Pharmacokinetics of Dabigatran Etexilate (Pradaxa®) During Haemodialysis

Cardiovascular Diseases Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01241539
• Other study ID #: 1160.121
• Secondary ID: 2010-021819-16
• Status: Completed
• Phase: Phase 1
• First received: November 15, 2010
• Last updated: February 24, 2014
• Start date: November 2010

Study information

• Verified date: February 2014
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 7
• Est. primary completion date: May 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 21 Years to 60 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Cardiovascular Diseases
• Kidney Failure, Chronic
• Renal Insufficiency

Intervention

Drug:
• Dabigatran etexilate
150 mg capsule
• Dabigatran etexilate
75 mg capsule
• Dabigatran etexilate
110 mg capsule

Locations

Country	Name	City	State
Germany	1160.121.1 Boehringer Ingelheim Investigational Site	Berlin

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	Additional Safety Parameters	By study design abnormalities could be due to dialysis or Dabigatran.	2 periods of 5 days each	No

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