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Bioavailability of Different Applications of Dabigatran in Healthy Volunteers

Relative Bioavailability of Dabigatran After Administration of Different Application Forms of a Single Oral Dose of 150 mg Dabigatran Etexilate (Capsule, Powder for Reconstitution Into Solution, Pellets on Food) in Healthy Male and Female Volunteers (an Open-label, Randomised, Three-way Crossover, Clinical Phase I Study)

Status
Completed
Phases
Phase 1
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT02171611
Enrollment
30
Registered
2014-06-24
Start date
2009-03-31
Completion date
Unknown
Last updated
2017-05-23

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Healthy

Brief summary

To determine the relative bioavailability of 150 mg of dabigatran etexilate as pellets on food and of 150 mg of dabigatran etexilate as powder resolved in reconstitution solution, both with 150 mg of dabigatran etexilate as capsule in healthy volunteers

Interventions

DRUGDabigatran etexilate pellets
DRUGDabigatran etexilate powder
DRUGDabigatran etexilate capsule

Sponsors

Boehringer Ingelheim
Lead SponsorINDUSTRY

Study design

Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes

Inclusion criteria

* Healthy males and females according to the following criteria: Based upon a complete medical history, including the physical examination, vital signs (BP, PR), 12-lead ECG, clinical laboratory tests * Age ≥18 and age ≤50 years * BMI ≥18.5 and BMI ≤29.9 kg/m2 (Body Mass Index) * Signed and dated written informed consent prior to admission to the study in accordance with GCP and the local legislation

Exclusion criteria

* Any finding of the medical examination (including BP, PR and ECG) deviating from normal and of clinical relevance * Any evidence of a clinically relevant concomitant disease * Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders * Surgery of the gastrointestinal tract (except appendectomy) * Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders * History of relevant orthostatic hypotension, fainting spells or blackouts * Chronic or relevant acute infections * History of relevant allergy/hypersensitivity (including allergy to drug or its excipients) * Intake of drugs with a long half-life (\> 24 hours) within at least one month or less than 10 half-lives of the respective drug prior to administration or during the trial * Use of drugs which could reasonably influence the results of the trial (especially unspecific inducing agents like St. John´s wort (Hypericum perforatum) or that prolong the QT/QTc interval based on the knowledge at the time of protocol preparation within 10 days prior to administration or during the trial * Participation in another trial with an investigational drug within two months prior to administration or during the trial * Smoker (\> 10 cigarettes or \> 3 cigars or \> 3 pipes/day) * Inability to refrain from smoking on trial days * Alcohol abuse (more than 60 g/day) * Drug abuse * Blood donation (more than 100 mL within four weeks prior to administration or during the trial) * Excessive physical activities (within one week prior to administration or during the trial) * Any laboratory value outside the reference range that was of clinical relevance * Inability to comply with dietary regimen of trial site * A marked baseline prolongation of QT/QTc interval (e.g. repeated demonstration of a QTc interval \>450 ms) * A history of additional risk factors for Torsade de Pointes (e.g. heart failure, hypokalemia, family history of Long QT Syndrome) * For female subjects: * Positive pregnancy test, pregnancy or planning to become pregnant during the study or within 1 month after study completion * No adequate contraception during the study and until 1 month after study completion, i.e. not any of the following: implants, injectables, combined oral contraceptives, intrauterine device (IUD), sexual abstinence for at least 1 month prior to enrolment, vasectomised partner (vasectomy performed at least 1 year prior to enrolment), or surgical sterilisation (including hysterectomy). Females, who did not have a vasectomised partner, were not sexually abstinent or surgically sterile were to be asked to use an additional barrier method (e.g. condom, diaphragm with spermicide) * Lactation * Intake of medication, which influences the blood clotting, i.e. acetylsalicylic acid, oral vitamin K antagonists etc.

Design outcomes

Primary

MeasureTime frameDescription
AUC0-inf for Total Dabigatran-0:30 hour(h) before drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 3:30h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h and 48:00h after drug administration.Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity (AUC0-inf) for total dabigatran.
AUC0-inf for Free Dabigatran-0:30 hour(h) before drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 3:30h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h and 48:00h after drug administration.Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity (AUC0-inf) for free dabigatran.
Cmax for Total Dabigatran-0:30 hour(h) before drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 3:30h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h and 48:00h after drug administration.Maximum measured concentration of the analyte in plasma (Cmax) for total dabigatran.
Cmax for Free Dabigatran-0:30 hour(h) before drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 3:30h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h and 48:00h after drug administration.Maximum measured concentration of the analyte in plasma (Cmax) for free dabigatran

Secondary

MeasureTime frameDescription
AUC0-tz for Free Dabigatran-0:30 hour(h) before drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 3:30h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h and 48:00h after drug administration.Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the time of the last quantifiable data point (AUC0-tz) for free dabigatran.
Tmax for Total Dabigatran-0:30 hour(h) before drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 3:30h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h and 48:00h after drug administration.Time from dosing to the maximum concentration of the analyte in plasma (tmax) for total dabigatran
λz for Free Dabigatran-0:30 hour(h) before drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 3:30h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h and 48:00h after drug administration.—
t1/2 for Free Dabigatran-0:30 hour(h) before drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 3:30h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h and 48:00h after drug administration.Terminal half-life of the analyte in plasma (t1/2) for free dabigatran.
MRTpo for Total Dabigatran-0:30 hour(h) before drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 3:30h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h and 48:00h after drug administration.Mean residence time of the analyte in the body after po administration (MRTpo) for total dabigatran.
MRTpo for Free Dabigatran-0:30 hour(h) before drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 3:30h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h and 48:00h after drug administration.Mean residence time of the analyte in the body after po administration (MRTpo) for free dabigatran.
t1/2 for Total Dabigatran-0:30 hour(h) before drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 3:30h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h and 48:00h after drug administration.Terminal half-life of the analyte in plasma (t1/2) for total dabigatran
CL/F for Free Dabigatran-0:30 hour(h) before drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 3:30h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h and 48:00h after drug administration.Apparent clearance of the analyte in plasma following extravascular administration (CL/F) for free dabigatran.
Vz/F for Total Dabigatran-0:30 hour(h) before drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 3:30h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h and 48:00h after drug administration.Apparent volume of distribution during the terminal phase λz following an extravascular dose (Vz/F) for total dabigatran.
Vz/F for Free Dabigatran-0:30 hour(h) before drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 3:30h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h and 48:00h after drug administration.Apparent volume of distribution during the terminal phase λz following an extravascular dose (Vz/F) for free dabigatran.
Percentage of Participants With Findings in Physical Examination, Vital Signs , Pulse Rate (PR)), 12-lead ECG, Clinical Laboratory Tests.From first drug administration until 7 days after the last drug administration of Dabigatran, ie., up to 10 days.Percentage of participants with findings in Physical examination, Vital signs (blood pressure (BP), pulse rate (PR)), 12-lead ECG (electrocardiogram), Clinical laboratory tests (haematology, clinical chemistry and urinalysis). Relevant findings or worsening of baseline conditions were reported as Adverse events. There were no clinically relevant finding reported for Physical examination, Vital signs (blood pressure, pulse rate), 12-lead ECG and Clinical laboratory tests.
Percentage of Participants With Drug-related Adverse EventsFrom first drug administration until 7 days after the last drug administration of Dabigatran, ie., up to 10 days.Percentage of participants with investigator defined drug-releated Adverse events.
Assessment of Tolerability by Investigator.From first drug administration until 7 days after the last drug administration of Dabigatran, ie., up to 10 days.Tolerability will be assessed by the investigator according to the categories good, satisfactory, not satisfactory and bad.
CL/F for Total Dabigatran-0:30 hour(h) before drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 3:30h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h and 48:00h after drug administration.Apparent clearance of the analyte in plasma following extravascular administration (CL/F) for total dabigatran.
Tmax for Free Dabigatran-0:30 hour(h) before drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 3:30h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h and 48:00h after drug administration.Time from dosing to the maximum concentration of the analyte in plasma (tmax) for free dabigatran
λz for Total Dabigatran-0:30 hour(h) before drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 3:30h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h and 48:00h after drug administration.Terminal rate constant in plasma (λz) for total dabigatran.
AUC0-tz for Total Dabigatran-0:30 hour(h) before drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 3:30h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h and 48:00h after drug administration.Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the time of the last quantifiable data point (AUC0-tz) for total dabigatran.

Participant flow

Participants by arm

ArmCount
Overall
This study is open-label, single dose, randomised, three-way crossover design having 3 treatment periods ie., Dabigatran etexilate 150 mg formulation capsule: Reference (A), Dabigatran etexilate 150 mg formulation pellets: Test 1 (B) and Dabigatran etexilate 150 mg formulation powder: Test 2 (C)
30
Total30

Baseline characteristics

CharacteristicOverall
Age, Continuous39.8 Years
STANDARD_DEVIATION 8.2
Sex: Female, Male
Female
10 Participants
Sex: Female, Male
Male
20 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
EG002
affected / at risk
deaths
Total, all-cause mortality
— / —— / —— / —
other
Total, other adverse events
2 / 307 / 308 / 30
serious
Total, serious adverse events
0 / 300 / 300 / 30

Outcome results

Primary

AUC0-inf for Free Dabigatran

Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity (AUC0-inf) for free dabigatran.

Time frame: -0:30 hour(h) before drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 3:30h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h and 48:00h after drug administration.

Population: pharmacokinetic per-protocol set

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
Dabigatran Etexilate 150 mg Capsule: Reference (A)AUC0-inf for Free Dabigatran464 ng*h/mLGeometric Coefficient of Variation 97.3
Dabigatran Etexilate 150 mg Pellets: Test 1 (B)AUC0-inf for Free Dabigatran815 ng*h/mLGeometric Coefficient of Variation 40
Dabigatran Etexilate 150 mg Powder: Test 2 (C)AUC0-inf for Free Dabigatran734 ng*h/mLGeometric Coefficient of Variation 38.2
Comparison: An Analysis of variance (ANOVA) model was used on the logarithmic scale in order to compare the Test treatment vs. the Reference treatment. This model included effects for 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.90% CI: [141.924, 216.772]
Comparison: An Analysis of variance (ANOVA) model was used on the logarithmic scale in order to compare the Test treatment vs. the Reference treatment. This model included effects for 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.90% CI: [130.052, 192.255]
Primary

AUC0-inf for Total Dabigatran

Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity (AUC0-inf) for total dabigatran.

Time frame: -0:30 hour(h) before drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 3:30h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h and 48:00h after drug administration.

Population: PK-Per protocol set (PK-PPS): This subject set included all subjects in the treated set who provided at least one observation for at least one primary (PK) endpoint without important protocol violations with respect to the evaluation of relative bioavailability and who did not vomit at or before 2 times the median tmax.

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
Dabigatran Etexilate 150 mg Capsule: Reference (A)AUC0-inf for Total Dabigatran599 ng(nanogram)*h(hour)/mL(milliliter)Geometric Coefficient of Variation 93.3
Dabigatran Etexilate 150 mg Pellets: Test 1 (B)AUC0-inf for Total Dabigatran1050 ng(nanogram)*h(hour)/mL(milliliter)Geometric Coefficient of Variation 33.8
Dabigatran Etexilate 150 mg Powder: Test 2 (C)AUC0-inf for Total Dabigatran928 ng(nanogram)*h(hour)/mL(milliliter)Geometric Coefficient of Variation 32.8
Comparison: An Analysis of variance (ANOVA) model was used on the logarithmic scale in order to compare the Test treatment vs. the Reference treatment. This model included effects for 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.90% CI: [141.904, 216.149]
Comparison: An Analysis of variance (ANOVA) model was used on the logarithmic scale in order to compare the Test treatment (T2) vs. the Reference treatment (R). This model included effects for 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.90% CI: [127.425, 188.161]
Primary

