Pharmacokinetics of Dabigatran Etexilate (Pradaxa®) During Haemodialysis

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

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

Study Overview

• Status: Completed
• Conditions: Cardiovascular Diseases; Kidney Failure, Chronic
• Intervention / Treatment: Drug: Dabigatran etexilate; Drug: Dabigatran etexilate; Drug: Dabigatran etexilate

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany
    • 1160.121.1 Boehringer Ingelheim Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dabigatran etexilate 110 mg; Capsule, oral	Drug: Dabigatran etexilate; 150 mg capsule; Drug: Dabigatran etexilate; 75 mg capsule; Drug: Dabigatran etexilate; 110 mg capsule
Experimental: Dabigatran etexilate 75 mg; Capsule, oral	Drug: Dabigatran etexilate; 150 mg capsule; Drug: Dabigatran etexilate; 75 mg capsule; Drug: Dabigatran etexilate; 110 mg capsule
Experimental: Dabigatran etexilate 150 mg; Capsule, oral	Drug: Dabigatran etexilate; 150 mg capsule; Drug: Dabigatran etexilate; 75 mg capsule; Drug: Dabigatran etexilate; 110 mg capsule

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info
• Related Info

Study record dates

Study Major Dates

• Study Start: November 1, 2010
• Primary Completion (Actual): May 1, 2011
• Study Completion: December 7, 2022

Study Registration Dates

• First Submitted: November 15, 2010
• First Submitted That Met QC Criteria: November 15, 2010
• First Posted (Estimate): November 16, 2010

Study Record Updates

• Last Update Posted (Estimate): April 7, 2014
• Last Update Submitted That Met QC Criteria: February 24, 2014
• Last Verified: February 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency, Chronic; Cardiovascular Diseases; Kidney Failure, Chronic; Renal Insufficiency; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Dabigatran
• Other Study ID Numbers: 1160.121; 2010-021819-16 (EudraCT Number: EudraCT)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No