Trial Outcomes & Findings for A Study to Assess the Safety, Tolerability and Pharmacokinetics of AZD7594 Inhaled Formulation in Healthy Japanese Men (NCT NCT02645253)

Results Overview

To assess the safety and tolerability of single and multiple doses of AZD7594

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

27 participants

Primary outcome timeframe

At screening (Day -28, Day -02 and Day -1), Treatment period (Days 1 to 20) and Follow-up (Day 29).

Results posted on

2018-02-19

Participant Flow

This study was conducted at PAREXEL Early Phase Clinical Unit - Los Angeles

Twenty-seven participants were randomized in 3 sequential cohorts. Each cohort consisted of nine participants in it. Within each cohort, 7 participants were randomly assigned to receive AZD7594 (different doses) and 2 subjects were randomly assigned to receive placebo.

Participant milestones

Participant milestones
Measure	AZD7594 200 μg Participants received 200 μg inhaled AZD7594 via multi-dose dry powder inhaler (DPI) (1 x 200 μg inhalation)	AZD7594 400 μg Participants received 400 μg inhaled AZD7594 via multi-dose DPI (1 x 400 μg inhalation)	AZD7594 1600 μg Participants received 1600 μg inhaled AZD7594 via multi-dose DPI (4 x 400 μg inhalations).	Palcebo Participants received placebo
Overall Study STARTED	7	7	7	6
Overall Study COMPLETED	7	7	7	6
Overall Study NOT COMPLETED	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Study to Assess the Safety, Tolerability and Pharmacokinetics of AZD7594 Inhaled Formulation in Healthy Japanese Men

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	AZD7594 200 μg n=7 Participants Participants received 200 μg inhaled AZD7594 via multi-dose dry powder inhaler (DPI) (1 x 200 μg inhalation)	AZD7594 400 μg n=7 Participants Participants received 400 μg inhaled AZD7594 via multi-dose DPI (1 x 400 μg inhalation)	AZD7594 1600 μg n=7 Participants Participants received 1600 μg inhaled AZD7594 via multi-dose DPI (4 x 400 μg inhalations).	Palcebo n=6 Participants Participants received placebo	Total n=27 Participants Total of all reporting groups
Age, Continuous	32.7 Years STANDARD_DEVIATION 5.41 • n=5 Participants	34.1 Years STANDARD_DEVIATION 6.41 • n=7 Participants	33.6 Years STANDARD_DEVIATION 6.43 • n=5 Participants	35.7 Years STANDARD_DEVIATION 5.54 • n=4 Participants	34.0 Years STANDARD_DEVIATION 5.73 • n=21 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	7 Participants n=7 Participants	7 Participants n=5 Participants	6 Participants n=4 Participants	27 Participants n=21 Participants

PRIMARY outcome

Timeframe: At screening (Day -28, Day -02 and Day -1), Treatment period (Days 1 to 20) and Follow-up (Day 29).

Population: All subjects who received at least one dose of IMP and for whom any post-dose data were available were included in the safety analysis set.

To assess the safety and tolerability of single and multiple doses of AZD7594

Outcome measures

Outcome measures
Measure	AZD7594 1600 μg n=7 Participants Participants received 1600 μg inhaled AZD7594 via multi-dose DPI (4 x 400 μg inhalations).	AZD7594 200 μg n=7 Participants Participants received 200 μg inhaled AZD7594 via multi-dose dry powder inhaler (DPI) (1 x 200 μg inhalation)	AZD7594 400 μg n=7 Participants Participants received 400 μg inhaled AZD7594 via multi-dose DPI (1 x 400 μg inhalation)	Placebo n=21 Participants Participants received placebo.	Placebo n=6 Participants Participants who received placebo.	All Subjects n=27 Participants Total number of participants in the study.
Safety and Tolerability of AZD7594 by Assessment of the Number of Participants With Adverse Events Any AE	1 Pariticpants	3 Pariticpants	1 Pariticpants	5 Pariticpants	1 Pariticpants	6 Pariticpants
Safety and Tolerability of AZD7594 by Assessment of the Number of Participants With Adverse Events Any AE with outcome = death	0 Pariticpants	0 Pariticpants	0 Pariticpants	0 Pariticpants	0 Pariticpants	0 Pariticpants
Safety and Tolerability of AZD7594 by Assessment of the Number of Participants With Adverse Events Any SAE including events with outcome =death	0 Pariticpants	0 Pariticpants	0 Pariticpants	0 Pariticpants	0 Pariticpants	0 Pariticpants
Safety and Tolerability of AZD7594 by Assessment of the Number of Participants With Adverse Events Any AE leading to discontinuation of IP	0 Pariticpants	0 Pariticpants	0 Pariticpants	0 Pariticpants	0 Pariticpants	0 Pariticpants

SECONDARY outcome

Timeframe: Day 1: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose.

Population: The pharmacokinetic (PK) analysis set consisted of all subjects in the safety analysis set who received AZD7594 and had at least 1 measured AZD7594 plasma concentration at a scheduled PK time point post-dose, with no major protocol deviations thought to impact on the analysis of the PK data.

Assessment of the plasma PK following a single dose of AZD7594. Cmax was defined as observed maximum plasma concentration, taken directly from the individual concentration-time curve.

Outcome measures

Outcome measures
Measure	AZD7594 1600 μg n=7 Participants Participants received 1600 μg inhaled AZD7594 via multi-dose DPI (4 x 400 μg inhalations).	AZD7594 200 μg n=7 Participants Participants received 200 μg inhaled AZD7594 via multi-dose dry powder inhaler (DPI) (1 x 200 μg inhalation)	AZD7594 400 μg n=7 Participants Participants received 400 μg inhaled AZD7594 via multi-dose DPI (1 x 400 μg inhalation)	Placebo Participants received placebo.	Placebo Participants who received placebo.	All Subjects Total number of participants in the study.
Rate and Extent of Absorption of AZD7594 (Inhalation/ Administration Via DPI) by Assessment of the Observed Maximum Plasma Concentration (Cmax)	430.8 pmol/L Geometric Coefficient of Variation 22.4	56.05 pmol/L Geometric Coefficient of Variation 22.0	76.93 pmol/L Geometric Coefficient of Variation 34.4	—	—	—

SECONDARY outcome

Timeframe: Day 1: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose.

Population: The PK analysis set consisted of all subjects in the safety analysis set who received AZD7594 and had at least 1 measured AZD7594 plasma concentration at a scheduled PK time point post-dose, with no major protocol deviations thought to impact on the analysis of the PK data.

Assessment of the plasma PK following a single dose of AZD7594. tmax was defined as time to reach maximum plasma concentration, taken directly from the individual concentration-time curve.

Outcome measures

Outcome measures
Measure	AZD7594 1600 μg n=7 Participants Participants received 1600 μg inhaled AZD7594 via multi-dose DPI (4 x 400 μg inhalations).	AZD7594 200 μg n=7 Participants Participants received 200 μg inhaled AZD7594 via multi-dose dry powder inhaler (DPI) (1 x 200 μg inhalation)	AZD7594 400 μg n=7 Participants Participants received 400 μg inhaled AZD7594 via multi-dose DPI (1 x 400 μg inhalation)	Placebo Participants received placebo.	Placebo Participants who received placebo.	All Subjects Total number of participants in the study.
Rate and Extent of Absorption of AZD7594 (Inhalation/ Administration Via DPI) by Assessment of the Time to Reach Maximum Plasma Concentration (Tmax)	0.50 Hours Interval 0.25 to 4.0	0.25 Hours Interval 0.25 to 0.98	0.52 Hours Interval 0.25 to 3.0	—	—	—

SECONDARY outcome

Timeframe: Day 1: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose

Population: The PK analysis set consisted of all subjects in the safety analysis set who received AZD7594 and had at least 1 measured AZD7594 plasma concentration at a scheduled PK time point post-dose, with no major protocol deviations thought to impact on the analysis of the PK data.

Assessment of the plasma PK following a single dose of AZD7594. AUC (0-last) was defined as the area under the plasma concentration-time curve from time zero to the time of last quantifiable analyte concentration.

Outcome measures

Outcome measures
Measure	AZD7594 1600 μg n=7 Participants Participants received 1600 μg inhaled AZD7594 via multi-dose DPI (4 x 400 μg inhalations).	AZD7594 200 μg n=7 Participants Participants received 200 μg inhaled AZD7594 via multi-dose dry powder inhaler (DPI) (1 x 200 μg inhalation)	AZD7594 400 μg n=7 Participants Participants received 400 μg inhaled AZD7594 via multi-dose DPI (1 x 400 μg inhalation)	Placebo Participants received placebo.	Placebo Participants who received placebo.	All Subjects Total number of participants in the study.
Rate and Extent of Absorption of AZD7594 (Inhalation/ Administration Via DPI) by Assessment of the Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to the Time of Last Quantifiable Analyte Concentration (AUC [0-last])	13960 h*pmol/L Geometric Coefficient of Variation 18.2	1314 h*pmol/L Geometric Coefficient of Variation 28.2	2736 h*pmol/L Geometric Coefficient of Variation 12.2	—	—	—

SECONDARY outcome

Timeframe: Day 1: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose

Population: The PK analysis set consisted of all subjects in the safety analysis set who received AZD7594 and had at least 1 measured AZD7594 plasma concentration at a scheduled PK time point post-dose, with no major protocol deviations thought to impact on the analysis of the PK data.

Assessment of the plasma PK following a single dose of AZD7594. AUC (0-24) was defined as area under the plasma concentration-time curve from time zero to 24 hours after dosing.

Outcome measures

Outcome measures
Measure	AZD7594 1600 μg n=7 Participants Participants received 1600 μg inhaled AZD7594 via multi-dose DPI (4 x 400 μg inhalations).	AZD7594 200 μg n=7 Participants Participants received 200 μg inhaled AZD7594 via multi-dose dry powder inhaler (DPI) (1 x 200 μg inhalation)	AZD7594 400 μg n=7 Participants Participants received 400 μg inhaled AZD7594 via multi-dose DPI (1 x 400 μg inhalation)	Placebo Participants received placebo.	Placebo Participants who received placebo.	All Subjects Total number of participants in the study.
Rate and Extent of Absorption of AZD7594 (Inhalation/ Administration Via DPI) by Assessment of the AUC From Time Zero to 24 Hours After Dosing (AUC [0-24]).	6060 h*pmol/L Geometric Coefficient of Variation 18.4	681.1 h*pmol/L Geometric Coefficient of Variation 11.5	1084 h*pmol/L Geometric Coefficient of Variation 19.4	—	—	—

SECONDARY outcome

Timeframe: Day 1: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose

Population: The PK analysis set consisted of all subjects in the safety analysis set who received AZD7594 and had at least 1 measured AZD7594 plasma concentration at a scheduled PK time point post-dose, with no major protocol deviations thought to impact on the analysis of the PK data.

