A Single-blind, Randomised, Placebo-controlled Study to Investigate the Safety, Tolerability, and Pharmacokinetics of Inhaled AZD4604 Following Single Ascending and Multiple Doses in Healthy Japanese and Chinese Participants
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 56
- 试验地点
- 1
- 主要终点
- Number of participants with adverse event (AEs)
研究概览
简要总结
The purpose of this study is to investigate the safety, tolerability, and pharmacokinetics (PK) of AZD4604 when administered as single or multiple inhaled doses to healthy Japanese and Chinese participants.
详细描述
This study will comprise of two parts: Part 1 and Part 2
Part 1 will investigate the safety, tolerability, and PK of inhaled AZD4604 following single ascending and multiple doses in healthy Japanese participants.
Part 1a will include three single ascending dose (SAD) cohorts and Part 1b will include one multiple dose cohort.
Part 2 will investigate the safety, tolerability, and PK of inhaled AZD4604 following single ascending and multiple doses in healthy Chinese participants.
Part 2a will include two SAD cohort and Part 2b will include one multiple dose cohort.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
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
- •Japanese participants who are born in Japan, has 2 Japanese biological parents, 4 Japanese grandparents as confirmed by the interview and has lived outside Japan for less than 10 years at the time of screening.
- •Chinese participants who are born in China, has 2 Chinese biological parents, 4 Chinese grandparents as confirmed by the interview and has lived outside China for less than 10 years at the time of screening.
- •Have body mass index (BMI) between 18 and 30 kg/m2 and weigh at least 45 kg.
- •Healthy participants must have a Forced Expiratory Volume at first breath (FEV1) ≥ 80% of the predicted value in accordance with American Thoracic Society (ATS)/European Respiratory Society (ERS) criteria at the Screening and admission visits.
- •Female participants must have a negative pregnancy test.
排除标准
- •History or presence of clinically important disease which may put participant at risk because of participation in study.
- •Participant has an increased risk of infection.
- •History of malignancy other than superficial basal cell carcinoma, having a first degree relative with lung cancer or disease history suggesting abnormal immune function.
- •Has received any vaccine 30 days prior to first dose.
- •Has a body temperature of > 37.7°C on Day -
- •History or presence of gastrointestinal, hepatic, or renal disease or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
- •Any clinically important illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of study intervention.
- •Known or suspected history of drug abuse, alcohol abuse or excessive intake of alcohol.
- •Current smokers or those who have smoked or used nicotine products (including e-cigarettes, vaping, and nicotine replacement therapy) within the previous 6 months or has a smoking history of > 5 pack-years.
- •History of a serious or severe adverse reaction to AZD4604 or any of its additive constituents.
- •History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity or history of hypersensitivity to drugs with a similar chemical structure or class to AZD
- •Plasma donation within 1 month of the Screening Visit or any blood donation/blood loss> 500 mL during the 3 months prior to the Screening Visit.
- •Any clinically important abnormalities in rhythm, conduction or morphology of the resting electrocardiogram (ECG) and any clinically important abnormalities in the 12-lead safety ECG.
- •Female participants who are planning a pregnancy during the study period or within 1 month after the last dose of study intervention.
- •Abnormal vital signs at the Screening Visit, after 5 minutes supine rest.
- •History of any significant respiratory disorders such as asthma (a history of childhood asthma without symptoms or treatment after the age of 10 years is allowable), chronic obstructive pulmonary disease, or idiopathic pulmonary fibrosis.
研究组 & 干预措施
Part 1a: AZD4604 (Dose 1) SAD
Japanese participants will receive single dose of AZD4604 (Dose 1) via inhalation on Day 1.
干预措施: AZD4604 (Drug)
Part 1a: AZD4604 (Dose 2) SAD
Japanese participants will receive single dose of AZD4604 (Dose 2) via inhalation on Day 1.
干预措施: AZD4604 (Drug)
Part 1a: AZD4604 (Dose 3) SAD
Japanese participants will receive single dose of AZD4604 (Dose 3) via inhalation on Day 1.
干预措施: AZD4604 (Drug)
Part 1a: Placebo
Japanese participants will receive single dose of matching placebo to AZD4604 on Day 1.
干预措施: Placebo (Drug)
Part 1b: AZD4604 (Dose 4) Multiple dose cohort
Japanese participants will receive AZD4604 (Dose 4) via inhalation twice daily (BID) from Day 1 to Day 6 and a single dose on Day 7.
干预措施: AZD4604 (Drug)
Part 1b: Placebo
Japanese participants will receive matching placebo to AZD4604 BID from day 1 to day 6 and a single dose of placebo on Day 7.
