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

• ClinicalTrials.gov Identifier: NCT02034591
• Recruitment Status: Completed
• First Posted: January 13, 2014
• Results First Posted: June 23, 2016
• Last Update Posted: June 23, 2016
• Sponsor: Bristol-Myers Squibb
• Collaborator: Pfizer
• Information provided by (Responsible Party): Bristol-Myers Squibb

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 (Clinical Trial)
• 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: October 2011
• Actual Primary Completion Date: November 2011
• Actual Study Completion Date: November 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 Name: 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 Name: 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 Name: BMS-562247

Outcome Measures

Primary Outcome Measures :

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

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

Criteria

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

United States, Texas

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

More Information

Additional Information:

BMS clinical trial educational resource 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Song Y, Wang X, Perlstein I, Wang J, Badawy S, Frost C, LaCreta F. Relative Bioavailability of Apixaban Solution or Crushed Tablet Formulations Administered by Mouth or Nasogastric Tube in Healthy Subjects. Clin Ther. 2015 Aug;37(8):1703-12. doi: 10.1016/j.clinthera.2015.05.497. Epub 2015 Jul 15.

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

Additional relevant MeSH terms:

Crush Injuries; Wounds and Injuries; Apixaban; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Anticoagulants