Bioavailability Study of Five Tablet Formulations of Dabigatran Etexilate Compared to Commercial Capsule Formulation in Healthy Male Subjects

Relative Bioavailability of Dabigatran After Single Oral Administration of Five Different Tablet Formulations of Dabigatran Etexilate Compared to Commercial Capsule Formulation in Healthy Male Subjects (an Open-label, Randomised, Single-dose, Six-period, Five-sequence Crossover Study)

The primary objective of this trial is to investigate the relative bioavailability of five different tablet formulations of Dabigatran Etexilate, Formulation A1, Formulation B1, Formulation C1, Formulation D1, and Formulation E1, compared to commercial capsule formulation of Dabigatran Etexilate.

The secondary objective is to evaluate and compare several pharmacokinetic parameters between the treatments.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Dabigatran etexilate capsule; Drug: Dabigatran etexilate tablet A1; Drug: Dabigatran etexilate tablet B1; Drug: Dabigatran etexilate tablet C1; Drug: Dabigatran etexilate tablet D1; Drug: Dabigatran etexilate tablet E1

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Tokyo, Sumida-ku, Japan, 133-0004
    • Souseikai Sumida Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 35 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion 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 <=35 years old
• Body mass index (BMI) >=18.0 and <=25.0 kg/m2
• Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice (GCP) and local legislation

Exclusion criteria:

• Any finding in the medical examination (including BP, Pulse Rate, or ECG) deviating from normal and judged as clinically relevant by the investigator at screening
• 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
• Any laboratory value outside the reference range that the investigator considers to be of clinical relevance
• Any relevant bleeding history considered by the investigator
• Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
• Surgery of the gastrointestinal tract that could interfere with kinetics of the trial medication (except appendectomy and simple hernia repair)
• Diseases of the central nervous system (including but not limited to any kind of seizures or stroke), and other relevant neurological or psychiatric disorders
• 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
• 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)
• Any evidence of a concomitant disease considered as clinically relevant by the investigator
• Intake of drugs with a long half-life (more than 24 hours) within 30 days or less than 10 half-lives of the respective drug prior to administration of trial medication
• Within 10 days prior to administration of trial medication, use of drugs that might reasonably influence the results of the trial
• Intake of medication, which influences the blood clotting, e.g., acetylsalicylic acid, coumarin etc. within 10 days prior to trial medication
• Participation in another trial where an investigational drug has been administered within 4 months or 5 half-lives (whichever is greater) prior to planned administration of trial medication
• Planned surgeries within four weeks following the end-of study examination
• Smoker (more than 10 cigarettes or 3 cigars or 3 pipes per day)
• Inability to refrain from smoking during 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 assessed as unsuitable for inclusion by the investigator because of, for instance, being considered not able to understand and comply with study requirements, or having a condition that would not allow safe participation in the study

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

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Dabigatran etexilate capsule	Drug: Dabigatran etexilate capsule
Experimental: Dabigatran etexilate tablet A1	Drug: Dabigatran etexilate tablet A1
Experimental: Dabigatran etexilate tablet B1	Drug: Dabigatran etexilate tablet B1
Experimental: Dabigatran etexilate tablet C1	Drug: Dabigatran etexilate tablet C1
Experimental: Dabigatran etexilate tablet D1	Drug: Dabigatran etexilate tablet D1
Experimental: Dabigatran etexilate tablet E1	Drug: Dabigatran etexilate tablet E1

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC0-tz (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)	This outcome measure presents 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.	1:00 [hour (h): minute] before drug administration and 1:00h, 1:30h, 2:00h, 3:00h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h, 48:00h after drug administration.
Cmax (Maximum Concentration of Free Dabigatran)	This outcome measure presents maximum concentration of analyte in plasma (Cmax).	1:00 [hour (h): minute] before drug administration and 1:00h, 1:30h, 2:00h, 3:00h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h, 48:00h after drug administration.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC0-infinity (Area Under the Concentration-time Curve of Free Dabigatran in Plasma Over the Time Interval From 0 Extrapolated to Infinity) (if Applicable)	This outcome measure presents area under the concentration-time curve of free Dabigatran in plasma over the time interval from 0 extrapolated to infinity)(if applicable).	1:00 [hour (h): minute] before drug administration and 1:00h, 1:30h, 2:00h, 3:00h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h, 48:00h after drug administration.
AUC0-tz (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)	This outcome measure presents 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.	1:00 [hour (h): minute] before drug administration and 1:00h, 1:30h, 2:00h, 3:00h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h, 48:00h after drug administration.
Cmax (Maximum Plasma Concentration of Total Dabigatran)	This outcome measure presents maximum concentration of analyte in plasma (Cmax).	1:00 [hour (h): minute] before drug administration and 1:00h, 1:30h, 2:00h, 3:00h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h, 48:00h after drug administration.
AUC0-infinity (Area Under the Concentration-time Curve of Total Dabigatran in Plasma Over the Time Interval From 0 Extrapolated to Infinity) (if Applicable)	This outcome measure presents area under the concentration-time curve of total Dabigatran in plasma over the time interval from 0 extrapolated to infinity)(if applicable).	1:00 [hour (h): minute] before drug administration and 1:00h, 1:30h, 2:00h, 3:00h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h, 48:00h after drug administration.

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): March 22, 2016
• Primary Completion (Actual): May 11, 2016
• Study Completion (Actual): June 10, 2016

Study Registration Dates

• First Submitted: March 14, 2016
• First Submitted That Met QC Criteria: March 14, 2016
• First Posted (Estimate): March 17, 2016

Study Record Updates

• Last Update Posted (Actual): November 6, 2017
• Last Update Submitted That Met QC Criteria: October 3, 2017
• Last Verified: October 1, 2017

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: 1160.246