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The purpose of this study is to assess the pharmacokinetics of a single oral dose of 5 mg Apixaban in subjects with normal renal function and subjects with end stage renal disease (ESRD) maintained with hemodialysis.
Primary Purpose : To provide a clear understanding of the pharmacokinetics of Apixaban in subjects with ESRD and to determine the effect of hemodialysis on Apixaban pharmacokinetics .
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group A: Apixaban | Experimental |
| |
| Group B: Apixaban | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Apixaban | Drug | Tablets, Oral, 5 mg, Once, 4 days |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Geometric Mean of Maximum Observed Plasma Concentration (Cmax) of Single 5mg Oral Dose of Apixaban | Maximum observed plasma concentration (Cmax) was measured by plasma concentration of apixaban over time. The geometric means are reported in nanograms per milliliter (ng/mL). | 24 hours pre-dose to 72 hours post-dose |
| Geometric Mean of Maximum Observed Plasma Concentration (Cmax) of Metabolite BMS-730823 | Maximum observed plasma concentration (Cmax) was measured by plasma concentration of BMS-730823 over time. The geometric means are reported in nanograms per milliliter (ng/mL). | From 24 hours pre-dose to 72 hours post-dose |
| Geometric Mean of Area Under the Concentration-time Curve From Time Zero to Time of the Last Quantifiable Concentration (AUC(0-T)) of Single 5mg Oral Dose of Apixaban | Area under the concentration-time curve from time zero to time of the last quantifiable concentration (AUC(0-T)) was measured by plasma concentration of apixaban over time. The geometric means are reported in nanogram hours per milliliter (ng*h/mL). | 24 hours pre-dose to 72 hours post-dose |
| Geometric Mean of Area Under the Concentration-time Curve From Time Zero to Time of the Last Quantifiable Concentration (AUC(0-T)) of Metabolite BMS-730823 | Area under the concentration-time curve from time zero to time of the last quantifiable concentration (AUC(0-T)) was measured by plasma concentration of BMS-730823 over time. The geometric means are reported in nanogram hours per milliliter (ng*h/mL). | From 24 hours pre-dose to 72 hours post-dose |
| Geometric Mean of Area Under the Concentration-time Curve From Time Zero Extrapolated to Infinite Time (AUC(INF)) of Single 5mg Oral Dose of Apixaban | The area under the concentration-time curve from time zero extrapolated to infinite time (AUC(INF)) was measured by plasma concentration of apixaban over time. The geometric means are reported in nanogram hours per milliliter (ng*h/mL). |
| Measure | Description | Time Frame |
|---|---|---|
| Mean Maximum Percent Change From Baseline International Normalized Ratio (INR) Following a Single 5 mg Oral Dose of Apixaban | The mean maximum percent change in baseline for INR was reported for each arm. Baseline measurements were assessed up to 24 hours prior to Day 1 dosing. | From 24 hours pre-dose to 72 hours post-dose |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Laboratory Marked Abnormalities | ULN=Upper Limit of Normal, LLN=Lower Limit of Normal, Pre-Rx= Baseline value. BUN=Blood Urea Nitrogen (mmol/L=millimoles per Liter): High if BUN > 1.1*ULN (if Pre-Rx>ULN: >1.25*Pre-Rx). Platelet count (*10^9 cell/L): Low if Platelet Count < 0.85*LLN (if Pre-Rx<LLN: <0.85*Pre-Rx). Creatine (umol/L=micromoles per Liter): High if Creatine > 1.5*ULN (if Pre-Rx>ULN: >1.33*Pre-Rx). Calcium, Total (mmol/L): High if Calcium > 1.5*ULN (if Pre-Rx>ULN: >1.33*Pre-Rx). Potassium, serum (mmol/L): High if Potassium > 1.1*ULN (if Pre-Rx>ULN: >1.1*Pre-Rx; if Pre-Rx<LLN: >ULN). Phosphorus, Inorganic (mmol/L): Low if Phosphate < 0.85*LLN (if Pre-Rx>ULN: <LLN). Lactate dehydrogenase (U/L=Units per Liter): High if Lactate Dehydrogenase > 1.25*ULN (if Pre-Rx>ULN: >1.5*Pre-Rx). |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Bristol-Myers Squibb | Bristol-Myers Squibb | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Orlando | Florida | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26331581 | Result | Wang X, Tirucherai G, Marbury TC, Wang J, Chang M, Zhang D, Song Y, Pursley J, Boyd RA, Frost C. Pharmacokinetics, pharmacodynamics, and safety of apixaban in subjects with end-stage renal disease on hemodialysis. J Clin Pharmacol. 2016 May;56(5):628-36. doi: 10.1002/jcph.628. Epub 2015 Dec 22. |
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A total of 18 participants were enrolled in this study. 16 participants were treated and completed the study. Two participants were enrolled but not treated (one withdrew consent, one enrolled as alternate).
