Deep Vein Thrombosis, Venous Thromboembolism
Conditions
Keywords
Pediatric, Pharmacokinetics (PK), Pharmacodynamics (PDy), Anticoagulant, Safety
Brief summary
This is the first evaluation of edoxaban in pediatric subjects. In this Phase 1 study, a single dose of edoxaban will be given to pediatric subjects who require anticoagulant therapy to see what the body does to the drug (pharmacokinetics) and what the drug does to the body (pharmacodynamics), and to compare if these effects are similar to those observed in adults.
Detailed description
Phase 1, open-label, multiple-center study in pediatric patients from 0 to \< 18 years of age. Patients will receive a single dose of edoxaban to match either the 30 mg (low dose) or the 60 mg (high dose) exposure in adults. Exact doses will be selected during the study on the basis of PK modeling of emerging data. If unanticipated exposures are observed, the target doses may be modified to best match expected exposure response relationships observed in adults. Enrollment in the study will start with the low dose, highest age group (adolescents) and will continue from low to high dose in each age group and from higher to lower age groups. Enrollment in the next dose/age cohort will begin after 50% of the subjects have completed the previous dose/age cohort. Age cohorts and dose groups: (6 participants each in low and high dose groups, for a total of 12 participants per age cohort) * 12 to \< 18 years of age * 6 to \<12 years of age * 2 to \<6 years of age * 6 months to \<2 years of age * 0 to \<6 months of age
Interventions
DRUGEdoxaban low dose
Edoxaban low dose
DRUGEdoxaban high dose
Edoxaban high dose
Sponsors
Daiichi Sankyo
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
0 Years to 18 Years
Healthy volunteers
No
Inclusion criteria
* Is a pediatric subject requiring anticoagulant therapy * Will abstain from the use of nonsteroidal anti-inflammatory drugs (such as ibuprofen), and other antiplatelet and anticoagulant agents (except for aspirin) from 24 hours prior to edoxaban dose until after the last PK sample is collected * Will follow food and concomitant medication restrictions
Exclusion criteria
* Any major or clinically relevant unexplained bleeding during prior anticoagulant therapy * History of abnormal bleeding or coagulation within last 6 months prior to study drug administration * Renal function with glomerular filtration rate (GFR) less than 50% of normal for age and size * Malabsorption disorders (e.g., cystic fibrosis or short bowel syndrome) * Hepatic disease associated with coagulopathy leading to a clinically relevant bleeding risk, alanine transaminase (ALT) \> 5 times the upper limit of normal (ULN) or total bilirubin \> 2 times the ULN with direct bilirubin \> 20% of the total
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic Parameter of Apparent Systemic Clearance (CL/F) | 0.25 to 1 hours, 1.5 to 3 hours, 4 to 8 hours, 9 to 14 hours, and 24 to 36 hours post-dose | A model-based pooled population pharmacokinetic (PK) method was used to estimate systemic clearance (CL/F). As prespecified in the protocol, arms were pooled due to sparse PK samples being collected. the median PK estimate is reported in all participants at a total of 5 blood samplings. |
| Pharmacokinetic Parameter of Apparent Volume of Distribution (V/F) | 0.25 to 1 hours, 1.5 to 3 hours, 4 to 8 hours, 9 to 14 hours, and 24 to 36 hours post-dose | A model-based pooled population pharmacokinetic (PK) method was used to estimate apparent volume of distribution (V/F). As prespecified in the protocol, arms were pooled due to sparse PK samples being collected. the median PK estimate is reported in all participants at a total of 5 blood samplings. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacodynamic Parameter Mean Prothrombin Time (PT) | Pre-dose and 0.25 to 1 hours (except for Cohorts 4a, 4b, 5a, and 5b, 0.5 to 2 hours), 1.5 to 3 hours, 4 to 8 hours, 9 to 14 hours, and 24 to 36 hours post-dose | Descriptive statistics were used to assess Mean Prothrombin Time (PT) by cohort at a total of 6 blood samplings. |
| Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT) | Pre-dose and 0.25 to 1 hours (except for Cohorts 4a, 4b, 5a, and 5b, 0.5 to 2 hours), 1.5 to 3 hours, 4 to 8 hours, 9 to 14 hours, and 24 to 36 hours post-dose | Descriptive statistics were used to assess Mean Activated Partial Thromboplastin Time by cohort for a total of 6 blood samplings. |
| Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa) | Pre-dose and 0.25 to 1 hours (except for Cohorts 4a, 4b, 5a, and 5b, 0.5 to 2 hours), 1.5 to 3 hours, 4 to 8 hours, 9 to 14 hours, and 24 to 36 hours post-dose | Descriptive statistics were used to assess Mean Anti-Factor Xa (FXa) by cohort for a total of 6 blood samplings. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Mean Palatability Score for the Liquid Formulation on a 100 mm Visual Analog Scale (VAS) | Baseline up to 30 minutes post-dose | Overall palatability, bitterness, sweetness, and overall taste or aroma were assessed by participants (or guardians) receiving the liquid oral suspension where each subscale used a 100 mm visual analog scale (VAS), where a 0 score corresponded to a sad face and indicated a low palatability, bitter (sharp, pungent taste or smell), not sweet, and no aroma score (eg, patients not pleased; worse outcome in terms of palatability) and a 100 score corresponded to a happy face and indicated a high palatability, not bitter, very sweet, very tasty, and high aroma score (eg, patients were pleased; best outcome in terms of palatability). Patients who were old enough scored the VAS themselves. For younger children, the parents provided this information, if possible. For the youngest children, there was free text input available to provide information on whether the patient spat it out or may not have liked the flavor, etc. |
Countries
Canada, France, India, Italy, Lebanon, Spain, Turkey (Türkiye), United Kingdom, United States
Participant flow
Recruitment details
A total of 66 participants who met all inclusion criteria and no exclusion criteria were enrolled in the study and received treatment at 32 clinical sites in the United States, Canada, France, India, Italy, Jordan, Lebanon, Spain, Turkey, and the United Kingdom.
Pre-assignment details
Participants were asked to fast for at least 4 hours before dosing and for an additional 2 hours after dosing. If this was not feasible because of the participant's age or other needs, (unflavored) milk, or an equivalent substitute liquid (but not fruit juices), was allowed until 1 hour before and starting at 1 hour postdose (total volume of liquids not to exceed 240 mL).
