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The purpose of this study is to assess the effect of renal function impairment on the single dose pharmacokinetics of Daclatasvir.
Treatment, Parallel Assignment, Open Label, Non-Randomized, Single Dose Adaptive Design, Pharmacokinetics Study
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group A (Normal renal function): Daclatasvir | Experimental | Daclatasvir 60 mg tablet by mouth single dose on Day 1 |
|
| Group B (End Stage Renal Disease): Daclatasvir | Experimental | Daclatasvir 60 mg tablet by mouth single dose on Day 1 |
|
| Group C (Moderate renal impairment): Daclatasvir | Experimental | Daclatasvir 60 mg tablet by mouth single dose on Day 1 |
|
| Group D (Severe renal impairment): Daclatasvir | Experimental | Daclatasvir 60 mg tablet by mouth single dose on Day 1 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Daclatasvir | Drug |
|
| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinite Time [AUC(INF)] of Daclatasvir | 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. | Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose |
| Measure | Description | Time Frame |
|---|---|---|
| Unbound Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity Time (AUC(INF)u) of Daclatasvir | 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. | Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose |
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Inclusion Criteria:
- Meet renal function criteria in one of four categories
Exclusion Criteria:
- Unstable or uncontrolled medical conditions
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| Name | Affiliation | Role |
|---|---|---|
| Bristol-Myers Squibb | Bristol-Myers Squibb | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Orlando Clinical Research Center | Orlando | Florida | 32809 | United States | ||
| Davita Clinical Research |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25654812 | Derived | Garimella T, Wang R, Luo WL, Hwang C, Sherman D, Kandoussi H, Marbury TC, Alcorn H, Bertz R, Bifano M. Single-dose pharmacokinetics and safety of daclatasvir in subjects with renal function impairment. Antivir Ther. 2015;20(5):535-43. doi: 10.3851/IMP2941. Epub 2015 Feb 5. |
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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.
The study was conducted at 2 centers in United States of America.
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| ID | Title | Description |
|---|---|---|
| FG000 | Normal Renal Function/Mild Renal Impairment | 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. |
| FG001 | Mild/Moderate Renal Impairment | 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. |
| FG002 | Mild/Severe Renal Impairment | 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. |
| FG003 | End Stage Renal Disease | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Normal Renal Function/Mild Renal Impairment | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinite Time [AUC(INF)] of Daclatasvir | 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanograms*hours/milliliter (ng*h/mL) | Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose |
First dose up to Day 5 post last dose of study treatment for AEs; up to 30 days post last dose for SAEs
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Group-A | 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. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 16.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Bristol-Myers Squibb Study Director | Bristol-Myers Squibb | Clinical.Trials@bms.com |
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| ID | Term |
|---|---|
| D006526 | Hepatitis C |
| ID | Term |
|---|---|
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D006525 | Hepatitis, Viral, Human |
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| ID | Term |
|---|---|
| C549273 | daclatasvir |
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|
| Maximum Observed Plasma Concentration (Cmax) of Daclatasvir | 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. | 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 of Daclatasvir | 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. | Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose |
| Area Under the Plasma Concentration-time Curve From Time Zero to Last Measurable Concentration [AUC(0-T)] of Daclatasvir | AUC(0-T) was calculated as the sum of linear trapezoids using non-compartmental analysis. | Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) of Daclatasvir | Tmax was defined as the time required to reach maximum observed plasma concentration. Tmax was directly determined from the raw plasma concentration-time data. | Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose |
| Plasma Half-life (T-half) of Daclatasvir | Terminal half-life was the time required for one half of the total amount of administered drug eliminated from the body. | 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 (CLT/F) of Daclatasvir | 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. | Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose |
| Unbound Apparent Clearance (CLU/F) of Daclatasvir | 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. | Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose |
| Percent Urinary Recovery (%UR) of Daclatasvir | 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. | Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose |
| Renal Clearance (CLR) of Daclatasvir | 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. | Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose |
| Apparent Volume of Distribution (Vd/F) of Daclatasvir | 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. | Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose |
| Number of Participants With Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events and Who Died | 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. | First dose up to Day 5 post last dose for AEs; up to 30 days post last dose for SAEs |
| Number of Participants With Clinically Significant Laboratory Marked Abnormalities Reported as Adverse Events | Significant laboratory abnormalities were defined as any test results which were observed beyond the clinically acceptable limits as per the discretion of investigator. | Baseline up to Day 5 post dose |
| Number of Participants With Clinically Relevant Changes in Electrocardiogram (ECG) Reported as Adverse Events | The number of participants with clinically relevant changes in ECG which were considered as adverse events was determined. | Baseline up to Day 5 post dose |
