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
Overview
- Phase
- Phase 1
- Intervention
- AZD4604
- Conditions
- Healthy Participants
- Sponsor
- AstraZeneca
- Enrollment
- 56
- Locations
- 1
- Primary Endpoint
- Number of participants with adverse event (AEs)
- Status
- Completed
- Last Updated
- 5 months ago
Overview
Brief Summary
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.
Detailed Description
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. Part 1a and Part 2a will comprise of: 1. A Screening Visit within 28 days before dosing. 2. A treatment period (Day 1 to Day 7) 3. A final assessment on Day 7 Part 1b and Part 2b will comprise of: 1. A Screening Visit within 28 days before dosing. 2. A treatment period (Day 1 to Day 13) 3. A final assessment on Day 13
Investigators
Eligibility Criteria
Inclusion Criteria
- •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.
Exclusion Criteria
- •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.
Arms & Interventions
Part 1a: AZD4604 (Dose 1) SAD
Japanese participants will receive single dose of AZD4604 (Dose 1) via inhalation on Day 1.
Intervention: AZD4604
Part 1a: AZD4604 (Dose 2) SAD
Japanese participants will receive single dose of AZD4604 (Dose 2) via inhalation on Day 1.
Intervention: AZD4604
Part 1a: AZD4604 (Dose 3) SAD
Japanese participants will receive single dose of AZD4604 (Dose 3) via inhalation on Day 1.
Intervention: AZD4604
Part 1a: Placebo
Japanese participants will receive single dose of matching placebo to AZD4604 on Day 1.
Intervention: Placebo
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.
Intervention: AZD4604
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.
Intervention: Placebo
Part 2a: AZD4604 (Dose 1) SAD
Chinese participants will receive single dose of AZD4604 (Dose 1) via inhalation on Day 1.
Intervention: AZD4604
Part 2a: AZD4604 (Dose 3) SAD
Chinese participants will receive single dose of AZD4604 (Dose 3) via inhalation on Day 1.
Intervention: AZD4604
Part 2a: Placebo
Chinese participants will receive single dose of matching placebo to AZD4604 on Day 1.
Intervention: Placebo
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.
Intervention: AZD4604
Part 2b: Placebo
Chinese participants will receive placebo via inhalation BID from Day 1 to Day 6 and a single dose on Day 7.
Intervention: Placebo
Outcomes
Primary Outcomes
Number of participants with adverse event (AEs)
Time Frame: 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).
Secondary Outcomes
- 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))