Bioavailability of Apixaban Crushed Tablet

Thrombosis Clinical Trial

Official title:

Relative Bioavailability of Crushed Apixaban Tablets Administered With Water or Apple Sauce Compared With Intact Tablet in Healthy Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02101112
• Other study ID #: CV185-292
• Status: Completed
• Phase: Phase 1
• First received: March 28, 2014
• Last updated: February 29, 2016
• Start date: March 2014
• Est. completion date: May 2014

Study information

• Verified date: February 2016
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 69
• Est. completion date: May 2014
• Est. primary completion date: May 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 45 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Bio-availability Study, Intervention Model: Crossover Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Thrombosis

Intervention

Drug:
• Apixaban

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No
Primary	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	No
Secondary	Number of Participants With Serious Adverse Events, Death, or Discontinuation Due to Adverse Events by Study Completion	Adverse Event (AE) = any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. Serious Adverse Event (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.	Randomization to May 2014; approximately 6 weeks	Yes
Secondary	Time of Maximum Observed Plasma Concentration (Tmax) of Apixaban	Time of maximum observed plasma concentration (Tmax) measured in hours (h)	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	No
Secondary	Terminal Plasma Half-life (T-HALF) of Apixaban	Terminal plasma half-life (T-HALF) was derived from plasma concentration versus time data. T-HALF was the time required for one half of the total amount of administered drug to be eliminated from the body.	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	No
Secondary	Relative Bioavailability (Frel) of Apixaban	Frel is calculated using the treatment ratio of AUC(INF) where the denominator is the AUC(INF) of the reference therapy, 10mg of Apixaban (whole tablet).	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	No

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