Pharmacokinetic and Safety Study of Daclatasvir in Patients With Renal Impairment

• Sponsor: Bristol-Myers Squibb (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01830205
• Collaborator: (none)
• Enrollment: 58
• Locations: 2
• Arms: 4
• Duration (Months): 9
• Patients Per Site: 29
• Patients Per Site Per Month: 3.2

Study Details

Study Description

Brief Summary

The purpose of this study is to assess the effect of renal function impairment on the single dose pharmacokinetics of Daclatasvir.

Condition or Disease	Intervention/Treatment	Phase
Hepatitis C	Drug: Daclatasvir	Phase 1

Detailed Description

Treatment, Parallel Assignment, Open Label, Non-Randomized, Single Dose Adaptive Design, Pharmacokinetics Study

Study Design

• Study Type: Interventional
• Actual Enrollment: 58 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Single Dose Pharmacokinetics and Safety of Daclatasvir in Subjects With Renal Function Impairment
• Study Start Date: Sep 1, 2012
• Actual Primary Completion Date: Jun 1, 2013
• Actual Study Completion Date: Jun 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group A (Normal renal function): Daclatasvir Daclatasvir 60 mg tablet by mouth single dose on Day 1	Drug: Daclatasvir; Other Names: BMS-790052
Experimental: Group B (End Stage Renal Disease): Daclatasvir Daclatasvir 60 mg tablet by mouth single dose on Day 1	Drug: Daclatasvir; Other Names: BMS-790052
Experimental: Group C (Moderate renal impairment): Daclatasvir Daclatasvir 60 mg tablet by mouth single dose on Day 1	Drug: Daclatasvir; Other Names: BMS-790052
Experimental: Group D (Severe renal impairment): Daclatasvir Daclatasvir 60 mg tablet by mouth single dose on Day 1	Drug: Daclatasvir; Other Names: BMS-790052

Outcome Measures

Primary Outcome Measures

1. Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinite Time [AUC(INF)] of Daclatasvir [Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose]

   AUC(INF) was estimated by summing the area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration and the extrapolated area, computed by the quotient of the last observable concentration and elimination rate constant. The pharmacokinetic (PK) analysis was based on Cockcroft-Gault (C-G) creatinine clearance (CLcr) grouping method: normal renal function, end stage renal disease (ESRD), moderate and severe renal impairment. Mild participants were counted as per their original allocation.

Secondary Outcome Measures

1. Unbound Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity Time (AUC(INF)u) of Daclatasvir [Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose]

   AUC(INF)u was calculated by multiplying the area under the plasma concentration-time curve from time zero extrapolated to infinite time by mean fraction of unbound drug from 1 hour post-dose time point.

2. Maximum Observed Plasma Concentration (Cmax) of Daclatasvir [Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose]

   Maximum observed plasma concentration following drug administration from the raw plasma concentration-time data. The plasma samples were analyzed for daclatasvir by using a validated liquid chromatography tandem mass spectrometric (LC-MS/MS) assay.

3. Unbound Maximum Observed Plasma Concentrations of Daclatasvir [Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose]

   Unbound Maximum observed plasma concentrations (Cmaxu) was calculated by multiplying maximum observed plasma concentrations by mean fraction of unbound drug from 1 hour post-dose time point.

4. Area Under the Plasma Concentration-time Curve From Time Zero to Last Measurable Concentration [AUC(0-T)] of Daclatasvir [Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose]

   AUC(0-T) was calculated as the sum of linear trapezoids using non-compartmental analysis.

5. Time to Reach Maximum Observed Plasma Concentration (Tmax) of Daclatasvir [Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose]

   Tmax was defined as the time required to reach maximum observed plasma concentration. Tmax was directly determined from the raw plasma concentration-time data.

6. Plasma Half-life (T-half) of Daclatasvir [Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose]

   Terminal half-life was the time required for one half of the total amount of administered drug eliminated from the body.

7. Apparent Total Body Clearance (CLT/F) of Daclatasvir [Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose]

   Apparent total body clearance was calculated by dividing the dose by area under the plasma concentration-time curve from time zero extrapolated to infinite time.

8. Unbound Apparent Clearance (CLU/F) of Daclatasvir [Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose]

   The CLU/F was calculated by dividing the apparent total body clearance by mean fraction of unbound drug from 1 hour post dose time point.

9. Percent Urinary Recovery (%UR) of Daclatasvir [Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose]

   The percentage of daclatasvir recovered in the urine was determined by using validated liquid chromatography-tandem mass spectrometry methods. The sum of the percentage of dose recovered in urine from all intervals was calculated to obtain the total percentage of urinary excretion.

10. Renal Clearance (CLR) of Daclatasvir [Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose]

    The CLR was calculated by dividing the total amount excreted in the urine from 0 to 96 hours by the area under the plasma concentration-time curve from time zero extrapolated to infinite time.

11. Apparent Volume of Distribution (Vd/F) of Daclatasvir [Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose]

    The Vd/F was calculated by dividing the product of the dose and mean residence time by area under the plasma concentration-time curve from time zero extrapolated to infinite time.

