A Phase 1, Open-Label Study to Examine the Effect of Ciprofloxacin, Itraconazole, and Rifampin on the Pharmacokinetics of Lumacaftor in Combination With Ivacaftor in Healthy Adult Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 80
- 主要终点
- Cohort 4: Change in lung function from before treatment with lumacaftor/ivacaftor to after treatment with lumacaftor/ivacaftor.
研究概览
简要总结
The purpose of this study is to examine the drug-drug interaction effects of ciprofloxacin, itraconazole, and rifampin on the pharmacokinetics of lumacaftor in combination with ivacaftor as well as to evaluate the potential effects of lumacaftor in combination with ivacaftor on lung function.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Male and female subjects must be between the ages of 18 and 55 years, inclusive
- •Body mass index (BMI) of 18 to 31 kg/m2, inclusive, and a total body weight >50 kg.
排除标准
- •History of any illness that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering study drug(s) to the subject. This may include, but is not limited to, a history of relevant drug or food allergies; history of cardiovascular or central nervous system disease; history or presence of clinically significant pathology; or history of mental disease.
- •History of febrile illness within 5 days before the first dose.
- •History of Gilbert's syndrome
- •Abnormal renal function as defined at screening
- •Blood donation of approximately 1 pint (500 mL) within 56 days before study drug administration
- •Treatment with an investigational drug within 30 days or 5 half-lives (or as determined by the local requirements, whichever is longer) preceding the first dose of study drug
- •Known hypersensitivity or prior adverse reaction to ciprofloxacin, or any member of the quinolone class of antimicrobial agents (Cohort 1 only); itraconazole, or to any of the other azoles (Cohort 2 only); rifampin, or to any of the rifamycins (Cohort 3 only)
研究组 & 干预措施
Treatment Group (Cohort 1)
Subjects will take lumacaftor in combination with ivacaftor for 14 days. Beginning on Day 15, subjects will take lumacaftor in combination with ivacaftor and ciprofloxacin through Day 21.
干预措施: Ivacaftor (Drug)
Treatment Group (Cohort 1)
Subjects will take lumacaftor in combination with ivacaftor for 14 days. Beginning on Day 15, subjects will take lumacaftor in combination with ivacaftor and ciprofloxacin through Day 21.
干预措施: Lumacaftor (Drug)
Treatment Group (Cohort 1)
Subjects will take lumacaftor in combination with ivacaftor for 14 days. Beginning on Day 15, subjects will take lumacaftor in combination with ivacaftor and ciprofloxacin through Day 21.
干预措施: Ciprofloxacin (Drug)
Treatment Group (Cohort 2)
Subjects will take lumacaftor in combination with ivacaftor for 14 days. Beginning on Day 15, subjects will take lumacaftor in combination with ivacaftor and itraconazole through Day 21.
干预措施: Lumacaftor (Drug)
Treatment Group (Cohort 2)
Subjects will take lumacaftor in combination with ivacaftor for 14 days. Beginning on Day 15, subjects will take lumacaftor in combination with ivacaftor and itraconazole through Day 21.
干预措施: Ivacaftor (Drug)
Treatment Group (Cohort 4)
Subjects will take a single dose of lumacaftor in combination with ivacaftor on 3 occasions separated by 7 days.
干预措施: Lumacaftor (Drug)
Treatment Group (Cohort 2)
Subjects will take lumacaftor in combination with ivacaftor for 14 days. Beginning on Day 15, subjects will take lumacaftor in combination with ivacaftor and itraconazole through Day 21.
干预措施: Itraconazole (Drug)
Treatment Group (Cohort 3)
Subjects will take lumacaftor in combination with ivacaftor for 14 days. Beginning on Day 15, subjects will take lumacaftor in combination with ivacaftor and rifampin through Day 24.
干预措施: Lumacaftor (Drug)
Treatment Group (Cohort 3)
Subjects will take lumacaftor in combination with ivacaftor for 14 days. Beginning on Day 15, subjects will take lumacaftor in combination with ivacaftor and rifampin through Day 24.
干预措施: Ivacaftor (Drug)
Treatment Group (Cohort 3)
Subjects will take lumacaftor in combination with ivacaftor for 14 days. Beginning on Day 15, subjects will take lumacaftor in combination with ivacaftor and rifampin through Day 24.
干预措施: Rifampin (Drug)
Treatment Group (Cohort 4)
Subjects will take a single dose of lumacaftor in combination with ivacaftor on 3 occasions separated by 7 days.
干预措施: Ivacaftor (Drug)
结局指标
主要结局
Cohort 4: Change in lung function from before treatment with lumacaftor/ivacaftor to after treatment with lumacaftor/ivacaftor.
时间窗: up to 21 days
Cohorts 1-3: PK parameters including Cmax, and AUC from time of dosing to time tau of lumacaftor and ivacaftor in the absence and presence of ciprofloxacin, itraconazole, and rifampin
时间窗: up to 24 days
次要结局
- Cohorts 1-4: Safety and tolerability as measured by adverse events (AEs) and changes in laboratory test values (serum chemistry, hematology, coagulation, and urinalysis), vital signs, standard 12 lead electrocardiograms (ECGs), and spirometry(up to 31 days)
- Cohort 4: PK parameters, including Cmax of lumacaftor/ivacaftor, and lung function(16 days)