- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02182024
Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of Dabigatran Etexilate in Patients With and Without Renal Impairment
July 17, 2014 updated by: Boehringer Ingelheim
Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of 150 mg Dabigatran Etexilate p.o. in Patients With Different Degrees of Renal Impairment in Comparison to Subjects With Normal Renal Function in a Monocentric, Open, Parallel-group Trial
To assess the effect of different degrees of renal impairment on the pharmacokinetics and pharmacodynamics of dabigatran etexilate administered orally.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
35
Phase
- Phase 1
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 75 years (Adult, Older Adult)
Accepts Healthy Volunteers
Yes
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Healthy male or female subjects determined by results of screening with a creatinine clearance >80 mL/min (group 1, control group)
Renally impaired male or female subjects determined by results of screening with the following creatinine clearance results:
- creatinine clearance >50 - ≤80 mL/min (group 2)
- creatinine clearance >30 - ≤50 mL/min (group 3)
- creatinine clearance ≤30 mL/min (group 4)
- uraemia requiring maintenance dialysis (group 5)
- Signed written informed consent in accordance with Good Clinical Practice (GCP) and local legislation
- Age >=18 and <=75 years
- BMI >=18.0 and <=32 kg/m2, at least 45 kg for females
Exclusion Criteria:
- Any finding of the medical examination (including blood pressure, pulse rate, and electrocardiogram) deviating from normal and of clinical relevance
- Clinically relevant gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunologic or hormonal disorders
- Surgery of gastrointestinal tract (except appendectomy, cholecystectomy or herniotomy)
- Clinically relevant diseases of the central nervous system
- Relevant history of orthostatic hypotension, fainting spells or blackouts
- Abnormal prothrombin time (PT), TT, aPTT (must be within the normal range after no more than one repeated test), thrombocytes <150000/μl (two repeats of the first test)
- Evidence of haematuria either macroscopically detectable or microscopic on urinalysis (normal microscopic results after no more than one repeated test)
- Evidence of blood dyscrasia, haemorrhagic diathesis, severe thrombocytopenia, cerebrovascular haemorrhage, bleeding tendencies associated with active ulceration or overt bleeding of gastrointestinal, respiratory or genitourinary tract or any disease or condition with haemorrhagic tendencies (e.g. cerebral aneurysm, dissecting aorta, central nervous system (CNS) trauma, retinopathy or nephrolithiasis)
- Recent or contemplated diagnostic or therapeutic procedures with potential for uncontrollable bleeding (e.g. spinal puncture, lumbar block anaesthesia, surgery of CNS or eye or surgery resulting in large open surfaces) within 14 days before or after drug administration of this clinical trial
- Chronic or relevant acute infections
- History of allergy/hypersensitivity (including drug allergy) which is deemed relevant to the trial as judged by the investigator
- For women with childbearing potential: no reliable contraception (accepted methods are intra uterine device, hormonal contraceptives, bilateral tubal ligation, hysterectomy, condoms) or pregnancy (known or detected by a positive pregnancy test) or breast feeding period
- Intake of drugs with a long half-life (>24 hours) (<1 month prior to administration or during the trial)
- Use of any drugs, within 14 days prior to administration or during the trial
- Participation in another trial with an investigational drug (<2 months prior to drug administration or during trial)
- Drug abuse
- Blood donation or loss >400 mL, <1 month prior to administration or during the trial
- Excessive physical activities <5 days prior to administration of study drug or during trial
- Clinically relevant laboratory abnormalities
Renally impaired subjects (groups 2, 3, 4 and 5) who met any of the following criteria were not be entered into this trial:
- Moderate and severe concurrent liver function impairment (e.g. due to hepatorenal syndrome)
- Clinically relevant gastrointestinal, respiratory, cardiovascular, metabolic, immunologic or hormonal disorders
- Surgery of gastrointestinal tract (except appendectomy, cholecystectomy or herniotomy)
- Clinically relevant diseases of the central nervous system
- Relevant history of orthostatic hypotension, fainting spells or blackouts
- Abnormal values for PT, TT, aPTT and thrombocytes considered by the investigator or one of the co-investigators to be clinically relevant
- Evidence of blood dyscrasia, haemorrhagic diathesis, severe thrombocytopenia, cerebrovascular haemorrhage, bleeding tendencies associated with active ulceration or overt bleeding of gastrointestinal, respiratory or genitourinary tract or any disease or condition with haemorrhagic tendencies (e.g. cerebral aneurysm, dissecting aorta, CNS trauma, retinopathy, nephrolithiasis) considered by the investigator or one of the co-investigators to be clinically relevant