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| ID | Title | Description |
|---|---|---|
| FG000 | Normal Renal Function | Healthy participants with normal renal function (calculated creatinine clearance (ClCr) > 80 mL/min) received a single oral dose of 5 mg apixaban on the morning of Day 1. |
| FG001 | ESRD Maintained With Hemodialysis | Participants with End Stage Renal Disease (ESRD) maintained with hemodialysis received two doses of apixaban separated by a washout period of at least 7 days; one oral dose of 5mg apixaban 2 hours prior to hemodialysis on Day 1 of Period 1, and a second oral dose of 5mg apixaban immediately following the hemodialysis session on Day 1, Period 2. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
All treated participants
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| ID | Title | Description |
|---|---|---|
| BG000 | Normal Renal Function | Healthy participants with normal renal function (calculated creatinine clearance (ClCr) > 80 mL/min) received a single oral dose of 5 mg apixaban on the morning of Day 1. |
| BG001 | ESRD Maintained With Hemodialysis |
| 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 | Geometric Mean of Maximum Observed Plasma Concentration (Cmax) of Single 5mg Oral Dose of Apixaban | Maximum observed plasma concentration (Cmax) was measured by plasma concentration of apixaban over time. The geometric means are reported in nanograms per milliliter (ng/mL). | All treated participants | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | 24 hours pre-dose to 72 hours post-dose |
|
From Day 1 until 30 days post discontinuation, up to September 2011 (approximately 3 months)
Study initiated: June 2011
Study completed: September 2011
Participants underwent regular laboratory testing and investigator assessment as outlined in the study protocol.
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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 | Normal Renal Function | Healthy participants with normal renal function (calculated creatinine clearance (ClCr) > 80 mL/min) received a single oral dose of 5 mg apixaban on the morning of Day 1. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | Nervous system disorders | MedDRA 14.1 | 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 |
|---|---|
| D007676 | Kidney Failure, Chronic |
| ID | Term |
|---|---|
| D051436 | Renal Insufficiency, Chronic |
| D051437 | Renal Insufficiency |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
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| ID | Term |
|---|---|
| C522181 | apixaban |
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| Apixaban |
| Drug |
Tablets, Oral, 5 mg, Twice, 15 days |
|
| From 24 hours pre-dose to 72 hours post-dose |
| Geometric Mean of Area Under the Concentration-time Curve From Time Zero Extrapolated to Infinite Time (AUC(INF)) of BMS-730823 | The area under the concentration-time curve from time zero extrapolated to infinite time (AUC(INF)) was measured by plasma concentration of BMS-730823 over time. The geometric means are reported in nanogram hours per milliliter (ng*h/mL). | 24 hours pre-dose to 72 hours post-dose |
| Mean Plasma Terminal Half-life (T-Half) of Single 5mg Oral Dose of Apixaban | Plasma terminal half-life (T-Half) for apixaban was derived from plasma concentrations versus time data. Means were reported in hours. | From 24 hours pre-dose to 72 hours post-dose |
| Mean Plasma Terminal Half-life (T-Half) of BMS-730823 | Mean plasma terminal half-life (T-Half) for BMS-730823 was derived from plasma concentrations versus time data. | 24 hours pre-dose to 72 hours post-dose |
| Median Time of Maximum Observed Plasma Concentration (Tmax) of a Single 5 mg Oral Dose of Apixaban | Time of maximum observed plasma concentration (Tmax) for apixaban was derived from plasma concentrations versus time data. Medians were reported in hours. | From 24 hours pre-dose to 72 hours post-dose |
