Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    NCT02034591
Previous Study | Return to List | Next Study

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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:
Collaborator:
Pfizer
Information provided by (Responsible Party):
Bristol-Myers Squibb

Tracking Information
First Submitted Date  ICMJE January 10, 2014
First Posted Date  ICMJE January 13, 2014
Results First Submitted Date  ICMJE May 16, 2016
Results First Posted Date  ICMJE June 23, 2016
Last Update Posted Date June 23, 2016
Study Start Date  ICMJE October 2011
Actual Primary Completion Date November 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 16, 2016)
  • 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)
  • 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)
  • 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)
Original Primary Outcome Measures  ICMJE
 (submitted: January 10, 2014)
Bioavailability of Apixaban oral solution (OS) administered through NGT in the presence of Boost Plus® relative to Apixaban solution administered orally in healthy subjects [ Time Frame: Up to Day 12 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 16, 2016)
  • 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)
  • 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)
  • 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)
  • 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
  • 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
Original Secondary Outcome Measures  ICMJE
 (submitted: January 10, 2014)
  • Bioavailability of Apixaban crushed tablet administered through NGT relative to Apixaban solution administered orally in healthy subjects [ Time Frame: Up to Day 12 ]
  • Maximum observed plasma concentration (Cmax) of Apixaban will be derived from plasma concentration versus time [ Time Frame: 48 timepoints up to Day 12 ]
  • Time of maximum observed plasma concentration (Tmax) of Apixaban will be derived from plasma concentration versus time [ Time Frame: 48 timepoints up to Day 12 ]
  • Area under the plasma concentration-time curve from zero to the last time of last quantifiable concentration [AUC(0-T)] of Apixaban will be derived from plasma concentration versus time [ Time Frame: 48 timepoints up to Day 12 ]
  • Area under the plasma concentration-time curve from time zero extrapolated to infinite time [AUC(INF)] of Apixaban will be derived from plasma concentration versus time [ Time Frame: 48 timepoints up to Day 12 ]
  • Plasma elimination half-life (T-HALF) of Apixaban will be derived from plasma concentration versus time [ Time Frame: 48 timepoints up to Day 12 ]
  • Relative bioavailability as calculated by ratio of AUC(INF) (Frel) of Apixaban will be derived from plasma concentration versus time [ Time Frame: 48 timepoints up to Day 12 ]
  • Safety assessed by incidence of adverse events, results of vital sign measurements, electrocardiograms (ECGs), physical examinations, and clinical laboratory tests [ Time Frame: Up to Day 12 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase 1 Oral Solution and Crushed Tablet Relative Bioavailability Study of Apixaban When Administered Through a Nasogastric Tube in Healthy Subjects
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Condition  ICMJE Healthy Subjects
Intervention  ICMJE
  • Drug: Apixaban
    Other Name: BMS-562247
  • Dietary Supplement: Boost Plus
Study Arms  ICMJE
  • Experimental: Arm A-Apixaban
    Solution Apixaban 5 mg ( 0.4 mg/ml oral solution x 12.5 ml) through mouth or oral syringe
    Intervention: Drug: Apixaban
  • 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
    Interventions:
    • Drug: Apixaban
    • 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
    Intervention: Drug: Apixaban
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 16, 2016)
37
Original Actual Enrollment  ICMJE
 (submitted: January 10, 2014)
21
Actual Study Completion Date  ICMJE November 2011
Actual Primary Completion Date November 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 45 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02034591
Other Study ID Numbers  ICMJE CV185-111
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Bristol-Myers Squibb
Study Sponsor  ICMJE Bristol-Myers Squibb
Collaborators  ICMJE Pfizer
Investigators  ICMJE
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
PRS Account Bristol-Myers Squibb
Verification Date May 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP