Renal Impairment
Conditions
Keywords
Betrixaban, Renal impairment, Healthy, Kidney dysfunction
Brief summary
The purpose of the study is to compare the pharmacokinetics, pharmacodynamics, and tolerability of betrixaban in patients with mild, moderate, and severe renal impairment to healthy volunteers.
Interventions
DRUGBetrixaban
80 mg betrixaban qd for 8 days
Sponsors
Merck Sharp & Dohme LLC
Portola Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
* Able to understand and sign the written informed consent. * Subjects should have either normal renal function or have stable renal disease
Exclusion criteria
* Subjects require dialysis * Evidence of active bleeding or bleeding disorder * Unstable or clinically significant other disorders such as respiratory, hepatic, metabolic, psychiatric or gastrointestinal disorder
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under The Plasma Concentration-Time Curve From Time Zero To 24 Hours (AUC0-24) Postdose Of Oral Doses Of Betrixaban On Day 8 | Predose up to 168 hours postdose | Blood and urine samples for pharmacokinetic analysis were collected and determined from the plasma and urine concentrations of betrixaban using non-compartmental procedures in WinNonlin Enterprise Version 5.2. Results were reported in nanogram multiplied by hour per milliliter (ng\*h/mL). |
| Maximum Observed Plasma Concentration (Cmax) Following Administration Of Oral Doses Of Betrixaban On Day 8 | Predose, up to 168 hours postdose | Blood and urine samples for pharmacokinetic analysis were collected and determined from the plasma and urine concentrations of betrixaban using non-compartmental procedures in WinNonlin Enterprise Version 5.2. Results were reported in nanogram per milliliter (ng/mL). |
| Plasma Terminal Elimination Half-Life (T½) Following Administration Of Oral Doses Of Betrixaban On Day 8 | Predose, up to 168 hours postdose | Blood and urine samples for pharmacokinetic analysis were collected and determined from the plasma and urine concentrations of betrixaban using non-compartmental procedures in WinNonlin Enterprise Version 5.2. Harmonic mean and Jackknife standard deviation was used to report this outcome and results were reported in hour. |
| Total Plasma Clearance (CL/F) Following Administration Of Oral Doses Of Betrixaban On Day 8 | Predose, up to 168 hours postdose | Blood and urine samples for pharmacokinetic analysis were collected and determined from the plasma and urine concentrations of betrixaban using non-compartmental procedures in WinNonlin Enterprise Version 5.2. Results were reported in milliliter per minute (mL/min). |
| Volume Of Distribution During The Terminal Phase (Vz/F) Following Administration Of Oral Doses Of Betrixaban On Day 8 | Predose, up to 168 hours postdose | Blood and urine samples for pharmacokinetic analysis were collected and determined from the plasma and urine concentrations of betrixaban using non-compartmental procedures in WinNonlin Enterprise Version 5.2. Results were reported in liter. |
| Percentage Of Dose Excreted In Urine From 0-24 (fe0-24) Postdose Of Oral Doses Of Betrixaban On Day 8 | Predose, up to 24 hours postdose | Blood and urine samples for pharmacokinetic analysis were collected and determined from the plasma and urine concentrations of betrixaban using non-compartmental procedures in WinNonlin Enterprise Version 5.2. Results were reported in percentage. |
| Percentage Of Betrixaban Bound To Plasma Proteins On Day 8 | 4 hours Postdose at Day 8 | Blood samples were collected for measurement of plasma protein binding for betrixaban for all participants. Results of protein binding assays were summarized by sample time and eGFR group. Results were reported in percent (%). |
| Thrombin Generation Following Administration Of Oral Doses Of Betrixaban On Day 8 | Day 1: predose; Day 8: 2, 3, 4, 8, 24, and 48 hours postdose | Blood samples were collected at the protocol-specified time points. Plasma samples were assayed for measurement of thrombin generation for all participants. |
| Anti-Factor Xa (fXa) Activity Following Administration Of Oral Doses Of Betrixaban On Day 8 | Day 8: 2, 3, 4, 8, 24, and 48 hours postdose | Blood samples were collected at the protocol-specified time points. Plasma samples were assayed for measurement of anti-fXa activity at baseline and steady state for all participants. Results were reported in international units per milliliter (IU/mL). |
Countries
Germany
Participant flow
Recruitment details
A total of 32 eligible participants were enrolled into 1 of 4 groups (8 participants per group) at screening according to the estimated glomerular filtration rate (eGFR).
