Bioavailability of Apixaban Crushed Tablet

NCT02101112 | Completed Phase 1 Results

• 1 other identifier: CV185-292
• Study Type: interventional
• Target: 69
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Thrombosis

Outcome Measures

Primary Outcomes (3)

• Adjusted Geometric Mean of Maximum Observed Plasma Concentration (Cmax) of Apixaban

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

  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

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

  Area Under the Plasma Concentration-time Curve (AUC) From Time of Zero Extrapolated to Infinite Time (INF) \[AUC (INF)\] is measured as nanograms multiplied by hours per milliliter (ng\*h/mL)

  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

• 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

  Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to the Last Quantifiable Concentration \[AUC (0-T)\] is measured as nanograms multiplied by hours per milliliter (ng\*h/mL)

  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 (4)

• Number of Participants With Serious Adverse Events, Death, or Discontinuation Due to Adverse Events by Study Completion

  Randomization to May 2014; approximately 6 weeks

• Time of Maximum Observed Plasma Concentration (Tmax) of Apixaban

  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

• Terminal Plasma Half-life (T-HALF) of Apixaban

  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

• Relative Bioavailability (Frel) of Apixaban

  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

Study Arms (3)

Apixaban, 10 mg (whole tablets)

EXPERIMENTAL

Participants received a single dose of apixaban, 10 mg, given orally as 2 5-mg whole commercial tablets (reference)

Drug: Apixaban

Apixaban, 10 mg (crushed and suspended in water)

EXPERIMENTAL

Participants received a single dose of apixaban, 10 mg, given by mouth as 2 5-mg whole commercial tablets crushed and suspended in 30 mL of water

Drug: Apixaban

Apixaban, 10 mg (crushed and mixed with applesauce)

EXPERIMENTAL

Participants received a single dose of 10 mg, given by mouth as 2 5-mg apixaban commercial tablets crushed and mixed with 30 g of applesauce

Drug: Apixaban

Interventions

Apixaban DRUG

Also known as: Eliquis®

Apixaban, 10 mg (crushed and mixed with applesauce); Apixaban, 10 mg (crushed and suspended in water); Apixaban, 10 mg (whole tablets)

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Related Publications (1)

• 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.

  PMID: 27292282 DERIVED

Related Links

• BMS clinical trial educational resource
• Investigator Inquiry form

MeSH Terms

Conditions

Thrombosis

Interventions

apixaban

Condition Hierarchy (Ancestors)

Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 28, 2014
• First Posted: April 1, 2014
• Study Start: March 1, 2014
• Primary Completion: May 1, 2014
• Study Completion: May 1, 2014
• Last Updated: March 3, 2016
• Results First Posted: March 3, 2016

Record last verified: 2016-02