Bioavailability of Apixaban Crushed Tablet

Phase 1

Completed

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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Apixaban, 10 mg (whole tablets)	Apixaban	Participants received a single dose of apixaban, 10 mg, given orally as 2 5-mg whole commercial tablets (reference)
Apixaban, 10 mg (crushed and suspended in water)	Apixaban	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
Apixaban, 10 mg (crushed and mixed with applesauce)	Apixaban	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

Primary Outcome Measures

Name	Time	Method
Adjusted Geometric Mean of Maximum Observed Plasma Concentration (Cmax) of Apixaban	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	Maximum observed plasma concentration (Cmax) measured in nanograms per milliliter (ng/mL)
Adjusted Geometric Mean of Area Under the Plasma Concentration-time Curve (AUC) From Time Zero Extrapolated to Infinite Time [AUC(INF)] of Apixaban	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	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)
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	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	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)

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Serious Adverse Events, Death, or Discontinuation Due to Adverse Events by Study Completion	Randomization to May 2014; approximately 6 weeks	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.
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	Time of maximum observed plasma concentration (Tmax) measured in hours (h)
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	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.
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	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).