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

NCT00999336 | Completed Phase 1 Results

• 1 other identifier: 08-016
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

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.

Conditions

Renal Impairment

Keywords

Betrixaban; Renal impairment; Healthy; Kidney dysfunction

Outcome Measures

Primary Outcomes (9)

• 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

Study Arms (4)

Group H

ACTIVE COMPARATOR

Healthy subjects matched to the renal impairment groups

Drug: Betrixaban

Group A

EXPERIMENTAL

Patients with mild renal impairment

Drug: Betrixaban

Group B

EXPERIMENTAL

Patients with moderate renal impairment

Drug: Betrixaban

Group C

EXPERIMENTAL

Patients with severe renal impairment

Drug: Betrixaban

Interventions

Betrixaban DRUG

80 mg betrixaban qd for 8 days

Group A; Group B; Group C; Group H

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able to understand and sign the written informed consent.
• Subjects should have either normal renal function or have stable renal disease

You may not qualify if:

• 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

Sponsors & Collaborators

• Portola Pharmaceuticals: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

APEX GmbH

Munich, Germany

Location

MeSH Terms

Conditions

Renal Insufficiency

Interventions

betrixaban

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Results Point of Contact

• Title: Alexion Pharmaceuticals, Inc.
• Organization: Alexion Pharmaceuticals, Inc.

clinicaltrials@alexion.com

855-752-2356

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 20, 2009
• First Posted: October 21, 2009
• Study Start: July 31, 2009
• Primary Completion: February 28, 2010
• Study Completion: February 28, 2010
• Last Updated: August 22, 2023
• Results First Posted: August 22, 2023

Record last verified: 2022-10

Locations

DE (1)