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CompletedNCT03143166Updated Jan 16, 2019Results posted

Pradaxa Tablet Proton Pump Inhibitor (PPI) Bioavailability (BA) Study in Japan

A Phase 1 interventional study of Dabigatran Etexilate and Rabeprazol sodium in Non-alcoholic Fatty Liver Disease, sponsored by Boehringer Ingelheim. Completed at 1 site in Japan. Open to male participants aged 20 Years to 40 Years. Per ClinicalTrials.gov, last updated 2019-01-16.

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

Phase
Phase 1
Study type
Interventional
Enrollment
36
Allocation
Not applicable
Ages
20 Years to 40 Years
Sex
Male
01

Study summary

The primary objective of this trial is to investigate the relative Bioavailability (BA) of tablet formulation of Dabigatran etexilate (DE) with and without co-administration of rabeprazole in healthy male subjects.

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

02

Conditions studied

  • Non-alcoholic Fatty Liver Disease
03

In context

Liver Diseases

2,081 studies on the registry are indexed under Liver Diseases; 390 are open to participants now.

This study's enrollment of 36 is below the median of 50 across 1,323 interventional studies indexed under Liver Diseases.

Browse Liver Diseases studies →

Lead sponsor

Boehringer Ingelheim is the lead sponsor of 2,245 studies on the registry; 58 are open to participants now.

Of its 162 completed or terminated interventional studies of FDA-regulated products, 116 (72%) have results posted.

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
No

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 ≤ 40 years at informed consent
  • Body mass index (BMI) of 18 ≥ and ≤ 25 kg/m2 at screening
  • Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice (GCP) and local legislation

Exclusion criteria

Exclusion Criteria:

  • 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 (BP) outside the range of 90 to 140 mmHg, diastolic blood pressure outside the range of 50 to 90 mmHg, or pulse rate (PR) outside the range of 45 to 90 bpm at screening
  • Any laboratory value outside the reference range before administration of DE that the investigator considers to be of clinical relevance
  • Any evidence of a concomitant disease judged 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
  • Any history of hypochlorhydria or achlorhydria
  • 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. QT/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 at 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 study requirements, or has a condition that would not allow safe participation in the study
05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
36 participants (actual)

Study arms

  • Experimental
    All participants

    Dabigatran etexilate given without rabeprazole and then Dabigatran etexilate given without rabeprazole.

    Drug: Dabigatran Etexilate · Drug: Rabeprazol sodium

Interventions

  • DrugDabigatran Etexilate

    Tablet, film coated

    Also known as: MICARDIS, PRITOR, TELMISARTAN

  • DrugRabeprazol sodium

    Tablet

06

What researchers measure

Primary outcomes

  1. Area Under the Plasma Concentration-time Curve From 0 to Time of Last Quantifiable Time Point (tz) of Total Dabigatran (AUC0-tz).

    This endpoint calculates area under the concentration-time curve of total dabigatran in plasma over the time interval from 0 to the time of last quantifiable time point.

    Time frame: Samples were collected 1 hour Pre-dose and at 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 12:00, 24:00 36:00 and 48:00 hours post dose.

  2. Maximum Concentration of Total Dabigatran in Plasma (Cmax).

    This outcome is maximum measured concentration of the total dabigatran in plasma

    Time frame: Samples were collected 1 hour Pre-dose and at 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 12:00, 24:00 36:00 and 48:00 hours post dose.

Secondary outcomes

  1. Area Under the Plasma Concentration-time Curve From 0 to Time of Last Quantifiable Time Point (tz) of Free Dabigatran (AUC0-tz).

    This endpoint calculates area under the concentration-time curve of free dabigatran in plasma over the time interval from 0 to the time of last quantifiable time point.

    Time frame: Samples were collected 1 hour Pre-dose and at 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 12:00, 24:00 36:00 and 48:00 hours post dose.

  2. Maximum Concentration of Free Dabigatran in Plasma (Cmax).

    This outcome is maximum measured concentration of the free dabigatran in plasma

    Time frame: Samples were collected 1 hour Pre-dose and at 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 12:00, 24:00 36:00 and 48:00 hours post dose.

  3. Area Under the Concentration-time Curve of Total Dabigatran in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞).

    This endpoint calculates area under the concentration-time curve of total dabigatran in plasma over the time interval from 0 extrapolated to infinity

    Time frame: Samples were collected 1 hour Pre-dose and at 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 12:00, 24:00 36:00 and 48:00 hours post dose.

  4. Area Under the Concentration-time Curve of Free Dabigatran in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞).

    This endpoint calculates area under the concentration-time curve of free dabigatran in plasma over the time interval from 0 extrapolated to infinity.

    Time frame: Samples were collected 1 hour Pre-dose and at 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 12:00, 24:00 36:00 and 48:00 hours post dose.

