Clinical trial NCT02074358: A Study to Assess the Effects of 2 Prothrombin Complex Concentrates on the Pharmacodynamics of Apixaban in Healthy Adult Subjects
Official title: A Study to Assess the Effects of 2 Prothrombin Complex Concentrates on the Pharmacodynamics of Apixaban in Healthy Adult Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Anticoagulation
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2014-02-28
Enrollment: 43
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: The purpose of this study is to assess the effect of two 4-Factor PCC formulations on Apixaban pharmacodynamics in healthy adult subjects.


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

Primary outcomes:
measure: 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
timeFrame: Day 4 at 3 hours post apixaban dose and prior to infusion (Pre-infusion Baseline), Day 4 at 30 minutes post infusion (PCC or Placebo)
measure: 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
timeFrame: Day 1 pre-dose apixaban (pre-apixaban Baseline), Day 4 at 30 minutes post infusion (PCC or Placebo)
Secondary outcomes:
measure: 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
timeFrame: Day 4 at 3 hours post apixaban dose and prior to infusion (Pre-infusion Baseline), Day 4 at 30 minutes post infusion.
measure: 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
timeFrame: Day 4 at 3 hours post apixaban dose and prior to infusion (Pre-infusion Baseline), Day 4 at 30 minutes post infusion.
measure: 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
timeFrame: Day 4 at 3 hours post apixaban dose and prior to infusion (Pre-infusion Baseline), Day 4 at 30 minutes post infusion.
measure: 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
timeFrame: Day 4 at 3 hours post apixaban dose and prior to infusion (Pre-infusion Baseline), Day 4 at 30 minutes post infusion.
measure: 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
timeFrame: Day 4 at 3 hours post apixaban dose and prior to infusion (Pre-infusion Baseline), Day 4 at 30 minutes post infusion.
measure: 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
timeFrame: Day 4 at 3 hours post apixaban dose and prior to infusion (Pre-infusion Baseline), Day 4 at 30 minutes post infusion.
measure: 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
timeFrame: Day 1, pre-dose apixaban (Baseline), Day 4, 30 minutes post infusion.
measure: 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
timeFrame: Day 1, pre-dose apixaban (Baseline), Day 4, 30 minutes post infusion.
measure: 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
timeFrame: Day 1, pre-dose apixaban (Baseline), Day 4, 30 minutes post infusion.
measure: 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
timeFrame: Day 1, pre-dose apixaban (Baseline), Day 4, 30 minutes post infusion.
measure: 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
timeFrame: Day 1, pre-dose apixaban (Baseline), Day 4, 30 minutes post infusion.
measure: Geometric Mean Maximum Observed Plasma Concentration (Cmax) of Apixaban on Day 4
timeFrame: Day 4
measure: Geometric Mean Time of Maximum Observed Plasma Concentration (Tmax) of Apixaban on Day 4
timeFrame: Day 4
measure: Geometric Mean Area Under the Plasma Concentration-Time Curve in One Dosing Interval [AUC(0-12)] of Apixaban on Day 4
timeFrame: Day 4
measure: Adjusted Geometric Mean AUC (0-12) of Apixaban on Day 4
timeFrame: Day 4
measure: 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
timeFrame: Day 4
measure: Adjusted Geometric Mean AUC (0-24) for Apixaban on Day 4
timeFrame: Day 4
measure: Geometric Mean Trough Observed Plasma Concentration at the End of One Dosing Interval (12h) [Cmin] of Apixaban on Day 4
timeFrame: Day 4
measure: Mean Terminal Elimination Half-Life (T-HALF) of Apixaban on Day 4
timeFrame: Day 4
measure: Number of Participants With Death, Serious Adverse Events (SAEs), Adverse Events (AEs), and Discontinuation Due to AEs - Treatment Population
timeFrame: Day 1 to 30 days Post Last Dose
measure: Number of Participants With Marked Abnormalities (MA) in Laboratory Tests - Treated Population
timeFrame: Day 1 (first dose) to Day of Study Discharge (Day 11 of Treatment Period 3)
measure: 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
timeFrame: Day -1 first treatment period, Days 4 and 7 each treatment period
measure: Mean Change From Baseline in Diastolic and Systolic Blood Pressure on Day 4 and Day 7
timeFrame: Screening, Day -1 first treatment period, Days 4 and 7 post treatment
measure: Mean Change From Baseline in Heart Rate on Day 4 and Day 7
timeFrame: Screening, Day -1 first treatment period, Days 4 and 7 post treatment
measure: Mean Change From Baseline in Respiration Rate on Day 4 and Day 7
timeFrame: Screening, Day -1 first treatment period, Days 4 and 7 post treatment
measure: Mean Change From Baseline Temperature on Day 4 and Day 7
timeFrame: Screening, Day -1 first treatment period, Days 4 and 7 post treatment
Other outcomes:
Locations:
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: