NCT02171624已完成1 期
A Two-way Crossover Study to Evaluate the Safety and Pharmacokinetics of Quinidine Sulfate Alone (200 mg Orally q2h to a Maximum of 1,000 mg), Dabigatran Etexilate Alone (150 mg BID for Three Days), and the Co-administration of Dabigatran Etexilate (150 mg BID) With Quinidine Sulfate (200 mg q2h)
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
- 42
- 主要终点
- Differences between treatments in systolic blood pressure profiles (using area under the BP-time curve)
研究概览
简要总结
Open-label, two-way crossover design with a quinidine sulfate run-in period followed by a randomised sequence of dabigatran etexilate plus quinidine sulfate or dabigatran etexilate alone to evaluate the safety of co-administration of dabigatran etexilate and quinidine. and the pharmacokinetic interaction between quinidine and dabigatran etexilate.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy male and female subjects
- •Age ≥18 and Age ≤55 years
- •Body Mass Index (BMI) ≥18.5 and BMI <30 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 finding of the medical examination (including Blood Pressure (BP), Pulse Rate (PR) and Electrocardiogram (ECG)) deviating from normal and of clinical relevance
- •Any evidence of a clinically relevant concomitant disease
- •Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
- •Surgery of the gastrointestinal tract (except appendectomy)
- •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 relevant allergy/hypersensitivity (including allergy to drug or its excipients)
- •Intake of drugs with a long half-life (>24 hours) within at least one month or less than 10 half-lives of the respective drug prior to administration or during the trial
- •Use of drugs which might reasonably influence the results of the trial or that prolong the QT/QTc interval based on the knowledge at the time of protocol preparation within 10 days prior to administration or during the trial
- •Participation in another trial with an investigational drug within thirty days prior to administration or during the trial
- •Inability to refrain from smoking on trial days Smoker (>10 cigarettes or >3 cigars or >3 pipes/day)
- •Alcohol abuse (more than 60 g/day)
- •Drug abuse
- •Blood donation (more than 100 mL within four weeks prior to administration or during the trial)
- •Excessive physical activities (within one week prior to administration or during the trial)
- •Any laboratory value outside the reference range that is of clinical relevance
- •Inability to comply with dietary regimen of trial site
- •A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval >450 ms)
- •A history of additional risk factors for Torsades de Pointes (e.g., heart failure, hypokalemia, family history of Long QT Syndrome)
- •Taking drugs which are known P-gp and/or CYP3A4 inhibitors or inducers (verapamil, phenothiazine antipsychotics, macrolide antibiotics (clarithromycin, erythromycin), antifungal drugs, antiviral drugs (protease inhibitors like nelfinavir) or St. John´s Wort) within the last 4 weeks before screening
- •Taking drugs which are known CYP2D6 substrates (antidepressants, antiarrhythmics, beta blockers) within the last 2 weeks before screening
- •For female subjects:
- •Pregnancy or planning to become pregnant within 2 months of study completion
- •Positive pregnancy test
- •No adequate contraception e.g., sterilisation, IUD (intrauterine device), have not been using a barrier method of contraception for at least 3 months prior to participation in the study
- •Are not willing or are unable to use a reliable method of barrier contraception (such as diaphragm with spermicidal cream/jelly or condoms with spermicidal foam), during and up to 2 months after completion/termination of the trial
- •Chronic use of oral contraception or hormone replacement containing ethinyl estradiol as the only method of contraception
- •Partner is unwilling to use condoms
- •Currently lactating
研究组 & 干预措施
dabigatran etexilate
Experimental
quinidine run-in, followed by dabigatran+quinine and dabigatran alone in randomized order
干预措施: dabigatran etexilate (Drug)
dabigatran etexilate
Experimental
quinidine run-in, followed by dabigatran+quinine and dabigatran alone in randomized order
干预措施: quinidine (Drug)
quinidine
Experimental
quinidine run-in, followed by dabigatran+quinine and dabigatran alone in randomized order
干预措施: dabigatran etexilate (Drug)
quinidine
Experimental
quinidine run-in, followed by dabigatran+quinine and dabigatran alone in randomized order
干预措施: quinidine (Drug)
结局指标
主要结局
Differences between treatments in systolic blood pressure profiles (using area under the BP-time curve)
时间窗: -0:15 before, and every 15 minutes for 2 hours post-dose, 3, 4 and 12 hours post dose
Incidence of symptomatic hypotension
时间窗: -0:15 before, and every 15 minutes for 2 hours post-dose, 3, 4 and 12 hours post dose
次要结局
- Area under the effect curve (AUEC) for activated partial thromboplastin time (aPTT), thrombin time (TT) and ecarin clotting time (ECT)(up to 48 hours after last dose)
- Maximum effect ratio (ERmax) for activated partial thromboplastin time (aPTT), thrombin time (TT) and ecarin clotting time (ECT)(up to 48 hours after last dose)
- Occurrence of Adverse Events(up to day 26)
- Abnormal findings in physical examination(up to day 26)
- Changes from baseline in Vital Signs (Blood Pressure (BP), Heart Rate (HR))(up to day 26)
- Changes from baseline in 12-lead ECG (electrocardiogram)(up to day 26)
- Changes from baseline in QT prolongation(up to day 26)
- Changes in clinical laboratory tests(up to day 26)
- Number of patients with adverse events leading to treatment discontinuation(up to day 26)
- AUC (area under the concentration-time curve of the analyte in plasma)(up to 48 hours after the last dose)
- Cmax (maximum measured concentration of the analyte in plasma)(up to 48 hours after the last dose)
- tmax (time from dosing to the maximum concentration of the analyte in plasma)(up to 48 hours after the last dose)
- λz (terminal rate constant in plasma)(up to 48 hours after the last dose)
- t½ (terminal half-life of the analyte in plasma)(up to 48 hours after the last dose)
- Cpre (pre-dose concentration of the analyte in plasma immediately before administration of the following dose)(up to 48 hours after the last dose)
- MRTpo,ss (mean residence time of the analyte in the body at steady state after po administration)(up to 48 hours after last dose)
- Vz/F,ss (apparent volume of distribution during the terminal phase λz at steady state following an extravascular dose)(up to 48 hours after last dose)
- CL/F,ss (apparent clearance of the analyte in the plasma at steady state after extravascular administration)(up to 48 hours after last dose)
- Cavg (average concentration of the analyte in plasma under steady-state conditions)(up to 48 hours after last dose)
- Cmin,ss (minimum measured concentration of the analyte in plasma at steady state)(up to 48 hours after last dose)
- PTF (peak trough fluctuation)(up to 48 hours after last administration)
- RAUCt1-t2, MET, 5 (ratio of AUCt1-t2 of 3-OH-quinidine/quinidine)(up to 48 hours after last dose)
研究者
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