07

Results

Posted Jan 16, 2019

Participant flow

This was open label, 2 period, fixed sequence (RT), single arm study in 36 healthy male Japanese subjects. All subjects were orally treated with single dose of 110 milligram (mg) dabigatran etexilate (DE) tablet formulation alone in period 1 and with 20 mg rabeprazole tablet in period 2 with 4 days of rabeprazole pre-medication.

Period 1
Participant flow — Period 1
MilestoneDabigatran Etexilate 110 mg With and Without Rabeprazole 20 mg
Started36
Completed36
Not completed0
Period 2 (Washout of at Least 4 Days)
Participant flow — Period 2 (Washout of at Least 4 Days)
MilestoneDabigatran Etexilate 110 mg With and Without Rabeprazole 20 mg
Started36
Completed35
Not completed1
Withdrew: Withdrawal by subject1

Outcome measures

PrimaryArea Under the Plasma Concentration-time Curve From 0 to Time of Last Quantifiable Time Point (tz) of Total Dabigatran (AUC0-tz).

This endpoint calculates area under the concentration-time curve of total dabigatran in plasma over the time interval from 0 to the time of last quantifiable time point.

Time frame:
Samples were collected 1 hour Pre-dose and at 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 12:00, 24:00 36:00 and 48:00 hours post dose.
Reported as:
Geometric mean · Nanogram*Hour/ millilitre (ng*h/mL)
Area Under the Plasma Concentration-time Curve From 0 to Time of Last Quantifiable Time Point (tz) of Total Dabigatran (AUC0-tz).
Nanogram*Hour/ millilitre (ng*h/mL)Dabigatran Etexilate 110 mg (Reference)Dabigatran Etexilate 110 mg + Rabeprazole 20 mg Tablet (Test)
Area Under the Plasma Concentration-time Curve From 0 to Time of Last Quantifiable Time Point (tz) of Total Dabigatran (AUC0-tz).667 ± 123192 ± 109
Statistical analysis
  • Dabigatran Etexilate 110 mg (Reference) vs Dabigatran Etexilate 110 mg + Rabeprazole 20 mg Tablet (Test) · ANOVA · Adjusted gmean ratio test/reference (%): 28.85 · 90% CI 21.346 to 38.996The dispersion value standard error of the mean is actually intra individual geometric coefficient of variation (gCV) (%).
PrimaryMaximum Concentration of Total Dabigatran in Plasma (Cmax).

This outcome is maximum measured concentration of the total dabigatran in plasma

Time frame:
Samples were collected 1 hour Pre-dose and at 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 12:00, 24:00 36:00 and 48:00 hours post dose.
Reported as:
Geometric mean · Nano gram per milliliter (ng/mL)
Maximum Concentration of Total Dabigatran in Plasma (Cmax).
Nano gram per milliliter (ng/mL)Dabigatran Etexilate 110 mg (Reference)Dabigatran Etexilate 110 mg + Rabeprazole 20 mg Tablet (Test)
Maximum Concentration of Total Dabigatran in Plasma (Cmax).83.1 ± 11821.8 ± 105
Statistical analysis
  • Dabigatran Etexilate 110 mg (Reference) vs Dabigatran Etexilate 110 mg + Rabeprazole 20 mg Tablet (Test) · ANOVA · Adjusted gmean ratio test/reference (%): 26.37 · 90% CI 20.066 to 34.665The dispersion value standard error of the mean is actually intra individual geometric coefficient of variation (gCV) (%).
SecondaryArea Under the Plasma Concentration-time Curve From 0 to Time of Last Quantifiable Time Point (tz) of Free Dabigatran (AUC0-tz).

This endpoint calculates area under the concentration-time curve of free dabigatran in plasma over the time interval from 0 to the time of last quantifiable time point.

Time frame:
Samples were collected 1 hour Pre-dose and at 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 12:00, 24:00 36:00 and 48:00 hours post dose.
Reported as:
Geometric mean · Nanogram*Hour/ millilitre (ng*h/mL)
Area Under the Plasma Concentration-time Curve From 0 to Time of Last Quantifiable Time Point (tz) of Free Dabigatran (AUC0-tz).
Nanogram*Hour/ millilitre (ng*h/mL)Dabigatran Etexilate 110 mg (Reference)Dabigatran Etexilate 110 mg + Rabeprazole 20 mg Tablet (Test)
Area Under the Plasma Concentration-time Curve From 0 to Time of Last Quantifiable Time Point (tz) of Free Dabigatran (AUC0-tz).588 ± 119164 ± 110
Statistical analysis
  • Dabigatran Etexilate 110 mg (Reference) vs Dabigatran Etexilate 110 mg + Rabeprazole 20 mg Tablet (Test) · ANOVA · Adjusted gmean ratio test/reference (%): 28.02 · 90% CI 20.914 to 37.537The dispersion value standard error of the mean is actually intra individual geometric coefficient of variation (gCV) (%).
SecondaryMaximum Concentration of Free Dabigatran in Plasma (Cmax).