| Median Time of Maximum Observed Plasma Concentration (Tmax) of Metabolite BMS-730823 | Time of maximum observed plasma concentration (Tmax) for BMS-730823 was derived from plasma concentrations versus time data. Medians were reported in hours. | From 24 hours pre-dose to 72 hours post-dose |
| Geometric Mean of Area Under the Plasma Concentration-Time Curve From 2 to 6 Hours (AUC(2-6)) for Apixaban | Area under the plasma concentration-time curve from 2 hours to 6 hours (AUC(2-6) for Apixaban was measured in participants with ESRD during dialysis in Period 1 only. Geometric Means were reported in nanogram hours per milliliter (ng*hr/mL) and were determined from blood samples both entering and exiting the dialyzer. | 2 to 6 hours post-dose |
| Geometric Mean of Area Under the Plasma Concentration-Time Curve From 2 to 6 Hours (AUC(2-6)) for BMS-730823 | Area under the plasma concentration-time curve from 2 hours to 6 hours (AUC(2-6) for BMS-730823 was measured in participants with ESRD during dialysis in Period 1 only. Geometric Means were reported in nanogram hours per milliliter (ng*hr/mL) and were determined from blood samples both entering and exiting the dialyzer. | 2 to 6 hours post-dose |
| Mean Percent Dose of Apixaban Recovered in Urine (%UR) | The percent dose recovered in urine was calculated by dividing the cumulative amount of unchanged apixaban excreted in urine from the time of dose up to 72 hours post-dose by the apixaban dose administered. | 24 hours pre-dose to 72 hours post-dose |
| Mean Percent Dose of Apixaban Recovered in Dialysate (%DR) | Percent dose of Apixaban recovered in dialysate (%DR) was calculated by dividing the cumulative amount of apixaban excreted in each dialysate collection over 2-6 hours (DR(2-6)) by the apixaban dose. %DR was recorded only in period 1. | 2 to 6 hours post-dose |
| Mean Renal Clearance (CLR) of Apixaban | Renal clearance (CLR) was calculated by dividing the cumulative amount of apixaban excreted in urine by the respective cumulative plasma AUC over the same urine collection interval. Geometric means were reported in milliliters per minute (mL/min). | 24 hours pre-dose to 72 hours post-dose |
| Mean Renal Clearance (CLR) of BMS-730823 | Renal clearance (CLR) was calculated by dividing the cumulative amount of BMS-730823 excreted in urine by the respective cumulative plasma AUC over the same urine collection interval. Geometric means were reported in milliliters per minute (mL/min). | 24 hours pre-dose to 72 hours post-dose |
| Mean Hemodialysis Clearance (CLD) of Apixaban | Hemodialysis clearance (CLD) was calculated by dividing the cumulative amount of apixaban excreted in dialysate by the respective cumulative plasma AUC over the same dialysate collection interval (AUC(2-6) entering). CLD measurements occurred only in period 1. Geometric means were reported in milliliters per minute (mL/min). | 2 to 6 hours post-dose |
| Mean Hemodialysis Clearance (CLD) of BMS-730823 | Hemodialysis clearance (CLD) was calculated by dividing the cumulative amount of BMS-730823 excreted in dialysate by the respective cumulative plasma AUC over the same dialysate collection interval (AUC(2-6) entering). CLD measurements occurred only in period 1. Geometric means were reported in milliliters per minute (mL/min). | 2 to 6 hours post-dose |
| Percentage of Apixaban Extracted During Hemodialysis | The percentage of apixaban extracted during hemodialysis (extraction ratio) was calculated using the formula [plasma AUC(2-6) exiting - AUC(2-6) entering] / [AUC(2-6) entering] and converted to a percentage. The extraction ratio was measured in period 1 only, and was reported as a percentage. | 2 to 6 hours post-dose |
| Percentage of BMS-730823 Extracted During Hemodialysis | The percentage of BMS-730823 extracted during hemodialysis (extraction ratio) was calculated using the formula [plasma AUC(2-6)exiting - AUC(2-6)entering] / [AUC(2-6) entering] and converted to a percentage. The extraction ratio was measured in period 1 only, and was reported as a percentage. | 2 to 6 hours post-dose |
| Mean Maximum Percent Change From Baseline Prothrombin Time (PT) Following a Single 5 mg Oral Dose of Apixaban |
The mean maximum percent change in Prothrombin Time (PT) from baseline was reported for all treated participants. Baseline measurements were assessed up to 24 hours prior to Day 1 dosing. |
| From 24 hours pre-dose to 72 hours post-dose |
| Mean Maximum Percent Change From Baseline Activated Partial Thromboplastin Time (aPTT) Following a Single Oral Dose of 5 mg Apixaban | The mean maximum percent change in Activated Partial Thromboplastin Time (aPTT) from baseline was reported for all treated participants. Baseline measurements were assessed up to 24 hours prior to Day 1 dosing. | From 24 hours pre-dose to 72 hours post-dose |
| Mean Peak Anti-FXa Activity Following a Single Oral Dose of 5 mg Apixaban | Anti-FXa activity was assessed from an activity-time profile for doses both before and after hemodialysis. Maximal means were reported in International Units per milliliter (IU/mL). | From 24 hours pre-dose to 72 hours post-dose |
| From 24 hours pre-dose to 72 hours post-dose |
| Number of Participants Who Died or Experienced Serious Adverse Events (SAEs) or Adverse Events Leading to Discontinuation | The number of participants who died or experienced SAEs or AEs leading to discontinuation was reported for each arm. 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. Treatment-related=having certain, probable, possible, or missing relationship to study drug. Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4= Potentially Life-threatening or disabling. | From Day 1 to 30 days post study discontinuation |
Participants with End Stage Renal Disease (ESRD) maintained with hemodialysis received two doses of apixaban separated by a washout period of at least 7 days; one oral dose of 5mg apixaban 2 hours prior to hemodialysis on Day 1 of Period 1, and a second oral dose of 5mg apixaban immediately following the hemodialysis session on Day 1, Period 2. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
Participants with ESRD received one oral dose of 5 mg apixaban 2 hours prior to hemodialysis.
| OG002 | ESRD Dose After Hemodialysis | Participants with ESRD received one oral dose of 5 mg apixaban immediately following the completion of hemodialysis. |
|
|
|
| Primary | Geometric Mean of Maximum Observed Plasma Concentration (Cmax) of Metabolite BMS-730823 | Maximum observed plasma concentration (Cmax) was measured by plasma concentration of BMS-730823 over time. The geometric means are reported in nanograms per milliliter (ng/mL). | All treated participants | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | From 24 hours pre-dose to 72 hours post-dose |
|
|
|
| Primary | Geometric Mean of Area Under the Concentration-time Curve From Time Zero to Time of the Last Quantifiable Concentration (AUC(0-T)) of Single 5mg Oral Dose of Apixaban | Area under the concentration-time curve from time zero to time of the last quantifiable concentration (AUC(0-T)) was measured by plasma concentration of apixaban over time. The geometric means are reported in nanogram hours per milliliter (ng*h/mL). | All treated participants | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL | 24 hours pre-dose to 72 hours post-dose |
|
|
|
|
| Primary | Geometric Mean of Area Under the Concentration-time Curve From Time Zero to Time of the Last Quantifiable Concentration (AUC(0-T)) of Metabolite BMS-730823 | Area under the concentration-time curve from time zero to time of the last quantifiable concentration (AUC(0-T)) was measured by plasma concentration of BMS-730823 over time. The geometric means are reported in nanogram hours per milliliter (ng*h/mL). | All treated participants | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL | From 24 hours pre-dose to 72 hours post-dose |
|
|
|
| Primary | Geometric Mean of Area Under the Concentration-time Curve From Time Zero Extrapolated to Infinite Time (AUC(INF)) of Single 5mg Oral Dose of Apixaban | The area under the concentration-time curve from time zero extrapolated to infinite time (AUC(INF)) was measured by plasma concentration of apixaban over time. The geometric means are reported in nanogram hours per milliliter (ng*h/mL). | All treated participants | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL | From 24 hours pre-dose to 72 hours post-dose |
