Phase 1
Completed N=15
A Study to Assess the Effects of 2 Prothrombin Complex Concentrates on the Pharmacodynamics of Apixaban in Healthy Adult Subjects
Anticoagulation
Source: ClinicalTrials.gov NCT02074358 ↗
Enrolled (actual)
15
Serious AEs
0.0%
Results posted
Aug 2015
Primary outcomePrimary: Pharmacodynamic (PD) Parameter: Adjusted Mean Change in Endogenous Thrombin Potential (ETP) From Day 4 Pre-Infusion (PCC or Placebo) Baseline at Day 4, 30 Minutes Post Infusion of PCC or Placebo — 95.8; 521.0; 186.3 nM*min — p=<0.001
Summary
The purpose of this study is to assess the effect of two 4-Factor PCC formulations on Apixaban pharmacodynamics in healthy adult subjects.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Pharmacodynamic (PD) Parameter: Adjusted Mean Change in Endogenous Thrombin Potential (ETP) From Day 4 Pre-Infusion (PCC or Placebo) Baseline at Day 4, 30 Minutes Post Infusion of PCC or Placebo |
95.8; 521.0; 186.3 | <0.001 sig |
| PRIMARY PD Parameter: Adjusted Mean Change in Endogenous Thrombin Potential (ETP) From Day 1 Pre-Dose Apixaban Baseline at Day 4, 30 Minutes Post Infusion of PCC or Placebo |
-708.0; -276.3; -607.7 | — |
| SECONDARY PD Parameters: Adjusted Mean Change in TGA Lag Time and Adjusted Mean Change in TGA Time to Peak From Day 4 Pre-Infusion (PCC or Placebo) Baseline at Day 4, 30 Minutes Post Infusion of PCC or Placebo |
-0.16; -0.38; -0.32; -1.29; 0.06; 3.32 | 0.389 |
| SECONDARY PD Parameter: Adjusted Mean Change in TGA Peak Height From Day 4 Pre-Infusion (PCC or Placebo) Baseline at Day 4, 30 Minutes Post Infusion of PCC or Placebo |
11.1; 32.1; 4.7 | 0.014 sig |
| SECONDARY PD Parameter: Adjusted Mean Change in TGA Velocity Index From Day 4 Pre-Infusion (PCC or Placebo) Baseline at Day 4, 30 Minutes Post Infusion of PCC or Placebo |
3.4; 3.4; -3.2 | 0.996 |
| SECONDARY PD Parameter: Adjusted Mean Change in Coagulation Parameters Prothrombin Time (PT) and Activated Partial Thromboplastin Time (aPTT) From Day 4 Pre-Infusion (PCC or Placebo) Baseline at Day 4, 30 Minutes Post Infusion of PCC or Placebo |
-0.21; -1.85; -1.68; 0.35; -2.24; -1.54 | <0.001 sig |
| SECONDARY PD Parameter: Adjusted Mean Change in Coagulation Parameter International Normalized Ratio (INR) From Day 4 Pre-Infusion (PCC or Placebo) Baseline at Day 4, 30 Minutes Post Infusion of PCC or Placebo |
-0.015; -0.213; -0.185; 0.032; -0.207; -0.144 | <0.001 sig |
| SECONDARY PD Parameter: Adjusted Mean Change in Plasma Anti-Xa Activity From Day 4 Pre-Infusion (PCC or Placebo) Baseline at Day 4, 30 Minutes Post Infusion of PCC or Placebo |
-0.368; -0.607; -0.538 | 0.204 |
| SECONDARY PD Parameter: Adjusted Mean Change in TGA Lag Time and TGA Time to Peak From Day 1 Pre-Dose Apixaban Baseline at Day 4, 30 Minutes Post Infusion of PCC or Placebo |
3.56; 3.36; 3.40; 6.42; 7.90; 10.81 | — |
| SECONDARY PD Parameter: Adjusted Mean Change in TGA Peak Height From Day 1 Pre-Dose Apixaban Baseline at Day 4, 30 Minutes Post Infusion of PCC or Placebo |
-196.1; -174.9; -202.7 | — |
| SECONDARY PD Parameter: Adjusted Mean Change in TGA Velocity Index From Day 1 Pre-Dose Apixaban Baseline at Day 4, 30 Minutes Post Infusion of PCC or Placebo |
-63.7; -63.6; -71.5 | — |
| SECONDARY PD Parameter: Adjusted Mean Change in Coagulation Parameters PT and aPTT From Day 1 Pre-Dose Apixaban Baseline at Day 4, 30 Minutes Post Infusion of PCC or Placebo |
2.74; 1.17; 1.31; 4.94; 2.30; 3.01 | — |
| SECONDARY PD Parameter: Adjusted Mean Change in Coagulation Parameter INR From Day 1 Pre-Dose Apixaban Baseline at Day 4, 30 Minutes Post Infusion of PCC or Placebo |
0.290; 0.103; 0.130; 0.460; 0.216; 0.281 | — |
| SECONDARY Geometric Mean Maximum Observed Plasma Concentration (Cmax) of Apixaban on Day 4 |
291; 310; 290 | — |