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1a: 30 mg Edoxaban Participants who were 12 to \< 18 years of age and received a single-dose, oral tablet of 30 mg edoxaban. | 8 |
| Cohort 1b: 60 mg Edoxaban Participants who were 12 to \< 18 years of age and received a single dose, oral tablet of 60 mg edoxaban. | 7 |
| Cohort 2a: 24 mg Edoxaban Participants who were 6 to \< 12 years of age and received a single dose, oral suspension of 24 mg edoxaban. | 7 |
| Cohort 2b: 45 mg Edoxaban Participants who were 6 to \< 12 years of age and received a single dose, oral suspension of 45 mg edoxaban. | 6 |
| Cohort 3a: 0.7 mg/kg Edoxaban Participants who were 2 to \< 6 years of age and received a single dose, oral suspension of 0.7 mg/kg (cap 24 mg) edoxaban. | 7 |
| Cohort 3b: 1.4 mg/kg Edoxaban Participants who were 2 to \< 6 years of age and received a single dose, oral suspension of 1.4 mg/kg (cap 45 mg) edoxaban. | 6 |
| Cohort 4a: 0.75 mg/kg Edoxaban Participants who were 6 months to \<2 years of age and received a single dose, oral suspension of 0.75 mg/kg edoxaban. | 7 |
| Cohort 4b: 1.5 mg/kg Edoxaban Participants who were 6 months to \<2 years of age and received a single dose, oral suspension of 1.5 mg/kg edoxaban. | 6 |
| Cohort 5a: 0.4 mg/kg Edoxaban Participants who were 0 to 6 months of age and received a single dose, oral suspension of 0.4 mg/kg edoxaban. | 6 |
| Cohort 5b: 0.8 mg/kg Edoxaban Participants who were 0 to 6 months of age and received a single dose, oral suspension of 0.8 mg/kg edoxaban. | 6 |
| Total | 66 |
Baseline characteristics
| Characteristic | Cohort 1b: 60 mg Edoxaban | Cohort 2a: 24 mg Edoxaban | Cohort 2b: 45 mg Edoxaban | Cohort 3a: 0.7 mg/kg Edoxaban | Cohort 3b: 1.4 mg/kg Edoxaban | Cohort 1a: 30 mg Edoxaban | Cohort 4a: 0.75 mg/kg Edoxaban | Cohort 4b: 1.5 mg/kg Edoxaban | Cohort 5a: 0.4 mg/kg Edoxaban | Cohort 5b: 0.8 mg/kg Edoxaban | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 7 Participants | 7 Participants | 6 Participants | 7 Participants | 6 Participants | 8 Participants | 7 Participants | 6 Participants | 6 Participants | 6 Participants | 66 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 15.3 years STANDARD_DEVIATION 1.3 | 9.6 years STANDARD_DEVIATION 1.1 | 9.5 years STANDARD_DEVIATION 1.9 | 4.3 years STANDARD_DEVIATION 1.6 | 4.3 years STANDARD_DEVIATION 1.4 | 15.9 years STANDARD_DEVIATION 1.1 | 1.2 years STANDARD_DEVIATION 0.5 | 1.0 years STANDARD_DEVIATION 0.5 | 0.2 years STANDARD_DEVIATION 0.2 | 0.3 years STANDARD_DEVIATION 0.2 | 6.5 years STANDARD_DEVIATION 6 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 3 Participants | 0 Participants | 4 Participants | 3 Participants | 11 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 2 Participants | 1 Participants | 2 Participants | 1 Participants | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 10 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) White | 6 Participants | 5 Participants | 5 Participants | 5 Participants | 3 Participants | 7 Participants | 2 Participants | 5 Participants | 2 Participants | 3 Participants | 43 Participants |
| Sex: Female, Male Female | 4 Participants | 3 Participants | 4 Participants | 3 Participants | 1 Participants | 5 Participants | 3 Participants | 3 Participants | 2 Participants | 3 Participants | 31 Participants |
| Sex: Female, Male Male | 3 Participants | 4 Participants | 2 Participants | 4 Participants | 5 Participants | 3 Participants | 4 Participants | 3 Participants | 4 Participants | 3 Participants | 35 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 7 | 0 / 7 | 0 / 6 | 0 / 7 | 0 / 6 | 0 / 7 | 0 / 6 | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 2 / 8 | 2 / 7 | 4 / 7 | 2 / 6 | 1 / 7 | 0 / 6 | 3 / 7 | 1 / 6 | 0 / 6 | 0 / 6 |
| serious Total, serious adverse events | 0 / 8 | 0 / 7 | 0 / 7 | 0 / 6 | 0 / 7 | 0 / 6 | 0 / 7 | 0 / 6 | 0 / 6 | 0 / 6 |
Outcome results
Primary
Pharmacokinetic Parameter of Apparent Systemic Clearance (CL/F)
A model-based pooled population pharmacokinetic (PK) method was used to estimate systemic clearance (CL/F). As prespecified in the protocol, arms were pooled due to sparse PK samples being collected. the median PK estimate is reported in all participants at a total of 5 blood samplings.
Time frame: 0.25 to 1 hours, 1.5 to 3 hours, 4 to 8 hours, 9 to 14 hours, and 24 to 36 hours post-dose
Population: Pharmacokinetic parameters were assessed in the Population Pharmacokinetic (PopPK) Analysis Set. As prespecified in the study protocol, PK parameters were reported from the pooled PopPK dataset in order to support dose determination in the ongoing Phase 3 DU176b-A-U312. The current pooled PopPK dataset included participants who were newborn to \<18 years of age (Cohort 1 to 5) as reported in the table.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| All Participants | Pharmacokinetic Parameter of Apparent Systemic Clearance (CL/F) | 42.9 L/h |
Primary
Pharmacokinetic Parameter of Apparent Volume of Distribution (V/F)
A model-based pooled population pharmacokinetic (PK) method was used to estimate apparent volume of distribution (V/F). As prespecified in the protocol, arms were pooled due to sparse PK samples being collected. the median PK estimate is reported in all participants at a total of 5 blood samplings.
Time frame: 0.25 to 1 hours, 1.5 to 3 hours, 4 to 8 hours, 9 to 14 hours, and 24 to 36 hours post-dose
Population: Pharmacokinetic parameters were assessed in the Population Pharmacokinetic (PopPK) Analysis Set. As prespecified in the study protocol, PK parameters were reported from the pooled PopPK dataset in order to support dose determination in the ongoing Phase 3 DU176b-A-U312. The current pooled PopPK dataset included participants who were newborn to \<18 years of age (Cohort 1 to 5) as reported in the table.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| All Participants | Pharmacokinetic Parameter of Apparent Volume of Distribution (V/F) | 198 Liters |
Secondary
Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT)
Descriptive statistics were used to assess Mean Activated Partial Thromboplastin Time by cohort for a total of 6 blood samplings.
Time frame: Pre-dose and 0.25 to 1 hours (except for Cohorts 4a, 4b, 5a, and 5b, 0.5 to 2 hours), 1.5 to 3 hours, 4 to 8 hours, 9 to 14 hours, and 24 to 36 hours post-dose
Population: Pharmacodynamic (PD) parameters were assessed in participants with available data in the Pharmacodynamic Analysis Set. PD data were not assessed at certain timepoints due to patients not being available for the analysis (ie, indicated by rows with 0 participants at certain timepoints). In addition, standard deviation was not calculated for rows with just 1 participant in the analysis; data are reported for the timepoints in which data were collected.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Participants | Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT) | Post-dose: 9 to 14 hours | 23.7 seconds | — |
| All Participants | Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT) | Post-dose: 1.5 to 3 hours | 27.7 seconds | Standard Deviation 1.1 |
| All Participants | Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT) | Post-dose: 6.5 to 8 hours | 26.4 seconds | Standard Deviation 1.2 |
| All Participants | Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT) | Pre-dose: 9 to 14 hours | 26.2 seconds | — |
| All Participants | Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT) | Pre-dose: 3.5 to 6 hours | 23.8 seconds | Standard Deviation 1.1 |
| All Participants | Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT) | Post-dose: 24 to 36 hours | 24.8 seconds | Standard Deviation 0.9 |
| All Participants | Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT) | Post-dose: 0.25 to 1 hours | 26.6 seconds | Standard Deviation 2 |
| All Participants | Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT) | Pre-dose: 6.5 to 8 hours | 23.8 seconds | Standard Deviation 1.1 |
| All Participants | Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT) | Pre-dose: 0.25 to 1 hours | 24.1 seconds | Standard Deviation 1.5 |
| All Participants | Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT) | Pre-dose: 24 to 36 hours | 24.4 seconds | Standard Deviation 1.3 |
| All Participants | Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT) | Pre-dose: 4 to 8 hours | 26.2 seconds | — |
| All Participants | Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT) | Pre-dose: 1.5 to 3 hours | 24.1 seconds | Standard Deviation 1.4 |
| All Participants | Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT) | Post-dose: 4 to 8 hours | 24.4 seconds | — |
| All Participants | Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT) | Post-dose: 3.5 to 6 hours | 26.9 seconds | Standard Deviation 1.4 |
| Cohort 1b: 60 mg Edoxaban | Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT) | Post-dose: 9 to 14 hours | 27.7 seconds | Standard Deviation 0.3 |
| Cohort 1b: 60 mg Edoxaban | Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT) | Pre-dose: 4 to 8 hours | 25.5 seconds | Standard Deviation 0.7 |
| Cohort 1b: 60 mg Edoxaban | Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT) | Post-dose: 1.5 to 3 hours | 32.8 seconds | Standard Deviation 3 |
| Cohort 1b: 60 mg Edoxaban | Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT) | Post-dose: 3.5 to 6 hours | 30.8 seconds | Standard Deviation 1.5 |
| Cohort 1b: 60 mg Edoxaban | Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT) | Pre-dose: 3.5 to 6 hours | 26.1 seconds | Standard Deviation 1.9 |
| Cohort 1b: 60 mg Edoxaban | Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT) | Post-dose: 24 to 36 hours | 25.8 seconds | Standard Deviation 1.9 |
| Cohort 1b: 60 mg Edoxaban | Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT) | Pre-dose: 9 to 14 hours | 25.5 seconds | Standard Deviation 0.7 |