12. Number of Participants With Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events and Who Died [First dose up to Day 5 post last dose for AEs; up to 30 days post last dose for SAEs]

    Adverse event (AE) was defined as any new unfavorable symptom, sign, or disease or worsening of a pre-existing condition that does not necessarily have a causal relationship with treatment. SAE was defined as a medical event that at any dose resulted in death, persistent or significant disability/incapacity, or drug dependency/abuse; was life-threatening, an important medical event, or a congenital anomaly/birth defect; or required or prolonged hospitalisation.

13. Number of Participants With Clinically Significant Laboratory Marked Abnormalities Reported as Adverse Events [Baseline up to Day 5 post dose]

    Significant laboratory abnormalities were defined as any test results which were observed beyond the clinically acceptable limits as per the discretion of investigator.

14. Number of Participants With Clinically Relevant Changes in Electrocardiogram (ECG) Reported as Adverse Events [Baseline up to Day 5 post dose]

    The number of participants with clinically relevant changes in ECG which were considered as adverse events was determined.

15. Number of Participants With Out-of-range Vital Signs Reported as Adverse Events [Baseline up to Day 5 post dose]

    The total number of participants with abnormal range vital signs which were considered as adverse events was determined.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Meet renal function criteria in one of four categories

Exclusion Criteria:

• Unstable or uncontrolled medical conditions

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Orlando Clinical Research Center	Orlando	Florida	United States	32809
2	Davita Clinical Research	Minneapolis	Minnesota	United States	55404

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: NCT01830205
• Other Study ID Numbers: AI444-063
• First Posted: Apr 12, 2013
• Last Update Posted: Nov 16, 2015
• Last Verified: Nov 1, 2015

• Additional relevant MeSH terms: Hepatitis C

Study Results

Participant Flow

Recruitment Details	The study was conducted at 2 centers in United States of America.
Pre-assignment Detail	A total of 58 participants were enrolled and 36 were treated with study drug. Remaining 22 were not treated (14 no longer met study criteria, 4 other reasons, 2 administrative reasons and 2 withdrew consent). Participants were grouped by Cockcroft-Gault creatine clearance method for primary analysis.

Arm/Group Title	Normal Renal Function/Mild Renal Impairment	Mild/Moderate Renal Impairment	Mild/Severe Renal Impairment	End Stage Renal Disease
Arm/Group Description	Participants with normal renal function and had creatinine clearance by the Cockcroft-Gault method >=90 milliliter per minute were administered with single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1. One participant from this group, who had estimated glomerular filtration rate (eGFR) 60-89 mL/min per 1.73 m^2, was reallocated into mild renal impairment reporting arm and was administered with a single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1. Original allocation was based on an estimated eGFR, while the reallocation was based on the eGFR measurement at baseline.	Participants with moderate renal impairment and had eGFR 30-59 mL/min per 1.73 m^2 were administered with single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1. Two participants from this group, who had eGFR 60-89 mL/min per 1.73 m^2, were reallocated into mild renal impairment reporting arm and were administered with a single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1. Original allocation was based on an estimated eGFR, while the reallocation was based on the eGFR measurement at baseline.	Participants with severe renal impairment and had eGFR 15 to 29 mL/min per 1.73 m^2 were administered with single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1. One participant from this group, who had eGFR 60-89 mL/min per 1.73 m^2, was reallocated into mild renal impairment reporting arm and was administered with a single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1. Original allocation was based on an estimated eGFR, while the reallocation was based on the eGFR measurement at baseline.	Participants with end stage renal disease and had eGFR <15 mL/ min per 1.73 m^2, with or without hemodialysis were administered with single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1.
Period Title: Overall Study
STARTED	12	6	6	12
COMPLETED	12	6	6	12
NOT COMPLETED	0	0	0	0

Baseline Characteristics

Arm/Group Title	Normal Renal Function/Mild Renal Impairment	Mild/Moderate Renal Impairment	Mild/Severe Renal Impairment	End Stage Renal Disease	Total
Arm/Group Description	Participants with normal renal function and had creatinine clearance by the Cockcroft-Gault method >=90 milliliter per minute were administered with single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1. One participant from this group, who had eGFR 60-89 mL/min per 1.73 m^2, was reallocated into mild renal impairment reporting arm and was administered with a single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1. Original allocation was based on an estimated eGFR, while the reallocation was based on the eGFR measurement at baseline.	Participants with moderate renal impairment and had eGFR 30-59 mL/min per 1.73 m^2 were administered with single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1. Two participants from this group, who had eGFR 60-89 mL/min per 1.73 m^2, were reallocated into mild renal impairment reporting arm and were administered with a single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1. Original allocation was based on an estimated eGFR, while the reallocation was based on the eGFR measurement at baseline.	Participants with severe renal impairment and had eGFR 15 to 29 mL/min per 1.73 m^2 were administered with single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1. One participant from this group, who had eGFR 60-89 mL/min per 1.73 m^2, was reallocated into mild renal impairment reporting arm and was administered with a single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1. Original allocation was based on an estimated eGFR, while the reallocation was based on the eGFR measurement at baseline.	Participants with end stage renal disease and had eGFR <15 mL/ min per 1.73 m^2, with or without hemodialysis were administered with single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1.	Total of all reporting groups
Overall Participants	12	6	6	12	36
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	48.6 (8.5)	62.0 (12.6)	66.3 (9.9)	49.0 (11.7)	53.9 (12.6)
Sex: Female, Male (Count of Participants)
Female	1 8.3%	2 33.3%	2 33.3%	1 8.3%	6 16.7%
Male	11 91.7%	4 66.7%	4 66.7%	11 91.7%	30 83.3%
Region of Enrollment (participants) [Number]
United States	12 100%	6 100%	6 100%	12 100%	36 100%