This outcome is maximum measured concentration of the free dabigatran in plasma

Time frame:
Samples were collected 1 hour Pre-dose and at 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 12:00, 24:00 36:00 and 48:00 hours post dose.
Reported as:
Geometric mean · Nanogram per milliliter (ng/mL)
Maximum Concentration of Free Dabigatran in Plasma (Cmax).
Nanogram per milliliter (ng/mL)Dabigatran Etexilate 110 mg (Reference)Dabigatran Etexilate 110 mg + Rabeprazole 20 mg Tablet (Test)
Maximum Concentration of Free Dabigatran in Plasma (Cmax).72.9 ± 11420.0 ± 103
Statistical analysis
  • Dabigatran Etexilate 110 mg (Reference) vs Dabigatran Etexilate 110 mg + Rabeprazole 20 mg Tablet (Test) · ANOVA · Adjusted gmean ratio test/reference (%): 27.56 · 90% CI 21.023 to 36.118The dispersion value standard error of the mean is actually intra individual geometric coefficient of variation (gCV) (%).
SecondaryArea Under the Concentration-time Curve of Total Dabigatran in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞).

This endpoint calculates area under the concentration-time curve of total dabigatran in plasma over the time interval from 0 extrapolated to infinity

Time frame:
Samples were collected 1 hour Pre-dose and at 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 12:00, 24:00 36:00 and 48:00 hours post dose.
Reported as:
Geometric mean · Nanogram*Hour/ millilitre (ng*h/mL)
Area Under the Concentration-time Curve of Total Dabigatran in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞).
Nanogram*Hour/ millilitre (ng*h/mL)Dabigatran Etexilate 110 mg (Reference)Dabigatran Etexilate 110 mg + Rabeprazole 20 mg Tablet (Test)
Area Under the Concentration-time Curve of Total Dabigatran in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞).702 ± 110214 ± 96.6
Statistical analysis
  • Dabigatran Etexilate 110 mg (Reference) vs Dabigatran Etexilate 110 mg + Rabeprazole 20 mg Tablet (Test) · ANOVA · Adjusted gmean ratio test/reference (%): 30.59 · 90% CI 23.260 to 40.234The dispersion value standard error of the mean is actually intra individual geometric coefficient of variation (gCV) (%).
SecondaryArea Under the Concentration-time Curve of Free Dabigatran in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞).

This endpoint calculates area under the concentration-time curve of free dabigatran in plasma over the time interval from 0 extrapolated to infinity.

Time frame:
Samples were collected 1 hour Pre-dose and at 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 12:00, 24:00 36:00 and 48:00 hours post dose.
Reported as:
Geometric mean · Nanogram*Hour/ millilitre (ng*h/mL)
Area Under the Concentration-time Curve of Free Dabigatran in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞).
Nanogram*Hour/ millilitre (ng*h/mL)Dabigatran Etexilate 110 mg (Reference)Dabigatran Etexilate 110 mg + Rabeprazole 20 mg Tablet (Test)
Area Under the Concentration-time Curve of Free Dabigatran in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞).618 ± 107188 ± 93.4
Statistical analysis
  • Dabigatran Etexilate 110 mg (Reference) vs Dabigatran Etexilate 110 mg + Rabeprazole 20 mg Tablet (Test) · ANOVA · Adjusted gmean ratio test/reference (%): 30.61 · 90% CI 23.404 to 40.037The dispersion value standard error of the mean is actually intra individual geometric coefficient of variation (gCV) (%).

Adverse events

Collected over From first drug administration until 3 days after the last drug administration. Up to 10 days.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Dabigatran Etexilate 110 mg (Reference)0/36 (0%)0/36 (0%)0/36 (0%)
Dabigatran Etexilate 110 mg + Rabeprazole 20 mg (Test)0/35 (0%)0/35 (0%)0/35 (0%)

Baseline characteristics

Treated set (TS) : All enrolled subjects provided with trial medication and documented to have taken at least 1 dose of trial medication were included in the TS.

Age, Continuous
Age, Continuous(Years)Total Subjects
Mean26.3 ± 4.7
Sex: Female, Male
Sex: Female, Male(Participants)Total Subjects
Female0
Male36
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Total Subjects
Hispanic or Latino0
Not Hispanic or Latino36
Unknown or Not Reported0
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Total Subjects
American Indian or Alaska Native0
Asian36
Native Hawaiian or Other Pacific Islander0
Black or African American0
White0
More than one race0
Unknown or Not Reported0
08

Study locations

1 site
  • Souseikai Hakata Clinic
    Fukuoka, Fukuoka, 812-0025, 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 · Aug 23, 2017
  • Study protocol · Apr 20, 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 16, 2019, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT03143166
Lead sponsor
Boehringer Ingelheim
Responsible party
Sponsor
First posted
May 8, 2017
Start date
May 22, 2017
Primary completion
Jul 27, 2017
Completion
Aug 2, 2017
Results posted
Jan 16, 2019
Last update
Jan 16, 2019

Oversight

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

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