| Number of Participants With Out-of-range Vital Signs Reported as Adverse Events | The total number of participants with abnormal range vital signs which were considered as adverse events was determined. | Baseline up to Day 5 post dose |
| Minneapolis |
| Minnesota |
| 55404 |
| United States |
| BG001 | Mild/Moderate Renal Impairment | 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. |
| BG002 | Mild/Severe Renal Impairment | 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. |
| BG003 | End Stage Renal Disease | 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. |
| BG004 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| ID |
|---|
| Title |
|---|
| Description |
|---|
| OG000 | Normal Renal Function | 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. |
| OG001 | Mild Renal Impairment | 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. |
| OG002 | Moderate Renal Impairment | 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. |
| OG003 | Severe Renal Impairment | 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. |
| OG004 | End Stage Renal Disease | 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. |
|
|
| Secondary | Unbound Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity Time (AUC(INF)u) of Daclatasvir | 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose |
|
|
|
| Secondary | Maximum Observed Plasma Concentration (Cmax) of Daclatasvir | 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose |
|
|
|
| Secondary | Unbound Maximum Observed Plasma Concentrations of Daclatasvir | 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose |
|
|
|
| Secondary | Area Under the Plasma Concentration-time Curve From Time Zero to Last Measurable Concentration [AUC(0-T)] of Daclatasvir | AUC(0-T) was calculated as the sum of linear trapezoids using non-compartmental analysis. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hour (h)/mL | Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose |
|
|
|
| Secondary | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Daclatasvir | Tmax was defined as the time required to reach maximum observed plasma concentration. Tmax was directly determined from the raw plasma concentration-time data. | 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. | Posted | Median | Full Range | hours | Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose |
|
|
|
| Secondary | Plasma Half-life (T-half) of Daclatasvir | Terminal half-life was the time required for one half of the total amount of administered drug eliminated from the body. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | hours | Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose |
|
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| Secondary | Apparent Total Body Clearance (CLT/F) of Daclatasvir | 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | milliliter/minute (mL/min) | Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose |
|
|
|
| Secondary | Unbound Apparent Clearance (CLU/F) of Daclatasvir | 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | mL/min | Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose |
|
|
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| Secondary | Percent Urinary Recovery (%UR) of Daclatasvir | 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | Percentage of daclatasvir recovered | Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose |
|
|
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| Secondary | Renal Clearance (CLR) of Daclatasvir | 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | mL/min | Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose |
|
|
|
| Secondary | Apparent Volume of Distribution (Vd/F) of Daclatasvir | 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | Liters | Pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose |
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| Secondary | Number of Participants With Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events and Who Died | 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. | Analysis was done in safety data set population, defined as all the participants who received the study medication. | Posted | Number | Participants | First dose up to Day 5 post last dose for AEs; up to 30 days post last dose for SAEs |
|
|
|
| Secondary | Number of Participants With Clinically Significant Laboratory Marked Abnormalities Reported as Adverse Events | Significant laboratory abnormalities were defined as any test results which were observed beyond the clinically acceptable limits as per the discretion of investigator. | The analysis was done in safety population. | Posted | Number | Participants | Baseline up to Day 5 post dose |
|
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| Secondary | Number of Participants With Clinically Relevant Changes in Electrocardiogram (ECG) Reported as Adverse Events | The number of participants with clinically relevant changes in ECG which were considered as adverse events was determined. | Analysis was done in safety data set population. | Posted | Number | Participants | Baseline up to Day 5 post dose |
|
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| Secondary | Number of Participants With Out-of-range Vital Signs Reported as Adverse Events | The total number of participants with abnormal range vital signs which were considered as adverse events was determined. | Analysis was done in safety data set population. | Posted | Number | Participants | Baseline up to Day 5 post dose |
|
|
|
| 0 |
| 12 |
| 0 |
| 12 |
| EG001 | Mild/Moderate Renal Impairment | 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. | 0 | 6 | 1 | 6 |
| EG002 | Mild/Severe Renal Impairment | 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. | 0 | 6 | 1 | 6 |
| EG003 | End Stage Renal Disease | 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. | 0 | 12 | 3 | 12 |
| Dizziness | Nervous system disorders | MedDRA 16.0 | Systematic Assessment |
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| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
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| Palpitations | Cardiac disorders | MedDRA 16.0 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
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| Hypotension | Vascular disorders | MedDRA 16.0 | Systematic Assessment |
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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.
| D014777 |
| Virus Diseases |
| D018178 | Flaviviridae Infections |
| D012327 | RNA Virus Infections |
| D006505 | Hepatitis |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| Death |
|
| Discontinuations due to AEs |
|