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CompletedNCT03070171Updated Jan 9, 2019Results posted

Bioequivalence of Tablet Formulation of Dabigatran Etexilate Compared to Commercial Capsule Formulation Following Oral Administration in Healthy Male Subjects

A Phase 1 interventional study of dabigatran etexilate in Healthy, sponsored by Boehringer Ingelheim. Completed at 1 site in Japan. Open to male participants aged 20 Years to 40 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2019-01-09.

Sponsored by Boehringer Ingelheim · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
160
Allocation
Randomized
Ages
20 Years to 40 Years
Sex
Male
01

Study summary

The primary objective of this trial is to establish the bioequivalence of tablet formulation of dabigatran etexilate compared to commercial capsule formulation following oral administration under fasted condition.

The secondary objective is the evaluation and comparison of several pharmacokinetic parameters between the treatments.

02

Conditions studied

  • Healthy
03

In context

Lead sponsor

Boehringer Ingelheim is the lead sponsor of 2,297 studies on the registry; 56 are open to participants now.

Of its 166 completed or terminated interventional studies of FDA-regulated products, 121 (73%) have results posted.

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Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
20 Years to 40 Years
Sexes eligible
Male
Accepts healthy volunteers
Yes

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

Subjects will only be included into the trial, if they meet the following 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 ≤40 years old at informed consent
  • BMI ≥18 and ≤25 kg/m2 at screening
  • Signed and dated written informed consent prior to admission to the trial in accordance with Good Clinical Practice (GCP) and local legislation

Exclusion criteria

Exclusion Criteria:

Subjects will not be allowed to participate if any of the following general criteria apply:

  • Any finding in the medical examination (including blood pressure (BP), pulse rate (PR)or electrocardiogram (ECG)) is deviating from normal and judged as clinically relevant by the investigator
  • 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. Based on the clinical judge by the investigator, repeated measurements are allowed.
  • Any laboratory value outside the reference range before randomisation that the investigator considers to be of clinical relevance
  • Any evidence of a concomitant disease considered as clinically relevant by the investigator
  • Any relevant bleeding history considered by the investigator
  • 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
  • Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
  • Cholecystectomy and/or surgery of the gastrointestinal tract that could interfere with the pharmacokinetics of the trial medication (except appendectomy and simple hernia repair)
  • Planned surgeries within four weeks following the end-of trial examination
  • Diseases of the central nervous system (including but not limited to any kind of seizures or stroke), and other relevant neurological or psychiatric disorders
  • 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)
  • Use of drugs within 30 days prior to administration of trial medication if that might reasonably influence the results of the trial (incl.Qc/QTc interval prolongation)
  • Participation in another trial where an investigational drug has been administered within 60 days prior to planned administration of trial medication, or current participation in another trial involving administration of investigational drug
  • Smoker (more than 10 cigarettes or 3 cigars or 3 pipes per day)
  • Inability to refrain from smoking 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 is assessed as unsuitable for inclusion by the investigator, for instance, because considered not able to understand and comply with trial requirements, or has a condition that would not allow safe participation in the trial
05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Crossover assignment
Masking
None (open label)
Enrollment
160 participants (actual)

Study arms

  • Experimental
    Dabigatran Etexilate Capsule

    Drug: dabigatran etexilate

  • Experimental
    Dabigatran Etexilate Tablet

    Drug: dabigatran etexilate

Interventions

06

What researchers measure

Primary outcomes

  1. AUC0-tz of Free Dabigatran

    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 (AUC0-tz). Geometric Mean (gMean) is actually Adjusted gMean \& Geometric Coefficient of Variation (gCV) is actually Intra individual gCV (%gCV). PK exclusion criteria: 1) The subject experienced emesis at or before 2 times median Time from (last) dosing to the maximum measured concentration of the analyte in plasma (tmax). Median tmax was to be taken either from the median tmax for reference product or test product, depending on whether the subject had experienced emesis after taken the test or reference product. Median tmax was to be determined excluding the subjects experiencing emesis. 2) Time deviations 3) Use of restricted medications 4) A pre-dose concentration was \>5% of the Cmax value of that subject.

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

  2. Cmax of Free Dabigatran

    Maximum plasma concentration of free dabigatran (Cmax). Geometric Mean is actually Adjusted geometric mean and Geometric Coefficient of Variation (gCV) is actually Intra individual gCV.

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

Secondary outcomes

  1. AUC0-tz of Total Dabigatran

    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 (AUC0-tz ). Geometric Mean is actually Adjusted geometric mean and Geometric Coefficient of Variation (gCV) is actually Intra individual gCV.

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

  2. Cmax of Total Dabigatran

    Maximum plasma concentration of total dabigatran (Cmax). Geometric Mean is actually Adjusted geometric mean and Geometric Coefficient of Variation (gCV) is actually Intra individual gCV.

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

  3. AUC0-∞ of Total Dabigatran

    Area under the concentration-time curve of total dabigatran in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞). Geometric Mean is actually Adjusted geometric mean and Geometric Coefficient of Variation (gCV) is actually Intra individual gCV.

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

  4. AUC0-∞ of Free Dabigatran

    Area under the concentration-time curve of free dabigatran in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞). Geometric Mean is actually Adjusted geometric mean and Geometric Coefficient of Variation (gCV) is actually Intra individual gCV.

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

07

Results

Posted Jan 9, 2019

Participant flow

Randomised, single-dose, open-label, replicate design in a two-treatments, four-period, two-sequence crossover design (T:Dabigatran etexilate tablet formulation 110 mg and R: Dabigatran etexilate capsule formulation 110 mg)

Treatment Period 1 + Washout
Participant flow — Treatment Period 1 + Washout
MilestoneT-R-R-TR-T-T-R
Started8080
Completed8080
Not completed00
Treatment Period 2 + Washout
Participant flow — Treatment Period 2 + Washout
MilestoneT-R-R-TR-T-T-R
Started8080
Completed8079
Not completed01
Withdrew: Other adverse event01
Treatment Period 3 + Washout
Participant flow — Treatment Period 3 + Washout
MilestoneT-R-R-TR-T-T-R
Started8079
Completed8079
Not completed00
Treatment Period 4 + Washout
Participant flow — Treatment Period 4 + Washout
MilestoneT-R-R-TR-T-T-R
Started8079
Completed8078
Not completed01
Withdrew: Withdrawal by subject01

Outcome measures

PrimaryAUC0-tz of Free Dabigatran

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 (AUC0-tz). Geometric Mean (gMean) is actually Adjusted gMean \& Geometric Coefficient of Variation (gCV) is actually Intra individual gCV (%gCV). PK exclusion criteria: 1) The subject experienced emesis at or before 2 times median Time from (last) dosing to the maximum measured concentration of the analyte in plasma (tmax). Median tmax was to be taken either from the median tmax for reference product or test product, depending on whether the subject had experienced emesis after taken the test or reference product. Median tmax was to be determined excluding the subjects experiencing emesis. 2) Time deviations 3) Use of restricted medications 4) A pre-dose concentration was \>5% of the Cmax value of that subject.

Time frame:
1:00h before drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 3:00h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h and 48:00h after drug administration.
Reported as:
Geometric mean · Nanogram*hour/milliliter (ng･h/mL)
AUC0-tz of Free Dabigatran
Nanogram*hour/milliliter (ng･h/mL)Dabigatran Etexilate Tablet (T)Dabigatran Etexilate Capsule (R)
AUC0-tz of Free Dabigatran725.03686 ± 57.00406668.42714 ± 52.33393
Statistical analysis
  • Dabigatran Etexilate Tablet (T) vs Dabigatran Etexilate Capsule (R) · ANOVA · T/r ratio: 108.46909 · 90% CI 101.44605 to 115.97833Confidence intervals were calculated based on the residual error from ANOVA. Ratio calculated as Dabigatran Etexilate Tablet (T) divided by Dabigatran Etexilate capsule (R).
PrimaryCmax of Free Dabigatran

Maximum plasma concentration of free dabigatran (Cmax). Geometric Mean is actually Adjusted geometric mean and Geometric Coefficient of Variation (gCV) is actually Intra individual gCV.

Time frame:
1:00h before drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 3:00h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h and 48:00h after drug administration.
Reported as:
Geometric mean · Nanogram/milliliter (ng/mL)
Cmax of Free Dabigatran
Nanogram/milliliter (ng/mL)Dabigatran Etexilate Tablet (T)Dabigatran Etexilate Capsule (R)
Cmax of Free Dabigatran86.26026 ± 56.4333879.16785 ± 55.20456
Statistical analysis
  • Dabigatran Etexilate Tablet (T) vs Dabigatran Etexilate Capsule (R) · ANOVA · T/r ratio: 108.9587 · 90% CI 101.78627 to 116.63654Confidence intervals were calculated based on the residual error from ANOVA. Ratio calculated as Dabigatran Etexilate Tablet (T) divided by Dabigatran Etexilate capsule (R).
SecondaryAUC0-tz of Total Dabigatran

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 (AUC0-tz ). Geometric Mean is actually Adjusted geometric mean and Geometric Coefficient of Variation (gCV) is actually Intra individual gCV.

Time frame:
1:00h before drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 3:00h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h and 48:00h after drug administration.
Reported as:
Geometric mean · ng•h/mL
AUC0-tz of Total Dabigatran
ng•h/mLDabigatran Etexilate Tablet (T)Dabigatran Etexilate Capsule (R)
AUC0-tz of Total Dabigatran847.26720 ± 57.32236787.31279 ± 52.53129
Statistical analysis
  • Dabigatran Etexilate Tablet (T) vs Dabigatran Etexilate Capsule (R) · ANOVA · T/r ratio: 107.61507 · 90% CI 100.61938 to 115.09714Confidence intervals were calculated based on the residual error from ANOVA. Ratio calculated as Dabigatran Etexilate Tablet (T) divided by Dabigatran Etexilate capsule (R).
SecondaryCmax of Total Dabigatran

Maximum plasma concentration of total dabigatran (Cmax). Geometric Mean is actually Adjusted geometric mean and Geometric Coefficient of Variation (gCV) is actually Intra individual gCV.

