Healthy
Conditions
Brief summary
The primary objective of this trial is to investigate the relative bioavailability of five different tablet formulations of Dabigatran Etexilate, Formulation A1, Formulation B1, Formulation C1, Formulation D1, and Formulation E1, compared to commercial capsule formulation of Dabigatran Etexilate. The secondary objective is to evaluate and compare several pharmacokinetic parameters between the treatments.
Interventions
DRUGDabigatran etexilate tablet E1
DRUGDabigatran etexilate tablet D1
DRUGDabigatran etexilate tablet C1
DRUGDabigatran etexilate tablet B1
DRUGDabigatran etexilate tablet A1
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
20 Years to 35 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy male subjects according to the investigator's assessment, based on a complete medical history including a physical examination, vital signs (blood pressure \[BP\], pulse rate \[PR\]), 12-lead electrocardiogram (ECG), and clinical laboratory tests * Age \>=20 and \<=35 years old * Body mass index (BMI) \>=18.0 and \<=25.0 kg/m2 * Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice (GCP) and local legislation
Exclusion criteria
* Any finding in the medical examination (including BP, Pulse Rate, or ECG) deviating from normal and judged as clinically relevant by the investigator at screening * Measurement of systolic blood pressure outside the range of 90 to 140 mmHg, diastolic blood pressure outside the range of 50 to 90 mmHg, or pulse rate outside the range of 45 to 90 bpm at screening * Any laboratory value outside the reference range that the investigator considers to be of clinical relevance * Any relevant bleeding history considered by the investigator * Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders * Surgery of the gastrointestinal tract that could interfere with kinetics of the trial medication (except appendectomy and simple hernia repair) * Diseases of the central nervous system (including but not limited to any kind of seizures or stroke), and other relevant neurological or psychiatric disorders * Any history or evidence of blood dyscrasia, haemorrhagic diathesis, severe thrombocytopenia, cerebrovascular haemorrhage, bleeding tendencies associated with active ulceration or overt bleeding of gastrointestinal, respiratory or genitourinary tract or any disease or condition with haemorrhagic tendencies * History of relevant orthostatic hypotension, fainting spells, or blackouts * Chronic or relevant acute infections * History of relevant allergy or hypersensitivity (including allergy to the trial medication or its excipients) * Any evidence of a concomitant disease considered as clinically relevant by the investigator * Intake of drugs with a long half-life (more than 24 hours) within 30 days or less than 10 half-lives of the respective drug prior to administration of trial medication * Within 10 days prior to administration of trial medication, use of drugs that might reasonably influence the results of the trial * Intake of medication, which influences the blood clotting, e.g., acetylsalicylic acid, coumarin etc. within 10 days prior to trial medication * Participation in another trial where an investigational drug has been administered within 4 months or 5 half-lives (whichever is greater) prior to planned administration of trial medication * Planned surgeries within four weeks following the end-of study examination * Smoker (more than 10 cigarettes or 3 cigars or 3 pipes per day) * Inability to refrain from smoking during in-house confinement at the trial site * Alcohol abuse (consumption of more than 30 g per day: e.g., 750 mL of beer, 1.5 gous \[equivalent to 270 mL\] of Sake) * Drug abuse or positive drug screening * Blood donation of more than 100 mL within 30 days prior to administration of trial medication or intended donation during the trial * Intention to perform excessive physical activities within one week prior to administration of trial medication or during the trial * Inability to comply with dietary regimen of trial site * Subject assessed as unsuitable for inclusion by the investigator because of, for instance, being considered not able to understand and comply with study requirements, or having a condition that would not allow safe participation in the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| AUC0-tz (Area Under the Concentration-time Curve of Free Dabigatran in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point) | 1:00 [hour (h): minute] before drug administration and 1:00h, 1:30h, 2:00h, 3:00h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h, 48:00h after drug administration. | This outcome measure presents area under the concentration-time curve of free Dabigatran in plasma over the time interval from 0 to the time of the last quantifiable data point. |