- Recent or contemplated diagnostic or therapeutic procedures with potential for uncontrollable bleeding (e.g. spinal puncture, lumbar block anaesthesia, surgery of CNS or eye or surgery resulting in large open surfaces) within 14 days before or after drug administration of this clinical trial
- Chronic or relevant acute infections
- History of allergy/hypersensitivity (including drug allergy) which is deemed relevant to the trial as judged by the investigator
- For women with childbearing potential: no reliable contraception (accepted methods are intra-uterine device, hormonal contraceptives, bilateral tubal ligation, hysterectomy or condoms) or pregnancy (known or detected by a positive pregnancy test) or breast-feeding period
- Participation in another trial with an investigational drug (<2 months prior to administration or during trial)
- Drug abuse
- Blood donation or loss >400 mL, <1 month prior to administration or during the trial
- Excessive physical activities < 5 days prior to administration of study drug or during trial
- Clinically relevant laboratory abnormalities except those values typical for renally impaired patients
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Dabigatran high dose in healthy subjects
healthy subjects with a creatinine clearance of >80 mL/m
|
|
Experimental: Dabigatran high dose in mild renal impairment
patients with a creatinine clearance of >50 up to 80 mL/min
|
|
Experimental: Dabigatran high dose in moderate renal impairment
patients with a creatinine clearance of >30 up to 50 mL/min
|
|
Experimental: Dabigatran high dose in severe renal impairment
patients with a creatinine clearance of up to 30 mL/min
|
|
Experimental: Dabigatran low dose in haemodialysis patients
patients requiring haemodialysis
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
AUC0-infinity (area under the concentration time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity)
Time Frame: pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 h after administration, additional 96 h in subjects with severe renal impairment and dialysis patients
|
pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 h after administration, additional 96 h in subjects with severe renal impairment and dialysis patients
|
Cmax (maximum concentration of the analyte in plasma)
Time Frame: pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 h after administration, additional 96 h in subjects with severe renal impairment and dialysis patients
|
pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 h after administration, additional 96 h in subjects with severe renal impairment and dialysis patients
|
CL/F (apparent clearance of the analyte in the plasma after extravascular administration)
Time Frame: pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 h after administration, additional 96 h in subjects with severe renal impairment and dialysis patients
|
pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 h after administration, additional 96 h in subjects with severe renal impairment and dialysis patients
|
international normalized ratio (INR)
Time Frame: pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 h after administration, additional 96 h in subjects with severe renal impairment and dialysis patients
|
pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 h after administration, additional 96 h in subjects with severe renal impairment and dialysis patients
|
activated partial thromboplastin time (aPTT)
Time Frame: pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 h after administration, additional 96 h in subjects with severe renal impairment and dialysis patients
|
pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 h after administration, additional 96 h in subjects with severe renal impairment and dialysis patients
|
Ecarin clotting time (ECT)
Time Frame: pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 h after administration, additional 96 h in subjects with severe renal impairment and dialysis patients
|
pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 h after administration, additional 96 h in subjects with severe renal impairment and dialysis patients
|
thrombin time (TT)
Time Frame: pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 h after administration, additional 96 h in subjects with severe renal impairment and dialysis patients
|
pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 h after administration, additional 96 h in subjects with severe renal impairment and dialysis patients
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
AUC0-tz (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)
Time Frame: pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 h after administration, additional 96 h in subjects with severe renal impairment and dialysis patients
|
pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 h after administration, additional 96 h in subjects with severe renal impairment and dialysis patients
|
AUCt1-t2 (area under the concentration-time curve of the analyte in plasma over the time interval t1 to t2, time interval to be determined)
Time Frame: pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 h after administration, additional 96 h in subjects with severe renal impairment and dialysis patients
|
pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 h after administration, additional 96 h in subjects with severe renal impairment and dialysis patients
|
tmax (time from dosing to the maximum concentration of the analyte in plasma, oral administration only)
Time Frame: pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 h after administration, additional 96 h in subjects with severe renal impairment and dialysis patients
|
pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 h after administration, additional 96 h in subjects with severe renal impairment and dialysis patients
|
λz (terminal rate constant in plasma)
Time Frame: pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 h after administration, additional 96 h in subjects with severe renal impairment and dialysis patients
|
pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 h after administration, additional 96 h in subjects with severe renal impairment and dialysis patients
|
t1/2 (terminal half-life of the analyte in plasma)
Time Frame: pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 h after administration, additional 96 h in subjects with severe renal impairment and dialysis patients
|
pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 h after administration, additional 96 h in subjects with severe renal impairment and dialysis patients
|
MRTpo (mean residence time of the analyte in the body after p.o. administration)
Time Frame: pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 h after administration, additional 96 h in subjects with severe renal impairment and dialysis patients
|
pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 h after administration, additional 96 h in subjects with severe renal impairment and dialysis patients
|
Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular dose)
Time Frame: pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 h after administration, additional 96 h in subjects with severe renal impairment and dialysis patients
|
pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 h after administration, additional 96 h in subjects with severe renal impairment and dialysis patients
|
Ae0-72 (amount of analyte that is eliminated in urine from the time interval 0 to 72 h)
Time Frame: pre-dose over 12 hours and post dose in fractions of 0 - 12, 12 - 24, 24 - 48, and 48-72 h, additional until 96 h in subjects with severe renal impairment
|
pre-dose over 12 hours and post dose in fractions of 0 - 12, 12 - 24, 24 - 48, and 48-72 h, additional until 96 h in subjects with severe renal impairment
|
fe0-72 (fraction of administered drug excreted unchanged in urine from time point 0 to 72 h)
Time Frame: pre-dose over 12 hours and post dose in fractions of 0 - 12, 12 - 24, 24 - 48, and 48-72 h, additional until 96 h in subjects with severe renal impairment
|
pre-dose over 12 hours and post dose in fractions of 0 - 12, 12 - 24, 24 - 48, and 48-72 h, additional until 96 h in subjects with severe renal impairment
|
CLR,0-72 (renal clearance of the analyte in plasma from the time point 0 h until the timepoint 72 h)
Time Frame: pre-dose over 12 hours and post dose in fractions of 0 - 12, 12 - 24, 24 - 48, and 48-72 h, additional until 96 h in subjects with severe renal impairment
|
pre-dose over 12 hours and post dose in fractions of 0 - 12, 12 - 24, 24 - 48, and 48-72 h, additional until 96 h in subjects with severe renal impairment
|
Plasma protein binding of dabigatran
Time Frame: within 1 h before study drug administration
|
within 1 h before study drug administration
|
Changes from baseline in pulse rate
Time Frame: Day 4, Day 5 in patients with renal impairment
|
Day 4, Day 5 in patients with renal impairment
|
Changes from baseline in systolic and diastolic blood pressure
Time Frame: Day 4, Day 5 in patients with renal impairment
|
Day 4, Day 5 in patients with renal impairment
|
Changes from baseline in ECG
Time Frame: Day 4, Day 5 in patients with renal impairment
|
Day 4, Day 5 in patients with renal impairment
|
Changes from baseline in routine laboratory
Time Frame: Day 4, Day 5 in patients with renal impairment
|
Day 4, Day 5 in patients with renal impairment
|
Occurrence of adverse events
Time Frame: up to day 4, up to day 5 in patients with renal impairment
|
up to day 4, up to day 5 in patients with renal impairment
|
Assessment of tolerability on a 4-point scale
Time Frame: Day 4, Day 5 in patients with renal impairment
|
Day 4, Day 5 in patients with renal impairment
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Helpful Links
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
April 1, 2005
Primary Completion (Actual)
March 1, 2006
Study Registration Dates
First Submitted
July 2, 2014
First Submitted That Met QC Criteria
July 2, 2014
First Posted (Estimate)
July 8, 2014
Study Record Updates
Last Update Posted (Estimate)
July 18, 2014
Last Update Submitted That Met QC Criteria
July 17, 2014
Last Verified
July 1, 2014
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 1160.23
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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