| Cohort 1b: 60 mg Edoxaban | Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT) | Pre-dose: 24 to 36 hours | 26.0 seconds | Standard Deviation 1.6 |
| Cohort 1b: 60 mg Edoxaban | Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT) | Pre-dose: 1.5 to 3 hours | 26.0 seconds | Standard Deviation 1.6 |
| Cohort 1b: 60 mg Edoxaban | Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT) | Pre-dose: 0.25 to 1 hours | 26.0 seconds | Standard Deviation 1.6 |
| Cohort 1b: 60 mg Edoxaban | Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT) | Post-dose: 6.5 to 8 hours | 30.2 seconds | Standard Deviation 2.3 |
| Cohort 1b: 60 mg Edoxaban | Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT) | Post-dose: 4 to 8 hours | 28.9 seconds | Standard Deviation 1 |
| Cohort 1b: 60 mg Edoxaban | Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT) | Pre-dose: 6.5 to 8 hours | 26.7 seconds | Standard Deviation 1.7 |
| Cohort 1b: 60 mg Edoxaban | Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT) | Post-dose: 0.25 to 1 hours | 28.4 seconds | Standard Deviation 4.8 |
| Cohort 2a: 24 mg Edoxaban | Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT) | Post-dose: 4 to 8 hours | 35.5 seconds | Standard Deviation 4.9 |
| Cohort 2a: 24 mg Edoxaban | Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT) | Pre-dose: 6.5 to 8 hours | 32.2 seconds | — |
| Cohort 2a: 24 mg Edoxaban | Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT) | Post-dose: 24 to 36 hours | 29.0 seconds | Standard Deviation 2.2 |
| Cohort 2a: 24 mg Edoxaban | Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT) | Pre-dose: 24 to 36 hours | 32.0 seconds | Standard Deviation 5.6 |
| Cohort 2a: 24 mg Edoxaban | Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT) | Post-dose: 0.25 to 1 hours | 57.9 seconds | Standard Deviation 26.3 |
| Cohort 2a: 24 mg Edoxaban | Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT) | Post-dose: 9 to 14 hours | 35.3 seconds | Standard Deviation 2.8 |
| Cohort 2a: 24 mg Edoxaban | Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT) | Pre-dose: 1.5 to 3 hours | 34.6 seconds | Standard Deviation 5.8 |
| Cohort 2a: 24 mg Edoxaban | Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT) | Post-dose: 1.5 to 3 hours | 62.5 seconds | Standard Deviation 35.7 |
| Cohort 2a: 24 mg Edoxaban | Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT) | Pre-dose: 9 to 14 hours | 35.8 seconds | Standard Deviation 7.6 |
| Cohort 2a: 24 mg Edoxaban | Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT) | Pre-dose: 3.5 to 6 hours | 32.2 seconds | — |
| Cohort 2a: 24 mg Edoxaban | Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT) | Post-dose: 3.5 to 6 hours | 39.0 seconds | — |
| Cohort 2a: 24 mg Edoxaban | Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT) | Pre-dose: 4 to 8 hours | 33.9 seconds | Standard Deviation 6.4 |
| Cohort 2a: 24 mg Edoxaban | Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT) | Pre-dose: 0.25 to 1 hours | 33.9 seconds | Standard Deviation 6.4 |
| Cohort 2a: 24 mg Edoxaban | Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT) | Post-dose: 6.5 to 8 hours | 34.5 seconds | — |
| Cohort 2b: 45 mg Edoxaban | Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT) | Post-dose: 9 to 14 hours | 35.9 seconds | Standard Deviation 5.7 |
| Cohort 2b: 45 mg Edoxaban | Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT) | Post-dose: 0.25 to 1 hours | 42.4 seconds | Standard Deviation 9.9 |
| Cohort 2b: 45 mg Edoxaban | Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT) | Post-dose: 24 to 36 hours | 38.2 seconds | Standard Deviation 10.7 |
| Cohort 2b: 45 mg Edoxaban | Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT) | Pre-dose: 4 to 8 hours | 32.8 seconds | Standard Deviation 3.2 |
| Cohort 2b: 45 mg Edoxaban | Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT) | Pre-dose: 0.25 to 1 hours | 32.7 seconds | Standard Deviation 2.8 |
| Cohort 2b: 45 mg Edoxaban | Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT) | Post-dose: 1.5 to 3 hours | 43.0 seconds | Standard Deviation 3.9 |
| Cohort 2b: 45 mg Edoxaban | Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT) | Post-dose: 4 to 8 hours | 38.8 seconds | Standard Deviation 5.7 |
| Cohort 2b: 45 mg Edoxaban | Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT) | Pre-dose: 9 to 14 hours | 32.7 seconds | Standard Deviation 2.8 |
| Cohort 2b: 45 mg Edoxaban | Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT) | Pre-dose: 1.5 to 3 hours | 32.7 seconds | Standard Deviation 2.8 |
| Cohort 2b: 45 mg Edoxaban | Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT) | Pre-dose: 24 to 36 hours | 32.7 seconds | Standard Deviation 2.8 |
| Cohort 3a: 0.7 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT) | Post-dose: 1.5 to 3 hours | 38.1 seconds | Standard Deviation 8.9 |
| Cohort 3a: 0.7 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT) | Pre-dose: 0.25 to 1 hours | 34.3 seconds | Standard Deviation 4.1 |
| Cohort 3a: 0.7 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT) | Post-dose: 0.25 to 1 hours | 39.4 seconds | Standard Deviation 6.4 |
| Cohort 3a: 0.7 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT) | Pre-dose: 1.5 to 3 hours | 30.10 seconds | Standard Deviation 7.2 |
| Cohort 3a: 0.7 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT) | Pre-dose: 4 to 8 hours | 30.1 seconds | Standard Deviation 7.2 |
| Cohort 3a: 0.7 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT) | Post-dose: 4 to 8 hours | 36.7 seconds | Standard Deviation 10.1 |
| Cohort 3a: 0.7 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT) | Pre-dose: 9 to 14 hours | 30.1 seconds | Standard Deviation 7.2 |
| Cohort 3a: 0.7 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT) | Post-dose: 9 to 14 hours | 33.8 seconds | Standard Deviation 7.4 |
| Cohort 3a: 0.7 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT) | Pre-dose: 24 to 36 hours | 29.9 seconds | Standard Deviation 8.1 |
| Cohort 3a: 0.7 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT) | Post-dose: 24 to 36 hours | 32.9 seconds | Standard Deviation 5.2 |
| Cohort 3b: 1.4 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT) | Pre-dose: 24 to 36 hours | 40.7 seconds | Standard Deviation 21 |
| Cohort 3b: 1.4 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT) | Pre-dose: 0.25 to 1 hours | 40.7 seconds | Standard Deviation 21 |
| Cohort 3b: 1.4 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT) | Post-dose: 9 to 14 hours | 35.1 seconds | Standard Deviation 7.3 |
| Cohort 3b: 1.4 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT) | Post-dose: 24 to 36 hours | 86.1 seconds | Standard Deviation 112.6 |
| Cohort 3b: 1.4 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT) | Pre-dose: 9 to 14 hours | 40.7 seconds | Standard Deviation 21 |
| Cohort 3b: 1.4 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT) | Post-dose: 0.25 to 1 hours | 45.3 seconds | Standard Deviation 20.1 |
| Cohort 3b: 1.4 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT) | Post-dose: 1.5 to 3 hours | 45.5 seconds | Standard Deviation 7.9 |
| Cohort 3b: 1.4 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT) | Pre-dose: 1.5 to 3 hours | 40.7 seconds | Standard Deviation 21 |
| Cohort 3b: 1.4 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT) | Pre-dose: 4 to 8 hours | 40.7 seconds | Standard Deviation 21 |
| Cohort 3b: 1.4 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT) | Post-dose: 4 to 8 hours | 35.7 seconds | Standard Deviation 4.6 |
| Cohort 4a: 0.75 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT) | Post-dose: 9 to 14 hours | 35.0 seconds | — |
| Cohort 4a: 0.75 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT) | Pre-dose: 1.5 to 3 hours | 37.4 seconds | — |
| Cohort 4a: 0.75 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT) | Pre-dose: 0.25 to 1 hours | 32.9 seconds | Standard Deviation 5.3 |
| Cohort 4a: 0.75 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT) | Pre-dose: 9 to 14 hours | 37.4 seconds | — |
| Cohort 4a: 0.75 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT) | Post-dose: 1.5 to 3 hours | 40.9 seconds | — |
| Cohort 4a: 0.75 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT) | Post-dose: 0.25 to 1 hours | 45.4 seconds | Standard Deviation 6.3 |
| Cohort 4a: 0.75 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT) | Post-dose: 24 to 36 hours | 32.5 seconds | — |
| Cohort 4a: 0.75 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT) | Pre-dose: 24 to 36 hours | 37.4 seconds | — |
| Cohort 4a: 0.75 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT) | Post-dose: 4 to 8 hours | 35.8 seconds | — |
| Cohort 4a: 0.75 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT) | Pre-dose: 4 to 8 hours | 37.4 seconds | — |
| Cohort 4b: 1.5 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT) | Pre-dose: 0.25 to 1 hours | 34.9 seconds | Standard Deviation 8.2 |
| Cohort 4b: 1.5 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT) | Post-dose: 0.25 to 1 hours | 46.0 seconds | Standard Deviation 10.9 |
| Cohort 5a: 0.4 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT) | Post-dose: 0.25 to 1 hours | 39.5 seconds | Standard Deviation 3.8 |
| Cohort 5a: 0.4 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT) | Pre-dose: 0.25 to 1 hours | 41.0 seconds | Standard Deviation 17.9 |
| Cohort 5b: 0.8 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT) | Pre-dose: 0.25 to 1 hours | 47.7 seconds | Standard Deviation 13 |
| Cohort 5b: 0.8 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Activated Partial Thromboplastin Time (aPTT) | Post-dose: 0.25 to 1 hours | 52.6 seconds | Standard Deviation 18.1 |
Secondary
Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa)
Descriptive statistics were used to assess Mean Anti-Factor Xa (FXa) by cohort for a total of 6 blood samplings.
