Healthy Volunteers
Conditions
Brief summary
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.
Interventions
DRUGDrug: Apixaban sprinkle capsules
Single dose (25 x 0.1 mg capsules), oral administration
DRUGExperimental: Apixaban tablets followed by apixaban sprinkle capsules
Apixaban sprinkle capsules Single dose (25 x 0.1 mg capsules), oral administration
Sponsors
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Concentration as Measured by Maximum Observed Plasma Concentration (Cmax) | Day 1 to Day 8 | Assessment of bioavailability of apixaban 0.5mg tablets relative to apixaban 0.1mg Sprinkle in terms of concentration |
| AUC (0-T) - Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration | Day 1 to Day 8 | Assessment of bioavailability of apixaban 0.5mg tablets relative to apixaban 0.1mg Sprinkle in terms of plasma concentration and time |
| AUC (INF) - Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinite Time | Day 1 to Day 8 | Assessment of bioavailability of apixaban 0.5mg tablets relative to apixaban 0.1mg Sprinkle in terms of plasma concentration and time |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events Regardless of Causality, Serious Adverse Events and Adverse Events Leading to Discontinuation | Day 1 to Day 38 | Adverse events regardless of causality, Serious Adverse Events & Adverse events leading to discontinuation |
| Physical Measurement - Height | Pre-treatment Screening | Average height of all participants treated |
| Physical Measurement - Weight | Pre-treatment screening to Day 8 | Average weight of all participants treated |
| Physical Measurement - Body Mass Index (BMI) | Pre-treatment Screening to Day 8 | Body mass index (BMI) of 18.0 to 30.0 kg/m2, inclusive. Body mass index = weight (kg)/\[height(m)\]2. |
| Number of Participants With a Given Clinical Laboratory Abnormality | Day 1 to Day 8 | Assessment of clinical laboratory abnormalities |
| Tmax - Time of Maximum Observed Plasma Concentration | Day 1 to Day 8 | Assessment of bioavailability of apixaban 0.5mg tablets relative to apixaban 0.1mg Sprinkle in terms time of maximum concentration |
| Number of Participants With Out-of Range Vital Signs: Heart Rate (Bpm) | Day 1 to Day 8 | Number of participants with Out-of Range Heart Rate changes as follows: \< 55 and change from baseline \< -16 \>100 and change from baseline \> 10 |
| Number of Participants With Out-of Range Vital Signs: Respiration Rate | Day 1 to Day 8 | 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 |
| Number of Participants With Out-of Range Vital Signs: Temperature | Day 1 to Day 8 | 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 |
| Number of Participants With Out-of Range ECG Evaluations | Day 1 to Day 8 | Number of participants with out-of-range ECG changes. ECG intervals are measured in milliseconds (msec) |
| Number of Participants With Out-of Range Vital Signs: Blood Pressure | Day 1 to Day 8 | 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 |
| T-Half - Terminal Plasma Half Life. | Day 1 to Day 8 | 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 |
| Frel - Relative Bioavailability | Day 1 to Day 8 | The relative bioavailability of 0.1mg apixaban sprinkle capsules as compared to 0.5mg tablet formulation |
Countries
United States
Participant flow
Pre-assignment details
94 Participants Enrolled; 30 participants Randomized; Reasons Not Randomized: 43 participants no longer meet study criteria; 12 were lost to follow up 9 other; 5 screening extras: 4 back ups
Participants by arm
| Arm | Count |
|---|---|
| Treatment A Apixaban tablets (treatment A) followed by apixaban sprinkle capsules (treatment B) | 15 |
| Treatment B Apixaban sprinkle capsules (treatment B) followed by apixaban tablets (treatment A) | 15 |
| Total | 30 |
Baseline characteristics
| Characteristic | Treatment B | Total | Treatment A |
|---|---|---|---|
