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

Primary Purpose

Renal Impairment

Status
Completed
Phase
Phase 1
Locations
Germany
Study Type
Interventional
Intervention
Betrixaban
Sponsored by
Portola Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Renal Impairment focused on measuring Betrixaban, Renal impairment, Healthy, Kidney dysfunction

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • APEX GmbH

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Active Comparator

Experimental

Experimental

Experimental

Arm Label

Group H

Group A

Group B

Group C

Arm Description

Healthy subjects matched to the renal impairment groups

Patients with mild renal impairment

Patients with moderate renal impairment

Patients with severe renal impairment

Outcomes

Primary Outcome Measures

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).
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).
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.
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).
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.
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.
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 (%).
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.
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).

Secondary Outcome Measures

Full Information

First Posted
October 20, 2009
Last Updated
October 13, 2022
Sponsor
Portola Pharmaceuticals
Collaborators
Merck Sharp & Dohme LLC
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1. Study Identification

Unique Protocol Identification Number
NCT00999336
Brief Title
A Study to Determine the Pharmacokinetics, Pharmacodynamics, and Tolerabiltiy of Betrixaban in Patients With Mild, Moderate, and Severe Renal Impairment
Official Title
Pharmacokinetics, Pharmacodynamics, and Tolerability of Betrixaban Administered Orally in Subjects With Normal and Reduced Renal Function.
Study Type
Interventional

2. Study Status

Record Verification Date
October 2022
Overall Recruitment Status
Completed
Study Start Date
July 31, 2009 (Actual)
Primary Completion Date
February 28, 2010 (Actual)
Study Completion Date
February 28, 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Portola Pharmaceuticals
Collaborators
Merck Sharp & Dohme LLC

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Renal Impairment
Keywords
Betrixaban, Renal impairment, Healthy, Kidney dysfunction

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
32 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Group H
Arm Type
Active Comparator
Arm Description
Healthy subjects matched to the renal impairment groups
Arm Title
Group A
Arm Type
Experimental
Arm Description
Patients with mild renal impairment
Arm Title
Group B
Arm Type
Experimental
Arm Description
Patients with moderate renal impairment
Arm Title
Group C
Arm Type
Experimental
Arm Description
Patients with severe renal impairment
Intervention Type
Drug
Intervention Name(s)
Betrixaban
Intervention Description
80 mg betrixaban qd for 8 days
Primary Outcome Measure Information:
Title
Area Under The Plasma Concentration-Time Curve From Time Zero To 24 Hours (AUC0-24) Postdose Of Oral Doses Of Betrixaban On Day 8
Description
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
Title
Maximum Observed Plasma Concentration (Cmax) Following Administration Of Oral Doses Of Betrixaban On Day 8
Description
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
Title
Plasma Terminal Elimination Half-Life (T½) Following Administration Of Oral Doses Of Betrixaban On Day 8
Description
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
Title
Total Plasma Clearance (CL/F) Following Administration Of Oral Doses Of Betrixaban On Day 8
Description
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
Title
Volume Of Distribution During The Terminal Phase (Vz/F) Following Administration Of Oral Doses Of Betrixaban On Day 8
Description
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
Title
Percentage Of Dose Excreted In Urine From 0-24 (fe0-24) Postdose Of Oral Doses Of Betrixaban On Day 8
Description
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
Title
Percentage Of Betrixaban Bound To Plasma Proteins On Day 8
Description
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
Title
Thrombin Generation Following Administration Of Oral Doses Of Betrixaban On Day 8
Description
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
Title
Anti-Factor Xa (fXa) Activity Following Administration Of Oral Doses Of Betrixaban On Day 8
Description
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Facility Information:
Facility Name
APEX GmbH
City
Munich
Country
Germany

12. IPD Sharing Statement

Learn more about this trial

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

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