Cmax for Free Dabigatran

Maximum measured concentration of the analyte in plasma (Cmax) for free dabigatran

Time frame: -0:30 hour(h) before drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 3:30h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h and 48:00h after drug administration.

Population: pharmacokinetic per-protocol set

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
Dabigatran Etexilate 150 mg Capsule: Reference (A)Cmax for Free Dabigatran61.5 ng/mLGeometric Coefficient of Variation 110
Dabigatran Etexilate 150 mg Pellets: Test 1 (B)Cmax for Free Dabigatran112 ng/mLGeometric Coefficient of Variation 40.4
Dabigatran Etexilate 150 mg Powder: Test 2 (C)Cmax for Free Dabigatran103 ng/mLGeometric Coefficient of Variation 40.7
Comparison: An Analysis of variance (ANOVA) model was used on the logarithmic scale in order to compare the Test treatment vs. the Reference treatment. This model included effects for 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.90% CI: [145.428, 226.776]
Comparison: An Analysis of variance (ANOVA) model was used on the logarithmic scale in order to compare the Test treatment vs. the Reference treatment. This model included effects for 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.90% CI: [134.25, 207.328]
Primary

Cmax for Total Dabigatran

Maximum measured concentration of the analyte in plasma (Cmax) for total dabigatran.

Time frame: -0:30 hour(h) before drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 3:30h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h and 48:00h after drug administration.

Population: pharmacokinetic per-protocol set

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
Dabigatran Etexilate 150 mg Capsule: Reference (A)Cmax for Total Dabigatran74.6 ng/mLGeometric Coefficient of Variation 110
Dabigatran Etexilate 150 mg Pellets: Test 1 (B)Cmax for Total Dabigatran139 ng/mLGeometric Coefficient of Variation 37.8
Dabigatran Etexilate 150 mg Powder: Test 2 (C)Cmax for Total Dabigatran124 ng/mLGeometric Coefficient of Variation 37
Comparison: An Analysis of variance (ANOVA) model was used on the logarithmic scale in order to compare the Test treatment vs. the Reference treatment. This model included effects for 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.90% CI: [147.659, 236.665]
Comparison: An Analysis of variance (ANOVA) model was used on the logarithmic scale in order to compare the Test treatment vs. the Reference treatment. This model included effects for 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.90% CI: [133.221, 208.326]
Secondary

Assessment of Tolerability by Investigator.

Tolerability will be assessed by the investigator according to the categories good, satisfactory, not satisfactory and bad.

Time frame: From first drug administration until 7 days after the last drug administration of Dabigatran, ie., up to 10 days.