Assessment of the plasma PK following a single dose of AZD7594. AUC was defined as area under the plasma concentration-time curve from time zero extrapolated to infinity. AUC is estimated by AUC(0-last) + Clast/λz where Clast is the last observed quantifiable concentration. NOTE: No results were available for participants belonging to AZD7594 2ug and AZD7594 400ug groups.

Outcome measures

Outcome measures
Measure	AZD7594 1600 μg n=7 Participants Participants received 1600 μg inhaled AZD7594 via multi-dose DPI (4 x 400 μg inhalations).	AZD7594 200 μg n=7 Participants Participants received 200 μg inhaled AZD7594 via multi-dose dry powder inhaler (DPI) (1 x 200 μg inhalation)	AZD7594 400 μg n=7 Participants Participants received 400 μg inhaled AZD7594 via multi-dose DPI (1 x 400 μg inhalation)	Placebo Participants received placebo.	Placebo Participants who received placebo.	All Subjects Total number of participants in the study.
Rate and Extent of Absorption of AZD7594 (Inhalation/ Administration Via DPI) by Assessment of the AUC From Time Zero Extrapolated to Infinity (AUC).	18260 h*pmol/L Geometric Coefficient of Variation 22.9	NA h*pmol/L Geometric Coefficient of Variation NA NA: Not applicable due to greater than 30% extrapolated area AUC values for most subjects were determined with \>30% extrapolated area, thus were excluded from statistical analysis.	NA h*pmol/L Geometric Coefficient of Variation NA NA: Not applicable due to greater than 30% extrapolated area AUC values for most subjects were determined with \>30% extrapolated area, thus were excluded from statistical analysis.	—	—	—

SECONDARY outcome

Timeframe: Day 1: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose

Population: The PK analysis set consisted of all subjects in the safety analysis set who received AZD7594 and had at least 1 measured AZD7594 plasma concentration at a scheduled PK time point post-dose, with no major protocol deviations thought to impact on the analysis of the PK data.

Assessment of the plasma PK following a single dose of AZD7594. λz was defined as terminal elimination rate constant, estimated by log-linear least squares regression of the terminal part of the concentration-time curve.

Outcome measures

Outcome measures
Measure	AZD7594 1600 μg n=7 Participants Participants received 1600 μg inhaled AZD7594 via multi-dose DPI (4 x 400 μg inhalations).	AZD7594 200 μg n=7 Participants Participants received 200 μg inhaled AZD7594 via multi-dose dry powder inhaler (DPI) (1 x 200 μg inhalation)	AZD7594 400 μg n=7 Participants Participants received 400 μg inhaled AZD7594 via multi-dose DPI (1 x 400 μg inhalation)	Placebo Participants received placebo.	Placebo Participants who received placebo.	All Subjects Total number of participants in the study.
Rate and Extent of Absorption of AZD7594 by Assessment of the Terminal Elimination Rate Constant, Estimated by Log-linear Least Squares Regression of the Terminal Part of the Concentration-time Curve(Lamda z or λz).	0.013862 l/h Geometric Coefficient of Variation 21.4	0.015573 l/h Geometric Coefficient of Variation 24.5	0.011058 l/h Geometric Coefficient of Variation 18.3	—	—	—

SECONDARY outcome

Timeframe: Day 1: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose

Population: The PK analysis set consisted of all subjects in the safety analysis set who received AZD7594 and had at least 1 measured AZD7594 plasma concentration at a scheduled PK time point post-dose, with no major protocol deviations thought to impact on the analysis of the PK data.

Assessment of the plasma PK following a single dose of AZD7594. t1/2λz was defined as half-life associated with terminal slope (λz) of a semi-logarithmic concentration-time curve. NOTE: No results were available for participants belonging to AZD7594 400ug group.

Outcome measures

Outcome measures
Measure	AZD7594 1600 μg n=7 Participants Participants received 1600 μg inhaled AZD7594 via multi-dose DPI (4 x 400 μg inhalations).	AZD7594 200 μg n=7 Participants Participants received 200 μg inhaled AZD7594 via multi-dose dry powder inhaler (DPI) (1 x 200 μg inhalation)	AZD7594 400 μg n=7 Participants Participants received 400 μg inhaled AZD7594 via multi-dose DPI (1 x 400 μg inhalation)	Placebo Participants received placebo.	Placebo Participants who received placebo.	All Subjects Total number of participants in the study.
Rate and Extent of Absorption of AZD7594 (Inhalation/ Administration Via DPI) by Assessment of the Half-life Associated With the Terminal Slope of a Semi-logarithmic Concentration-time Curve (t1/2λz).	43.57 Hours Standard Deviation 3.815	39.88 Hours Standard Deviation 5.441	NA Hours Standard Deviation NA NA - Not applicable. When t½λz was greater than half of total sampling interval (48 hours) or percentage of AUC obtained by extrapolating area under plasma concentration-time curve (%AUCextr) was \> 30%, t½λz was excluded from descriptive statistics	—	—	—

SECONDARY outcome

Timeframe: Day 1: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose

Population: The PK analysis set consisted of all subjects in the safety analysis set who received AZD7594 and had at least 1 measured AZD7594 plasma concentration at a scheduled PK time point post-dose, with no major protocol deviations thought to impact on the analysis of the PK data.

Assessment of the plasma PK following a single dose of AZD7594. MRT was defined as Mean residence time from time zero extrapolated to infinity. NOTE: No results were available for participants belonging to AZD7594 200ug and AZD7594 400ug groups.

Outcome measures

Outcome measures
Measure	AZD7594 1600 μg n=7 Participants Participants received 1600 μg inhaled AZD7594 via multi-dose DPI (4 x 400 μg inhalations).	AZD7594 200 μg n=7 Participants Participants received 200 μg inhaled AZD7594 via multi-dose dry powder inhaler (DPI) (1 x 200 μg inhalation)	AZD7594 400 μg n=7 Participants Participants received 400 μg inhaled AZD7594 via multi-dose DPI (1 x 400 μg inhalation)	Placebo Participants received placebo.	Placebo Participants who received placebo.	All Subjects Total number of participants in the study.
Rate and Extent of Absorption of AZD7594 (Inhalation/ Administration Via DPI) by Assessment of the Mean Residence Time From Time Zero Extrapolated to Infinity (MRT).	65.03 Hours Geometric Coefficient of Variation 4.7	NA Hours Geometric Coefficient of Variation NA NA - Not applicable. When t½λz was greater than half of the total sampling interval (48 hours) or %AUCextr was \> 30%, the terminal elimination phase dependent parameter (MRT) was excluded from descriptive statistics.	NA Hours Geometric Coefficient of Variation NA NA - Not applicable. When t½λz was greater than half of the total sampling interval (48 hours) or %AUCextr was \> 30%, the terminal elimination phase dependent parameter (MRT) was excluded from descriptive statistics.	—	—	—

SECONDARY outcome

Timeframe: Day 1: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose.

Population: The PK analysis set consisted of all subjects in the safety analysis set who received AZD7594 and had at least 1 measured AZD7594 plasma concentration at a scheduled PK time point post-dose, with no major protocol deviations thought to impact on the analysis of the PK data.

Assessment of the plasma PK following a single dose of AZD7594. CL/F was defined as apparent total body clearance after extravascular administration estimated as dose divided by AUC (AZD7594). NOTE: No results were available for participants belonging to AZD7594 200ug and AZD7594 400ug groups.

Outcome measures

Outcome measures
Measure	AZD7594 1600 μg n=7 Participants Participants received 1600 μg inhaled AZD7594 via multi-dose DPI (4 x 400 μg inhalations).	AZD7594 200 μg n=7 Participants Participants received 200 μg inhaled AZD7594 via multi-dose dry powder inhaler (DPI) (1 x 200 μg inhalation)	AZD7594 400 μg n=7 Participants Participants received 400 μg inhaled AZD7594 via multi-dose DPI (1 x 400 μg inhalation)	Placebo Participants received placebo.	Placebo Participants who received placebo.	All Subjects Total number of participants in the study.
Rate and Extent of Absorption of AZD7594 by Assessment of the Apparent Total Body Clearance After Extravascular Administration Estimated as Dose Divided by AUC (AZD7594) (CL/F).	144.5 L/h Geometric Coefficient of Variation 22.9	NA L/h Geometric Coefficient of Variation NA NA - Not applicable. When t½λz was greater than half of the total sampling interval (48 hours) or %AUCextr was \> 30%, the terminal elimination phase dependent parameter (CL/F) was excluded from descriptive statistics	NA L/h Geometric Coefficient of Variation NA NA - Not applicable. When t½λz was greater than half of the total sampling interval (48 hours) or %AUCextr was \> 30%, the terminal elimination phase dependent parameter (CL/F) was excluded from descriptive statistics	—	—	—

SECONDARY outcome

Timeframe: Day 1: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose.

Population: The PK analysis set consisted of all subjects in the safety analysis set who received AZD7594 and had at least 1 measured AZD7594 plasma concentration at a scheduled PK time point post-dose, with no major protocol deviations thought to impact on the analysis of the PK data.

Assessment of the plasma PK following a single dose of AZD7594. Vz/F was defined as apparent volume of distribution during the terminal phase after extravascular administration, estimated by dividing the apparent clearance (CL/F) by λz. NOTE: No results were available for participants belonging to AZD7594 200ug and AZD7594 400ug groups.

