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

• Sponsor: Bristol-Myers Squibb (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00663208
• Collaborator: (none)
• Enrollment: 167
• Locations: 8
• Arms: 6
• Duration (Months): 13
• Patients Per Site: 20.9
• Patients Per Site Per Month: 1.6

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Chronic Hepatitis C	Drug: Daclatasvir; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 167 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: May 1, 2008
• Actual Primary Completion Date: Jun 1, 2009
• Actual Study Completion Date: Jun 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Group 1 Daclatasvir (1 mg), once daily or Matching Placebo, once daily	Drug: Daclatasvir; Capsule, Oral, Approximately 182 days from initial dosing; Drug: Placebo; Capsule, Oral, After 28 days from initial dosing and unblinding of the dose panel
Active Comparator: Group 2 Daclatasvir (10 mg), once daily or Matching Placebo, once daily	Drug: Daclatasvir; Capsule, Oral, Approximately 182 days from initial dosing; Drug: Placebo; Capsule, Oral, After 28 days from initial dosing and unblinding of the dose panel
Active Comparator: Group 3 Daclatasvir (1-100 mg), once or twice daily or Matching Placebo, once or twice daily	Drug: Daclatasvir; Capsule, Oral, Approximately 182 days from initial dosing; Drug: Placebo; Capsule, Oral, After 28 days from initial dosing and unblinding of the dose panel
Active Comparator: Group 4 Daclatasvir (1-100 mg), once or twice daily or Matching Placebo, once or twice daily	Drug: Daclatasvir; Capsule, Oral, Approximately 182 days from initial dosing; Drug: Placebo; Capsule, Oral, After 28 days from initial dosing and unblinding of the dose panel
Active Comparator: Group 5 Group 5: Active Comparator Daclatasvir (1-100 mg), once or twice daily or Matching Placebo, once or twice daily	Drug: Daclatasvir; Capsule, Oral, Approximately 182 days from initial dosing; Drug: Placebo; Capsule, Oral, After 28 days from initial dosing and unblinding of the dose panel
Active Comparator: Group 6 Group 6: Active Comparator Daclatasvir (1-100 mg), once or twice daily or Matching Placebo, once or twice daily	Drug: Daclatasvir; Capsule, Oral, Approximately 182 days from initial dosing; Drug: Placebo; Capsule, Oral, After 28 days from initial dosing and unblinding of the dose panel

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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

2. 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.

3. 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.

4. 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.

5. 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.

6. 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.

7. 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.

8. 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.

9. 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.

10. 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.

11. 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.

12. 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).

13. 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.

14. 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).

15. 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.

16. 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.

17. 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.

18. 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.

19. 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.

20. 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.

21. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Advanced Clinical Res Inst	Anaheim	California	United States	92801
2	West Coast Clinical Trials, Llc	Cypress	California	United States	90630
3	Yale University School of Medicine	New Haven	Connecticut	United States	06510
4	Elite Research Institute	Miami	Florida	United States	33169
5	Orlando Clinical Research Center	Orlando	Florida	United States	32809
6	Parexel International Corporation	Baltimore	Maryland	United States	21225
7	Alamo Medical Research	San Antonio	Texas	United States	78215
8	Local Institution	Santurce		Puerto Rico	00909

Sponsors and Collaborators

• Bristol-Myers Squibb

Investigators

• Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Bristol-Myers Squibb
• ClinicalTrials.gov Identifier: NCT00663208
• Other Study ID Numbers: AI444-004
• First Posted: Apr 22, 2008
• Last Update Posted: Oct 14, 2015
• Last Verified: Sep 1, 2015

• Additional relevant MeSH terms: Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Hepatitis

Study Results

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 Detail	A total of 30 participants received study treatment.

