HealthyPhase 1NCT03070171

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

A Phase 1 study testing dabigatran etexilate in people with Healthy, run by Boehringer Ingelheim at 1 site in Japan.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial 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. Read more about this study

Who is it for?: Ages 20 to 40 years, men onlyHealthy volunteers can take part
Conditions the study is for: Healthy
What is being tested?: dabigatran etexilate
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 160 participants
Where: 1 siteJapan
Study dates: 21 Mar 2017to 20 Jun 2017
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 20 to 40 years
Men only
Healthy volunteers accepted
Adult

Who may be able to join

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

Who cannot join

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

Show all 24Show fewer

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

Trial locations and contacts

1 site in 1 country.

Japan1 site

SOUSEIKAI Sumida Hospital
Tokyo, Sumida-ku, 130-0004

Other trials in Japan

About this study

Official title: Bioequivalence of Tablet Formulation of Dabigatran Etexilate Compared to Commercial Capsule Formulation Following Oral Administration in Healthy Male Subjects (an Open-label, Randomised, Single-dose, Replicate Design in a Two-treatment, Four-period, Two-sequence Crossover Study)

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

Conditions: Healthy
Being tested: dabigatran etexilate

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

dabigatran etexilateDrug
Also called PRADAXA
single dose

Study groups in NCT03070171
Study group	Role	What they receive
Dabigatran Etexilate Capsule	Experimental	Not described Receives: Drug: dabigatran etexilate
Dabigatran Etexilate Tablet	Experimental	Not described Receives: Drug: dabigatran etexilate

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
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.
Measured: 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 (4)

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.
Measured: 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.
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.
Measured: 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.
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.
Measured: 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.
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.
Measured: 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.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

21 Mar 201720 Jun 2017

First posted3 Mar 2017
Study start21 Mar 2017
Primary completion16 Jun 2017
Study completion20 Jun 2017

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for HealthyStudies of the same condition, open and under way.
More trials run by Boehringer IngelheimThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Enrolment: 160 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03070171
Sponsor's protocol ID: 1160-0271
Status last verified: Jan 2019
First submitted: 28 Feb 2017
Last updated: 9 Jan 2019
Results posted: Yes, on ClinicalTrials.gov
FDA-regulated drug: No
FDA-regulated device: No

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

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 9 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Bioequivalence of Tablet Formulation of Dabigatran Etexilate Compared to Commercial Capsule Formulation Following Oral Administration in Healthy Male Subjects (an Open-label, Randomised, Single-dose, Replicate Design in a Two-treatment, Four-period, Two-sequence Crossover Study)
ClinicalTrials.gov ID: NCT03070171
Acronym / sponsor ID: 1160-0271
Conditions: Healthy
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 160 participants (actual)
Lead sponsor: Boehringer IngelheimIndustry (pharma, biotech, devices)
Study start: 21 Mar 2017 (actual)
Primary completion: 16 Jun 2017 (actual)
Study completion: 20 Jun 2017 (actual)
First posted: 3 Mar 2017 (actual)
Results: Posted 9 Jan 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Dabigatran Etexilate Capsule	Experimental	Drug: dabigatran etexilate
Dabigatran Etexilate Tablet	Experimental	Drug: dabigatran etexilate

Who may qualify

Ages: 20 to 40 years
Sex: Male only
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (5 listed)

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

Key exclusion criteria (24 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
dabigatran etexilateAlso: PRADAXAsingle dose	Drug	Dabigatran Etexilate Capsule, Dabigatran Etexilate Tablet

Primary outcome

AUC0-tz of Free Dabigatran
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.
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.
Cmax of Free Dabigatran
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.
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.

4 secondary outcomes

AUC0-tz of Total Dabigatran
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.
Cmax of Total Dabigatran
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.
AUC0-∞ of Total Dabigatran
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.
AUC0-∞ of Free Dabigatran
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.

Results and safety

Results posted to the registry on 9 Jan 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
T-R-R-T	80	80
R-T-T-R	80	80

Primary outcome: AUC0-tz of Free Dabigatran

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.. Geometric mean (Geometric Coefficient of Variation). Unit: Nanogram*hour/milliliter (ng･h/mL)

Measure	Dabigatran Etexilate Tablet (T) n = 159	Dabigatran Etexilate Capsule (R) n = 160
Value	725.03686 (57.00406)	668.42714 (52.33393)

Dabigatran Etexilate Tablet (T) vs Dabigatran Etexilate Capsule (R): T/R Ratio: 108.46909 (90% CI 101.44605 to 115.97833), ANOVA

Population analysed: Pharmacokinetic set (PKS): All subjects from Treated Set (TS) who provided at least 1 observation for at least 1 primary endpoint that was not excluded as per PK exclusion criteria (defined in the description).

Primary outcome: Cmax of Free Dabigatran

Measure	Dabigatran Etexilate Tablet (T) n = 159	Dabigatran Etexilate Capsule (R) n = 160
Value	86.26026 (56.43338)	79.16785 (55.20456)

Dabigatran Etexilate Tablet (T) vs Dabigatran Etexilate Capsule (R): T/R Ratio: 108.9587 (90% CI 101.78627 to 116.63654), ANOVA

Population analysed: PKS

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: From first drug administration until 3 day after the last drug administration, ie upto 7 days. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Dabigatran Etexilate Tablet (T)	0 of 159 (0%)	0 of 159 (0%)	0 of 159
Dabigatran Etexilate Capsule (R)	0 of 160 (0%)	0 of 160 (0%)	0 of 160

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 9 Jan 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 31667735Harada 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.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing dabigatran etexilate in people with Healthy, run by Boehringer Ingelheim at 1 site in Japan.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 9 Jan 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

AUC0-tz of Free Dabigatran (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.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03070171, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jan 2019.