Clinical trial NCT02171611: Bioavailability of Different Applications of Dabigatran in Healthy Volunteers
Official title: Relative Bioavailability of Dabigatran After Administration of Different Application Forms of a Single Oral Dose of 150 mg Dabigatran Etexilate (Capsule, Powder for Reconstitution Into Solution, Pellets on Food) in Healthy Male and Female Volunteers (an Open-label, Randomised, Three-way Crossover, Clinical Phase I Study)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2014-06-24
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: To determine the relative bioavailability of 150 mg of dabigatran etexilate as pellets on food and of 150 mg of dabigatran etexilate as powder resolved in reconstitution solution, both with 150 mg of dabigatran etexilate as capsule in healthy volunteers


Eligibility criteria: Inclusion Criteria:

* Healthy males and females according to the following criteria: Based upon a complete medical history, including the physical examination, vital signs (BP, PR), 12-lead ECG, clinical laboratory tests
* Age ≥18 and age ≤50 years
* BMI ≥18.5 and BMI ≤29.9 kg/m2 (Body Mass Index)
* Signed and dated written informed consent prior to admission to the study in accordance with GCP and the local legislation

Exclusion Criteria:

* Any finding of the medical examination (including BP, PR and ECG) deviating from normal and of clinical relevance
* Any evidence of a clinically relevant concomitant disease
* Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
* Surgery of the gastrointestinal tract (except appendectomy)
* Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders
* History of relevant orthostatic hypotension, fainting spells or blackouts
* Chronic or relevant acute infections
* History of relevant allergy/hypersensitivity (including allergy to drug or its excipients)
* 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
* Use of drugs which could reasonably influence the results of the trial (especially unspecific inducing agents like St. John´s wort (Hypericum perforatum) or that prolong the QT/QTc interval based on the knowledge at the time of protocol preparation within 10 days prior to administration or during the trial
* Participation in another trial with an investigational drug within two months prior to administration or during the trial
* Smoker (\> 10 cigarettes or \> 3 cigars or \> 3 pipes/day)
* Inability to refrain from smoking on trial days
* Alcohol abuse (more than 60 g/day)
* Drug abuse
* Blood donation (more than 100 mL within four weeks prior to administration or during the trial)
* Excessive physical activities (within one week prior to administration or during the trial)
* Any laboratory value outside the reference range that was of clinical relevance
* Inability to comply with dietary regimen of trial site
* A marked baseline prolongation of QT/QTc interval (e.g. repeated demonstration of a QTc interval \>450 ms)
* A history of additional risk factors for Torsade de Pointes (e.g. heart failure, hypokalemia, family history of Long QT Syndrome)
* For female subjects:

  * Positive pregnancy test, pregnancy or planning to become pregnant during the study or within 1 month after study completion
  * No adequate contraception during the study and until 1 month after study completion, i.e. not any of the following: implants, injectables, combined oral contraceptives, intrauterine device (IUD), sexual abstinence for at least 1 month prior to enrolment, vasectomised partner (vasectomy performed at least 1 year prior to enrolment), or surgical sterilisation (including hysterectomy). Females, who did not have a vasectomised partner, were not sexually abstinent or surgically sterile were to be asked to use an additional barrier method (e.g. condom, diaphragm with spermicide)
  * Lactation
* Intake of medication, which influences the blood clotting, i.e. acetylsalicylic acid, oral vitamin K antagonists etc.

Primary outcomes:
measure: AUC0-inf for Total Dabigatran
timeFrame: -0:30 hour(h) before drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 3:30h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h and 48:00h after drug administration.
measure: AUC0-inf for Free Dabigatran
timeFrame: -0:30 hour(h) before drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 3:30h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h and 48:00h after drug administration.
measure: Cmax for Total Dabigatran
timeFrame: -0:30 hour(h) before drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 3:30h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h and 48:00h after drug administration.
measure: Cmax for Free Dabigatran
timeFrame: -0:30 hour(h) before drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 3:30h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h and 48:00h after drug administration.
Secondary outcomes:
measure: AUC0-tz for Total Dabigatran
timeFrame: -0:30 hour(h) before drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 3:30h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h and 48:00h after drug administration.
measure: AUC0-tz for Free Dabigatran
timeFrame: -0:30 hour(h) before drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 3:30h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h and 48:00h after drug administration.
measure: Tmax for Total Dabigatran
timeFrame: -0:30 hour(h) before drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 3:30h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h and 48:00h after drug administration.
measure: Tmax for Free Dabigatran
timeFrame: -0:30 hour(h) before drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 3:30h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h and 48:00h after drug administration.
measure: λz for Total Dabigatran
timeFrame: -0:30 hour(h) before drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 3:30h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h and 48:00h after drug administration.
measure: λz for Free Dabigatran
timeFrame: -0:30 hour(h) before drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 3:30h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h and 48:00h after drug administration.
measure: t1/2 for Total Dabigatran
timeFrame: -0:30 hour(h) before drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 3:30h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h and 48:00h after drug administration.
measure: t1/2 for Free Dabigatran
timeFrame: -0:30 hour(h) before drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 3:30h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h and 48:00h after drug administration.
measure: MRTpo for Total Dabigatran
timeFrame: -0:30 hour(h) before drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 3:30h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h and 48:00h after drug administration.
measure: MRTpo for Free Dabigatran
timeFrame: -0:30 hour(h) before drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 3:30h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h and 48:00h after drug administration.
measure: CL/F for Total Dabigatran
timeFrame: -0:30 hour(h) before drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 3:30h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h and 48:00h after drug administration.
measure: CL/F for Free Dabigatran
timeFrame: -0:30 hour(h) before drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 3:30h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h and 48:00h after drug administration.
measure: Vz/F for Total Dabigatran
timeFrame: -0:30 hour(h) before drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 3:30h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h and 48:00h after drug administration.
measure: Vz/F for Free Dabigatran
timeFrame: -0:30 hour(h) before drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 3:30h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h and 48:00h after drug administration.
measure: Percentage of Participants With Findings in Physical Examination, Vital Signs , Pulse Rate (PR)), 12-lead ECG, Clinical Laboratory Tests.
timeFrame: From first drug administration until 7 days after the last drug administration of Dabigatran, ie., up to 10 days.
measure: Percentage of Participants With Drug-related Adverse Events
timeFrame: From first drug administration until 7 days after the last drug administration of Dabigatran, ie., up to 10 days.
measure: Assessment of Tolerability by Investigator.
timeFrame: From first drug administration until 7 days after the last drug administration of Dabigatran, ie., up to 10 days.
Other outcomes:
Locations:
Study officials:
References: