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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| All participants | Experimental | Dabigatran etexilate given without rabeprazole and then Dabigatran etexilate given without rabeprazole. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Dabigatran Etexilate | Drug | Tablet, film coated |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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. |
| Maximum Concentration of Total Dabigatran in Plasma (Cmax). | This outcome is maximum measured concentration of the total dabigatran in plasma | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Souseikai Hakata Clinic | Fukuoka, Fukuoka | 812-0025 | Japan |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31667735 | Derived | 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. |
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After it had been determined that the subject met all eligibility criteria, a unique subject number was assigned. The number was recorded on electronic Case Report Forms and correspondence regarding the subject. Once a subject number had been assigned, it could not be reassigned to any other subject. Randomisation was not planned in this study.
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.
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| ID | Title | Description |
|---|---|---|
| FG000 | Dabigatran Etexilate 110 mg With and Without Rabeprazole 20 mg | Subjects were treated orally with dabigatran etexilate 110 mg tablet alone (Reference) after an overnight fast of at least 10 hours (h) without pretreatment with rabeprazole 20 mg tablet in period 1 followed by single dose of dabigatran etexilate 110 mg tablet and rabeprazole 20 mg tablets (Test) once daily with 4 days of rabeprazole pre-treatment in period 2. The treatments of dabigatran etexilate were separated by a wash-out phase of at least 4 days. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Period 1 |
| |||||||||||||
| Period 2 (Washout of at Least 4 Days) |
|
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.
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| ID | Title | Description |
|---|---|---|
| BG000 | Total Subjects | Subjects were treated orally with dabigatran etexilate 110 mg tablet alone (Reference) after an overnight fast of at least 10 hours (h) without pretreatment with rabeprazole 20 mg tablet in period 1 followed by single dose of dabigatran etexilate 110 mg tablet and rabeprazole 20 mg tablets (Test) once daily with 4 days of rabeprazole pre-treatment in period 2. The treatments of dabigatran etexilate were separated by a wash-out phase of at least 4 days. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Age of all subjects enrolled in the study. |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Pharmacokinetic set (PKS): All treated subjects who provided at least 1 observation for at least 1 primary endpoint without important protocol violations with respect to the statistical evaluation of Pharmacokinetic (PK) endpoints were included in PKS. | Posted | Geometric Mean | Geometric Coefficient of Variation | Nanogram*Hour/ millilitre (ng*h/mL) | 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. |
|
From first drug administration until 3 days after the last drug administration. Up to 10 days.
An adverse event (AE) was defined as any untoward medical occurrence in a subject or clinical investigation subject administered a medicinal product and which did not necessarily have to have a causal relationship with this treatment. Treated Set was used for assessment of AEs.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Dabigatran Etexilate 110 mg (Reference) | Subjects were treated orally with dabigatran etexilate 110 mg tablet alone after an overnight fast of at least 10 hours (h) without pre-treatment with rabeprazole 20 mg tablet. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Boehringer Ingelheim, Call Center | Boehringer Ingelheim | 1-800-243-0127 | clintriage.rdg@boehringer-ingelheim.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| SAP | No | Yes | No | Statistical Analysis Plan | Aug 23, 2017 | Jul 24, 2018 | SAP_000.pdf |
| Prot | Yes | No | No | Study Protocol | Apr 20, 2017 | Jul 24, 2018 | Prot_001.pdf |
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| ID | Term |
|---|---|
| D065626 | Non-alcoholic Fatty Liver Disease |
| ID | Term |
|---|---|
| D005234 | Fatty Liver |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
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| ID | Term |
|---|---|
| D000069604 | Dabigatran |
| D000077333 | Telmisartan |
| ID | Term |
|---|---|
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D001562 | Benzimidazoles |
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| Rabeprazol sodium | Drug | Tablet |
|
| Maximum Concentration of Free Dabigatran in Plasma (Cmax). | This outcome is maximum measured concentration of the free dabigatran in plasma | 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. |
| 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 | 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. |
| 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. | 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. |
|
TS
| Mean |
| Standard Deviation |
| Years |
|
| Sex: Female, Male | Gender distribution of all subjects enrolled in the study. | TS | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Ethnicity of all subjects enrolled in the study. | TS | Count of Participants | Participants |
|
| Race (NIH/OMB) | Race of all subjects enrolled in the study. | TS | Count of Participants | Participants |
|
| OG001 | Dabigatran Etexilate 110 mg + Rabeprazole 20 mg Tablet (Test) | Subjects were treated orally with single dose of dabigatran etexilate 110 mg tablet and rabeprazole 20 mg tablets once daily with 4 days of rabeprazole pre-treatment. |
|
|
|
| Primary | Maximum Concentration of Total Dabigatran in Plasma (Cmax). | This outcome is maximum measured concentration of the total dabigatran in plasma | PKS | Posted | Geometric Mean | Geometric Coefficient of Variation | Nano gram per milliliter (ng/mL) | 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 | 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. | PKS | Posted | Geometric Mean | Geometric Coefficient of Variation | Nanogram*Hour/ millilitre (ng*h/mL) | 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 | Maximum Concentration of Free Dabigatran in Plasma (Cmax). | This outcome is maximum measured concentration of the free dabigatran in plasma | PKS | Posted | Geometric Mean | Geometric Coefficient of Variation | Nanogram per milliliter (ng/mL) | 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 | 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 | PKS | Posted | Geometric Mean | Geometric Coefficient of Variation | Nanogram*Hour/ millilitre (ng*h/mL) | 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 | 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. | PKS | Posted | Geometric Mean | Geometric Coefficient of Variation | Nanogram*Hour/ millilitre (ng*h/mL) | 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. |
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|
| 0 |
| 36 |
| 0 |
| 36 |
| 0 |
| 36 |
| EG001 | Dabigatran Etexilate 110 mg + Rabeprazole 20 mg (Test) | Subjects were treated orally with single dose of dabigatran etexilate 110 mg tablet and rabeprazole 20 mg tablets once daily with 4 days of rabeprazole pre-treatment. | 0 | 35 | 0 | 35 | 0 | 35 |
Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
| D006574 |
| Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D001713 | Biphenyl Compounds |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |