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

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

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.

Study Overview

• Status: Completed
• Conditions: Renal Impairment
• Intervention / Treatment: Drug: Betrixaban

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Munich, Germany
    • APEX GmbH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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

Secondary Outcome Measures

Outcome Measure	Time Frame
Safety assessments will include vital signs, electrocardiograms and adverse events	17 days
Measures of anti-coagulation	3 days

Collaborators and Investigators

• Sponsor: Portola Pharmaceuticals
• Collaborators: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start (Actual): July 31, 2009
• Primary Completion (Actual): February 28, 2010
• Study Completion (Actual): February 28, 2010

Study Registration Dates

• First Submitted: October 20, 2009
• First Submitted That Met QC Criteria: October 20, 2009
• First Posted (Estimated): October 21, 2009

Study Record Updates

• Last Update Posted (Actual): August 22, 2023
• Last Update Submitted That Met QC Criteria: October 13, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: Healthy; Renal impairment; Kidney dysfunction; Betrixaban
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Renal Insufficiency; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Betrixaban
• Other Study ID Numbers: 08-016