Outcome measures

Outcome measures
Measure	AZD7594 1600 μg n=7 Participants Participants received 1600 μg inhaled AZD7594 via multi-dose DPI (4 x 400 μg inhalations).	AZD7594 200 μg n=7 Participants Participants received 200 μg inhaled AZD7594 via multi-dose dry powder inhaler (DPI) (1 x 200 μg inhalation)	AZD7594 400 μg n=7 Participants Participants received 400 μg inhaled AZD7594 via multi-dose DPI (1 x 400 μg inhalation)	Placebo Participants received placebo.	Placebo Participants who received placebo.	All Subjects Total number of participants in the study.
Rate and Extent of Absorption of AZD7594 by Assessment of the Apparent Volume of Distribution During the Terminal Phase After Extravascular Administration, Estimated by Dividing CL/F by Lamda z (Vz/F)	9297 Litres Geometric Coefficient of Variation 24.1	NA Litres Geometric Coefficient of Variation NA NA - Not applicable. When t½λz was greater than half of the total sampling interval (48 hours) or %AUCextr was \> 30%, the terminal elimination phase dependent parameter (Vz/F) was excluded from descriptive statistics	NA Litres Geometric Coefficient of Variation NA NA - Not applicable. When t½λz was greater than half of the total sampling interval (48 hours) or %AUCextr was \> 30%, the terminal elimination phase dependent parameter (Vz/F) was excluded from descriptive statistics	—	—	—

SECONDARY outcome

Timeframe: Day 1: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose

Population: The PK analysis set consisted of all subjects in the safety analysis set who received AZD7594 and had at least 1 measured AZD7594 plasma concentration at a scheduled PK time point post-dose, with no major protocol deviations thought to impact on the analysis of the PK data.

Assessment of the plasma PK following a single dose of AZD7594. Cmax/D was defined as observed maximum plasma concentration divided by the dose administered.

Outcome measures

Outcome measures
Measure	AZD7594 1600 μg n=7 Participants Participants received 1600 μg inhaled AZD7594 via multi-dose DPI (4 x 400 μg inhalations).	AZD7594 200 μg n=7 Participants Participants received 200 μg inhaled AZD7594 via multi-dose dry powder inhaler (DPI) (1 x 200 μg inhalation)	AZD7594 400 μg n=7 Participants Participants received 400 μg inhaled AZD7594 via multi-dose DPI (1 x 400 μg inhalation)	Placebo Participants received placebo.	Placebo Participants who received placebo.	All Subjects Total number of participants in the study.
Rate and Extent of Absorption of AZD7594 by Assessment of the Cmax Divided by the Dose Administered (Cmax/D).	163.2 (pmol/L)/umol Geometric Coefficient of Variation 22.4	169.9 (pmol/L)/umol Geometric Coefficient of Variation 22.0	116.7 (pmol/L)/umol Geometric Coefficient of Variation 34.4	—	—	—

SECONDARY outcome

Timeframe: Day 1: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose.

Population: The PK analysis set consisted of all subjects in the safety analysis set who received AZD7594 and had at least 1 measured AZD7594 plasma concentration at a scheduled PK time point post-dose, with no major protocol deviations thought to impact on the analysis of the PK data.

Assessment of the plasma PK following a single dose of AZD7594. AUC/D was defined as Area under the plasma concentration-time curve from time zero extrapolated to infinity divided by the dose administered. NOTE: No results were available for participants belonging to AZD7594 200ug and AZD7594 400ug groups.

Outcome measures

Outcome measures
Measure	AZD7594 1600 μg n=7 Participants Participants received 1600 μg inhaled AZD7594 via multi-dose DPI (4 x 400 μg inhalations).	AZD7594 200 μg n=7 Participants Participants received 200 μg inhaled AZD7594 via multi-dose dry powder inhaler (DPI) (1 x 200 μg inhalation)	AZD7594 400 μg n=7 Participants Participants received 400 μg inhaled AZD7594 via multi-dose DPI (1 x 400 μg inhalation)	Placebo Participants received placebo.	Placebo Participants who received placebo.	All Subjects Total number of participants in the study.
Rate and Extent of Absorption of AZD7594 by Assessment of the AUC Divided by the Dose Administered (AUC/D).	6918 (pmol*h/L)/umol Geometric Coefficient of Variation 22.9	NA (pmol*h/L)/umol Geometric Coefficient of Variation NA NA - Not available For 6 participants, %AUCextr was \> 30%. Hence, values were excluded from descriptive statistics.	NA (pmol*h/L)/umol Geometric Coefficient of Variation NA NA - Not available NA - Not available For all participants, %AUCextr was \> 30%. Hence, values were excluded from descriptive statistics.	—	—	—

SECONDARY outcome

Timeframe: Day 1: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose.

Population: The PK analysis set consisted of all subjects in the safety analysis set who received AZD7594 and had at least 1 measured AZD7594 plasma concentration at a scheduled PK time point post-dose, with no major protocol deviations thought to impact on the analysis of the PK data.

Assessment of the plasma PK following a single dose of AZD7594. AUC(0-24)/D was defined as area under the plasma concentration-time curve from time zero to 24 hours after dosing divided by the dose administered.

Outcome measures

Outcome measures
Measure	AZD7594 1600 μg n=7 Participants Participants received 1600 μg inhaled AZD7594 via multi-dose DPI (4 x 400 μg inhalations).	AZD7594 200 μg n=7 Participants Participants received 200 μg inhaled AZD7594 via multi-dose dry powder inhaler (DPI) (1 x 200 μg inhalation)	AZD7594 400 μg n=7 Participants Participants received 400 μg inhaled AZD7594 via multi-dose DPI (1 x 400 μg inhalation)	Placebo Participants received placebo.	Placebo Participants who received placebo.	All Subjects Total number of participants in the study.
Rate and Extent of Absorption of AZD7594 by Assessment of the AUC(0-24) Divided by the Dose Administered (AUC(0-24)/D)	2295 (pmol*h/L)/umol Geometric Coefficient of Variation 18.4	2064 (pmol*h/L)/umol Geometric Coefficient of Variation 11.5	1645 (pmol*h/L)/umol Geometric Coefficient of Variation 19.4	—	—	—

SECONDARY outcome

Timeframe: Days 5 to 15: Pre-dose

Population: The pharmacokinetic (PK) analysis set consisted of all subjects in the safety analysis set who received AZD7594 and had at least 1 measured AZD7594 plasma concentration at a scheduled PK time point post-dose, with no major protocol deviations thought to impact on the analysis of the PK data.

Cmin was defined as observed minimum plasma concentration, taken directly from the individual concentration-time curve

Outcome measures

Outcome measures
Measure	AZD7594 1600 μg n=7 Participants Participants received 1600 μg inhaled AZD7594 via multi-dose DPI (4 x 400 μg inhalations).	AZD7594 200 μg n=7 Participants Participants received 200 μg inhaled AZD7594 via multi-dose dry powder inhaler (DPI) (1 x 200 μg inhalation)	AZD7594 400 μg n=7 Participants Participants received 400 μg inhaled AZD7594 via multi-dose DPI (1 x 400 μg inhalation)	Placebo Participants received placebo.	Placebo Participants who received placebo.	All Subjects Total number of participants in the study.
Rate and Extent of Absorption of AZD7594 by Assessment of the Observed Minimum Plasma Concentration (Cmin) Day 15 - Pre-dose	694.9 pmol/L Geometric Coefficient of Variation 11.67	82.40 pmol/L Geometric Coefficient of Variation 13.30	151.9 pmol/L Geometric Coefficient of Variation 35.42	—	—	—
Rate and Extent of Absorption of AZD7594 by Assessment of the Observed Minimum Plasma Concentration (Cmin) Day 5 - Pre-dose	68.91 pmol/L Geometric Coefficient of Variation 21.55	NA pmol/L Geometric Coefficient of Variation NA NA: Not applicable 6 participants were in below lower limit of quantification (10 pmol/L) category	16.27 pmol/L Geometric Coefficient of Variation 13.13	—	—	—
Rate and Extent of Absorption of AZD7594 by Assessment of the Observed Minimum Plasma Concentration (Cmin) Day 5 - 1 hour	404.2 pmol/L Geometric Coefficient of Variation 22.74	59.81 pmol/L Geometric Coefficient of Variation 27.60	77.10 pmol/L Geometric Coefficient of Variation 26.92	—	—	—
Rate and Extent of Absorption of AZD7594 by Assessment of the Observed Minimum Plasma Concentration (Cmin) Day 6 - Pre-dose	252.2 pmol/L Geometric Coefficient of Variation 24.53	29.35 pmol/L Geometric Coefficient of Variation 17.83	47.75 pmol/L Geometric Coefficient of Variation 20.76	—	—	—
Rate and Extent of Absorption of AZD7594 by Assessment of the Observed Minimum Plasma Concentration (Cmin) Day 7 - Pre-dose	369.0 pmol/L Geometric Coefficient of Variation 20.88	41.59 pmol/L Geometric Coefficient of Variation 10.33	76.91 pmol/L Geometric Coefficient of Variation 16.27	—	—	—
Rate and Extent of Absorption of AZD7594 by Assessment of the Observed Minimum Plasma Concentration (Cmin) Day 8 - Pre-dose	458.4 pmol/L Geometric Coefficient of Variation 22.39	51.99 pmol/L Geometric Coefficient of Variation 12.29	92.18 pmol/L Geometric Coefficient of Variation 18.17	—	—	—
Rate and Extent of Absorption of AZD7594 by Assessment of the Observed Minimum Plasma Concentration (Cmin) Day 8 - 1 hour	793.0 pmol/L Geometric Coefficient of Variation 26.60	106.4 pmol/L Geometric Coefficient of Variation 19.69	162.3 pmol/L Geometric Coefficient of Variation 20.93	—	—	—
Rate and Extent of Absorption of AZD7594 by Assessment of the Observed Minimum Plasma Concentration (Cmin) Day 9 - Pre-dose	548.3 pmol/L Geometric Coefficient of Variation 25.72	60.37 pmol/L Geometric Coefficient of Variation 16.48	108.2 pmol/L Geometric Coefficient of Variation 25.11	—	—	—
Rate and Extent of Absorption of AZD7594 by Assessment of the Observed Minimum Plasma Concentration (Cmin) Day 10 - Pre-dose	554.2 pmol/L Geometric Coefficient of Variation 23.65	61.88 pmol/L Geometric Coefficient of Variation 21.52	119.3 pmol/L Geometric Coefficient of Variation 31.01	—	—	—
Rate and Extent of Absorption of AZD7594 by Assessment of the Observed Minimum Plasma Concentration (Cmin) Day 11 - Pre-dose	623.5 pmol/L Geometric Coefficient of Variation 21.10	68.39 pmol/L Geometric Coefficient of Variation 19.83	136.3 pmol/L Geometric Coefficient of Variation 26.20	—	—	—
Rate and Extent of Absorption of AZD7594 by Assessment of the Observed Minimum Plasma Concentration (Cmin) Day 12 - Pre-dose	603.8 pmol/L Geometric Coefficient of Variation 16.84	78.39 pmol/L Geometric Coefficient of Variation 9.019	142.6 pmol/L Geometric Coefficient of Variation 30.88	—	—	—
Rate and Extent of Absorption of AZD7594 by Assessment of the Observed Minimum Plasma Concentration (Cmin) Day 12 - 1 hour	925.8 pmol/L Geometric Coefficient of Variation 16.61	139.5 pmol/L Geometric Coefficient of Variation 8.216	219.8 pmol/L Geometric Coefficient of Variation 26.21	—	—	—
Rate and Extent of Absorption of AZD7594 by Assessment of the Observed Minimum Plasma Concentration (Cmin) Day 13 - Pre-dose	698.3 pmol/L Geometric Coefficient of Variation 19.89	79.31 pmol/L Geometric Coefficient of Variation 12.92	145.5 pmol/L Geometric Coefficient of Variation 38.15	—	—	—
Rate and Extent of Absorption of AZD7594 by Assessment of the Observed Minimum Plasma Concentration (Cmin) Day 14 - Pre-dose	718.4 pmol/L Geometric Coefficient of Variation 23.65	77.04 pmol/L Geometric Coefficient of Variation 7.165	147.0 pmol/L Geometric Coefficient of Variation 34.87	—	—	—