| Cmax (Maximum Concentration of Free Dabigatran) | 1:00 [hour (h): minute] before drug administration and 1:00h, 1:30h, 2:00h, 3:00h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h, 48:00h after drug administration. | This outcome measure presents maximum concentration of analyte in plasma (Cmax). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AUC0-infinity (Area Under the Concentration-time Curve of Free Dabigatran in Plasma Over the Time Interval From 0 Extrapolated to Infinity) (if Applicable) | 1:00 [hour (h): minute] before drug administration and 1:00h, 1:30h, 2:00h, 3:00h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h, 48:00h after drug administration. | This outcome measure presents area under the concentration-time curve of free Dabigatran in plasma over the time interval from 0 extrapolated to infinity)(if applicable). |
| AUC0-tz (Area Under the Concentration-time Curve of Total Dabigatran in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point) | 1:00 [hour (h): minute] before drug administration and 1:00h, 1:30h, 2:00h, 3:00h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h, 48:00h after drug administration. | This outcome measure presents area under the concentration-time curve of total Dabigatran in plasma over the time interval from 0 to the time of the last quantifiable data point. |
| Cmax (Maximum Plasma Concentration of Total Dabigatran) | 1:00 [hour (h): minute] before drug administration and 1:00h, 1:30h, 2:00h, 3:00h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h, 48:00h after drug administration. | This outcome measure presents maximum concentration of analyte in plasma (Cmax). |
| AUC0-infinity (Area Under the Concentration-time Curve of Total Dabigatran in Plasma Over the Time Interval From 0 Extrapolated to Infinity) (if Applicable) | 1:00 [hour (h): minute] before drug administration and 1:00h, 1:30h, 2:00h, 3:00h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h, 48:00h after drug administration. | This outcome measure presents area under the concentration-time curve of total Dabigatran in plasma over the time interval from 0 extrapolated to infinity)(if applicable). |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ref-A1-B1-C1-D1-E1 All subjects were treated with the reference treatment (Ref), Dabigatran Etexilate (BIBR 1048) commercial capsule formulation, 110 mg orally (one day, single dose) with 200 mL of water after an overnight fast of at least 10 hours in period 1, followed by one of the 5 investigational treatment in the following sequence, i.e., test formulation Dabigatran Etexilate tablet formulations in the sequence Test Formulation A1 (TF-A1) in period 2, followed by Test Formulation B1 (TF-B1) in period 3, followed by Test Formulation C1 (TF-C1) in period 4, followed by Test Formulation D1 (TF-D1) in period 5, followed by Test Formulation E1 (TF-E1) in period 6, 110 mg orally (one day, single dose) with 200 mL of water after an overnight fast of at least 10 hours.
A washout period of at least 4 days was set following the drug administration in each period. | 7 |
| Ref-B1-C1-D1-E1-A1 All subjects were treated with the reference treatment (Ref), Dabigatran Etexilate (BIBR 1048) commercial capsule formulation, 110 mg orally (one day, single dose) with 200 mL of water after an overnight fast of at least 10 hours in period 1, followed by one of the 5 investigational treatment in the following sequence, i.e., test formulation Dabigatran Etexilate tablet formulations in the sequence Test Formulation B1 (TF-B1) in period 2, followed by Test Formulation C1 (TF-C1) in period 3, followed by Test Formulation D1 (TF-D1) in period 4, followed by Test Formulation E1 (TF-E1) in period 5, followed by Test Formulation A1 (TF-A1) in period 6, 110 mg orally (one day, single dose) with 200 mL of water after an overnight fast of at least 10 hours.
A washout period of at least 4 days was set following the drug administration in each period. | 7 |
| Ref-C1-D1-E1-A1-B1 All subjects were treated with the reference treatment (Ref), Dabigatran Etexilate (BIBR 1048) commercial capsule formulation, 110 mg orally (one day, single dose) with 200 mL of water after an overnight fast of at least 10 hours in period 1, followed by one of the 5 investigational treatment in the following sequence, i.e., test formulation Dabigatran Etexilate tablet formulations in the sequence Test Formulation C1 (TF-C1) in period 2, followed by Test Formulation D1 (TF-D1) in period 3, followed by Test Formulation E1 (TF-E1) in period 4, followed by Test Formulation A1 (TF-A1) in period 5, followed by Test Formulation B1 (TF-B1) in period 6, 110 mg orally (one day, single dose) with 200 mL of water after an overnight fast of at least 10 hours.
