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Trial record 99 of 333 for:    DABIGATRAN

Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of Dabigatran Etexilate in Patients With and Without Renal Impairment

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ClinicalTrials.gov Identifier: NCT02182024
Recruitment Status : Completed
First Posted : July 8, 2014
Last Update Posted : July 18, 2014
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim

Brief Summary:
To assess the effect of different degrees of renal impairment on the pharmacokinetics and pharmacodynamics of dabigatran etexilate administered orally.

Condition or disease Intervention/treatment Phase
Renal Insufficiency Drug: Dabigatran etexilate high dose Drug: Dabigatran etexilate low dose Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 35 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : April 2005
Actual Primary Completion Date : March 2006

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Dabigatran high dose in healthy subjects
healthy subjects with a creatinine clearance of >80 mL/m
Drug: Dabigatran etexilate high dose
Experimental: Dabigatran high dose in mild renal impairment
patients with a creatinine clearance of >50 up to 80 mL/min
Drug: Dabigatran etexilate high dose
Experimental: Dabigatran high dose in moderate renal impairment
patients with a creatinine clearance of >30 up to 50 mL/min
Drug: Dabigatran etexilate high dose
Experimental: Dabigatran high dose in severe renal impairment
patients with a creatinine clearance of up to 30 mL/min
Drug: Dabigatran etexilate high dose
Experimental: Dabigatran low dose in haemodialysis patients
patients requiring haemodialysis
Drug: Dabigatran etexilate low dose



Primary Outcome Measures :
  1. 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 ]
  2. 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 ]
  3. 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 ]
  4. 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 ]
  5. 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 ]
  6. 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 ]
  7. 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 ]

Secondary Outcome Measures :
  1. 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 ]
  2. 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 ]
  3. 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 ]
  4. 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 ]
  5. 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 ]
  6. 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 ]
  7. 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 ]
  8. 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 ]
  9. 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 ]
  10. 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 ]
  11. Plasma protein binding of dabigatran [ Time Frame: within 1 h before study drug administration ]
  12. Changes from baseline in pulse rate [ Time Frame: Day 4, Day 5 in patients with renal impairment ]
  13. Changes from baseline in systolic and diastolic blood pressure [ Time Frame: Day 4, Day 5 in patients with renal impairment ]
  14. Changes from baseline in ECG [ Time Frame: Day 4, Day 5 in patients with renal impairment ]
  15. Changes from baseline in routine laboratory [ Time Frame: Day 4, Day 5 in patients with renal impairment ]
  16. Occurrence of adverse events [ Time Frame: up to day 4, up to day 5 in patients with renal impairment ]
  17. Assessment of tolerability on a 4-point scale [ Time Frame: Day 4, Day 5 in patients with renal impairment ]


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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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

Additional Information:
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Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT02182024     History of Changes
Other Study ID Numbers: 1160.23
First Posted: July 8, 2014    Key Record Dates
Last Update Posted: July 18, 2014
Last Verified: July 2014
Additional relevant MeSH terms:
Layout table for MeSH terms
Renal Insufficiency
Kidney Diseases
Urologic Diseases
Dabigatran
Antithrombins
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anticoagulants