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

• Sponsor: Bristol-Myers Squibb (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02034591
• Collaborator: Pfizer (Industry)
• Enrollment: 37
• Location: 1
• Arms: 3
• Duration (Months): 1
• Patients Per Site Per Month: 36.3

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Healthy Subjects	Drug: Apixaban; Dietary Supplement: Boost Plus	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 37 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: 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
• Study Start Date: Oct 1, 2011
• Actual Primary Completion Date: Nov 1, 2011
• Actual Study Completion Date: Nov 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A-Apixaban Solution Apixaban 5 mg ( 0.4 mg/ml oral solution x 12.5 ml) through mouth or oral syringe	Drug: Apixaban; Other Names: BMS-562247
Experimental: Arm B-Apixaban 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; Other Names: BMS-562247 ; Dietary Supplement: Boost Plus
Experimental: Arm C-Apixaban 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; Other Names: BMS-562247

Outcome Measures

Primary Outcome Measures

1. Adjusted Geometric Mean of the Maximum Observed Plasma Concentration (Cmax) of Apixaban [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]

   Maximum observed plasma concentration (Cmax) is measured in nanograms per milliliter (ng/mL)

2. Adjusted Geometric Mean of the Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero Extrapolated to Infinite Time AUC(INF) of Apixaban [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]

   AUC(INF) is measured in nanogram hours per milliliter (ng*h/mL)

3. 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 [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]

   AUC(0-T) is measured in nanogram hours per milliliter (ng*h/mL)

Secondary Outcome Measures

1. Adjusted Geometric Mean of the Maximum Observed Plasma Concentration (Cmax) of Apixaban [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]

   Maximum observed plasma concentration (Cmax) is measured in nanograms per milliliter (ng/mL)

2. Adjusted Geometric Mean of the Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinite Time [AUC(INF)] of Apixaban [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]

   AUC(INF) is measured in nanogram hours per milliliter (ng*h/mL)

3. 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 [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]

   AUC(0-T) is measured in nanogram hours per milliliter (ng*h/mL)

4. Number of Participants With Serious Adverse Events (SAEs), Treatment-Related AEs, Deaths or Discontinuation of Study Drug Due to AEs [Day 1 to 30 days after last dose of study drug]

   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

5. Number of Participants With Marked Laboratory Abnormalities [Day 1 to 30 days after last dose of study drug]

   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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 45 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Healthcare Discoveries, LLC D/B/A Icon Development Solutions	San Antonio	Texas	United States	78209

Sponsors and Collaborators

• Bristol-Myers Squibb
• Pfizer

Investigators

• Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• BMS clinical trial educational resource

Publications

None provided.

• Responsible Party: Bristol-Myers Squibb
• ClinicalTrials.gov Identifier: NCT02034591
• Other Study ID Numbers: CV185-111
• First Posted: Jan 13, 2014
• Last Update Posted: Jun 23, 2016
• Last Verified: May 1, 2016

• Additional relevant MeSH terms: Crush Injuries; Apixaban

Study Results

Participant Flow

Pre-assignment Detail	37 participants were enrolled; 21 were randomized and treated. Reasons for non-randomization include 11 no longer met study criteria, 1 withdrew consent and 4 for other, not specified reasons. 20 participants completed the study; 1 withdrew consent on day 4 of treatment.

