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

Boehringer Ingelheim0 个研究点目标入组 35 人开始时间: 2005年4月最近更新: 2014年7月18日

适应症

干预措施

试验速览

阶段: 1 期
状态: 已完成
发起方: Boehringer Ingelheim
入组人数: 35
主要终点: AUC0-infinity (area under the concentration time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity)

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者记录与标识符相似试验

研究概览

简要总结

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

研究设计

研究类型: Interventional
分配方式: Non Randomized
干预模型: Parallel
主要目的: Treatment
盲法: None

入排标准

年龄范围: 18 Years 至 75 Years（Adult, Older Adult）
性别: All
接受健康志愿者: 是

入选标准

•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

排除标准

•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

研究组 & 干预措施

Dabigatran high dose in healthy subjects

Experimental

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

干预措施: Dabigatran etexilate high dose (Drug)

Dabigatran high dose in mild renal impairment

Experimental

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

干预措施: Dabigatran etexilate high dose (Drug)

Dabigatran high dose in moderate renal impairment

Experimental

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

干预措施: Dabigatran etexilate high dose (Drug)

Dabigatran high dose in severe renal impairment

Experimental

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

干预措施: Dabigatran etexilate high dose (Drug)

Dabigatran low dose in haemodialysis patients

Experimental

patients requiring haemodialysis

干预措施: Dabigatran etexilate low dose (Drug)

结局指标

主要结局

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