Bioavailability of Apixaban Crushed Tablet

Study Overview
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Brief Summary
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The purpose of this study is to determine whether the bioavailability of apixaban crushed tablets suspended in water or mixed with applesauce is similar to the bioavailability of apixaban whole tablets administered orally.

Detailed Description
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This study will investigate the bioavailability of apixaban administered as crushed tablets suspended in water and as crushed tablets mixed with applesauce compared with that of whole tablets. The study results may allow enhancement of the apixaban label to include alternative methods of apixaban administration, which may be of benefit to patients who have difficulty swallowing.

Official Title
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Relative Bioavailability of Crushed Apixaban Tablets Administered With Water or Apple Sauce Compared With Intact Tablet in Healthy Subjects

Conditions
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Thrombosis

Intervention / Treatment
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* Drug: Apixaban


Participation Criteria
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Eligibility Criteria
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For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com Inclusion Criteria: Healthy participants as determined by no clinically significant deviation from normal in findings of medical history, physical examination, electrocardiograms, vital signs, and clinical laboratory tests. Women of childbearing potential allowed. Must be following highly effective methods of contraception Exclusion Criteria: Any significant acute or chronic medical illness History of significant head injury within the last 2 years, including individuals with base of skull fractures Any major surgery within 4 weeks of study drug administration or anticipated within 2 weeks after completion of the study Any gastrointestinal (GI) surgery or GI disease that could impact absorption of study drug History of Gilbert's Syndrome Inability to tolerate oral medication Inability to be venipunctured and/or tolerate venous access Use of tobacco- or nicotine-containing products (including, but not limited to, cigarettes, pipes, cigars, chewing tobacco, nicotine patches, nicotine lozenges, or nicotine gum) within 6 months prior to study drug administration Any laboratory test results outside of the range of normal, confirmed by repeat results of: Platelet count <150,000 cells/µL Activated partial thromboplastin time >upper limit of normal (ULN) International normalized ratio >ULN Alanine aminotransferase >ULN Aspartate aminotransferase >ULN Total bilirubin >ULN Serum creatinine ≥1.5 mg/dL Hemoglobin <lower limit of normal (LLN) Hematocrit <LLN

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

Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Apixaban, 10 mg (whole tablets)<br>Participants received a single dose of apixaban, 10 mg, given orally as 2 5-mg whole commercial tablets (reference) | Drug: Apixaban<br> <br> * Other names: Eliquis®;|
| Experimental: Apixaban, 10 mg (crushed and suspended in water)<br>Participants received a single dose of apixaban, 10 mg, given by mouth as 2 5-mg whole commercial tablets crushed and suspended in 30 mL of water | Drug: Apixaban<br> <br> * Other names: Eliquis®;|
| Experimental: Apixaban, 10 mg (crushed and mixed with applesauce)<br>Participants received a single dose of 10 mg, given by mouth as 2 5-mg apixaban commercial tablets crushed and mixed with 30 g of applesauce | Drug: Apixaban<br> <br> * Other names: Eliquis®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adjusted Geometric Mean of Maximum Observed Plasma Concentration (Cmax) of Apixaban | Maximum observed plasma concentration (Cmax) measured in nanograms per milliliter (ng/mL) | Days 1, 5, and 9 predose and 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 24, 36, 48, 60 and 72 hours post dose | 
| Adjusted Geometric Mean of Area Under the Plasma Concentration-time Curve (AUC) From Time Zero Extrapolated to Infinite Time [AUC(INF)] of Apixaban | Area Under the Plasma Concentration-time Curve (AUC) From Time of Zero Extrapolated to Infinite Time (INF) [AUC (INF)] is measured as nanograms multiplied by hours per milliliter (ng*h/mL) | Days 1, 5, and 9 predose and 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 24, 36, 48, 60, and 72 hours post dose | 
| Adjusted Geometric Mean of Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to the Time of the Last Quantifiable Concentration [AUC(0-T)] of Apixaban | Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to the Last Quantifiable Concentration [AUC (0-T)] is measured as nanograms multiplied by hours per milliliter (ng*h/mL) | Days 1, 5, and 9 predose and 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 24, 36, 48, 60, and 72 hours post dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Serious Adverse Events, Death, or Discontinuation Due to Adverse Events by Study Completion | Adverse Event (AE) = any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. Serious Adverse Event (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. | Randomization to May 2014; approximately 6 weeks | 
| Time of Maximum Observed Plasma Concentration (Tmax) of Apixaban | Time of maximum observed plasma concentration (Tmax) measured in hours (h) | Days 1, 5 and 9 pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 9, 12 24, 36, 48, 60 and 72 hrs post dose | 
| Terminal Plasma Half-life (T-HALF) of Apixaban | Terminal plasma half-life (T-HALF) was derived from plasma concentration versus time data. T-HALF was the time required for one half of the total amount of administered drug to be eliminated from the body. | Days 1, 5 and 9 pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 9, 12 24, 36, 48, 60 and 72 hrs post dose | 
| Relative Bioavailability (Frel) of Apixaban | Frel is calculated using the treatment ratio of AUC(INF) where the denominator is the AUC(INF) of the reference therapy, 10mg of Apixaban (whole tablet). | Days 1, 5 and 9 pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 9, 12 24, 36, 48, 60 and 72 hrs post dose |