Arm/Group Title	Daclatasvir (1 mg) QD	Daclatasvir (10 mg) QD	Daclatasvir (30 mg) QD	Daclatasvir (60 mg) QD	Daclatasvir (30 mg) BID	Daclatasvir (100 mg) QD	Placebo
Arm/Group Description	Participants received once daily (QD) dose of daclatasvir 1 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	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.	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.	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.	Participants received twice daily (BID) dose of daclatasvir 30 mg during 14 day treatment period. Participants who received daclatasvir were followed up at Day 28, Day 42, Day 98 and Day 182.	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.	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.
Period Title: Treatment Period
STARTED	4	4	4	4	4	4	6
COMPLETED	4	3	4	4	4	4	6
NOT COMPLETED	0	1	0	0	0	0	0
Period Title: Treatment Period
STARTED	4	3	4	4	4	4	6
COMPLETED	1	3	1	2	4	4	5
NOT COMPLETED	3	0	3	2	0	0	1

Baseline Characteristics

Arm/Group Title	Daclatasvir (1 mg) QD	Daclatasvir (10 mg) QD	Daclatasvir (30 mg) QD	Daclatasvir (60 mg) QD	Daclatasvir (30 mg) BID	Daclatasvir (100 mg) QD	Placebo	Total
Arm/Group Description	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.	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.	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.	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.	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.	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.	Participants received QD/BID dose of placebo matched to daclatasvir during 14 day treatment period. Participants who received placebo were discharged after Day 28 and after unblinding of the dose panel.	Total of all reporting groups
Overall Participants	4	4	4	4	4	4	6	30
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	39.5 (9.95)	46.5 (13.00)	47.5 (3.70)	39.5 (7.55)	44.8 (6.40)	44.3 (6.90)	48.0 (4.20)	44.5 (7.65)
Sex: Female, Male (Count of Participants)
Female	1 25%	1 25%	0 0%	1 25%	0 0%	1 25%	1 16.7%	5 16.7%
Male	3 75%	3 75%	4 100%	3 75%	4 100%	3 75%	5 83.3%	25 83.3%

Outcome Measures

1. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Daclatasvir (1 mg) QD	Daclatasvir (10 mg) QD	Daclatasvir (30 mg) QD	Daclatasvir (60 mg) QD	Daclatasvir (30 mg) BID	Daclatasvir (100 mg) QD	Placebo
Arm/Group Description	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.	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.	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.	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.	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.	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.	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.
Measure Participants	4	4	4	3	3	3	6
Mean (90% Confidence Interval) [log10 IU/mL]	-2.13	-3.31	-2.91	-2.58	-3.03	-3.56	0.00

2. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Daclatasvir (1 mg) QD	Daclatasvir (10 mg) QD	Daclatasvir (30 mg) QD	Daclatasvir (60 mg) QD	Daclatasvir (30 mg) BID	Daclatasvir (100 mg) QD	Placebo
Arm/Group Description	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.	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.	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.	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.	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.	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.	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.
Measure Participants	4	4	4	4	4	4	6
Mean (90% Confidence Interval) [log10 IU/mL]	-2.13	-3.31	-2.91	-2.58	-3.03	-3.56	0.00

3. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Daclatasvir (1 mg) QD	Daclatasvir (10 mg) QD	Daclatasvir (30 mg) QD	Daclatasvir (60 mg) QD	Daclatasvir (30 mg) BID	Daclatasvir (100 mg) QD	Placebo
Arm/Group Description	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.	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.	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.	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..	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.	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.	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.
Measure Participants	4	4	4	3	3	3	6
Change at Hour 2	0.02 (0.137)	-0.00 (0.083)	-0.21 (0.244)	-0.43 (0.324)	-0.35 (0.284)	0.04 (0.107)	-0.00 (0.216)
Change at Hour 4	-0.78 (0.273)	-0.91 (0.206)	-1.22 (0.202)	-1.24 (0.711)	-1.24 (0.397)	-1.01 (0.345)	0.07 (0.248)
Change at Hour 6	-1.47 (0.466)	-1.73 (0.272)	-2.05 (0.237)	-1.96 (0.717)	-1.99 (0.552)	-1.36 (0.473)	0.00 (0.209)
Change at Hour 8	-1.92 (0.516)	-2.12 (0.216)	-2.62 (0.195)	-2.47 (0.733)	-2.59 (0.509)	-1.74 (0.917)	-0.01 (0.251)
Change at Hour 12	-2.18 (0.439)	-2.44 (0.092)	-2.91 (0.083)	-3.08 (0.562)	-2.92 (0.511)	-2.00 (1.158)	-0.01 (0.284)
Change at Hour 16	-2.09 (0.420)	-2.76 (0.183)	-2.95 (0.250)	-3.38 (0.521)	-3.04 (0.535)	-2.03 (1.009)	-0.00 (0.246)
Change at Hour 20	-1.92 (0.447)	-2.80 (0.095)	-3.02 (0.086)	-3.50 (0.312)	-3.38 (0.477)	-2.29 (1.240)	0.01 (0.155)
Change at Hour 24	-1.82 (0.480)	-2.97 (0.216)	-3.24 (0.103)	-3.60 (0.204)	-3.53 (0.624)	-2.58 (1.292)	0.02 (0.246)

4. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Daclatasvir (1 mg) QD	Daclatasvir (10 mg) QD	Daclatasvir (30 mg) QD	Daclatasvir (60 mg) QD	Daclatasvir (30 mg) BID	Daclatasvir (100 mg) QD	Placebo
Arm/Group Description	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.	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.	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.	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.	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.	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.	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.
Measure Participants	4	4	4	3	3	3	6
Mean (90% Confidence Interval) [log10 IU/mL]	-2.16	-3.29	-3.04	-3.85	-3.82	-3.14	-0.07

5. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Daclatasvir (1 mg) QD	Daclatasvir (10 mg) QD	Daclatasvir (30 mg) QD	Daclatasvir (60 mg) QD	Daclatasvir (30 mg) BID	Daclatasvir (100 mg) QD	Placebo
Arm/Group Description	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.	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.	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.	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.	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.	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.	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.
Measure Participants	4	4	4	3	3	3	6
Mean (90% Confidence Interval) [log10 IU/mL]	-1.89	-2.32	-1.68	-1.34	-3.55	-1.35	-0.59

6. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Daclatasvir (1 mg) QD	Daclatasvir (10 mg) QD	Daclatasvir (30 mg) QD	Daclatasvir (60 mg) QD	Daclatasvir (30 mg) BID	Daclatasvir (100 mg) QD	Placebo
Arm/Group Description	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.	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.	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.	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.	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.	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.	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.
Measure Participants	4	4	4	3	3	3	6
Mean (Standard Deviation) [Days]	4.50 (4.726)	5.25 (2.363)	3.50 (2.380)	3.33 (1.528)	10.33 (6.028)	7.67 (6.429)	10.17 (6.524)

7. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Daclatasvir (1 mg) QD	Daclatasvir (10 mg) QD	Daclatasvir (30 mg) QD	Daclatasvir (60 mg) QD	Daclatasvir (30 mg) BID	Daclatasvir (100 mg) QD	Placebo
Arm/Group Description	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.	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.	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.	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.	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.	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.	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.
Measure Participants	4	4	4	3	3	3	6
Mean (Standard Deviation) [log10 IU/mL]	-2.81 (0.700)	-3.63 (0.776)	-3.31 (0.050)	-4.03 (0.626)	-4.88 (1.335)	-3.62 (0.170)	-1.32 (1.629)

8. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Daclatasvir (1 mg) QD	Daclatasvir (10 mg) QD	Daclatasvir (30 mg) QD	Daclatasvir (60 mg) QD	Daclatasvir (30 mg) BID	Daclatasvir (100 mg) QD
Arm/Group Description	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.	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.	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.	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.	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.	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.
Measure Participants	4	4	4	4	4	4
Cmax at Day 1	15.731 (48)	159.665 (41)	483.365 (25)	1409.202 (13)	563.569 (26)	1960.732 (21)
Cmax at Day 14	10.430 (76)	154.196 (49)	555.878 (38)	1726.383 (21)	831.792 (37)	1853.925 (26)
Cmin at Day 1	1.212 (105)	15.141 (49)	41.114 (34)	129.822 (25)	171.330 (53)	174.642 (21)
Cmin at Day 14	1.234 (95)	23.674 (53)	61.635 (42)	254.602 (42)	206.941 (74)	287.852 (37)

9. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Daclatasvir (1 mg) QD	Daclatasvir (10 mg) QD	Daclatasvir (30 mg) QD	Daclatasvir (60 mg) QD	Daclatasvir (30 mg) BID	Daclatasvir (100 mg) QD
Arm/Group Description	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.	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.	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.	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.	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.	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.
Measure Participants	4	4	4	4	4	4
Day 1	111.8 (54)	1113.6 (38)	3528.6 (19)	10691.5 (20)	3307.2 (36)	15136.1 (19)
Day 14	92.0 (80)	1332.1 (46)	4391.3 (27)	15120.9 (35)	5431.6 (35)	17592.8 (15)

10. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Daclatasvir (1 mg) QD	Daclatasvir (10 mg) QD	Daclatasvir (30 mg) QD	Daclatasvir (60 mg) QD	Daclatasvir (30 mg) BID	Daclatasvir (100 mg) QD
Arm/Group Description	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.	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.	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.	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.	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.	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.
Measure Participants	4	4	4	4	4	4
Mean (Standard Deviation) [h]	11.68 (2.214)	14.31 (3.848)	12.99 (2.039)	12.81 (1.233)	13.04 (3.654)	15.19 (3.411)

11. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Daclatasvir (1 mg) QD	Daclatasvir (10 mg) QD	Daclatasvir (30 mg) QD	Daclatasvir (60 mg) QD	Daclatasvir (30 mg) BID	Daclatasvir (100 mg) QD
Arm/Group Description	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.	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.	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.	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.	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.	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.
Measure Participants	4	4	4	4	4	4
Geometric Mean (Geometric Coefficient of Variation) [mL/min]	181.118 (52)	125.119 (52)	113.861 (25)	66.133 (29)	92.054 (35)	94.736 (15)

12. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Daclatasvir (1 mg) QD	Daclatasvir (10 mg) QD	Daclatasvir (30 mg) QD	Daclatasvir (60 mg) QD	Daclatasvir (30 mg) BID	Daclatasvir (100 mg) QD
Arm/Group Description	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.	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.	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.	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.	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.	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.
Measure Participants	4	4	4	4	4	4
Day 1	4.659 (54)	46.401 (38)	147.024 (19)	445.478 (20)	275.596 (36)	630.673 (19)
Day 14	3.834 (80)	55.503 (46)	182.972 (27)	630.039 (35)	452.634 (35)	733.035 (15)

13. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Daclatasvir (1 mg) QD	Daclatasvir (10 mg) QD	Daclatasvir (30 mg) QD	Daclatasvir (60 mg) QD	Daclatasvir (30 mg) BID	Daclatasvir (100 mg) QD
Arm/Group Description	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.	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.	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.	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.	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.	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.
Measure Participants	4	4	4	4	4	4
AI AUC(TAU)	0.823 (29)	1.196 (16)	1.245 (20)	1.414 (17)	1.642 (16)	1.162 (25)
AI Cmax	0.663 (57)	0.966 (26)	1.150 (28)	1.225 (10)	1.476 (32)	0.946 (42)
Degree of Fluctuation	2.389 (13)	2.335 (18)	2.659 (25)	2.321 (24)	1.251 (18)	2.133 (12)

14. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Daclatasvir (1 mg) QD	Daclatasvir (10 mg) QD	Daclatasvir (30 mg) QD	Daclatasvir (60 mg) QD	Daclatasvir (30 mg) BID	Daclatasvir (100 mg) QD
Arm/Group Description	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.	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.	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.	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.	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.	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.
Measure Participants	4	4	4	4	4	4
Day 1	2.000	1.000	1.000	1.500	2.500	1.500
Day 14	1.250	1.250	1.000	1.000	1.750	1.750

15. Secondary Outcome

Title	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
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	All Daclatasvir Treated Participants
Arm/Group Description	All participants who received daclatasvir during 14 day treatment period.
Measure Participants	21
Cmax and Delta log10 HCV RNA at Day 4	-0.61
AUC(Tau) and Delta log10 HCV RNA at Day 4	-0.61
Cmin and Delta log10 HCV RNA at Day 4	-0.63
Cmax and Maximum Decline in log10 HCV RNA	-0.51
AUC(Tau) and Maximum Decline in log10 HCV RNA	-0.50
Cmin and Maximum Decline in log10 HCV RNA	-0.59

16. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

All participants who received study drug were summarized.

Arm/Group Title	Daclatasvir (1 mg) QD	Daclatasvir (10 mg) QD	Daclatasvir (30 mg) QD	Daclatasvir (60 mg) QD	Daclatasvir (30 mg) BID	Daclatasvir (100 mg) QD	Placebo
Arm/Group Description	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.	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.	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.	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.	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.	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.	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.
Measure Participants	4	4	4	4	4	4	6
SAEs	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Discontinuation Due to AEs	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Death	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

17. Secondary Outcome

Title	Number of Participants With Marked Laboratory Abnormalities in Hematology
Description	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

Outcome Measure Data

Analysis Population Description

All participants treated with study drug were summarized.

Arm/Group Title	Daclatasvir (1 mg) QD	Daclatasvir (10 mg) QD	Daclatasvir (30 mg) QD	Daclatasvir (60 mg) QD	Daclatasvir (30 mg) BID	Daclatasvir (100 mg) QD	Placebo
Arm/Group Description	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.	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.	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.	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.	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.	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.	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.
Measure Participants	4	4	4	4	4	4	6
Low Hematocrit	0 0%	0 0%	0 0%	1 25%	0 0%	0 0%	0 0%
Low Hemoglobin	1 25%	0 0%	0 0%	1 25%	0 0%	0 0%	1 16.7%
Low Platelet	0 0%	0 0%	0 0%	0 0%	0 0%	1 25%	0 0%
High Eosinophils	0 0%	0 0%	0 0%	0 0%	0 0%	1 25%	0 0%
High Leukocytes	0 0%	0 0%	0 0%	0 0%	0 0%	1 25%	0 0%

18. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

All participants who were treated with study drug were summarized.

Arm/Group Title	Daclatasvir (1 mg) QD	Daclatasvir (10 mg) QD	Daclatasvir (30 mg) QD	Daclatasvir (60 mg) QD	Daclatasvir (30 mg) BID	Daclatasvir (100 mg) QD	Placebo
Arm/Group Description	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.	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.	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.	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.	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.	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.	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.
Measure Participants	4	4	4	4	4	4	6
ALT High	0 0%	1 25%	0 0%	1 25%	2 50%	2 50%	0 0%
AST High	0 0%	1 25%	0 0%	0 0%	2 50%	2 50%	1 16.7%
ALP High	0 0%	0 0%	0 0%	0 0%	0 0%	1 25%	0 0%
GGT	0 0%	0 0%	2 50%	0 0%	2 50%	1 25%	2 33.3%
Phosporus Low	1 25%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Potassium High	0 0%	0 0%	1 25%	0 0%	0 0%	0 0%	1 16.7%

19. Secondary Outcome

Title	Number of Participants With Marked Laboratory Abnormalities in Lipase and Glucose
Description	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

Outcome Measure Data

Analysis Population Description

All participants treated with study drug were summarized.

Arm/Group Title	Daclatasvir (1 mg) QD	Daclatasvir (10 mg) QD	Daclatasvir (30 mg) QD	Daclatasvir (60 mg) QD	Daclatasvir (30 mg) BID	Daclatasvir (100 mg) QD	Placebo
Arm/Group Description	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.	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.	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.	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.	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.	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.	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.
Measure Participants	4	4	4	4	4	4	6
Lipase High	0 0%	1 25%	0 0%	0 0%	1 25%	0 0%	0 0%
Glucose Fasting High	0 0%	0 0%	0 0%	0 0%	0 0%	1 25%	1 16.7%

20. Secondary Outcome

Title	Number of Participants With Marked Laboratory Abnormalities in Urinalysis
Description	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

Outcome Measure Data

Analysis Population Description

All participants treated with study drug were summarized.

Arm/Group Title	Daclatasvir (1 mg) QD	Daclatasvir (10 mg) QD	Daclatasvir (30 mg) QD	Daclatasvir (60 mg) QD	Daclatasvir (30 mg) BID	Daclatasvir (100 mg) QD	Placebo
Arm/Group Description	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.	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.	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.	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.	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.	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.	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.
Measure Participants	4	4	4	4	4	4	6
Urine Blood High	1 25%	1 25%	0 0%	1 25%	0 0%	0 0%	1 16.7%
Urine Glucose High	1 25%	0 0%	0 0%	0 0%	0 0%	0 0%	2 33.3%

21. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

All participants treated with study drug were summarized.

Arm/Group Title	Daclatasvir (1 mg) QD	Daclatasvir (10 mg) QD	Daclatasvir (30 mg) QD	Daclatasvir (60 mg) QD	Daclatasvir (30 mg) BID	Daclatasvir (100 mg) QD	Placebo
Arm/Group Description	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.	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.	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.	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.	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.	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.	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.
Measure Participants	4	4	4	4	4	4	6
Number [participants]	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

22. Secondary Outcome

Title	Number of Participants Meeting Pre-Specified Criteria in Electrocardiogram Parameters
Description	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

Outcome Measure Data

Analysis Population Description

All participants treated with study drug were summarized.

Arm/Group Title	Daclatasvir (1 mg) QD	Daclatasvir (10 mg) QD	Daclatasvir (30 mg) QD	Daclatasvir (60 mg) QD	Daclatasvir (30 mg) BID	Daclatasvir (100 mg) QD	Placebo
Arm/Group Description	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.	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.	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.	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.	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.	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.	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.
Measure Participants	4	4	4	4	4	4	6
Heart Rate <=50 bpm	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Heart Rate > 100 bpm	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
HR Change from baseline <-20bpm	0 0%	0 0%	0 0%	0 0%	4 100%	0 0%	0 0%
Maximum QTcF <= 450 msec	4 100%	4 100%	4 100%	4 100%	4 100%	4 100%	6 100%
Maximum QTcF >450 msec	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Maximum Delta QTcF<=30	4 100%	4 100%	4 100%	4 100%	4 100%	4 100%	6 100%
Maximum Delta QTcF >30 msec	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Maximum QRS <=120 msec	4 100%	4 100%	4 100%	4 100%	4 100%	4 100%	6 100%
Maximum QRS > 120 msec	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Maximum PR <=200 msec	4 100%	4 100%	4 100%	4 100%	4 100%	4 100%	6 100%
Maximum PR > 200 msec	0 0%	0 0%	0 0%	0 0%	0 0%	1 25%	0 0%

