Clinical trial NCT02044367: Relative Bioavailability of Dabigatran Capsules, Pellets and Oral Solution in Healthy Volunteers
Official title: Relative Bioavailability of Dabigatran After Administration of Different Dosage Forms of Multiple Doses of 150 mg Dabigatran Etexilate (Hard Capsule, Granules Resolved in Reconstitution Solution, Pellets on Food) in Healthy Male Volunteers (an Open-label, Randomised, Multiple-dose, Three Way Crossover Study)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2014-01-24
Enrollment: 54
Sex: MALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: To investigate the relative bioavailability of dabigatran etexilate as pellets on food and of dabigatran etexilate as granules resolved in reconstitution solution, each with dabigatran etexilate as capsule following oral administration. To evaluate acceptability and palatability of Pellets sprinkled on food and Oral Liquid Formulation


Eligibility criteria: Inclusion criteria:

1. Healthy males according to the investigator's assessment, as based on the following criteria: a complete medical history including a physical examination, vital signs (Blood Pressure, Pulse Rate), 12-lead electrocardiogram, and clinical laboratory tests
2. Age 18 to 55 years (incl.)
3. Body Mass Index 18.5 to 29.9 kg/m2 (incl.)
4. Signed and dated written informed consent prior to admission to the study in accordance with GCP and local legislation

Exclusion criteria:

1. Any finding in the medical examination (including Blood Pressure, Pulse Rate or electrocardiogram) deviating from normal and judged clinically relevant by the investigator.
2. Repeated measurement of systolic blood pressure greater than 140 mm Hg or diastolic blood pressure greater than 90 mm Hg
3. Any laboratory value outside the reference range that the investigator considers to be of clinical relevance
4. Any evidence of a concomitant disease judged clinically relevant by the investigator
5. Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
6. Surgery of the gastrointestinal tract that could interfere with kinetics of the study drug
7. Diseases of the central nervous system (such as epilepsy), other neurological disorders or psychiatric disorders
8. Subjects who in the investigator's judgement are perceived as having an increased risk of bleeding, for example because of:

   * Hemorrhagic disorders or bleeding diathesis
   * Occult blood in faeces or haematuria
   * Trauma or surgery within the last month or as long as an excessive risk of bleeding persists after these events, or planned surgery during trial participation
   * History of arteriovenous malformation or aneurysm
   * History of gastroduodenal ulcer disease or gastrointestinal haemorrhage
   * History of intracranial, intraocular, spinal, retroperitoneal, or atraumatic intraarticular bleeding
   * Anemia at screening
   * Thrombocytopenia (platelet count less than 100/nL)

Primary outcomes:
measure: Area Under the Concentration-time Curve of the Analyte in Plasma at Steady State Over a Uniform Dosing Interval t for Total Dabigatran.
timeFrame: 47:55, 48:30, 49:00, 49:30, 50:00, 50:30, 51:00, 51:30, 52:00, 54:00, 56:00, 58:00, 60:00 relative to first drug administration
measure: Maximum Measured Concentration of the Analyte in Plasma at Steady State Over a Uniform Dosing Interval t for Total Dabigatran.
timeFrame: 47:55, 48:30, 49:00, 49:30, 50:00, 50:30, 51:00, 51:30, 52:00, 54:00, 56:00, 58:00, 60:00 relative to first drug administration
Secondary outcomes:
measure: Area Under the Concentration-time Curve of the Analyte in Plasma at Steady State Over a Uniform Dosing Interval t for Free Dabigatran.
timeFrame: 47:55, 48:30, 49:00, 49:30, 50:00, 50:30, 51:00, 51:30, 52:00, 54:00, 56:00, 58:00, 60:00 relative to first drug administration
measure: Maximum Measured Concentration of the Analyte in Plasma at Steady State Over a Uniform Dosing Interval t for Free Dabigatran.
timeFrame: 47:55, 48:30, 49:00, 49:30, 50:00, 50:30, 51:00, 51:30, 52:00, 54:00, 56:00, 58:00, 60:00 relative to first drug administration
measure: Acceptability Rating for Pellets (on Food) and Oral Solution Will be Assessed by Asking the Subjects 1 Multiple Choice Verbal Question.
timeFrame: once on day 3 (48 hours after first dose)
measure: Palatability Rating for Pellets (on Food) and Oral Solution Will be Assessed by Asking the Subjects 1 Multiple Choice Verbal Question.
timeFrame: once on day 3 (48 hours after first dose)
Other outcomes:
Locations:
city: Biberach
country: Germany
facility: 1160.194.1 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References: