepatitis C Virus (HCV) RNA of All Participants

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

Time frame: Baseline, Day 7

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

Arm	Measure	Value (MEAN)
Daclatasvir (1 mg) QD	Change From Baseline at Day 7 in log10 Hepatitis C Virus (HCV) RNA of All Participants	-2.13 log10 IU/mL
Daclatasvir (10 mg) QD	Change From Baseline at Day 7 in log10 Hepatitis C Virus (HCV) RNA of All Participants	-3.31 log10 IU/mL
Daclatasvir (30 mg) QD	Change From Baseline at Day 7 in log10 Hepatitis C Virus (HCV) RNA of All Participants	-2.91 log10 IU/mL
Daclatasvir (60 mg) QD	Change From Baseline at Day 7 in log10 Hepatitis C Virus (HCV) RNA of All Participants	-2.58 log10 IU/mL
Daclatasvir (30 mg) BID	Change From Baseline at Day 7 in log10 Hepatitis C Virus (HCV) RNA of All Participants	-3.03 log10 IU/mL
Daclatasvir (100 mg) QD	Change From Baseline at Day 7 in log10 Hepatitis C Virus (HCV) RNA of All Participants	-3.56 log10 IU/mL
Placebo	Change From Baseline at Day 7 in log10 Hepatitis C Virus (HCV) RNA of All Participants	0.00 log10 IU/mL

Secondary

Accumulation Index (AI) AUC(TAU), AI Cmax, and Degree of Fluctuation (DF) of Daclatasvir on Day 14

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).

Time frame: 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.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Daclatasvir (1 mg) QD	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
Daclatasvir (1 mg) QD	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
Daclatasvir (1 mg) QD	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
Daclatasvir (10 mg) QD	Accumulation Index (AI) AUC(TAU), AI Cmax, and Degree of Fluctuation (DF) of Daclatasvir on Day 14	AI Cmax	0.966 ratio	Geometric Coefficient of Variation 26
Daclatasvir (10 mg) QD	Accumulation Index (AI) AUC(TAU), AI Cmax, and Degree of Fluctuation (DF) of Daclatasvir on Day 14	AI AUC(TAU)	1.196 ratio	Geometric Coefficient of Variation 16
Daclatasvir (10 mg) QD	Accumulation Index (AI) AUC(TAU), AI Cmax, and Degree of Fluctuation (DF) of Daclatasvir on Day 14	Degree of Fluctuation	2.335 ratio	Geometric Coefficient of Variation 18
Daclatasvir (30 mg) QD	Accumulation Index (AI) AUC(TAU), AI Cmax, and Degree of Fluctuation (DF) of Daclatasvir on Day 14	AI Cmax	1.150 ratio	Geometric Coefficient of Variation 28
Daclatasvir (30 mg) QD	Accumulation Index (AI) AUC(TAU), AI Cmax, and Degree of Fluctuation (DF) of Daclatasvir on Day 14	AI AUC(TAU)	1.245 ratio	Geometric Coefficient of Variation 20
Daclatasvir (30 mg) QD	Accumulation Index (AI) AUC(TAU), AI Cmax, and Degree of Fluctuation (DF) of Daclatasvir on Day 14	Degree of Fluctuation	2.659 ratio	Geometric Coefficient of Variation 25
Daclatasvir (60 mg) QD	Accumulation Index (AI) AUC(TAU), AI Cmax, and Degree of Fluctuation (DF) of Daclatasvir on Day 14	AI Cmax	1.225 ratio	Geometric Coefficient of Variation 10
Daclatasvir (60 mg) QD	Accumulation Index (AI) AUC(TAU), AI Cmax, and Degree of Fluctuation (DF) of Daclatasvir on Day 14	AI AUC(TAU)	1.414 ratio	Geometric Coefficient of Variation 17
Daclatasvir (60 mg) QD	Accumulation Index (AI) AUC(TAU), AI Cmax, and Degree of Fluctuation (DF) of Daclatasvir on Day 14	Degree of Fluctuation	2.321 ratio	Geometric Coefficient of Variation 24
Daclatasvir (30 mg) BID	Accumulation Index (AI) AUC(TAU), AI Cmax, and Degree of Fluctuation (DF) of Daclatasvir on Day 14	AI Cmax	1.476 ratio	Geometric Coefficient of Variation 32
Daclatasvir (30 mg) BID	Accumulation Index (AI) AUC(TAU), AI Cmax, and Degree of Fluctuation (DF) of Daclatasvir on Day 14	AI AUC(TAU)	1.642 ratio	Geometric Coefficient of Variation 16
Daclatasvir (30 mg) BID	Accumulation Index (AI) AUC(TAU), AI Cmax, and Degree of Fluctuation (DF) of Daclatasvir on Day 14	Degree of Fluctuation	1.251 ratio	Geometric Coefficient of Variation 18
Daclatasvir (100 mg) QD	Accumulation Index (AI) AUC(TAU), AI Cmax, and Degree of Fluctuation (DF) of Daclatasvir on Day 14	AI AUC(TAU)	1.162 ratio	Geometric Coefficient of Variation 25
Daclatasvir (100 mg) QD	Accumulation Index (AI) AUC(TAU), AI Cmax, and Degree of Fluctuation (DF) of Daclatasvir on Day 14	Degree of Fluctuation	2.133 ratio	Geometric Coefficient of Variation 12
Daclatasvir (100 mg) QD	Accumulation Index (AI) AUC(TAU), AI Cmax, and Degree of Fluctuation (DF) of Daclatasvir on Day 14	AI Cmax	0.946 ratio	Geometric Coefficient of Variation 42

Secondary

Apparent Total Body Clearance (CLT/F) of Daclatasvir on Day 14

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.

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

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Daclatasvir (1 mg) QD	Apparent Total Body Clearance (CLT/F) of Daclatasvir on Day 14	181.118 mL/min	Geometric Coefficient of Variation 52
Daclatasvir (10 mg) QD	Apparent Total Body Clearance (CLT/F) of Daclatasvir on Day 14	125.119 mL/min	Geometric Coefficient of Variation 52
Daclatasvir (30 mg) QD	Apparent Total Body Clearance (CLT/F) of Daclatasvir on Day 14	113.861 mL/min	Geometric Coefficient of Variation 25
Daclatasvir (60 mg) QD	Apparent Total Body Clearance (CLT/F) of Daclatasvir on Day 14	66.133 mL/min	Geometric Coefficient of Variation 29
Daclatasvir (30 mg) BID	Apparent Total Body Clearance (CLT/F) of Daclatasvir on Day 14	92.054 mL/min	Geometric Coefficient of Variation 35
Daclatasvir (100 mg) QD	Apparent Total Body Clearance (CLT/F) of Daclatasvir on Day 14	94.736 mL/min	Geometric Coefficient of Variation 15

Secondary

Area Under the Concentration-time Curve (AUC) in 1 Dosing Interval of Daclatasvir at Days 1 and 14

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.

Time frame: 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.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Daclatasvir (1 mg) QD	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
Daclatasvir (1 mg) QD	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
Daclatasvir (10 mg) QD	Area Under the Concentration-time Curve (AUC) in 1 Dosing Interval of Daclatasvir at Days 1 and 14	Day 1	1113.6 ng*h/mL	Geometric Coefficient of Variation 38
Daclatasvir (10 mg) QD	Area Under the Concentration-time Curve (AUC) in 1 Dosing Interval of Daclatasvir at Days 1 and 14	Day 14	1332.1 ng*h/mL	Geometric Coefficient of Variation 46
Daclatasvir (30 mg) QD	Area Under the Concentration-time Curve (AUC) in 1 Dosing Interval of Daclatasvir at Days 1 and 14	Day 1	3528.6 ng*h/mL	Geometric Coefficient of Variation 19
Daclatasvir (30 mg) QD	Area Under the Concentration-time Curve (AUC) in 1 Dosing Interval of Daclatasvir at Days 1 and 14	Day 14	4391.3 ng*h/mL	Geometric Coefficient of Variation 27
Daclatasvir (60 mg) QD	Area Under the Concentration-time Curve (AUC) in 1 Dosing Interval of Daclatasvir at Days 1 and 14	Day 1	10691.5 ng*h/mL	Geometric Coefficient of Variation 20
Daclatasvir (60 mg) QD	Area Under the Concentration-time Curve (AUC) in 1 Dosing Interval of Daclatasvir at Days 1 and 14	Day 14	15120.9 ng*h/mL	Geometric Coefficient of Variation 35
Daclatasvir (30 mg) BID	Area Under the Concentration-time Curve (AUC) in 1 Dosing Interval of Daclatasvir at Days 1 and 14	Day 1	3307.2 ng*h/mL	Geometric Coefficient of Variation 36
Daclatasvir (30 mg) BID	Area Under the Concentration-time Curve (AUC) in 1 Dosing Interval of Daclatasvir at Days 1 and 14	Day 14	5431.6 ng*h/mL	Geometric Coefficient of Variation 35
Daclatasvir (100 mg) QD	Area Under the Concentration-time Curve (AUC) in 1 Dosing Interval of Daclatasvir at Days 1 and 14	Day 1	15136.1 ng*h/mL	Geometric Coefficient of Variation 19
Daclatasvir (100 mg) QD	Area Under the Concentration-time Curve (AUC) in 1 Dosing Interval of Daclatasvir at Days 1 and 14	Day 14	17592.8 ng*h/mL	Geometric Coefficient of Variation 15

Secondary

Average Observed Plasma Concentration (Css-av) at Steady State of Daclatasvir at Days 1 and 14

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.

