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| Name | Class |
|---|---|
| Merck Sharp & Dohme LLC | INDUSTRY |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group H | Active Comparator | Healthy subjects matched to the renal impairment groups |
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| Group A | Experimental | Patients with mild renal impairment |
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| Group B | Experimental | Patients with moderate renal impairment |
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| Group C | Experimental | Patients with severe renal impairment |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Betrixaban | Drug | 80 mg betrixaban qd for 8 days |
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| Measure | Description | Time Frame |
|---|---|---|
| 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). | Predose up to 168 hours postdose |
| 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). | Predose, up to 168 hours postdose |
| 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. | Predose, up to 168 hours postdose |
| 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). | Predose, up to 168 hours postdose |
| Volume Of Distribution During The Terminal Phase (Vz/F) Following Administration Of Oral Doses Of Betrixaban On Day 8 |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| APEX GmbH | Munich | Germany |
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.
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).
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| ID | Title | Description |
|---|---|---|
| FG000 | Normal Renal Function | Participants with normal renal function according to the eGFR. |
| FG001 | Mild Renal Impairment | Participants with mild renal impairment according to the eGFR. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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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. |
| Predose, up to 168 hours postdose |
| 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. | Predose, up to 24 hours postdose |
| 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 (%). | 4 hours Postdose at Day 8 |
| 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. | Day 1: predose; Day 8: 2, 3, 4, 8, 24, and 48 hours postdose |
| 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). | Day 8: 2, 3, 4, 8, 24, and 48 hours postdose |
| FG002 | Moderate Renal Impairment | Participants with moderate renal impairment according to the eGFR. |
| FG003 | Severe Renal Impairment | Participants with severe renal impairment according to the eGFR. |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Normal Renal Function | Participants with normal renal function according to the eGFR. |
| BG001 | Mild Renal Impairment | Participants with mild renal impairment according to the eGFR. |
| BG002 | Moderate Renal Impairment | Participants with moderate renal impairment according to the eGFR. |
| BG003 | Severe Renal Impairment | Participants with severe renal impairment according to the eGFR. |
| BG004 | Total | Total of all reporting groups |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Population of participants based on their race. | Number | participants |
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| Race/Ethnicity, Customized | Population of participants based on their ethnicity. | Number | participants |
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| 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 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). | All participants with varying degrees of renal function who received the study intervention. | Posted | Mean | Standard Deviation | ng*h/mL | Predose up to 168 hours postdose |
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| 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). | All participants with varying degrees of renal function who received the study intervention. | Posted | Mean | Standard Deviation | ng/mL | Predose, up to 168 hours postdose |
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| 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. | All participants with varying degrees of renal function who received the study intervention. | Posted | Mean | Standard Deviation | hour | Predose, up to 168 hours postdose |
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| 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). | All participants with varying degrees of renal function who received the study intervention. | Posted | Mean | Standard Deviation | mL/min | Predose, up to 168 hours postdose |
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| 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. | All participants with varying degrees of renal function who received the study intervention. | Posted | Mean | Standard Deviation | liter | Predose, up to 168 hours postdose |
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| 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. | All participants with varying degrees of renal function who received the study intervention. | Posted | Mean | Standard Deviation | percentage of excreted dose | Predose, up to 24 hours postdose |
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| 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 (%). | All participants with varying degrees of renal function who received the study intervention. | Posted | Mean | Standard Deviation | percentage of bound betrixaban | 4 hours Postdose at Day 8 |
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| 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. | All participants with varying degrees of renal function who received the study intervention. | Posted | Mean | Standard Error | relative fluorescence units (RFU) | Day 1: predose; Day 8: 2, 3, 4, 8, 24, and 48 hours postdose |
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| 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). | All participants with varying degrees of renal function who received the study intervention. | Posted | Mean | Standard Deviation | IU/mL | Day 8: 2, 3, 4, 8, 24, and 48 hours postdose |
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Day 1 through up to Day 12