Adverse Events

Arm/Group Title	Daclatasvir (1 mg) QD		Daclatasvir (10 mg) QD		Daclatasvir (100 mg) QD		Daclatasvir (30 mg) BID		Daclatasvir (30 mg) QD		Daclatasvir (60 mg) QD		Placebo
Arm/Group Description	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.		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.		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.		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.		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.		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.		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.
All Cause Mortality
	Daclatasvir (1 mg) QD		Daclatasvir (10 mg) QD		Daclatasvir (100 mg) QD		Daclatasvir (30 mg) BID		Daclatasvir (30 mg) QD		Daclatasvir (60 mg) QD		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Daclatasvir (1 mg) QD		Daclatasvir (10 mg) QD		Daclatasvir (100 mg) QD		Daclatasvir (30 mg) BID		Daclatasvir (30 mg) QD		Daclatasvir (60 mg) QD		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/4 (0%)		0/4 (0%)		0/4 (0%)		0/6 (0%)
Other (Not Including Serious) Adverse Events
	Daclatasvir (1 mg) QD		Daclatasvir (10 mg) QD		Daclatasvir (100 mg) QD		Daclatasvir (30 mg) BID		Daclatasvir (30 mg) QD		Daclatasvir (60 mg) QD		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/4 (25%)		4/4 (100%)		2/4 (50%)		2/4 (50%)		3/4 (75%)		4/4 (100%)		4/6 (66.7%)
Eye disorders
Vision blurred	0/4 (0%)		0/4 (0%)		0/4 (0%)		1/4 (25%)		0/4 (0%)		0/4 (0%)		0/6 (0%)
Visual acuity reduced	0/4 (0%)		1/4 (25%)		0/4 (0%)		0/4 (0%)		0/4 (0%)		0/4 (0%)		0/6 (0%)
Gastrointestinal disorders
Vomiting	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/4 (0%)		0/4 (0%)		0/4 (0%)		1/6 (16.7%)
Diarrhoea	0/4 (0%)		1/4 (25%)		1/4 (25%)		0/4 (0%)		0/4 (0%)		0/4 (0%)		0/6 (0%)
Flatulence	0/4 (0%)		1/4 (25%)		0/4 (0%)		0/4 (0%)		0/4 (0%)		0/4 (0%)		0/6 (0%)
Abdominal discomfort	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/4 (0%)		0/4 (0%)		1/4 (25%)		0/6 (0%)
Abdominal pain	0/4 (0%)		0/4 (0%)		1/4 (25%)		0/4 (0%)		0/4 (0%)		0/4 (0%)		1/6 (16.7%)
Dyspepsia	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/4 (0%)		0/4 (0%)		0/4 (0%)		1/6 (16.7%)
Nausea	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/4 (0%)		0/4 (0%)		0/4 (0%)		1/6 (16.7%)
Dry mouth	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/4 (0%)		0/4 (0%)		1/4 (25%)		0/6 (0%)
Gingival pain	0/4 (0%)		1/4 (25%)		0/4 (0%)		0/4 (0%)		0/4 (0%)		0/4 (0%)		0/6 (0%)
Abdominal pain upper	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/4 (0%)		0/4 (0%)		1/4 (25%)		0/6 (0%)
Faeces discoloured	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/4 (0%)		0/4 (0%)		1/4 (25%)		0/6 (0%)
General disorders
Energy increased	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/4 (0%)		1/4 (25%)		0/4 (0%)		0/6 (0%)
Fatigue	1/4 (25%)		1/4 (25%)		0/4 (0%)		0/4 (0%)		0/4 (0%)		0/4 (0%)		0/6 (0%)
Infections and infestations
Sinusitis	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/4 (0%)		1/4 (25%)		0/4 (0%)		0/6 (0%)
Urethritis	0/4 (0%)		0/4 (0%)		1/4 (25%)		0/4 (0%)		0/4 (0%)		0/4 (0%)		0/6 (0%)
Injury, poisoning and procedural complications
Eye injury	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/4 (0%)		1/4 (25%)		0/4 (0%)		0/6 (0%)
Tongue injury	0/4 (0%)		1/4 (25%)		0/4 (0%)		0/4 (0%)		0/4 (0%)		0/4 (0%)		0/6 (0%)
Investigations
Electrocardiogram T wave abnormal	0/4 (0%)		1/4 (25%)		0/4 (0%)		0/4 (0%)		0/4 (0%)		0/4 (0%)		0/6 (0%)
Musculoskeletal and connective tissue disorders
Pain in extremity	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/4 (0%)		0/4 (0%)		0/4 (0%)		1/6 (16.7%)
Cervical spinal stenosis	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/4 (0%)		0/4 (0%)		1/4 (25%)		0/6 (0%)
Back pain	0/4 (0%)		1/4 (25%)		0/4 (0%)		0/4 (0%)		0/4 (0%)		1/4 (25%)		0/6 (0%)
Arthralgia	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/4 (0%)		1/4 (25%)		0/4 (0%)		0/6 (0%)
Muscle spasms	0/4 (0%)		1/4 (25%)		0/4 (0%)		0/4 (0%)		0/4 (0%)		0/4 (0%)		0/6 (0%)
Nervous system disorders
Headache	0/4 (0%)		1/4 (25%)		1/4 (25%)		1/4 (25%)		0/4 (0%)		2/4 (50%)		2/6 (33.3%)
Syncope	0/4 (0%)		1/4 (25%)		0/4 (0%)		0/4 (0%)		0/4 (0%)		0/4 (0%)		0/6 (0%)
Dizziness	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/4 (0%)		0/4 (0%)		1/4 (25%)		0/6 (0%)
Sinus headache	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/4 (0%)		0/4 (0%)		0/4 (0%)		1/6 (16.7%)
Somnolence	0/4 (0%)		0/4 (0%)		0/4 (0%)		1/4 (25%)		0/4 (0%)		0/4 (0%)		0/6 (0%)
Psychiatric disorders
Insomnia	1/4 (25%)		0/4 (0%)		0/4 (0%)		0/4 (0%)		0/4 (0%)		1/4 (25%)		0/6 (0%)
Restlessness	1/4 (25%)		0/4 (0%)		0/4 (0%)		0/4 (0%)		0/4 (0%)		0/4 (0%)		0/6 (0%)
Nightmare	0/4 (0%)		1/4 (25%)		0/4 (0%)		0/4 (0%)		0/4 (0%)		0/4 (0%)		0/6 (0%)
Sleep disorder	1/4 (25%)		0/4 (0%)		0/4 (0%)		0/4 (0%)		0/4 (0%)		0/4 (0%)		0/6 (0%)
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/4 (0%)		1/4 (25%)		0/4 (0%)		0/6 (0%)
Skin and subcutaneous tissue disorders
Photosensitivity reaction	0/4 (0%)		0/4 (0%)		0/4 (0%)		1/4 (25%)		0/4 (0%)		0/4 (0%)		0/6 (0%)
Dry skin	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/4 (0%)		1/4 (25%)		0/4 (0%)		0/6 (0%)
Vascular disorders
Hot flush	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/4 (0%)		0/4 (0%)		1/4 (25%)		0/6 (0%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.