Bioequivalence of Two Different Capsule Types of Dabigatran

Study Overview
=================
Brief Summary
-----------------
The objective of this Phase I trial is to demonstrate the bioequivalence of two capsules of dabigatran etexilate made from two different drug product batches. The reference batch is dabigatran etexilate hard capsules 150 mg using the currently approved capsule shell (Qualicaps). The test batch is dabigatran etexilate 150 mg hard capsules using a new capsule shell (Capsugel). The test batch is the drug product intended for future commercial use.

Official Title
-----------------
Bioequivalence of Two Different Capsule Types of 150 mg Dabigatran Etexilate Made From Two Different Drug Product Batches, Following Oral Administration in Healthy Male and Female Volunteers (Open-label, Randomised, Single Dose, Replicate Design in a Two Treatments, Four Periods Crossover Phase I Study)

Conditions
-----------------
Healthy

Intervention / Treatment
-----------------
* Drug: Dabigatran etexilate
* Drug: Dabigatran etexilate


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria: Healthy males and females according to the following criteria: Based upon a complete medical history, including the physical examination, vital signs (blood pressure (BP), pulse rate (PR)), 12-lead electrocardiogram (ECG), clinical laboratory tests Age =21 and = 55 years Body Mass Index (BMI) =18.5 and BMI = 29.9 kg/m^2 Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice (GCP) and the local legislation Exclusion criteria: Clinically relevant gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders Clinically relevant surgery of gastrointestinal tract or evidence of significant gastrointestinal motility problems that could affect absorption of the drug Diseases of the central nervous system (included but not limited to any kind of seizures, stroke or psychiatric disorders) within the past 6 month Any history or evidence of blood dyscrasia, hemorrhagic diathesis, severe thrombocytopenia, cerebrovascular hemorrhage, bleeding tendencies associated with active ulceration or overt bleeding of gastrointestinal, respiratory or genitourinary tract or any disease or condition with hemorrhagic tendencies History of relevant orthostatic hypotension, fainting spells or blackouts Chronic or relevant acute infections History of allergy/hypersensitivity (including drug allergy in particular to study drug or its excipients) which is deemed relevant to the trial as judged by the investigator Use of drugs which might reasonably influence the results of the trial based on the knowledge at the time of protocol preparation within 10 days prior to administration or during the trial Alcohol abuse (more than 20 g/day) Drug abuse Any laboratory value outside the reference range that is of clinical relevance (especially hemoglobin, thrombocytes, prothrombin time (PT) and Activated Partial Thromboplastin Time (Measure of the clotting time) (aPTT) or positive drug or virus screening Planned surgeries within four weeks following the end-of study examination Recent or contemplated diagnostic or therapeutic procedures with potential for uncontrollable bleeding within 14 days before or after end-of study examination

Ages Eligible for Study
-----------------
Minimum Age: 21 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dabigatran etexilate 150 mg (T)<br>Capsugel (T), oral administration | Drug: Dabigatran etexilate<br>* 150 mg Capsugel (T)<br>|
| Experimental: Dabigatran etexilate 150 mg (R)<br>Qualicaps (R), oral administration | Drug: Dabigatran etexilate<br>* 150 mg Qualicaps (R)<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Curve 0 to tz (AUC0-tz) of Total Dabigatran | Area under the concentration-time curve of total dabigatran in plasma from time 0 to the time of the last quantifiable data point, adjusted for treatment, period and sequence (all fixed effects), and random subject effect. | 60 hours | 
| Maximum Measured Concentration (Cmax) of Total Dabigatran in Plasma | Adjusted for treatment, period and sequence (all fixed effects), and random subject effect. | 60 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Curve 0 to Infinity (AUC0-∞) of Total Dabigatran. | Area under the concentration-time curve of total dabigatran in plasma over the time interval from 0 extrapolated to infinity. Adjusted for treatment, period and sequence (all fixed effects), and random subject effect. | 60 hours | 
| AUC0-tz of Free Dabigatran. | Area under the concentration-time curve of free dabigatran in plasma from time 0 to the time of the last quantifiable data point. Adjusted for treatment, period and sequence (all fixed effects), and random subject effect. | 60 hours | 
| Cmax of Free Dabigatran in Plasma. | Adjusted for treatment, period and sequence (all fixed effects), and random subject effect. | 60 hours | 
| AUC0-∞ of Free Dabigatran. | Area under the concentration-time curve of free dabigatran in plasma over the time interval from 0 extrapolated to infinity. Adjusted for treatment, period and sequence (all fixed effects), and random subject effect. | 60 hours |