A Study to Determine the Pharmacokinetics, Pharmacodynamics, and Tolerabiltiy of Betrixaban in Patients With Mild, Moderate, and Severe Renal Impairment

Study Overview
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Brief Summary
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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.

Official Title
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Pharmacokinetics, Pharmacodynamics, and Tolerability of Betrixaban Administered Orally in Subjects With Normal and Reduced Renal Function.

Conditions
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Renal Impairment

Intervention / Treatment
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* Drug: Betrixaban


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group H<br>Healthy subjects matched to the renal impairment groups | Drug: Betrixaban<br>* 80 mg betrixaban qd for 8 days<br>|
| Experimental: Group A<br>Patients with mild renal impairment | Drug: Betrixaban<br>* 80 mg betrixaban qd for 8 days<br>|
| Experimental: Group B<br>Patients with moderate renal impairment | Drug: Betrixaban<br>* 80 mg betrixaban qd for 8 days<br>|
| Experimental: Group C<br>Patients with severe renal impairment | Drug: Betrixaban<br>* 80 mg betrixaban qd for 8 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | 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 | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Betrixaban, Renal impairment, Healthy, Kidney dysfunction