Time frame: 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.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Daclatasvir (1 mg) QD	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
Daclatasvir (1 mg) QD	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
Daclatasvir (10 mg) QD	Average Observed Plasma Concentration (Css-av) at Steady State of Daclatasvir at Days 1 and 14	Day 1	46.401 ng/mL	Geometric Coefficient of Variation 38
Daclatasvir (10 mg) QD	Average Observed Plasma Concentration (Css-av) at Steady State of Daclatasvir at Days 1 and 14	Day 14	55.503 ng/mL	Geometric Coefficient of Variation 46
Daclatasvir (30 mg) QD	Average Observed Plasma Concentration (Css-av) at Steady State of Daclatasvir at Days 1 and 14	Day 1	147.024 ng/mL	Geometric Coefficient of Variation 19
Daclatasvir (30 mg) QD	Average Observed Plasma Concentration (Css-av) at Steady State of Daclatasvir at Days 1 and 14	Day 14	182.972 ng/mL	Geometric Coefficient of Variation 27
Daclatasvir (60 mg) QD	Average Observed Plasma Concentration (Css-av) at Steady State of Daclatasvir at Days 1 and 14	Day 1	445.478 ng/mL	Geometric Coefficient of Variation 20
Daclatasvir (60 mg) QD	Average Observed Plasma Concentration (Css-av) at Steady State of Daclatasvir at Days 1 and 14	Day 14	630.039 ng/mL	Geometric Coefficient of Variation 35
Daclatasvir (30 mg) BID	Average Observed Plasma Concentration (Css-av) at Steady State of Daclatasvir at Days 1 and 14	Day 1	275.596 ng/mL	Geometric Coefficient of Variation 36
Daclatasvir (30 mg) BID	Average Observed Plasma Concentration (Css-av) at Steady State of Daclatasvir at Days 1 and 14	Day 14	452.634 ng/mL	Geometric Coefficient of Variation 35
Daclatasvir (100 mg) QD	Average Observed Plasma Concentration (Css-av) at Steady State of Daclatasvir at Days 1 and 14	Day 1	630.673 ng/mL	Geometric Coefficient of Variation 19
Daclatasvir (100 mg) QD	Average Observed Plasma Concentration (Css-av) at Steady State of Daclatasvir at Days 1 and 14	Day 14	733.035 ng/mL	Geometric Coefficient of Variation 15

Secondary

Change From Baseline at 24 h Post Dose on Day 1 in log10 Hepatitis C Virus (HCV) RNA of Participants Without Baseline Drug Resistance

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

Time frame: 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.

Arm	Measure	Group	Value (MEAN)	Dispersion
Daclatasvir (1 mg) QD	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
Daclatasvir (1 mg) QD	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
Daclatasvir (1 mg) QD	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
Daclatasvir (1 mg) QD	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
Daclatasvir (1 mg) QD	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
Daclatasvir (1 mg) QD	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 0.42
Daclatasvir (1 mg) QD	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
Daclatasvir (1 mg) QD	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 0.48
Daclatasvir (10 mg) QD	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	-0.91 log10 IU/mL	Standard Deviation 0.206
Daclatasvir (10 mg) QD	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	-2.97 log10 IU/mL	Standard Deviation 0.216
Daclatasvir (10 mg) QD	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	-1.73 log10 IU/mL	Standard Deviation 0.272
Daclatasvir (10 mg) QD	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	-2.12 log10 IU/mL	Standard Deviation 0.216
Daclatasvir (10 mg) QD	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	-2.44 log10 IU/mL	Standard Deviation 0.092
Daclatasvir (10 mg) QD	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	-2.76 log10 IU/mL	Standard Deviation 0.183
Daclatasvir (10 mg) QD	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	-2.80 log10 IU/mL	Standard Deviation 0.095
Daclatasvir (10 mg) QD	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	-0.00 log10 IU/mL	Standard Deviation 0.083
Daclatasvir (30 mg) QD	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	-2.05 log10 IU/mL	Standard Deviation 0.237
Daclatasvir (30 mg) QD	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	-3.24 log10 IU/mL	Standard Deviation 0.103
Daclatasvir (30 mg) QD	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	-2.62 log10 IU/mL	Standard Deviation 0.195
Daclatasvir (30 mg) QD	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	-2.91 log10 IU/mL	Standard Deviation 0.083
Daclatasvir (30 mg) QD	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	-2.95 log10 IU/mL	Standard Deviation 0.25
Daclatasvir (30 mg) QD	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	-3.02 log10 IU/mL	Standard Deviation 0.086
Daclatasvir (30 mg) QD	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	-1.22 log10 IU/mL	Standard Deviation 0.202
Daclatasvir (30 mg) QD	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	-0.21 log10 IU/mL	Standard Deviation 0.244
Daclatasvir (60 mg) QD	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	-2.47 log10 IU/mL	Standard Deviation 0.733
Daclatasvir (60 mg) QD	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	-3.60 log10 IU/mL	Standard Deviation 0.204
Daclatasvir (60 mg) QD	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	-3.08 log10 IU/mL	Standard Deviation 0.562
Daclatasvir (60 mg) QD	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	-3.38 log10 IU/mL	Standard Deviation 0.521
Daclatasvir (60 mg) QD	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	-3.50 log10 IU/mL	Standard Deviation 0.312
Daclatasvir (60 mg) QD	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	-1.96 log10 IU/mL	Standard Deviation 0.717
Daclatasvir (60 mg) QD	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	-0.43 log10 IU/mL	Standard Deviation 0.324
Daclatasvir (60 mg) QD	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	-1.24 log10 IU/mL	Standard Deviation 0.711
Daclatasvir (30 mg) BID	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	-2.92 log10 IU/mL	Standard Deviation 0.511
Daclatasvir (30 mg) BID	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	-3.53 log10 IU/mL	Standard Deviation 0.624
Daclatasvir (30 mg) BID	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	-3.04 log10 IU/mL	Standard Deviation 0.535
Daclatasvir (30 mg) BID	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	-3.38 log10 IU/mL	Standard Deviation 0.477
Daclatasvir (30 mg) BID	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	-2.59 log10 IU/mL	Standard Deviation 0.509
Daclatasvir (30 mg) BID	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	-0.35 log10 IU/mL	Standard Deviation 0.284
Daclatasvir (30 mg) BID	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	-1.24 log10 IU/mL	Standard Deviation 0.397
Daclatasvir (30 mg) BID	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	-1.99 log10 IU/mL	Standard Deviation 0.552
Daclatasvir (100 mg) QD	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	-2.03 log10 IU/mL	Standard Deviation 1.009
Daclatasvir (100 mg) QD	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	-2.58 log10 IU/mL	Standard Deviation 1.292
Daclatasvir (100 mg) QD	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	-2.29 log10 IU/mL	Standard Deviation 1.24
Daclatasvir (100 mg) QD	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	-2.00 log10 IU/mL	Standard Deviation 1.158
Daclatasvir (100 mg) QD	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	0.04 log10 IU/mL	Standard Deviation 0.107
Daclatasvir (100 mg) QD	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	-1.01 log10 IU/mL	Standard Deviation 0.345
Daclatasvir (100 mg) QD	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	-1.36 log10 IU/mL	Standard Deviation 0.473
Daclatasvir (100 mg) QD	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	-1.74 log10 IU/mL	Standard Deviation 0.917
Placebo	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	0.01 log10 IU/mL	Standard Deviation 0.155
Placebo	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	-0.00 log10 IU/mL	Standard Deviation 0.246
Placebo	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	0.02 log10 IU/mL	Standard Deviation 0.246
Placebo	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	-0.00 log10 IU/mL	Standard Deviation 0.216
Placebo	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	0.07 log10 IU/mL	Standard Deviation 0.248
Placebo	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	0.00 log10 IU/mL	Standard Deviation 0.209
Placebo	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	-0.01 log10 IU/mL	Standard Deviation 0.251
Placebo	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	-0.01 log10 IU/mL	Standard Deviation 0.284

Secondary

Change From Baseline at Day 7 in log10 Hepatitis C Virus (HCV) RNA Levels of Participants Without Baseline Drug Resistance

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

Time frame: Baseline, Day 7

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

Arm	Measure	Value (MEAN)
Daclatasvir (1 mg) QD	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
Daclatasvir (10 mg) QD	Change From Baseline at Day 7 in log10 Hepatitis C Virus (HCV) RNA Levels of Participants Without Baseline Drug Resistance	-3.31 log10 IU/mL
Daclatasvir (30 mg) QD	Change From Baseline at Day 7 in log10 Hepatitis C Virus (HCV) RNA Levels of Participants Without Baseline Drug Resistance	-2.91 log10 IU/mL
Daclatasvir (60 mg) QD	Change From Baseline at Day 7 in log10 Hepatitis C Virus (HCV) RNA Levels of Participants Without Baseline Drug Resistance	-2.58 log10 IU/mL
Daclatasvir (30 mg) BID	Change From Baseline at Day 7 in log10 Hepatitis C Virus (HCV) RNA Levels of Participants Without Baseline Drug Resistance	-3.03 log10 IU/mL
Daclatasvir (100 mg) QD	Change From Baseline at Day 7 in log10 Hepatitis C Virus (HCV) RNA Levels of Participants Without Baseline Drug Resistance	-3.56 log10 IU/mL
Placebo	Change From Baseline at Day 7 in log10 Hepatitis C Virus (HCV) RNA Levels of Participants Without Baseline Drug Resistance	0.00 log10 IU/mL

Secondary

Change From Baseline to Day 14 in Log10 Hepatitis C Virus (HCV) RNA in Participants Without Baseline Drug Resistance

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

Time frame: 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.

