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临床试验/NCT02173717
NCT02173717已完成1 期

Relative Bioavailability of Single Doses of 150 mg Dabigatran Etexilate (Capsule)When Administered Alone, After Seven Days of Dosing With 600 mg Rifampicin(Tablet), and Seven Days and Fourteen Days After Last Administration of Rifampicin in Healthy Male and Female Volunteers (an Open Label, Fixed Sequence, Phase I Study)

Boehringer Ingelheim0 个研究点目标入组 24 人开始时间: 2009年6月最近更新:
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适应症
干预措施
相关药物

试验速览

阶段
1 期
状态
已完成
入组人数
24
主要终点
Area under the concentration-time curve over the time interval from 0 extrapolated to infinity (AUC0-inf) of total dabigatran
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

Study to investigate whether and to what extent the suggested P-glycoprotein (P-gp) inducer rifampicin affects plasma exposure of dabigatran.

研究设计

研究类型
Interventional
分配方式
Na
干预模型
Single Group
主要目的
Treatment
盲法
None

入排标准

年龄范围
18 Years 至 45 Years（Adult）
性别
All
接受健康志愿者
是

入选标准

  • •Healthy male or female subjects according to the following criteria: based upon a complete medical history, including the physical examination, vital signs (BP, pulse rate), 12-lead ECG, clinical laboratory tests
  • •Age ≥18 and Age ≤45 years
  • •Body Mass Index (BMI) ≥18.5 and ≤29.9 kg/m2
  • •Signed and dated written informed consent prior to admission to the study in accordance with GCP and the local legislation

排除标准

  • •Any gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological, or hormonal disorders
  • •Subjects who in the investigator's judgement were perceived as having an increased risk of bleeding, for example because of:
  • •Hemorrhagic disorders or bleeding diathesis
  • •Occult blood in faeces or haematocryal
  • •Trauma or surgery within the last month or as long as an excessive risk of bleeding persisted after these events, or planned surgery during trial participation
  • •History of arteriovenous malformation or aneurysm
  • •History of gastroduodenal ulcer disease, gastrointestinal haemorrhage, and haemorrhoids
  • •History of intracranial, intraocular, spinal, retroperitoneal, or atraumatic intraarticular bleeding
  • •Use of drugs that may have interfered with haemostasis during trial conduct (e.g. acetylic salicylic acid or other non-steroidal anti-inflammatory drugs)
  • •Relevant surgery of gastrointestinal tract
  • •Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders
  • •History of relevant orthostatic hypotension, fainting spells, or blackouts
  • •Chronic or relevant acute infections
  • •History of allergy/hypersensitivity (including drug allergy) which was deemed relevant to the trial as judged by the investigator
  • •Use of drugs which might have reasonably influenced the results of the trial based on the knowledge at the time of protocol preparation within four weeks prior to administration or during the trial, especially inhibitors or inducers of P-gp, CYP3A4, CYP2C9, or CYP2C19 trial (comment: CYP3A4 inhibitors are for example azole antimycotics, macrolides or grapefruit juice, CYP3A inducers are for example St. John's Wort or certain anticonvulsants)
  • •Intake of medication, which influences the blood clotting, i.e. acetylsalicylic acid, nonsteroidal anti-rheumatic drugs, cumarin, etc. within 14 days prior to screening or during the trial
  • •Participation in another trial with an investigational drug within one month prior to administration or during the trial
  • •Alcohol abuse (more than 60 g/day in males, more than 40 g/day in females)
  • •Drug abuse
  • •Blood donation (more than 100 mL within 4 weeks prior to administration)
  • •Any laboratory value outside the reference range that was of clinical relevance
  • •Inability to comply with dietary regimen of study centre
  • •Previous intake of rifampicin
  • •For female subjects:
  • •Pregnancy / positive pregnancy test, or planning to become pregnant during the study or within 1 month of study completion
  • •No adequate contraception in women of childbearing potential
  • •Lactation period

研究组 & 干预措施

Dabigatran etexilate

Experimental

Four treatments of 150 mg Dabigatran etexilate (single oral administration) in a fixed sequence.

  1. Single oral administration of dabigatran etexilate on Day 1;
  2. Oral administration of 600 mg rifampicin q.d. in the evening for 7 days (Days 2 to 8) followed by an oral morning dose of dabigatran etexilate on Day 9;
  3. Single oral administration of dabigatran etexilate on Day 16, after 7 days of rifampicin washout;
  4. Single oral administration of dabigatran etexilate on Day 23, after 14 days of rifampicin washout

干预措施: Dabigatran etexilate (Drug)

Dabigatran etexilate

Experimental

Four treatments of 150 mg Dabigatran etexilate (single oral administration) in a fixed sequence.

  1. Single oral administration of dabigatran etexilate on Day 1;
  2. Oral administration of 600 mg rifampicin q.d. in the evening for 7 days (Days 2 to 8) followed by an oral morning dose of dabigatran etexilate on Day 9;
  3. Single oral administration of dabigatran etexilate on Day 16, after 7 days of rifampicin washout;
  4. Single oral administration of dabigatran etexilate on Day 23, after 14 days of rifampicin washout

干预措施: Rifampicin (Drug)

结局指标

主要结局

Area under the concentration-time curve over the time interval from 0 extrapolated to infinity (AUC0-inf) of total dabigatran

时间窗: 30 min pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 and 34 hours after treatment on Day1, 9, 16 and 23

Maximum measured concentration (Cmax) of total dabigatran

时间窗: 30 min pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 and 334hours after treatment on Day1, 9, 16 and 23

次要结局

  • AUC0-inf of free dabigatran(30 min pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 and 34 hours after treatment on Day1, 9, 16 and 23)
  • Cmax of free dabigatran(30 min pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 and 34 hours after treatment on Day1, 9, 16 and 23)
  • Cmax of dabigatran etexilate(30 min pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 and 34 hours after treatment on Day1, 9, 16 and 23)
  • Time from dosing to the maximum concentration (tmax) of dabigatran etexilate(30 min pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 and 34 hours after treatment on Day1, 9, 16 and 23)
  • Cmax of BIBR 1087SE(30 min pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 and 34 hours after treatment on Day1, 9, 16 and 23)
  • tmax of BIBR 1087SE(30 min pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 and 34 hours after treatment on Day1, 9, 16 and 23)
  • Cmax of BIBR 951BS(30 min pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 and 34 hours after treatment on Day1, 9, 16 and 23)
  • tmax of BIBR 951BS(30 min pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 and 34 hours after treatment on Day1, 9, 16 and 23)
  • Area under the concentration-time curve over the time interval from 0 to the time of the last quantifiable data point (AUC0-tz) of free dabigatran(30 min pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 and 34 hours after treatment on Day1, 9, 16 and 23)
  • AUC0-tz of total dabigatran(30 min pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 and 34 hours after treatment on Day1, 9, 16 and 23)
  • Area under the concentration-time curve over the time interval from timepoints t1 to t2 (AUCt1-t2) of free dabigatran(30 min pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 and 34 hours after treatment on Day1, 9, 16 and 23)
  • AUCt1-t2 of total dabigatran(30 min pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 and 34 hours after treatment on Day1, 9, 16 and 23)
  • Area under the concentration-time curve over the time interval from 0 to 24 h (AUC0-24) of free dabigatran(30 min pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 and 34 hours after treatment on Day1, 9, 16 and 23)
  • AUC0-24 of total dabigatran(30 min pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 and 34 hours after treatment on Day1, 9, 16 and 23)
  • tmax of free dabigatran(30 min pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 and 34 hours after treatment on Day1, 9, 16 and 23)
  • tmax of total dabigatran(30 min pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 and 34 hours after treatment on Day1, 9, 16 and 23)
  • Terminal rate constant (λz) of free dabigatran(30 min pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 and 34 hours after treatment on Day1, 9, 16 and 23)
  • λz of total dabigatran(30 min pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 and 34 hours after treatment on Day1, 9, 16 and 23)
  • Terminal half-life (t1/2) of free dabigatran(30 min pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 and 34 hours after treatment on Day1, 9, 16 and 23)
  • t1/2 of total dabigatran(30 min pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 and 34 hours after treatment on Day1, 9, 16 and 23)
  • Mean residence time after oral administration (MRTpo) of free dabigatran(30 min pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 and 34 hours after treatment on Day1, 9, 16 and 23)
  • MRTpo of total dabigatran(30 min pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 and 34 hours after treatment on Day1, 9, 16 and 23)
  • Apparent clearance after extravascular administration (CL/F) of free dabigatran(30 min pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 and 34 hours after treatment on Day1, 9, 16 and 23)
  • CL/F of total dabigatran(30 min pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 and 34 hours after treatment on Day1, 9, 16 and 23)
  • Apparent volume of distribution during the terminal phase λz following an extravascular dose (Vz/F) of free dabigatran(30 min pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 and 34 hours after treatment on Day1, 9, 16 and 23)
  • Vz/F of total dabigatran(30 min pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 and 34 hours after treatment on Day1, 9, 16 and 23)
  • Amount that is eliminated in urine from the time interval 0- 24h (Ae0-24) of total dabigatran(Day 1 and 9)
  • Fraction excreted unchanged in urine from time point 0-24h (fe0-24) of total dabigatran(Day 1 and 9)
  • Renal clearance from the time point 0 until the point 0-24h (CLR, 0-24) of total dabigatran(Day 1 and 9)
  • Ratio of 6-ß-hydroxycortisol/cortisol in morning spot urine as a marker of CYP 3A induction(Day 1 and 9)

研究者

申办方类型
Industry
责任方
Sponsor

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