Outcome Measures

1. Primary Outcome

Title	Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinite Time [AUC(INF)] of Daclatasvir
Description	AUC(INF) was estimated by summing the area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration and the extrapolated area, computed by the quotient of the last observable concentration and elimination rate constant. The pharmacokinetic (PK) analysis was based on Cockcroft-Gault (C-G) creatinine clearance (CLcr) grouping method: normal renal function, end stage renal disease (ESRD), moderate and severe renal impairment. Mild participants were counted as per their original allocation.
Time Frame	Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose

Outcome Measure Data

Analysis Population Description

PK data set included all participants who received at least 1 dose of daclatasvir with adequate PK profiles. The PK analysis was based on the C-G CLcr grouping method: normal renal function (n=11), ESRD (n=10), moderate (n=5) and severe renal impairment (n=6). Mild participants (n=4) are also counted as per their original allocation.

Arm/Group Title	Normal Renal Function	Mild Renal Impairment	Moderate Renal Impairment	Severe Renal Impairment	End Stage Renal Disease
Arm/Group Description	Participants with normal renal function and had creatinine clearance by the Cockcroft-Gault method >= 90 milliliter per minute were administered with single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1.	Participants were reallocated from other arms (normal, moderate and severe renal impairment) with mild renal impairment who had eGFR 60-89 mL/min per 1.73 m^2 were administered with single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1.	Participants with moderate renal impairment and had eGFR 30-59 mL/min per 1.73 m^2 were administered with single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1.	Participants with severe renal impairment and had eGFR 15 to 29 mL/min per 1.73 m^2 were administered with single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1.	Participants with end stage renal disease and had estimated glomerular filtration rate (eGFR) < 15 mL/ min per 1.73 m^2, with or without hemodialysis were administered with single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1.
Measure Participants	11	4	5	6	10
Geometric Mean (Geometric Coefficient of Variation) [nanograms*hours/milliliter (ng*h/mL)]	11215.264 (40)	21261.199 (62)	24789.951 (35)	21946.450 (39)	14257.489 (25)

2. Secondary Outcome

Title	Unbound Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity Time (AUC(INF)u) of Daclatasvir
Description	AUC(INF)u was calculated by multiplying the area under the plasma concentration-time curve from time zero extrapolated to infinite time by mean fraction of unbound drug from 1 hour post-dose time point.
Time Frame	Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) data set included all participants who received at least 1 dose of daclatasvir with adequate PK profiles. The PK analysis was based on C-G CLcr grouping method: normal renal function (n=11), ESRD (n=10), moderate (n=5) and severe renal impairment (n=6). Mild participants (n=4) are also counted as per their original allocation.

Arm/Group Title	Normal Renal Function	Mild Renal Impairment	Moderate Renal Impairment	Severe Renal Impairment	End Stage Renal Disease
Arm/Group Description	Participants with normal renal function and had creatinine clearance by the Cockcroft-Gault method >= 90 milliliter per minute were administered with single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1.	Participants were reallocated from other arms (normal, moderate and severe renal impairment) with mild renal impairment who had eGFR 60-89 mL/min per 1.73 m^2 were administered with single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1.	Participants with moderate renal impairment and had eGFR 30-59 mL/min per 1.73 m^2 were administered with single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1.	Participants with severe renal impairment and had eGFR 15 to 29 mL/min per 1.73 m^2 were administered with single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1	Participants with end stage renal disease and had estimated glomerular filtration rate (eGFR) <15 mL/ min per 1.73 m^2, with or without hemodialysis were administered with single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1.
Measure Participants	11	4	5	6	10
Geometric Mean (Geometric Coefficient of Variation) [ng*h/mL]	83.845 (37)	128.157 (41)	144.915 (13)	139.576 (43)	100.736 (31)

3. Secondary Outcome

Title	Maximum Observed Plasma Concentration (Cmax) of Daclatasvir
Description	Maximum observed plasma concentration following drug administration from the raw plasma concentration-time data. The plasma samples were analyzed for daclatasvir by using a validated liquid chromatography tandem mass spectrometric (LC-MS/MS) assay.
Time Frame	Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) data set included all participants who received at least 1 dose of daclatasvir with adequate PK profiles. The PK analysis was based on C-G CLcr grouping method: normal renal function (n=11), ESRD (n=10), moderate (n=5) and severe renal impairment (n=6). Mild participants (n=4) are also counted as per their original allocation.

Arm/Group Title	Normal Renal Function	Mild Renal Impairment	Moderate Renal Impairment	Severe Renal Impairment	End Stage Renal Disease
Arm/Group Description	Participants with normal renal function and had creatinine clearance by the Cockcroft-Gault method >= 90 milliliter per minute were administered with single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1	Participants were reallocated from other arms (normal, moderate and severe renal impairment) with mild renal impairment who had eGFR 60-89 mL/min per 1.73 m^2 were administered with single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1.	Participants with moderate renal impairment and had eGFR 30-59 mL/min per 1.73 m^2 were administered with single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1	Participants with severe renal impairment and had eGFR 15 to 29 mL/min per 1.73 m^2 were administered with single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1.	Participants with end stage renal disease and had estimated glomerular filtration rate (eGFR) <15 mL/ min per 1.73 m^2, with or without hemodialysis were administered with single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1.
Measure Participants	11	4	5	6	10
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	1111.497 (39)	1619.572 (13)	1745.845 (31)	1207.137 (33)	1085.344 (15)

4. Secondary Outcome

Title	Unbound Maximum Observed Plasma Concentrations of Daclatasvir
Description	Unbound Maximum observed plasma concentrations (Cmaxu) was calculated by multiplying maximum observed plasma concentrations by mean fraction of unbound drug from 1 hour post-dose time point.
Time Frame	Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) data set included all participants who received at least 1 dose of daclatasvir with adequate PK profiles. The PK analysis was based on C-G CLcr grouping method: normal renal function (n=11), ESRD (n=10), moderate (n=5) and severe renal impairment (n=6). Mild participants (n=4) are also counted as per their original allocation.

Arm/Group Title	Normal Renal Function	Mild Renal Impairment	Moderate Renal Impairment	Severe Renal Impairment	End Stage Renal Disease
Arm/Group Description	Participants with normal renal function and had creatinine clearance by the Cockcroft-Gault method >= 90 milliliter per minute were administered with single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1.	Participants were reallocated from other arms (normal, moderate and severe renal impairment) with mild renal impairment who had eGFR 60-89 mL/min per 1.73 m^2 were administered with single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1.	Participants with moderate renal impairment and had eGFR 30-59 mL/min per 1.73 m^2 were administered with single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1.	Participants with severe renal impairment and had eGFR 15 to 29 mL/min per 1.73 m^2 were administered with single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1	Participants with end stage renal disease and had estimated glomerular filtration rate (eGFR) <15 mL/ min per 1.73 m^2, with or without hemodialysis were administered with single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1.
Measure Participants	11	4	5	6	10
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	8.309 (34)	9.762 (14)	10.206 (20)	7.677 (33)	7.668 (36)

5. Secondary Outcome

Title	Area Under the Plasma Concentration-time Curve From Time Zero to Last Measurable Concentration [AUC(0-T)] of Daclatasvir
Description	AUC(0-T) was calculated as the sum of linear trapezoids using non-compartmental analysis.
Time Frame	Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) data set included all participants who received at least 1 dose of daclatasvir with adequate PK profiles. The analysis was based on C-G CLcr grouping method: normal renal function (n=11), ESRD (n=10), moderate (n=5) and severe renal impairment (n=6). Mild participants (n=4) are also counted as per their original allocation.

Arm/Group Title	Normal Renal Function	Mild Renal Impairment	Moderate Renal Impairment	Severe Renal Impairment	End Stage Renal Disease
Arm/Group Description	Participants with normal renal function and had creatinine clearance by the Cockcroft-Gault method >= 90 milliliter per minute were administered with single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1.	Participants were reallocated from other arms (normal, moderate and severe renal impairment) with mild renal impairment who had eGFR 60-89 mL/min per 1.73 m^2 were administered with single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1.	Participants with moderate renal impairment and had eGFR 30-59 mL/min per 1.73 m^2 were administered with single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1.	Participants with severe renal impairment and had eGFR 15 to 29 mL/min per 1.73 m^2 were administered with single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1.	Participants with end stage renal disease and had estimated glomerular filtration rate (eGFR) <15 mL/ min per 1.73 m^2, with or without hemodialysis were administered with single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1.
Measure Participants	11	4	5	6	10
Geometric Mean (Geometric Coefficient of Variation) [ng*hour (h)/mL]	11092.967 (40)	20852.129 (60)	24343.711 (36)	21238.909 (37)	13934.562 (25)

6. Secondary Outcome

Title	Time to Reach Maximum Observed Plasma Concentration (Tmax) of Daclatasvir
Description	Tmax was defined as the time required to reach maximum observed plasma concentration. Tmax was directly determined from the raw plasma concentration-time data.
Time Frame	Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) data set included all participants who received at least 1 dose of daclatasvir with adequate PK profiles. The PK analysis was based on C-G CLcr grouping method: normal renal function (n=11), ESRD (n=10), moderate (n=5) and severe renal impairment (n=6). Mild participants (n=4) are also counted as per their original allocation.

Arm/Group Title	Normal Renal Function	Mild Renal Impairment	Moderate Renal Impairment	Severe Renal Impairment	End Stage Renal Disease
Arm/Group Description	Participants with normal renal function and had creatinine clearance by the Cockcroft-Gault method >= 90 milliliter per minute were administered with single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1.	Participants were reallocated from other arms (normal, moderate and severe renal impairment) with mild renal impairment who had eGFR 60-89 mL/min per 1.73 m^2 were administered with single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1.	Participants with moderate renal impairment and had eGFR 30-59 mL/min per 1.73 m^2 were administered with single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1.	Participants with severe renal impairment and had eGFR 15 to 29 mL/min per 1.73 m^2 were administered with single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1.	Participants with end stage renal disease and had estimated glomerular filtration rate (eGFR) <15 mL/ min per 1.73 m^2, with or without hemodialysis were administered with single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1.
Measure Participants	11	4	5	6	10
Median (Full Range) [hours]	1.000	1.250	1.000	1.500	1.250

7. Secondary Outcome

Title	Plasma Half-life (T-half) of Daclatasvir
Description	Terminal half-life was the time required for one half of the total amount of administered drug eliminated from the body.
Time Frame	Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) data set included all participants who received at least 1 dose of daclatasvir with adequate PK profiles. The PK analysis was based on C-G CLcr grouping method: normal renal function (n=11), ESRD (n=10), moderate (n=5) and severe renal impairment (n=6). Mild participants (n=4) are also counted as per their original allocation.