Arm	Measure	Value (MEAN)
Daclatasvir (1 mg) QD	Change From Baseline to Day 14 in Log10 Hepatitis C Virus (HCV) RNA in Participants Without Baseline Drug Resistance	-1.89 log10 IU/mL
Daclatasvir (10 mg) QD	Change From Baseline to Day 14 in Log10 Hepatitis C Virus (HCV) RNA in Participants Without Baseline Drug Resistance	-2.32 log10 IU/mL
Daclatasvir (30 mg) QD	Change From Baseline to Day 14 in Log10 Hepatitis C Virus (HCV) RNA in Participants Without Baseline Drug Resistance	-1.68 log10 IU/mL
Daclatasvir (60 mg) QD	Change From Baseline to Day 14 in Log10 Hepatitis C Virus (HCV) RNA in Participants Without Baseline Drug Resistance	-1.34 log10 IU/mL
Daclatasvir (30 mg) BID	Change From Baseline to Day 14 in Log10 Hepatitis C Virus (HCV) RNA in Participants Without Baseline Drug Resistance	-3.55 log10 IU/mL
Daclatasvir (100 mg) QD	Change From Baseline to Day 14 in Log10 Hepatitis C Virus (HCV) RNA in Participants Without Baseline Drug Resistance	-1.35 log10 IU/mL
Placebo	Change From Baseline to Day 14 in Log10 Hepatitis C Virus (HCV) RNA in Participants Without Baseline Drug Resistance	-0.59 log10 IU/mL

Secondary

Change From Baseline to Day 4 in log10 Hepatitis C Virus (HCV) RNA in Participants Without Baseline Drug Resistance

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

Time frame: 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.

Arm	Measure	Value (MEAN)
Daclatasvir (1 mg) QD	Change From Baseline to Day 4 in log10 Hepatitis C Virus (HCV) RNA in Participants Without Baseline Drug Resistance	-2.16 log10 IU/mL
Daclatasvir (10 mg) QD	Change From Baseline to Day 4 in log10 Hepatitis C Virus (HCV) RNA in Participants Without Baseline Drug Resistance	-3.29 log10 IU/mL
Daclatasvir (30 mg) QD	Change From Baseline to Day 4 in log10 Hepatitis C Virus (HCV) RNA in Participants Without Baseline Drug Resistance	-3.04 log10 IU/mL
Daclatasvir (60 mg) QD	Change From Baseline to Day 4 in log10 Hepatitis C Virus (HCV) RNA in Participants Without Baseline Drug Resistance	-3.85 log10 IU/mL
Daclatasvir (30 mg) BID	Change From Baseline to Day 4 in log10 Hepatitis C Virus (HCV) RNA in Participants Without Baseline Drug Resistance	-3.82 log10 IU/mL
Daclatasvir (100 mg) QD	Change From Baseline to Day 4 in log10 Hepatitis C Virus (HCV) RNA in Participants Without Baseline Drug Resistance	-3.14 log10 IU/mL
Placebo	Change From Baseline to Day 4 in log10 Hepatitis C Virus (HCV) RNA in Participants Without Baseline Drug Resistance	-0.07 log10 IU/mL

Secondary

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

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).

Time frame: 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.

Arm	Measure	Group	Value (NUMBER)
Daclatasvir (1 mg) QD	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
Daclatasvir (1 mg) QD	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
Daclatasvir (1 mg) QD	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
Daclatasvir (1 mg) QD	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
Daclatasvir (1 mg) QD	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
Daclatasvir (1 mg) QD	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

Maximum Decline From Baseline in Log10 Hepatitis C Virus (HCV) RNA in Participants Without Baseline Drug Resistance

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

Time frame: 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.

Arm	Measure	Value (MEAN)	Dispersion
Daclatasvir (1 mg) QD	Maximum Decline From Baseline in Log10 Hepatitis C Virus (HCV) RNA in Participants Without Baseline Drug Resistance	-2.81 log10 IU/mL	Standard Deviation 0.7
Daclatasvir (10 mg) QD	Maximum Decline From Baseline in Log10 Hepatitis C Virus (HCV) RNA in Participants Without Baseline Drug Resistance	-3.63 log10 IU/mL	Standard Deviation 0.776
Daclatasvir (30 mg) QD	Maximum Decline From Baseline in Log10 Hepatitis C Virus (HCV) RNA in Participants Without Baseline Drug Resistance	-3.31 log10 IU/mL	Standard Deviation 0.05
Daclatasvir (60 mg) QD	Maximum Decline From Baseline in Log10 Hepatitis C Virus (HCV) RNA in Participants Without Baseline Drug Resistance	-4.03 log10 IU/mL	Standard Deviation 0.626
Daclatasvir (30 mg) BID	Maximum Decline From Baseline in Log10 Hepatitis C Virus (HCV) RNA in Participants Without Baseline Drug Resistance	-4.88 log10 IU/mL	Standard Deviation 1.335
Daclatasvir (100 mg) QD	Maximum Decline From Baseline in Log10 Hepatitis C Virus (HCV) RNA in Participants Without Baseline Drug Resistance	-3.62 log10 IU/mL	Standard Deviation 0.17
Placebo	Maximum Decline From Baseline in Log10 Hepatitis C Virus (HCV) RNA in Participants Without Baseline Drug Resistance	-1.32 log10 IU/mL	Standard Deviation 1.629

Secondary

Maximum Observed Plasma Concentration (Cmax) and Minimum Observed Plasma Concentration (Cmin) of Daclatasvir on Days 1 and 14

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.

Time frame: 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.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Daclatasvir (1 mg) QD	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
Daclatasvir (1 mg) QD	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
Daclatasvir (1 mg) QD	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
Daclatasvir (1 mg) QD	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
Daclatasvir (10 mg) QD	Maximum Observed Plasma Concentration (Cmax) and Minimum Observed Plasma Concentration (Cmin) of Daclatasvir on Days 1 and 14	Cmin at Day 1	15.141 nanograms/milliliters(ng/mL)	Geometric Coefficient of Variation 49
Daclatasvir (10 mg) QD	Maximum Observed Plasma Concentration (Cmax) and Minimum Observed Plasma Concentration (Cmin) of Daclatasvir on Days 1 and 14	Cmax at Day 14	154.196 nanograms/milliliters(ng/mL)	Geometric Coefficient of Variation 49
Daclatasvir (10 mg) QD	Maximum Observed Plasma Concentration (Cmax) and Minimum Observed Plasma Concentration (Cmin) of Daclatasvir on Days 1 and 14	Cmax at Day 1	159.665 nanograms/milliliters(ng/mL)	Geometric Coefficient of Variation 41
Daclatasvir (10 mg) QD	Maximum Observed Plasma Concentration (Cmax) and Minimum Observed Plasma Concentration (Cmin) of Daclatasvir on Days 1 and 14	Cmin at Day 14	23.674 nanograms/milliliters(ng/mL)	Geometric Coefficient of Variation 53
Daclatasvir (30 mg) QD	Maximum Observed Plasma Concentration (Cmax) and Minimum Observed Plasma Concentration (Cmin) of Daclatasvir on Days 1 and 14	Cmin at Day 14	61.635 nanograms/milliliters(ng/mL)	Geometric Coefficient of Variation 42
Daclatasvir (30 mg) QD	Maximum Observed Plasma Concentration (Cmax) and Minimum Observed Plasma Concentration (Cmin) of Daclatasvir on Days 1 and 14	Cmin at Day 1	41.114 nanograms/milliliters(ng/mL)	Geometric Coefficient of Variation 34
Daclatasvir (30 mg) QD	Maximum Observed Plasma Concentration (Cmax) and Minimum Observed Plasma Concentration (Cmin) of Daclatasvir on Days 1 and 14	Cmax at Day 14	555.878 nanograms/milliliters(ng/mL)	Geometric Coefficient of Variation 38
Daclatasvir (30 mg) QD	Maximum Observed Plasma Concentration (Cmax) and Minimum Observed Plasma Concentration (Cmin) of Daclatasvir on Days 1 and 14	Cmax at Day 1	483.365 nanograms/milliliters(ng/mL)	Geometric Coefficient of Variation 25
Daclatasvir (60 mg) QD	Maximum Observed Plasma Concentration (Cmax) and Minimum Observed Plasma Concentration (Cmin) of Daclatasvir on Days 1 and 14	Cmax at Day 1	1409.202 nanograms/milliliters(ng/mL)	Geometric Coefficient of Variation 13
Daclatasvir (60 mg) QD	Maximum Observed Plasma Concentration (Cmax) and Minimum Observed Plasma Concentration (Cmin) of Daclatasvir on Days 1 and 14	Cmin at Day 14	254.602 nanograms/milliliters(ng/mL)	Geometric Coefficient of Variation 42
Daclatasvir (60 mg) QD	Maximum Observed Plasma Concentration (Cmax) and Minimum Observed Plasma Concentration (Cmin) of Daclatasvir on Days 1 and 14	Cmax at Day 14	1726.383 nanograms/milliliters(ng/mL)	Geometric Coefficient of Variation 21
Daclatasvir (60 mg) QD	Maximum Observed Plasma Concentration (Cmax) and Minimum Observed Plasma Concentration (Cmin) of Daclatasvir on Days 1 and 14	Cmin at Day 1	129.822 nanograms/milliliters(ng/mL)	Geometric Coefficient of Variation 25
Daclatasvir (30 mg) BID	Maximum Observed Plasma Concentration (Cmax) and Minimum Observed Plasma Concentration (Cmin) of Daclatasvir on Days 1 and 14	Cmin at Day 1	171.330 nanograms/milliliters(ng/mL)	Geometric Coefficient of Variation 53
Daclatasvir (30 mg) BID	Maximum Observed Plasma Concentration (Cmax) and Minimum Observed Plasma Concentration (Cmin) of Daclatasvir on Days 1 and 14	Cmin at Day 14	206.941 nanograms/milliliters(ng/mL)	Geometric Coefficient of Variation 74
Daclatasvir (30 mg) BID	Maximum Observed Plasma Concentration (Cmax) and Minimum Observed Plasma Concentration (Cmin) of Daclatasvir on Days 1 and 14	Cmax at Day 14	831.792 nanograms/milliliters(ng/mL)	Geometric Coefficient of Variation 37
Daclatasvir (30 mg) BID	Maximum Observed Plasma Concentration (Cmax) and Minimum Observed Plasma Concentration (Cmin) of Daclatasvir on Days 1 and 14	Cmax at Day 1	563.569 nanograms/milliliters(ng/mL)	Geometric Coefficient of Variation 26
Daclatasvir (100 mg) QD	Maximum Observed Plasma Concentration (Cmax) and Minimum Observed Plasma Concentration (Cmin) of Daclatasvir on Days 1 and 14	Cmax at Day 14	1853.925 nanograms/milliliters(ng/mL)	Geometric Coefficient of Variation 26
Daclatasvir (100 mg) QD	Maximum Observed Plasma Concentration (Cmax) and Minimum Observed Plasma Concentration (Cmin) of Daclatasvir on Days 1 and 14	Cmin at Day 1	174.642 nanograms/milliliters(ng/mL)	Geometric Coefficient of Variation 21
Daclatasvir (100 mg) QD	Maximum Observed Plasma Concentration (Cmax) and Minimum Observed Plasma Concentration (Cmin) of Daclatasvir on Days 1 and 14	Cmin at Day 14	287.852 nanograms/milliliters(ng/mL)	Geometric Coefficient of Variation 37
Daclatasvir (100 mg) QD	Maximum Observed Plasma Concentration (Cmax) and Minimum Observed Plasma Concentration (Cmin) of Daclatasvir on Days 1 and 14	Cmax at Day 1	1960.732 nanograms/milliliters(ng/mL)	Geometric Coefficient of Variation 21

Secondary

Number of Participants Meeting Pre-Specified Criteria in Electrocardiogram Parameters

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.

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

Population: All participants treated with study drug were summarized.

Arm	Measure	Group	Value (NUMBER)
Daclatasvir (1 mg) QD	Number of Participants Meeting Pre-Specified Criteria in Electrocardiogram Parameters	Maximum QTcF <= 450 msec	4 participants
Daclatasvir (1 mg) QD	Number of Participants Meeting Pre-Specified Criteria in Electrocardiogram Parameters	Maximum PR > 200 msec	0 participants
Daclatasvir (1 mg) QD	Number of Participants Meeting Pre-Specified Criteria in Electrocardiogram Parameters	Heart Rate <=50 bpm	0 participants
Daclatasvir (1 mg) QD	Number of Participants Meeting Pre-Specified Criteria in Electrocardiogram Parameters	Heart Rate > 100 bpm	0 participants
Daclatasvir (1 mg) QD	Number of Participants Meeting Pre-Specified Criteria in Electrocardiogram Parameters	Maximum QRS <=120 msec	4 participants
Daclatasvir (1 mg) QD	Number of Participants Meeting Pre-Specified Criteria in Electrocardiogram Parameters	Maximum QTcF >450 msec	0 participants
Daclatasvir (1 mg) QD	Number of Participants Meeting Pre-Specified Criteria in Electrocardiogram Parameters	Maximum Delta QTcF >30 msec	0 participants
Daclatasvir (1 mg) QD	Number of Participants Meeting Pre-Specified Criteria in Electrocardiogram Parameters	Maximum Delta QTcF<=30	4 participants
Daclatasvir (1 mg) QD	Number of Participants Meeting Pre-Specified Criteria in Electrocardiogram Parameters	Maximum PR <=200 msec	4 participants
Daclatasvir (1 mg) QD	Number of Participants Meeting Pre-Specified Criteria in Electrocardiogram Parameters	HR Change from baseline <-20bpm	0 participants
Daclatasvir (1 mg) QD	Number of Participants Meeting Pre-Specified Criteria in Electrocardiogram Parameters	Maximum QRS > 120 msec	0 participants
Daclatasvir (10 mg) QD	Number of Participants Meeting Pre-Specified Criteria in Electrocardiogram Parameters	Heart Rate <=50 bpm	0 participants
Daclatasvir (10 mg) QD	Number of Participants Meeting Pre-Specified Criteria in Electrocardiogram Parameters	Maximum QTcF <= 450 msec	4 participants
Daclatasvir (10 mg) QD	Number of Participants Meeting Pre-Specified Criteria in Electrocardiogram Parameters	Maximum Delta QTcF >30 msec	0 participants
Daclatasvir (10 mg) QD	Number of Participants Meeting Pre-Specified Criteria in Electrocardiogram Parameters	Maximum PR <=200 msec	4 participants
Daclatasvir (10 mg) QD	Number of Participants Meeting Pre-Specified Criteria in Electrocardiogram Parameters	Maximum PR > 200 msec	0 participants
Daclatasvir (10 mg) QD	Number of Participants Meeting Pre-Specified Criteria in Electrocardiogram Parameters	Maximum QRS <=120 msec	4 participants
Daclatasvir (10 mg) QD	Number of Participants Meeting Pre-Specified Criteria in Electrocardiogram Parameters	Maximum QRS > 120 msec	0 participants
Daclatasvir (10 mg) QD	Number of Participants Meeting Pre-Specified Criteria in Electrocardiogram Parameters	HR Change from baseline <-20bpm	0 participants
Daclatasvir (10 mg) QD	Number of Participants Meeting Pre-Specified Criteria in Electrocardiogram Parameters	Maximum QTcF >450 msec	0 participants
Daclatasvir (10 mg) QD	Number of Participants Meeting Pre-Specified Criteria in Electrocardiogram Parameters	Heart Rate > 100 bpm	0 participants
Daclatasvir (10 mg) QD	Number of Participants Meeting Pre-Specified Criteria in Electrocardiogram Parameters	Maximum Delta QTcF<=30	4 participants
Daclatasvir (30 mg) QD	Number of Participants Meeting Pre-Specified Criteria in Electrocardiogram Parameters	Maximum PR > 200 msec	0 participants
Daclatasvir (30 mg) QD	Number of Participants Meeting Pre-Specified Criteria in Electrocardiogram Parameters	Maximum Delta QTcF<=30	4 participants
Daclatasvir (30 mg) QD	Number of Participants Meeting Pre-Specified Criteria in Electrocardiogram Parameters	Heart Rate > 100 bpm	0 participants
Daclatasvir (30 mg) QD	Number of Participants Meeting Pre-Specified Criteria in Electrocardiogram Parameters	Maximum PR <=200 msec	4 participants
Daclatasvir (30 mg) QD	Number of Participants Meeting Pre-Specified Criteria in Electrocardiogram Parameters	HR Change from baseline <-20bpm	0 participants
Daclatasvir (30 mg) QD	Number of Participants Meeting Pre-Specified Criteria in Electrocardiogram Parameters	Heart Rate <=50 bpm	0 participants
Daclatasvir (30 mg) QD	Number of Participants Meeting Pre-Specified Criteria in Electrocardiogram Parameters	Maximum QRS > 120 msec	0 participants
Daclatasvir (30 mg) QD	Number of Participants Meeting Pre-Specified Criteria in Electrocardiogram Parameters	Maximum QTcF <= 450 msec	4 participants
Daclatasvir (30 mg) QD	Number of Participants Meeting Pre-Specified Criteria in Electrocardiogram Parameters	Maximum QRS <=120 msec	4 participants
Daclatasvir (30 mg) QD	Number of Participants Meeting Pre-Specified Criteria in Electrocardiogram Parameters	Maximum QTcF >450 msec	0 participants
Daclatasvir (30 mg) QD	Number of Participants Meeting Pre-Specified Criteria in Electrocardiogram Parameters	Maximum Delta QTcF >30 msec	0 participants
Daclatasvir (60 mg) QD	Number of Participants Meeting Pre-Specified Criteria in Electrocardiogram Parameters	Maximum PR <=200 msec	4 participants
Daclatasvir (60 mg) QD	Number of Participants Meeting Pre-Specified Criteria in Electrocardiogram Parameters	Heart Rate <=50 bpm	0 participants
Daclatasvir (60 mg) QD	Number of Participants Meeting Pre-Specified Criteria in Electrocardiogram Parameters	Heart Rate > 100 bpm	0 participants
Daclatasvir (60 mg) QD	Number of Participants Meeting Pre-Specified Criteria in Electrocardiogram Parameters	HR Change from baseline <-20bpm	0 participants
Daclatasvir (60 mg) QD	Number of Participants Meeting Pre-Specified Criteria in Electrocardiogram Parameters	Maximum QTcF <= 450 msec	4 participants
Daclatasvir (60 mg) QD	Number of Participants Meeting Pre-Specified Criteria in Electrocardiogram Parameters	Maximum QTcF >450 msec	0 participants
Daclatasvir (60 mg) QD	Number of Participants Meeting Pre-Specified Criteria in Electrocardiogram Parameters	Maximum Delta QTcF<=30	4 participants
Daclatasvir (60 mg) QD	Number of Participants Meeting Pre-Specified Criteria in Electrocardiogram Parameters	Maximum Delta QTcF >30 msec	0 participants
Daclatasvir (60 mg) QD	Number of Participants Meeting Pre-Specified Criteria in Electrocardiogram Parameters	Maximum QRS <=120 msec	4 participants
Daclatasvir (60 mg) QD	Number of Participants Meeting Pre-Specified Criteria in Electrocardiogram Parameters	Maximum QRS > 120 msec	0 participants
Daclatasvir (60 mg) QD	Number of Participants Meeting Pre-Specified Criteria in Electrocardiogram Parameters	Maximum PR > 200 msec	0 participants
Daclatasvir (30 mg) BID	Number of Participants Meeting Pre-Specified Criteria in Electrocardiogram Parameters	Maximum Delta QTcF >30 msec	0 participants
Daclatasvir (30 mg) BID	Number of Participants Meeting Pre-Specified Criteria in Electrocardiogram Parameters	Heart Rate > 100 bpm	0 participants
Daclatasvir (30 mg) BID	Number of Participants Meeting Pre-Specified Criteria in Electrocardiogram Parameters	Maximum QRS > 120 msec	0 participants
Daclatasvir (30 mg) BID	Number of Participants Meeting Pre-Specified Criteria in Electrocardiogram Parameters	Maximum QTcF >450 msec	0 participants
Daclatasvir (30 mg) BID	Number of Participants Meeting Pre-Specified Criteria in Electrocardiogram Parameters	HR Change from baseline <-20bpm	4 participants
Daclatasvir (30 mg) BID	Number of Participants Meeting Pre-Specified Criteria in Electrocardiogram Parameters	Heart Rate <=50 bpm	0 participants
Daclatasvir (30 mg) BID	Number of Participants Meeting Pre-Specified Criteria in Electrocardiogram Parameters	Maximum PR <=200 msec	4 participants
Daclatasvir (30 mg) BID	Number of Participants Meeting Pre-Specified Criteria in Electrocardiogram Parameters	Maximum Delta QTcF<=30	4 participants
Daclatasvir (30 mg) BID	Number of Participants Meeting Pre-Specified Criteria in Electrocardiogram Parameters	Maximum QTcF <= 450 msec	4 participants
Daclatasvir (30 mg) BID	Number of Participants Meeting Pre-Specified Criteria in Electrocardiogram Parameters	Maximum PR > 200 msec	0 participants
Daclatasvir (30 mg) BID	Number of Participants Meeting Pre-Specified Criteria in Electrocardiogram Parameters	Maximum QRS <=120 msec	4 participants
Daclatasvir (100 mg) QD	Number of Participants Meeting Pre-Specified Criteria in Electrocardiogram Parameters	Maximum QTcF >450 msec	0 participants
Daclatasvir (100 mg) QD	Number of Participants Meeting Pre-Specified Criteria in Electrocardiogram Parameters	Maximum Delta QTcF >30 msec	0 participants
Daclatasvir (100 mg) QD	Number of Participants Meeting Pre-Specified Criteria in Electrocardiogram Parameters	Maximum QTcF <= 450 msec	4 participants
Daclatasvir (100 mg) QD	Number of Participants Meeting Pre-Specified Criteria in Electrocardiogram Parameters	Maximum QRS <=120 msec	4 participants
Daclatasvir (100 mg) QD	Number of Participants Meeting Pre-Specified Criteria in Electrocardiogram Parameters	HR Change from baseline <-20bpm	0 participants
Daclatasvir (100 mg) QD	Number of Participants Meeting Pre-Specified Criteria in Electrocardiogram Parameters	Maximum PR > 200 msec	1 participants
Daclatasvir (100 mg) QD	Number of Participants Meeting Pre-Specified Criteria in Electrocardiogram Parameters	Maximum QRS > 120 msec	0 participants
Daclatasvir (100 mg) QD	Number of Participants Meeting Pre-Specified Criteria in Electrocardiogram Parameters	Heart Rate > 100 bpm	0 participants
Daclatasvir (100 mg) QD	Number of Participants Meeting Pre-Specified Criteria in Electrocardiogram Parameters	Maximum PR <=200 msec	4 participants
Daclatasvir (100 mg) QD	Number of Participants Meeting Pre-Specified Criteria in Electrocardiogram Parameters	Heart Rate <=50 bpm	0 participants
Daclatasvir (100 mg) QD	Number of Participants Meeting Pre-Specified Criteria in Electrocardiogram Parameters	Maximum Delta QTcF<=30	4 participants
Placebo	Number of Participants Meeting Pre-Specified Criteria in Electrocardiogram Parameters	Maximum QRS <=120 msec	6 participants
Placebo	Number of Participants Meeting Pre-Specified Criteria in Electrocardiogram Parameters	Maximum PR <=200 msec	6 participants
Placebo	Number of Participants Meeting Pre-Specified Criteria in Electrocardiogram Parameters	Maximum QTcF <= 450 msec	6 participants
Placebo	Number of Participants Meeting Pre-Specified Criteria in Electrocardiogram Parameters	Maximum QTcF >450 msec	0 participants
Placebo	Number of Participants Meeting Pre-Specified Criteria in Electrocardiogram Parameters	Heart Rate <=50 bpm	0 participants
Placebo	Number of Participants Meeting Pre-Specified Criteria in Electrocardiogram Parameters	Maximum Delta QTcF<=30	6 participants
Placebo	Number of Participants Meeting Pre-Specified Criteria in Electrocardiogram Parameters	HR Change from baseline <-20bpm	0 participants
Placebo	Number of Participants Meeting Pre-Specified Criteria in Electrocardiogram Parameters	Maximum Delta QTcF >30 msec	0 participants
Placebo	Number of Participants Meeting Pre-Specified Criteria in Electrocardiogram Parameters	Maximum QRS > 120 msec	0 participants
Placebo	Number of Participants Meeting Pre-Specified Criteria in Electrocardiogram Parameters	Heart Rate > 100 bpm	0 participants
Placebo	Number of Participants Meeting Pre-Specified Criteria in Electrocardiogram Parameters	Maximum PR > 200 msec	0 participants

Secondary

Number of Participants With Clinically Relevant Change From Baseline in Vital Signs

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.

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

Population: All participants treated with study drug were summarized.

Arm	Measure	Value (NUMBER)
Daclatasvir (1 mg) QD	Number of Participants With Clinically Relevant Change From Baseline in Vital Signs	0 participants
Daclatasvir (10 mg) QD	Number of Participants With Clinically Relevant Change From Baseline in Vital Signs	0 participants
Daclatasvir (30 mg) QD	Number of Participants With Clinically Relevant Change From Baseline in Vital Signs	0 participants
Daclatasvir (60 mg) QD	Number of Participants With Clinically Relevant Change From Baseline in Vital Signs	0 participants
Daclatasvir (30 mg) BID	Number of Participants With Clinically Relevant Change From Baseline in Vital Signs	0 participants
Daclatasvir (100 mg) QD	Number of Participants With Clinically Relevant Change From Baseline in Vital Signs	0 participants
Placebo	Number of Participants With Clinically Relevant Change From Baseline in Vital Signs	0 participants

Secondary

Number of Participants With Marked Abnormalities in Liver and Kidney Function Laboratory Tests and Electrolytes

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.

