Bioavailability of Apixaban Sprinkle Compared to Apixaban Capsules

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the absorption of apixaban (BMS-562247) into the bloodstream of healthy volunteers, when administered as sprinkle capsules compared to tablets. Eligible participants will be randomly assigned to 1 of 2 treatment sequences and will receive a single oral dose of apixaban twice during the course of the study.

Official Title
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A Study to Assess the Absorption of Apixaban (BMS-562247) Sprinkle Capsules Compared With Tablets in Healthy Volunteers

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: Drug: Apixaban sprinkle capsules
* Drug: Experimental: Apixaban tablets followed by apixaban sprinkle capsules


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent form. Healthy male and female participants determined by no clinically significant deviation from normal in medical history, physical examination, 12-lead ECGs (electrocardiograms), vital signs and clinical laboratory determinations. Women of childbearing potential (WOCBP) must have negative serum pregnancy tests (performed at screening and Day 1), must not be breastfeeding, and must agree to follow instructions for method(s) of contraception for duration of treatment with study drug apixaban, and for a total of 33 days after last dose of apixaban. Males sexually active with women of childbearing potential must agree to follow instructions for method(s) of contraception for duration of treatment with study drug apixaban, and for a total of 93 days after the last dose of apixaban; and must be willing to refrain from sperm donation during this time. Body mass index (BMI) of 18.0 to 30.0 kg/m², inclusive. Body mass index = weight (kg)/[height(m)]². Exclusion Criteria: History of chronic headaches (occurring 15 days or more a month) over the previous 3 months. History of gastroesophageal reflux disease, dyspepsia, protracted nausea, or chronic diarrhea. History or evidence of abnormal bleeding or coagulation disorders, hypermenorrhea, intracranial hemorrhage, or abnormal bleeding or coagulation disorders. Inability to comply with restrictions and prohibited treatments (e.g. women currently taking hormonal contraception). Use of tobacco- or nicotine-containing products (e.g. cigarettes, pipes, cigars, chewing tobacco, nicotine patches, nicotine lozenges, nicotine gum) within 6 months prior to study drug administration. Donation of blood to a blood bank or in a clinical study (except screening or follow-up visit) within 4 weeks of study drug administration (within 2 weeks for plasma only). Other protocol defined inclusion/exclusion criteria could apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Apixaban sprinkle capsules followed by apixaban tablets<br>Apixaban (BMS-562247) sprinkle capsules followed by apixaban tablets | Drug: Drug: Apixaban sprinkle capsules<br>* Single dose (25 x 0.1 mg capsules), oral administration<br>* Other names: •Eliquis;Drug: Experimental: Apixaban tablets followed by apixaban sprinkle capsules<br>* Apixaban sprinkle capsules Single dose (25 x 0.1 mg capsules), oral administration<br>* Other names: •BMS-562247;|
| Active Comparator: Apixaban tablets followed by apixaban sprinkle capsules<br>Apixaban (BMS-562247) tablets followed by apixaban sprinkle capsules | Drug: Drug: Apixaban sprinkle capsules<br>* Single dose (25 x 0.1 mg capsules), oral administration<br>* Other names: •Eliquis;Drug: Experimental: Apixaban tablets followed by apixaban sprinkle capsules<br>* Apixaban sprinkle capsules Single dose (25 x 0.1 mg capsules), oral administration<br>* Other names: •BMS-562247;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentration as Measured by Maximum Observed Plasma Concentration (Cmax) | Assessment of bioavailability of apixaban 0.5mg tablets relative to apixaban 0.1mg Sprinkle in terms of concentration | Day 1 to Day 8 | 
| AUC (0-T) - Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration | Assessment of bioavailability of apixaban 0.5mg tablets relative to apixaban 0.1mg Sprinkle in terms of plasma concentration and time | Day 1 to Day 8 | 
| AUC (INF) - Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinite Time | Assessment of bioavailability of apixaban 0.5mg tablets relative to apixaban 0.1mg Sprinkle in terms of plasma concentration and time | Day 1 to Day 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tmax - Time of Maximum Observed Plasma Concentration | Assessment of bioavailability of apixaban 0.5mg tablets relative to apixaban 0.1mg Sprinkle in terms time of maximum concentration | Day 1 to Day 8 | 
| T-Half - Terminal Plasma Half Life. | Assessment of bioavailability of apixaban 0.5mg tablets relative to apixaban 0.1mg Sprinkle in terms of time required to reach to half of plasma concentration | Day 1 to Day 8 | 
| Frel - Relative Bioavailability | The relative bioavailability of 0.1mg apixaban sprinkle capsules as compared to 0.5mg tablet formulation | Day 1 to Day 8 | 
| Number of Participants With Adverse Events Regardless of Causality, Serious Adverse Events and Adverse Events Leading to Discontinuation | Adverse events regardless of causality, Serious Adverse Events & Adverse events leading to discontinuation | Day 1 to Day 38 | 
| Physical Measurement - Height | Average height of all participants treated | Pre-treatment Screening | 
| Physical Measurement - Weight | Average weight of all participants treated | Pre-treatment screening to Day 8 | 
| Physical Measurement - Body Mass Index (BMI) | Body mass index (BMI) of 18.0 to 30.0 kg/m2, inclusive. Body mass index = weight (kg)/[height(m)]2. | Pre-treatment Screening to Day 8 | 
| Number of Participants With a Given Clinical Laboratory Abnormality | Assessment of clinical laboratory abnormalities | Day 1 to Day 8 | 
| Number of Participants With Out-of Range Vital Signs: Blood Pressure | Number of participants with Out-of Range Blood Pressure changes as follows: Systolic Blood Pressure (SBP) mmHg < 90 and change from baseline < -20 > 140 and change from baseline > 20 Diastolic Blood Pressure (DBP) mmHg < 55 and change from baseline < -10 > 90 and change from baseline > 10 | Day 1 to Day 8 | 
| Number of Participants With Out-of Range Vital Signs: Heart Rate (Bpm) | Number of participants with Out-of Range Heart Rate changes as follows: < 55 and change from baseline < -16 >100 and change from baseline > 10 | Day 1 to Day 8 | 
| Number of Participants With Out-of Range Vital Signs: Respiration Rate | Number of participants with Out-of Range respiration rate changes as follows: Respiration Rate is measured by number of respiration per min (rpm) > 16 rpm Change from baseline >10 rpm > 16 rpm or change from baseline > 10 rpm | Day 1 to Day 8 | 
| Number of Participants With Out-of Range Vital Signs: Temperature | Number of participants with Out-of Range temperature changes as follows: Temperature is measured in Degrees centigrade (°C) >38.3°C Change from baseline > 1.6°C >38.3°C or change from baseline > 1.6°C | Day 1 to Day 8 | 
| Number of Participants With Out-of Range ECG Evaluations | Number of participants with out-of-range ECG changes. ECG intervals are measured in milliseconds (msec) | Day 1 to Day 8 |