| Age, Continuous | 32.8 Years STANDARD_DEVIATION 7.3 | 32.0 Years STANDARD_DEVIATION 7.4 | 31.3 Years STANDARD_DEVIATION 7.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants | 13 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants | 17 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 10 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 9 Participants | 19 Participants | 10 Participants |
| Sex: Female, Male Female | 8 Participants | 16 Participants | 8 Participants |
| Sex: Female, Male Male | 7 Participants | 14 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 30 | 0 / 30 |
| other Total, other adverse events | 2 / 30 | 0 / 30 |
| serious Total, serious adverse events | 0 / 30 | 0 / 30 |
Outcome results
Primary
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
Time frame: Day 1 to Day 8
Population: All Treated Participants
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | AUC (0-T) - Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration | 695.9 ng*h/mL | Geometric Coefficient of Variation 27.3 |
| Treatment B | AUC (0-T) - Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration | 769.2 ng*h/mL | Geometric Coefficient of Variation 23.7 |
Primary
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
Time frame: Day 1 to Day 8
Population: All Treated Participants
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | AUC (INF) - Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinite Time | 714.7 ng*h/mL | Geometric Coefficient of Variation 26.9 |
| Treatment B | AUC (INF) - Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinite Time | 787.9 ng*h/mL | Geometric Coefficient of Variation 23.1 |
Primary
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
Time frame: Day 1 to Day 8
Population: All Treated Participants
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | Concentration as Measured by Maximum Observed Plasma Concentration (Cmax) | 77.4 ng/mL | Geometric Coefficient of Variation 26.5 |
| Treatment B | Concentration as Measured by Maximum Observed Plasma Concentration (Cmax) | 99.3 ng/mL | Geometric Coefficient of Variation 24.6 |
Secondary
Frel - Relative Bioavailability
The relative bioavailability of 0.1mg apixaban sprinkle capsules as compared to 0.5mg tablet formulation
Time frame: Day 1 to Day 8
Population: All Treated Participants
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | Frel - Relative Bioavailability | 110.24 Percentage | Geometric Coefficient of Variation 9.3 |
Secondary
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
Time frame: Day 1 to Day 38
Population: All Treated Participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment A | Number of Participants With Adverse Events Regardless of Causality, Serious Adverse Events and Adverse Events Leading to Discontinuation | Adverse Events | 7 Participants |
| Treatment A | Number of Participants With Adverse Events Regardless of Causality, Serious Adverse Events and Adverse Events Leading to Discontinuation | Serious Adverse Events | 0 Participants |
| Treatment A | Number of Participants With Adverse Events Regardless of Causality, Serious Adverse Events and Adverse Events Leading to Discontinuation | Adverse Events leading to Discontinuation | 0 Participants |
| Treatment B | Number of Participants With Adverse Events Regardless of Causality, Serious Adverse Events and Adverse Events Leading to Discontinuation | Adverse Events | 3 Participants |
| Treatment B | Number of Participants With Adverse Events Regardless of Causality, Serious Adverse Events and Adverse Events Leading to Discontinuation | Serious Adverse Events | 0 Participants |
| Treatment B | Number of Participants With Adverse Events Regardless of Causality, Serious Adverse Events and Adverse Events Leading to Discontinuation | Adverse Events leading to Discontinuation | 0 Participants |
Secondary
Number of Participants With a Given Clinical Laboratory Abnormality
Assessment of clinical laboratory abnormalities
Time frame: Day 1 to Day 8
Population: All Treated Participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment A | Number of Participants With a Given Clinical Laboratory Abnormality | Hematocrit abnormal low | 0 participants |