Pre-assignment details
Criteria based on age, gender, and weight were planned in order to match participants in the renal function groups and to ensure that renal function groups were comparable to each other.
Participants by arm
| Arm | Count |
|---|---|
| Normal Renal Function Participants with normal renal function according to the eGFR. | 8 |
| Mild Renal Impairment Participants with mild renal impairment according to the eGFR. | 8 |
| Moderate Renal Impairment Participants with moderate renal impairment according to the eGFR. | 8 |
| Severe Renal Impairment Participants with severe renal impairment according to the eGFR. | 8 |
| Total | 32 |
Baseline characteristics
| Characteristic | Normal Renal Function | Mild Renal Impairment | Moderate Renal Impairment | Severe Renal Impairment | Total |
|---|---|---|---|---|---|
| Age, Continuous | 60 years STANDARD_DEVIATION 11.1 | 66 years STANDARD_DEVIATION 6.2 | 69 years STANDARD_DEVIATION 9.3 | 61 years STANDARD_DEVIATION 12.1 | 64 years STANDARD_DEVIATION 10.2 |
| Race/Ethnicity, Customized Hispanic or Latino | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 8 participants | 8 participants | 8 participants | 8 participants | 32 participants |
| Race/Ethnicity, Customized White | 8 participants | 8 participants | 8 participants | 8 participants | 32 participants |
| Sex: Female, Male Female | 3 Participants | 4 Participants | 3 Participants | 1 Participants | 11 Participants |
| Sex: Female, Male Male | 5 Participants | 4 Participants | 5 Participants | 7 Participants | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 |
| other Total, other adverse events | 5 / 8 | 3 / 8 | 5 / 8 | 3 / 8 |
| serious Total, serious adverse events | 0 / 8 | 0 / 8 | 0 / 8 | 1 / 8 |
Outcome results
Primary
Anti-Factor Xa (fXa) Activity Following Administration Of Oral Doses Of Betrixaban On Day 8
Blood samples were collected at the protocol-specified time points. Plasma samples were assayed for measurement of anti-fXa activity at baseline and steady state for all participants. Results were reported in international units per milliliter (IU/mL).
Time frame: Day 8: 2, 3, 4, 8, 24, and 48 hours postdose
Population: All participants with varying degrees of renal function who received the study intervention.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Normal Renal Function | Anti-Factor Xa (fXa) Activity Following Administration Of Oral Doses Of Betrixaban On Day 8 | Day 8 4 h | 0.22 IU/mL | Standard Deviation 0.302 |
| Normal Renal Function | Anti-Factor Xa (fXa) Activity Following Administration Of Oral Doses Of Betrixaban On Day 8 | Day 8 24 h | 0.06 IU/mL | Standard Deviation 0.054 |
| Normal Renal Function | Anti-Factor Xa (fXa) Activity Following Administration Of Oral Doses Of Betrixaban On Day 8 | Day 8 8 h | 0.10 IU/mL | Standard Deviation 0.066 |
| Normal Renal Function | Anti-Factor Xa (fXa) Activity Following Administration Of Oral Doses Of Betrixaban On Day 8 | Day 8 48 h | NA IU/mL | — |
| Normal Renal Function | Anti-Factor Xa (fXa) Activity Following Administration Of Oral Doses Of Betrixaban On Day 8 | Day 8 2 h | 0.18 IU/mL | Standard Deviation 0.113 |
| Normal Renal Function | Anti-Factor Xa (fXa) Activity Following Administration Of Oral Doses Of Betrixaban On Day 8 | Day 8 3 h | 0.27 IU/mL | Standard Deviation 0.302 |
| Mild Renal Impairment | Anti-Factor Xa (fXa) Activity Following Administration Of Oral Doses Of Betrixaban On Day 8 | Day 8 2 h | 0.36 IU/mL | Standard Deviation 0.293 |