|
|
|
|
| Primary | Geometric Mean of Area Under the Concentration-time Curve From Time Zero Extrapolated to Infinite Time (AUC(INF)) of BMS-730823 | The area under the concentration-time curve from time zero extrapolated to infinite time (AUC(INF)) was measured by plasma concentration of BMS-730823 over time. The geometric means are reported in nanogram hours per milliliter (ng*h/mL). | All treated participants | Posted | Mean | Standard Deviation | ng*h/mL | 24 hours pre-dose to 72 hours post-dose |
|
|
|
| Primary | Mean Plasma Terminal Half-life (T-Half) of Single 5mg Oral Dose of Apixaban | Plasma terminal half-life (T-Half) for apixaban was derived from plasma concentrations versus time data. Means were reported in hours. | All treated participants | Posted | Mean | Standard Deviation | hours | From 24 hours pre-dose to 72 hours post-dose |
|
|
|
| Primary | Mean Plasma Terminal Half-life (T-Half) of BMS-730823 | Mean plasma terminal half-life (T-Half) for BMS-730823 was derived from plasma concentrations versus time data. | All treated participants with ESRD maintained with hemodialysis | Posted | Mean | Standard Deviation | hours | 24 hours pre-dose to 72 hours post-dose |
|
|
|
| Primary | Median Time of Maximum Observed Plasma Concentration (Tmax) of a Single 5 mg Oral Dose of Apixaban | Time of maximum observed plasma concentration (Tmax) for apixaban was derived from plasma concentrations versus time data. Medians were reported in hours. | All treated participants | Posted | Median | Full Range | hours | From 24 hours pre-dose to 72 hours post-dose |
|
|
|
| Primary | Median Time of Maximum Observed Plasma Concentration (Tmax) of Metabolite BMS-730823 | Time of maximum observed plasma concentration (Tmax) for BMS-730823 was derived from plasma concentrations versus time data. Medians were reported in hours. | All treated participants | Posted | Median | Full Range | hours | From 24 hours pre-dose to 72 hours post-dose |
|
|
|
| Primary | Geometric Mean of Area Under the Plasma Concentration-Time Curve From 2 to 6 Hours (AUC(2-6)) for Apixaban | Area under the plasma concentration-time curve from 2 hours to 6 hours (AUC(2-6) for Apixaban was measured in participants with ESRD during dialysis in Period 1 only. Geometric Means were reported in nanogram hours per milliliter (ng*hr/mL) and were determined from blood samples both entering and exiting the dialyzer. | All participants with ESRD maintained with hemodialysis | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL | 2 to 6 hours post-dose |
|
|
|
| Primary | Geometric Mean of Area Under the Plasma Concentration-Time Curve From 2 to 6 Hours (AUC(2-6)) for BMS-730823 | Area under the plasma concentration-time curve from 2 hours to 6 hours (AUC(2-6) for BMS-730823 was measured in participants with ESRD during dialysis in Period 1 only. Geometric Means were reported in nanogram hours per milliliter (ng*hr/mL) and were determined from blood samples both entering and exiting the dialyzer. | All participants with ESRD maintained with hemodialysis | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL | 2 to 6 hours post-dose |
|
|
|
| Primary | Mean Percent Dose of Apixaban Recovered in Urine (%UR) | The percent dose recovered in urine was calculated by dividing the cumulative amount of unchanged apixaban excreted in urine from the time of dose up to 72 hours post-dose by the apixaban dose administered. | All treated participants | Posted | Mean | Standard Deviation | percent of dose recovered in urine | 24 hours pre-dose to 72 hours post-dose |
|
|
|
| Primary | Mean Percent Dose of Apixaban Recovered in Dialysate (%DR) | Percent dose of Apixaban recovered in dialysate (%DR) was calculated by dividing the cumulative amount of apixaban excreted in each dialysate collection over 2-6 hours (DR(2-6)) by the apixaban dose. %DR was recorded only in period 1. | All treated participants with ESRD maintained with hemodialysis | Posted | Mean | Standard Deviation | percent of dose recovered in dialysate | 2 to 6 hours post-dose |
