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

Renal Impairment Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00999336
• Other study ID #: 08-016
• Status: Completed
• Phase: Phase 1
• Start date: July 31, 2009
• Est. completion date: February 28, 2010

Study information

• Verified date: October 2022
• Source: Alexion
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: February 28, 2010
• Est. primary completion date: February 28, 2010
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Renal Impairment
• Renal Insufficiency

Intervention

Drug:
• Betrixaban
80 mg betrixaban qd for 8 days

Locations

Country	Name	City	State
Germany	APEX GmbH	Munich

Sponsors (2)

Lead Sponsor	Collaborator
Portola Pharmaceuticals	Merck Sharp & Dohme LLC

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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).	Predose up to 168 hours postdose
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).	Predose, up to 168 hours postdose
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.	Predose, up to 168 hours postdose
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).	Predose, up to 168 hours postdose
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.	Predose, up to 168 hours postdose
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.	Predose, up to 24 hours postdose
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 (%).	4 hours Postdose at Day 8
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.	Day 1: predose; Day 8: 2, 3, 4, 8, 24, and 48 hours postdose
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).	Day 8: 2, 3, 4, 8, 24, and 48 hours postdose