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

Bristol-Myers Squibb (BMS)

Status and phase: Completed; Phase 1

Conditions: Anticoagulation

Treatments: Drug: Cofact (4-Factor PCC); Drug: Apixaban; Drug: Beriplex P/N (4-Factor PCC); Drug: Placebo (Saline solution)

Study type: Interventional

Funder types: Industry

Identifiers

NCT02074358

2013-000646-18 (EudraCT Number)

CV185-156

Details and patient eligibility

About

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

Enrollment: 43 patients

Sex: All

Ages: 18 to 45 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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43 participants in 3 patient groups

Treatment A: Apixaban + Placebo (Saline solution)

Experimental group

Description:

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

Treatment:

Drug: Placebo (Saline solution)

Drug: Apixaban

Treatment B: Apixaban + Cofact (4-Factor PCC)

Experimental group

Description:

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

Treatment:

Drug: Cofact (4-Factor PCC)

Drug: Apixaban

Treatment C: Apixaban + Beriplex P/N (4-Factor PCC)

Experimental group

Description:

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

Treatment:

Drug: Beriplex P/N (4-Factor PCC)

Drug: Apixaban