Bioequivalence of Two Different Drug Product Batches of Dabigatran Etexilate Following Oral Administration in Healthy Male and Female Volunteers

Study Overview
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Brief Summary
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To establish the bioequivalence of two drug product batches of dabigatran etexilate, one batch containing only polymorph I vs. the other batch containing 17% of dabigatran etexilate polymorph II in addition to polymorph I

Official Title
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Bioequivalence of Two Different Drug Product Batches of 150 mg of Dabigatran Etexilate Following Oral Administration in Healthy Male and Female Volunteers (Double Blind, Randomised, Single-dose, Replicate Design in a Two-treatments, Four Periods Crossover Study)

Conditions
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Healthy

Intervention / Treatment
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* Drug: Dabigatran polymorph I (≈ 83%) and polymorph II (≈17%)
* Drug: Dabigatran polymorph I


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy males and females according to the following criteria: Based upon a complete medical history, including the physical examination, vital signs (BP, PR), 12-lead ECG, clinical laboratory tests Age ≥65 and ≤85 years BMI ≥18.5 and BMI ≤32.0 kg/m2 (Body Mass Index) Signed and dated written informed consent prior to admission to the study in accordance with 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 Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders Any relevant bleeding history History of relevant orthostatic hypotension, fainting spells or blackouts Chronic or relevant acute infections History of allergy/hypersensitivity (including drug allergy) which is deemed relevant to the trial as judged by the investigator Intake of drugs with a long half-life (>24 hours) within at least one month or less than 10 half-lives of the respective drug prior to administration or during the trial 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 Participation in another trial with an investigational drug within four weeks prior to administration or during the trial Alcohol abuse (more than 60 g/day) Drug abuse Blood donation (more than 100 mL within four weeks prior to administration or during the trial) Excessive physical activities (within one week prior to administration or during the trial) Any laboratory value outside the reference range that is of clinical relevance Inability to comply with dietary regimen of study centre

Ages Eligible for Study
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Minimum Age: 65 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dabigatran etexilate batch A<br> | Drug: Dabigatran polymorph I (≈ 83%) and polymorph II (≈17%)<br> <br> |
| Experimental: Dabigatran etexilate batch B<br> | Drug: Dabigatran polymorph I<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the concentration-time curve of total BIBR 953 ZW in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞) |  | Up to 72 hours after drug administration | 
| Maximum measured concentration of total BIBR 953 ZW in plasma (Cmax) |  | Up to 72 hours after drug administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the concentration-time curve of free BIBR 953 ZW in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞) |  | Up to 72 hours after drug administration | 
| Maximum measured concentration of free BIBR 953 ZW in plasma (Cmax) |  | Up to 72 hours after drug administration | 
| Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the time of the last quantifiable data point (AUC0-tz) |  | Up to 72 hours after drug administration | 
| Area under the concentration time curve of the analyte in plasma over the time interval t1 to t2 (AUCt1-t2) |  | t1 = 0 and t2 = 24, 48, 72 hours after drug administration | 
| Time from dosing to the maximum concentration of the analyte in plasma (tmax) |  | Up to 72 hours after drug administration | 
| Terminal rate constant in plasma (λz) |  | Up to 72 hours after drug administration | 
| Terminal half-life of the analyte in plasma (t1/2) |  | Up to 72 hours after drug administration | 
| Mean residence time of the analyte in the body after oral administration (MRTpo) |  | Up to 72 hours after drug administration | 
| Apparent clearance of the analyte in the plasma after extravascular administration (CL/F ) |  | Up to 72 hours after drug administration | 
| Apparent volume of distribution during the terminal phase λz following an extravascular dose (Vz/F) |  | Up to 72 hours after drug administration | 
| Change from baseline in physical examination |  | Baseline, day 73 | 
| Change from baseline in vital signs (blood pressure, pulse rate) |  | Baseline, day 73 | 
| Change from baseline in 12-lead ECG (electrocardiogram) |  | Baseline, day 73 | 
| Change from baseline in clinical laboratory tests |  | Baseline, day 73 | 
| Number of Participants with Serious and Non-Serious Adverse Events |  | Up to day 73 | 
| Assessment of tolerability by investigator on a four point scale (good, satisfactory, not satisfactory, bad) |  | Day 73 |