Phase 1 Oral Solution and Crushed Tablet Relative Bioavailability Study of Apixaban When Administered Through a Nasogastric Tube in Healthy Subjects

Study Overview
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Brief Summary
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The purpose of this study is to assess the bioavailability of Apixaban oral solution administered through an Nasogastric Tube (NGT) in the presence of Boost® Plus and Apixaban administered as crushed tablet through a nasogastric tube relative to Apixaban solution administered orally in healthy subjects.

Official Title
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Bioavailability of Apixaban Oral Solution Administered Through a Nasogastric Tube in the Presence of Boost® Plus and Apixaban Administered as Crushed Tablet Through a Nasogastric Tube Relative to Apixaban Oral Solution in Healthy Subjects

Conditions
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Healthy Subjects

Intervention / Treatment
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* Drug: Apixaban
* Dietary Supplement: Boost Plus


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 Any history or evidence of abnormal bleeding or coagulation disorders, intracranial hemorrhage, or abnormal bleeding (including heavy menstrual bleeding that has resulted in anemia within the past 1 year) or coagulation disorders in a first degree relative

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: Arm A-Apixaban<br>Solution Apixaban 5 mg ( 0.4 mg/ml oral solution x 12.5 ml) through mouth or oral syringe | Drug: Apixaban<br> <br> * Other names: BMS-562247;|
| Experimental: Arm B-Apixaban<br>Oral Solution Apixaban 5 mg single dose (0.4 mg/mL oral solution x 12.5 mL) after 180 mL of Boost Plus®, followed by 60 mL of Boost Plus® via same NGT | Drug: Apixaban<br> <br> * Other names: BMS-562247;Dietary Supplement: Boost Plus<br> <br> |
| Experimental: Arm C-Apixaban<br>Single dose crushed Apixaban tablet 5 mg (5 mg tablet crushed and suspended in 60 mL Dextrose 5% in water (D5W)) through NGT | 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 | 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 for each 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 | 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 for each 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 | 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 for each intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adjusted Geometric Mean of the Maximum Observed Plasma Concentration (Cmax) of Apixaban | 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 for each intervention | 
| Adjusted Geometric Mean of the Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinite Time [AUC(INF)] of Apixaban | 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 for each 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 | 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 for each intervention | 
| Number of Participants With Serious Adverse Events (SAEs), Treatment-Related 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, v15.1) and graded using the Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0 | Day 1 to 30 days after last dose of study drug | 
| Number of Participants With Marked Laboratory Abnormalities | Marked laboratory abnormalities were defined as laboratory assessments meeting the following investigator-specified criteria: Leukocytes >1.2* upper limits of normal (ULN) , Basophils >3%, Eosinophils >1.5*ULN, Blood Urine >=2, Red Blood Cell (RBC) Urine >=2, White Blood Cell (WBC) Urine >=2 | Day 1 to 30 days after last dose of study drug |