Pharmacokinetics of Dabigatran Etexilate (Pradaxa®) During Haemodialysis

Study Overview
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Brief Summary
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The current study will allow the assessment of pharmacokinetics, pharmacodynamics, elimination rate and clearance of dabigatran etexilate during and following haemodialysis in ESRD patients.

Official Title
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Open Label, Non Randomized, Multiple Dose Phase I Study to Investigate the Elimination, Pharmacokinetics, Pharmacodynamics and Safety of Dabigatran Etexilate (Pradaxa) Under Steady State Conditions Before, During and After Haemodialysis in Patients With End Stage Renal Disease (ESRD) Undergoing Regular Haemodialysis

Conditions
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Cardiovascular Diseases, Kidney Failure, Chronic

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


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: End stage renally disease (ESRD), undergoing haemodialysis ESRD patients in relatively good health Age 21 - 60 years inclusive Signed and dated written informed consent prior to admission to the study Exclusion criteria: Clinically relevant laboratory or physical examination abnormalities (except for renal function tests or deviation of clinical laboratory values) that are related to renal impairment Moderate and severe concurrent liver function impairment Surgery of gastrointestinal tract (except appendectomy or herniotomy) or evidence of significant gastrointestinal motility problems Recent or contemplated diagnostic or therapeutic procedures with potential for uncontrollable bleeding Intake of medication, which influences the blood clotting Subjects not able to understand and comply with protocol requirements, instructions and protocol-stated restrictions For women with childbearing potential: no reliable contraception Participation in another trial with an investigational drug (<2 months prior to administration or during trial) Scheduled to receive a donor kidney transplant during the course of the study

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dabigatran etexilate 110 mg<br>Capsule, oral | Drug: Dabigatran etexilate<br>* 110 mg capsule<br>|
| Experimental: Dabigatran etexilate 75 mg<br>Capsule, oral | Drug: Dabigatran etexilate<br>* 75 mg capsule<br>|
| Experimental: Dabigatran etexilate 150 mg<br>Capsule, oral | Drug: Dabigatran etexilate<br>* 150 mg capsule<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dialysis Clearance of Dabigatran | Dialysis clearance of dabigatran from blood (CLD,b) and dialysis clearance of dabigatran from plasma (CLD) were calculated and indicate how quickly dabigatran is cleared out from blood or plasma. | 4 hours | 
| Extent Cleared From Circulation (Plasma) During 1 Complete Cycle of Dialysis | Extent of dabigatran that is removed from blood during one complete 4-hour cycle of dialysis was computed by the difference of plasma concentration at the start and at the end of dialysis relative to the start concentration and is therefore measured as a percentage. | 4 hours | 
| Plasma Concentration Extraction Ratio | Plasma concentration extraction ratio was measured directly at the dialysis machine and computed as the difference of the predialysis plasma concentration and the postdialysis plasma concentration relative to the predialysis concentration on the percentage scale (minimum: 0 percent of extraction (worst), maximum: 100 percent of extraction). | 4 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Curve Exposure to Dabigatran During the First 8 Hours Post Dose (AUC0-8h) | Area under the concentration-time curve of total and free dabigatran in plasma over the time interval from 0 to 8 hours after the second and third administration of dabigatran. | Days 2 and 3 | 
| Maximum Plasma Concentrations of Dabigatran (Cmax) | Maximum measured concentration of total and free dabigatran in plasma after the second and third administration of dabigatran. | Days 2 and 3 | 
| Time to Maximum Plasma Concentration (Tmax) | Time to maximum plasma concentration of total and free dabigatran in plasma after the third administration of dabigatran. | Day 3 | 
| Coagulation Parameters | Assessment of blood coagulation parameters 'activated partial thromboplastin time' (aPTT) and 'factor IIa inhibition' (anti-FIIa) measured with the diluted thrombin time assay. Time to the formation of a fibrin clot (coagulation) is measured in seconds. | Day 3 | 
| Safety and Tolerability | Tolerability refers to the number of non-tolerable patients as assessed through the subjective examination of adverse events (AE). Safety refers to the number of patients with treatment emergent AEs. These numbers are presented on the overall Dabigatran treatment. | 2 periods of 5 days each | 
| Additional Safety Parameters | By study design abnormalities could be due to dialysis or Dabigatran. | 2 periods of 5 days each |