干预措施: Placebo (Drug)
Part 2a: AZD4604 (Dose 1) SAD
Chinese participants will receive single dose of AZD4604 (Dose 1) via inhalation on Day 1.
干预措施: AZD4604 (Drug)
Part 2a: AZD4604 (Dose 3) SAD
Chinese participants will receive single dose of AZD4604 (Dose 3) via inhalation on Day 1.
干预措施: AZD4604 (Drug)
Part 2a: Placebo
Chinese participants will receive single dose of matching placebo to AZD4604 on Day 1.
干预措施: Placebo (Drug)
Part 2 b: AZD4604 (Dose 4) Multiple dose cohort
Chinese participants will receive AZD4604 (Dose 4) via inhalation BID from Day 1 to Day 6 and a single dose on Day 7.
干预措施: AZD4604 (Drug)
Part 2b: Placebo
Chinese participants will receive placebo via inhalation BID from Day 1 to Day 6 and a single dose on Day 7.
干预措施: Placebo (Drug)
结局指标
主要结局
Number of participants with adverse event (AEs)
时间窗: From Day -28 to 5 weeks (Parts 1a and 2a); Day -28 to 6 weeks (Parts 1b and 2b)
To assess the safety and tolerability of AZD4604 following inhaled administration of AZD4604 as single ascending doses (Parts 1a and 2a), and multiple doses (Parts 1b and 2b).
次要结局
- Partial area under concentration-time curve from time 0 to 24 hours (AUC [0-24])(From Day 1 to Day 7 (Parts 1a and 2a); From Day 1 to Day 13 (Parts 1b and 2b))
- Area under the plasma concentration curve from zero to infinity (AUCinf)(From Day 1 to Day 7 (Parts 1a and 2a))
- Apparent total body clearance of drug from plasma after extravascular administration (CL/F)(From Day 1 to Day 7 (Parts 1a and 2a); From Day 1 to Day 13 (Parts 1b and 2b))
- Area under the plasma concentration curve from zero to infinity, divided by dose (AUCinf/D)(From Day 1 to Day 7 (Parts 1a and 2a))
- Half-life associated with terminal slope of a semi-logarithmic concentration time curve (t½λz)(From Day 1 to Day 7 (Parts 1a and 2a); From Day 1 to Day 13 (Parts 1b and 2b))
- Volume of distribution (apparent) at steady state following extravascular administration based on terminal phase (Vz/F)(From Day 1 to Day 7 (Parts 1a and 2a); From Day 1 to Day 13 (Parts 1b and 2b))
- Time to reach peak or maximum observed concentration following drug administration (tmax)(From Day 1 to Day 7 (Parts 1a and 2a); From Day 1 to Day 13 (Parts 1b and 2b))
- Partial area under concentration-time curve from time 0 to 12 hours (AUC [0-12])(From Day 1 to Day 7 (Parts 1a and 2a); On Day 1 (Parts 1b and 2b))
- Area under the plasma concentration curve from zero to last quantifiable concentration (AUClast)(From Day 1 to Day 7 (Parts 1a and 2a); From Day 1 to Day 13 (Parts 1b and 2b))
- The last time point at which the concentration is measured (tlast)(From Day 1 to Day 7 (Parts 1a and 2a); From Day 1 to Day 13 (Parts 1b and 2b))
- Area under plasma concentration time curve from zero to end of dosing interval (AUCτ)(From Day 1 to Day 13 (Parts 1b and 2b))
- Cough Severity self-assessment as measured by Visual Analogue Scale (VAS)(From Day 1 to Day 8 (Parts 1b and 2b))
- Maximum observed plasma (peak) drug concentration (Cmax)(From Day 1 to Day 7 (Parts 1a and 2a); From Day 1 to Day 13 (Parts 1b and 2b))
- Terminal elimination rate constant (λz)(From Day 1 to Day 7 (Parts 1a and 2a); From Day 1 to Day 13 (Parts 1b and 2b))
- Area under the plasma concentration time curve from zero to the last quantifiable concentration, divided by dose (AUClast/D)(From Day 1 to Day 7 (Parts 1a and 2a); From Day 1 to Day 13 (Parts 1b and 2b))
- Area under plasma concentration time curve from zero to end of dosing interval, by dose (AUCτ/D)(From Day 1 to Day 13 (Parts 1b to 2b))
- Maximum observed plasma (peak) drug concentration, by dose (Cmax/D)(From Day 1 to Day 7 (Parts 1a and 2a); From Day 1 to Day 13 (Parts 1b and 2b))