Time frame: Screening, Day 3, Day 7, Day 11, Day 14, and Day 28

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

Arm	Measure	Group	Value (NUMBER)
Daclatasvir (1 mg) QD	Number of Participants With Marked Abnormalities in Liver and Kidney Function Laboratory Tests and Electrolytes	Potassium High	0 participants
Daclatasvir (1 mg) QD	Number of Participants With Marked Abnormalities in Liver and Kidney Function Laboratory Tests and Electrolytes	AST High	0 participants
Daclatasvir (1 mg) QD	Number of Participants With Marked Abnormalities in Liver and Kidney Function Laboratory Tests and Electrolytes	GGT	0 participants
Daclatasvir (1 mg) QD	Number of Participants With Marked Abnormalities in Liver and Kidney Function Laboratory Tests and Electrolytes	ALT High	0 participants
Daclatasvir (1 mg) QD	Number of Participants With Marked Abnormalities in Liver and Kidney Function Laboratory Tests and Electrolytes	ALP High	0 participants
Daclatasvir (1 mg) QD	Number of Participants With Marked Abnormalities in Liver and Kidney Function Laboratory Tests and Electrolytes	Phosporus Low	1 participants
Daclatasvir (10 mg) QD	Number of Participants With Marked Abnormalities in Liver and Kidney Function Laboratory Tests and Electrolytes	ALT High	1 participants
Daclatasvir (10 mg) QD	Number of Participants With Marked Abnormalities in Liver and Kidney Function Laboratory Tests and Electrolytes	GGT	0 participants
Daclatasvir (10 mg) QD	Number of Participants With Marked Abnormalities in Liver and Kidney Function Laboratory Tests and Electrolytes	Potassium High	0 participants
Daclatasvir (10 mg) QD	Number of Participants With Marked Abnormalities in Liver and Kidney Function Laboratory Tests and Electrolytes	AST High	1 participants
Daclatasvir (10 mg) QD	Number of Participants With Marked Abnormalities in Liver and Kidney Function Laboratory Tests and Electrolytes	Phosporus Low	0 participants
Daclatasvir (10 mg) QD	Number of Participants With Marked Abnormalities in Liver and Kidney Function Laboratory Tests and Electrolytes	ALP High	0 participants
Daclatasvir (30 mg) QD	Number of Participants With Marked Abnormalities in Liver and Kidney Function Laboratory Tests and Electrolytes	Phosporus Low	0 participants
Daclatasvir (30 mg) QD	Number of Participants With Marked Abnormalities in Liver and Kidney Function Laboratory Tests and Electrolytes	ALP High	0 participants
Daclatasvir (30 mg) QD	Number of Participants With Marked Abnormalities in Liver and Kidney Function Laboratory Tests and Electrolytes	Potassium High	1 participants
Daclatasvir (30 mg) QD	Number of Participants With Marked Abnormalities in Liver and Kidney Function Laboratory Tests and Electrolytes	GGT	2 participants
Daclatasvir (30 mg) QD	Number of Participants With Marked Abnormalities in Liver and Kidney Function Laboratory Tests and Electrolytes	ALT High	0 participants
Daclatasvir (30 mg) QD	Number of Participants With Marked Abnormalities in Liver and Kidney Function Laboratory Tests and Electrolytes	AST High	0 participants
Daclatasvir (60 mg) QD	Number of Participants With Marked Abnormalities in Liver and Kidney Function Laboratory Tests and Electrolytes	Phosporus Low	0 participants
Daclatasvir (60 mg) QD	Number of Participants With Marked Abnormalities in Liver and Kidney Function Laboratory Tests and Electrolytes	ALT High	1 participants
Daclatasvir (60 mg) QD	Number of Participants With Marked Abnormalities in Liver and Kidney Function Laboratory Tests and Electrolytes	AST High	0 participants
Daclatasvir (60 mg) QD	Number of Participants With Marked Abnormalities in Liver and Kidney Function Laboratory Tests and Electrolytes	ALP High	0 participants
Daclatasvir (60 mg) QD	Number of Participants With Marked Abnormalities in Liver and Kidney Function Laboratory Tests and Electrolytes	GGT	0 participants
Daclatasvir (60 mg) QD	Number of Participants With Marked Abnormalities in Liver and Kidney Function Laboratory Tests and Electrolytes	Potassium High	0 participants
Daclatasvir (30 mg) BID	Number of Participants With Marked Abnormalities in Liver and Kidney Function Laboratory Tests and Electrolytes	GGT	2 participants
Daclatasvir (30 mg) BID	Number of Participants With Marked Abnormalities in Liver and Kidney Function Laboratory Tests and Electrolytes	AST High	2 participants
Daclatasvir (30 mg) BID	Number of Participants With Marked Abnormalities in Liver and Kidney Function Laboratory Tests and Electrolytes	Phosporus Low	0 participants
Daclatasvir (30 mg) BID	Number of Participants With Marked Abnormalities in Liver and Kidney Function Laboratory Tests and Electrolytes	Potassium High	0 participants
Daclatasvir (30 mg) BID	Number of Participants With Marked Abnormalities in Liver and Kidney Function Laboratory Tests and Electrolytes	ALP High	0 participants
Daclatasvir (30 mg) BID	Number of Participants With Marked Abnormalities in Liver and Kidney Function Laboratory Tests and Electrolytes	ALT High	2 participants
Daclatasvir (100 mg) QD	Number of Participants With Marked Abnormalities in Liver and Kidney Function Laboratory Tests and Electrolytes	ALP High	1 participants
Daclatasvir (100 mg) QD	Number of Participants With Marked Abnormalities in Liver and Kidney Function Laboratory Tests and Electrolytes	GGT	1 participants
Daclatasvir (100 mg) QD	Number of Participants With Marked Abnormalities in Liver and Kidney Function Laboratory Tests and Electrolytes	AST High	2 participants
Daclatasvir (100 mg) QD	Number of Participants With Marked Abnormalities in Liver and Kidney Function Laboratory Tests and Electrolytes	Phosporus Low	0 participants
Daclatasvir (100 mg) QD	Number of Participants With Marked Abnormalities in Liver and Kidney Function Laboratory Tests and Electrolytes	ALT High	2 participants
Daclatasvir (100 mg) QD	Number of Participants With Marked Abnormalities in Liver and Kidney Function Laboratory Tests and Electrolytes	Potassium High	0 participants
Placebo	Number of Participants With Marked Abnormalities in Liver and Kidney Function Laboratory Tests and Electrolytes	ALP High	0 participants
Placebo	Number of Participants With Marked Abnormalities in Liver and Kidney Function Laboratory Tests and Electrolytes	AST High	1 participants
Placebo	Number of Participants With Marked Abnormalities in Liver and Kidney Function Laboratory Tests and Electrolytes	Potassium High	1 participants
Placebo	Number of Participants With Marked Abnormalities in Liver and Kidney Function Laboratory Tests and Electrolytes	GGT	2 participants
Placebo	Number of Participants With Marked Abnormalities in Liver and Kidney Function Laboratory Tests and Electrolytes	Phosporus Low	0 participants
Placebo	Number of Participants With Marked Abnormalities in Liver and Kidney Function Laboratory Tests and Electrolytes	ALT High	0 participants

Secondary

Number of Participants With Marked Laboratory Abnormalities in Hematology

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.

Time frame: Screening, Day 3, Day 7, Day 11, Day 14, and Day 28

Population: All participants treated with study drug were summarized.

Arm	Measure	Group	Value (NUMBER)
Daclatasvir (1 mg) QD	Number of Participants With Marked Laboratory Abnormalities in Hematology	Low Platelet	0 participants
Daclatasvir (1 mg) QD	Number of Participants With Marked Laboratory Abnormalities in Hematology	Low Hematocrit	0 participants
Daclatasvir (1 mg) QD	Number of Participants With Marked Laboratory Abnormalities in Hematology	High Leukocytes	0 participants
Daclatasvir (1 mg) QD	Number of Participants With Marked Laboratory Abnormalities in Hematology	Low Hemoglobin	1 participants
Daclatasvir (1 mg) QD	Number of Participants With Marked Laboratory Abnormalities in Hematology	High Eosinophils	0 participants
Daclatasvir (10 mg) QD	Number of Participants With Marked Laboratory Abnormalities in Hematology	Low Platelet	0 participants
Daclatasvir (10 mg) QD	Number of Participants With Marked Laboratory Abnormalities in Hematology	Low Hemoglobin	0 participants
Daclatasvir (10 mg) QD	Number of Participants With Marked Laboratory Abnormalities in Hematology	High Eosinophils	0 participants
Daclatasvir (10 mg) QD	Number of Participants With Marked Laboratory Abnormalities in Hematology	Low Hematocrit	0 participants
Daclatasvir (10 mg) QD	Number of Participants With Marked Laboratory Abnormalities in Hematology	High Leukocytes	0 participants
Daclatasvir (30 mg) QD	Number of Participants With Marked Laboratory Abnormalities in Hematology	High Leukocytes	0 participants
Daclatasvir (30 mg) QD	Number of Participants With Marked Laboratory Abnormalities in Hematology	Low Hemoglobin	0 participants
Daclatasvir (30 mg) QD	Number of Participants With Marked Laboratory Abnormalities in Hematology	Low Hematocrit	0 participants
Daclatasvir (30 mg) QD	Number of Participants With Marked Laboratory Abnormalities in Hematology	Low Platelet	0 participants
Daclatasvir (30 mg) QD	Number of Participants With Marked Laboratory Abnormalities in Hematology	High Eosinophils	0 participants
Daclatasvir (60 mg) QD	Number of Participants With Marked Laboratory Abnormalities in Hematology	Low Platelet	0 participants
Daclatasvir (60 mg) QD	Number of Participants With Marked Laboratory Abnormalities in Hematology	Low Hematocrit	1 participants
Daclatasvir (60 mg) QD	Number of Participants With Marked Laboratory Abnormalities in Hematology	Low Hemoglobin	1 participants
Daclatasvir (60 mg) QD	Number of Participants With Marked Laboratory Abnormalities in Hematology	High Eosinophils	0 participants
Daclatasvir (60 mg) QD	Number of Participants With Marked Laboratory Abnormalities in Hematology	High Leukocytes	0 participants
Daclatasvir (30 mg) BID	Number of Participants With Marked Laboratory Abnormalities in Hematology	Low Hematocrit	0 participants
Daclatasvir (30 mg) BID	Number of Participants With Marked Laboratory Abnormalities in Hematology	High Leukocytes	0 participants
Daclatasvir (30 mg) BID	Number of Participants With Marked Laboratory Abnormalities in Hematology	Low Platelet	0 participants
Daclatasvir (30 mg) BID	Number of Participants With Marked Laboratory Abnormalities in Hematology	High Eosinophils	0 participants
Daclatasvir (30 mg) BID	Number of Participants With Marked Laboratory Abnormalities in Hematology	Low Hemoglobin	0 participants
Daclatasvir (100 mg) QD	Number of Participants With Marked Laboratory Abnormalities in Hematology	Low Hematocrit	0 participants
Daclatasvir (100 mg) QD	Number of Participants With Marked Laboratory Abnormalities in Hematology	High Leukocytes	1 participants
Daclatasvir (100 mg) QD	Number of Participants With Marked Laboratory Abnormalities in Hematology	High Eosinophils	1 participants
Daclatasvir (100 mg) QD	Number of Participants With Marked Laboratory Abnormalities in Hematology	Low Hemoglobin	0 participants
Daclatasvir (100 mg) QD	Number of Participants With Marked Laboratory Abnormalities in Hematology	Low Platelet	1 participants
Placebo	Number of Participants With Marked Laboratory Abnormalities in Hematology	High Eosinophils	0 participants
Placebo	Number of Participants With Marked Laboratory Abnormalities in Hematology	Low Hemoglobin	1 participants
Placebo	Number of Participants With Marked Laboratory Abnormalities in Hematology	Low Platelet	0 participants
Placebo	Number of Participants With Marked Laboratory Abnormalities in Hematology	Low Hematocrit	0 participants
Placebo	Number of Participants With Marked Laboratory Abnormalities in Hematology	High Leukocytes	0 participants

Secondary

Number of Participants With Marked Laboratory Abnormalities in Lipase and Glucose

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.

Time frame: Screening, Day 3, Day 7, Day 11, Day 14, and Day 28

Population: All participants treated with study drug were summarized.

Arm	Measure	Group	Value (NUMBER)
Daclatasvir (1 mg) QD	Number of Participants With Marked Laboratory Abnormalities in Lipase and Glucose	Lipase High	0 participants
Daclatasvir (1 mg) QD	Number of Participants With Marked Laboratory Abnormalities in Lipase and Glucose	Glucose Fasting High	0 participants
Daclatasvir (10 mg) QD	Number of Participants With Marked Laboratory Abnormalities in Lipase and Glucose	Lipase High	1 participants
Daclatasvir (10 mg) QD	Number of Participants With Marked Laboratory Abnormalities in Lipase and Glucose	Glucose Fasting High	0 participants
Daclatasvir (30 mg) QD	Number of Participants With Marked Laboratory Abnormalities in Lipase and Glucose	Lipase High	0 participants
Daclatasvir (30 mg) QD	Number of Participants With Marked Laboratory Abnormalities in Lipase and Glucose	Glucose Fasting High	0 participants
Daclatasvir (60 mg) QD	Number of Participants With Marked Laboratory Abnormalities in Lipase and Glucose	Lipase High	0 participants
Daclatasvir (60 mg) QD	Number of Participants With Marked Laboratory Abnormalities in Lipase and Glucose	Glucose Fasting High	0 participants
Daclatasvir (30 mg) BID	Number of Participants With Marked Laboratory Abnormalities in Lipase and Glucose	Lipase High	1 participants
Daclatasvir (30 mg) BID	Number of Participants With Marked Laboratory Abnormalities in Lipase and Glucose	Glucose Fasting High	0 participants
Daclatasvir (100 mg) QD	Number of Participants With Marked Laboratory Abnormalities in Lipase and Glucose	Lipase High	0 participants
Daclatasvir (100 mg) QD	Number of Participants With Marked Laboratory Abnormalities in Lipase and Glucose	Glucose Fasting High	1 participants
Placebo	Number of Participants With Marked Laboratory Abnormalities in Lipase and Glucose	Lipase High	0 participants
Placebo	Number of Participants With Marked Laboratory Abnormalities in Lipase and Glucose	Glucose Fasting High	1 participants

Secondary

Number of Participants With Marked Laboratory Abnormalities in Urinalysis

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.

Time frame: Screening, Day 3, Day 7, Day 11, Day 14, and Day 28

Population: All participants treated with study drug were summarized.

Arm	Measure	Group	Value (NUMBER)
Daclatasvir (1 mg) QD	Number of Participants With Marked Laboratory Abnormalities in Urinalysis	Urine Blood High	1 participants
Daclatasvir (1 mg) QD	Number of Participants With Marked Laboratory Abnormalities in Urinalysis	Urine Glucose High	1 participants
Daclatasvir (10 mg) QD	Number of Participants With Marked Laboratory Abnormalities in Urinalysis	Urine Blood High	1 participants
Daclatasvir (10 mg) QD	Number of Participants With Marked Laboratory Abnormalities in Urinalysis	Urine Glucose High	0 participants
Daclatasvir (30 mg) QD	Number of Participants With Marked Laboratory Abnormalities in Urinalysis	Urine Blood High	0 participants
Daclatasvir (30 mg) QD	Number of Participants With Marked Laboratory Abnormalities in Urinalysis	Urine Glucose High	0 participants
Daclatasvir (60 mg) QD	Number of Participants With Marked Laboratory Abnormalities in Urinalysis	Urine Glucose High	0 participants
Daclatasvir (60 mg) QD	Number of Participants With Marked Laboratory Abnormalities in Urinalysis	Urine Blood High	1 participants
Daclatasvir (30 mg) BID	Number of Participants With Marked Laboratory Abnormalities in Urinalysis	Urine Blood High	0 participants
Daclatasvir (30 mg) BID	Number of Participants With Marked Laboratory Abnormalities in Urinalysis	Urine Glucose High	0 participants
Daclatasvir (100 mg) QD	Number of Participants With Marked Laboratory Abnormalities in Urinalysis	Urine Blood High	0 participants
Daclatasvir (100 mg) QD	Number of Participants With Marked Laboratory Abnormalities in Urinalysis	Urine Glucose High	0 participants
Placebo	Number of Participants With Marked Laboratory Abnormalities in Urinalysis	Urine Glucose High	2 participants
Placebo	Number of Participants With Marked Laboratory Abnormalities in Urinalysis	Urine Blood High	1 participants

Secondary

Number of Participants With Serious Adverse Events (SAEs), Discontinuation Due to Adverse Events (AEs), and Who Died

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.

Time frame: Day 1 to Day 182 or Day of Discharge

Population: All participants who received study drug were summarized.