|
|
|
| Primary | Mean Renal Clearance (CLR) of Apixaban | Renal clearance (CLR) was calculated by dividing the cumulative amount of apixaban excreted in urine by the respective cumulative plasma AUC over the same urine collection interval. Geometric means were reported in milliliters per minute (mL/min). | All treated participants | Posted | Geometric Mean | Geometric Coefficient of Variation | mL/min | 24 hours pre-dose to 72 hours post-dose |
|
|
|
| Primary | Mean Renal Clearance (CLR) of BMS-730823 | Renal clearance (CLR) was calculated by dividing the cumulative amount of BMS-730823 excreted in urine by the respective cumulative plasma AUC over the same urine collection interval. Geometric means were reported in milliliters per minute (mL/min). | All treated participants | Posted | Geometric Mean | Geometric Coefficient of Variation | mL/min | 24 hours pre-dose to 72 hours post-dose |
|
|
|
| Primary | Mean Hemodialysis Clearance (CLD) of Apixaban | Hemodialysis clearance (CLD) was calculated by dividing the cumulative amount of apixaban excreted in dialysate by the respective cumulative plasma AUC over the same dialysate collection interval (AUC(2-6) entering). CLD measurements occurred only in period 1. Geometric means were reported in milliliters per minute (mL/min). | All treated participants with ESRD maintained with hemodialysis | Posted | Geometric Mean | Geometric Coefficient of Variation | mL/min | 2 to 6 hours post-dose |
|
|
|
| Primary | Mean Hemodialysis Clearance (CLD) of BMS-730823 | Hemodialysis clearance (CLD) was calculated by dividing the cumulative amount of BMS-730823 excreted in dialysate by the respective cumulative plasma AUC over the same dialysate collection interval (AUC(2-6) entering). CLD measurements occurred only in period 1. Geometric means were reported in milliliters per minute (mL/min). | All participants with ESRD maintained with hemodialysis | Posted | Mean | Standard Deviation | mL/min | 2 to 6 hours post-dose |
|
|
|
| Primary | Percentage of Apixaban Extracted During Hemodialysis | The percentage of apixaban extracted during hemodialysis (extraction ratio) was calculated using the formula [plasma AUC(2-6) exiting - AUC(2-6) entering] / [AUC(2-6) entering] and converted to a percentage. The extraction ratio was measured in period 1 only, and was reported as a percentage. | All treated participants with ESRD maintained with hemodialysis | Posted | Mean | Standard Deviation | percentage of apixaban extracted | 2 to 6 hours post-dose |
|
|
|
| Primary | Percentage of BMS-730823 Extracted During Hemodialysis | The percentage of BMS-730823 extracted during hemodialysis (extraction ratio) was calculated using the formula [plasma AUC(2-6)exiting - AUC(2-6)entering] / [AUC(2-6) entering] and converted to a percentage. The extraction ratio was measured in period 1 only, and was reported as a percentage. | All treated participants with ESRD maintained with hemodialysis | Posted | Mean | Standard Deviation | percentage of BMS-730823 extracted | 2 to 6 hours post-dose |
|
|
|
| Secondary | Mean Maximum Percent Change From Baseline International Normalized Ratio (INR) Following a Single 5 mg Oral Dose of Apixaban | The mean maximum percent change in baseline for INR was reported for each arm. Baseline measurements were assessed up to 24 hours prior to Day 1 dosing. | All treated participants | Posted | Mean | Standard Deviation | maximum percent change from baseline | From 24 hours pre-dose to 72 hours post-dose |
|
|
|
| Secondary | Mean Maximum Percent Change From Baseline Prothrombin Time (PT) Following a Single 5 mg Oral Dose of Apixaban | The mean maximum percent change in Prothrombin Time (PT) from baseline was reported for all treated participants. Baseline measurements were assessed up to 24 hours prior to Day 1 dosing. | All treated participants | Posted | Mean | Standard Deviation | maximum percent change from baseline | From 24 hours pre-dose to 72 hours post-dose |
