Clinical trial NCT01340586: Pharmacokinetics and Pharmacodynamics of Apixaban in Subjects on Hemodialysis
Official title: Single-Dose Study to Evaluate the Pharmacokinetics, Pharmacodynamics, and Safety of Apixaban in Subjects on Hemodialysis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: End Stage Renal Disease
Keywords: PHARMACOKINETIC
NOS
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2011-04-22
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL

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.

Detailed description: Primary Purpose : To provide a clear understanding of the pharmacokinetics of Apixaban in subjects with ESRD and to determine the effect of hemodialysis on Apixaban pharmacokinetics .

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Geometric Mean of Maximum Observed Plasma Concentration (Cmax) of Single 5mg Oral Dose of Apixaban
timeFrame: 24 hours pre-dose to 72 hours post-dose
measure: Geometric Mean of Maximum Observed Plasma Concentration (Cmax) of Metabolite BMS-730823
timeFrame: From 24 hours pre-dose to 72 hours post-dose
measure: 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
timeFrame: 24 hours pre-dose to 72 hours post-dose
measure: 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
timeFrame: From 24 hours pre-dose to 72 hours post-dose
measure: 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
timeFrame: From 24 hours pre-dose to 72 hours post-dose
measure: Geometric Mean of Area Under the Concentration-time Curve From Time Zero Extrapolated to Infinite Time (AUC(INF)) of BMS-730823
timeFrame: 24 hours pre-dose to 72 hours post-dose
measure: Mean Plasma Terminal Half-life (T-Half) of Single 5mg Oral Dose of Apixaban
timeFrame: From 24 hours pre-dose to 72 hours post-dose
measure: Mean Plasma Terminal Half-life (T-Half) of BMS-730823
timeFrame: 24 hours pre-dose to 72 hours post-dose
measure: Median Time of Maximum Observed Plasma Concentration (Tmax) of a Single 5 mg Oral Dose of Apixaban
timeFrame: From 24 hours pre-dose to 72 hours post-dose
measure: Median Time of Maximum Observed Plasma Concentration (Tmax) of Metabolite BMS-730823
timeFrame: From 24 hours pre-dose to 72 hours post-dose
measure: Geometric Mean of Area Under the Plasma Concentration-Time Curve From 2 to 6 Hours (AUC(2-6)) for Apixaban
timeFrame: 2 to 6 hours post-dose
measure: Geometric Mean of Area Under the Plasma Concentration-Time Curve From 2 to 6 Hours (AUC(2-6)) for BMS-730823
timeFrame: 2 to 6 hours post-dose
measure: Mean Percent Dose of Apixaban Recovered in Urine (%UR)
timeFrame: 24 hours pre-dose to 72 hours post-dose
measure: Mean Percent Dose of Apixaban Recovered in Dialysate (%DR)
timeFrame: 2 to 6 hours post-dose
measure: Mean Renal Clearance (CLR) of Apixaban
timeFrame: 24 hours pre-dose to 72 hours post-dose
measure: Mean Renal Clearance (CLR) of BMS-730823
timeFrame: 24 hours pre-dose to 72 hours post-dose
measure: Mean Hemodialysis Clearance (CLD) of Apixaban
timeFrame: 2 to 6 hours post-dose
measure: Mean Hemodialysis Clearance (CLD) of BMS-730823
timeFrame: 2 to 6 hours post-dose
measure: Percentage of Apixaban Extracted During Hemodialysis
timeFrame: 2 to 6 hours post-dose
measure: Percentage of BMS-730823 Extracted During Hemodialysis
timeFrame: 2 to 6 hours post-dose
Secondary outcomes:
measure: Mean Maximum Percent Change From Baseline International Normalized Ratio (INR) Following a Single 5 mg Oral Dose of Apixaban
timeFrame: From 24 hours pre-dose to 72 hours post-dose
measure: Mean Maximum Percent Change From Baseline Prothrombin Time (PT) Following a Single 5 mg Oral Dose of Apixaban
timeFrame: From 24 hours pre-dose to 72 hours post-dose
measure: Mean Maximum Percent Change From Baseline Activated Partial Thromboplastin Time (aPTT) Following a Single Oral Dose of 5 mg Apixaban
timeFrame: From 24 hours pre-dose to 72 hours post-dose
measure: Mean Peak Anti-FXa Activity Following a Single Oral Dose of 5 mg Apixaban
timeFrame: From 24 hours pre-dose to 72 hours post-dose
Other outcomes:
measure: Number of Participants With Laboratory Marked Abnormalities
timeFrame: From 24 hours pre-dose to 72 hours post-dose
measure: Number of Participants Who Died or Experienced Serious Adverse Events (SAEs) or Adverse Events Leading to Discontinuation
timeFrame: From Day 1 to 30 days post study discontinuation
Locations:
city: Orlando
country: United States
state: Florida
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: 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.