SECONDARY outcome

Timeframe: Day 16: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose

Population: The PK analysis set consisted of all subjects in the safety analysis set who received AZD7594 and had at least 1 measured AZD7594 plasma concentration at a scheduled PK time point post-dose, with no major protocol deviations thought to impact on the analysis of the PK data.

Assessment of the plasma PK following a single dose of AZD7594. Css,max was defined as observed maximum plasma concentration at steady state, taken directly from the individual concentration-time curve.

Outcome measures

Outcome measures
Measure	AZD7594 1600 μg n=7 Participants Participants received 1600 μg inhaled AZD7594 via multi-dose DPI (4 x 400 μg inhalations).	AZD7594 200 μg n=7 Participants Participants received 200 μg inhaled AZD7594 via multi-dose dry powder inhaler (DPI) (1 x 200 μg inhalation)	AZD7594 400 μg n=7 Participants Participants received 400 μg inhaled AZD7594 via multi-dose DPI (1 x 400 μg inhalation)	Placebo Participants received placebo.	Placebo Participants who received placebo.	All Subjects Total number of participants in the study.
Rate and Extent of Absorption of AZD7594 (Inhalation/ Administration Via DPI) by Assessment of the Cmax at Steady State (Css,Max).	1206 pmol/L Geometric Coefficient of Variation 14.7	164.3 pmol/L Geometric Coefficient of Variation 14.0	261.2 pmol/L Geometric Coefficient of Variation 37.0	—	—	—

SECONDARY outcome

Timeframe: Day 16: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose.

Population: The PK analysis set consisted of all subjects in the safety analysis set who received AZD7594 and had at least 1 measured AZD7594 plasma concentration at a scheduled PK time point post-dose, with no major protocol deviations thought to impact on the analysis of the PK data.

Assessment of the plasma PK following a single dose of AZD7594. Cmin, ss was defined as observed minimum concentration, taken directly from the individual concentration-time curve.

Outcome measures

Outcome measures
Measure	AZD7594 1600 μg n=7 Participants Participants received 1600 μg inhaled AZD7594 via multi-dose DPI (4 x 400 μg inhalations).	AZD7594 200 μg n=7 Participants Participants received 200 μg inhaled AZD7594 via multi-dose dry powder inhaler (DPI) (1 x 200 μg inhalation)	AZD7594 400 μg n=7 Participants Participants received 400 μg inhaled AZD7594 via multi-dose DPI (1 x 400 μg inhalation)	Placebo Participants received placebo.	Placebo Participants who received placebo.	All Subjects Total number of participants in the study.
Rate and Extent of Absorption of AZD7594 (Inhalation/ Administration Via DPI) by Assessment of the Cmin at Steady State (Cmin, ss)	600.0 pmol/L Geometric Coefficient of Variation 27.0	82.15 pmol/L Geometric Coefficient of Variation 12.8	140.6 pmol/L Geometric Coefficient of Variation 38.5	—	—	—

SECONDARY outcome

Timeframe: Day 16: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose.

Population: The PK analysis set consisted of all subjects in the safety analysis set who received AZD7594 and had at least 1 measured AZD7594 plasma concentration at a scheduled PK time point post-dose, with no major protocol deviations thought to impact on the analysis of the PK data.

Assessment of the plasma PK following a single dose of AZD7594. Cav was defined as average concentration over one dosing interval.

Outcome measures

Outcome measures
Measure	AZD7594 1600 μg n=7 Participants Participants received 1600 μg inhaled AZD7594 via multi-dose DPI (4 x 400 μg inhalations).	AZD7594 200 μg n=7 Participants Participants received 200 μg inhaled AZD7594 via multi-dose dry powder inhaler (DPI) (1 x 200 μg inhalation)	AZD7594 400 μg n=7 Participants Participants received 400 μg inhaled AZD7594 via multi-dose DPI (1 x 400 μg inhalation)	Placebo Participants received placebo.	Placebo Participants who received placebo.	All Subjects Total number of participants in the study.
Rate and Extent of Absorption of AZD7594 (Inhalation/ Administration Via DPI) by Assessment of the Average Concentration Over One Dosing Interval (Cav)	867.8 pmol/L Geometric Coefficient of Variation 13.2	101.1 pmol/L Geometric Coefficient of Variation 13.4	183.7 pmol/L Geometric Coefficient of Variation 33.4	—	—	—

SECONDARY outcome

Timeframe: Day 16: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose.

Population: The PK analysis set consisted of all subjects in the safety analysis set who received AZD7594 and had at least 1 measured AZD7594 plasma concentration at a scheduled PK time point post-dose, with no major protocol deviations thought to impact on the analysis of the PK data.

Assessment of the plasma PK following a single dose of AZD7594. tss,max was defined as Time to reach maximum concentration, taken directly from the individual concentration-time curve.

Outcome measures

Outcome measures
Measure	AZD7594 1600 μg n=7 Participants Participants received 1600 μg inhaled AZD7594 via multi-dose DPI (4 x 400 μg inhalations).	AZD7594 200 μg n=7 Participants Participants received 200 μg inhaled AZD7594 via multi-dose dry powder inhaler (DPI) (1 x 200 μg inhalation)	AZD7594 400 μg n=7 Participants Participants received 400 μg inhaled AZD7594 via multi-dose DPI (1 x 400 μg inhalation)	Placebo Participants received placebo.	Placebo Participants who received placebo.	All Subjects Total number of participants in the study.
Rate and Extent of Absorption of AZD7594 (Inhalation/ Administration Via DPI) by Assessment of the Tmax at Steady State (Tss,Max).	1.50 Hours Interval 0.25 to 4.0	0.25 Hours Interval 0.25 to 4.02	1.50 Hours Interval 0.25 to 8.0	—	—	—

SECONDARY outcome

Timeframe: Day 16: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose.

Population: The PK analysis set consisted of all subjects in the safety analysis set who received AZD7594 and had at least 1 measured AZD7594 plasma concentration at a scheduled PK time point post-dose, with no major protocol deviations thought to impact on the analysis of the PK data.

Assessment of the plasma PK following a single dose of AZD7594. AUC(0-last) was defined as Area under the plasma concentration-time curve from time zero to the time of the last quantifiable analyte concentration.

Outcome measures

Outcome measures
Measure	AZD7594 1600 μg n=7 Participants Participants received 1600 μg inhaled AZD7594 via multi-dose DPI (4 x 400 μg inhalations).	AZD7594 200 μg n=7 Participants Participants received 200 μg inhaled AZD7594 via multi-dose dry powder inhaler (DPI) (1 x 200 μg inhalation)	AZD7594 400 μg n=7 Participants Participants received 400 μg inhaled AZD7594 via multi-dose DPI (1 x 400 μg inhalation)	Placebo Participants received placebo.	Placebo Participants who received placebo.	All Subjects Total number of participants in the study.
Rate and Extent of Absorption of AZD7594 by Assessment of the AUC(0-last)	54120 pmol*h/L Geometric Coefficient of Variation 11.5	6136 pmol*h/L Geometric Coefficient of Variation 16.2	11490 pmol*h/L Geometric Coefficient of Variation 36.9	—	—	—

SECONDARY outcome

Timeframe: Day 16: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose.

Population: The PK analysis set consisted of all subjects in the safety analysis set who received AZD7594 and had at least 1 measured AZD7594 plasma concentration at a scheduled PK time point post-dose, with no major protocol deviations thought to impact on the analysis of the PK data

Assessment of the plasma PK following a single dose of AZD7594. AUC(0-24) was defined as area under the plasma concentration-time curve from time zero to 24 hours after dosing

Outcome measures

Outcome measures
Measure	AZD7594 1600 μg n=7 Participants Participants received 1600 μg inhaled AZD7594 via multi-dose DPI (4 x 400 μg inhalations).	AZD7594 200 μg n=7 Participants Participants received 200 μg inhaled AZD7594 via multi-dose dry powder inhaler (DPI) (1 x 200 μg inhalation)	AZD7594 400 μg n=7 Participants Participants received 400 μg inhaled AZD7594 via multi-dose DPI (1 x 400 μg inhalation)	Placebo Participants received placebo.	Placebo Participants who received placebo.	All Subjects Total number of participants in the study.
Rate and Extent of Absorption of AZD7594 by Assessment of AUC(0-24)	20830 pmol*h/L Geometric Coefficient of Variation 13.2	2426 pmol*h/L Geometric Coefficient of Variation 13.4	4409 pmol*h/L Geometric Coefficient of Variation 33.4	—	—	—

SECONDARY outcome

Timeframe: Day 16: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose.

