Phase 1
Completed N=16
Pharmacokinetics and Pharmacodynamics of Apixaban in Subjects on Hemodialysis
Source: ClinicalTrials.gov NCT01340586 ↗Enrolled (actual)
16
Serious AEs
0.0%
Results posted
Oct 2016
Primary outcomePrimary: Geometric Mean of Maximum Observed Plasma Concentration (Cmax) of Single 5mg Oral Dose of Apixaban — 125.6; 98.9; 113.6 ng/mL
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Geometric Mean of Maximum Observed Plasma Concentration (Cmax) of Single 5mg Oral Dose of Apixaban |
125.6; 98.9; 113.6 | — |
| PRIMARY Geometric Mean of Maximum Observed Plasma Concentration (Cmax) of Metabolite BMS-730823 |
10.8; 15.9; 20.0 | — |
| PRIMARY 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 |
1205; 1430; 1673 | — |
| PRIMARY 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 |
205; 746; 953 | — |
| PRIMARY 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 |
1265; 1474; 1717 | — |
| PRIMARY Geometric Mean of Area Under the Concentration-time Curve From Time Zero Extrapolated to Infinite Time (AUC(INF)) of BMS-730823 |
NA; NA; NA | — |
| PRIMARY Mean Plasma Terminal Half-life (T-Half) of Single 5mg Oral Dose of Apixaban |
20.0; 12.5; 12.7 | — |
| PRIMARY Mean Plasma Terminal Half-life (T-Half) of BMS-730823 |
NA | — |
| PRIMARY Median Time of Maximum Observed Plasma Concentration (Tmax) of a Single 5 mg Oral Dose of Apixaban |
2.00; 2.00; 2.00 | — |
| PRIMARY Median Time of Maximum Observed Plasma Concentration (Tmax) of Metabolite BMS-730823 |
9.00; 15.00; 21.00 | — |
| PRIMARY Geometric Mean of Area Under the Plasma Concentration-Time Curve From 2 to 6 Hours (AUC(2-6)) for Apixaban |
309; 312 | — |
| PRIMARY Geometric Mean of Area Under the Plasma Concentration-Time Curve From 2 to 6 Hours (AUC(2-6)) for BMS-730823 |
15.0; 17.7 | — |
| PRIMARY Mean Percent Dose of Apixaban Recovered in Urine (%UR) |
18.397; 0.145; 0.181 | — |
| PRIMARY Mean Percent Dose of Apixaban Recovered in Dialysate (%DR) |
6.68 | — |
| PRIMARY Mean Renal Clearance (CLR) of Apixaban |
11.263; 0.020; 0.020 | — |
| PRIMARY Mean Renal Clearance (CLR) of BMS-730823 |
6.36; NA; NA | — |
| PRIMARY Mean Hemodialysis Clearance (CLD) of Apixaban |
17.7 | — |
| PRIMARY Mean Hemodialysis Clearance (CLD) of BMS-730823 |
NA | — |
| PRIMARY Percentage of Apixaban Extracted During Hemodialysis |
-1.1 | — |
| PRIMARY Percentage of BMS-730823 Extracted During Hemodialysis |
-19.9 | — |
| SECONDARY Mean Maximum Percent Change From Baseline International Normalized Ratio (INR) Following a Single 5 mg Oral Dose of Apixaban |
31.5; 16.6; 16.8 | — |
| SECONDARY Mean Maximum Percent Change From Baseline Prothrombin Time (PT) Following a Single 5 mg Oral Dose of Apixaban |
32.4; 16.9; 17.4 | — |
| SECONDARY Mean Maximum Percent Change From Baseline Activated Partial Thromboplastin Time (aPTT) Following a Single Oral Dose of 5 mg Apixaban |
19.9; 7.0; 23.0 | — |
| SECONDARY Mean Peak Anti-FXa Activity Following a Single Oral Dose of 5 mg Apixaban |
1.47; 1.03; 1.29 | — |
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.
Data sourced from ClinicalTrials.gov (NCT01340586). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.