Arm/Group Title	Treatment A, Then Treatment B, Then Treatment C	Treatment A, Then Treatment C, Then Treatment B	Treatment B, Then Treatment A, Then Treatment C	Treatment B, Then Treatment C, Then Treatment A	Treatment C, Then Treatment A, Then Treatment B	Treatment C, Then Treatment B, Then Treatment A
Arm/Group Description	Each participant was given three interventions, one per period, with a 4 day washout in between periods Treatment A: Single dose apixaban 5 milligrams (mg) oral solution (OS) (0.4 milligrams per milliliter (mg/mL) x 12.5 milliliters (mL) administered by mouth via oral syringe Treatment B: Single dose apixaban 5 mg OS (0.4 mg/mL x 12.5 mL) administered via nasogastric tube (NGT) after 180 mL of Boost® Plus, followed by 60 mL of Boost® Plus via same NGT Treatment C: Single dose apixaban 5 mg (5 mg tablet crushed and suspended in 60 mL 5% dextrose in water (D5W) administered via NGT	Each participant was given three interventions, one per period, with a 4 day washout in between periods Treatment A: Single dose apixaban 5 milligrams (mg) oral solution (OS) (0.4 milligrams per milliliter (mg/mL) x 12.5 milliliters (mL) administered by mouth via oral syringe Treatment B: Single dose apixaban 5 mg OS (0.4 mg/mL x 12.5 mL) administered via nasogastric tube (NGT) after 180 mL of Boost® Plus, followed by 60 mL of Boost® Plus via same NGT Treatment C: Single dose apixaban 5 mg (5 mg tablet crushed and suspended in 60 mL 5% dextrose in water (D5W) administered via NGT	Each participant was given three interventions, one per period, with a 4 day washout in between periods Treatment A: Single dose apixaban 5 milligrams (mg) oral solution (OS) (0.4 milligrams per milliliter (mg/mL) x 12.5 milliliters (mL) administered by mouth via oral syringe Treatment B: Single dose apixaban 5 mg OS (0.4 mg/mL x 12.5 mL) administered via nasogastric tube (NGT) after 180 mL of Boost® Plus, followed by 60 mL of Boost® Plus via same NGT Treatment C: Single dose apixaban 5 mg (5 mg tablet crushed and suspended in 60 mL 5% dextrose in water (D5W) administered via NGT	Each participant was given three interventions, one per period, with a 4 day washout in between periods Treatment A: Single dose apixaban 5 milligrams (mg) oral solution (OS) (0.4 milligrams per milliliter (mg/mL) x 12.5 milliliters (mL) administered by mouth via oral syringe Treatment B: Single dose apixaban 5 mg OS (0.4 mg/mL x 12.5 mL) administered via nasogastric tube (NGT) after 180 mL of Boost® Plus, followed by 60 mL of Boost® Plus via same NGT Treatment C: Single dose apixaban 5 mg (5 mg tablet crushed and suspended in 60 mL 5% dextrose in water (D5W) administered via NGT	Each participant was given three interventions, one per period, with a 4 day washout in between periods Treatment A: Single dose apixaban 5 milligrams (mg) oral solution (OS) (0.4 milligrams per milliliter (mg/mL) x 12.5 milliliters (mL) administered by mouth via oral syringe Treatment B: Single dose apixaban 5 mg OS (0.4 mg/mL x 12.5 mL) administered via nasogastric tube (NGT) after 180 mL of Boost® Plus, followed by 60 mL of Boost® Plus via same NGT Treatment C: Single dose apixaban 5 mg (5 mg tablet crushed and suspended in 60 mL 5% dextrose in water (D5W) administered via NGT	Each participant was given three interventions, one per period, with a 4 day washout in between periods Treatment A: Single dose apixaban 5 milligrams (mg) oral solution (OS) (0.4 milligrams per milliliter (mg/mL) x 12.5 milliliters (mL) administered by mouth via oral syringe Treatment B: Single dose apixaban 5 mg OS (0.4 mg/mL x 12.5 mL) administered via nasogastric tube (NGT) after 180 mL of Boost® Plus, followed by 60 mL of Boost® Plus via same NGT Treatment C: Single dose apixaban 5 mg (5 mg tablet crushed and suspended in 60 mL 5% dextrose in water (D5W) administered via NGT
Period Title: Overall Study
STARTED	4	3	4	3	4	3
COMPLETED	4	3	4	3	3	3
NOT COMPLETED	0	0	0	0	1	0

Baseline Characteristics

Arm/Group Title	All Treatment Groups
Arm/Group Description	All Randomized Participants
Overall Participants	21
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	36.7
Sex: Female, Male (Count of Participants)
Female	8 38.1%
Male	13 61.9%

Outcome Measures

1. Primary Outcome

Title	Adjusted Geometric Mean of the Maximum Observed Plasma Concentration (Cmax) of Apixaban
Description	Maximum observed plasma concentration (Cmax) is measured in nanograms per milliliter (ng/mL)
Time Frame	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

Outcome Measure Data

Analysis Population Description

All randomized participants with available pharmacokinetic (PK) data

Arm/Group Title	Treatment A	Treatment B
Arm/Group Description	Single dose apixaban 5 milligrams (mg) oral solution (OS) (0.4 milligrams per milliliter (mg/mL) x 12.5 milliliters (mL) administered by mouth via oral syringe	Single dose apixaban 5 mg OS (0.4 mg/mL x 12.5 mL) administered via nasogastric tube (NGT) after 180 mL of Boost® Plus, followed by 60 mL of Boost® Plus via same NGT
Measure Participants	20	20
Geometric Mean (90% Confidence Interval) [ng/mL]	179.116	122.145

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment A, Treatment B
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of Adjusted Geometric Means
	Estimated Value	0.682
	Confidence Interval	(2-Sided) 90%; 0.621 to 0.748
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Adjusted Geometric Mean of the Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero Extrapolated to Infinite Time AUC(INF) of Apixaban
Description	AUC(INF) is measured in nanogram hours per milliliter (ng*h/mL)
Time Frame	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

Outcome Measure Data

Analysis Population Description

All randomized participants with available PK data

Arm/Group Title	Treatment A	Treatment B
Arm/Group Description	Single dose apixaban 5 milligrams (mg) oral solution (OS) (0.4 milligrams per milliliter (mg/mL) x 12.5 milliliters (mL) administered by mouth via oral syringe	Single dose apixaban 5 mg OS (0.4 mg/mL x 12.5 mL) administered via nasogastric tube (NGT) after 180 mL of Boost® Plus, followed by 60 mL of Boost® Plus via same NGT
Measure Participants	20	20
Geometric Mean (90% Confidence Interval) [ng*h/mL]	1397.666	1136.380

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment A, Treatment B
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of Adjusted Geometric Means
	Estimated Value	0.813
	Confidence Interval	(2-Sided) 90%; 0.766 to 0.863
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Primary Outcome

Title	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
Description	AUC(0-T) is measured in nanogram hours per milliliter (ng*h/mL)
Time Frame	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

Outcome Measure Data

Analysis Population Description

All randomized participants with available PK data

Arm/Group Title	Treatment A	Treatment B
Arm/Group Description	Single dose apixaban 5 milligrams (mg) oral solution (OS) (0.4 milligrams per milliliter (mg/mL) x 12.5 milliliters (mL) administered by mouth via oral syringe	Single dose apixaban 5 mg OS (0.4 mg/mL x 12.5 mL) administered via nasogastric tube (NGT) after 180 mL of Boost® Plus, followed by 60 mL of Boost® Plus via same NGT
Measure Participants	20	20
Geometric Mean (90% Confidence Interval) [ng*h/mL]	1372.836	1112.493

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment A, Treatment B
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of Adjusted Geometric Means
	Estimated Value	0.810
	Confidence Interval	(2-Sided) 90%; 0.764 to 0.860
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Adjusted Geometric Mean of the Maximum Observed Plasma Concentration (Cmax) of Apixaban
Description	Maximum observed plasma concentration (Cmax) is measured in nanograms per milliliter (ng/mL)
Time Frame	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

Outcome Measure Data

Analysis Population Description

All randomized participants with available PK data

Arm/Group Title	Treatment A	Treatment C
Arm/Group Description	Single dose apixaban 5 milligrams (mg) oral solution (OS) (0.4 milligrams per milliliter (mg/mL) x 12.5 milliliters (mL) administered by mouth via oral syringe	Single dose apixaban 5 mg (5 mg tablet crushed and suspended in 60 mL 5% dextrose in water (D5W) administered via NGT
Measure Participants	20	21
Geometric Mean (90% Confidence Interval) [ng/mL]	179.116	158.371

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment A, Treatment B
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of Adjusted Geometric Means
	Estimated Value	0.884
	Confidence Interval	(2-Sided) 90%; 0.830 to 0.942
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Adjusted Geometric Mean of the Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinite Time [AUC(INF)] of Apixaban
Description	AUC(INF) is measured in nanogram hours per milliliter (ng*h/mL)
Time Frame	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

Outcome Measure Data

Analysis Population Description

All randomized participants with available PK data

Arm/Group Title	Treatment A	Treatment C
Arm/Group Description	Single dose apixaban 5 milligrams (mg) oral solution (OS) (0.4 milligrams per milliliter (mg/mL) x 12.5 milliliters (mL) administered by mouth via oral syringe	Single dose apixaban 5 mg (5 mg tablet crushed and suspended in 60 mL 5% dextrose in water (D5W) administered via NGT
Measure Participants	20	21
Geometric Mean (90% Confidence Interval) [ng*h/mL]	1397.666	1327.248

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment A, Treatment B
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of Adjusted Geometric Means
	Estimated Value	0.950
	Confidence Interval	(2-Sided) 90%; 0.905 to 0.997
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	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
Description	AUC(0-T) is measured in nanogram hours per milliliter (ng*h/mL)
Time Frame	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

Outcome Measure Data

Analysis Population Description

All randomized participants with available PK data

Arm/Group Title	Treatment A	Treatment C
Arm/Group Description	Single dose apixaban 5 milligrams (mg) oral solution (OS) (0.4 milligrams per milliliter (mg/mL) x 12.5 milliliters (mL) administered by mouth via oral syringe	Single dose apixaban 5 mg (5 mg tablet crushed and suspended in 60 mL 5% dextrose in water (D5W) administered via NGT
Measure Participants	20	21
Geometric Mean (90% Confidence Interval) [ng*h/mL]	1372.836	1300.728

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment A, Treatment B
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of adjusted geometric means
	Estimated Value	0.947
	Confidence Interval	(2-Sided) 90%; 0.903 to 0.994
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Number of Participants With Serious Adverse Events (SAEs), Treatment-Related AEs, Deaths or Discontinuation of Study Drug Due to AEs
Description	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
Time Frame	Day 1 to 30 days after last dose of study drug

Outcome Measure Data

Analysis Population Description

All randomized participants

Arm/Group Title	Treatment A	Treatment B	Treatment C
Arm/Group Description	Single dose apixaban 5 milligrams (mg) oral solution (OS) (0.4 milligrams per milliliter (mg/mL) x 12.5 milliliters (mL) administered by mouth via oral syringe	Single dose apixaban 5 mg OS (0.4 mg/mL x 12.5 mL) administered via nasogastric tube (NGT) after 180 mL of Boost® Plus, followed by 60 mL of Boost® Plus via same NGT	Single dose apixaban 5 mg (5 mg tablet crushed and suspended in 60 mL 5% dextrose in water (D5W) administered via NGT
Measure Participants	20	20	21
SAE	0 0%	0 NaN	1 NaN
Treatment-Related AE	0 0%	1 NaN	1 NaN
Deaths	0 0%	0 NaN	0 NaN
Treatment-Related Deaths	0 0%	0 NaN	0 NaN
Discontinuation of Study Drug Due to AEs	0 0%	0 NaN	0 NaN

8. Secondary Outcome

Title	Number of Participants With Marked Laboratory Abnormalities
Description	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
Time Frame	Day 1 to 30 days after last dose of study drug

Outcome Measure Data

Analysis Population Description

All randomized participants

Arm/Group Title	Treatment A	Treatment B	Treatment C
Arm/Group Description	Single dose apixaban 5 milligrams (mg) oral solution (OS) (0.4 milligrams per milliliter (mg/mL) x 12.5 milliliters (mL) administered by mouth via oral syringe	Single dose apixaban 5 mg OS (0.4 mg/mL x 12.5 mL) administered via nasogastric tube (NGT) after 180 mL of Boost® Plus, followed by 60 mL of Boost® Plus via same NGT	Single dose apixaban 5 mg (5 mg tablet crushed and suspended in 60 mL 5% dextrose in water (D5W) administered via NGT
Measure Participants	20	20	21
Leukocytes	0 0%	1 NaN	0 NaN
Basophils	1 4.8%	0 NaN	0 NaN
Eosinophils	0 0%	1 NaN	0 NaN
Blood, Urine	1 4.8%	1 NaN	0 NaN
RBC, Urine	0 0%	2 NaN	1 NaN
WBC, Urine	0 0%	2 NaN	1 NaN

Adverse Events

Time Frame	Day 1 to 30 days after last dose of study drug
Arm/Group Title	Treatment A		Treatment B		Treatment C
Arm/Group Description	Single dose apixaban 5 milligrams (mg) oral solution (OS) (0.4 milligrams per milliliter (mg/mL) x 12.5 milliliters (mL) administered by mouth via oral syringe		Single dose apixaban 5 mg OS (0.4 mg/mL x 12.5 mL) administered via nasogastric tube (NGT) after 180 mL of Boost® Plus, followed by 60 mL of Boost® Plus via same NGT		Single dose apixaban 5 mg (5 mg tablet crushed and suspended in 60 mL 5% dextrose in water (D5W) administered via NGT
All Cause Mortality
	Treatment A		Treatment B		Treatment C
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Treatment A		Treatment B		Treatment C
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/20 (0%)		1/21 (4.8%)
Gastrointestinal disorders
Gastritis	0/20 (0%)		0/20 (0%)		1/21 (4.8%)
Other (Not Including Serious) Adverse Events
	Treatment A		Treatment B		Treatment C
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/20 (30%)		3/20 (15%)		1/21 (4.8%)
Eye disorders
Vision blurred	1/20 (5%)		0/20 (0%)		0/21 (0%)
Musculoskeletal and connective tissue disorders
Pain in extremity	1/20 (5%)		0/20 (0%)		0/21 (0%)
Nervous system disorders
Headache	1/20 (5%)		1/20 (5%)		1/21 (4.8%)
Renal and urinary disorders
Pyuria	1/20 (5%)		0/20 (0%)		0/21 (0%)
Respiratory, thoracic and mediastinal disorders
Epistaxis	1/20 (5%)		0/20 (0%)		0/21 (0%)
Oropharyngeal pain	0/20 (0%)		1/20 (5%)		0/21 (0%)
Skin and subcutaneous tissue disorders
Rash macular	1/20 (5%)		0/20 (0%)		0/21 (0%)
Rash papular	0/20 (0%)		1/20 (5%)		0/21 (0%)
Vascular disorders
Haematoma	0/20 (0%)		1/20 (5%)		0/21 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.