Arm/Group Title	Normal Renal Function	Mild Renal Impairment	Moderate Renal Impairment	Severe Renal Impairment	End Stage Renal Disease
Arm/Group Description	Participants with normal renal function and had creatinine clearance by the Cockcroft-Gault method >= 90 milliliter per minute were administered with single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1.	Participants were reallocated from other arms (normal, moderate and severe renal impairment) with mild renal impairment who had eGFR 60-89 mL/min per 1.73 m^2 were administered with single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1.	Participants with moderate renal impairment and had eGFR 30-59 mL/min per 1.73 m^2 were administered with single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1.	Participants with severe renal impairment and had eGFR 15 to 29 mL/min per 1.73 m^2 were administered with single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1.	Participants with end stage renal disease and had estimated glomerular filtration rate (eGFR) <15 mL/ min per 1.73 m^2, with or without hemodialysis were administered with single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1.
Measure Participants	11	4	5	6	10
Geometric Mean (Geometric Coefficient of Variation) [hours]	13.625 (25)	15.661 (31)	16.912 (19)	20.224 (24)	15.678 (37)

8. Secondary Outcome

Title	Apparent Total Body Clearance (CLT/F) of Daclatasvir
Description	Apparent total body clearance was calculated by dividing the dose by area under the plasma concentration-time curve from time zero extrapolated to infinite time.
Time Frame	Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) data set included all participants who received at least 1 dose of daclatasvir with adequate PK profiles. The PK analysis was based on C-G CLcr grouping method: normal renal function (n=11), ESRD (n=10), moderate (n=5) and severe renal impairment (n=6). Mild participants (n=4) are also counted as per their original allocation.

Arm/Group Title	Normal Renal Function	Mild Renal Impairment	Moderate Renal Impairment	Severe Renal Impairment	End Stage Renal Disease
Arm/Group Description	Participants with normal renal function and had creatinine clearance by the Cockcroft-Gault method >= 90 milliliter per minute were administered with single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1.	Participants were reallocated from other arms (normal, moderate and severe renal impairment) with mild renal impairment who had eGFR 60-89 mL/min per 1.73 m^2 were administered with single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1.	Participants with moderate renal impairment and had eGFR 30-59 mL/min per 1.73 m^2 were administered with single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1.	Participants with severe renal impairment and had eGFR 15 to 29 mL/min per 1.73 m^2 were administered with single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1.	Participants with end stage renal disease and had estimated glomerular filtration rate (eGFR) <15 mL/ min per 1.73 m^2, with or without hemodialysis were administered with single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1.
Measure Participants	11	4	5	6	10
Geometric Mean (Geometric Coefficient of Variation) [milliliter/minute (mL/min)]	89.164 (26)	47.034 (43)	40.339 (27)	45.565 (31)	70.139 (33)

9. Secondary Outcome

Title	Unbound Apparent Clearance (CLU/F) of Daclatasvir
Description	The CLU/F was calculated by dividing the apparent total body clearance by mean fraction of unbound drug from 1 hour post dose time point.
Time Frame	Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) data set included all participants who received at least 1 dose of daclatasvir with adequate PK profiles. The PK analysis was based on C-G CLcr grouping method: normal renal function (n=11), ESRD (n=10), moderate (n=5) and severe renal impairment (n=6). Mild participants (n=4) are also counted as per their original allocation.

Arm/Group Title	Normal Renal Function	Mild Renal Impairment	Moderate Renal Impairment	Severe Renal Impairment	End Stage Renal Disease
Arm/Group Description	Participants with normal renal function and had creatinine clearance by the Cockcroft-Gault method >= 90 milliliter per minute were administered with single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1.	Participants were reallocated from other arms (normal, moderate and severe renal impairment) with mild renal impairment who had eGFR 60-89 mL/min per 1.73 m^2 were administered with single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1.	Participants with moderate renal impairment and had eGFR 30-59 mL/min per 1.73 m^2 were administered with single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1.	Participants with severe renal impairment and had eGFR 15 to 29 mL/min per 1.73 m^2 were administered with single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1.	Participants with end stage renal disease and had estimated glomerular filtration rate (eGFR) <15 mL/ min per 1.73 m^2, with or without hemodialysis were administered with single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1.
Measure Participants	11	4	5	6	10
Geometric Mean (Geometric Coefficient of Variation) [mL/min]	11926.796 (53)	7802.955 (33)	6900.602 (13)	7164.575 (41)	9926.962 (35)

10. Secondary Outcome

Title	Percent Urinary Recovery (%UR) of Daclatasvir
Description	The percentage of daclatasvir recovered in the urine was determined by using validated liquid chromatography-tandem mass spectrometry methods. The sum of the percentage of dose recovered in urine from all intervals was calculated to obtain the total percentage of urinary excretion.
Time Frame	Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) data set included all participants who received at least 1 dose of daclatasvir with adequate PK profiles. The PK analysis was based on C-G CLcr grouping method: normal renal function (n=11), ESRD (n=3), moderate (n=5) and severe renal impairment (n=5). Mild participants (n=4) are also counted as per their original allocation.

