Phase 1 Bioavailability Study of Apixaban Solution Formulation Relative to Apixaban Tablets in Healthy Subjects

Study Overview
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Brief Summary
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The purpose of this study is to assess the oral bioavailability of Apixaban solution formulation (Treatment B, 10 mg as 25 mL x 0.4 mg/mL) relative to Apixaban tablets (Treatment A, 10 mg as 2 x 5 mg tablets) in healthy subjects.

Official Title
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Study of Bioavailability of Apixaban Solution Formulation Relative to Apixaban Tablets in Healthy Subjects

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: Apixaban


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy subjects as determined by no clinically significant deviation from normal in medical history, physical examination, ECGs, and clinical laboratory determinations Exclusion Criteria: Any significant acute or chronic medical illness or relevant trauma (e.g., history of chronic hypertension, bacterial endocarditis, hemorrhagic stroke, motor vehicle accident resulting in significant head trauma or internal injuries) History or evidence of abnormal bleeding or coagulation disorder (e.g., easy bruising or gingival bleeding, prolonged bleeding after dental extraction, postpartum, or after trauma, wounds or surgery)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment A: Apixaban tablet<br>Apixaban Film coated Tablet Single dose 10 mg orally | Drug: Apixaban<br> <br> * Other names: BMS - 562247;|
| Experimental: Treatment B: Apixaban oral solution<br>Apixaban Solution Single dose 10 mg orally | Drug: Apixaban<br> <br> * Other names: BMS - 562247;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adjusted Geometric Mean of the Maximum Observed Plasma Concentration (Cmax) of Apixaban | Serial blood samples for pharmacokinetic analysis were collected at selected times up to 72 hours after each dose. Maximum observed plasma concentration (Cmax) is measured in nanograms per milliliter (ng/mL) | Pre-dose and 0.25, 0.50, 1, 2, 3, 4, 5, 6, 9, 12, 24, 36, 48, 60, 72 hours post-dose per intervention | 
| Adjusted Geometric Mean of the Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero Extrapolated to Infinite Time AUC(INF) of Apixaban | Serial blood samples for pharmacokinetic analysis were collected at selected times up to 72 hours after each dose. AUC(INF) is measured in nanogram hours per milliliter (ng*h/mL) | Pre-dose and 0.25, 0.50, 1, 2, 3, 4, 5, 6, 9, 12, 24, 36, 48, 60, 72 hours post-dose per intervention | 
| Adjusted Geometric Mean of the Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration [AUC(0-T)] of Apixaban | Serial blood samples for pharmacokinetic analysis were collected at selected times up to 72 hours after each dose. AUC(0-T) is measured in nanogram hours per milliliter (ng*h/mL) | Pre-dose and 0.25, 0.50, 1, 2, 3, 4, 5, 6, 9, 12, 24, 36, 48, 60, 72 hours post-dose per intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Serious Adverse Events (SAEs), Treatment-Related Adverse Events (AEs), Deaths or Discontinuation of Study Drug Due to AEs | AE=any new unfavorable symptom, sign or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity or drug dependency/abuse; is life-threatening, an important medical event or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=having certain, probable, possible or missing relationship to study drug. Death=during the study and up to 28 days past study discontinuation. The select AEs were determined using the Medical Dictionary for Regulatory Activities (MedDRA, v13). | Day 1 to 30 days after last dose of study drug | 
| Number of Participants With Marked Laboratory Abnormalities | Clinical laboratory tests were performed pre-study and at selected times throughout the study. Marked laboratory abnormalities were defined as laboratory assessments meeting the following investigator-specified criteria: Leukocytes < 0.9* lower limits of normal (LLN), absolute neutrophils + bands <= 1.500 10*3 cells/microliter, white blood cells (WBC) urine value >= 2+. These laboratory abnormalities were not considered clinically significant and therefore not adverse events. | Pre-study screen (Day -1) to Day 8 or day of study discharge |