Population: The PK analysis set consisted of all subjects in the safety analysis set who received AZD7594 and had at least 1 measured AZD7594 plasma concentration at a scheduled PK time point post-dose, with no major protocol deviations thought to impact on the analysis of the PK data.

Assessment of the plasma PK following a single dose of AZD7594. Css,max/D was defined as observed maximum plasma concentration divided by the dose administered.

Outcome measures

Outcome measures
Measure	AZD7594 1600 μg n=7 Participants Participants received 1600 μg inhaled AZD7594 via multi-dose DPI (4 x 400 μg inhalations).	AZD7594 200 μg n=7 Participants Participants received 200 μg inhaled AZD7594 via multi-dose dry powder inhaler (DPI) (1 x 200 μg inhalation)	AZD7594 400 μg n=7 Participants Participants received 400 μg inhaled AZD7594 via multi-dose DPI (1 x 400 μg inhalation)	Placebo Participants received placebo.	Placebo Participants who received placebo.	All Subjects Total number of participants in the study.
Rate and Extent of Absorption of AZD7594 by Assessment of the Css,Max Divided by the Dose Administered (Css,Max/D).	456.9 (pmol/L)/umol Geometric Coefficient of Variation 14.7	498.0 (pmol/L)/umol Geometric Coefficient of Variation 14.0	396.4 (pmol/L)/umol Geometric Coefficient of Variation 37.0	—	—	—

SECONDARY outcome

Timeframe: Day 16: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose.

Population: The PK analysis set consisted of all subjects in the safety analysis set who received AZD7594 and had at least 1 measured AZD7594 plasma concentration at a scheduled PK time point post-dose, with no major protocol deviations thought to impact on the analysis of the PK data.

Assessment of the plasma PK following a single dose of AZD7594. AUC(0-24)/D was defined as the area under the plasma concentration-time curve from time zero to 24 hours after dosing divided by the dose administered.

Outcome measures

Outcome measures
Measure	AZD7594 1600 μg n=7 Participants Participants received 1600 μg inhaled AZD7594 via multi-dose DPI (4 x 400 μg inhalations).	AZD7594 200 μg n=7 Participants Participants received 200 μg inhaled AZD7594 via multi-dose dry powder inhaler (DPI) (1 x 200 μg inhalation)	AZD7594 400 μg n=7 Participants Participants received 400 μg inhaled AZD7594 via multi-dose DPI (1 x 400 μg inhalation)	Placebo Participants received placebo.	Placebo Participants who received placebo.	All Subjects Total number of participants in the study.
Rate and Extent of Absorption of AZD7594 by Assessment AUC(0-24)/D.	7889 (pmol*h/L)/umol Geometric Coefficient of Variation 13.2	7351 (pmol*h/L)/umol Geometric Coefficient of Variation 13.4	6691 (pmol*h/L)/umol Geometric Coefficient of Variation 33.4	—	—	—

SECONDARY outcome

Timeframe: Day 16: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose.

Population: The PK analysis set consisted of all subjects in the safety analysis set who received AZD7594 and had at least 1 measured AZD7594 plasma concentration at a scheduled PK time point post-dose, with no major protocol deviations thought to impact on the analysis of the PK data.

Assessment of the plasma PK following a single dose of AZD7594. λz was defined as terminal elimination rate constant, estimated by log-linear least.

Outcome measures

Outcome measures
Measure	AZD7594 1600 μg n=7 Participants Participants received 1600 μg inhaled AZD7594 via multi-dose DPI (4 x 400 μg inhalations).	AZD7594 200 μg n=7 Participants Participants received 200 μg inhaled AZD7594 via multi-dose dry powder inhaler (DPI) (1 x 200 μg inhalation)	AZD7594 400 μg n=7 Participants Participants received 400 μg inhaled AZD7594 via multi-dose DPI (1 x 400 μg inhalation)	Placebo Participants received placebo.	Placebo Participants who received placebo.	All Subjects Total number of participants in the study.
Rate and Extent of Absorption of AZD7594 by Assessment of Lamda z (λz)	0.010660 l/hour Geometric Coefficient of Variation 27.4	0.013393 l/hour Geometric Coefficient of Variation 19.8	0.011465 l/hour Geometric Coefficient of Variation 38.8	—	—	—

SECONDARY outcome

Timeframe: Day 16: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose

Population: The PK analysis set consisted of all subjects in the safety analysis set who received AZD7594 and had at least 1 measured AZD7594 plasma concentration at a scheduled PK time point post-dose, with no major protocol deviations thought to impact on the analysis of the PK data.

Assessment of the plasma PK following a single dose of AZD7594. t1/2λz was defined as half-life associated with terminal slope (λz) of a semi-logarithmic concentration-time curve. Participant count analyzed = 1

Outcome measures

Outcome measures
Measure	AZD7594 1600 μg n=7 Participants Participants received 1600 μg inhaled AZD7594 via multi-dose DPI (4 x 400 μg inhalations).	AZD7594 200 μg n=7 Participants Participants received 200 μg inhaled AZD7594 via multi-dose dry powder inhaler (DPI) (1 x 200 μg inhalation)	AZD7594 400 μg n=7 Participants Participants received 400 μg inhaled AZD7594 via multi-dose DPI (1 x 400 μg inhalation)	Placebo Participants received placebo.	Placebo Participants who received placebo.	All Subjects Total number of participants in the study.
Rate and Extent of Absorption of AZD7594 by Assessment of t1/2λz.	NA Hours Geometric Coefficient of Variation NA NA - Not applicable When Rsq\_adj (regression co-efficient adjusted for λz) was \< 0.7 or estimated t1/2λz was greater than half of the total sampling interval (48 hours), t½λz was excluded from descriptive statistics	NA Hours Geometric Coefficient of Variation NA NA - Not applicable When Rsq\_adj (regression co-efficient adjusted for λz) was \< 0.7 or estimated t1/2λz was greater than half of the total sampling interval (48 hours), t½λz was excluded from descriptive statistics	NA Hours Geometric Coefficient of Variation NA NA - Not applicable When Rsq\_adj (regression co-efficient adjusted for λz) was \< 0.7 or estimated t1/2λz was greater than half of the total sampling interval (48 hours), t½λz was excluded from descriptive statistics	—	—	—

SECONDARY outcome

Timeframe: Day 16: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose.

Population: The pharmacodynamics analysis set will include all subjects who receive at least 1 dose of IMP and for whom it is possible to calculate the cortisol AUEC on Day -1, Day 1 and/or Day 16 and with no major protocol deviations considered to impact on the analysis of the PD (cortisol, plasma DHEAS and osteocalcin) data.

Assessment of the plasma PK following a single dose of AZD7594. Peak trough fluctuation calculated as \[100\*(Css,max- Css,min)/Cav\].

Outcome measures

Outcome measures
Measure	AZD7594 1600 μg n=7 Participants Participants received 1600 μg inhaled AZD7594 via multi-dose DPI (4 x 400 μg inhalations).	AZD7594 200 μg n=7 Participants Participants received 200 μg inhaled AZD7594 via multi-dose dry powder inhaler (DPI) (1 x 200 μg inhalation)	AZD7594 400 μg n=7 Participants Participants received 400 μg inhaled AZD7594 via multi-dose DPI (1 x 400 μg inhalation)	Placebo Participants received placebo.	Placebo Participants who received placebo.	All Subjects Total number of participants in the study.
Rate and Extent of Absorption of AZD7594 by Assessment of the Peak Trough Fluctuation (%Fluctuation).	68.08 Percentage of fluctuation Geometric Coefficient of Variation 21.0	80.12 Percentage of fluctuation Geometric Coefficient of Variation 23.8	64.61 Percentage of fluctuation Geometric Coefficient of Variation 21.8	—	—	—

SECONDARY outcome

Timeframe: Day 16: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose.

Population: The PK analysis set consisted of all subjects in the safety analysis set who received AZD7594 and had at least 1 measured AZD7594 plasma concentration at a scheduled PK time point post-dose, with no major protocol deviations thought to impact on the analysis of the PK data.

Assessment of the plasma PK following a single dose of AZD7594. Accumulation ratio calculated as AUC(0-24) on Day 16/AUC(0-24) on Day 1.

Outcome measures

Outcome measures
Measure	AZD7594 1600 μg n=7 Participants Participants received 1600 μg inhaled AZD7594 via multi-dose DPI (4 x 400 μg inhalations).	AZD7594 200 μg n=7 Participants Participants received 200 μg inhaled AZD7594 via multi-dose dry powder inhaler (DPI) (1 x 200 μg inhalation)	AZD7594 400 μg n=7 Participants Participants received 400 μg inhaled AZD7594 via multi-dose DPI (1 x 400 μg inhalation)	Placebo Participants received placebo.	Placebo Participants who received placebo.	All Subjects Total number of participants in the study.
Rate and Extent of Absorption of AZD7594 by Assessment of the Accumulation Ratio Calculated as AUC(0-24) on Day 16/AUC (0-24) on Day 1 (RAC).	3.437 Ratio Geometric Coefficient of Variation 7.3	3.562 Ratio Geometric Coefficient of Variation 15.7	4.067 Ratio Geometric Coefficient of Variation 43.7	—	—	—

SECONDARY outcome

Timeframe: Day 16: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose.

Population: The PK analysis set consisted of all subjects in the safety analysis set who received AZD7594 and had at least 1 measured AZD7594 plasma concentration at a scheduled PK time point post-dose, with no major protocol deviations thought to impact on the analysis of the PK data.

Assessment of the plasma PK following a single dose of AZD7594. Temporal change parameter, calculated as AUC(0-24) \[Day 16\]/AUC \[Day 1\]. NOTE: No results were available for participants belonging to AZD7594 200ug and AZD7594 400ug groups.