Arm/Group Title	Normal Renal Function	Mild Renal Impairment	Moderate Renal Impairment	Severe Renal Impairment	End Stage Renal Disease
Arm/Group Description	Participants with normal renal function and had creatinine clearance by the Cockcroft-Gault method >= 90 milliliter per minute were administered with single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1.	Participants were reallocated from other arms (normal, moderate and severe renal impairment) with mild renal impairment who had eGFR 60-89 mL/min per 1.73 m^2 were administered with single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1.	Participants with moderate renal impairment and had eGFR 30-59 mL/min per 1.73 m^2 were administered with single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1.	Participants with severe renal impairment and had eGFR 15 to 29 mL/min per 1.73 m^2 were administered with single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1.	Participants with end stage renal disease and had estimated glomerular filtration rate (eGFR) <15 mL/ min per 1.73 m^2, with or without hemodialysis were administered with single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1.
Measure Participants	11	4	5	5	3
Geometric Mean (Geometric Coefficient of Variation) [Percentage of daclatasvir recovered]	5.007 (36)	5.820 (27)	3.530 (40)	2.658 (58)	0.199 (131)

11. Secondary Outcome

Title	Renal Clearance (CLR) of Daclatasvir
Description	The CLR was calculated by dividing the total amount excreted in the urine from 0 to 96 hours by the area under the plasma concentration-time curve from time zero extrapolated to infinite time.
Time Frame	Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) data set included all participants who received at least 1 dose of daclatasvir with adequate PK profiles. The PK analysis was based on C-G CLcr grouping method: normal renal function (n=11), ESRD (n=3), moderate (n=5) and severe renal impairment (n=5). Mild participants (n=4) are also counted as per their original allocation.

Arm/Group Title	Normal Renal Function	Mild Renal Impairment	Moderate Renal Impairment	Severe Renal Impairment	End Stage Renal Disease
Arm/Group Description	Participants with normal renal function and had creatinine clearance by the Cockcroft-Gault method >= 90 milliliter per minute were administered with single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1.	Participants were reallocated from other arms (normal, moderate and severe renal impairment) with mild renal impairment who had eGFR 60-89 mL/min per 1.73 m^2 were administered with single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1.	Participants with moderate renal impairment and had eGFR 30-59 mL/min per 1.73 m^2 were administered with single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1.	Participants with severe renal impairment and had eGFR 15 to 29 mL/min per 1.73 m^2 were administered with single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1.	Participants with end stage renal disease and had estimated glomerular filtration rate (eGFR) <15 mL/ min per 1.73 m^2, with or without hemodialysis were administered with single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1.
Measure Participants	11	4	5	5	3
Geometric Mean (Geometric Coefficient of Variation) [mL/min]	4.465 (29)	2.737 (28)	1.424 (48)	1.165 (37)	0.147 (114)

12. Secondary Outcome

Title	Apparent Volume of Distribution (Vd/F) of Daclatasvir
Description	The Vd/F was calculated by dividing the product of the dose and mean residence time by area under the plasma concentration-time curve from time zero extrapolated to infinite time.
Time Frame	Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) data set included all participants who received at least 1 dose of daclatasvir with adequate PK profiles. The PK analysis was based on C-G CLcr grouping method: normal renal function (n=11), ESRD (n=10), moderate (n=5) and severe renal impairment (n=6). Mild participants (n=4) are also counted as per their original allocation.

Arm/Group Title	Normal Renal Function	Mild Renal Impairment	Moderate Renal Impairment	Severe Renal Impairment	End Stage Renal Disease
Arm/Group Description	Participants with normal renal function and had creatinine clearance by the Cockcroft-Gault method >= 90 milliliter per minute were administered with single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1.	Participants were re-randomized from other arms (normal, moderate and severe renal impairment) with mild renal impairment who had eGFR 60-89 mL/min per 1.73 m^2 were administered with single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1.	Participants with moderate renal impairment and had eGFR 30-59 mL/min per 1.73 m^2 were administered with single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1	Participants with severe renal impairment and had eGFR 15 to 29 mL/min per 1.73 m^2 were administered with single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1.	Participants with end stage renal disease and had estimated glomerular filtration rate (eGFR) <15 mL/ min per 1.73 m^2, with or without hemodialysis were administered with single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1.
Measure Participants	11	4	5	6	10
Geometric Mean (Geometric Coefficient of Variation) [Liters]	105.157 (37)	63.761 (30)	59.054 (36)	79.769 (35)	95.186 (37)

13. Secondary Outcome

Title	Number of Participants With Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events and Who Died
Description	Adverse event (AE) was defined as any new unfavorable symptom, sign, or disease or worsening of a pre-existing condition that does not necessarily have a causal relationship with treatment. SAE was defined as a medical event that at any dose resulted in death, persistent or significant disability/incapacity, or drug dependency/abuse; was life-threatening, an important medical event, or a congenital anomaly/birth defect; or required or prolonged hospitalisation.
Time Frame	First dose up to Day 5 post last dose for AEs; up to 30 days post last dose for SAEs

Outcome Measure Data

Analysis Population Description

Analysis was done in safety data set population, defined as all the participants who received the study medication.