A washout period of at least 4 days was set following the drug administration in each period. | 7 |
| Ref-D1-E1-A1-B1-C1 All subjects were treated with the reference treatment (Ref), Dabigatran Etexilate (BIBR 1048) commercial capsule formulation, 110 mg orally (one day, single dose) with 200 mL of water after an overnight fast of at least 10 hours in period 1, followed by one of the 5 investigational treatment in the following sequence, i.e., test formulation Dabigatran Etexilate tablet formulations in the sequence Test Formulation D1 (TF-D1) in period 2, followed by Test Formulation E1 (TF-E1) in period 3, followed by Test Formulation A1 (TF-A1) in period 4, followed by Test Formulation B1 (TF-B1) in period 5, followed by Test Formulation C1 (TF-C1) in period 6, 110 mg orally (one day, single dose) with 200 mL of water after an overnight fast of at least 10 hours.
A washout period of at least 4 days was set following the drug administration in each period. | 7 |
| Ref-E1-A1-B1-C1-D1 All subjects were treated with the reference treatment (Ref), Dabigatran Etexilate (BIBR 1048) commercial capsule formulation, 110 mg orally (one day, single dose) with 200 mL of water after an overnight fast of at least 10 hours in period 1, followed by one of the 5 investigational treatment in the following sequence, i.e., test formulation Dabigatran Etexilate tablet formulations in the sequence Test Formulation E1 (TF-E1) in period 2, followed by Test Formulation A1 (TF-A1) in period 3, followed by Test Formulation B1 (TF-B1) in period 4, followed by Test Formulation C1 (TF-C1) in period 5, followed by Test Formulation D1 (TF-D1) in period 6, 110 mg orally (one day, single dose) with 200 mL of water after an overnight fast of at least 10 hours.
A washout period of at least 4 days was set following the drug administration in each period. | 7 |
| Total | 35 |
Baseline characteristics
| Characteristic | Ref-A1-B1-C1-D1-E1 | Ref-B1-C1-D1-E1-A1 | Ref-C1-D1-E1-A1-B1 | Ref-D1-E1-A1-B1-C1 | Ref-E1-A1-B1-C1-D1 | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 26.9 Years STANDARD_DEVIATION 2.4 | 28.1 Years STANDARD_DEVIATION 3.4 | 27.3 Years STANDARD_DEVIATION 3.4 | 29.1 Years STANDARD_DEVIATION 3.6 | 27.4 Years STANDARD_DEVIATION 3.4 | 27.8 Years STANDARD_DEVIATION 3.2 |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 7 Participants | 7 Participants | 7 Participants | 7 Participants | 7 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 |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 35 | 0 / 34 | 0 / 35 | 0 / 35 | 0 / 35 | 0 / 35 |
| serious Total, serious adverse events | 0 / 35 | 0 / 34 | 0 / 35 | 0 / 35 | 0 / 35 | 0 / 35 |
Outcome results
Primary
AUC0-tz (Area Under the Concentration-time Curve of Free Dabigatran in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point)
This outcome measure presents area under the concentration-time curve of free Dabigatran in plasma over the time interval from 0 to the time of the last quantifiable data point.
Time frame: 1:00 [hour (h): minute] before drug administration and 1:00h, 1:30h, 2:00h, 3:00h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h, 48:00h after drug administration.
Population: The PharmacoKinetic (PK) parameter analysis Set (PKS): This analysis set included all subjects of the treated set who provided at least one primary or secondary PK parameter. Thus, a subject was included in the PKS, even if the subject contributed only one PK parameter value for one period to the statistical assessment.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Dabigatran Etexilate Capsule: Ref | AUC0-tz (Area Under the Concentration-time Curve of Free Dabigatran in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point) | 600 ng*h/mL | Geometric Coefficient of Variation 51.8 |
| Dabigatran Etexilate Tablet: A1 | AUC0-tz (Area Under the Concentration-time Curve of Free Dabigatran in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point) | 714 ng*h/mL | Geometric Coefficient of Variation 42.1 |
| Dabigatran Etexilate Tablet: B1 | AUC0-tz (Area Under the Concentration-time Curve of Free Dabigatran in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point) | 318 ng*h/mL | Geometric Coefficient of Variation 327 |
| Dabigatran Etexilate Tablet: C1 | AUC0-tz (Area Under the Concentration-time Curve of Free Dabigatran in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point) | 354 ng*h/mL | Geometric Coefficient of Variation 96.6 |
| Dabigatran Etexilate Tablet: D1 | AUC0-tz (Area Under the Concentration-time Curve of Free Dabigatran in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point) | 649 ng*h/mL | Geometric Coefficient of Variation 78.6 |
| Dabigatran Etexilate Tablet: E1 | AUC0-tz (Area Under the Concentration-time Curve of Free Dabigatran in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point) | 661 ng*h/mL | Geometric Coefficient of Variation 54.8 |
90% CI: [101.838, 139.834]
90% CI: [33.341, 84.158]
90% CI: [45.255, 76.955]
90% CI: [87.698, 133.53]
90% CI: [93.939, 129.297]
Primary
Cmax (Maximum Concentration of Free Dabigatran)
This outcome measure presents maximum concentration of analyte in plasma (Cmax).