Outcome measures

Outcome measures
Measure	AZD7594 1600 μg n=7 Participants Participants received 1600 μg inhaled AZD7594 via multi-dose DPI (4 x 400 μg inhalations).	AZD7594 200 μg n=7 Participants Participants received 200 μg inhaled AZD7594 via multi-dose dry powder inhaler (DPI) (1 x 200 μg inhalation)	AZD7594 400 μg n=7 Participants Participants received 400 μg inhaled AZD7594 via multi-dose DPI (1 x 400 μg inhalation)	Placebo Participants received placebo.	Placebo Participants who received placebo.	All Subjects Total number of participants in the study.
Rate and Extent of Absorption of AZD7594 by Assessment of the Temporal Change Parameter (TCP)	1.147 Ratio Geometric Coefficient of Variation 7.7	NA Ratio Geometric Coefficient of Variation NA NA - Not available For all participants, AUC value on Day 1 could not be reliably determined. Hence, values were excluded from descriptive statistics	NA Ratio Geometric Coefficient of Variation NA NA - Not available For all participants, AUC value on Day 1 could not be reliably determined. Hence, values were excluded from descriptive statistics	—	—	—

SECONDARY outcome

Timeframe: Day 1 predose spot-collection and interval collection up to 96 hours postdose

Population: The PK analysis set consisted of all subjects in the safety analysis set who received AZD7594 and had at least 1 measured AZD7594 plasma concentration at a scheduled PK time point post-dose, with no major protocol deviations thought to impact on the analysis of the PK data.

Assessment of the urine PK following a single dose of AZD7594. Ae (t1-t2) was defined as the amount of AZD7594 excreted into the urine from time t1 to t2.

Outcome measures

Outcome measures
Measure	AZD7594 1600 μg n=7 Participants Participants received 1600 μg inhaled AZD7594 via multi-dose DPI (4 x 400 μg inhalations).	AZD7594 200 μg n=7 Participants Participants received 200 μg inhaled AZD7594 via multi-dose dry powder inhaler (DPI) (1 x 200 μg inhalation)	AZD7594 400 μg n=7 Participants Participants received 400 μg inhaled AZD7594 via multi-dose DPI (1 x 400 μg inhalation)	Placebo Participants received placebo.	Placebo Participants who received placebo.	All Subjects Total number of participants in the study.
Rate and Extent of Absorption of AZD7594 by Assessment of the Amount of AZD7594 Excreted Into the Urine From Time t1 to t2 (Ae [t1-t2]) 0-6h	55.64 pmol Standard Deviation 58.01	1.856 pmol Standard Deviation 4.910	6.738 pmol Standard Deviation 9.751	—	—	—
Rate and Extent of Absorption of AZD7594 by Assessment of the Amount of AZD7594 Excreted Into the Urine From Time t1 to t2 (Ae [t1-t2]) 6-12h	73.15 pmol Standard Deviation 53.23	1.434 pmol Standard Deviation 3.795	5.031 pmol Standard Deviation 6.645	—	—	—
Rate and Extent of Absorption of AZD7594 by Assessment of the Amount of AZD7594 Excreted Into the Urine From Time t1 to t2 (Ae [t1-t2]) 12-24h	73.13 pmol Standard Deviation 50.96	1.893 pmol Standard Deviation 5.008	1.907 pmol Standard Deviation 5.046	—	—	—
Rate and Extent of Absorption of AZD7594 by Assessment of the Amount of AZD7594 Excreted Into the Urine From Time t1 to t2 (Ae [t1-t2]) 24-48h	107.9 pmol Standard Deviation 76.97	NA pmol Standard Deviation NA NA - Not available Participants concentration values were below lower limit of quantitation (10 pmol/L) category	NA pmol Standard Deviation NA NA - Not available Participants concentration values were below lower limit of quantitation (10 pmol/L) category	—	—	—
Rate and Extent of Absorption of AZD7594 by Assessment of the Amount of AZD7594 Excreted Into the Urine From Time t1 to t2 (Ae [t1-t2]) 48-72h	72.43 pmol Standard Deviation 58.77	NA pmol Standard Deviation NA NA - Not available Participants concentration values were below lower limit of quantitation (10 pmol/L) category	NA pmol Standard Deviation NA NA - Not available Participants concentration values were below lower limit of quantitation (10 pmol/L) category	—	—	—
Rate and Extent of Absorption of AZD7594 by Assessment of the Amount of AZD7594 Excreted Into the Urine From Time t1 to t2 (Ae [t1-t2]) 72-96h	48.95 pmol Standard Deviation 48.49	NA pmol Standard Deviation NA NA - Not available Participants concentration values were below lower limit of quantitation (10 pmol/L) category	NA pmol Standard Deviation NA NA - Not available Participants concentration values were below lower limit of quantitation (10 pmol/L) category	—	—	—

SECONDARY outcome

Timeframe: Day 1 predose spot-collection and interval collection up to 96 hours postdose

Population: The PK analysis set consisted of all subjects in the safety analysis set who received AZD7594 and had at least 1 measured AZD7594 plasma concentration at a scheduled PK time point post-dose, with no major protocol deviations thought to impact on the analysis of the PK data.

Assessment of the urine PK following a single dose of AZD7594. Ae(0-last) was defined as Cumulative amount of AZD7594 excreted from time zero to the last sampling interval.

Outcome measures

Outcome measures
Measure	AZD7594 1600 μg n=7 Participants Participants received 1600 μg inhaled AZD7594 via multi-dose DPI (4 x 400 μg inhalations).	AZD7594 200 μg n=7 Participants Participants received 200 μg inhaled AZD7594 via multi-dose dry powder inhaler (DPI) (1 x 200 μg inhalation)	AZD7594 400 μg n=7 Participants Participants received 400 μg inhaled AZD7594 via multi-dose DPI (1 x 400 μg inhalation)	Placebo Participants received placebo.	Placebo Participants who received placebo.	All Subjects Total number of participants in the study.
Rate and Extent of Absorption of AZD7594 by Assessment of the Cumulative Amount of AZD7594 Excreted From Time Zero to the Last Sampling Interval (Ae [0-last]) 0-6h	55.64 pmol Standard Deviation 58.01	1.856 pmol Standard Deviation 4.910	6.738 pmol Standard Deviation 9.751	—	—	—
Rate and Extent of Absorption of AZD7594 by Assessment of the Cumulative Amount of AZD7594 Excreted From Time Zero to the Last Sampling Interval (Ae [0-last]) 0-12h	128.8 pmol Standard Deviation 83.03	3.290 pmol Standard Deviation 8.705	11.77 pmol Standard Deviation 15.25	—	—	—
Rate and Extent of Absorption of AZD7594 by Assessment of the Cumulative Amount of AZD7594 Excreted From Time Zero to the Last Sampling Interval (Ae [0-last]) 0-24h	201.9 pmol Standard Deviation 117.9	5.183 pmol Standard Deviation 13.71	13.68 pmol Standard Deviation 17.07	—	—	—
Rate and Extent of Absorption of AZD7594 by Assessment of the Cumulative Amount of AZD7594 Excreted From Time Zero to the Last Sampling Interval (Ae [0-last]) 0-48h	309.9 pmol Standard Deviation 175.6	5.183 pmol Standard Deviation 13.71	13.68 pmol Standard Deviation 17.07	—	—	—
Rate and Extent of Absorption of AZD7594 by Assessment of the Cumulative Amount of AZD7594 Excreted From Time Zero to the Last Sampling Interval (Ae [0-last]) 0-72h	382.3 pmol Standard Deviation 219.7	5.183 pmol Standard Deviation 13.71	13.68 pmol Standard Deviation 17.07	—	—	—
Rate and Extent of Absorption of AZD7594 by Assessment of the Cumulative Amount of AZD7594 Excreted From Time Zero to the Last Sampling Interval (Ae [0-last]) 0-96h	431.2 pmol Standard Deviation 262.2	5.183 pmol Standard Deviation 13.71	13.68 pmol Standard Deviation 17.07	—	—	—

SECONDARY outcome

Timeframe: Day 1 predose spot-collection and interval collection up to 96 hours postdose

Population: The PK analysis set consisted of all subjects in the safety analysis set who received AZD7594 and had at least 1 measured AZD7594 plasma concentration at a scheduled PK time point post-dose, with no major protocol deviations thought to impact on the analysis of the PK data.

Assessment of the urine PK following a single dose of AZD7594. fe(0-last)% was defined as Percentage of dose excreted unchanged into the urine from time zero to the last measured time point for an AZD7594, estimated by dividing Ae(0-last) by dose.

Outcome measures

Outcome measures
Measure	AZD7594 1600 μg n=7 Participants Participants received 1600 μg inhaled AZD7594 via multi-dose DPI (4 x 400 μg inhalations).	AZD7594 200 μg n=7 Participants Participants received 200 μg inhaled AZD7594 via multi-dose dry powder inhaler (DPI) (1 x 200 μg inhalation)	AZD7594 400 μg n=7 Participants Participants received 400 μg inhaled AZD7594 via multi-dose DPI (1 x 400 μg inhalation)	Placebo Participants received placebo.	Placebo Participants who received placebo.	All Subjects Total number of participants in the study.
Rate and Extent of Absorption of AZD7594 by Assessment of the Percentage of Dose Excreted Unchanged Into the Urine From Time Zero to the Last Measured Time Point for an AZD7594, Estimated by Dividing Ae(0-last) by Dose (fe(0-last)%) 0-6h	0.002108 Percentage of dose excreted unchanged Standard Deviation 0.002197	0.0005623 Percentage of dose excreted unchanged Standard Deviation 0.001488	0.001022 Percentage of dose excreted unchanged Standard Deviation 0.001480	—	—	—
Rate and Extent of Absorption of AZD7594 by Assessment of the Percentage of Dose Excreted Unchanged Into the Urine From Time Zero to the Last Measured Time Point for an AZD7594, Estimated by Dividing Ae(0-last) by Dose (fe(0-last)%) 6-12h	0.002771 Percentage of dose excreted unchanged Standard Deviation 0.002016	0.0004346 Percentage of dose excreted unchanged Standard Deviation 0.001150	0.0007634 Percentage of dose excreted unchanged Standard Deviation 0.001008	—	—	—
Rate and Extent of Absorption of AZD7594 by Assessment of the Percentage of Dose Excreted Unchanged Into the Urine From Time Zero to the Last Measured Time Point for an AZD7594, Estimated by Dividing Ae(0-last) by Dose (fe(0-last)%) 12-24h	0.002770 Percentage of dose excreted unchanged Standard Deviation 0.001930	0.0005736 Percentage of dose excreted unchanged Standard Deviation 0.001518	0.0002894 Percentage of dose excreted unchanged Standard Deviation 0.0007657	—	—	—
Rate and Extent of Absorption of AZD7594 by Assessment of the Percentage of Dose Excreted Unchanged Into the Urine From Time Zero to the Last Measured Time Point for an AZD7594, Estimated by Dividing Ae(0-last) by Dose (fe(0-last)%) 24-48h	0.004088 Percentage of dose excreted unchanged Standard Deviation 0.002915	NA Percentage of dose excreted unchanged Standard Deviation NA NA - Not available Participants concentration values were below lower limit of quantitation (10 pmol/L) category	NA Percentage of dose excreted unchanged Standard Deviation NA NA - Not available Participants concentration values were below lower limit of quantitation (10 pmol/L) category	—	—	—
Rate and Extent of Absorption of AZD7594 by Assessment of the Percentage of Dose Excreted Unchanged Into the Urine From Time Zero to the Last Measured Time Point for an AZD7594, Estimated by Dividing Ae(0-last) by Dose (fe(0-last)%) 48-72h	0.002743 Percentage of dose excreted unchanged Standard Deviation 0.002226	NA Percentage of dose excreted unchanged Standard Deviation NA NA - Not available Participants concentration values were below lower limit of quantitation (10 pmol/L) category	NA Percentage of dose excreted unchanged Standard Deviation NA NA - Not available Participants concentration values were below lower limit of quantitation (10 pmol/L) category	—	—	—
Rate and Extent of Absorption of AZD7594 by Assessment of the Percentage of Dose Excreted Unchanged Into the Urine From Time Zero to the Last Measured Time Point for an AZD7594, Estimated by Dividing Ae(0-last) by Dose (fe(0-last)%) 72-96h	0.001854 Percentage of dose excreted unchanged Standard Deviation 0.001837	NA Percentage of dose excreted unchanged Standard Deviation NA NA - Not available Participants concentration values were below lower limit of quantitation (10 pmol/L) category	NA Percentage of dose excreted unchanged Standard Deviation NA NA - Not available Participants concentration values were below lower limit of quantitation (10 pmol/L) category	—	—	—