Arm/Group Title	Normal Renal Function/Mild Renal Impairment	Mild/Moderate Renal Impairment	Mild/Severe Renal Impairment	End Stage Renal Disease
Arm/Group Description	Participants with normal renal function and had creatinine clearance by the Cockcroft-Gault method >=90 milliliter per minute were administered with single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1. One participant from this group, who had eGFR 60-89 mL/min per 1.73 m^2, was reallocated into mild renal impairment reporting arm and was administered with a single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1. Original allocation was based on an estimated eGFR, while the reallocation was based on the eGFR measurement at baseline.	Participants with moderate renal impairment and had eGFR 30-59 mL/min per 1.73 m^2 were administered with single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1. Two participants from this group, who had eGFR 60-89 mL/min per 1.73 m^2, were reallocated into mild renal impairment reporting arm and were administered with a single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1.Original allocation was based on an estimated eGFR, while the reallocation was based on the eGFR measurement at baseline.	Participants with severe renal impairment and had eGFR 15 to 29 mL/min per 1.73 m^2 were administered with single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1. One participant from this group, who had eGFR 60-89 mL/min per 1.73 m^2, was reallocated into mild renal impairment reporting arm and was administered with a single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1. Original allocation was based on an estimated eGFR, while the reallocation was based on the eGFR measurement at baseline.	Participants with end stage renal disease and had eGFR <15 mL/ min per 1.73 m^2, with or without hemodialysis were administered with single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1.
Measure Participants	12	6	6	12
SAEs	0 0%	0 0%	0 0%	0 0%
Death	0 0%	0 0%	0 0%	0 0%
Discontinuations due to AEs	0 0%	0 0%	0 0%	0 0%

14. Secondary Outcome

Title	Number of Participants With Clinically Significant Laboratory Marked Abnormalities Reported as Adverse Events
Description	Significant laboratory abnormalities were defined as any test results which were observed beyond the clinically acceptable limits as per the discretion of investigator.
Time Frame	Baseline up to Day 5 post dose

Outcome Measure Data

Analysis Population Description

The analysis was done in safety population.

Arm/Group Title	Normal Renal Function/Mild Renal Impairment	Mild/Moderate Renal Impairment	Mild/Severe Renal Impairment	End Stage Renal Disease
Arm/Group Description	Participants with normal renal function and had creatinine clearance by the Cockcroft-Gault method >=90 milliliter per minute were administered with single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1. One participant from this group, who had eGFR 60-89 mL/min per 1.73 m^2, was reallocated into mild renal impairment reporting arm and was administered with a single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1. Original allocation was based on an estimated eGFR, while the reallocation was based on the eGFR measurement at baseline.	Participants with moderate renal impairment and had eGFR 30-59 mL/min per 1.73 m^2 were administered with single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1. Two participants from this group, who had eGFR 60-89 mL/min per 1.73 m^2, were reallocated into mild renal impairment reporting arm and were administered with a single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1. Original allocation was based on an estimated eGFR, while the reallocation was based on the eGFR measurement at baseline.	Participants with severe renal impairment and had eGFR 15 to 29 mL/min per 1.73 m^2 were administered with single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1. One participant from this group, who had eGFR 60-89 mL/min per 1.73 m^2, was reallocated into mild renal impairment reporting arm and was administered with a single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1. Original allocation was based on an estimated eGFR, while the reallocation was based on the eGFR measurement at baseline.	Participants with end stage renal disease and had eGFR <15 mL/ min per 1.73 m^2, with or without hemodialysis were administered with single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1.
Measure Participants	12	6	6	12
Number [Participants]	0 0%	0 0%	0 0%	0 0%

15. Secondary Outcome

Title	Number of Participants With Clinically Relevant Changes in Electrocardiogram (ECG) Reported as Adverse Events
Description	The number of participants with clinically relevant changes in ECG which were considered as adverse events was determined.
Time Frame	Baseline up to Day 5 post dose

Outcome Measure Data

Analysis Population Description

Analysis was done in safety data set population.

Arm/Group Title	Normal Renal Function/Mild Renal Impairment	Mild/Moderate Renal Impairment	Mild/Severe Renal Impairment	End Stage Renal Disease
Arm/Group Description	Participants with normal renal function and had creatinine clearance by the Cockcroft-Gault method >=90 milliliter per minute were administered with single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1. One participant from this group, who had eGFR 60-89 mL/min per 1.73 m^2, was reallocated into mild renal impairment reporting arm and was administered with a single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1. Original allocation was based on an estimated eGFR, while the reallocation was based on the eGFR measurement at baseline.	Participants with moderate renal impairment and had eGFR 30-59 mL/min per 1.73 m^2 were administered with single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1. Two participants from this group, who had eGFR 60-89 mL/min per 1.73 m^2, were reallocated into mild renal impairment reporting arm and were administered with a single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1. Original allocation was based on an estimated eGFR, while the reallocation was based on the eGFR measurement at baseline.	Participants with severe renal impairment and had eGFR 15 to 29 mL/min per 1.73 m^2 were administered with single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1. One participant from this group, who had eGFR 60-89 mL/min per 1.73 m^2, was reallocated into mild renal impairment reporting arm and was administered with a single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1. Original allocation was based on an estimated eGFR, while the reallocation was based on the eGFR measurement at baseline.	Participants with end stage renal disease and had eGFR <15 mL/ min per 1.73 m^2, with or without hemodialysis were administered with single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1.
Measure Participants	12	6	6	12
Number [Participants]	0 0%	0 0%	0 0%	0 0%

16. Secondary Outcome

Title	Number of Participants With Out-of-range Vital Signs Reported as Adverse Events
Description	The total number of participants with abnormal range vital signs which were considered as adverse events was determined.
Time Frame	Baseline up to Day 5 post dose

Outcome Measure Data

Analysis Population Description

Analysis was done in safety data set population.