Time frame: 1:00 [hour (h): minute] before drug administration and 1:00h, 1:30h, 2:00h, 3:00h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h, 48:00h after drug administration.
Population: The PharmacoKinetic (PK) parameter analysis Set (PKS): This analysis set included all subjects of the treated set who provided at least one primary or secondary PK parameter. Thus, a subject was included in the PKS, even if the subject contributed only one PK parameter value for one period to the statistical assessment.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Dabigatran Etexilate Capsule: Ref | Cmax (Maximum Concentration of Free Dabigatran) | 73.5 ng/mL | Geometric Coefficient of Variation 60 |
| Dabigatran Etexilate Tablet: A1 | Cmax (Maximum Concentration of Free Dabigatran) | 86.8 ng/mL | Geometric Coefficient of Variation 39.3 |
| Dabigatran Etexilate Tablet: B1 | Cmax (Maximum Concentration of Free Dabigatran) | 42.3 ng/mL | Geometric Coefficient of Variation 213 |
| Dabigatran Etexilate Tablet: C1 | Cmax (Maximum Concentration of Free Dabigatran) | 45.5 ng/mL | Geometric Coefficient of Variation 81.5 |
| Dabigatran Etexilate Tablet: D1 | Cmax (Maximum Concentration of Free Dabigatran) | 79.6 ng/mL | Geometric Coefficient of Variation 73.5 |
| Dabigatran Etexilate Tablet: E1 | Cmax (Maximum Concentration of Free Dabigatran) | 79.2 ng/mL | Geometric Coefficient of Variation 52.7 |
90% CI: [99.569, 140.579]
90% CI: [38.502, 85.837]
90% CI: [48.13, 79.72]
90% CI: [87.704, 133.629]
90% CI: [91.238, 127.281]
Secondary
AUC0-infinity (Area Under the Concentration-time Curve of Free Dabigatran in Plasma Over the Time Interval From 0 Extrapolated to Infinity) (if Applicable)
This outcome measure presents area under the concentration-time curve of free Dabigatran in plasma over the time interval from 0 extrapolated to infinity)(if applicable).
Time frame: 1:00 [hour (h): minute] before drug administration and 1:00h, 1:30h, 2:00h, 3:00h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h, 48:00h after drug administration.