Time frame: Pre-dose and 0.25 to 1 hours (except for Cohorts 4a, 4b, 5a, and 5b, 0.5 to 2 hours), 1.5 to 3 hours, 4 to 8 hours, 9 to 14 hours, and 24 to 36 hours post-dose
Population: Pharmacodynamic (PD) parameters were assessed in participants with available data in the Pharmacodynamic Analysis Set. PD data were not assessed at certain timepoints due to patients not being available for the analysis (ie, indicated by rows with 0 participants at certain timepoints). In addition, standard deviation was not calculated for rows with just 1 participant in the analysis; data are reported for the timepoints in which data were collected.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Participants | Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa) | Post-dose: 1.5 to 3 hours | 1.3 IU/mL | Standard Deviation 0.4 |
| All Participants | Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa) | Pre-dose: 4 to 8 hours | 0.1 IU/mL | — |
| All Participants | Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa) | Post-dose: 24 to 36 hours | 0.1 IU/mL | Standard Deviation 0 |
| All Participants | Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa) | Pre-dose: 3.5 to 6 hours | 0.1 IU/mL | Standard Deviation 0 |
| All Participants | Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa) | Post-dose: 4 to 8 hours | 1.0 IU/mL | — |
| All Participants | Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa) | Post-dose: 3.5 to 6 hours | 0.9 IU/mL | Standard Deviation 0.4 |
| All Participants | Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa) | Pre-dose: 6.5 to 8 hours | 0.1 IU/mL | Standard Deviation 0 |
| All Participants | Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa) | Post-dose: 0.25 to 1 hours | 0.5 IU/mL | Standard Deviation 0.4 |
| All Participants | Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa) | Pre-dose: 9 to 14 hours | 0.1 IU/mL | — |
| All Participants | Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa) | Pre-dose: 24 to 36 hours | 0.1 IU/mL | Standard Deviation 0 |
| All Participants | Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa) | Post-dose: 6.5 to 8 hours | 0.4 IU/mL | Standard Deviation 0.1 |
| All Participants | Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa) | Post-dose: 9 to 14 hours | 0.4 IU/mL | — |
| All Participants | Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa) | Pre-dose: 1.5 to 3 hours | 0.1 IU/mL | Standard Deviation 0 |
| All Participants | Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa) | Pre-dose: 0.25 to 1 hours | 0.1 IU/mL | Standard Deviation 0 |
| Cohort 1b: 60 mg Edoxaban | Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa) | Post-dose: 0.25 to 1 hours | 1.0 IU/mL | Standard Deviation 1 |
| Cohort 1b: 60 mg Edoxaban | Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa) | Post-dose: 1.5 to 3 hours | 2.6 IU/mL | Standard Deviation 1 |
| Cohort 1b: 60 mg Edoxaban | Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa) | Post-dose: 24 to 36 hours | 0.1 IU/mL | Standard Deviation 0.1 |
| Cohort 1b: 60 mg Edoxaban | Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa) | Pre-dose: 6.5 to 8 hours | 0.1 IU/mL | Standard Deviation 0 |
| Cohort 1b: 60 mg Edoxaban | Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa) | Pre-dose: 0.25 to 1 hours | 0.1 IU/mL | Standard Deviation 0 |
| Cohort 1b: 60 mg Edoxaban | Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa) | Post-dose: 3.5 to 6 hours | 1.7 IU/mL | Standard Deviation 0.4 |
| Cohort 1b: 60 mg Edoxaban | Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa) | Post-dose: 4 to 8 hours | 1.2 IU/mL | Standard Deviation 0.7 |
| Cohort 1b: 60 mg Edoxaban | Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa) | Post-dose: 6.5 to 8 hours | 0.9 IU/mL | Standard Deviation 0.4 |
| Cohort 1b: 60 mg Edoxaban | Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa) | Pre-dose: 3.5 to 6 hours | 0.1 IU/mL | Standard Deviation 0 |
| Cohort 1b: 60 mg Edoxaban | Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa) | Pre-dose: 4 to 8 hours | 0.1 IU/mL | Standard Deviation 0 |
| Cohort 1b: 60 mg Edoxaban | Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa) | Pre-dose: 9 to 14 hours | 0.1 IU/mL | Standard Deviation 0 |
| Cohort 1b: 60 mg Edoxaban | Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa) | Pre-dose: 1.5 to 3 hours | 0.1 IU/mL | Standard Deviation 0 |
| Cohort 1b: 60 mg Edoxaban | Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa) | Pre-dose: 24 to 36 hours | 0.1 IU/mL | Standard Deviation 0 |
| Cohort 1b: 60 mg Edoxaban | Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa) | Post-dose: 9 to 14 hours | 0.6 IU/mL | Standard Deviation 0.3 |
| Cohort 2a: 24 mg Edoxaban | Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa) | Pre-dose: 0.25 to 1 hours | 0.1 IU/mL | Standard Deviation 0 |
| Cohort 2a: 24 mg Edoxaban | Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa) | Post-dose: 6.5 to 8 hours | 0.8 IU/mL | — |
| Cohort 2a: 24 mg Edoxaban | Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa) | Pre-dose: 6.5 to 8 hours | 0.1 IU/mL | — |
| Cohort 2a: 24 mg Edoxaban | Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa) | Pre-dose: 24 to 36 hours | 0.1 IU/mL | Standard Deviation 0 |
| Cohort 2a: 24 mg Edoxaban | Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa) | Post-dose: 0.25 to 1 hours | 1.8 IU/mL | Standard Deviation 0.3 |
| Cohort 2a: 24 mg Edoxaban | Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa) | Post-dose: 24 to 36 hours | 0.1 IU/mL | Standard Deviation 0 |
| Cohort 2a: 24 mg Edoxaban | Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa) | Post-dose: 9 to 14 hours | 0.3 IU/mL | Standard Deviation 0.1 |
| Cohort 2a: 24 mg Edoxaban | Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa) | Pre-dose: 1.5 to 3 hours | 0.1 IU/mL | Standard Deviation 0 |
| Cohort 2a: 24 mg Edoxaban | Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa) | Post-dose: 1.5 to 3 hours | 1.3 IU/mL | Standard Deviation 0.7 |
| Cohort 2a: 24 mg Edoxaban | Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa) | Pre-dose: 9 to 14 hours | 0.1 IU/mL | Standard Deviation 0 |
| Cohort 2a: 24 mg Edoxaban | Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa) | Pre-dose: 3.5 to 6 hours | 0.1 IU/mL | — |
| Cohort 2a: 24 mg Edoxaban | Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa) | Post-dose: 3.5 to 6 hours | 1.4 IU/mL | — |
| Cohort 2a: 24 mg Edoxaban | Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa) | Pre-dose: 4 to 8 hours | 0.1 IU/mL | Standard Deviation 0 |
