Pharmacokinetics and Pharmacodynamics of Apixaban in Subjects on Hemodialysis

NCT01340586 | Completed Phase 1 Results

• 1 other identifier: CV185-087
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to assess the pharmacokinetics of a single oral dose of 5 mg Apixaban in subjects with normal renal function and subjects with end stage renal disease (ESRD) maintained with hemodialysis.

Conditions

End Stage Renal Disease

Keywords

PHARMACOKINETIC; NOS

Outcome Measures

Primary Outcomes (20)

• Geometric Mean of Maximum Observed Plasma Concentration (Cmax) of Single 5mg Oral Dose of Apixaban

  Maximum observed plasma concentration (Cmax) was measured by plasma concentration of apixaban over time. The geometric means are reported in nanograms per milliliter (ng/mL).

  24 hours pre-dose to 72 hours post-dose

• Geometric Mean of Maximum Observed Plasma Concentration (Cmax) of Metabolite BMS-730823

  Maximum observed plasma concentration (Cmax) was measured by plasma concentration of BMS-730823 over time. The geometric means are reported in nanograms per milliliter (ng/mL).

  From 24 hours pre-dose to 72 hours post-dose

• Geometric Mean of Area Under the Concentration-time Curve From Time Zero to Time of the Last Quantifiable Concentration (AUC(0-T)) of Single 5mg Oral Dose of Apixaban

  Area under the concentration-time curve from time zero to time of the last quantifiable concentration (AUC(0-T)) was measured by plasma concentration of apixaban over time. The geometric means are reported in nanogram hours per milliliter (ng\*h/mL).

  24 hours pre-dose to 72 hours post-dose

• Geometric Mean of Area Under the Concentration-time Curve From Time Zero to Time of the Last Quantifiable Concentration (AUC(0-T)) of Metabolite BMS-730823

  Area under the concentration-time curve from time zero to time of the last quantifiable concentration (AUC(0-T)) was measured by plasma concentration of BMS-730823 over time. The geometric means are reported in nanogram hours per milliliter (ng\*h/mL).

  From 24 hours pre-dose to 72 hours post-dose

• Geometric Mean of Area Under the Concentration-time Curve From Time Zero Extrapolated to Infinite Time (AUC(INF)) of Single 5mg Oral Dose of Apixaban

  The area under the concentration-time curve from time zero extrapolated to infinite time (AUC(INF)) was measured by plasma concentration of apixaban over time. The geometric means are reported in nanogram hours per milliliter (ng\*h/mL).

  From 24 hours pre-dose to 72 hours post-dose

• Geometric Mean of Area Under the Concentration-time Curve From Time Zero Extrapolated to Infinite Time (AUC(INF)) of BMS-730823

  The area under the concentration-time curve from time zero extrapolated to infinite time (AUC(INF)) was measured by plasma concentration of BMS-730823 over time. The geometric means are reported in nanogram hours per milliliter (ng\*h/mL).

  24 hours pre-dose to 72 hours post-dose

• Mean Plasma Terminal Half-life (T-Half) of Single 5mg Oral Dose of Apixaban

  Plasma terminal half-life (T-Half) for apixaban was derived from plasma concentrations versus time data. Means were reported in hours.

  From 24 hours pre-dose to 72 hours post-dose

• Mean Plasma Terminal Half-life (T-Half) of BMS-730823

  Mean plasma terminal half-life (T-Half) for BMS-730823 was derived from plasma concentrations versus time data.

  24 hours pre-dose to 72 hours post-dose

• Median Time of Maximum Observed Plasma Concentration (Tmax) of a Single 5 mg Oral Dose of Apixaban

  Time of maximum observed plasma concentration (Tmax) for apixaban was derived from plasma concentrations versus time data. Medians were reported in hours.

  From 24 hours pre-dose to 72 hours post-dose

• Median Time of Maximum Observed Plasma Concentration (Tmax) of Metabolite BMS-730823

  Time of maximum observed plasma concentration (Tmax) for BMS-730823 was derived from plasma concentrations versus time data. Medians were reported in hours.

  From 24 hours pre-dose to 72 hours post-dose

• Geometric Mean of Area Under the Plasma Concentration-Time Curve From 2 to 6 Hours (AUC(2-6)) for Apixaban

  Area under the plasma concentration-time curve from 2 hours to 6 hours (AUC(2-6) for Apixaban was measured in participants with ESRD during dialysis in Period 1 only. Geometric Means were reported in nanogram hours per milliliter (ng\*hr/mL) and were determined from blood samples both entering and exiting the dialyzer.

  2 to 6 hours post-dose

• Geometric Mean of Area Under the Plasma Concentration-Time Curve From 2 to 6 Hours (AUC(2-6)) for BMS-730823

  Area under the plasma concentration-time curve from 2 hours to 6 hours (AUC(2-6) for BMS-730823 was measured in participants with ESRD during dialysis in Period 1 only. Geometric Means were reported in nanogram hours per milliliter (ng\*hr/mL) and were determined from blood samples both entering and exiting the dialyzer.

  2 to 6 hours post-dose

• Mean Percent Dose of Apixaban Recovered in Urine (%UR)

  The percent dose recovered in urine was calculated by dividing the cumulative amount of unchanged apixaban excreted in urine from the time of dose up to 72 hours post-dose by the apixaban dose administered.

  24 hours pre-dose to 72 hours post-dose

• Mean Percent Dose of Apixaban Recovered in Dialysate (%DR)

  Percent dose of Apixaban recovered in dialysate (%DR) was calculated by dividing the cumulative amount of apixaban excreted in each dialysate collection over 2-6 hours (DR(2-6)) by the apixaban dose. %DR was recorded only in period 1.

