Relative Bioavailability of Dabigatran Capsules, Pellets and Oral Solution in Healthy Volunteers

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)

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

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Dabigatran etexilate; Drug: Dabigatran etexilate; Drug: Dabigatran etexilate

• Study Type: Interventional
• Enrollment (Actual): 54
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Biberach, Germany
    • 1160.194.1 Boehringer Ingelheim Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Test 1 (Treatment A); multiple dose of dabigatran	Drug: Dabigatran etexilate; Pellets (multiple dose of dabigatran); Drug: Dabigatran etexilate; Granules resolved in reconstitution solution (multiple dose of dabigatran); Drug: Dabigatran etexilate; Hard capsule (multiple dose of dabigatran)
Experimental: Test 2 (Treatment B); multiple dose of dabigatran	Drug: Dabigatran etexilate; Pellets (multiple dose of dabigatran); Drug: Dabigatran etexilate; Granules resolved in reconstitution solution (multiple dose of dabigatran); Drug: Dabigatran etexilate; Hard capsule (multiple dose of dabigatran)
Experimental: Reference; multiple dose of dabigatran	Drug: Dabigatran etexilate; Pellets (multiple dose of dabigatran); Drug: Dabigatran etexilate; Granules resolved in reconstitution solution (multiple dose of dabigatran); Drug: Dabigatran etexilate; Hard capsule (multiple dose of dabigatran)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Concentration-time Curve of the Analyte in Plasma at Steady State Over a Uniform Dosing Interval t for Total Dabigatran.	Area under the concentration-time curve of the analyte in plasma at steady state over a uniform dosing interval t for total dabigatran.	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
Maximum Measured Concentration of the Analyte in Plasma at Steady State Over a Uniform Dosing Interval t for Total Dabigatran.	Maximum measured concentration of the analyte in plasma at steady state over a uniform dosing interval t for total dabigatran.	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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Concentration-time Curve of the Analyte in Plasma at Steady State Over a Uniform Dosing Interval t for Free Dabigatran.	Area under the concentration-time curve of the analyte in plasma at steady state over a uniform dosing interval t for free dabigatran.	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
Maximum Measured Concentration of the Analyte in Plasma at Steady State Over a Uniform Dosing Interval t for Free Dabigatran.	Maximum measured concentration of the analyte in plasma at steady state over a uniform dosing interval t for free dabigatran.	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
Acceptability Rating for Pellets (on Food) and Oral Solution Will be Assessed by Asking the Subjects 1 Multiple Choice Verbal Question.	Acceptability question: "Would you accept to take this medication for chronic use?" with 3 possible answers: Yes - No - I am not sure.	once on day 3 (48 hours after first dose)
Palatability Rating for Pellets (on Food) and Oral Solution Will be Assessed by Asking the Subjects 1 Multiple Choice Verbal Question.	Palatability question: "How do you rank the taste?" with 5 possible answers: Very good - Good - Fair - Acceptable - Not acceptable.	once on day 3 (48 hours after first dose)

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: January 1, 2014
• Primary Completion (Actual): April 1, 2014
• Study Completion (Actual): April 1, 2014

Study Registration Dates

• First Submitted: January 22, 2014
• First Submitted That Met QC Criteria: January 22, 2014
• First Posted (Estimate): January 24, 2014

Study Record Updates

• Last Update Posted (Estimate): May 20, 2015
• Last Update Submitted That Met QC Criteria: May 1, 2015
• Last Verified: May 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Dabigatran
• Other Study ID Numbers: 1160.194; 2013-002498-23 (EudraCT Number: EudraCT)