|
|
|
| Secondary | Mean Maximum Percent Change From Baseline Activated Partial Thromboplastin Time (aPTT) Following a Single Oral Dose of 5 mg Apixaban | The mean maximum percent change in Activated Partial Thromboplastin Time (aPTT) from baseline was reported for all treated participants. Baseline measurements were assessed up to 24 hours prior to Day 1 dosing. | All treated participants | Posted | Mean | Standard Deviation | maximum percent change from baseline | From 24 hours pre-dose to 72 hours post-dose |
|
|
|
| Secondary | Mean Peak Anti-FXa Activity Following a Single Oral Dose of 5 mg Apixaban | Anti-FXa activity was assessed from an activity-time profile for doses both before and after hemodialysis. Maximal means were reported in International Units per milliliter (IU/mL). | All treated participants | Posted | Mean | Standard Deviation | IU/mL | From 24 hours pre-dose to 72 hours post-dose |
|
|
|
| Other Pre-specified | Number of Participants With Laboratory Marked Abnormalities | ULN=Upper Limit of Normal, LLN=Lower Limit of Normal, Pre-Rx= Baseline value. BUN=Blood Urea Nitrogen (mmol/L=millimoles per Liter): High if BUN > 1.1*ULN (if Pre-Rx>ULN: >1.25*Pre-Rx). Platelet count (*10^9 cell/L): Low if Platelet Count < 0.85*LLN (if Pre-Rx<LLN: <0.85*Pre-Rx). Creatine (umol/L=micromoles per Liter): High if Creatine > 1.5*ULN (if Pre-Rx>ULN: >1.33*Pre-Rx). Calcium, Total (mmol/L): High if Calcium > 1.5*ULN (if Pre-Rx>ULN: >1.33*Pre-Rx). Potassium, serum (mmol/L): High if Potassium > 1.1*ULN (if Pre-Rx>ULN: >1.1*Pre-Rx; if Pre-Rx<LLN: >ULN). Phosphorus, Inorganic (mmol/L): Low if Phosphate < 0.85*LLN (if Pre-Rx>ULN: <LLN). Lactate dehydrogenase (U/L=Units per Liter): High if Lactate Dehydrogenase > 1.25*ULN (if Pre-Rx>ULN: >1.5*Pre-Rx). | All treated participants | Posted | Number | participants | From 24 hours pre-dose to 72 hours post-dose |
|
|
|
| Other Pre-specified | Number of Participants Who Died or Experienced Serious Adverse Events (SAEs) or Adverse Events Leading to Discontinuation | The number of participants who died or experienced SAEs or AEs leading to discontinuation was reported for each arm. 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. Treatment-related=having certain, probable, possible, or missing relationship to study drug. Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4= Potentially Life-threatening or disabling. | All treated participants | Posted | Number | participants | From Day 1 to 30 days post study discontinuation |
|
|
|
| 0 |
| 8 |
| 0 |
| 8 |
| EG001 | ESRD Dose Before Hemodialysis | Participants with ESRD received one oral dose of 5 mg apixaban 2 hours prior to hemodialysis on Day 1. | 0 | 8 | 2 | 8 |
| EG002 | ESRD Dose After Hemodialysis | Participants with ESRD received one oral dose of 5 mg apixaban immediately following the completion of hemodialysis. | 0 | 8 | 1 | 8 |
| Constipation | Gastrointestinal disorders | MedDRA 14.1 | Systematic Assessment |
|
| Influenza like illness | General disorders | MedDRA 14.1 | Systematic Assessment |
|
| Somnolence | Nervous system disorders | MedDRA 14.1 | Systematic Assessment |
|
| Procedural hypotension | Injury, poisoning and procedural complications | MedDRA 14.1 | Systematic Assessment |
|
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.
| D052776 |
| Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| Geometric Mean Ratio |
| 1.389 |
| 2-Sided |
| 90 |
| 1.097 |
| 1.758 |
| No |
| Superiority or Other |
| Geometric Mean Ratio: ESRD Dose before hemodialysis over ESRD Dose after hemodialysis | Geometric Mean Ratio | 0.855 | 2-Sided | 90 | 0.707 | 1.033 | No | Superiority or Other |
| Geometric Mean Ratio |
| 1.357 |
| 2-Sided |
| 90 |
| 1.066 |
| 1.728 |
| No |
| Superiority or Other |
| Geometric Mean Ratio: ESRD Dose before hemodialysis over ESRD Dose after hemodialysis | Geometric Mean Ratio | 0.858 | 2-Sided | 90 | 0.707 | 1.042 | No | Superiority or Other |
| Creatine |
|
| Potassium |
|
| Phosphorus |
|
| Lactate dehydrogenase |
|
| AEs leading to discontinuation |
|