| Cohort 2a: 24 mg Edoxaban | Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa) | Post-dose: 4 to 8 hours | 0.8 IU/mL | Standard Deviation 0.3 |
| Cohort 2b: 45 mg Edoxaban | Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa) | Pre-dose: 1.5 to 3 hours | 0.1 IU/mL | Standard Deviation 0 |
| Cohort 2b: 45 mg Edoxaban | Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa) | Post-dose: 4 to 8 hours | 1.5 IU/mL | Standard Deviation 0.3 |
| Cohort 2b: 45 mg Edoxaban | Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa) | Pre-dose: 4 to 8 hours | 0.1 IU/mL | Standard Deviation 0 |
| Cohort 2b: 45 mg Edoxaban | Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa) | Pre-dose: 0.25 to 1 hours | 0.1 IU/mL | Standard Deviation 0 |
| Cohort 2b: 45 mg Edoxaban | Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa) | Post-dose: 9 to 14 hours | 0.8 IU/mL | Standard Deviation 0.5 |
| Cohort 2b: 45 mg Edoxaban | Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa) | Post-dose: 0.25 to 1 hours | 1.6 IU/mL | Standard Deviation 0.8 |
| Cohort 2b: 45 mg Edoxaban | Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa) | Pre-dose: 24 to 36 hours | 0.1 IU/mL | Standard Deviation 0 |
| Cohort 2b: 45 mg Edoxaban | Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa) | Pre-dose: 9 to 14 hours | 0.1 IU/mL | Standard Deviation 0 |
| Cohort 2b: 45 mg Edoxaban | Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa) | Post-dose: 24 to 36 hours | 0.2 IU/mL | Standard Deviation 0.1 |
| Cohort 2b: 45 mg Edoxaban | Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa) | Post-dose: 1.5 to 3 hours | 1.9 IU/mL | Standard Deviation 0.1 |
| Cohort 3a: 0.7 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa) | Pre-dose: 9 to 14 hours | 0.1 IU/mL | Standard Deviation 0 |
| Cohort 3a: 0.7 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa) | Pre-dose: 0.25 to 1 hours | 0.1 IU/mL | Standard Deviation 0 |
| Cohort 3a: 0.7 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa) | Post-dose: 0.25 to 1 hours | 1.2 IU/mL | Standard Deviation 0.6 |
| Cohort 3a: 0.7 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa) | Pre-dose: 1.5 to 3 hours | 0.1 IU/mL | Standard Deviation 0 |
| Cohort 3a: 0.7 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa) | Post-dose: 1.5 to 3 hours | 1.7 IU/mL | Standard Deviation 0.3 |
| Cohort 3a: 0.7 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa) | Pre-dose: 4 to 8 hours | 0.1 IU/mL | Standard Deviation 0 |
| Cohort 3a: 0.7 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa) | Post-dose: 4 to 8 hours | 0.7 IU/mL | Standard Deviation 0.2 |
| Cohort 3a: 0.7 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa) | Post-dose: 9 to 14 hours | 0.2 IU/mL | Standard Deviation 0.1 |
| Cohort 3a: 0.7 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa) | Pre-dose: 24 to 36 hours | 0.1 IU/mL | Standard Deviation 0 |
| Cohort 3a: 0.7 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa) | Post-dose: 24 to 36 hours | 0.3 IU/mL | Standard Deviation 0.5 |
| Cohort 3b: 1.4 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa) | Pre-dose: 4 to 8 hours | 0.1 IU/mL | Standard Deviation 0.1 |
| Cohort 3b: 1.4 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa) | Post-dose: 1.5 to 3 hours | 1.9 IU/mL | Standard Deviation 0.2 |
| Cohort 3b: 1.4 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa) | Pre-dose: 9 to 14 hours | 0.1 IU/mL | Standard Deviation 0.1 |
| Cohort 3b: 1.4 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa) | Pre-dose: 1.5 to 3 hours | 0.1 IU/mL | Standard Deviation 0.1 |
| Cohort 3b: 1.4 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa) | Post-dose: 9 to 14 hours | 0.4 IU/mL | Standard Deviation 0.2 |
| Cohort 3b: 1.4 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa) | Post-dose: 0.25 to 1 hours | 1.9 IU/mL | Standard Deviation 0.2 |
| Cohort 3b: 1.4 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa) | Post-dose: 24 to 36 hours | 0.4 IU/mL | Standard Deviation 0.7 |
| Cohort 3b: 1.4 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa) | Pre-dose: 24 to 36 hours | 0.1 IU/mL | Standard Deviation 0.1 |
| Cohort 3b: 1.4 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa) | Pre-dose: 0.25 to 1 hours | 0.1 IU/mL | Standard Deviation 0.1 |
| Cohort 3b: 1.4 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa) | Post-dose: 4 to 8 hours | 0.8 IU/mL | Standard Deviation 0.6 |
| Cohort 4a: 0.75 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa) | Post-dose: 0.25 to 1 hours | 2.0 IU/mL | Standard Deviation 0 |
| Cohort 4a: 0.75 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa) | Pre-dose: 0.25 to 1 hours | 0.1 IU/mL | Standard Deviation 0 |
| Cohort 4a: 0.75 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa) | Post-dose: 9 to 14 hours | 0.3 IU/mL | — |
| Cohort 4a: 0.75 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa) | Pre-dose: 4 to 8 hours | 0.1 IU/mL | — |
| Cohort 4a: 0.75 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa) | Post-dose: 1.5 to 3 hours | 2.0 IU/mL | — |
| Cohort 4a: 0.75 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa) | Pre-dose: 1.5 to 3 hours | 0.1 IU/mL | — |
| Cohort 4a: 0.75 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa) | Post-dose: 24 to 36 hours | 0.1 IU/mL | — |
| Cohort 4a: 0.75 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa) | Post-dose: 4 to 8 hours | 1.2 IU/mL | — |
| Cohort 4a: 0.75 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa) | Pre-dose: 9 to 14 hours | 0.1 IU/mL | — |
| Cohort 4a: 0.75 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa) | Pre-dose: 24 to 36 hours | 0.1 IU/mL | — |
| Cohort 4b: 1.5 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa) | Pre-dose: 0.25 to 1 hours | 0.5 IU/mL | Standard Deviation 0.3 |
| Cohort 4b: 1.5 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa) | Post-dose: 0.25 to 1 hours | 2.0 IU/mL | Standard Deviation 0 |
| Cohort 5a: 0.4 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa) | Pre-dose: 0.25 to 1 hours | 0.1 IU/mL | Standard Deviation 0.1 |
| Cohort 5a: 0.4 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa) | Post-dose: 0.25 to 1 hours | 1.1 IU/mL | Standard Deviation 0.8 |
| Cohort 5b: 0.8 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa) | Pre-dose: 0.25 to 1 hours | 0.4 IU/mL | Standard Deviation 0.4 |
| Cohort 5b: 0.8 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Anti-Factor Xa (FXa) | Post-dose: 0.25 to 1 hours | 1.7 IU/mL | Standard Deviation 0.7 |
Secondary
Pharmacodynamic Parameter Mean Prothrombin Time (PT)
Descriptive statistics were used to assess Mean Prothrombin Time (PT) by cohort at a total of 6 blood samplings.
Time frame: Pre-dose and 0.25 to 1 hours (except for Cohorts 4a, 4b, 5a, and 5b, 0.5 to 2 hours), 1.5 to 3 hours, 4 to 8 hours, 9 to 14 hours, and 24 to 36 hours post-dose
Population: Pharmacodynamic (PD) parameters were assessed in participants with available data in the Pharmacodynamic Analysis Set. PD data were not assessed at certain timepoints due to patients not being available for the analysis (ie, indicated by rows with 0 participants at certain timepoints). In addition, standard deviation was not calculated for rows with just 1 participant in the analysis; data are reported for the timepoints in which data were collected.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Participants | Pharmacodynamic Parameter Mean Prothrombin Time (PT) | Post-dose: 4 to 8 hours | 15.9 seconds | — |
| All Participants | Pharmacodynamic Parameter Mean Prothrombin Time (PT) | Post-dose: 6.5 to 8 hours | 14.7 seconds | Standard Deviation 1.4 |
| All Participants | Pharmacodynamic Parameter Mean Prothrombin Time (PT) | Pre-dose: 0.25 to 1 hours | 13.3 seconds | Standard Deviation 1.1 |
| All Participants | Pharmacodynamic Parameter Mean Prothrombin Time (PT) | Pre-dose: 1.5 to 3 hours | 13.3 seconds | Standard Deviation 1 |
| All Participants | Pharmacodynamic Parameter Mean Prothrombin Time (PT) | Pre-dose: 3.5 to 6 hours | 13.4 seconds | Standard Deviation 1.1 |
| All Participants | Pharmacodynamic Parameter Mean Prothrombin Time (PT) | Post-dose: 9 to 14 hours | 13.9 seconds | — |
| All Participants | Pharmacodynamic Parameter Mean Prothrombin Time (PT) | Pre-dose: 9 to 14 hours | 12.9 seconds | — |
| All Participants | Pharmacodynamic Parameter Mean Prothrombin Time (PT) | Pre-dose: 6.5 to 8 hours | 13.4 seconds | Standard Deviation 1.1 |
| All Participants | Pharmacodynamic Parameter Mean Prothrombin Time (PT) | Post-dose: 3.5 to 6 hours | 17.9 seconds | Standard Deviation 4.6 |
| All Participants | Pharmacodynamic Parameter Mean Prothrombin Time (PT) | Post-dose: 24 to 36 hours | 13.1 seconds | Standard Deviation 1 |
| All Participants | Pharmacodynamic Parameter Mean Prothrombin Time (PT) | Post-dose: 1.5 to 3 hours | 17.6 seconds | Standard Deviation 2.5 |
| All Participants | Pharmacodynamic Parameter Mean Prothrombin Time (PT) | Pre-dose: 4 to 8 hours | 12.9 seconds | — |
| All Participants | Pharmacodynamic Parameter Mean Prothrombin Time (PT) | Pre-dose: 24 to 36 hours | 13.4 seconds | Standard Deviation 1.1 |
| All Participants | Pharmacodynamic Parameter Mean Prothrombin Time (PT) | Post-dose: 0.25 to 1 hours | 15.0 seconds | Standard Deviation 1.8 |
| Cohort 1b: 60 mg Edoxaban | Pharmacodynamic Parameter Mean Prothrombin Time (PT) | Pre-dose: 3.5 to 6 hours | 13.6 seconds | Standard Deviation 0.6 |
| Cohort 1b: 60 mg Edoxaban | Pharmacodynamic Parameter Mean Prothrombin Time (PT) | Pre-dose: 4 to 8 hours | 13.4 seconds | Standard Deviation 0.1 |
| Cohort 1b: 60 mg Edoxaban | Pharmacodynamic Parameter Mean Prothrombin Time (PT) | Post-dose: 4 to 8 hours | 17.5 seconds | Standard Deviation 2.3 |
| Cohort 1b: 60 mg Edoxaban | Pharmacodynamic Parameter Mean Prothrombin Time (PT) | Post-dose: 24 to 36 hours | 13.8 seconds | Standard Deviation 0.7 |
| Cohort 1b: 60 mg Edoxaban | Pharmacodynamic Parameter Mean Prothrombin Time (PT) | Pre-dose: 24 to 36 hours | 13.5 seconds | Standard Deviation 0.5 |
| Cohort 1b: 60 mg Edoxaban | Pharmacodynamic Parameter Mean Prothrombin Time (PT) | Post-dose: 0.25 to 1 hours | 17.3 seconds | Standard Deviation 4.1 |
| Cohort 1b: 60 mg Edoxaban | Pharmacodynamic Parameter Mean Prothrombin Time (PT) | Post-dose: 9 to 14 hours | 15.9 seconds | Standard Deviation 1.6 |
| Cohort 1b: 60 mg Edoxaban | Pharmacodynamic Parameter Mean Prothrombin Time (PT) | Pre-dose: 9 to 14 hours | 13.4 seconds | Standard Deviation 0.1 |
| Cohort 1b: 60 mg Edoxaban | Pharmacodynamic Parameter Mean Prothrombin Time (PT) | Pre-dose: 1.5 to 3 hours | 13.5 seconds | Standard Deviation 0.5 |
| Cohort 1b: 60 mg Edoxaban | Pharmacodynamic Parameter Mean Prothrombin Time (PT) | Post-dose: 6.5 to 8 hours | 16.7 seconds | Standard Deviation 1.5 |
| Cohort 1b: 60 mg Edoxaban | Pharmacodynamic Parameter Mean Prothrombin Time (PT) | Post-dose: 1.5 to 3 hours | 23.0 seconds | Standard Deviation 3.8 |
| Cohort 1b: 60 mg Edoxaban | Pharmacodynamic Parameter Mean Prothrombin Time (PT) | Pre-dose: 0.25 to 1 hours | 13.5 seconds | Standard Deviation 0.5 |
| Cohort 1b: 60 mg Edoxaban | Pharmacodynamic Parameter Mean Prothrombin Time (PT) | Pre-dose: 6.5 to 8 hours | 13.6 seconds | Standard Deviation 0.7 |
| Cohort 1b: 60 mg Edoxaban | Pharmacodynamic Parameter Mean Prothrombin Time (PT) | Post-dose: 3.5 to 6 hours | 20.1 seconds | Standard Deviation 2 |
| Cohort 2a: 24 mg Edoxaban | Pharmacodynamic Parameter Mean Prothrombin Time (PT) | Pre-dose: 3.5 to 6 hours | 13.4 seconds | — |
| Cohort 2a: 24 mg Edoxaban | Pharmacodynamic Parameter Mean Prothrombin Time (PT) | Post-dose: 0.25 to 1 hours | 19.1 seconds | Standard Deviation 3.1 |
| Cohort 2a: 24 mg Edoxaban | Pharmacodynamic Parameter Mean Prothrombin Time (PT) | Pre-dose: 6.5 to 8 hours | 13.7 seconds | Standard Deviation 0.4 |
| Cohort 2a: 24 mg Edoxaban | Pharmacodynamic Parameter Mean Prothrombin Time (PT) | Pre-dose: 24 to 36 hours | 14.2 seconds | Standard Deviation 0.5 |
| Cohort 2a: 24 mg Edoxaban | Pharmacodynamic Parameter Mean Prothrombin Time (PT) | Pre-dose: 0.25 to 1 hours | 14.0 seconds | Standard Deviation 0.4 |
| Cohort 2a: 24 mg Edoxaban | Pharmacodynamic Parameter Mean Prothrombin Time (PT) | Post-dose: 1.5 to 3 hours | 26.8 seconds | Standard Deviation 14.9 |
| Cohort 2a: 24 mg Edoxaban | Pharmacodynamic Parameter Mean Prothrombin Time (PT) | Pre-dose: 4 to 8 hours | 14.2 seconds | Standard Deviation 0.2 |
| Cohort 2a: 24 mg Edoxaban | Pharmacodynamic Parameter Mean Prothrombin Time (PT) | Post-dose: 3.5 to 6 hours | 16.5 seconds | — |
| Cohort 2a: 24 mg Edoxaban | Pharmacodynamic Parameter Mean Prothrombin Time (PT) | Pre-dose: 9 to 14 hours | 14.4 seconds | Standard Deviation 0.5 |
| Cohort 2a: 24 mg Edoxaban | Pharmacodynamic Parameter Mean Prothrombin Time (PT) | Post-dose: 6.5 to 8 hours | 15.8 seconds | Standard Deviation 1.1 |
| Cohort 2a: 24 mg Edoxaban | Pharmacodynamic Parameter Mean Prothrombin Time (PT) | Post-dose: 9 to 14 hours | 15.8 seconds | Standard Deviation 1.1 |
| Cohort 2a: 24 mg Edoxaban | Pharmacodynamic Parameter Mean Prothrombin Time (PT) | Post-dose: 24 to 36 hours | 14.5 seconds | Standard Deviation 0.6 |
| Cohort 2a: 24 mg Edoxaban | Pharmacodynamic Parameter Mean Prothrombin Time (PT) | Pre-dose: 1.5 to 3 hours | 14.0 seconds | Standard Deviation 0.4 |
| Cohort 2a: 24 mg Edoxaban | Pharmacodynamic Parameter Mean Prothrombin Time (PT) | Post-dose: 4 to 8 hours | 17.9 seconds | Standard Deviation 1.3 |
| Cohort 2b: 45 mg Edoxaban | Pharmacodynamic Parameter Mean Prothrombin Time (PT) | Pre-dose: 9 to 14 hours | 14.9 seconds | Standard Deviation 2.2 |
| Cohort 2b: 45 mg Edoxaban | Pharmacodynamic Parameter Mean Prothrombin Time (PT) | Pre-dose: 0.25 to 1 hours | 13.9 seconds | Standard Deviation 0.5 |
| Cohort 2b: 45 mg Edoxaban | Pharmacodynamic Parameter Mean Prothrombin Time (PT) | Post-dose: 0.25 to 1 hours | 21.3 seconds | Standard Deviation 7 |
| Cohort 2b: 45 mg Edoxaban | Pharmacodynamic Parameter Mean Prothrombin Time (PT) | Pre-dose: 1.5 to 3 hours | 14.9 seconds | Standard Deviation 2.2 |
