Pharmacokinetics of Dabigatran Etexilate (Pradaxa®) During Haemodialysis

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT01241539
First received: November 15, 2010
Last updated: February 24, 2014
Last verified: February 2014
  Purpose

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


Condition Intervention Phase
Cardiovascular Diseases
Kidney Failure, Chronic
Drug: Dabigatran etexilate
Phase 1

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

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Dialysis Clearance of Dabigatran [ Time Frame: 4 hours ] [ Designated as safety issue: No ]
    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.

  • Extent Cleared From Circulation (Plasma) During 1 Complete Cycle of Dialysis [ Time Frame: 4 hours ] [ Designated as safety issue: No ]
    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.

  • Plasma Concentration Extraction Ratio [ Time Frame: 4 hours ] [ Designated as safety issue: No ]
    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).


Secondary Outcome Measures:
  • Area Under the Curve Exposure to Dabigatran During the First 8 Hours Post Dose (AUC0-8h) [ Time Frame: Days 2 and 3 ] [ Designated as safety issue: No ]
    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.

  • Maximum Plasma Concentrations of Dabigatran (Cmax) [ Time Frame: Days 2 and 3 ] [ Designated as safety issue: No ]
    Maximum measured concentration of total and free dabigatran in plasma after the second and third administration of dabigatran.

  • Time to Maximum Plasma Concentration (Tmax) [ Time Frame: Day 3 ] [ Designated as safety issue: No ]
    Time to maximum plasma concentration of total and free dabigatran in plasma after the third administration of dabigatran.

  • Coagulation Parameters [ Time Frame: Day 3 ] [ Designated as safety issue: No ]
    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.

  • Safety and Tolerability [ Time Frame: 2 periods of 5 days each ] [ Designated as safety issue: No ]
    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.

  • Additional Safety Parameters [ Time Frame: 2 periods of 5 days each ] [ Designated as safety issue: No ]
    By study design abnormalities could be due to dialysis or Dabigatran.


Enrollment: 7
Study Start Date: November 2010
Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dabigatran etexilate 110 mg
Capsule, oral
Drug: Dabigatran etexilate
110 mg capsule
Experimental: Dabigatran etexilate 75 mg
Capsule, oral
Drug: Dabigatran etexilate
75 mg capsule
Experimental: Dabigatran etexilate 150 mg
Capsule, oral
Drug: Dabigatran etexilate
150 mg capsule

  Eligibility

Ages Eligible for Study:   21 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01241539

Locations
Germany
1160.121.1 Boehringer Ingelheim Investigational Site
Berlin, Germany
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

Additional Information:
No publications provided

Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01241539     History of Changes
Other Study ID Numbers: 1160.121, 2010-021819-16
Study First Received: November 15, 2010
Results First Received: May 10, 2012
Last Updated: February 24, 2014
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Additional relevant MeSH terms:
Cardiovascular Diseases
Kidney Failure, Chronic
Renal Insufficiency
Renal Insufficiency, Chronic
Kidney Diseases
Urologic Diseases

ClinicalTrials.gov processed this record on July 23, 2014