  2 to 6 hours post-dose

• Mean Renal Clearance (CLR) of Apixaban

  Renal clearance (CLR) was calculated by dividing the cumulative amount of apixaban excreted in urine by the respective cumulative plasma AUC over the same urine collection interval. Geometric means were reported in milliliters per minute (mL/min).

  24 hours pre-dose to 72 hours post-dose

• Mean Renal Clearance (CLR) of BMS-730823

  Renal clearance (CLR) was calculated by dividing the cumulative amount of BMS-730823 excreted in urine by the respective cumulative plasma AUC over the same urine collection interval. Geometric means were reported in milliliters per minute (mL/min).

  24 hours pre-dose to 72 hours post-dose

• Mean Hemodialysis Clearance (CLD) of Apixaban

  Hemodialysis clearance (CLD) was calculated by dividing the cumulative amount of apixaban excreted in dialysate by the respective cumulative plasma AUC over the same dialysate collection interval (AUC(2-6) entering). CLD measurements occurred only in period 1. Geometric means were reported in milliliters per minute (mL/min).

  2 to 6 hours post-dose

• Mean Hemodialysis Clearance (CLD) of BMS-730823

  Hemodialysis clearance (CLD) was calculated by dividing the cumulative amount of BMS-730823 excreted in dialysate by the respective cumulative plasma AUC over the same dialysate collection interval (AUC(2-6) entering). CLD measurements occurred only in period 1. Geometric means were reported in milliliters per minute (mL/min).

  2 to 6 hours post-dose

• Percentage of Apixaban Extracted During Hemodialysis

  The percentage of apixaban extracted during hemodialysis (extraction ratio) was calculated using the formula \[plasma AUC(2-6) exiting - AUC(2-6) entering\] / \[AUC(2-6) entering\] and converted to a percentage. The extraction ratio was measured in period 1 only, and was reported as a percentage.

  2 to 6 hours post-dose

• Percentage of BMS-730823 Extracted During Hemodialysis

  The percentage of BMS-730823 extracted during hemodialysis (extraction ratio) was calculated using the formula \[plasma AUC(2-6)exiting - AUC(2-6)entering\] / \[AUC(2-6) entering\] and converted to a percentage. The extraction ratio was measured in period 1 only, and was reported as a percentage.

  2 to 6 hours post-dose

Secondary Outcomes (4)

• Mean Maximum Percent Change From Baseline International Normalized Ratio (INR) Following a Single 5 mg Oral Dose of Apixaban

  From 24 hours pre-dose to 72 hours post-dose

• Mean Maximum Percent Change From Baseline Prothrombin Time (PT) Following a Single 5 mg Oral Dose of Apixaban

  From 24 hours pre-dose to 72 hours post-dose

• Mean Maximum Percent Change From Baseline Activated Partial Thromboplastin Time (aPTT) Following a Single Oral Dose of 5 mg Apixaban

  From 24 hours pre-dose to 72 hours post-dose

• Mean Peak Anti-FXa Activity Following a Single Oral Dose of 5 mg Apixaban

  From 24 hours pre-dose to 72 hours post-dose

Other Outcomes (2)

• Number of Participants With Laboratory Marked Abnormalities

  From 24 hours pre-dose to 72 hours post-dose

• Number of Participants Who Died or Experienced Serious Adverse Events (SAEs) or Adverse Events Leading to Discontinuation

  From Day 1 to 30 days post study discontinuation

Study Arms (2)

Group A: Apixaban

EXPERIMENTAL

Drug: Apixaban

Group B: Apixaban

EXPERIMENTAL

Drug: Apixaban

Interventions

Apixaban DRUG

Tablets, Oral, 5 mg, Once, 4 days

Group A: Apixaban

Eligibility Criteria

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

You may qualify if:

• The signed informed consent form.
• Subjects with normal renal function classified based on calculated creatinine clearance (CLCr) determined by the cockcroft-gault calculation.
• Eligible subjects with ESRD that is maintained with chronic and stable hemodialysis.

You may not qualify if:

• Any history of abnormal bleeding or coagulation disorders including those in a first degree relative under 50 years of age.
• History of significant head injury within the last two years.
• Any gastrointestinal surgery that could impact the absorption of study drug.
• Not expected to continue the hemodialysis treatment for the duration of the study.
• INR, PT, or aPTT above the upper limit of normal, unless agreed upon between the investigator and BMS medical monitor.
• History of allergy to Apixaban or Factor Xa inhibitors.

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (1)

Unknown Facility

Orlando, Florida, United States

Location

Related Publications (1)

• Wang X, Tirucherai G, Marbury TC, Wang J, Chang M, Zhang D, Song Y, Pursley J, Boyd RA, Frost C. Pharmacokinetics, pharmacodynamics, and safety of apixaban in subjects with end-stage renal disease on hemodialysis. J Clin Pharmacol. 2016 May;56(5):628-36. doi: 10.1002/jcph.628. Epub 2015 Dec 22.

  PMID: 26331581 RESULT

Related Links

• BMS clinical trial educational resource
• Investigator Inquiry form

MeSH Terms

Conditions

Kidney Failure, Chronic

Interventions

apixaban

Condition Hierarchy (Ancestors)

Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: April 21, 2011
• First Posted: April 22, 2011
• Study Start: June 1, 2011
• Primary Completion: September 1, 2011
• Study Completion: September 1, 2011
• Last Updated: October 11, 2016
• Results First Posted: October 11, 2016

Record last verified: 2016-08

Locations

US (1)