| Cohort 2b: 45 mg Edoxaban | Pharmacodynamic Parameter Mean Prothrombin Time (PT) | Post-dose: 1.5 to 3 hours | 25.3 seconds | Standard Deviation 5.9 |
| Cohort 2b: 45 mg Edoxaban | Pharmacodynamic Parameter Mean Prothrombin Time (PT) | Pre-dose: 4 to 8 hours | 13.9 seconds | Standard Deviation 0.5 |
| Cohort 2b: 45 mg Edoxaban | Pharmacodynamic Parameter Mean Prothrombin Time (PT) | Post-dose: 4 to 8 hours | 18.0 seconds | Standard Deviation 2.2 |
| Cohort 2b: 45 mg Edoxaban | Pharmacodynamic Parameter Mean Prothrombin Time (PT) | Post-dose: 9 to 14 hours | 17.7 seconds | Standard Deviation 5.1 |
| Cohort 2b: 45 mg Edoxaban | Pharmacodynamic Parameter Mean Prothrombin Time (PT) | Pre-dose: 24 to 36 hours | 13.9 seconds | Standard Deviation 0.5 |
| Cohort 2b: 45 mg Edoxaban | Pharmacodynamic Parameter Mean Prothrombin Time (PT) | Post-dose: 24 to 36 hours | 14.5 seconds | Standard Deviation 0.9 |
| Cohort 3a: 0.7 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Prothrombin Time (PT) | Post-dose: 9 to 14 hours | 16.1 seconds | Standard Deviation 1.2 |
| Cohort 3a: 0.7 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Prothrombin Time (PT) | Post-dose: 24 to 36 hours | 15.5 seconds | Standard Deviation 0.9 |
| Cohort 3a: 0.7 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Prothrombin Time (PT) | Post-dose: 0.25 to 1 hours | 18.7 seconds | Standard Deviation 2 |
| Cohort 3a: 0.7 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Prothrombin Time (PT) | Pre-dose: 9 to 14 hours | 14.7 seconds | Standard Deviation 1.3 |
| Cohort 3a: 0.7 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Prothrombin Time (PT) | Post-dose: 4 to 8 hours | 17.3 seconds | Standard Deviation 0.8 |
| Cohort 3a: 0.7 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Prothrombin Time (PT) | Post-dose: 1.5 to 3 hours | 21.0 seconds | Standard Deviation 2.5 |
| Cohort 3a: 0.7 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Prothrombin Time (PT) | Pre-dose: 4 to 8 hours | 14.7 seconds | Standard Deviation 1.3 |
| Cohort 3a: 0.7 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Prothrombin Time (PT) | Pre-dose: 24 to 36 hours | 14.7 seconds | Standard Deviation 1.3 |
| Cohort 3a: 0.7 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Prothrombin Time (PT) | Pre-dose: 1.5 to 3 hours | 14.7 seconds | Standard Deviation 1.3 |
| Cohort 3a: 0.7 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Prothrombin Time (PT) | Pre-dose: 0.25 to 1 hours | 14.6 seconds | Standard Deviation 1.3 |
| Cohort 3b: 1.4 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Prothrombin Time (PT) | Post-dose: 0.25 to 1 hours | 22.0 seconds | Standard Deviation 0.8 |
| Cohort 3b: 1.4 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Prothrombin Time (PT) | Post-dose: 4 to 8 hours | 16.1 seconds | Standard Deviation 2 |
| Cohort 3b: 1.4 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Prothrombin Time (PT) | Post-dose: 1.5 to 3 hours | 21.3 seconds | Standard Deviation 2.3 |
| Cohort 3b: 1.4 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Prothrombin Time (PT) | Pre-dose: 1.5 to 3 hours | 13.7 seconds | Standard Deviation 0.5 |
| Cohort 3b: 1.4 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Prothrombin Time (PT) | Pre-dose: 9 to 14 hours | 13.7 seconds | Standard Deviation 0.5 |
| Cohort 3b: 1.4 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Prothrombin Time (PT) | Post-dose: 9 to 14 hours | 16.0 seconds | Standard Deviation 2.5 |
| Cohort 3b: 1.4 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Prothrombin Time (PT) | Post-dose: 24 to 36 hours | 14.9 seconds | Standard Deviation 1.1 |
| Cohort 3b: 1.4 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Prothrombin Time (PT) | Pre-dose: 24 to 36 hours | 13.7 seconds | Standard Deviation 0.5 |
| Cohort 3b: 1.4 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Prothrombin Time (PT) | Pre-dose: 0.25 to 1 hours | 13.7 seconds | Standard Deviation 0.5 |
| Cohort 3b: 1.4 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Prothrombin Time (PT) | Pre-dose: 4 to 8 hours | 13.7 seconds | Standard Deviation 0.5 |
| Cohort 4a: 0.75 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Prothrombin Time (PT) | Post-dose: 0.25 to 1 hours | 21.4 seconds | Standard Deviation 2.4 |
| Cohort 4a: 0.75 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Prothrombin Time (PT) | Pre-dose: 0.25 to 1 hours | 13.6 seconds | Standard Deviation 0.7 |
| Cohort 4a: 0.75 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Prothrombin Time (PT) | Post-dose: 9 to 14 hours | 16.7 seconds | — |
| Cohort 4a: 0.75 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Prothrombin Time (PT) | Pre-dose: 1.5 to 3 hours | 14.3 seconds | — |
| Cohort 4a: 0.75 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Prothrombin Time (PT) | Pre-dose: 9 to 14 hours | 14.3 seconds | — |
| Cohort 4a: 0.75 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Prothrombin Time (PT) | Post-dose: 1.5 to 3 hours | 20.0 seconds | — |
| Cohort 4a: 0.75 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Prothrombin Time (PT) | Post-dose: 24 to 36 hours | 14.1 seconds | — |
| Cohort 4a: 0.75 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Prothrombin Time (PT) | Pre-dose: 4 to 8 hours | 14.3 seconds | — |
| Cohort 4a: 0.75 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Prothrombin Time (PT) | Post-dose: 4 to 8 hours | 17.4 seconds | — |
| Cohort 4a: 0.75 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Prothrombin Time (PT) | Pre-dose: 24 to 36 hours | 14.3 seconds | — |
| Cohort 4b: 1.5 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Prothrombin Time (PT) | Pre-dose: 0.25 to 1 hours | 13.8 seconds | Standard Deviation 1.6 |
| Cohort 4b: 1.5 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Prothrombin Time (PT) | Post-dose: 0.25 to 1 hours | 26.5 seconds | Standard Deviation 7.6 |
| Cohort 5a: 0.4 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Prothrombin Time (PT) | Post-dose: 0.25 to 1 hours | 18.3 seconds | Standard Deviation 3 |
| Cohort 5a: 0.4 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Prothrombin Time (PT) | Pre-dose: 0.25 to 1 hours | 16.3 seconds | Standard Deviation 4 |
| Cohort 5b: 0.8 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Prothrombin Time (PT) | Post-dose: 0.25 to 1 hours | 21.8 seconds | Standard Deviation 4.1 |
| Cohort 5b: 0.8 mg/kg Edoxaban | Pharmacodynamic Parameter Mean Prothrombin Time (PT) | Pre-dose: 0.25 to 1 hours | 15.3 seconds | Standard Deviation 1.8 |
Other Pre-specified
Mean Palatability Score for the Liquid Formulation on a 100 mm Visual Analog Scale (VAS)
Overall palatability, bitterness, sweetness, and overall taste or aroma were assessed by participants (or guardians) receiving the liquid oral suspension where each subscale used a 100 mm visual analog scale (VAS), where a 0 score corresponded to a sad face and indicated a low palatability, bitter (sharp, pungent taste or smell), not sweet, and no aroma score (eg, patients not pleased; worse outcome in terms of palatability) and a 100 score corresponded to a happy face and indicated a high palatability, not bitter, very sweet, very tasty, and high aroma score (eg, patients were pleased; best outcome in terms of palatability). Patients who were old enough scored the VAS themselves. For younger children, the parents provided this information, if possible. For the youngest children, there was free text input available to provide information on whether the patient spat it out or may not have liked the flavor, etc.
