A Study to Assess the Effects of 2 Prothrombin Complex Concentrates on the Pharmacodynamics of Apixaban in Healthy Adult Subjects | RxWiki

A Study to Assess the Effects of 2 Prothrombin Complex Concentrates on the Pharmacodynamics of Apixaban in Healthy Adult Subjects

Overview[ - collapse ][ - ]

Purpose	The purpose of this study is to assess the effect of two 4-Factor PCC formulations on Apixaban pharmacodynamics in healthy adult subjects.
Condition	Anticoagulation
Intervention	Drug: Apixaban Drug: Cofact (4-Factor PCC) Drug: Beriplex P/N (4-Factor PCC) Drug: Placebo (Saline solution)
Phase	Phase 1
Sponsor	Bristol-Myers Squibb
Responsible Party	Bristol-Myers Squibb
ClinicalTrials.gov Identifier	NCT02074358
First Received	February 26, 2014
Last Updated	February 26, 2014
Last verified	February 2014

Tracking Information[ + expand ][ + ]

First Received Date	February 26, 2014
Last Updated Date	February 26, 2014
Start Date	February 2014
Estimated Primary Completion Date	April 2014
Current Primary Outcome Measures	Pharmacodynamic Measure: Endogenous thrombin potential (ETP) change from pre-prothrombin complex concentrate (PCC) baseline and Day 1 pre-Apixaban baseline [Time Frame: Day 1-7] [Designated as safety issue: No]ETP is a Thrombin Generation Assay (TGA) Parameter Pre-PCC baseline is defined as the predose sample collected on Day 4, 3 hours after the Apixaban dose of each period Day 1 pre-Apixaban baseline is defined as the predose sample collected on Day 1, prior to first Apixaban dose (0 hour)
Current Secondary Outcome Measures	Pharmacodynamic Measures:Change from pre-PCC baseline and Day 1 pre-Apixaban baseline for other TGA parameters (Lag Time, Peak, Time to Peak and Velocity Index), PT, INR, aPTT and AXA [Time Frame: Day 1-7] [Designated as safety issue: No]Prothrombin time (PT), International Normalized Ratio (INR), activated partial thromboplastin time (aPTT) and activated anti-factor Xa activity (AXA) Safety assessments based on medical review of adverse event reports and the results of vital sign measurements, electrocardiograms, physical examinations, and clinical laboratory tests [Time Frame: Up to 41 days] [Designated as safety issue: Yes]The incidence of adverse events will be tabulated and reviewed for potential significance and clinical importance Multiple-dose pharmacokinetic parameter: Maximum observed plasma concentration (Cmax) of Apixaban [Time Frame: 45 timepoints up to day 35] [Designated as safety issue: No] Multiple-dose pharmacokinetic parameter: Time of maximum observed plasma concentration (Tmax) of Apixaban [Time Frame: 45 timepoints up to day 35] [Designated as safety issue: No] Multiple-dose pharmacokinetic parameter: Area under the concentration-time curve in one dosing interval [AUC(0-12)] of Apixaban [Time Frame: 45 timepoints up to day 35] [Designated as safety issue: No] Multiple-dose pharmacokinetic parameter: Area under the plasma concentration-time curve from time zero to 24 hours after dose administration [AUC(0-24)] of Apixaban [Time Frame: 45 timepoints up to day 35] [Designated as safety issue: No] Multiple-dose pharmacokinetic parameter: Trough observed plasma concentration at the end of one dosing interval (12h) [Cmin] of Apixaban [Time Frame: 45 timepoints up to day 35] [Designated as safety issue: No] Multiple-dose pharmacokinetic parameter: Terminal elimination half-life (T-HALF) of Apixaban [Time Frame: 45 timepoints up to day 35] [Designated as safety issue: No]

Descriptive Information[ + expand ][ + ]

Brief Title	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
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.
Detailed Description	Not Provided
Study Type	Interventional
Study Phase	Phase 1
Study Design	Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Basic Science
Condition	Anticoagulation
Intervention	Drug: Apixaban Other Names: BMS-562247Drug: Cofact (4-Factor PCC) Drug: Beriplex P/N (4-Factor PCC) Drug: Placebo (Saline solution)
Study Arm (s)	Experimental: Treatment A: Apixaban + Placebo (Saline solution) Apixaban 10 mg Tablet orally [Day 1-Day 3: twice daily (BID), Day 4: Single Dose (SD)] followed 3hr later by Saline solution (placebo) 0 IU/kg infusion for 30 min Intravenously Experimental: Treatment B: Apixaban + Cofact (4-Factor PCC) Apixaban 10 mg Tablet orally [Day 1-Day 3: twice daily (BID), Day 4: Single Dose (SD)] followed 3hr later by a Cofact (4-Factor PCC) 50 IU/kg infusion for 30 min Intravenously Experimental: Treatment C: Apixaban + Beriplex P/N (4-Factor PCC) Apixaban 10 mg Tablet orally [Day 1-Day 3: twice daily (BID), Day 4: Single Dose (SD)] followed 3hr later by a Beriplex P/N (4-Factor PCC) 50 IU/kg infusion for 30 min Intravenously

Recruitment Information[ + expand ][ + ]

Recruitment Status	Not yet recruiting
Estimated Enrollment	15
Estimated Completion Date	April 2014
Estimated Primary Completion Date	April 2014
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
Gender	Both
Ages	18 Years
Accepts Healthy Volunteers	Accepts Healthy Volunteers
Contacts	Not Provided
Location Countries	Not Provided

Administrative Information[ + expand ][ + ]

NCT Number	NCT02074358
Other Study ID Numbers	CV185-156
Has Data Monitoring Committee	No
Information Provided By	Bristol-Myers Squibb
Study Sponsor	Bristol-Myers Squibb
Collaborators	Not Provided
Investigators	Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
Verification Date	February 2014