Arm	Measure	Group	Value (NUMBER)
Daclatasvir (1 mg) QD	Number of Participants With Serious Adverse Events (SAEs), Discontinuation Due to Adverse Events (AEs), and Who Died	Death	0 participants
Daclatasvir (1 mg) QD	Number of Participants With Serious Adverse Events (SAEs), Discontinuation Due to Adverse Events (AEs), and Who Died	Discontinuation Due to AEs	0 participants
Daclatasvir (1 mg) QD	Number of Participants With Serious Adverse Events (SAEs), Discontinuation Due to Adverse Events (AEs), and Who Died	SAEs	0 participants
Daclatasvir (10 mg) QD	Number of Participants With Serious Adverse Events (SAEs), Discontinuation Due to Adverse Events (AEs), and Who Died	Discontinuation Due to AEs	0 participants
Daclatasvir (10 mg) QD	Number of Participants With Serious Adverse Events (SAEs), Discontinuation Due to Adverse Events (AEs), and Who Died	SAEs	0 participants
Daclatasvir (10 mg) QD	Number of Participants With Serious Adverse Events (SAEs), Discontinuation Due to Adverse Events (AEs), and Who Died	Death	0 participants
Daclatasvir (30 mg) QD	Number of Participants With Serious Adverse Events (SAEs), Discontinuation Due to Adverse Events (AEs), and Who Died	Death	0 participants
Daclatasvir (30 mg) QD	Number of Participants With Serious Adverse Events (SAEs), Discontinuation Due to Adverse Events (AEs), and Who Died	SAEs	0 participants
Daclatasvir (30 mg) QD	Number of Participants With Serious Adverse Events (SAEs), Discontinuation Due to Adverse Events (AEs), and Who Died	Discontinuation Due to AEs	0 participants
Daclatasvir (60 mg) QD	Number of Participants With Serious Adverse Events (SAEs), Discontinuation Due to Adverse Events (AEs), and Who Died	Discontinuation Due to AEs	0 participants
Daclatasvir (60 mg) QD	Number of Participants With Serious Adverse Events (SAEs), Discontinuation Due to Adverse Events (AEs), and Who Died	SAEs	0 participants
Daclatasvir (60 mg) QD	Number of Participants With Serious Adverse Events (SAEs), Discontinuation Due to Adverse Events (AEs), and Who Died	Death	0 participants
Daclatasvir (30 mg) BID	Number of Participants With Serious Adverse Events (SAEs), Discontinuation Due to Adverse Events (AEs), and Who Died	Discontinuation Due to AEs	0 participants
Daclatasvir (30 mg) BID	Number of Participants With Serious Adverse Events (SAEs), Discontinuation Due to Adverse Events (AEs), and Who Died	SAEs	0 participants
Daclatasvir (30 mg) BID	Number of Participants With Serious Adverse Events (SAEs), Discontinuation Due to Adverse Events (AEs), and Who Died	Death	0 participants
Daclatasvir (100 mg) QD	Number of Participants With Serious Adverse Events (SAEs), Discontinuation Due to Adverse Events (AEs), and Who Died	SAEs	0 participants
Daclatasvir (100 mg) QD	Number of Participants With Serious Adverse Events (SAEs), Discontinuation Due to Adverse Events (AEs), and Who Died	Death	0 participants
Daclatasvir (100 mg) QD	Number of Participants With Serious Adverse Events (SAEs), Discontinuation Due to Adverse Events (AEs), and Who Died	Discontinuation Due to AEs	0 participants
Placebo	Number of Participants With Serious Adverse Events (SAEs), Discontinuation Due to Adverse Events (AEs), and Who Died	Death	0 participants
Placebo	Number of Participants With Serious Adverse Events (SAEs), Discontinuation Due to Adverse Events (AEs), and Who Died	Discontinuation Due to AEs	0 participants
Placebo	Number of Participants With Serious Adverse Events (SAEs), Discontinuation Due to Adverse Events (AEs), and Who Died	SAEs	0 participants

Secondary

Plasma Half-life (T-half) of Daclatasvir at Day 14

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.

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

Arm	Measure	Value (MEAN)	Dispersion
Daclatasvir (1 mg) QD	Plasma Half-life (T-half) of Daclatasvir at Day 14	11.68 h	Standard Deviation 2.214
Daclatasvir (10 mg) QD	Plasma Half-life (T-half) of Daclatasvir at Day 14	14.31 h	Standard Deviation 3.848
Daclatasvir (30 mg) QD	Plasma Half-life (T-half) of Daclatasvir at Day 14	12.99 h	Standard Deviation 2.039
Daclatasvir (60 mg) QD	Plasma Half-life (T-half) of Daclatasvir at Day 14	12.81 h	Standard Deviation 1.233
Daclatasvir (30 mg) BID	Plasma Half-life (T-half) of Daclatasvir at Day 14	13.04 h	Standard Deviation 3.654
Daclatasvir (100 mg) QD	Plasma Half-life (T-half) of Daclatasvir at Day 14	15.19 h	Standard Deviation 3.411

Secondary

Time of Maximum Observed Plasma Concentration (Tmax) of Daclatasvir on Days 1 and 14

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.

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

Arm	Measure	Group	Value (MEDIAN)
Daclatasvir (1 mg) QD	Time of Maximum Observed Plasma Concentration (Tmax) of Daclatasvir on Days 1 and 14	Day 1	2.000 h
Daclatasvir (1 mg) QD	Time of Maximum Observed Plasma Concentration (Tmax) of Daclatasvir on Days 1 and 14	Day 14	1.250 h
Daclatasvir (10 mg) QD	Time of Maximum Observed Plasma Concentration (Tmax) of Daclatasvir on Days 1 and 14	Day 1	1.000 h
Daclatasvir (10 mg) QD	Time of Maximum Observed Plasma Concentration (Tmax) of Daclatasvir on Days 1 and 14	Day 14	1.250 h
Daclatasvir (30 mg) QD	Time of Maximum Observed Plasma Concentration (Tmax) of Daclatasvir on Days 1 and 14	Day 1	1.000 h
Daclatasvir (30 mg) QD	Time of Maximum Observed Plasma Concentration (Tmax) of Daclatasvir on Days 1 and 14	Day 14	1.000 h
Daclatasvir (60 mg) QD	Time of Maximum Observed Plasma Concentration (Tmax) of Daclatasvir on Days 1 and 14	Day 14	1.000 h
Daclatasvir (60 mg) QD	Time of Maximum Observed Plasma Concentration (Tmax) of Daclatasvir on Days 1 and 14	Day 1	1.500 h
Daclatasvir (30 mg) BID	Time of Maximum Observed Plasma Concentration (Tmax) of Daclatasvir on Days 1 and 14	Day 1	2.500 h
Daclatasvir (30 mg) BID	Time of Maximum Observed Plasma Concentration (Tmax) of Daclatasvir on Days 1 and 14	Day 14	1.750 h
Daclatasvir (100 mg) QD	Time of Maximum Observed Plasma Concentration (Tmax) of Daclatasvir on Days 1 and 14	Day 1	1.500 h
Daclatasvir (100 mg) QD	Time of Maximum Observed Plasma Concentration (Tmax) of Daclatasvir on Days 1 and 14	Day 14	1.750 h

Secondary

Time to Maximum Decline From Baseline in Hepatitis C Virus (HCV) RNA in Participants Without Baseline Drug Resistance

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

Time frame: 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.

Arm	Measure	Value (MEAN)	Dispersion
Daclatasvir (1 mg) QD	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
Daclatasvir (10 mg) QD	Time to Maximum Decline From Baseline in Hepatitis C Virus (HCV) RNA in Participants Without Baseline Drug Resistance	5.25 Days	Standard Deviation 2.363
Daclatasvir (30 mg) QD	Time to Maximum Decline From Baseline in Hepatitis C Virus (HCV) RNA in Participants Without Baseline Drug Resistance	3.50 Days	Standard Deviation 2.38
Daclatasvir (60 mg) QD	Time to Maximum Decline From Baseline in Hepatitis C Virus (HCV) RNA in Participants Without Baseline Drug Resistance	3.33 Days	Standard Deviation 1.528
Daclatasvir (30 mg) BID	Time to Maximum Decline From Baseline in Hepatitis C Virus (HCV) RNA in Participants Without Baseline Drug Resistance	10.33 Days	Standard Deviation 6.028
Daclatasvir (100 mg) QD	Time to Maximum Decline From Baseline in Hepatitis C Virus (HCV) RNA in Participants Without Baseline Drug Resistance	7.67 Days	Standard Deviation 6.429
Placebo	Time to Maximum Decline From Baseline in Hepatitis C Virus (HCV) RNA in Participants Without Baseline Drug Resistance	10.17 Days	Standard Deviation 6.524

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026

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

Conditions

Brief summary

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Recruitment details

Pre-assignment details

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

Change From Baseline at Day 7 in log10 Hepatitis C Virus (HCV) RNA of All Participants

Accumulation Index (AI) AUC(TAU), AI Cmax, and Degree of Fluctuation (DF) of Daclatasvir on Day 14

Apparent Total Body Clearance (CLT/F) of Daclatasvir on Day 14

Area Under the Concentration-time Curve (AUC) in 1 Dosing Interval of Daclatasvir at Days 1 and 14

Average Observed Plasma Concentration (Css-av) at Steady State of Daclatasvir at Days 1 and 14

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 From Baseline at Day 7 in log10 Hepatitis C Virus (HCV) RNA Levels of Participants Without Baseline Drug Resistance

Change From Baseline to Day 14 in Log10 Hepatitis C Virus (HCV) RNA in Participants Without Baseline Drug Resistance

Change From Baseline to Day 4 in log10 Hepatitis C Virus (HCV) RNA in Participants Without Baseline Drug Resistance

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

Maximum Decline From Baseline in Log10 Hepatitis C Virus (HCV) RNA in Participants Without Baseline Drug Resistance

Maximum Observed Plasma Concentration (Cmax) and Minimum Observed Plasma Concentration (Cmin) of Daclatasvir on Days 1 and 14

Number of Participants Meeting Pre-Specified Criteria in Electrocardiogram Parameters

Number of Participants With Clinically Relevant Change From Baseline in Vital Signs

Number of Participants With Marked Abnormalities in Liver and Kidney Function Laboratory Tests and Electrolytes

Number of Participants With Marked Laboratory Abnormalities in Hematology

Number of Participants With Marked Laboratory Abnormalities in Lipase and Glucose

Number of Participants With Marked Laboratory Abnormalities in Urinalysis

Number of Participants With Serious Adverse Events (SAEs), Discontinuation Due to Adverse Events (AEs), and Who Died

Plasma Half-life (T-half) of Daclatasvir at Day 14

Time of Maximum Observed Plasma Concentration (Tmax) of Daclatasvir on Days 1 and 14

Time to Maximum Decline From Baseline in Hepatitis C Virus (HCV) RNA in Participants Without Baseline Drug Resistance