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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 | Participants with normal renal function according to the estimated eGFR. | 0 | 8 | 0 | 8 | 5 | 8 |
| EG001 | Mild Renal Impairment | Participants with mild renal impairment according to the eGFR. | 0 | 8 | 0 | 8 | 3 | 8 |
| EG002 | Moderate Renal Impairment | Participants with moderate renal impairment according to the eGFR. | 0 | 8 | 0 | 8 | 5 | 8 |
| EG003 | Severe Renal Impairment | Participants with severe renal impairment according to the eGFR. | 0 | 8 | 1 | 8 | 3 | 8 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Blood creatinine increased | Investigations | Merck MedDRA | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Gingival Bleeding | Vascular disorders | Merck MedDRA | Systematic Assessment |
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| Epistaxis | Vascular disorders | Merck MedDRA | Systematic Assessment |
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| Anaemia | Blood and lymphatic system disorders | Merck MedDRA | Systematic Assessment |
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| Headache | Nervous system disorders | Merck MedDRA | Systematic Assessment |
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| Dizziness | Nervous system disorders | Merck MedDRA | Systematic Assessment |
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| Dysgeusia | Nervous system disorders | Merck MedDRA | Systematic Assessment |
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| Vision Blurred | Eye disorders | Merck MedDRA | Systematic Assessment |
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| Fatigue | General disorders | Merck MedDRA | Systematic Assessment |
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| Insomnia | Psychiatric disorders | Merck MedDRA | Systematic Assessment |
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| Abdominal Pain Upper | Gastrointestinal disorders | Merck MedDRA | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | Merck MedDRA | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | Merck MedDRA | Systematic Assessment |
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| Dry Mouth | Gastrointestinal disorders | Merck MedDRA | Systematic Assessment |
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| Dyspepsia | Gastrointestinal disorders | Merck MedDRA | Systematic Assessment |
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| Flatulence | Gastrointestinal disorders | Merck MedDRA | Systematic Assessment |
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| Glossodynia | Gastrointestinal disorders | Merck MedDRA | Systematic Assessment |
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| Menorrhagia | Reproductive system and breast disorders | Merck MedDRA | Systematic Assessment |
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| Pollakiuria | Renal and urinary disorders | Merck MedDRA | Systematic Assessment |
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| Dry Skin | Skin and subcutaneous tissue disorders | Merck MedDRA | Systematic Assessment |
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| Hyperhidrosis | Skin and subcutaneous tissue disorders | Merck MedDRA | Systematic Assessment |
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| Back Pain | Musculoskeletal and connective tissue disorders | Merck MedDRA | Systematic Assessment |
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| Joint Swelling | Musculoskeletal and connective tissue disorders | Merck MedDRA | Systematic Assessment |
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| Pain In Extremity | Musculoskeletal and connective tissue disorders | Merck MedDRA | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | Merck MedDRA | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Alexion Pharmaceuticals, Inc. | Alexion Pharmaceuticals, Inc. | 855-752-2356 | clinicaltrials@alexion.com |
| ID | Term |
|---|---|
| D051437 | Renal Insufficiency |
| ID | Term |
|---|---|
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
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| ID | Term |
|---|---|
| C543086 | betrixaban |
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| Male |
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| Not Hispanic or Latino |
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| Ratio |
| 2.27 |
| 2-Sided |
| 90 |
| 1.43 |
| 3.59 |
Statistical comparison of AUC0-24 on Day 8 for participants grouped using 186 as multiplier in the MDRD equation. |
| Other |
Geometric least squares means, ratios, and CIs were estimated from an ANCOVA of natural log transformed values. |
| Ratio | 2.63 | 2-Sided | 90 | 1.71 | 4.06 | Statistical comparison of AUC0-24 on Day 8 for participants grouped using 186 as multiplier in the MDRD equation. | Other | Geometric least squares means, ratios, and CIs were estimated from an ANCOVA of natural log transformed values. |
| Ratio | 1.39 | 2-Sided | 90 | 0.888 | 2.18 | Statistical comparison of AUC0-24 on Day 8 for participants grouped using 186 as multiplier in the MDRD equation. | Other | Geometric least squares means, ratios, and CIs were estimated from an ANCOVA of natural log transformed values. |
| Ratio | 1.94 | 2-Sided | 90 | 1.14 | 3.31 | Statistical comparison of AUC0-24 on Day 8 for participants grouped using 175 as multiplier in the MDRD equation. | Other | Geometric least squares means, ratios, and CIs were estimated from an ANCOVA of natural log transformed values. |
| Ratio | 2.44 | 2-Sided | 90 | 1.41 | 4.22 | Statistical comparison of AUC0-24 on Day 8 for participants grouped using 175 as multiplier in the MDRD equation. | Other | Geometric least squares means, ratios, and CIs were estimated from an ANCOVA of natural log transformed values. |
| Ratio | 2.86 | 2-Sided | 90 | 1.74 | 4.7 | Statistical comparison of AUC0-24 on Day 8 for participants grouped using 175 as multiplier in the MDRD equation. | Other | Geometric least squares means, ratios, and CIs were estimated from an ANCOVA of natural log transformed values. |
| Ratio | 1.47 | 2-Sided | 90 | 0.944 | 2.3 | Statistical comparison of AUC0-24 on Day 8 for participants grouped using 175 as multiplier in the MDRD equation. | Other | Geometric least squares means, ratios, and CIs were estimated from an ANCOVA of natural log transformed values. |
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