Population: Treated Set

ArmMeasureGroupValue (NUMBER)
Dabigatran Etexilate 150 mg Capsule: Reference (A)Assessment of Tolerability by Investigator.Bad0.0 Percentage of Participants
Dabigatran Etexilate 150 mg Capsule: Reference (A)Assessment of Tolerability by Investigator.Not satisfactory0.0 Percentage of Participants
Dabigatran Etexilate 150 mg Capsule: Reference (A)Assessment of Tolerability by Investigator.Good100.0 Percentage of Participants
Dabigatran Etexilate 150 mg Capsule: Reference (A)Assessment of Tolerability by Investigator.Satisfactory0.0 Percentage of Participants
Dabigatran Etexilate 150 mg Capsule: Reference (A)Assessment of Tolerability by Investigator.Not assessable0.0 Percentage of Participants
Dabigatran Etexilate 150 mg Pellets: Test 1 (B)Assessment of Tolerability by Investigator.Not satisfactory0.0 Percentage of Participants
Dabigatran Etexilate 150 mg Pellets: Test 1 (B)Assessment of Tolerability by Investigator.Good100.0 Percentage of Participants
Dabigatran Etexilate 150 mg Pellets: Test 1 (B)Assessment of Tolerability by Investigator.Satisfactory0.0 Percentage of Participants
Dabigatran Etexilate 150 mg Pellets: Test 1 (B)Assessment of Tolerability by Investigator.Bad0.0 Percentage of Participants
Dabigatran Etexilate 150 mg Pellets: Test 1 (B)Assessment of Tolerability by Investigator.Not assessable0.0 Percentage of Participants
Dabigatran Etexilate 150 mg Powder: Test 2 (C)Assessment of Tolerability by Investigator.Not assessable0.0 Percentage of Participants
Dabigatran Etexilate 150 mg Powder: Test 2 (C)Assessment of Tolerability by Investigator.Bad0.0 Percentage of Participants
Dabigatran Etexilate 150 mg Powder: Test 2 (C)Assessment of Tolerability by Investigator.Good100.0 Percentage of Participants
Dabigatran Etexilate 150 mg Powder: Test 2 (C)Assessment of Tolerability by Investigator.Not satisfactory0.0 Percentage of Participants
Dabigatran Etexilate 150 mg Powder: Test 2 (C)Assessment of Tolerability by Investigator.Satisfactory0.0 Percentage of Participants
Secondary

AUC0-tz for Free Dabigatran

Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the time of the last quantifiable data point (AUC0-tz) for free dabigatran.

Time frame: -0:30 hour(h) before drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 3:30h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h and 48:00h after drug administration.

Population: pharmacokinetic per-protocol set

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
Dabigatran Etexilate 150 mg Capsule: Reference (A)AUC0-tz for Free Dabigatran436 ng*h/mLGeometric Coefficient of Variation 110
Dabigatran Etexilate 150 mg Pellets: Test 1 (B)AUC0-tz for Free Dabigatran794 ng*h/mLGeometric Coefficient of Variation 41.3
Dabigatran Etexilate 150 mg Powder: Test 2 (C)AUC0-tz for Free Dabigatran715 ng*h/mLGeometric Coefficient of Variation 39.5
Comparison: An Analysis of variance (ANOVA) model was used on the logarithmic scale in order to compare the Test treatment vs. the Reference treatment. This model included effects for 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.90% CI: [144.993, 229.075]
Comparison: An Analysis of variance (ANOVA) model was used on the logarithmic scale in order to compare the Test treatment vs. the Reference treatment. This model included effects for 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.90% CI: [132.421, 203.14]
Secondary

AUC0-tz for Total Dabigatran

Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the time of the last quantifiable data point (AUC0-tz) for total dabigatran.

Time frame: -0:30 hour(h) before drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 3:30h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h and 48:00h after drug administration.

Population: pharmacokinetic per-protocol set

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
Dabigatran Etexilate 150 mg Capsule: Reference (A)AUC0-tz for Total Dabigatran565 ng*h/mLGeometric Coefficient of Variation 106
Dabigatran Etexilate 150 mg Pellets: Test 1 (B)AUC0-tz for Total Dabigatran1030 ng*h/mLGeometric Coefficient of Variation 34.2
Dabigatran Etexilate 150 mg Powder: Test 2 (C)AUC0-tz for Total Dabigatran908 ng*h/mLGeometric Coefficient of Variation 33.5
Comparison: An Analysis of variance (ANOVA) model was used on the logarithmic scale in order to compare the Test treatment vs. the Reference treatment. This model included effects for 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.90% CI: [144.727, 229.297]
Comparison: An Analysis of variance (ANOVA) model was used on the logarithmic scale in order to compare the Test treatment vs. the Reference treatment. This model included effects for 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.90% CI: [129.633, 199.306]
Secondary

CL/F for Free Dabigatran

Apparent clearance of the analyte in plasma following extravascular administration (CL/F) for free dabigatran.