| SECONDARY Geometric Mean Time of Maximum Observed Plasma Concentration (Tmax) of Apixaban on Day 4 |
2.00; 2.00; 2.00 | — |
| SECONDARY Geometric Mean Area Under the Plasma Concentration-Time Curve in One Dosing Interval [AUC(0-12)] of Apixaban on Day 4 |
1965; 2046; 2010 | — |
| SECONDARY Adjusted Geometric Mean AUC (0-12) of Apixaban on Day 4 |
1972; 2049; 2014 | — |
| SECONDARY Geometric Mean Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours After Dose Administration [AUC(0-24)] of Apixaban on Day 4 |
2537; 2583; 2585 | — |
| SECONDARY Adjusted Geometric Mean AUC (0-24) for Apixaban on Day 4 |
2546; 2594; 2592 | — |
| SECONDARY Geometric Mean Trough Observed Plasma Concentration at the End of One Dosing Interval (12h) [Cmin] of Apixaban on Day 4 |
86.0; 93.7; 95.5 | — |
| SECONDARY Mean Terminal Elimination Half-Life (T-HALF) of Apixaban on Day 4 |
10.9; 10.8; 11.0 | — |
| SECONDARY Number of Participants With Death, Serious Adverse Events (SAEs), Adverse Events (AEs), and Discontinuation Due to AEs - Treatment Population |
1; 5; 2; 0; 0; 0 | — |
| SECONDARY Number of Participants With Marked Abnormalities (MA) in Laboratory Tests - Treated Population |
0; 1; 0; 1; 1; 0 | — |
| SECONDARY Number of Participants With Out of Range Electrocardiogram (ECG) Intervals and Number of Participants With a Change From Baseline of Greater Than 30 Milliseconds in QT and QTcF |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Mean Change From Baseline in Diastolic and Systolic Blood Pressure on Day 4 and Day 7 |
0.9; -2.1; -2.9; 2.1; 3.7; 1.3 | — |
| SECONDARY Mean Change From Baseline in Heart Rate on Day 4 and Day 7 |
-4.3; -4.9; -5.5; -1.8; 0.4; -2.1 | — |
| SECONDARY Mean Change From Baseline in Respiration Rate on Day 4 and Day 7 |
-0.7; -1.3; -1.4; -0.4; -0.3; -0.5 | — |
| SECONDARY Mean Change From Baseline Temperature on Day 4 and Day 7 |
-0.15; -0.14; -0.22; -0.20; -0.08; -0.17 | — |
Eligibility Criteria
For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com
Inclusion Criteria
- Healthy subjects
- Body Mass Index (BMI) of 18 to 30 kg/m2
- Ages 18 to 45 years, including
- Women of childbearing potential (WOCBP) on acceptable contraception and with negative pregnancy test and not breastfeeding
Exclusion Criteria
- History or evidence of coagulopathy
- History or evidence of thrombosis such as deep vein thrombosis or other thromboembolic disease or having a first degree relative under 50 years of age with a history of thromboembolic disease
- Any significant acute or chronic medical illness or relevant trauma
- Any major surgery within 4 weeks of dosing (prior to dosing) or planned within 2 weeks after completion of the study
- History of heavy menstrual bleeding that has produced anemia within the past 1 year
- Current symptomatic or recent gastrointestinal disease or surgery that could impact the absorption of study drug
- History of smoking within 1 month prior to dosing
- Recent history (within 6 months of dosing) of pregnancy
- Use of hormonal contraceptives
- Exposure to any investigational drug or placebo within 4 weeks of study drug administration
- Use of any agent, including but not limited to Aspirin, Nonsteroidal anti-inflammatory drugs (NSAIDs), Anticoagulants, Fish oil capsules, Gingko, etc, that are known to increase the potential for bleeding, within 2 weeks prior to dosing
- History of any severe drug allergy including allergy to Heparin or history of Heparin-induced thrombocytopenia, hypersensitivity to PCCs or Factor Xa inhibitors, or history of allergy to human blood plasma derived products; history of any adverse drug reaction to Anticoagulants or Antiplatelet agents that resulted in excessive bleeding requiring medical intervention
Data sourced from ClinicalTrials.gov (NCT02074358). 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.