Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 12 of 332 for:    DABIGATRAN

Relative Bioavailability of Single Doses of Dabigatran Etexilate in Healthy Volunteers

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02173717
Recruitment Status : Completed
First Posted : June 25, 2014
Last Update Posted : June 25, 2014
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim

Brief Summary:
Study to investigate whether and to what extent the suggested P-glycoprotein (P-gp) inducer rifampicin affects plasma exposure of dabigatran.

Condition or disease Intervention/treatment Phase
Healthy Drug: Dabigatran etexilate Drug: Rifampicin Phase 1

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 24 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Relative Bioavailability of Single Doses of 150 mg Dabigatran Etexilate (Capsule)When Administered Alone, After Seven Days of Dosing With 600 mg Rifampicin(Tablet), and Seven Days and Fourteen Days After Last Administration of Rifampicin in Healthy Male and Female Volunteers (an Open Label, Fixed Sequence, Phase I Study)
Study Start Date : June 2009
Actual Primary Completion Date : July 2009

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Dabigatran etexilate

Four treatments of 150 mg Dabigatran etexilate (single oral administration) in a fixed sequence.

  1. Single oral administration of dabigatran etexilate on Day 1;
  2. Oral administration of 600 mg rifampicin q.d. in the evening for 7 days (Days 2 to 8) followed by an oral morning dose of dabigatran etexilate on Day 9;
  3. Single oral administration of dabigatran etexilate on Day 16, after 7 days of rifampicin washout;
  4. Single oral administration of dabigatran etexilate on Day 23, after 14 days of rifampicin washout
Drug: Dabigatran etexilate
150 mg Dabigatran etexilate
Other Names:
  • Pradaxa®
  • BIBR 1048 MS

Drug: Rifampicin
600 mg Rifampicin
Other Name: Rifa® 600




Primary Outcome Measures :
  1. Area under the concentration-time curve over the time interval from 0 extrapolated to infinity (AUC0-inf) of total dabigatran [ Time Frame: 30 min pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 and 34 hours after treatment on Day1, 9, 16 and 23 ]
  2. Maximum measured concentration (Cmax) of total dabigatran [ Time Frame: 30 min pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 and 334hours after treatment on Day1, 9, 16 and 23 ]

Secondary Outcome Measures :
  1. AUC0-inf of free dabigatran [ Time Frame: 30 min pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 and 34 hours after treatment on Day1, 9, 16 and 23 ]
  2. Cmax of free dabigatran [ Time Frame: 30 min pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 and 34 hours after treatment on Day1, 9, 16 and 23 ]
  3. Cmax of dabigatran etexilate [ Time Frame: 30 min pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 and 34 hours after treatment on Day1, 9, 16 and 23 ]
  4. Time from dosing to the maximum concentration (tmax) of dabigatran etexilate [ Time Frame: 30 min pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 and 34 hours after treatment on Day1, 9, 16 and 23 ]
  5. Cmax of BIBR 1087SE [ Time Frame: 30 min pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 and 34 hours after treatment on Day1, 9, 16 and 23 ]
  6. tmax of BIBR 1087SE [ Time Frame: 30 min pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 and 34 hours after treatment on Day1, 9, 16 and 23 ]
  7. Cmax of BIBR 951BS [ Time Frame: 30 min pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 and 34 hours after treatment on Day1, 9, 16 and 23 ]
  8. tmax of BIBR 951BS [ Time Frame: 30 min pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 and 34 hours after treatment on Day1, 9, 16 and 23 ]
  9. Area under the concentration-time curve over the time interval from 0 to the time of the last quantifiable data point (AUC0-tz) of free dabigatran [ Time Frame: 30 min pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 and 34 hours after treatment on Day1, 9, 16 and 23 ]
  10. AUC0-tz of total dabigatran [ Time Frame: 30 min pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 and 34 hours after treatment on Day1, 9, 16 and 23 ]
  11. Area under the concentration-time curve over the time interval from timepoints t1 to t2 (AUCt1-t2) of free dabigatran [ Time Frame: 30 min pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 and 34 hours after treatment on Day1, 9, 16 and 23 ]
  12. AUCt1-t2 of total dabigatran [ Time Frame: 30 min pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 and 34 hours after treatment on Day1, 9, 16 and 23 ]
  13. Area under the concentration-time curve over the time interval from 0 to 24 h (AUC0-24) of free dabigatran [ Time Frame: 30 min pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 and 34 hours after treatment on Day1, 9, 16 and 23 ]
  14. AUC0-24 of total dabigatran [ Time Frame: 30 min pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 and 34 hours after treatment on Day1, 9, 16 and 23 ]
  15. tmax of free dabigatran [ Time Frame: 30 min pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 and 34 hours after treatment on Day1, 9, 16 and 23 ]
  16. tmax of total dabigatran [ Time Frame: 30 min pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 and 34 hours after treatment on Day1, 9, 16 and 23 ]
  17. Terminal rate constant (λz) of free dabigatran [ Time Frame: 30 min pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 and 34 hours after treatment on Day1, 9, 16 and 23 ]
  18. λz of total dabigatran [ Time Frame: 30 min pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 and 34 hours after treatment on Day1, 9, 16 and 23 ]
  19. Terminal half-life (t1/2) of free dabigatran [ Time Frame: 30 min pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 and 34 hours after treatment on Day1, 9, 16 and 23 ]
  20. t1/2 of total dabigatran [ Time Frame: 30 min pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 and 34 hours after treatment on Day1, 9, 16 and 23 ]
  21. Mean residence time after oral administration (MRTpo) of free dabigatran [ Time Frame: 30 min pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 and 34 hours after treatment on Day1, 9, 16 and 23 ]
  22. MRTpo of total dabigatran [ Time Frame: 30 min pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 and 34 hours after treatment on Day1, 9, 16 and 23 ]
  23. Apparent clearance after extravascular administration (CL/F) of free dabigatran [ Time Frame: 30 min pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 and 34 hours after treatment on Day1, 9, 16 and 23 ]
  24. CL/F of total dabigatran [ Time Frame: 30 min pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 and 34 hours after treatment on Day1, 9, 16 and 23 ]
  25. Apparent volume of distribution during the terminal phase λz following an extravascular dose (Vz/F) of free dabigatran [ Time Frame: 30 min pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 and 34 hours after treatment on Day1, 9, 16 and 23 ]
  26. Vz/F of total dabigatran [ Time Frame: 30 min pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 and 34 hours after treatment on Day1, 9, 16 and 23 ]
  27. Amount that is eliminated in urine from the time interval 0- 24h (Ae0-24) of total dabigatran [ Time Frame: Day 1 and 9 ]
  28. Fraction excreted unchanged in urine from time point 0-24h (fe0-24) of total dabigatran [ Time Frame: Day 1 and 9 ]
  29. Renal clearance from the time point 0 until the point 0-24h (CLR, 0-24) of total dabigatran [ Time Frame: Day 1 and 9 ]
  30. Ratio of 6-ß-hydroxycortisol/cortisol in morning spot urine as a marker of CYP 3A induction [ Time Frame: Day 1 and 9 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy male or female subjects according to the following criteria: based upon a complete medical history, including the physical examination, vital signs (BP, pulse rate), 12-lead ECG, clinical laboratory tests
  • Age ≥18 and Age ≤45 years
  • Body Mass Index (BMI) ≥18.5 and ≤29.9 kg/m2
  • Signed and dated written informed consent prior to admission to the study in accordance with GCP and the local legislation

