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

NCT02182024 | Completed Phase 1

• 1 other identifier: 1160.23
• Study Type: interventional
• Target: 35
• Locations: 0 countries
• Sites: N/A

Brief Summary

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

Conditions

Renal Insufficiency

Outcome Measures

Primary Outcomes (7)

• AUC0-infinity (area under the concentration time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity)

  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)

  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)

  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)

  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)

  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)

  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)

  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 Outcomes (17)

• 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)

  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)

  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)

  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)

  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)

  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

Study Arms (5)

Dabigatran high dose in healthy subjects

EXPERIMENTAL

healthy subjects with a creatinine clearance of \>80 mL/m

Drug: Dabigatran etexilate high dose

Dabigatran high dose in mild renal impairment

EXPERIMENTAL

patients with a creatinine clearance of \>50 up to 80 mL/min

Drug: Dabigatran etexilate high dose

Dabigatran high dose in moderate renal impairment

EXPERIMENTAL

patients with a creatinine clearance of \>30 up to 50 mL/min

Drug: Dabigatran etexilate high dose

Dabigatran high dose in severe renal impairment

EXPERIMENTAL

patients with a creatinine clearance of up to 30 mL/min

Drug: Dabigatran etexilate high dose

Dabigatran low dose in haemodialysis patients

EXPERIMENTAL

patients requiring haemodialysis

Drug: Dabigatran etexilate low dose

Interventions

Dabigatran etexilate high dose DRUG

Dabigatran high dose in healthy subjects; Dabigatran high dose in mild renal impairment; Dabigatran high dose in moderate renal impairment; Dabigatran high dose in severe renal impairment

Dabigatran etexilate low dose DRUG

Dabigatran low dose in haemodialysis patients

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Boehringer Ingelheim: lead

MeSH Terms

Conditions

Renal Insufficiency

Interventions

Dabigatran

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 2, 2014
• First Posted: July 8, 2014
• Study Start: April 1, 2005
• Primary Completion: March 1, 2006
• Last Updated: July 18, 2014

Record last verified: 2014-07