| Mild Renal Impairment | Anti-Factor Xa (fXa) Activity Following Administration Of Oral Doses Of Betrixaban On Day 8 | Day 8 24 h | 0.13 IU/mL | Standard Deviation 0.056 |
| Mild Renal Impairment | Anti-Factor Xa (fXa) Activity Following Administration Of Oral Doses Of Betrixaban On Day 8 | Day 8 4 h | 0.33 IU/mL | Standard Deviation 0.116 |
| Mild Renal Impairment | Anti-Factor Xa (fXa) Activity Following Administration Of Oral Doses Of Betrixaban On Day 8 | Day 8 3 h | 0.40 IU/mL | Standard Deviation 0.163 |
| Mild Renal Impairment | Anti-Factor Xa (fXa) Activity Following Administration Of Oral Doses Of Betrixaban On Day 8 | Day 8 48 h | 0.08 IU/mL | Standard Deviation 0.032 |
| Mild Renal Impairment | Anti-Factor Xa (fXa) Activity Following Administration Of Oral Doses Of Betrixaban On Day 8 | Day 8 8 h | 0.18 IU/mL | Standard Deviation 0.07 |
| Moderate Renal Impairment | Anti-Factor Xa (fXa) Activity Following Administration Of Oral Doses Of Betrixaban On Day 8 | Day 8 2 h | 0.48 IU/mL | Standard Deviation 0.352 |
| Moderate Renal Impairment | Anti-Factor Xa (fXa) Activity Following Administration Of Oral Doses Of Betrixaban On Day 8 | Day 8 3 h | 0.60 IU/mL | Standard Deviation 0.393 |
| Moderate Renal Impairment | Anti-Factor Xa (fXa) Activity Following Administration Of Oral Doses Of Betrixaban On Day 8 | Day 8 4 h | 0.58 IU/mL | Standard Deviation 0.381 |
| Moderate Renal Impairment | Anti-Factor Xa (fXa) Activity Following Administration Of Oral Doses Of Betrixaban On Day 8 | Day 8 48 h | 0.13 IU/mL | Standard Deviation 0.082 |
| Moderate Renal Impairment | Anti-Factor Xa (fXa) Activity Following Administration Of Oral Doses Of Betrixaban On Day 8 | Day 8 8 h | 0.32 IU/mL | Standard Deviation 0.245 |
| Moderate Renal Impairment | Anti-Factor Xa (fXa) Activity Following Administration Of Oral Doses Of Betrixaban On Day 8 | Day 8 24 h | 0.18 IU/mL | Standard Deviation 0.138 |
| Severe Renal Impairment | Anti-Factor Xa (fXa) Activity Following Administration Of Oral Doses Of Betrixaban On Day 8 | Day 8 4 h | 0.58 IU/mL | Standard Deviation 0.31 |
| Severe Renal Impairment | Anti-Factor Xa (fXa) Activity Following Administration Of Oral Doses Of Betrixaban On Day 8 | Day 8 48 h | 0.12 IU/mL | Standard Deviation 0.092 |
| Severe Renal Impairment | Anti-Factor Xa (fXa) Activity Following Administration Of Oral Doses Of Betrixaban On Day 8 | Day 8 24 h | 0.18 IU/mL | Standard Deviation 0.123 |
| Severe Renal Impairment | Anti-Factor Xa (fXa) Activity Following Administration Of Oral Doses Of Betrixaban On Day 8 | Day 8 2 h | 0.44 IU/mL | Standard Deviation 0.237 |
| Severe Renal Impairment | Anti-Factor Xa (fXa) Activity Following Administration Of Oral Doses Of Betrixaban On Day 8 | Day 8 3 h | 0.77 IU/mL | Standard Deviation 0.453 |
| Severe Renal Impairment | Anti-Factor Xa (fXa) Activity Following Administration Of Oral Doses Of Betrixaban On Day 8 | Day 8 8 h | 0.30 IU/mL | Standard Deviation 0.276 |
Primary
Area Under The Plasma Concentration-Time Curve From Time Zero To 24 Hours (AUC0-24) Postdose Of Oral Doses Of Betrixaban On Day 8
Blood and urine samples for pharmacokinetic analysis were collected and determined from the plasma and urine concentrations of betrixaban using non-compartmental procedures in WinNonlin Enterprise Version 5.2. Results were reported in nanogram multiplied by hour per milliliter (ng\*h/mL).
