An Open-label, Randomized, Two-period Crossover Study to Evaluate the Effect of Multiple Doses of Ketoconazole on the Pharmacokinetics of Darexaban and Metabolites in Young Healthy Male Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 26
- 试验地点
- 1
- 主要终点
- Pharmacokinetics of darexaban and its metabolites assessed by plasma concentration
研究概览
简要总结
The primary objective of this study is to determine the effect of ketoconazole on the blood concentrations of darexaban and its metabolites (drug degradation products). The secondary objective of the study is to evaluate the safety and tolerability of a single dose of darexaban alone and when administered together with ketoconazole.
详细描述
This is an open-label, 2-period crossover study in young healthy male subjects to evaluate the effect of multiple once daily doses of ketoconazole on the pharmacokinetics (PK) of darexaban and metabolites after a single dose of darexaban. In addition, safety and tolerability of darexaban administered alone and in combination with ketoconazole, is evaluated. Eligible subjects are admitted to the clinical unit in the morning of Day -1. The subjects are randomized to receive either first darexaban plus ketaconazole and then darexaban alone, or first darexaban alone followed by darexaban plus ketoconazole.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Body mass index (BMI) between 18.5-30.0 kg/m2
- •Male subjects must be non-fertile, i.e. surgically sterilized or must practice an adequate contraceptive method to prevent pregnancies
排除标准
- •Known or suspected hypersensitivity to darexaban or ketoconazole or any components of the formulation used
- •Any of the liver function tests (i.e. ALT, AST and bilirubin) above the upper limit of normal at repeated measures
- •Any clinically significant history of any other disease or disorder - gastrointestinal, cardiovascular, respiratory, renal, hepatic, neurological, dermatological, psychiatric or metabolic as judged by the medical investigator
- •Any clinically significant abnormality following the investigator's review of the pre-study physical examination, ECG and clinical laboratory tests
- •Use of any prescribed or OTC (over-the-counter) drugs (including vitamins, natural and herbal remedies, e.g. St. John's wort) in the 2 weeks prior to admission to the Clinical Unit, except for occasional use of paracetamol (up to 3 g/day)
- •Regular use of any inducer of liver metabolism (e.g. barbiturates, rifampicin) in the 3 months prior to admission to the Clinical Unit
- •Donation of blood or blood products within 3 months prior to admission to the Clinical Unit
- •Any use of drugs of abuse, or smoking of more than 10 cigarettes (or equivalent) or more than 21 units (210 g) of alcohol per week within the 3 months prior to study
- •Participation in any clinical study within 3 months or participation in more than 3 clinical studies within 12 months, prior to the expected date of enrolment into the study, provided that the clinical study did not entail a biological compound with a long terminal half life
研究组 & 干预措施
Treatment arm A
darexaban, wash-out, ketoconazole + darexaban
干预措施: darexaban (Drug)
Treatment arm A
darexaban, wash-out, ketoconazole + darexaban
干预措施: ketoconazole (Drug)
Treatment arm B
ketoconazole + darexaban, wash-out, darexaban
干预措施: darexaban (Drug)
Treatment arm B
ketoconazole + darexaban, wash-out, darexaban
干预措施: ketoconazole (Drug)
结局指标
主要结局
Pharmacokinetics of darexaban and its metabolites assessed by plasma concentration
时间窗: Plasma samples are taken until 72 hours (darexaban alone) or 144 hours (combination of darexaban and ketoconazole) after darexaban dosing
次要结局
- Monitoring of safety and tolerability through assessment of vital signs, Electrocardiogram (ECG), clinical safety laboratory and adverse events(16 days)