Effect of BIA 9-1067 on the Pharmacokinetics and Pharmacodynamics of Warfarin in Healthy Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Cmax - Maximum Observed Plasma Concentration (BIA 9-1067 + Warfarin)
研究概览
简要总结
The purpose of this study is to investigate CYP2C9 inhibition by BIA 9-1067 through the assessment of its effect on the pharmacokinetics of S-warfarin, a substrate of CYP2C9.
详细描述
Single-centre, open-label, randomised, two-way crossover study in healthy young male and female volunteers. The study was to consist of 2 treatment periods separated by a washout period of 14 days or more. In one period, subjects were to receive a single-dose of 25 mg BIA 9-1067 with a single-dose of racemic 25 mg warfarin. In the other period, a 25 mg warfarin single-dose was to be administered alone.
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 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Able and willing to give written informed consent.
- •Male or female subjects aged between 18 and 45 years, inclusive.
- •Subjects of body mass index (BMI) between 19 and 30 kg/m2, inclusive.
- •Healthy as determined by pre-study medical history, physical examination, vital signs, complete neurological examination and 12-lead ECG.
- •Negative tests for HBsAg, anti-HCVAb and HIV-1 and HIV-2 Ab at screening.
- •Clinical laboratory test results clinically acceptable at screening and admission to each treatment period.
- •Negative screen for alcohol and drugs of abuse at screening and admission to each treatment period.
- •Non-smokers or ex-smokers for at least 3 months.
- •(If female) She was not of childbearing potential by reason of surgery or, if of childbearing potential, she used one of the following methods of contraception: double barrier or intrauterine device.
- •(If female) She had a negative urine pregnancy test at screening and admission to each treatment period.
排除标准
- •Clinically relevant history or presence of respiratory, gastrointestinal, renal, hepatic, haematological, lymphatic, neurological, cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological, dermatological, endocrine, connective tissue diseases or disorders.
- •Clinically relevant surgical history.
- •Personal or family history of haemostatic disorder.
- •Personal or family history of bleeding complications after surgery or tooth extraction, nose or gingival bleeding, or haemorrhagic diathesis.
- •Any abnormality in the coagulation tests.
- •Any abnormality in the liver function tests.
- •A history of relevant atopy or drug hypersensitivity.
- •History of alcoholism or drug abuse.
- •Consumed more than 14 units of alcohol a week.
- •Significant infection or known inflammatory process at screening or admission to each treatment period.
- •Acute gastrointestinal symptoms (e.g., nausea, vomiting, diarrhoea, heartburn) at the time of screening or admission to each treatment period.
- •Had used medicines within 2 weeks of admission to first period that may have affected the safety or other study assessments, in the investigator's opinion.
- •Had previously received BIA 9-
- •Had used any investigational drug or participated in any clinical trial within 6 months prior to screening.
- •Had participated in more than 2 clinical trials within the 12 months prior to screening.
- •Had donated or received any blood or blood products within the 3 months prior to screening.
- •Vegetarians, vegans or had medical dietary restrictions.
- •Cannot communicate reliably with the investigator.
- •Unlikely to co-operate with the requirements of the study.
- •Unwilling or unable to gave written informed consent.
- •Employees at BIAL - Portela & Co, SA.
- •(If female) She was pregnant or breast-feeding.
- •(If female) She was of childbearing potential and she did not used an approved effective contraceptive method (double-barrier or intra-uterine device) or she used oral contraceptives.
研究组 & 干预措施
Group 1
Period 1: BIA 9-1067 + warfarin Period 2: warfarin
干预措施: BIA 9-1067 (Drug)
Group 1
Period 1: BIA 9-1067 + warfarin Period 2: warfarin
干预措施: Warfarin (Drug)
Group 2
Period 1: warfarin Period 2: BIA 9-1067 + warfarin
干预措施: BIA 9-1067 (Drug)
Group 2
Period 1: warfarin Period 2: BIA 9-1067 + warfarin
干预措施: Warfarin (Drug)
结局指标
主要结局
Cmax - Maximum Observed Plasma Concentration (BIA 9-1067 + Warfarin)
时间窗: before dose and ½, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120 and 144 h post- dose.
Mean plasma BIA 9-1067 pharmacokinetic parameters obtained following an oral single dose of 25 mg warfarin co-administered with 25 mg BIA 9-1067
Tmax - Time to Maximum Observed Plasma Concentration (BIA 9-1067 + Warfarin)
时间窗: before dose and ½, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120 and 144 h post- dose.
Mean plasma BIA 9-1067 pharmacokinetic parameters obtained following an oral single dose of 25 mg warfarin co-administered with 25 mg BIA 9-1067
AUC0-t - Area Under the Plasma Concentration-time Curve From Time 0 to Last Observed Concentration (BIA 9-1067 + Warfarin)
时间窗: before dose and ½, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120 and 144 h post- dose.
Mean plasma BIA 9-1067 pharmacokinetic parameters obtained following an oral single dose of 25 mg warfarin co-administered with 25 mg BIA 9-1067
Cmax = Maximum Plasma Concentration (Warfarin Alone)
时间窗: before dose and ½, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120 and 144 h post- dose.
Mean plasma S-warfarin pharmacokinetic parameters obtained following an oral singledose of 25 mg warfarin administered alone
Tmax - Time to Maximum Observed Plasma Concentration (Warfarin Alone)
时间窗: before dose and ½, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120 and 144 h post- dose.
Mean plasma S-warfarin pharmacokinetic parameters obtained following an oral singledose of 25 mg warfarin administered alone
AUC0-t - Area Under the Plasma Concentration-time Curve From Time 0 to Last Observed Concentration (Warfarin Alone)
时间窗: before dose and ½, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120 and 144 h post- dose.
Mean plasma S-warfarin pharmacokinetic parameters obtained following an oral singledose of 25 mg warfarin administered alone
Cmax - Maximum Observed Plasma Concentration (Warfarin + BIA 9-1067)
时间窗: before dose and ½, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120 and 144 h post- dose.
Mean plasma S-warfarin pharmacokinetic parameters obtained following an oral single dose of 25 mg warfarin co-administered with 25 mg BIA 9-1067
Tmax - Time to Maximum Observed Plasma Concentration (Warfarin + BIA 9-1067)
时间窗: before dose and ½, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120 and 144 h post- dose.
Mean plasma S-warfarin pharmacokinetic parameters obtained following an oral single dose of 25 mg warfarin co-administered with 25 mg BIA 9-1067
AUC0-t - Area Under the Plasma Concentration-time Curve From Time 0 to Last Observed Concentration (Warfarin + BIA 9-1067)
时间窗: before dose and ½, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120 and 144 h post- dose.
Mean plasma S-warfarin pharmacokinetic parameters obtained following an oral single dose of 25 mg warfarin co-administered with 25 mg BIA 9-1067
次要结局
未报告次要终点