Time frame: Predose up to 168 hours postdose
Population: All participants with varying degrees of renal function who received the study intervention.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Normal Renal Function | Area Under The Plasma Concentration-Time Curve From Time Zero To 24 Hours (AUC0-24) Postdose Of Oral Doses Of Betrixaban On Day 8 | 437 ng*h/mL | Standard Deviation 237 |
| Mild Renal Impairment | Area Under The Plasma Concentration-Time Curve From Time Zero To 24 Hours (AUC0-24) Postdose Of Oral Doses Of Betrixaban On Day 8 | 807 ng*h/mL | Standard Deviation 254 |
| Moderate Renal Impairment | Area Under The Plasma Concentration-Time Curve From Time Zero To 24 Hours (AUC0-24) Postdose Of Oral Doses Of Betrixaban On Day 8 | 1033 ng*h/mL | Standard Deviation 549 |
| Severe Renal Impairment | Area Under The Plasma Concentration-Time Curve From Time Zero To 24 Hours (AUC0-24) Postdose Of Oral Doses Of Betrixaban On Day 8 | 995 ng*h/mL | Standard Deviation 445 |
90% CI: [1.18, 3.03]
90% CI: [1.43, 3.59]
90% CI: [1.71, 4.06]
90% CI: [0.888, 2.18]
90% CI: [1.14, 3.31]
90% CI: [1.41, 4.22]
90% CI: [1.74, 4.7]
90% CI: [0.944, 2.3]
Primary
Maximum Observed Plasma Concentration (Cmax) Following Administration Of Oral Doses Of Betrixaban On Day 8
Blood and urine samples for pharmacokinetic analysis were collected and determined from the plasma and urine concentrations of betrixaban using non-compartmental procedures in WinNonlin Enterprise Version 5.2. Results were reported in nanogram per milliliter (ng/mL).
Time frame: Predose, up to 168 hours postdose
Population: All participants with varying degrees of renal function who received the study intervention.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Normal Renal Function | Maximum Observed Plasma Concentration (Cmax) Following Administration Of Oral Doses Of Betrixaban On Day 8 | 44.0 ng/mL | Standard Deviation 24.4 |
| Mild Renal Impairment | Maximum Observed Plasma Concentration (Cmax) Following Administration Of Oral Doses Of Betrixaban On Day 8 | 84.3 ng/mL | Standard Deviation 37 |
| Moderate Renal Impairment | Maximum Observed Plasma Concentration (Cmax) Following Administration Of Oral Doses Of Betrixaban On Day 8 | 108 ng/mL | Standard Deviation 59.1 |
| Severe Renal Impairment | Maximum Observed Plasma Concentration (Cmax) Following Administration Of Oral Doses Of Betrixaban On Day 8 | 104 ng/mL | Standard Deviation 58 |
90% CI: [1.05, 3.35]
90% CI: [1.32, 4.07]
90% CI: [1.48, 4.29]
90% CI: [0.772, 2.32]
90% CI: [1.01, 3.78]
90% CI: [1.21, 4.67]
90% CI: [1.46, 4.96]
90% CI: [0.793, 2.38]
Primary
Percentage Of Betrixaban Bound To Plasma Proteins On Day 8
Blood samples were collected for measurement of plasma protein binding for betrixaban for all participants. Results of protein binding assays were summarized by sample time and eGFR group. Results were reported in percent (%).
