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.
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
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
56
Research Site
Harrow, United Kingdom
Number of participants with adverse event (AEs)
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).
Time frame: From Day -28 to 5 weeks (Parts 1a and 2a); Day -28 to 6 weeks (Parts 1b and 2b)
Maximum observed plasma (peak) drug concentration (Cmax)
To characterise the plasma PK of AZD4604 following inhaled administration of AZD4604 as single ascending doses (Parts 1a and 2a), and multiple doses (Parts 1b and 2b).
Time frame: 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)
To characterise the plasma PK of AZD4604 following inhaled administration of AZD4604 as single ascending doses (Parts 1a and 2a), and multiple doses (Parts 1b and 2b).
Time frame: 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)
To characterise the plasma PK of AZD4604 following inhaled administration of AZD4604 as single ascending doses (Parts 1a and 2a), and multiple doses (Parts 1b and 2b).
Time frame: From Day 1 to Day 7 (Parts 1a and 2a); From Day 1 to Day 13 (Parts 1b and 2b)
Half-life associated with terminal slope of a semi-logarithmic concentration time curve (t½λz)
To characterise the plasma PK of AZD4604 following inhaled administration of AZD4604 as single ascending doses (Parts 1a and 2a), and multiple doses (Parts 1b and 2b).
Time frame: From Day 1 to Day 7 (Parts 1a and 2a); From Day 1 to Day 13 (Parts 1b and 2b)
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Partial area under concentration-time curve from time 0 to 12 hours (AUC [0-12])
To characterise the plasma PK of AZD4604 following inhaled administration of AZD4604 as single ascending doses (Parts 1a and 2a), and multiple doses (Parts 1b and 2b).
Time frame: From Day 1 to Day 7 (Parts 1a and 2a); On Day 1 (Parts 1b and 2b)
Partial area under concentration-time curve from time 0 to 24 hours (AUC [0-24])
To characterise the plasma PK of AZD4604 following inhaled administration of AZD4604 as single ascending doses (Parts 1a and 2a), and multiple doses (Parts 1b and 2b).
Time frame: 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 last quantifiable concentration (AUClast)
To characterise the plasma PK of AZD4604 following inhaled administration of AZD4604 as single ascending doses (Parts 1a and 2a), and multiple doses (Parts 1b and 2b).
Time frame: 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)
To characterise the plasma PK of AZD4604 following inhaled administration of AZD4604 as single ascending doses (Parts 1a and 2a).
Time frame: From Day 1 to Day 7 (Parts 1a and 2a)
Apparent total body clearance of drug from plasma after extravascular administration (CL/F)
To characterise the plasma PK of AZD4604 following inhaled administration of AZD4604 as single ascending doses (Parts 1a and 2a), and multiple doses (Parts 1b and 2b).
Time frame: 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)
To characterise the plasma PK of AZD4604 following inhaled administration of AZD4604 as single ascending doses (Parts 1a and 2a), and multiple doses (Parts 1b and 2b).
Time frame: 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)
To characterise the plasma PK of AZD4604 following inhaled administration of AZD4604 as single ascending doses (Parts 1a and 2a), and multiple doses (Parts 1b and 2b).
Time frame: 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)
To characterise the plasma PK of AZD4604 following inhaled administration of AZD4604 as single ascending doses (Parts 1a and 2a).
Time frame: From Day 1 to Day 7 (Parts 1a and 2a)
Maximum observed plasma (peak) drug concentration, by dose (Cmax/D)
To characterise the plasma PK of AZD4604 following inhaled administration of AZD4604 as single ascending doses (Parts 1a and 2a), and multiple doses (Parts 1b and 2b).
Time frame: 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)
To characterise the plasma PK of AZD4604 following inhaled administration of AZD4604 as single ascending doses (Parts 1a and 2a), and multiple doses (Parts 1b and 2b).
Time frame: 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)
To characterise the plasma PK of AZD4604 following inhaled administration of AZD4604 as multiple doses (Parts 1b and 2b).
Time frame: 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)
To characterise the plasma PK of AZD4604 following inhaled administration of AZD4604 as multiple doses (Parts 1b and 2b).
Time frame: From Day 1 to Day 13 (Parts 1b to 2b)
Cough Severity self-assessment as measured by Visual Analogue Scale (VAS)
The cough VAS is a brief and simple measure of cough severity. It consists of a 100 mm vertical scale on which the participant is asked to place a cross at the point that indicates the severity of his/her cough in the last 24 hours between "No cough" and "Worst cough ever". The position of the cross is measured from the "No cough" reference point. A minimal clinically important difference is considered to be a 17 mm change from previous.
Time frame: From Day 1 to Day 8 (Parts 1b and 2b)