Open-label, Non-randomized, One Sequence Cross-over Study to Investigate the Effect of Inhibition of CYP3A4/5 by Itraconazole on the Pharmacokinetics of CHF6001 in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Pharmacokinetic parameter (Cmax)
研究概览
简要总结
The objective of this proposed study is to investigate the pharmacokinetics interaction between CHF6001 as substrate and Itraconazole as inhibitor of CYP3A4/5 in a drug-drug interaction study.
详细描述
This clinical trial is a single centre, single dose Phase I study, with a non-randomized, open label, one sequence cross-over design.
A total of 24 healthy male and female are planned to be included.
Participants will be dosed with CHF6001 before and during co-administration of Itraconazole and will act as their own control. The study will be run with a one-sequence crossover design, where all subjects will be treated with CHF6001 in the first treatment period and CHF6001+Itraconazole in the second treatment period in order to avoid the need of a very long washout from the CYP3A4/5 inhibitor.
Standard safety assessments will be conducted during the Study, including safety blood and urine laboratory tests, vital signs, physical examinations, ECGs and observations of any adverse events. Blood samples will be also collected for PK analysis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Crossover
- 主要目的
- Other
- 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
- •Subject's written informed consent obtained prior to any study-related procedure;
- •Healthy male and female subjects aged 18-55 years inclusive;
- •Ability to understand the study procedures, the risks involved and ability to be trained to use the inhalers correctly and to generate sufficient PIF using the In-Check device.
- •Body Mass Index (BMI) between 18,0 and 35,0 kg/m2 extremes inclusive;
- •Non- or ex-smokers who smoked < 5 pack years and stopped smoking > 1 year prior to screening;
- •Good physical and mental status
- •Vital signs within normal limits
- •12 -lead digitalized Electrocardiogram (12-lead ECG) considered as normal
- •Pulmonary function test within normal limits
- •Women of Childbearing Potential (WOCBP) with fertile male partners: they and/or their partner must be willing to use a highly effective birth control method in addition to a barrier contraception method from the signature of the informed consent and until the follow-up visit. Males with non-pregnant WOCBP partners: they and or/ their partner must be willing to use a highly effective birth control method in addition to the male condom from the signature of the informed consent and until the follow-up visit. Males with pregnant WOCBP partner: they must be willing to use male contraception (condom) from the signature of the informed consent and until the follow-up visit
排除标准
- •Participation to another clinical trial where investigational drug was received, and last investigations were performed less than 8 weeks prior to screening;
- •Clinically relevant and uncontrolled respiratory, cardiac, hepatic, gastrointestinal, renal, endocrine, metabolic, neurologic, or psychiatric disorders, gastric surgery recent or in the past, and/or impaired gastric motility
- •Clinically relevant abnormal laboratory values
- •Abnormal liver enzymes at screening
- •Subjects with history of breathing problems
- •Positive HIV1 or HIV2 serology
- •Positive results from the Hepatitis serology
- •Blood donation or blood loss (equal or more than 450 ml) less than 2 months prior to screening or before the first dosing;
- •Positive urine test for cotinine
- •Documented history of alcohol abuse within 12 months prior to screening or a positive alcohol breath test
- •Documented history of drug abuse within 12 months prior to screening or a positive urine drug screen
- •Intake of non-permitted concomitant medications in the predefined period
- •Presence of any current infection, or previous infection that resolved less than 7 days prior to screening or before the first dosing;
- •Known intolerance and/or hypersensitivity to any of the excipients contained in the formulation used in the trial;
- •Known allergy to antifungal medicines;
- •Unsuitable veins for repeated venipuncture;
- •Heavy caffeine drinker
- •For females only: pregnant or lactating women. Serum pregnancy test to be performed at screening and urine pregnancy test to be performed before the first dosing;
- •Subjects receiving treatment with any drug known to have a well-defined potential for hepatotoxicity (e.g. isoniazide, nimesulide, ketoconazole) within the previous 3 months before the screening visit
- •Subjects using e-cigarettes within 6 months before screening.
- •Positive documented COVID-19 test before admission
研究组 & 干预措施
Treatment R
Single dose of CHF6001
干预措施: CHF6001 DPI (Drug)
Treatment T
Single dose of CHF6001 administered after repeated doses of oral Itraconazole
干预措施: CHF6001 DPI (Drug)
Treatment T
Single dose of CHF6001 administered after repeated doses of oral Itraconazole
干预措施: Itraconazole (Drug)
结局指标
主要结局
Pharmacokinetic parameter (Cmax)
时间窗: Over 96 hours after administration in blood
Peak Plasma Concentration (Cmax) for CHF6001
Pharmacokinetic parameter (AUCt)
时间窗: Over 96 hours after administration in blood
Area under the plasma concentration versus time curve (AUCt) for CHF6001
次要结局
- Pharmacokinetic parameter (t1/2)(Over 96 hours after administration in blood)
- Pharmacokinetic parameter (AUC0-∞)(Over 96 hours after administration in blood)
- Pharmacokinetic parameter (tmax)(Over 96 hours after administration in blood)
- Pharmacokinetic parameter (AUC0-96)(Over 96 hours after administration in blood)
- Pharmacokinetic parameter (CL/F)(Over 96 hours after administration in blood)
- Pharmacokinetic parameter (AUCt)(Over 96 hours after administration in blood)
- Pharmacokinetic parameter (Cmax)(Over 96 hours after administration in blood)