| Treatment A | Number of Participants With a Given Clinical Laboratory Abnormality | Sodium, Serum Abnormal High | 0 participants |
| Treatment A | Number of Participants With a Given Clinical Laboratory Abnormality | Eosinophils (absolute) Abnormal High | 0 participants |
| Treatment A | Number of Participants With a Given Clinical Laboratory Abnormality | Potassium Abnormal Low | 0 participants |
| Treatment A | Number of Participants With a Given Clinical Laboratory Abnormality | Neutrophils (Absolute) Abnormal low | 2 participants |
| Treatment A | Number of Participants With a Given Clinical Laboratory Abnormality | Potassium, Serum Abnormal High | 0 participants |
| Treatment A | Number of Participants With a Given Clinical Laboratory Abnormality | Prothrombin Time (PT) Abnormal High | 0 participants |
| Treatment A | Number of Participants With a Given Clinical Laboratory Abnormality | Chloride, Serum Abnormal Low | 0 participants |
| Treatment A | Number of Participants With a Given Clinical Laboratory Abnormality | hemoglobin abnormal low | 0 participants |
| Treatment A | Number of Participants With a Given Clinical Laboratory Abnormality | Chloride, Serum Abnormal High | 0 participants |
| Treatment A | Number of Participants With a Given Clinical Laboratory Abnormality | International Normalized Ratio (INR) Abnormal High | 0 participants |
| Treatment A | Number of Participants With a Given Clinical Laboratory Abnormality | Calcium, Serum Abnormal Low | 0 participants |
| Treatment A | Number of Participants With a Given Clinical Laboratory Abnormality | Lymphocytes abnormal low | 0 participants |
| Treatment A | Number of Participants With a Given Clinical Laboratory Abnormality | Calcium, Serum Abnormal High | 0 participants |
| Treatment A | Number of Participants With a Given Clinical Laboratory Abnormality | Alkaline Phosphate (ALP) Abnormal High | 0 participants |
| Treatment A | Number of Participants With a Given Clinical Laboratory Abnormality | Phosphorus, Inorganic Abnormal Low | 0 participants |
| Treatment A | Number of Participants With a Given Clinical Laboratory Abnormality | Leukocytes abnormal low | 0 participants |
| Treatment A | Number of Participants With a Given Clinical Laboratory Abnormality | Phosphorus, Inorganic Abnormal High | 0 participants |
| Treatment A | Number of Participants With a Given Clinical Laboratory Abnormality | Aspartate Aminotransferase (AST) Abnormal High | 0 participants |
| Treatment A | Number of Participants With a Given Clinical Laboratory Abnormality | Glucose, Fasting Serum Abnormal Low | 0 participants |
| Treatment A | Number of Participants With a Given Clinical Laboratory Abnormality | Lymphocytes Abnormal high | 0 participants |
| Treatment A | Number of Participants With a Given Clinical Laboratory Abnormality | Glucose, Fasting Serum Abnormal High | 0 participants |
| Treatment A | Number of Participants With a Given Clinical Laboratory Abnormality | Alanine Aminotransferase (ALT) Abnormal High | 0 participants |
| Treatment A | Number of Participants With a Given Clinical Laboratory Abnormality | Protein, Total Abnormal Low | 0 participants |
| Treatment A | Number of Participants With a Given Clinical Laboratory Abnormality | Platelet count abnormal low | 0 participants |
| Treatment A | Number of Participants With a Given Clinical Laboratory Abnormality | Protein, Total Abnormal High | 0 participants |
| Treatment A | Number of Participants With a Given Clinical Laboratory Abnormality | Bilirubin, Total Abnormal High | 0 participants |
| Treatment A | Number of Participants With a Given Clinical Laboratory Abnormality | Albumin Abnormal Low | 0 participants |
| Treatment A | Number of Participants With a Given Clinical Laboratory Abnormality | Monocytes (Absolute) Abnormal High | 0 participants |
| Treatment A | Number of Participants With a Given Clinical Laboratory Abnormality | Lactate Dehydrogenase (LDH) Abnormal High | 0 participants |
| Treatment A | Number of Participants With a Given Clinical Laboratory Abnormality | Blood Urea Nitrogen (BUN) Abnormal High | 0 participants |