Population: The PharmacoKinetic (PK) parameter analysis Set (PKS): Included all subjects of the treated set who provided at least one primary or secondary PK parameter.~PK Set 2 (PKS2): Included all subjects in the PKS who had evaluable PK variable of the reference treatment and at least one of the 5 test treatments.~PKS2 was used for statistical analyses.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Dabigatran Etexilate Capsule: Ref | AUC0-infinity (Area Under the Concentration-time Curve of Free Dabigatran in Plasma Over the Time Interval From 0 Extrapolated to Infinity) (if Applicable) | 623 ng*h/mL | Geometric Coefficient of Variation 49 |
| Dabigatran Etexilate Tablet: A1 | AUC0-infinity (Area Under the Concentration-time Curve of Free Dabigatran in Plasma Over the Time Interval From 0 Extrapolated to Infinity) (if Applicable) | 735 ng*h/mL | Geometric Coefficient of Variation 40.2 |
| Dabigatran Etexilate Tablet: B1 | AUC0-infinity (Area Under the Concentration-time Curve of Free Dabigatran in Plasma Over the Time Interval From 0 Extrapolated to Infinity) (if Applicable) | 544 ng*h/mL | Geometric Coefficient of Variation 71.9 |
| Dabigatran Etexilate Tablet: C1 | AUC0-infinity (Area Under the Concentration-time Curve of Free Dabigatran in Plasma Over the Time Interval From 0 Extrapolated to Infinity) (if Applicable) | 444 ng*h/mL | Geometric Coefficient of Variation 60.3 |
| Dabigatran Etexilate Tablet: D1 | AUC0-infinity (Area Under the Concentration-time Curve of Free Dabigatran in Plasma Over the Time Interval From 0 Extrapolated to Infinity) (if Applicable) | 725 ng*h/mL | Geometric Coefficient of Variation 53 |
| Dabigatran Etexilate Tablet: E1 | AUC0-infinity (Area Under the Concentration-time Curve of Free Dabigatran in Plasma Over the Time Interval From 0 Extrapolated to Infinity) (if Applicable) | 684 ng*h/mL | Geometric Coefficient of Variation 51.9 |
90% CI: [101.627, 137.621]
90% CI: [69.404, 109.722]
90% CI: [58.828, 86.648]
90% CI: [100.516, 135.41]
90% CI: [94.452, 127.75]
Secondary
AUC0-infinity (Area Under the Concentration-time Curve of Total Dabigatran in Plasma Over the Time Interval From 0 Extrapolated to Infinity) (if Applicable)
This outcome measure presents area under the concentration-time curve of total Dabigatran in plasma over the time interval from 0 extrapolated to infinity)(if applicable).
Time frame: 1:00 [hour (h): minute] before drug administration and 1:00h, 1:30h, 2:00h, 3:00h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h, 48:00h after drug administration.
Population: The PharmacoKinetic (PK) parameter analysis Set (PKS): Included all subjects of the treated set who provided at least one primary or secondary PK parameter.~PK Set 2 (PKS2): Included all subjects in the PKS who had evaluable PK variable of the reference treatment and at least one of the 5 test treatments.~PKS2 was used for statistical analyses.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Dabigatran Etexilate Capsule: Ref | AUC0-infinity (Area Under the Concentration-time Curve of Total Dabigatran in Plasma Over the Time Interval From 0 Extrapolated to Infinity) (if Applicable) | 750 ng*h/mL | Geometric Coefficient of Variation 50.5 |
| Dabigatran Etexilate Tablet: A1 | AUC0-infinity (Area Under the Concentration-time Curve of Total Dabigatran in Plasma Over the Time Interval From 0 Extrapolated to Infinity) (if Applicable) | 863 ng*h/mL | Geometric Coefficient of Variation 39.1 |
| Dabigatran Etexilate Tablet: B1 | AUC0-infinity (Area Under the Concentration-time Curve of Total Dabigatran in Plasma Over the Time Interval From 0 Extrapolated to Infinity) (if Applicable) | 628 ng*h/mL | Geometric Coefficient of Variation 75.6 |
| Dabigatran Etexilate Tablet: C1 | AUC0-infinity (Area Under the Concentration-time Curve of Total Dabigatran in Plasma Over the Time Interval From 0 Extrapolated to Infinity) (if Applicable) | 515 ng*h/mL | Geometric Coefficient of Variation 60.1 |
| Dabigatran Etexilate Tablet: D1 | AUC0-infinity (Area Under the Concentration-time Curve of Total Dabigatran in Plasma Over the Time Interval From 0 Extrapolated to Infinity) (if Applicable) | 804 ng*h/mL | Geometric Coefficient of Variation 70.1 |
| Dabigatran Etexilate Tablet: E1 | AUC0-infinity (Area Under the Concentration-time Curve of Total Dabigatran in Plasma Over the Time Interval From 0 Extrapolated to Infinity) (if Applicable) | 800 ng*h/mL | Geometric Coefficient of Variation 51.9 |
90% CI: [99.063, 134.13]
90% CI: [66.033, 106.163]
90% CI: [56.452, 83.782]
90% CI: [88.616, 129.51]
90% CI: [91.625, 124.114]
Secondary
AUC0-tz (Area Under the Concentration-time Curve of Total Dabigatran in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point)
This outcome measure presents area under the concentration-time curve of total Dabigatran in plasma over the time interval from 0 to the time of the last quantifiable data point.
Time frame: 1:00 [hour (h): minute] before drug administration and 1:00h, 1:30h, 2:00h, 3:00h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h, 48:00h after drug administration.
Population: The PharmacoKinetic (PK) parameter analysis Set (PKS): Included all subjects of the treated set who provided at least one primary or secondary PK parameter.~PK Set 2 (PKS2): Included all subjects in the PKS who had evaluable PK variable of the reference treatment and at least one of the 5 test treatments.~PKS2 was used for statistical analyses.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Dabigatran Etexilate Capsule: Ref | AUC0-tz (Area Under the Concentration-time Curve of Total Dabigatran in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point) | 726 ng*h/mL | Geometric Coefficient of Variation 52.9 |
| Dabigatran Etexilate Tablet: A1 | AUC0-tz (Area Under the Concentration-time Curve of Total Dabigatran in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point) | 838 ng*h/mL | Geometric Coefficient of Variation 41.1 |
| Dabigatran Etexilate Tablet: B1 | AUC0-tz (Area Under the Concentration-time Curve of Total Dabigatran in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point) | 366 ng*h/mL | Geometric Coefficient of Variation 341 |
| Dabigatran Etexilate Tablet: C1 | AUC0-tz (Area Under the Concentration-time Curve of Total Dabigatran in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point) | 412 ng*h/mL | Geometric Coefficient of Variation 97.1 |
| Dabigatran Etexilate Tablet: D1 | AUC0-tz (Area Under the Concentration-time Curve of Total Dabigatran in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point) | 777 ng*h/mL | Geometric Coefficient of Variation 74.9 |
| Dabigatran Etexilate Tablet: E1 | AUC0-tz (Area Under the Concentration-time Curve of Total Dabigatran in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point) | 778 ng*h/mL | Geometric Coefficient of Variation 53.6 |
90% CI: [98.783, 135.491]
90% CI: [31.519, 80.689]
90% CI: [43.388, 74.122]
90% CI: [87.554, 130.732]
90% CI: [91.399, 125.432]
Secondary
Cmax (Maximum Plasma Concentration of Total Dabigatran)
This outcome measure presents maximum concentration of analyte in plasma (Cmax).
Time frame: 1:00 [hour (h): minute] before drug administration and 1:00h, 1:30h, 2:00h, 3:00h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h, 48:00h after drug administration.
Population: The PharmacoKinetic (PK) parameter analysis Set (PKS): Included all subjects of the treated set who provided at least one primary or secondary PK parameter.~PK Set 2 (PKS2): Included all subjects in the PKS who had evaluable PK variable of the reference treatment and at least one of the 5 test treatments.~PKS2 was used for statistical analyses.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Dabigatran Etexilate Capsule: Ref | Cmax (Maximum Plasma Concentration of Total Dabigatran) | 88.6 ng/mL | Geometric Coefficient of Variation 62 |
| Dabigatran Etexilate Tablet: A1 | Cmax (Maximum Plasma Concentration of Total Dabigatran) | 102 ng/mL | Geometric Coefficient of Variation 39 |
| Dabigatran Etexilate Tablet: B1 | Cmax (Maximum Plasma Concentration of Total Dabigatran) | 47.9 ng/mL | Geometric Coefficient of Variation 227 |
| Dabigatran Etexilate Tablet: C1 | Cmax (Maximum Plasma Concentration of Total Dabigatran) | 52.2 ng/mL | Geometric Coefficient of Variation 83.6 |
| Dabigatran Etexilate Tablet: D1 | Cmax (Maximum Plasma Concentration of Total Dabigatran) | 94.2 ng/mL | Geometric Coefficient of Variation 75.7 |
| Dabigatran Etexilate Tablet: E1 | Cmax (Maximum Plasma Concentration of Total Dabigatran) | 91.9 ng/mL | Geometric Coefficient of Variation 54.1 |
90% CI: [96.74, 137.644]
90% CI: [35.818, 81.774]
90% CI: [45.489, 76.431]
90% CI: [85.846, 131.836]
90% CI: [87.74, 122.628]