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Bioequivalence of Tablet Formulation of Dabigatran Etexilate Compared to Commercial Capsule Formulation Following Oral Administration in Healthy Male Subjects

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ClinicalTrials.gov Identifier: NCT03070171
Recruitment Status : Completed
First Posted : March 3, 2017
Results First Posted : January 9, 2019
Last Update Posted : January 9, 2019
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim

Brief Summary:

The primary objective of this trial is to establish the bioequivalence of tablet formulation of dabigatran etexilate compared to commercial capsule formulation following oral administration under fasted condition.

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


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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 160 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Bioequivalence of Tablet Formulation of Dabigatran Etexilate Compared to Commercial Capsule Formulation Following Oral Administration in Healthy Male Subjects (an Open-label, Randomised, Single-dose, Replicate Design in a Two-treatment, Four-period, Two-sequence Crossover Study)
Actual Study Start Date : March 21, 2017
Actual Primary Completion Date : June 16, 2017
Actual Study Completion Date : June 20, 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Dabigatran Etexilate Capsule Drug: dabigatran etexilate
single dose
Other Name: PRADAXA

Experimental: Dabigatran Etexilate Tablet Drug: dabigatran etexilate
single dose
Other Name: PRADAXA




Primary Outcome Measures :
  1. AUC0-tz of Free Dabigatran [ Time Frame: 1:00h before drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 3:00h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h and 48:00h after drug administration. ]

    Area under the concentration-time curve of free dabigatran in plasma over the time interval from 0 to the time of the last quantifiable data point (AUC0-tz). Geometric Mean (gMean) is actually Adjusted gMean & Geometric Coefficient of Variation (gCV) is actually Intra individual gCV (%gCV).

    PK exclusion criteria: 1) The subject experienced emesis at or before 2 times median Time from (last) dosing to the maximum measured concentration of the analyte in plasma (tmax). Median tmax was to be taken either from the median tmax for reference product or test product, depending on whether the subject had experienced emesis after taken the test or reference product. Median tmax was to be determined excluding the subjects experiencing emesis. 2) Time deviations 3) Use of restricted medications 4) A pre-dose concentration was >5% of the Cmax value of that subject.


  2. Cmax of Free Dabigatran [ Time Frame: 1:00h before drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 3:00h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h and 48:00h after drug administration. ]
    Maximum plasma concentration of free dabigatran (Cmax). Geometric Mean is actually Adjusted geometric mean and Geometric Coefficient of Variation (gCV) is actually Intra individual gCV.


Secondary Outcome Measures :
  1. AUC0-tz of Total Dabigatran [ Time Frame: 1:00h before drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 3:00h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h and 48:00h after drug administration. ]

    Area under the concentration-time curve of total dabigatran in plasma over the time interval from 0 to the time of the last quantifiable data point (AUC0-tz ).

    Geometric Mean is actually Adjusted geometric mean and Geometric Coefficient of Variation (gCV) is actually Intra individual gCV.


  2. Cmax of Total Dabigatran [ Time Frame: 1:00h before drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 3:00h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h and 48:00h after drug administration. ]
    Maximum plasma concentration of total dabigatran (Cmax). Geometric Mean is actually Adjusted geometric mean and Geometric Coefficient of Variation (gCV) is actually Intra individual gCV.

  3. AUC0-∞ of Total Dabigatran [ Time Frame: 1:00h before drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 3:00h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h and 48:00h after drug administration. ]

    Area under the concentration-time curve of total dabigatran in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞).

    Geometric Mean is actually Adjusted geometric mean and Geometric Coefficient of Variation (gCV) is actually Intra individual gCV.


  4. AUC0-∞ of Free Dabigatran [ Time Frame: 1:00h before drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 3:00h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h and 48:00h after drug administration. ]

    Area under the concentration-time curve of free dabigatran in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞).

    Geometric Mean is actually Adjusted geometric mean and Geometric Coefficient of Variation (gCV) is actually Intra individual gCV.




Information from the National Library of Medicine

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Ages Eligible for Study:   20 Years to 40 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

Subjects will only be included into the trial, if they meet the following 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 old at informed consent
  • BMI ≥18 and ≤25 kg/m2 at screening
  • Signed and dated written informed consent prior to admission to the trial in accordance with Good Clinical Practice (GCP) and local legislation

Exclusion Criteria:

Subjects will not be allowed to participate if any of the following general criteria apply:

  • 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 outside the range of 90 to 140 mmHg, diastolic blood pressure outside the range of 50 to 90 mmHg, or pulse rate outside the range of 45 to 90 bpm at screening. Based on the clinical judge by the investigator, repeated measurements are allowed.
  • Any laboratory value outside the reference range before randomisation that the investigator considers to be of clinical relevance
  • Any evidence of a concomitant disease considered 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
  • 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.Qc/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 in-house confinement at the 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 trial requirements, or has a condition that would not allow safe participation in the trial

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03070171


Locations
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Japan
SOUSEIKAI Sumida Hospital
Tokyo, Sumida-ku, Japan, 130-0004
Sponsors and Collaborators
Boehringer Ingelheim
  Study Documents (Full-Text)

Documents provided by Boehringer Ingelheim:
Statistical Analysis Plan  [PDF] July 12, 2017
Study Protocol  [PDF] February 10, 2017


Additional Information:
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Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT03070171     History of Changes
Other Study ID Numbers: 1160-0271
First Posted: March 3, 2017    Key Record Dates
Results First Posted: January 9, 2019
Last Update Posted: January 9, 2019
Last Verified: January 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Dabigatran
Antithrombins
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anticoagulants