| Treatment A | Number of Participants With a Given Clinical Laboratory Abnormality | Protein, Urine Abnormal High | 0 participants |
| Treatment A | Number of Participants With a Given Clinical Laboratory Abnormality | Leukocytes Abnormal high | 0 participants |
| Treatment A | Number of Participants With a Given Clinical Laboratory Abnormality | Glucose, Urine Abnormal High | 0 participants |
| Treatment A | Number of Participants With a Given Clinical Laboratory Abnormality | Creatinine Abnormal High | 0 participants |
| Treatment A | Number of Participants With a Given Clinical Laboratory Abnormality | Blood, Urine Abnormal High | 2 participants |
| Treatment A | Number of Participants With a Given Clinical Laboratory Abnormality | Basophils (absolute) Abnormal High | 0 participants |
| Treatment A | Number of Participants With a Given Clinical Laboratory Abnormality | WBC, Urine Abnormal High | 2 participants |
| Treatment A | Number of Participants With a Given Clinical Laboratory Abnormality | Sodium Abnormal Low | 0 participants |
| Treatment A | Number of Participants With a Given Clinical Laboratory Abnormality | RBC, Urine Abnormal High | 1 participants |
| Treatment A | Number of Participants With a Given Clinical Laboratory Abnormality | platelet count abnormal high | 0 participants |
| Treatment B | Number of Participants With a Given Clinical Laboratory Abnormality | RBC, Urine Abnormal High | 0 participants |
| Treatment B | Number of Participants With a Given Clinical Laboratory Abnormality | hemoglobin abnormal low | 0 participants |
| Treatment B | Number of Participants With a Given Clinical Laboratory Abnormality | Hematocrit abnormal low | 0 participants |
| Treatment B | Number of Participants With a Given Clinical Laboratory Abnormality | Platelet count abnormal low | 0 participants |
| Treatment B | Number of Participants With a Given Clinical Laboratory Abnormality | platelet count abnormal high | 0 participants |
| Treatment B | Number of Participants With a Given Clinical Laboratory Abnormality | Leukocytes abnormal low | 0 participants |
| Treatment B | Number of Participants With a Given Clinical Laboratory Abnormality | Leukocytes Abnormal high | 0 participants |
| Treatment B | Number of Participants With a Given Clinical Laboratory Abnormality | Neutrophils (Absolute) Abnormal low | 1 participants |
| Treatment B | Number of Participants With a Given Clinical Laboratory Abnormality | Lymphocytes abnormal low | 0 participants |
| Treatment B | Number of Participants With a Given Clinical Laboratory Abnormality | Lymphocytes Abnormal high | 0 participants |
| Treatment B | Number of Participants With a Given Clinical Laboratory Abnormality | Monocytes (Absolute) Abnormal High | 0 participants |
| Treatment B | Number of Participants With a Given Clinical Laboratory Abnormality | Basophils (absolute) Abnormal High | 0 participants |
| Treatment B | Number of Participants With a Given Clinical Laboratory Abnormality | Eosinophils (absolute) Abnormal High | 0 participants |
| Treatment B | Number of Participants With a Given Clinical Laboratory Abnormality | Prothrombin Time (PT) Abnormal High | 0 participants |
| Treatment B | Number of Participants With a Given Clinical Laboratory Abnormality | International Normalized Ratio (INR) Abnormal High | 0 participants |
| Treatment B | Number of Participants With a Given Clinical Laboratory Abnormality | Alkaline Phosphate (ALP) Abnormal High | 0 participants |
| Treatment B | Number of Participants With a Given Clinical Laboratory Abnormality | Aspartate Aminotransferase (AST) Abnormal High | 0 participants |
| Treatment B | Number of Participants With a Given Clinical Laboratory Abnormality | Alanine Aminotransferase (ALT) Abnormal High | 0 participants |
| Treatment B | Number of Participants With a Given Clinical Laboratory Abnormality | Bilirubin, Total Abnormal High | 0 participants |
| Treatment B | Number of Participants With a Given Clinical Laboratory Abnormality | Blood Urea Nitrogen (BUN) Abnormal High | 0 participants |