Time frame: 4 hours Postdose at Day 8
Population: All participants with varying degrees of renal function who received the study intervention.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Normal Renal Function | Percentage Of Betrixaban Bound To Plasma Proteins On Day 8 | 58.6 percentage of bound betrixaban | Standard Deviation 2.76 |
| Mild Renal Impairment | Percentage Of Betrixaban Bound To Plasma Proteins On Day 8 | 61.3 percentage of bound betrixaban | Standard Deviation 1.86 |
| Moderate Renal Impairment | Percentage Of Betrixaban Bound To Plasma Proteins On Day 8 | 59.4 percentage of bound betrixaban | Standard Deviation 3.05 |
| Severe Renal Impairment | Percentage Of Betrixaban Bound To Plasma Proteins On Day 8 | 59.9 percentage of bound betrixaban | Standard Deviation 3.62 |
Primary
Percentage Of Dose Excreted In Urine From 0-24 (fe0-24) Postdose Of Oral Doses Of Betrixaban On Day 8
Blood and urine samples for pharmacokinetic analysis were collected and determined from the plasma and urine concentrations of betrixaban using non-compartmental procedures in WinNonlin Enterprise Version 5.2. Results were reported in percentage.
Time frame: Predose, up to 24 hours postdose
Population: All participants with varying degrees of renal function who received the study intervention.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Normal Renal Function | Percentage Of Dose Excreted In Urine From 0-24 (fe0-24) Postdose Of Oral Doses Of Betrixaban On Day 8 | 5.07 percentage of excreted dose | Standard Deviation 2.32 |
| Mild Renal Impairment | Percentage Of Dose Excreted In Urine From 0-24 (fe0-24) Postdose Of Oral Doses Of Betrixaban On Day 8 | 5.40 percentage of excreted dose | Standard Deviation 2.24 |
| Moderate Renal Impairment | Percentage Of Dose Excreted In Urine From 0-24 (fe0-24) Postdose Of Oral Doses Of Betrixaban On Day 8 | 5.04 percentage of excreted dose | Standard Deviation 2.38 |
| Severe Renal Impairment | Percentage Of Dose Excreted In Urine From 0-24 (fe0-24) Postdose Of Oral Doses Of Betrixaban On Day 8 | 2.72 percentage of excreted dose | Standard Deviation 1.02 |
Primary
Plasma Terminal Elimination Half-Life (T½) Following Administration Of Oral Doses Of Betrixaban On Day 8
Blood and urine samples for pharmacokinetic analysis were collected and determined from the plasma and urine concentrations of betrixaban using non-compartmental procedures in WinNonlin Enterprise Version 5.2. Harmonic mean and Jackknife standard deviation was used to report this outcome and results were reported in hour.
Time frame: Predose, up to 168 hours postdose
Population: All participants with varying degrees of renal function who received the study intervention.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Normal Renal Function | Plasma Terminal Elimination Half-Life (T½) Following Administration Of Oral Doses Of Betrixaban On Day 8 | 54.4 hour | Standard Deviation 9.2 |
| Mild Renal Impairment | Plasma Terminal Elimination Half-Life (T½) Following Administration Of Oral Doses Of Betrixaban On Day 8 | 56.0 hour | Standard Deviation 5.09 |
| Moderate Renal Impairment | Plasma Terminal Elimination Half-Life (T½) Following Administration Of Oral Doses Of Betrixaban On Day 8 | 60.7 hour | Standard Deviation 8.17 |
| Severe Renal Impairment | Plasma Terminal Elimination Half-Life (T½) Following Administration Of Oral Doses Of Betrixaban On Day 8 | 55.6 hour | Standard Deviation 5.19 |
Primary
Thrombin Generation Following Administration Of Oral Doses Of Betrixaban On Day 8
Blood samples were collected at the protocol-specified time points. Plasma samples were assayed for measurement of thrombin generation for all participants.
