Clinical trial NCT02101112: Bioavailability of Apixaban Crushed Tablet
Official title: Relative Bioavailability of Crushed Apixaban Tablets Administered With Water or Apple Sauce Compared With Intact Tablet in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Thrombosis
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2014-04-01
Enrollment: 69
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Adjusted Geometric Mean of Maximum Observed Plasma Concentration (Cmax) of Apixaban
timeFrame: 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
measure: Adjusted Geometric Mean of Area Under the Plasma Concentration-time Curve (AUC) From Time Zero Extrapolated to Infinite Time [AUC(INF)] of Apixaban
timeFrame: 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
measure: 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
timeFrame: 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 outcomes:
measure: Number of Participants With Serious Adverse Events, Death, or Discontinuation Due to Adverse Events by Study Completion
timeFrame: Randomization to May 2014; approximately 6 weeks
measure: Time of Maximum Observed Plasma Concentration (Tmax) of Apixaban
timeFrame: 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
measure: Terminal Plasma Half-life (T-HALF) of Apixaban
timeFrame: 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
measure: Relative Bioavailability (Frel) of Apixaban
timeFrame: 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
Other outcomes:
Locations:
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: Song Y, Chang M, Suzuki A, Frost RJ, Kelly A, LaCreta F, Frost C. Evaluation of Crushed Tablet for Oral Administration and the Effect of Food on Apixaban Pharmacokinetics in Healthy Adults. Clin Ther. 2016 Jul;38(7):1674-1685.e1. doi: 10.1016/j.clinthera.2016.05.004. Epub 2016 Jun 10.