| Treatment B | Number of Participants With a Given Clinical Laboratory Abnormality | Creatinine Abnormal High | 0 participants |
| Treatment B | Number of Participants With a Given Clinical Laboratory Abnormality | Sodium Abnormal Low | 0 participants |
| Treatment B | Number of Participants With a Given Clinical Laboratory Abnormality | Sodium, Serum Abnormal High | 0 participants |
| Treatment B | Number of Participants With a Given Clinical Laboratory Abnormality | Potassium Abnormal Low | 0 participants |
| Treatment B | Number of Participants With a Given Clinical Laboratory Abnormality | Potassium, Serum Abnormal High | 0 participants |
| Treatment B | Number of Participants With a Given Clinical Laboratory Abnormality | Chloride, Serum Abnormal Low | 0 participants |
| Treatment B | Number of Participants With a Given Clinical Laboratory Abnormality | Chloride, Serum Abnormal High | 0 participants |
| Treatment B | Number of Participants With a Given Clinical Laboratory Abnormality | Calcium, Serum Abnormal Low | 0 participants |
| Treatment B | Number of Participants With a Given Clinical Laboratory Abnormality | Calcium, Serum Abnormal High | 0 participants |
| Treatment B | Number of Participants With a Given Clinical Laboratory Abnormality | Phosphorus, Inorganic Abnormal Low | 0 participants |
| Treatment B | Number of Participants With a Given Clinical Laboratory Abnormality | Phosphorus, Inorganic Abnormal High | 0 participants |
| Treatment B | Number of Participants With a Given Clinical Laboratory Abnormality | Glucose, Fasting Serum Abnormal Low | 0 participants |
| Treatment B | Number of Participants With a Given Clinical Laboratory Abnormality | Glucose, Fasting Serum Abnormal High | 0 participants |
| Treatment B | Number of Participants With a Given Clinical Laboratory Abnormality | Protein, Total Abnormal Low | 0 participants |
| Treatment B | Number of Participants With a Given Clinical Laboratory Abnormality | Protein, Total Abnormal High | 0 participants |
| Treatment B | Number of Participants With a Given Clinical Laboratory Abnormality | Albumin Abnormal Low | 0 participants |
| Treatment B | Number of Participants With a Given Clinical Laboratory Abnormality | Lactate Dehydrogenase (LDH) Abnormal High | 0 participants |
| Treatment B | Number of Participants With a Given Clinical Laboratory Abnormality | Protein, Urine Abnormal High | 0 participants |
| Treatment B | Number of Participants With a Given Clinical Laboratory Abnormality | Glucose, Urine Abnormal High | 0 participants |
| Treatment B | Number of Participants With a Given Clinical Laboratory Abnormality | Blood, Urine Abnormal High | 2 participants |
| Treatment B | Number of Participants With a Given Clinical Laboratory Abnormality | WBC, Urine Abnormal High | 2 participants |
Secondary
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)
Time frame: Day 1 to Day 8
Population: All treated participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment A | Number of Participants With Out-of Range ECG Evaluations | PR Interval Maximum on Treatment ≤ 200 | 29 participants |
| Treatment A | Number of Participants With Out-of Range ECG Evaluations | QT Interval Maximum on Treatment ≤ 500 | 30 participants |
| Treatment A | Number of Participants With Out-of Range ECG Evaluations | QRS Interval Baseline >200 | 0 participants |
| Treatment A | Number of Participants With Out-of Range ECG Evaluations | QT Interval Maximum on Treatment > 500 | 0 participants |
| Treatment A | Number of Participants With Out-of Range ECG Evaluations | PR Interval Baseline >200 | 0 participants |
| Treatment A | Number of Participants With Out-of Range ECG Evaluations | QT Interval Increase from Baseline ≤ 30 | 29 participants |
| Treatment A | Number of Participants With Out-of Range ECG Evaluations | QRS Interval Maximum on Treatment ≤ 120 | 30 participants |
| Treatment A | Number of Participants With Out-of Range ECG Evaluations | QT Interval Increase from Baseline > 30 | 1 participants |