Time frame:
1:00h before drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 3:00h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h and 48:00h after drug administration.
Reported as:
Geometric mean · ng/mL
Cmax of Total Dabigatran
ng/mLDabigatran Etexilate Tablet (T)Dabigatran Etexilate Capsule (R)
Cmax of Total Dabigatran99.81133 ± 58.3184693.54769 ± 56.54651
Statistical analysis
  • Dabigatran Etexilate Tablet (T) vs Dabigatran Etexilate Capsule (R) · ANOVA · T/r ratio: 106.69566 · 90% CI 99.50139 to 114.41010Confidence intervals were calculated based on the residual error from ANOVA. Ratio calculated as Dabigatran Etexilate Tablet (T) divided by Dabigatran Etexilate capsule (R).
SecondaryAUC0-∞ of Total Dabigatran

Area under the concentration-time curve of total dabigatran in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞). Geometric Mean is actually Adjusted geometric mean and Geometric Coefficient of Variation (gCV) is actually Intra individual gCV.

Time frame:
1:00h before drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 3:00h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h and 48:00h after drug administration.
Reported as:
Geometric mean · ng•h/mL
AUC0-∞ of Total Dabigatran
ng•h/mLDabigatran Etexilate Tablet (T)Dabigatran Etexilate Capsule (R)
AUC0-∞ of Total Dabigatran877.70198 ± 52.04260813.94379 ± 49.99079
Statistical analysis
  • Dabigatran Etexilate Tablet (T) vs Dabigatran Etexilate Capsule (R) · ANOVA · T/r ratio: 107.83324 · 90% CI 101.25584 to 114.83790Confidence intervals were calculated based on the residual error from ANOVA. Ratio calculated as Dabigatran Etexilate Tablet (T) divided by Dabigatran Etexilate capsule (R).
SecondaryAUC0-∞ of Free Dabigatran

Area under the concentration-time curve of free dabigatran in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞). Geometric Mean is actually Adjusted geometric mean and Geometric Coefficient of Variation (gCV) is actually Intra individual gCV.

Time frame:
1:00h before drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 3:00h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h and 48:00h after drug administration.
Reported as:
Geometric mean · ng•h/mL
AUC0-∞ of Free Dabigatran
ng•h/mLDabigatran Etexilate Tablet (T)Dabigatran Etexilate Capsule (R)
AUC0-∞ of Free Dabigatran753.13668 ± 51.62318694.57320 ± 49.42941
Statistical analysis
  • Dabigatran Etexilate Tablet (T) vs Dabigatran Etexilate Capsule (R) · ANOVA · T/r ratio: 108.43158 · 90% CI 101.87254 to 115.41292Confidence intervals were calculated based on the residual error from ANOVA. Ratio calculated as Dabigatran Etexilate Tablet (T) divided by Dabigatran Etexilate capsule (R).

Adverse events

Collected over From first drug administration until 3 day after the last drug administration, ie upto 7 days. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Dabigatran Etexilate Tablet (T)0/159 (0%)0/159 (0%)0/159 (0%)
Dabigatran Etexilate Capsule (R)0/160 (0%)0/160 (0%)0/160 (0%)

Baseline characteristics

Treated set (TS): This subject set included all subjects from the Randomised Set (RS) who were dispensed study medication and were documented to have taken at least 1 dose of investigational treatment.

Age, Continuous
Age, Continuous(Years)T-R-R-TR-T-T-RTotal
Mean27.2 ± 4.227.3 ± 4.227.2 ± 4.2
Sex: Female, Male
Sex: Female, Male(Participants)T-R-R-TR-T-T-RTotal
Female000
Male8080160
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)T-R-R-TR-T-T-RTotal
Hispanic or Latino000
Not Hispanic or Latino8080160
Unknown or Not Reported000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)T-R-R-TR-T-T-RTotal
American Indian or Alaska Native000
Asian8080160
Native Hawaiian or Other Pacific Islander000
Black or African American000
White000
More than one race000
Unknown or Not Reported000
08

Study locations

1 site
  • SOUSEIKAI Sumida Hospital
    Tokyo, Sumida-ku, 130-0004, Japan
09

References and documents

Publications

  • Harada A, Ikushima I, Haranaka M, Yanagihara A, Nakayama D. Bioequivalence of a Newly Developed Dabigatran Etexilate Tablet Versus the Commercial Capsule and Impact of Rabeprazole-Induced Elevated Gastric pH on Exposure in Healthy Subjects. Am J Cardiovasc Drugs. 2020 Jun;20(3):249-258. doi: 10.1007/s40256-019-00377-x. PubMed 31667735 ↗

Study documents

  • Statistical analysis plan · Jul 12, 2017
  • Study protocol · Feb 10, 2017

Documents are hosted by the registry — open the source record to download them.

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jan 9, 2019, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT03070171
Lead sponsor
Boehringer Ingelheim
Responsible party
Sponsor
First posted
Mar 3, 2017
Start date
Mar 21, 2017
Primary completion
Jun 16, 2017
Completion
Jun 20, 2017
Results posted
Jan 9, 2019
Last update
Jan 9, 2019

Oversight

FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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