Arm/Group Title	Normal Renal Function/Mild Renal Impairment	Mild/Moderate Renal Impairment	Mild/Severe Renal Impairment	End Stage Renal Disease
Arm/Group Description	Participants with normal renal function and had creatinine clearance by the Cockcroft-Gault method >=90 milliliter per minute were administered with single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1. One participant from this group, who had eGFR 60-89 mL/min per 1.73 m^2, was reallocated into mild renal impairment reporting arm and was administered with a single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1. Original allocation was based on an estimated eGFR, while the reallocation was based on the eGFR measurement at baseline.	Participants with moderate renal impairment and had eGFR 30-59 mL/min per 1.73 m^2 were administered with single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1. Two participants from this group, who had eGFR 60-89 mL/min per 1.73 m^2, were reallocated into mild renal impairment reporting arm and were administered with a single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1. Original allocation was based on an estimated eGFR, while the reallocation was based on the eGFR measurement at baseline.	Participants with severe renal impairment and had eGFR 15 to 29 mL/min per 1.73 m^2 were administered with single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1. One participant from this group, who had eGFR 60-89 mL/min per 1.73 m^2, was reallocated into mild renal impairment reporting arm and was administered with a single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1. Original allocation was based on an estimated eGFR, while the reallocation was based on the eGFR measurement at baseline.	Participants with end stage renal disease and had eGFR <15 mL/ min per 1.73 m^2, with or without hemodialysis were administered with single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1.
Measure Participants	12	6	6	12
Number [Participants]	0 0%	0 0%	0 0%	1 8.3%

Adverse Events

Time Frame	First dose up to Day 5 post last dose of study treatment for AEs; up to 30 days post last dose for SAEs
Arm/Group Title	Group-A		Mild/Moderate Renal Impairment		Mild/Severe Renal Impairment		End Stage Renal Disease
Arm/Group Description	Participants with normal renal function and had creatinine clearance by the Cockcroft-Gault method >=90 milliliter per minute were administered with single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1. One participant from this group, who had eGFR 60-89 mL/min per 1.73 m^2, was reallocated into mild renal impairment reporting arm and was administered with a single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1. Original allocation was based on an estimated eGFR, while the reallocation was based on the eGFR measurement at baseline.		Participants with moderate renal impairment and had eGFR 30-59 mL/min per 1.73 m^2 were administered with single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1. Two participants from this group, who had eGFR 60-89 mL/min per 1.73 m^2, were reallocated into mild renal impairment reporting arm and were administered with a single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1. Original allocation was based on an estimated eGFR, while the reallocation was based on the eGFR measurement at baseline.		Participants with severe renal impairment and had eGFR 15 to 29 mL/min per 1.73 m^2 were administered with single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1. One participant from this group, who had eGFR 60-89 mL/min per 1.73 m^2, was reallocated into mild renal impairment reporting arm and was administered with a single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1. Original allocation was based on an estimated eGFR, while the reallocation was based on the eGFR measurement at baseline.		Participants with end stage renal disease and had eGFR <15 mL/ min per 1.73 m^2, with or without hemodialysis were administered with single oral dose of daclatasvir 60 mg tablet after 10 hours of overnight fasting on Day 1.
All Cause Mortality
	Group-A		Mild/Moderate Renal Impairment		Mild/Severe Renal Impairment		End Stage Renal Disease
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Group-A		Mild/Moderate Renal Impairment		Mild/Severe Renal Impairment		End Stage Renal Disease
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/6 (0%)		0/6 (0%)		0/12 (0%)
Other (Not Including Serious) Adverse Events
	Group-A		Mild/Moderate Renal Impairment		Mild/Severe Renal Impairment		End Stage Renal Disease
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		1/6 (16.7%)		1/6 (16.7%)		3/12 (25%)
Cardiac disorders
Palpitations	0/12 (0%)		0/6 (0%)		0/6 (0%)		1/12 (8.3%)
Gastrointestinal disorders
Gastrooesophageal reflux disease	0/12 (0%)		1/6 (16.7%)		0/6 (0%)		0/12 (0%)
Nausea	0/12 (0%)		0/6 (0%)		0/6 (0%)		1/12 (8.3%)
Metabolism and nutrition disorders
Hyperglycaemia	0/12 (0%)		0/6 (0%)		1/6 (16.7%)		0/12 (0%)
Nervous system disorders
Dizziness	0/12 (0%)		0/6 (0%)		0/6 (0%)		1/12 (8.3%)
Vascular disorders
Hypotension	0/12 (0%)		0/6 (0%)		0/6 (0%)		1/12 (8.3%)

Limitations/Caveats

[Not Specified]

More Information

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.