| Treatment A | Number of Participants With Out-of Range ECG Evaluations | PR Interval Maximum on Treatment >200 | 1 participants |
| Treatment A | Number of Participants With Out-of Range ECG Evaluations | QTcF Interval Baseline ≤ 450 | 30 participants |
| Treatment A | Number of Participants With Out-of Range ECG Evaluations | QRS Interval Maximum on Treatment > 120 | 0 participants |
| Treatment A | Number of Participants With Out-of Range ECG Evaluations | QTcF Interval Baseline >450 | 0 participants |
| Treatment A | Number of Participants With Out-of Range ECG Evaluations | PR Interval Baseline ≤ 200 | 30 participants |
| Treatment A | Number of Participants With Out-of Range ECG Evaluations | QTcF Interval Maximum on Treatment ≤ 450 | 30 participants |
| Treatment A | Number of Participants With Out-of Range ECG Evaluations | QT Interval Baseline ≤ 500 | 30 participants |
| Treatment A | Number of Participants With Out-of Range ECG Evaluations | QTcF Interval Maximum on Treatment > 450 | 0 participants |
| Treatment A | Number of Participants With Out-of Range ECG Evaluations | QTcF Interval Increase from Baseline ≤ 30 | 30 participants |
| Treatment A | Number of Participants With Out-of Range ECG Evaluations | QRS Interval Baseline ≤ 120 | 30 participants |
| Treatment A | Number of Participants With Out-of Range ECG Evaluations | QTcF Interval Increase from Baseline > 30 | 0 participants |
| Treatment A | Number of Participants With Out-of Range ECG Evaluations | QT Interval Baseline >500 | 0 participants |
| Treatment B | Number of Participants With Out-of Range ECG Evaluations | QTcF Interval Increase from Baseline > 30 | 0 participants |
| Treatment B | Number of Participants With Out-of Range ECG Evaluations | PR Interval Baseline ≤ 200 | 30 participants |
| Treatment B | Number of Participants With Out-of Range ECG Evaluations | PR Interval Baseline >200 | 0 participants |
| Treatment B | Number of Participants With Out-of Range ECG Evaluations | PR Interval Maximum on Treatment ≤ 200 | 30 participants |
| Treatment B | Number of Participants With Out-of Range ECG Evaluations | PR Interval Maximum on Treatment >200 | 0 participants |
| Treatment B | Number of Participants With Out-of Range ECG Evaluations | QRS Interval Baseline ≤ 120 | 30 participants |
| Treatment B | Number of Participants With Out-of Range ECG Evaluations | QRS Interval Baseline >200 | 0 participants |
| Treatment B | Number of Participants With Out-of Range ECG Evaluations | QRS Interval Maximum on Treatment ≤ 120 | 30 participants |
| Treatment B | Number of Participants With Out-of Range ECG Evaluations | QRS Interval Maximum on Treatment > 120 | 0 participants |
| Treatment B | Number of Participants With Out-of Range ECG Evaluations | QT Interval Baseline ≤ 500 | 30 participants |
| Treatment B | Number of Participants With Out-of Range ECG Evaluations | QT Interval Baseline >500 | 0 participants |
| Treatment B | Number of Participants With Out-of Range ECG Evaluations | QT Interval Maximum on Treatment ≤ 500 | 30 participants |
| Treatment B | Number of Participants With Out-of Range ECG Evaluations | QT Interval Maximum on Treatment > 500 | 0 participants |
| Treatment B | Number of Participants With Out-of Range ECG Evaluations | QT Interval Increase from Baseline ≤ 30 | 29 participants |
| Treatment B | Number of Participants With Out-of Range ECG Evaluations | QT Interval Increase from Baseline > 30 | 1 participants |
| Treatment B | Number of Participants With Out-of Range ECG Evaluations | QTcF Interval Baseline ≤ 450 | 30 participants |
| Treatment B | Number of Participants With Out-of Range ECG Evaluations | QTcF Interval Baseline >450 | 0 participants |
| Treatment B | Number of Participants With Out-of Range ECG Evaluations | QTcF Interval Maximum on Treatment ≤ 450 | 30 participants |
| Treatment B | Number of Participants With Out-of Range ECG Evaluations | QTcF Interval Increase from Baseline ≤ 30 | 30 participants |
| Treatment B | Number of Participants With Out-of Range ECG Evaluations | QTcF Interval Maximum on Treatment > 450 | 0 participants |