Exclusion Criteria:

  • Any gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological, or hormonal disorders
  • Subjects who in the investigator's judgement were perceived as having an increased risk of bleeding, for example because of:

    • Hemorrhagic disorders or bleeding diathesis
    • Occult blood in faeces or haematocryal
    • Trauma or surgery within the last month or as long as an excessive risk of bleeding persisted after these events, or planned surgery during trial participation
    • History of arteriovenous malformation or aneurysm
    • History of gastroduodenal ulcer disease, gastrointestinal haemorrhage, and haemorrhoids
    • History of intracranial, intraocular, spinal, retroperitoneal, or atraumatic intraarticular bleeding
    • Use of drugs that may have interfered with haemostasis during trial conduct (e.g. acetylic salicylic acid or other non-steroidal anti-inflammatory drugs)
    • Relevant surgery of gastrointestinal tract
  • 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 allergy/hypersensitivity (including drug allergy) which was deemed relevant to the trial as judged by the investigator
  • Use of drugs which might have reasonably influenced the results of the trial based on the knowledge at the time of protocol preparation within four weeks prior to administration or during the trial, especially inhibitors or inducers of P-gp, CYP3A4, CYP2C9, or CYP2C19 trial (comment: CYP3A4 inhibitors are for example azole antimycotics, macrolides or grapefruit juice, CYP3A inducers are for example St. John's Wort or certain anticonvulsants)
  • Intake of medication, which influences the blood clotting, i.e. acetylsalicylic acid, nonsteroidal anti-rheumatic drugs, cumarin, etc. within 14 days prior to screening or during the trial
  • Participation in another trial with an investigational drug within one month prior to administration or during the trial
  • Alcohol abuse (more than 60 g/day in males, more than 40 g/day in females)
  • Drug abuse
  • Blood donation (more than 100 mL within 4 weeks prior to administration)
  • Any laboratory value outside the reference range that was of clinical relevance
  • Inability to comply with dietary regimen of study centre
  • Previous intake of rifampicin
  • For female subjects:

    • Pregnancy / positive pregnancy test, or planning to become pregnant during the study or within 1 month of study completion
    • No adequate contraception in women of childbearing potential
    • Lactation period

Layout table for additonal information
Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT02173717     History of Changes
Other Study ID Numbers: 1160.100
First Posted: June 25, 2014    Key Record Dates
Last Update Posted: June 25, 2014
Last Verified: June 2014
Additional relevant MeSH terms:
Layout table for MeSH terms
Dabigatran
Rifampin
Antithrombins
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anticoagulants
Antibiotics, Antitubercular
Antitubercular Agents
Anti-Bacterial Agents
Anti-Infective Agents
Leprostatic Agents
Nucleic Acid Synthesis Inhibitors
Cytochrome P-450 CYP2B6 Inducers
Cytochrome P-450 Enzyme Inducers
Cytochrome P-450 CYP2C8 Inducers
Cytochrome P-450 CYP2C19 Inducers
Cytochrome P-450 CYP2C9 Inducers
Cytochrome P-450 CYP3A Inducers