Relative Bioavailability of Dabigatran and Diclofenac After Dabigatran Etexilate and Diclofenac Single Dose Alone or Following Concomitant Multiple Oral Administrations in Healthy Male and Female Volunteers

June 20, 2014 updated by: Boehringer Ingelheim

Relative Bioavailability of Dabigatran and Diclofenac After 150 mg b.i.d. Dabigatran Etexilate and Diclofenac at 50 mg Single Dose Alone or Following Concomitant Multiple Oral Administrations in Healthy Male and Female Volunteers (an Open Label, Randomised, Multiple- Dose, Three-way Crossover Study)

To investigate the relative bioavailability of dabigatran with and without concomitant administration of diclofenac and the relative bioavailability of diclofenac with and without concomitant administration of dabigatran etexilate

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
24

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 55 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion criteria:

  1. Healthy males and females according to the following criteria: Based upon a complete medical history, including the physical examination, vital signs (blood pressure, pulse rate), 12-lead electrocardiogram, clinical laboratory tests
  2. Age ≥18 and ≤55 years
  3. Body mass index (BMI) ≥18.5 and BMI ≤29.9 kg/m2
  4. Signed and dated written informed consent prior to admission to the study in accordance with GCP (Good Clinical Practice) and the local legislation

Exclusion criteria:

  1. Clinically relevant gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
  2. Relevant surgery of gastrointestinal tract
  3. History of any bleeding disorder including history of gastrointestinal erosions and ulcer or acute blood coagulation defect
  4. Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders
  5. History of relevant orthostatic hypotension, fainting spells or blackouts
  6. Chronic or relevant acute infections
  7. History of allergy/hypersensitivity (including drug allergy) which is deemed relevant to the objectives of the trial as judged by the investigator
  8. 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
  9. Use of drugs which might reasonably influence the results of the trial based on the knowledge at the time of protocol preparation within 10 days prior to administration or during the trial
  10. Participation in another trial with an investigational drug within two months prior to administration or during the trial
  11. Alcohol abuse (more than 60 g/day)
  12. Drug abuse
  13. Blood donation (more than 100 mL within four weeks prior to administration or during the trial)
  14. Excessive physical activities (within one week prior to administration or during the trial)
  15. Any laboratory value outside the reference range that is of clinical relevance
  16. Subjects with abnormal thrombocyte counts and any relevant deviation in the assessment of platelet function (PFA test) must be excluded
  17. Inability to comply with dietary regimen of study centre
  18. Females of child bearing potential who are pregnant, breast feeding or who are either not surgically sterile or are sexually active and not using an acceptable form of contraception as either the oral contraceptives since at least two months and the double barrier method, i.e. intrauterine device with spermicide and condom for the male partner
  19. Male subjects must agree to minimize the risk of female partners becoming pregnant from the first dosing day until 3 months after the completion of the post study medical examination. Acceptable methods of contraception comprises barrier contraception and a medically accepted contraceptive method for the female partner (intra-uterine device with spermicide, hormonal contraceptive since at least two month)
  20. Planned surgeries within four weeks following the end-of study examination
  21. Intake of medication, which influences the blood clotting, i.e., acetylsalicylic acid, cumarin etc.
  22. The subject is able to understand and comply with protocol requirements, instructions and protocol-stated restrictions
  23. Vulnerable subjects (e.g. persons kept in detention).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Diclofenac
Drug: Diclofenac
Active Comparator: Dabigatran etexilate
Drug: Dabigatran etexilate
Experimental: Dabigatran etexilate + diclofenac
Drug: Dabigatran etexilate
Drug: Diclofenac

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
AUCτ,ss on Day 4 (area under the concentration-time curve of dabigatran in plasma at steady state over one dosing interval)
Time Frame: from pre-dose up to 72 hours post-dose
from pre-dose up to 72 hours post-dose
Cmax,ss (maximum concentration of dabigatran in plasma at steady state)
Time Frame: from pre-dose up to 72 hours post-dose
from pre-dose up to 72 hours post-dose
Cmax (maximal concentration of diclofenac in plasma)
Time Frame: from pre-dose up to 72 hours post-dose
from pre-dose up to 72 hours post-dose
AUC0-infinity (area under the concentration-time curve of diclofenac in plasma extrapolated to infinity)
Time Frame: from pre-dose up to 72 hours post-dose
from pre-dose up to 72 hours post-dose
aPTT (activated partial thromboplastin time) and ECT (Ecarin clotting time) with and without diclofenac
Time Frame: from pre-dose up to 72 hours post-dose
from pre-dose up to 72 hours post-dose
AUERτ,ss (area under the effect ratio-time curve of dabigatran in plasma at steady state over a uniform dosing interval τ)
Time Frame: from pre-dose up to 72 hours post-dose
from pre-dose up to 72 hours post-dose
ERmax,ss (maximal effect ratio of dabigatran in plasma at steady state)
Time Frame: from pre-dose up to 72 hours post-dose
from pre-dose up to 72 hours post-dose

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
AUC0-tz,ss (area under the concentration-time curve of dabigatran in plasma from the time point 0 after the last dose at steady state to the last quantifiable dabigatran plasma concentration within the uniform dosing interval τ)
Time Frame: from pre-dose up to 72 hours post-dose
from pre-dose up to 72 hours post-dose
tz,ss (time of last measurable concentration of dabigatran in plasma within the dosing interval τ at steady state)
Time Frame: from pre-dose up to 72 hours post-dose
from pre-dose up to 72 hours post-dose
tmax,ss (time from last dosing to the maximum concentration of dabigatran in plasma at steady state on Day 4)
Time Frame: from pre-dose up to 72 hours post-dose
from pre-dose up to 72 hours post-dose
CL/Fss (apparent clearance of dabigatran in the plasma at steady state after extravascular multiple dose administration)
Time Frame: from pre-dose up to 72 hours post-dose
from pre-dose up to 72 hours post-dose
CLR,ss (renal clearance of dabigatran at steady state determined over the dosing interval τ)
Time Frame: from pre-dose up to 72 hours post-dose
from pre-dose up to 72 hours post-dose
C min,ss (minimum measured concentration of dabigatran in plasma at steady state over a uniform dosing interval τ)
Time Frame: from pre-dose up to 72 hours post-dose
from pre-dose up to 72 hours post-dose
tmin,ss (time from last dosing to the minimum concentration of dabigatran in plasma at steady state over a uniform dosing interval τ)
Time Frame: from pre-dose up to 72 hours post-dose
from pre-dose up to 72 hours post-dose
Cpre,ss (pre-dose concentration of dabigatran in plasma at steady state immediately before administration of the next dose)
Time Frame: from pre-dose up to 72 hours post-dose
from pre-dose up to 72 hours post-dose
MRTp.o.,ss (mean residence time of dabigatran in the body at steady state after oral administration)
Time Frame: from pre-dose up to 72 hours post-dose
from pre-dose up to 72 hours post-dose
Vz/Fss (apparent volume of distribution during the terminal phase λz at steady state following an extravascular administration)
Time Frame: from pre-dose up to 72 hours post-dose
from pre-dose up to 72 hours post-dose
Aeτ,ss (amount of dabigatran that is eliminated in urine at steady state over a uniform dosing interval τ)
Time Frame: 0 to 12 h and 12 to 24 h after administration on day 4
0 to 12 h and 12 to 24 h after administration on day 4
feτ,ss (fraction of parent drug eliminated in urine at steady state over a uniform dosing interval τ)
Time Frame: 0 to 12 h and 12 to 24 h after administration on day 4
0 to 12 h and 12 to 24 h after administration on day 4
AUC0-tz (area under the concentration-time curve of diclofenac and 4´- hydroxydiclofenac in plasma over the time interval 0 to the last quantifiable analyte plasma concentration after single dose administration)
Time Frame: from pre-dose up to 72 hours post-dose
from pre-dose up to 72 hours post-dose
tz (time of last measurable concentration of diclofenac and 4´- hydroxydiclofenac in plasma following a single dose)
Time Frame: from pre-dose up to 72 hours post-dose
from pre-dose up to 72 hours post-dose
%AUCtz-infinity (percentage of the AUC0-infinity that is obtained by extrapolation) for diclofenac and 4´- hydroxydiclofenac
Time Frame: from pre-dose up to 72 hours post-dose
from pre-dose up to 72 hours post-dose
tmax (time from dosing to the maximum concentration of diclofenac and 4´- hydroxydiclofenac in plasma following a single dose)
Time Frame: from pre-dose up to 72 hours post-dose
from pre-dose up to 72 hours post-dose
λz (terminal rate constant in plasma after a single dose) for diclofenac and 4´- hydroxydiclofenac
Time Frame: from pre-dose up to 72 hours post-dose
from pre-dose up to 72 hours post-dose
t1/2 (terminal half-life of diclofenac and 4´- hydroxydiclofenac in plasma after a single dose)
Time Frame: from pre-dose up to 72 hours post-dose
from pre-dose up to 72 hours post-dose
MRTp.o. (mean residence time of diclofenac and 4´- hydroxydiclofenac in the body after single dose oral administration)
Time Frame: from pre-dose up to 72 hours post-dose
from pre-dose up to 72 hours post-dose
CL/F (apparent clearance of diclofenac and 4´- hydroxydiclofenac in the plasma after extravascular single dose administration)
Time Frame: from pre-dose up to 72 hours post-dose
from pre-dose up to 72 hours post-dose
Vz/F (apparent volume of distribution during the terminal phase λz following extravascular dose) for diclofenac and 4´- hydroxydiclofenac
Time Frame: from pre-dose up to 72 hours post-dose
from pre-dose up to 72 hours post-dose

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Boehringer Ingelheim

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 1, 2006

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 1, 2006

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 20, 2014

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 20, 2014

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 24, 2014

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 24, 2014

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 20, 2014

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2014

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 1160.7

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