Secondary
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
Time frame: Day 1 to Day 8
Population: All treated participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment A | Number of Participants With Out-of Range Vital Signs: Blood Pressure | SBP < 90 and change from baseline < -20 | 0 participants |
| Treatment A | Number of Participants With Out-of Range Vital Signs: Blood Pressure | SBP >140 and change from baseline >20 | 0 participants |
| Treatment A | Number of Participants With Out-of Range Vital Signs: Blood Pressure | DBP < 55 and change from baseline < -10 | 0 participants |
| Treatment A | Number of Participants With Out-of Range Vital Signs: Blood Pressure | DBP >90 and change from baseline >10 | 0 participants |
| Treatment B | Number of Participants With Out-of Range Vital Signs: Blood Pressure | DBP >90 and change from baseline >10 | 0 participants |
| Treatment B | Number of Participants With Out-of Range Vital Signs: Blood Pressure | SBP < 90 and change from baseline < -20 | 0 participants |
| Treatment B | Number of Participants With Out-of Range Vital Signs: Blood Pressure | DBP < 55 and change from baseline < -10 | 1 participants |
| Treatment B | Number of Participants With Out-of Range Vital Signs: Blood Pressure | SBP >140 and change from baseline >20 | 0 participants |
Secondary
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
Time frame: Day 1 to Day 8
Population: All treated participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment A | Number of Participants With Out-of Range Vital Signs: Heart Rate (Bpm) | <55 and change from baseline < -16 | 0 participants |
| Treatment A | Number of Participants With Out-of Range Vital Signs: Heart Rate (Bpm) | >100 and change from baseline > 10 | 0 participants |
| Treatment B | Number of Participants With Out-of Range Vital Signs: Heart Rate (Bpm) | <55 and change from baseline < -16 | 0 participants |
| Treatment B | Number of Participants With Out-of Range Vital Signs: Heart Rate (Bpm) | >100 and change from baseline > 10 | 0 participants |
Secondary
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
Time frame: Day 1 to Day 8
Population: All treated participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment A | Number of Participants With Out-of Range Vital Signs: Respiration Rate | >16 rpm | 1 participants |
| Treatment A | Number of Participants With Out-of Range Vital Signs: Respiration Rate | change from baseline > 10 rpm | 0 participants |
| Treatment A | Number of Participants With Out-of Range Vital Signs: Respiration Rate | >16 or change from baseline >10 rpm | 1 participants |
| Treatment B | Number of Participants With Out-of Range Vital Signs: Respiration Rate | >16 rpm | 1 participants |
| Treatment B | Number of Participants With Out-of Range Vital Signs: Respiration Rate | change from baseline > 10 rpm | 0 participants |
| Treatment B | Number of Participants With Out-of Range Vital Signs: Respiration Rate | >16 or change from baseline >10 rpm | 1 participants |
Secondary
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
Time frame: Day 1 to Day 8
Population: All treated participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment A | Number of Participants With Out-of Range Vital Signs: Temperature | >38.3°C | 0 participants |
| Treatment A | Number of Participants With Out-of Range Vital Signs: Temperature | change from baseline > 1.6°C | 0 participants |
| Treatment A | Number of Participants With Out-of Range Vital Signs: Temperature | >38.3°C or change from baseline > 1.6°C | 0 participants |
| Treatment B | Number of Participants With Out-of Range Vital Signs: Temperature | >38.3°C | 0 participants |
| Treatment B | Number of Participants With Out-of Range Vital Signs: Temperature | change from baseline > 1.6°C | 0 participants |
| Treatment B | Number of Participants With Out-of Range Vital Signs: Temperature | >38.3°C or change from baseline > 1.6°C | 0 participants |
Secondary
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.
Time frame: Pre-treatment Screening to Day 8
Population: All treated participants
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment A | Physical Measurement - Body Mass Index (BMI) | Pre-treatment | 22.96 kilograms / Meters² (kg/m²) | Standard Deviation 3.35 |
| Treatment A | Physical Measurement - Body Mass Index (BMI) | Day 1 | 25.87 kilograms / Meters² (kg/m²) | Standard Deviation 3.5 |
| Treatment A | Physical Measurement - Body Mass Index (BMI) | Day 8 | 25.31 kilograms / Meters² (kg/m²) | Standard Deviation 3.25 |
| Treatment B | Physical Measurement - Body Mass Index (BMI) | Pre-treatment | 25.85 kilograms / Meters² (kg/m²) | Standard Deviation 2.91 |
| Treatment B | Physical Measurement - Body Mass Index (BMI) | Day 1 | 25.84 kilograms / Meters² (kg/m²) | Standard Deviation 2.87 |
| Treatment B | Physical Measurement - Body Mass Index (BMI) | Day 8 | 25.55 kilograms / Meters² (kg/m²) | Standard Deviation 2.79 |
Secondary
Physical Measurement - Height
Average height of all participants treated
Time frame: Pre-treatment Screening
Population: All treated participants
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | Physical Measurement - Height | 173.23 centimeter (cm) | Standard Deviation 5.81 |
| Treatment B | Physical Measurement - Height | 165.86 centimeter (cm) | Standard Deviation 8.86 |
Secondary
Physical Measurement - Weight
Average weight of all participants treated
Time frame: Pre-treatment screening to Day 8
Population: All treated participants
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment A | Physical Measurement - Weight | Pre-treatment | 78.09 kilograms (kg) | Standard Deviation 5.81 |
| Treatment A | Physical Measurement - Weight | Day 1 | 77.83 kilograms (kg) | Standard Deviation 3.35 |
| Treatment A | Physical Measurement - Weight | Day 8 | 76.15 kilograms (kg) | Standard Deviation 11.6 |
| Treatment B | Physical Measurement - Weight | Pre-treatment | 165.86 kilograms (kg) | Standard Deviation 8.86 |
| Treatment B | Physical Measurement - Weight | Day 1 | 71.47 kilograms (kg) | Standard Deviation 12.55 |
| Treatment B | Physical Measurement - Weight | Day 8 | 70.64 kilograms (kg) | Standard Deviation 12.28 |
Secondary
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
Time frame: Day 1 to Day 8
Population: All Treated Participants
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | T-Half - Terminal Plasma Half Life. | 8.81 h (hours) | Geometric Coefficient of Variation 39.2 |
| Treatment B | T-Half - Terminal Plasma Half Life. | 7.91 h (hours) | Geometric Coefficient of Variation 32.7 |
Secondary
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
Time frame: Day 1 to Day 8
Population: All Treated Participants
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | Tmax - Time of Maximum Observed Plasma Concentration | 2.30 h (hours) | Geometric Coefficient of Variation 36.4 |
| Treatment B | Tmax - Time of Maximum Observed Plasma Concentration | 0.98 h (hours) | Geometric Coefficient of Variation 43.8 |