Time frame: -0:30 hour(h) before drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 3:30h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h and 48:00h after drug administration.

Population: pharmacokinetic per-protocol set

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
Dabigatran Etexilate 150 mg Capsule: Reference (A)CL/F for Free Dabigatran4040 mL (milliliter)/min (minute)Geometric Coefficient of Variation 97.3
Dabigatran Etexilate 150 mg Pellets: Test 1 (B)CL/F for Free Dabigatran2310 mL (milliliter)/min (minute)Geometric Coefficient of Variation 40
Dabigatran Etexilate 150 mg Powder: Test 2 (C)CL/F for Free Dabigatran2560 mL (milliliter)/min (minute)Geometric Coefficient of Variation 38.2
Secondary

CL/F for Total Dabigatran

Apparent clearance of the analyte in plasma following extravascular administration (CL/F) for total dabigatran.

Time frame: -0:30 hour(h) before drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 3:30h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h and 48:00h after drug administration.

Population: pharmacokinetic per-protocol set

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
Dabigatran Etexilate 150 mg Capsule: Reference (A)CL/F for Total Dabigatran3130 mL (milliliter)/min (minute)Geometric Coefficient of Variation 93.3
Dabigatran Etexilate 150 mg Pellets: Test 1 (B)CL/F for Total Dabigatran1790 mL (milliliter)/min (minute)Geometric Coefficient of Variation 33.8
Dabigatran Etexilate 150 mg Powder: Test 2 (C)CL/F for Total Dabigatran2020 mL (milliliter)/min (minute)Geometric Coefficient of Variation 32.8
Secondary

MRTpo for Free Dabigatran

Mean residence time of the analyte in the body after po administration (MRTpo) for free dabigatran.

Time frame: -0:30 hour(h) before drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 3:30h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h and 48:00h after drug administration.

Population: pharmacokinetic per-protocol set

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
Dabigatran Etexilate 150 mg Capsule: Reference (A)MRTpo for Free Dabigatran9.9 hourGeometric Coefficient of Variation 14
Dabigatran Etexilate 150 mg Pellets: Test 1 (B)MRTpo for Free Dabigatran9.58 hourGeometric Coefficient of Variation 14.1
Dabigatran Etexilate 150 mg Powder: Test 2 (C)MRTpo for Free Dabigatran9.15 hourGeometric Coefficient of Variation 12.2
Secondary

MRTpo for Total Dabigatran

Mean residence time of the analyte in the body after po administration (MRTpo) for total dabigatran.

Time frame: -0:30 hour(h) before drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 3:30h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h and 48:00h after drug administration.

Population: pharmacokinetic per-protocol set

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
Dabigatran Etexilate 150 mg Capsule: Reference (A)MRTpo for Total Dabigatran10.8 hourGeometric Coefficient of Variation 12
Dabigatran Etexilate 150 mg Pellets: Test 1 (B)MRTpo for Total Dabigatran10.1 hourGeometric Coefficient of Variation 11.4
Dabigatran Etexilate 150 mg Powder: Test 2 (C)MRTpo for Total Dabigatran10 hourGeometric Coefficient of Variation 12.2
Secondary

Percentage of Participants With Drug-related Adverse Events

Percentage of participants with investigator defined drug-releated Adverse events.

Time frame: From first drug administration until 7 days after the last drug administration of Dabigatran, ie., up to 10 days.