Time frame: Baseline up to 30 minutes post-dose
Population: Palatability scores were assessed in patients who received an oral suspension of edoxaban.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Participants | Mean Palatability Score for the Liquid Formulation on a 100 mm Visual Analog Scale (VAS) | Overall palatability | 53.6 mm | Standard Deviation 35.8 |
| All Participants | Mean Palatability Score for the Liquid Formulation on a 100 mm Visual Analog Scale (VAS) | Aroma | 53.4 mm | Standard Deviation 38.4 |
| All Participants | Mean Palatability Score for the Liquid Formulation on a 100 mm Visual Analog Scale (VAS) | Overall taste | 57.9 mm | Standard Deviation 42.3 |
| All Participants | Mean Palatability Score for the Liquid Formulation on a 100 mm Visual Analog Scale (VAS) | Sweetness | 39.1 mm | Standard Deviation 34.9 |
| All Participants | Mean Palatability Score for the Liquid Formulation on a 100 mm Visual Analog Scale (VAS) | Bitterness | 66.1 mm | Standard Deviation 44.5 |
| Cohort 1b: 60 mg Edoxaban | Mean Palatability Score for the Liquid Formulation on a 100 mm Visual Analog Scale (VAS) | Bitterness | 53.2 mm | Standard Deviation 46.3 |
| Cohort 1b: 60 mg Edoxaban | Mean Palatability Score for the Liquid Formulation on a 100 mm Visual Analog Scale (VAS) | Overall taste | 78.2 mm | Standard Deviation 43.2 |
| Cohort 1b: 60 mg Edoxaban | Mean Palatability Score for the Liquid Formulation on a 100 mm Visual Analog Scale (VAS) | Aroma | 57.7 mm | Standard Deviation 34 |
| Cohort 1b: 60 mg Edoxaban | Mean Palatability Score for the Liquid Formulation on a 100 mm Visual Analog Scale (VAS) | Sweetness | 54.3 mm | Standard Deviation 36.9 |
| Cohort 1b: 60 mg Edoxaban | Mean Palatability Score for the Liquid Formulation on a 100 mm Visual Analog Scale (VAS) | Overall palatability | 63.2 mm | Standard Deviation 48.9 |
| Cohort 2a: 24 mg Edoxaban | Mean Palatability Score for the Liquid Formulation on a 100 mm Visual Analog Scale (VAS) | Bitterness | 40.6 mm | Standard Deviation 43.5 |
| Cohort 2a: 24 mg Edoxaban | Mean Palatability Score for the Liquid Formulation on a 100 mm Visual Analog Scale (VAS) | Aroma | 58.7 mm | Standard Deviation 39.5 |
| Cohort 2a: 24 mg Edoxaban | Mean Palatability Score for the Liquid Formulation on a 100 mm Visual Analog Scale (VAS) | Overall palatability | 55.3 mm | Standard Deviation 40.6 |
| Cohort 2a: 24 mg Edoxaban | Mean Palatability Score for the Liquid Formulation on a 100 mm Visual Analog Scale (VAS) | Overall taste | 62.6 mm | Standard Deviation 44.9 |
| Cohort 2a: 24 mg Edoxaban | Mean Palatability Score for the Liquid Formulation on a 100 mm Visual Analog Scale (VAS) | Sweetness | 65.9 mm | Standard Deviation 42.1 |
| Cohort 2b: 45 mg Edoxaban | Mean Palatability Score for the Liquid Formulation on a 100 mm Visual Analog Scale (VAS) | Sweetness | 81.7 mm | Standard Deviation 21.6 |
| Cohort 2b: 45 mg Edoxaban | Mean Palatability Score for the Liquid Formulation on a 100 mm Visual Analog Scale (VAS) | Aroma | 75.0 mm | Standard Deviation 27.4 |
| Cohort 2b: 45 mg Edoxaban | Mean Palatability Score for the Liquid Formulation on a 100 mm Visual Analog Scale (VAS) | Overall palatability | 83.3 mm | Standard Deviation 20.4 |
| Cohort 2b: 45 mg Edoxaban | Mean Palatability Score for the Liquid Formulation on a 100 mm Visual Analog Scale (VAS) | Bitterness | 66.7 mm | Standard Deviation 37.6 |
| Cohort 2b: 45 mg Edoxaban | Mean Palatability Score for the Liquid Formulation on a 100 mm Visual Analog Scale (VAS) | Overall taste | 83.3 mm | Standard Deviation 25.8 |
| Cohort 3a: 0.7 mg/kg Edoxaban | Mean Palatability Score for the Liquid Formulation on a 100 mm Visual Analog Scale (VAS) | Sweetness | 86.2 mm | Standard Deviation 26.1 |
| Cohort 3a: 0.7 mg/kg Edoxaban | Mean Palatability Score for the Liquid Formulation on a 100 mm Visual Analog Scale (VAS) | Overall palatability | 77.3 mm | Standard Deviation 27.7 |
| Cohort 3a: 0.7 mg/kg Edoxaban | Mean Palatability Score for the Liquid Formulation on a 100 mm Visual Analog Scale (VAS) | Bitterness | 77.5 mm | Standard Deviation 27.2 |
| Cohort 3a: 0.7 mg/kg Edoxaban | Mean Palatability Score for the Liquid Formulation on a 100 mm Visual Analog Scale (VAS) | Overall taste | 82.8 mm | Standard Deviation 24.3 |
| Cohort 3a: 0.7 mg/kg Edoxaban | Mean Palatability Score for the Liquid Formulation on a 100 mm Visual Analog Scale (VAS) | Aroma | 84.5 mm | Standard Deviation 23.9 |
| Cohort 3b: 1.4 mg/kg Edoxaban | Mean Palatability Score for the Liquid Formulation on a 100 mm Visual Analog Scale (VAS) | Sweetness | 76.2 mm | Standard Deviation 20.2 |
| Cohort 3b: 1.4 mg/kg Edoxaban | Mean Palatability Score for the Liquid Formulation on a 100 mm Visual Analog Scale (VAS) | Overall taste | 80.5 mm | Standard Deviation 10 |
| Cohort 3b: 1.4 mg/kg Edoxaban | Mean Palatability Score for the Liquid Formulation on a 100 mm Visual Analog Scale (VAS) | Bitterness | 36.3 mm | Standard Deviation 41.2 |
| Cohort 3b: 1.4 mg/kg Edoxaban | Mean Palatability Score for the Liquid Formulation on a 100 mm Visual Analog Scale (VAS) | Overall palatability | 73.0 mm | Standard Deviation 22.9 |
| Cohort 3b: 1.4 mg/kg Edoxaban | Mean Palatability Score for the Liquid Formulation on a 100 mm Visual Analog Scale (VAS) | Aroma | 72.3 mm | Standard Deviation 19.7 |
| Cohort 4a: 0.75 mg/kg Edoxaban | Mean Palatability Score for the Liquid Formulation on a 100 mm Visual Analog Scale (VAS) | Sweetness | 68.5 mm | Standard Deviation 19 |
| Cohort 4a: 0.75 mg/kg Edoxaban | Mean Palatability Score for the Liquid Formulation on a 100 mm Visual Analog Scale (VAS) | Overall palatability | 67.3 mm | Standard Deviation 18.4 |
| Cohort 4a: 0.75 mg/kg Edoxaban | Mean Palatability Score for the Liquid Formulation on a 100 mm Visual Analog Scale (VAS) | Bitterness | 47.0 mm | Standard Deviation 32.6 |
| Cohort 4a: 0.75 mg/kg Edoxaban | Mean Palatability Score for the Liquid Formulation on a 100 mm Visual Analog Scale (VAS) | Aroma | 73.2 mm | Standard Deviation 13.9 |
| Cohort 4a: 0.75 mg/kg Edoxaban | Mean Palatability Score for the Liquid Formulation on a 100 mm Visual Analog Scale (VAS) | Overall taste | 70.8 mm | Standard Deviation 17 |
| Cohort 4b: 1.5 mg/kg Edoxaban | Mean Palatability Score for the Liquid Formulation on a 100 mm Visual Analog Scale (VAS) | Aroma | 74.2 mm | Standard Deviation 23.3 |
| Cohort 4b: 1.5 mg/kg Edoxaban | Mean Palatability Score for the Liquid Formulation on a 100 mm Visual Analog Scale (VAS) | Overall taste | 85.2 mm | Standard Deviation 11.2 |
| Cohort 4b: 1.5 mg/kg Edoxaban | Mean Palatability Score for the Liquid Formulation on a 100 mm Visual Analog Scale (VAS) | Overall palatability | 83.2 mm | Standard Deviation 14.1 |
| Cohort 4b: 1.5 mg/kg Edoxaban | Mean Palatability Score for the Liquid Formulation on a 100 mm Visual Analog Scale (VAS) | Sweetness | 86.0 mm | Standard Deviation 13.3 |
| Cohort 4b: 1.5 mg/kg Edoxaban | Mean Palatability Score for the Liquid Formulation on a 100 mm Visual Analog Scale (VAS) | Bitterness | 65.7 mm | Standard Deviation 36.8 |