Time frame: Day 1: predose; Day 8: 2, 3, 4, 8, 24, and 48 hours postdose
Population: All participants with varying degrees of renal function who received the study intervention.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Normal Renal Function | Thrombin Generation Following Administration Of Oral Doses Of Betrixaban On Day 8 | Day 1 Predose | 12494 relative fluorescence units (RFU) | Standard Error 2256.4 |
| Normal Renal Function | Thrombin Generation Following Administration Of Oral Doses Of Betrixaban On Day 8 | Day 8 24 h | 8616 relative fluorescence units (RFU) | Standard Error 2336.2 |
| Normal Renal Function | Thrombin Generation Following Administration Of Oral Doses Of Betrixaban On Day 8 | Day 8 8 h | 9716 relative fluorescence units (RFU) | Standard Error 1386.6 |
| Normal Renal Function | Thrombin Generation Following Administration Of Oral Doses Of Betrixaban On Day 8 | Day 8 2 h | 6359 relative fluorescence units (RFU) | Standard Error 2819.6 |
| Normal Renal Function | Thrombin Generation Following Administration Of Oral Doses Of Betrixaban On Day 8 | Day 8 48 h | 12233 relative fluorescence units (RFU) | Standard Error 3872.4 |
| Normal Renal Function | Thrombin Generation Following Administration Of Oral Doses Of Betrixaban On Day 8 | Day 8 3 h | 6611 relative fluorescence units (RFU) | Standard Error 1544.6 |
| Normal Renal Function | Thrombin Generation Following Administration Of Oral Doses Of Betrixaban On Day 8 | Day 8 4 h | 6899 relative fluorescence units (RFU) | Standard Error 1528.6 |
| Mild Renal Impairment | Thrombin Generation Following Administration Of Oral Doses Of Betrixaban On Day 8 | Day 8 24 h | 5870 relative fluorescence units (RFU) | Standard Error 2205.7 |
| Mild Renal Impairment | Thrombin Generation Following Administration Of Oral Doses Of Betrixaban On Day 8 | Day 8 4 h | 5103 relative fluorescence units (RFU) | Standard Error 1406.7 |
| Mild Renal Impairment | Thrombin Generation Following Administration Of Oral Doses Of Betrixaban On Day 8 | Day 8 3 h | 5356 relative fluorescence units (RFU) | Standard Error 1632.2 |
| Mild Renal Impairment | Thrombin Generation Following Administration Of Oral Doses Of Betrixaban On Day 8 | Day 8 8 h | 8789 relative fluorescence units (RFU) | Standard Error 2923.8 |
| Mild Renal Impairment | Thrombin Generation Following Administration Of Oral Doses Of Betrixaban On Day 8 | Day 8 48 h | 8350 relative fluorescence units (RFU) | Standard Error 2863.9 |
| Mild Renal Impairment | Thrombin Generation Following Administration Of Oral Doses Of Betrixaban On Day 8 | Day 8 2 h | 4484 relative fluorescence units (RFU) | Standard Error 1411.4 |
| Mild Renal Impairment | Thrombin Generation Following Administration Of Oral Doses Of Betrixaban On Day 8 | Day 1 Predose | 14168 relative fluorescence units (RFU) | Standard Error 3387.2 |
| Moderate Renal Impairment | Thrombin Generation Following Administration Of Oral Doses Of Betrixaban On Day 8 | Day 8 4 h | 6216 relative fluorescence units (RFU) | Standard Error 3092.5 |
| Moderate Renal Impairment | Thrombin Generation Following Administration Of Oral Doses Of Betrixaban On Day 8 | Day 1 Predose | 11833 relative fluorescence units (RFU) | Standard Error 3283.1 |
| Moderate Renal Impairment | Thrombin Generation Following Administration Of Oral Doses Of Betrixaban On Day 8 | Day 8 2 h | 4873 relative fluorescence units (RFU) | Standard Error 1466.4 |
| Moderate Renal Impairment | Thrombin Generation Following Administration Of Oral Doses Of Betrixaban On Day 8 | Day 8 3 h | 5098 relative fluorescence units (RFU) | Standard Error 1850.4 |
| Moderate Renal Impairment | Thrombin Generation Following Administration Of Oral Doses Of Betrixaban On Day 8 | Day 8 8 h | 7907 relative fluorescence units (RFU) | Standard Error 2851 |
| Moderate Renal Impairment | Thrombin Generation Following Administration Of Oral Doses Of Betrixaban On Day 8 | Day 8 24 h | 7386 relative fluorescence units (RFU) | Standard Error 1275.8 |
| Moderate Renal Impairment | Thrombin Generation Following Administration Of Oral Doses Of Betrixaban On Day 8 | Day 8 48 h | 8119 relative fluorescence units (RFU) | Standard Error 1742.7 |
| Severe Renal Impairment | Thrombin Generation Following Administration Of Oral Doses Of Betrixaban On Day 8 | Day 8 3 h | 5547 relative fluorescence units (RFU) | Standard Error 2994.4 |
| Severe Renal Impairment | Thrombin Generation Following Administration Of Oral Doses Of Betrixaban On Day 8 | Day 8 48 h | 8485 relative fluorescence units (RFU) | Standard Error 2858 |
| Severe Renal Impairment | Thrombin Generation Following Administration Of Oral Doses Of Betrixaban On Day 8 | Day 8 24 h | 8013 relative fluorescence units (RFU) | Standard Error 2710.4 |
| Severe Renal Impairment | Thrombin Generation Following Administration Of Oral Doses Of Betrixaban On Day 8 | Day 8 2 h | 4773 relative fluorescence units (RFU) | Standard Error 2059.1 |
| Severe Renal Impairment | Thrombin Generation Following Administration Of Oral Doses Of Betrixaban On Day 8 | Day 1 Predose | 10021 relative fluorescence units (RFU) | Standard Error 6034.7 |
| Severe Renal Impairment | Thrombin Generation Following Administration Of Oral Doses Of Betrixaban On Day 8 | Day 8 8 h | 7482 relative fluorescence units (RFU) | Standard Error 1959.3 |
| Severe Renal Impairment | Thrombin Generation Following Administration Of Oral Doses Of Betrixaban On Day 8 | Day 8 4 h | 6154 relative fluorescence units (RFU) | Standard Error 2818.6 |
Primary
Total Plasma Clearance (CL/F) Following Administration Of Oral Doses Of Betrixaban On Day 8
Blood and urine samples for pharmacokinetic analysis were collected and determined from the plasma and urine concentrations of betrixaban using non-compartmental procedures in WinNonlin Enterprise Version 5.2. Results were reported in milliliter per minute (mL/min).
Time frame: Predose, up to 168 hours postdose
Population: All participants with varying degrees of renal function who received the study intervention.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Normal Renal Function | Total Plasma Clearance (CL/F) Following Administration Of Oral Doses Of Betrixaban On Day 8 | 4042 mL/min | Standard Deviation 2376 |
| Mild Renal Impairment | Total Plasma Clearance (CL/F) Following Administration Of Oral Doses Of Betrixaban On Day 8 | 1815 mL/min | Standard Deviation 623 |
| Moderate Renal Impairment | Total Plasma Clearance (CL/F) Following Administration Of Oral Doses Of Betrixaban On Day 8 | 1887 mL/min | Standard Deviation 1468 |
| Severe Renal Impairment | Total Plasma Clearance (CL/F) Following Administration Of Oral Doses Of Betrixaban On Day 8 | 1715 mL/min | Standard Deviation 1052 |
Primary
Volume Of Distribution During The Terminal Phase (Vz/F) Following Administration Of Oral Doses Of Betrixaban On Day 8
Blood and urine samples for pharmacokinetic analysis were collected and determined from the plasma and urine concentrations of betrixaban using non-compartmental procedures in WinNonlin Enterprise Version 5.2. Results were reported in liter.
Time frame: Predose, up to 168 hours postdose
Population: All participants with varying degrees of renal function who received the study intervention.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Normal Renal Function | Volume Of Distribution During The Terminal Phase (Vz/F) Following Administration Of Oral Doses Of Betrixaban On Day 8 | 20128 liter | Standard Deviation 13391 |
| Mild Renal Impairment | Volume Of Distribution During The Terminal Phase (Vz/F) Following Administration Of Oral Doses Of Betrixaban On Day 8 | 8795 liter | Standard Deviation 2780 |
| Moderate Renal Impairment | Volume Of Distribution During The Terminal Phase (Vz/F) Following Administration Of Oral Doses Of Betrixaban On Day 8 | 9518 liter | Standard Deviation 6183 |
| Severe Renal Impairment | Volume Of Distribution During The Terminal Phase (Vz/F) Following Administration Of Oral Doses Of Betrixaban On Day 8 | 9562 liter | Standard Deviation 6132 |