Population: Treated set

ArmMeasureValue (NUMBER)
Dabigatran Etexilate 150 mg Capsule: Reference (A)Percentage of Participants With Drug-related Adverse Events6.7 Percentage of participants
Dabigatran Etexilate 150 mg Pellets: Test 1 (B)Percentage of Participants With Drug-related Adverse Events23.3 Percentage of participants
Dabigatran Etexilate 150 mg Powder: Test 2 (C)Percentage of Participants With Drug-related Adverse Events26.7 Percentage of participants
Secondary

Percentage of Participants With Findings in Physical Examination, Vital Signs , Pulse Rate (PR)), 12-lead ECG, Clinical Laboratory Tests.

Percentage of participants with findings in Physical examination, Vital signs (blood pressure (BP), pulse rate (PR)), 12-lead ECG (electrocardiogram), Clinical laboratory tests (haematology, clinical chemistry and urinalysis). Relevant findings or worsening of baseline conditions were reported as Adverse events. There were no clinically relevant finding reported for Physical examination, Vital signs (blood pressure, pulse rate), 12-lead ECG and Clinical laboratory tests.

Time frame: From first drug administration until 7 days after the last drug administration of Dabigatran, ie., up to 10 days.

Population: Treated Set

ArmMeasureValue (NUMBER)
Dabigatran Etexilate 150 mg Capsule: Reference (A)Percentage of Participants With Findings in Physical Examination, Vital Signs , Pulse Rate (PR)), 12-lead ECG, Clinical Laboratory Tests.0.0 Percentage of participants
Dabigatran Etexilate 150 mg Pellets: Test 1 (B)Percentage of Participants With Findings in Physical Examination, Vital Signs , Pulse Rate (PR)), 12-lead ECG, Clinical Laboratory Tests.0.0 Percentage of participants
Dabigatran Etexilate 150 mg Powder: Test 2 (C)Percentage of Participants With Findings in Physical Examination, Vital Signs , Pulse Rate (PR)), 12-lead ECG, Clinical Laboratory Tests.0.0 Percentage of participants
Secondary

t1/2 for Free Dabigatran

Terminal half-life of the analyte in plasma (t1/2) for free dabigatran.

Time frame: -0:30 hour(h) before drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 3:30h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h and 48:00h after drug administration.

Population: pharmacokinetic per-protocol set

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
Dabigatran Etexilate 150 mg Capsule: Reference (A)t1/2 for Free Dabigatran7.62 hourGeometric Coefficient of Variation 16
Dabigatran Etexilate 150 mg Pellets: Test 1 (B)t1/2 for Free Dabigatran8.54 hourGeometric Coefficient of Variation 18.6
Dabigatran Etexilate 150 mg Powder: Test 2 (C)t1/2 for Free Dabigatran7.76 hourGeometric Coefficient of Variation 15.7
Secondary

t1/2 for Total Dabigatran

Terminal half-life of the analyte in plasma (t1/2) for total dabigatran

Time frame: -0:30 hour(h) before drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 3:30h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h and 48:00h after drug administration.

Population: pharmacokinetic per-protocol set

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
Dabigatran Etexilate 150 mg Capsule: Reference (A)t1/2 for Total Dabigatran8.77 hourGeometric Coefficient of Variation 13.5
Dabigatran Etexilate 150 mg Pellets: Test 1 (B)t1/2 for Total Dabigatran9.37 hourGeometric Coefficient of Variation 14.5
Dabigatran Etexilate 150 mg Powder: Test 2 (C)t1/2 for Total Dabigatran9.16 hourGeometric Coefficient of Variation 16.4
Secondary

Tmax for Free Dabigatran

Time from dosing to the maximum concentration of the analyte in plasma (tmax) for free dabigatran

Time frame: -0:30 hour(h) before drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 3:30h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h and 48:00h after drug administration.

