A Randomised, Double-blind, Placebo-controlled Proof-of-pharmacology Study of EP395 in Healthy Adults
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 49
- 试验地点
- 1
- 主要终点
- Bronchoalveolar lavage fluid interleukin 8 at Day 21
研究概览
简要总结
This study aims to assess the effect of EP395 against an induced inflammation of the lung. In addition, further data about the safety and tolerability of EP395 will be collected.
To investigate the efficacy of EP395 at the end of the treatment with EP395 or placebo (dummy), all participants will inhale a lipopolysaccharide (a molecule composed of sugar and fat) that artificially induces an acute inflammation of the airways. It is assumed that participants who received EP395 will show less inflammation of the airways than participants who received placebo.
详细描述
This is a study to assess the pharmacological effect of repeated doses of EP395 in healthy subjects with the aim to assess the effects of EP395 on lung and blood markers of inflammation after inhaled lipopolysaccharide (LPS), and the safety, tolerability, and systemic exposure of EP395.
The study will be randomised in a 1:1 ratio to take either high dose EP395 or placebo as oral capsules once daily for 21 days starting on Day 1 with scheduled visits at Days 7, 14, and 21 for assessments of safety and tolerability and systemic exposure of EP395. At Day 21, 2 hours after the last investigational product (IP) intake, participants will undergo an inhaled LPS challenge to induce airway inflammation, which will be followed by bronchoscopy and BAL 6 hours later. A final safety follow-up visit will be performed at Day 37.
If the data from the high dose EP395 arm (variability, effect size) indicate that it may be possible to detect effects on IL-8 at a lower dose of EP395, an additional lower dose EP395 arm will be added.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
盲法说明
During the study, study participants, investigators, the sponsor, and all other persons involved in the conduct of the study will be blinded to treatment.
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
- 未提供
排除标准
- •History or presence of any clinically relevant medical condition that could affect the participant's safety or interfere with the objectives of the study
- •Presence or history of lung disease, eg, asthma, chronic obstructive pulmonary disease
- •Clinically significant abnormality on 12-lead ECG including prolonged corrected QT interval by Fredericia (>450 msec men or >470 msec women)
- •Use of prescribed or nonprescribed medications or herbal remedies within 28 days of first dosing and during the study with the exception of
- •hormone replacement therapy (HRT)
- •contraception
- •occasional use of paracetamol
- •Positive hepatitis B surface antigen, hepatitis C antibodies, HIV-1 or -2 antibodies
- •Positive drugs of abuse, smoking, or alcohol test at Screening
- •History of alcohol or drug misuse
- •Pregnant and lactating women
- •Prior recovery from recent infection, including but not limited to COVID-19, within the last 14 days before first dosing with IP
- •History of hypersensitivity to any constituents of the IMP or LPS
- •Any clinically significant allergy
- •Participation in a clinical study with an IP within 3 months or 5 half-lives before first dosing, whichever is longer
- •Employees of the sponsor or employees or relatives of the investigator
研究组 & 干预措施
Placebo
Matched placebo capsule, once-daily administration of 3 placebo capsules for 21 days
干预措施: Placebo (Drug)
EP395 low dose
EP395 in repeated doses. Orally, once-daily administration of 1 EP395 capsule and 2 placebo capsules for 21 days
干预措施: EP395 (Drug)
EP395 high dose
EP395 in repeated doses. Orally, once-daily administration of 3 EP395 capsules for 21 days
干预措施: EP395 (Drug)
结局指标
主要结局
Bronchoalveolar lavage fluid interleukin 8 at Day 21
时间窗: Day 21
次要结局
- Height and weight(Screening (Day -21 to Day -1), Day 37 (±3 days))
- ECG ventricular rate(Screening (Day -21 to Day -1), Days 1, 7 (±2 days), 14 (±2 days), Day 21 (±2 days), Day 37 (±3 days))
- Assessment of laboratory values (blood biochemistry)(Screening (Day -21 to Day -1), Days 1, 7 (±2 days), 14 (±2 days), Day 21 (±2 days), Day 37 (±3 days))
- Vital signs: Systolic and diastolic blood pressure(Screening (Day -21 to Day -1), Days 1, 7 (±2 days), 14 (±2 days), Day 21 (±2 days))
- Assessment of laboratory values (haematology)(Screening (Day -21 to Day -1), Days 1, 7 (±2 days), 14 (±2 days), Day 21 (±2 days), Day 37 (±3 days))
- Exhaled particles IL-6 and IL-8(Day 21 (±2 days))
- ECG RR interval(Screening (Day -21 to Day -1), Days 1, 7 (±2 days), 14 (±2 days), Day 21 (±2 days), Day 37 (±3 days))
- ECG PR interval(Screening (Day -21 to Day -1), Days 1, 7 (±2 days), 14 (±2 days), Day 21 (±2 days), Day 37 (±3 days))
- Assessment of blood coagulation(Screening (Day -21 to Day -1), Days 1, 7 (±2 days), 14 (±2 days), Day 21 (±2 days), Day 37 (±3 days))
- BALF cell count (total and differential) and mediators(Day 21 (±2 days))
- ECG QRS duration(Screening (Day -21 to Day -1), Days 1, 7 (±2 days), 14 (±2 days), Day 21 (±2 days), Day 37 (±3 days))
- ECG QT interval (uncorrected)(Screening (Day -21 to Day -1), Days 1, 7 (±2 days), 14 (±2 days), Day 21 (±2 days), Day 37 (±3 days))
- ECG QTcF intervals(Screening (Day -21 to Day -1), Days 1, 7 (±2 days), 14 (±2 days), Day 21 (±2 days), Day 37 (±3 days))
- Urinalysis(Screening (Day -21 to Day -1), Days 1, 7 (±2 days), 14 (±2 days), Day 21 (±2 days), Day 37 (±3 days))
- Vital signs: Body temperature(Screening (Day -21 to Day -1), Days 1, 7 (±2 days), 14 (±2 days), Day 21 (±2 days))
- Plasma EP395(Day 7 (±2 days) [only applicable for trough levels of EP395], Day 14 (±2 days) and Day 21 (±2 days))
- Standard routine physical examination(Screening (Day -21 to Day -1), Days 1, Day 21 (±2 days), Day 37 (±3 days))
- Assessment of adverse event (AE) occurrence(From Screening (Day -21 to Day -1), to Day 37 (±3 days))
- Vital signs: Pulse(Screening (Day -21 to Day -1), Days 1, 7 (±2 days), 14 (±2 days), Day 21 (±2 days))
- Blood inflammatory markers including C-reactive protein, TNF-α, IL-6, IL-8, and α2-macroglobulin(Day 21 (±2 days))