An Open Label Study in Healthy Volunteers to Evaluate the Potential for Drug/Drug Interactions Between F901318 and Fluconazole
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Treatment emergent adverse events
研究概览
简要总结
This will be an open label study in two parts. In the first part, F901318 (dose 2 mg/kg IV over 4 hours, Day 1) will be followed by F901318 (2 mg/kg IV over 4 hours) given on Day 8, after dosing with fluconazole 800 mg daily for 1 day (Day 4) and 400 mg daily orally for 4 days (Days 5 to 8). Up to twenty subjects will be included in two cohorts which will undergo the same dosing schedules of fluconazole and F901318 and undergo the same procedures. The first cohort will consist of 12 subjects studied in two groups of six subjects each. If there is clearly a difference in F901318 kinetics detectable before and after dosing with fluconazole in this first cohort, the second cohort will not be studied. If there is no clear difference, the second cohort will also be studied to give a final result. In this cohort, based on the pharmacokinetic findings in cohort 1, the dose of F901318 may be increased to up to 4 mg/kg to establish a dose suitable for phase 2 evaluation. PK sampling for plasma F901318 will continue from before the first dose up to and including 72 hours after dosing. PK sampling for fluconazole will continue from before the first dose and up to 72 hours after the fifth dose. A follow up visit will be conducted 7 +/- 2 days after discharge from the clinical unit following completion of blood sampling following the second dose of F901318 and the fifth dose of fluconazole.
The second part of the study will take place if no appreciable change in the pharmacokinetics of either F901318 or fluconazole has been observed in either the first or the second cohorts in the first part of the study. This second part will enrol 12 subjects. These subjects will receive fluconazole 800 mg daily for one day (Day 1) and 400 mg daily orally for 4 days (Days 2 to 5) in combination with F901318 which will be given in a dose of up to 4 mg/kg IV bid for one day (Day 1) followed by 7 doses of intravenous F901318 up to 2.5 mg/kg bid (Days 2 to 5). Pharmacokinetic profiles of F901318 and fluconazole will be obtained during dosing and over a 72-hour period following the final dose of both compounds.
详细描述
Part 1
Treatment Period (Day -1 to Day 11; visit 2):
Subjects will be admitted to the clinical unit in the afternoon of Day -1 and will remain on site until completion of the 72-hour post fluconazole and F901318 dose study-related procedures on Day 11. Admission procedures (Day -1) include a review of inclusion/exclusion criteria, weight, vital signs, test for drugs of abuse, alcohol and smoking and pregnancy where appropriate (must be negative), and a review of concomitant medication and adverse events. Blood (haematology, clinical chemistry and coagulation function) and urine (urinalysis) will be obtained for safety evaluations. Breakfast will be taken 30-60 minutes prior to dosing)
Days 1 - 4: F901318 (2 mg/kg IV for cohort 1 and up to 4 mg/kg IV for cohort 2) over 4 hours will be administered on Day 1. Blood samples for determination of plasma levels of F901318 will be collected predose and at the following time points up to 72 hours post-dose:
1, 2, 3, 4, 4.25, 4.5, 5, 6, 8, 10, 12, 16, 20, 24, 38, 48, 72 hours
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
- •Subjects will be males and females of any ethnic origin aged between 18 and 45 years of age and weighing 50-100 kg inclusive.
- •Subjects must be in good health, as determined by a medical history, physical examination, 12-lead electrocardiogram (ECG) and clinical laboratory evaluations (congenital non haemolytic hyperbilirubinaemia is acceptable).
- •Subjects will have given their written informed consent to participate in the study and to abide by the study restrictions.
排除标准
- •Male and female subjects who are not willing to use appropriate contraception during the study and for three months thereafter.
- •Subjects who have received any prescribed systemic or topical medication within 14 days of the dose administration unless in the opinion of the Investigator and the Medical Monitor the medication will not interfere with the study procedures or compromise safety.
- •Subjects who have used any non-prescribed systemic or topical medication (including herbal remedies) within 7 days of the dose administration (with the exception of vitamin/mineral supplements and paracetamol) unless in the opinion of the Investigator and the Medical Monitor the medication will not interfere with the study procedures or compromise safety.
- •Subjects who have received any medications, including St John's Wort, known to chronically alter drug absorption or elimination processes within 30 days of the dose administration unless in the opinion of the Investigator and the Medical Monitor the medication will not interfere with the study procedures or compromise safety. For at least 2 weeks prior to dosing and until all blood samples and observations are completed on Day 18 +/- 2 (Part 1) or Day 15 +/- 2 (Part 2), subjects will not be allowed to eat any food or drink any beverage containing alcohol, grapefruit or grapefruit juice, apple or orange juice, vegetables from the mustard green family e.g. kale, broccoli, watercress, spring greens, kohlrabi, Brussels sprouts, mustard and charbroiled meats.
研究组 & 干预措施
Single dose F901318 with fluconazole
AUC0-t for F901318 will be assessed before and after 5 days of treatment with fluconazole oral
干预措施: F901318 (Drug)
Single dose F901318 with fluconazole
AUC0-t for F901318 will be assessed before and after 5 days of treatment with fluconazole oral
干预措施: Fluconazole (Drug)
结局指标
主要结局
Treatment emergent adverse events
时间窗: 5 days
Adverse events
次要结局
- Pharmacokinetics area under concentration/time curve 0-t(5 days)