Population: pharmacokinetic per-protocol set

ArmMeasureValue (MEDIAN)
Dabigatran Etexilate 150 mg Capsule: Reference (A)Tmax for Free Dabigatran2.0 hour
Dabigatran Etexilate 150 mg Pellets: Test 1 (B)Tmax for Free Dabigatran1.51 hour
Dabigatran Etexilate 150 mg Powder: Test 2 (C)Tmax for Free Dabigatran1.5 hour
Secondary

Tmax for Total Dabigatran

Time from dosing to the maximum concentration of the analyte in plasma (tmax) for total dabigatran

Time frame: -0:30 hour(h) before drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 3:30h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h and 48:00h after drug administration.

Population: pharmacokinetic per-protocol set

ArmMeasureValue (MEDIAN)
Dabigatran Etexilate 150 mg Capsule: Reference (A)Tmax for Total Dabigatran2.0 hour
Dabigatran Etexilate 150 mg Pellets: Test 1 (B)Tmax for Total Dabigatran1.5 hour
Dabigatran Etexilate 150 mg Powder: Test 2 (C)Tmax for Total Dabigatran1.5 hour
Secondary

Vz/F for Free Dabigatran

Apparent volume of distribution during the terminal phase λz following an extravascular dose (Vz/F) for free dabigatran.

Time frame: -0:30 hour(h) before drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 3:30h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h and 48:00h after drug administration.

Population: pharmacokinetic per-protocol set

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
Dabigatran Etexilate 150 mg Capsule: Reference (A)Vz/F for Free Dabigatran2670 LiterGeometric Coefficient of Variation 91
Dabigatran Etexilate 150 mg Pellets: Test 1 (B)Vz/F for Free Dabigatran1700 LiterGeometric Coefficient of Variation 41.4
Dabigatran Etexilate 150 mg Powder: Test 2 (C)Vz/F for Free Dabigatran1720 LiterGeometric Coefficient of Variation 37.6
Secondary

Vz/F for Total Dabigatran

Apparent volume of distribution during the terminal phase λz following an extravascular dose (Vz/F) for total dabigatran.

Time frame: -0:30 hour(h) before drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 3:30h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h and 48:00h after drug administration.

Population: pharmacokinetic per-protocol set

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
Dabigatran Etexilate 150 mg Capsule: Reference (A)Vz/F for Total Dabigatran2380 LiterGeometric Coefficient of Variation 92.8
Dabigatran Etexilate 150 mg Pellets: Test 1 (B)Vz/F for Total Dabigatran1450 LiterGeometric Coefficient of Variation 35
Dabigatran Etexilate 150 mg Powder: Test 2 (C)Vz/F for Total Dabigatran1610 LiterGeometric Coefficient of Variation 35.9
Secondary

λz for Free Dabigatran

Time frame: -0:30 hour(h) before drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 3:30h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h and 48:00h after drug administration.

Population: pharmacokinetic per-protocol set

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
Dabigatran Etexilate 150 mg Capsule: Reference (A)λz for Free Dabigatran0.091 1/hourGeometric Coefficient of Variation 16
Dabigatran Etexilate 150 mg Pellets: Test 1 (B)λz for Free Dabigatran0.0811 1/hourGeometric Coefficient of Variation 18.6
Dabigatran Etexilate 150 mg Powder: Test 2 (C)λz for Free Dabigatran0.0893 1/hourGeometric Coefficient of Variation 15.7
Secondary

λz for Total Dabigatran

Terminal rate constant in plasma (λz) for total dabigatran.

Time frame: -0:30 hour(h) before drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 3:30h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h and 48:00h after drug administration.

Population: pharmacokinetic per-protocol set

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
Dabigatran Etexilate 150 mg Capsule: Reference (A)λz for Total Dabigatran0.079 1/hourGeometric Coefficient of Variation 13.5
Dabigatran Etexilate 150 mg Pellets: Test 1 (B)λz for Total Dabigatran0.074 1/hourGeometric Coefficient of Variation 14.5
Dabigatran Etexilate 150 mg Powder: Test 2 (C)λz for Total Dabigatran0.0756 1/hourGeometric Coefficient of Variation 16.4

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026