SECONDARY outcome

Timeframe: Day 1 predose spot-collection and interval collection up to 96 hours postdose

Population: The PK analysis set consisted of all subjects in the safety analysis set who received AZD7594 and had at least 1 measured AZD7594 plasma concentration at a scheduled PK time point post-dose, with no major protocol deviations thought to impact on the analysis of the PK data.

Assessment of the urine PK following a single dose of AZD7594. CLR was defined as the renal clearance, estimated by dividing Ae(0-96) by AUC(0-96).

Outcome measures

Outcome measures
Measure	AZD7594 1600 μg n=7 Participants Participants received 1600 μg inhaled AZD7594 via multi-dose DPI (4 x 400 μg inhalations).	AZD7594 200 μg n=7 Participants Participants received 200 μg inhaled AZD7594 via multi-dose dry powder inhaler (DPI) (1 x 200 μg inhalation)	AZD7594 400 μg n=7 Participants Participants received 400 μg inhaled AZD7594 via multi-dose DPI (1 x 400 μg inhalation)	Placebo Participants received placebo.	Placebo Participants who received placebo.	All Subjects Total number of participants in the study.
Rate and Extent of Absorption of AZD7594 by Assessment of the Renal Clearance, Estimated by Dividing Ae(0-96) by AUC(0-96) (CLR)	0.02329 L/h Geometric Coefficient of Variation 98.8	NA L/h Geometric Coefficient of Variation NA NA - Not available Since, %AUCextr was \> 30%, values were excluded from descriptive statistics	NA L/h Geometric Coefficient of Variation NA NA - Not available Since, %AUCextr was \> 30%, values were excluded from descriptive statistics	—	—	—

SECONDARY outcome

Timeframe: Day -1 (- 24 hours predose) up to 24 hours postdose; Day 1 and Day 16

Population: The pharmacodynamics analysis set will include all subjects who receive at least 1 dose of IMP and for whom it is possible to calculate the cortisol AUEC on Day -1, Day 1 and/or Day 16 and with no major protocol deviations considered to impact on the analysis of the PD (cortisol, plasma DHEAS and osteocalcin) data.

Assessment of the plasma pharmacodynamics (PD) effects of AZD7594 after single and multiple ascending inhaled doses. AUEC(0-24) was defined as area under the effect curve for plasma cortisol from time zero to 24 hours after dosing.

Outcome measures

Outcome measures
Measure	AZD7594 1600 μg n=7 Participants Participants received 1600 μg inhaled AZD7594 via multi-dose DPI (4 x 400 μg inhalations).	AZD7594 200 μg n=7 Participants Participants received 200 μg inhaled AZD7594 via multi-dose dry powder inhaler (DPI) (1 x 200 μg inhalation)	AZD7594 400 μg n=7 Participants Participants received 400 μg inhaled AZD7594 via multi-dose DPI (1 x 400 μg inhalation)	Placebo n=6 Participants Participants received placebo.	Placebo Participants who received placebo.	All Subjects Total number of participants in the study.
Pharmacodynamic Analysis of AZD7594 by Assessment of the Area Under the Effect Curve for Plasma Cortisol From Time Zero to 24 Hours After Dosing (AUEC [0-24]). Day -1	298827.031 min*nmol/L Standard Deviation 57082.835	294273.817 min*nmol/L Standard Deviation 66921.717	286677.610 min*nmol/L Standard Deviation 41429.744	275402.666 min*nmol/L Standard Deviation 42811.506	—	—
Pharmacodynamic Analysis of AZD7594 by Assessment of the Area Under the Effect Curve for Plasma Cortisol From Time Zero to 24 Hours After Dosing (AUEC [0-24]). Day 1	264104.101 min*nmol/L Standard Deviation 47619.269	268228.553 min*nmol/L Standard Deviation 34086.352	274458.997 min*nmol/L Standard Deviation 36894.669	256226.560 min*nmol/L Standard Deviation 48755.915	—	—
Pharmacodynamic Analysis of AZD7594 by Assessment of the Area Under the Effect Curve for Plasma Cortisol From Time Zero to 24 Hours After Dosing (AUEC [0-24]). Day 16	213505.523 min*nmol/L Standard Deviation 40857.201	253767.846 min*nmol/L Standard Deviation 11407.064	249097.459 min*nmol/L Standard Deviation 46925.914	273268.869 min*nmol/L Standard Deviation 57797.995	—	—

SECONDARY outcome

Timeframe: Day 1 (predose) and Day 16 (24 hours postdose)

Population: The pharmacodynamics analysis set will include all subjects who receive at least 1 dose of IMP and for whom it is possible to calculate the cortisol AUEC on Day -1, Day 1 and/or Day 16 and with no major protocol deviations considered to impact on the analysis of the PD (cortisol, plasma DHEAS and osteocalcin) data.

Assessment of the plasma PD following a single dose of AZD7594

Outcome measures

Outcome measures
Measure	AZD7594 1600 μg n=7 Participants Participants received 1600 μg inhaled AZD7594 via multi-dose DPI (4 x 400 μg inhalations).	AZD7594 200 μg n=7 Participants Participants received 200 μg inhaled AZD7594 via multi-dose dry powder inhaler (DPI) (1 x 200 μg inhalation)	AZD7594 400 μg n=7 Participants Participants received 400 μg inhaled AZD7594 via multi-dose DPI (1 x 400 μg inhalation)	Placebo n=6 Participants Participants received placebo.	Placebo Participants who received placebo.	All Subjects Total number of participants in the study.
Pharmacodynamic Analysis of AZD7594 by Assessment of Plasma Concentration of Dehydroepiandrosterone Sulphate (DHEAS) Result: Day 1 / pre-dose	6.747 μmol/L Standard Deviation 2.936	6.716 μmol/L Standard Deviation 1.405	7.380 μmol/L Standard Deviation 2.429	6.280 μmol/L Standard Deviation 1.829	—	—
Pharmacodynamic Analysis of AZD7594 by Assessment of Plasma Concentration of Dehydroepiandrosterone Sulphate (DHEAS) Result: Day 17 / 24 h	7.125 μmol/L Standard Deviation 2.708	6.104 μmol/L Standard Deviation 0.862	6.250 μmol/L Standard Deviation 1.005	6.392 μmol/L Standard Deviation 2.179	—	—

SECONDARY outcome

Timeframe: Day 1 (predose) and Day 16 (24 hours postdose)

Population: The pharmacodynamics analysis set will include all subjects who receive at least 1 dose of IMP and for whom it is possible to calculate the cortisol AUEC on Day -1, Day 1 and/or Day 16 and with no major protocol deviations considered to impact on the analysis of the PD (cortisol, plasma DHEAS and osteocalcin) data.

Assessment of the plasma PD following a single dose of AZD7594

Outcome measures

Outcome measures
Measure	AZD7594 1600 μg n=7 Participants Participants received 1600 μg inhaled AZD7594 via multi-dose DPI (4 x 400 μg inhalations).	AZD7594 200 μg n=7 Participants Participants received 200 μg inhaled AZD7594 via multi-dose dry powder inhaler (DPI) (1 x 200 μg inhalation)	AZD7594 400 μg n=7 Participants Participants received 400 μg inhaled AZD7594 via multi-dose DPI (1 x 400 μg inhalation)	Placebo n=6 Participants Participants received placebo.	Placebo Participants who received placebo.	All Subjects Total number of participants in the study.
Pharmacodynamic Analysis of AZD7594 by Assessment of Plasma Concentration of Osteocalcin Day 1 / pre-dose	20.01 μg/L Standard Deviation 5.77	21.31 μg/L Standard Deviation 17.22	23.13 μg/L Standard Deviation 10.02	22.92 μg/L Standard Deviation 20.13	—	—
Pharmacodynamic Analysis of AZD7594 by Assessment of Plasma Concentration of Osteocalcin Day 17 / 24 h	13.37 μg/L Standard Deviation 8.26	17.81 μg/L Standard Deviation 8.55	19.66 μg/L Standard Deviation 11.56	17.03 μg/L Standard Deviation 5.60	—	—

Adverse Events

AZD7594 200 μg

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

AZD7594 400 μg

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

AZD7594 1600 μg

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Palcebo

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Total AZD7594

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

All Subjects

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	AZD7594 200 μg n=7 participants at risk Participants received 200 μg inhaled AZD7594 via multi-dose dry powder inhaler (DPI) (1 x 200 μg inhalation)	AZD7594 400 μg n=7 participants at risk Participants received 400 μg inhaled AZD7594 via multi-dose DPI (1 x 400 μg inhalation)	AZD7594 1600 μg n=7 participants at risk Participants received 1600 μg inhaled AZD7594 via multi-dose DPI (4 x 400 μg inhalations).	Palcebo n=6 participants at risk Participants received placebo	Total AZD7594 n=21 participants at risk Overall number of subjects who received AZD7594 therapy.	All Subjects n=27 participants at risk Overall number of subjects who participated in the study.
Respiratory, thoracic and mediastinal disorders Dry throat	14.3% 1/7 • Number of events 1 • Serious adverse events (SAEs) were recorded from the signing of informed consent and adverse events (AEs) were recorded from randomization until the final follow-up visit. An AE is an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. AEs which met the "Definitions of Serious Adverse Event" defined in the clinical study protocol were regarded as SAEs.	0.00% 0/7 • Serious adverse events (SAEs) were recorded from the signing of informed consent and adverse events (AEs) were recorded from randomization until the final follow-up visit. An AE is an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. AEs which met the "Definitions of Serious Adverse Event" defined in the clinical study protocol were regarded as SAEs.	0.00% 0/7 • Serious adverse events (SAEs) were recorded from the signing of informed consent and adverse events (AEs) were recorded from randomization until the final follow-up visit. An AE is an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. AEs which met the "Definitions of Serious Adverse Event" defined in the clinical study protocol were regarded as SAEs.	0.00% 0/6 • Serious adverse events (SAEs) were recorded from the signing of informed consent and adverse events (AEs) were recorded from randomization until the final follow-up visit. An AE is an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. AEs which met the "Definitions of Serious Adverse Event" defined in the clinical study protocol were regarded as SAEs.	4.8% 1/21 • Number of events 1 • Serious adverse events (SAEs) were recorded from the signing of informed consent and adverse events (AEs) were recorded from randomization until the final follow-up visit. An AE is an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. AEs which met the "Definitions of Serious Adverse Event" defined in the clinical study protocol were regarded as SAEs.	3.7% 1/27 • Number of events 1 • Serious adverse events (SAEs) were recorded from the signing of informed consent and adverse events (AEs) were recorded from randomization until the final follow-up visit. An AE is an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. AEs which met the "Definitions of Serious Adverse Event" defined in the clinical study protocol were regarded as SAEs.
Respiratory, thoracic and mediastinal disorders Nasal congestion	14.3% 1/7 • Number of events 1 • Serious adverse events (SAEs) were recorded from the signing of informed consent and adverse events (AEs) were recorded from randomization until the final follow-up visit. An AE is an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. AEs which met the "Definitions of Serious Adverse Event" defined in the clinical study protocol were regarded as SAEs.	0.00% 0/7 • Serious adverse events (SAEs) were recorded from the signing of informed consent and adverse events (AEs) were recorded from randomization until the final follow-up visit. An AE is an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. AEs which met the "Definitions of Serious Adverse Event" defined in the clinical study protocol were regarded as SAEs.	0.00% 0/7 • Serious adverse events (SAEs) were recorded from the signing of informed consent and adverse events (AEs) were recorded from randomization until the final follow-up visit. An AE is an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. AEs which met the "Definitions of Serious Adverse Event" defined in the clinical study protocol were regarded as SAEs.	0.00% 0/6 • Serious adverse events (SAEs) were recorded from the signing of informed consent and adverse events (AEs) were recorded from randomization until the final follow-up visit. An AE is an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. AEs which met the "Definitions of Serious Adverse Event" defined in the clinical study protocol were regarded as SAEs.	4.8% 1/21 • Number of events 1 • Serious adverse events (SAEs) were recorded from the signing of informed consent and adverse events (AEs) were recorded from randomization until the final follow-up visit. An AE is an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. AEs which met the "Definitions of Serious Adverse Event" defined in the clinical study protocol were regarded as SAEs.	3.7% 1/27 • Number of events 1 • Serious adverse events (SAEs) were recorded from the signing of informed consent and adverse events (AEs) were recorded from randomization until the final follow-up visit. An AE is an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. AEs which met the "Definitions of Serious Adverse Event" defined in the clinical study protocol were regarded as SAEs.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	14.3% 1/7 • Number of events 1 • Serious adverse events (SAEs) were recorded from the signing of informed consent and adverse events (AEs) were recorded from randomization until the final follow-up visit. An AE is an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. AEs which met the "Definitions of Serious Adverse Event" defined in the clinical study protocol were regarded as SAEs.	0.00% 0/7 • Serious adverse events (SAEs) were recorded from the signing of informed consent and adverse events (AEs) were recorded from randomization until the final follow-up visit. An AE is an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. AEs which met the "Definitions of Serious Adverse Event" defined in the clinical study protocol were regarded as SAEs.	0.00% 0/7 • Serious adverse events (SAEs) were recorded from the signing of informed consent and adverse events (AEs) were recorded from randomization until the final follow-up visit. An AE is an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. AEs which met the "Definitions of Serious Adverse Event" defined in the clinical study protocol were regarded as SAEs.	0.00% 0/6 • Serious adverse events (SAEs) were recorded from the signing of informed consent and adverse events (AEs) were recorded from randomization until the final follow-up visit. An AE is an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. AEs which met the "Definitions of Serious Adverse Event" defined in the clinical study protocol were regarded as SAEs.	4.8% 1/21 • Number of events 1 • Serious adverse events (SAEs) were recorded from the signing of informed consent and adverse events (AEs) were recorded from randomization until the final follow-up visit. An AE is an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. AEs which met the "Definitions of Serious Adverse Event" defined in the clinical study protocol were regarded as SAEs.	3.7% 1/27 • Number of events 1 • Serious adverse events (SAEs) were recorded from the signing of informed consent and adverse events (AEs) were recorded from randomization until the final follow-up visit. An AE is an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. AEs which met the "Definitions of Serious Adverse Event" defined in the clinical study protocol were regarded as SAEs.
Infections and infestations Folliculitis	0.00% 0/7 • Serious adverse events (SAEs) were recorded from the signing of informed consent and adverse events (AEs) were recorded from randomization until the final follow-up visit. An AE is an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. AEs which met the "Definitions of Serious Adverse Event" defined in the clinical study protocol were regarded as SAEs.	14.3% 1/7 • Number of events 1 • Serious adverse events (SAEs) were recorded from the signing of informed consent and adverse events (AEs) were recorded from randomization until the final follow-up visit. An AE is an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. AEs which met the "Definitions of Serious Adverse Event" defined in the clinical study protocol were regarded as SAEs.	0.00% 0/7 • Serious adverse events (SAEs) were recorded from the signing of informed consent and adverse events (AEs) were recorded from randomization until the final follow-up visit. An AE is an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. AEs which met the "Definitions of Serious Adverse Event" defined in the clinical study protocol were regarded as SAEs.	0.00% 0/6 • Serious adverse events (SAEs) were recorded from the signing of informed consent and adverse events (AEs) were recorded from randomization until the final follow-up visit. An AE is an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. AEs which met the "Definitions of Serious Adverse Event" defined in the clinical study protocol were regarded as SAEs.	4.8% 1/21 • Number of events 1 • Serious adverse events (SAEs) were recorded from the signing of informed consent and adverse events (AEs) were recorded from randomization until the final follow-up visit. An AE is an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. AEs which met the "Definitions of Serious Adverse Event" defined in the clinical study protocol were regarded as SAEs.	3.7% 1/27 • Number of events 1 • Serious adverse events (SAEs) were recorded from the signing of informed consent and adverse events (AEs) were recorded from randomization until the final follow-up visit. An AE is an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. AEs which met the "Definitions of Serious Adverse Event" defined in the clinical study protocol were regarded as SAEs.
Metabolism and nutrition disorders Gout	0.00% 0/7 • Serious adverse events (SAEs) were recorded from the signing of informed consent and adverse events (AEs) were recorded from randomization until the final follow-up visit. An AE is an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. AEs which met the "Definitions of Serious Adverse Event" defined in the clinical study protocol were regarded as SAEs.	0.00% 0/7 • Serious adverse events (SAEs) were recorded from the signing of informed consent and adverse events (AEs) were recorded from randomization until the final follow-up visit. An AE is an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. AEs which met the "Definitions of Serious Adverse Event" defined in the clinical study protocol were regarded as SAEs.	0.00% 0/7 • Serious adverse events (SAEs) were recorded from the signing of informed consent and adverse events (AEs) were recorded from randomization until the final follow-up visit. An AE is an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. AEs which met the "Definitions of Serious Adverse Event" defined in the clinical study protocol were regarded as SAEs.	16.7% 1/6 • Number of events 1 • Serious adverse events (SAEs) were recorded from the signing of informed consent and adverse events (AEs) were recorded from randomization until the final follow-up visit. An AE is an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. AEs which met the "Definitions of Serious Adverse Event" defined in the clinical study protocol were regarded as SAEs.	0.00% 0/21 • Serious adverse events (SAEs) were recorded from the signing of informed consent and adverse events (AEs) were recorded from randomization until the final follow-up visit. An AE is an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. AEs which met the "Definitions of Serious Adverse Event" defined in the clinical study protocol were regarded as SAEs.	3.7% 1/27 • Number of events 1 • Serious adverse events (SAEs) were recorded from the signing of informed consent and adverse events (AEs) were recorded from randomization until the final follow-up visit. An AE is an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. AEs which met the "Definitions of Serious Adverse Event" defined in the clinical study protocol were regarded as SAEs.
Nervous system disorders Presyncope	0.00% 0/7 • Serious adverse events (SAEs) were recorded from the signing of informed consent and adverse events (AEs) were recorded from randomization until the final follow-up visit. An AE is an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. AEs which met the "Definitions of Serious Adverse Event" defined in the clinical study protocol were regarded as SAEs.	0.00% 0/7 • Serious adverse events (SAEs) were recorded from the signing of informed consent and adverse events (AEs) were recorded from randomization until the final follow-up visit. An AE is an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. AEs which met the "Definitions of Serious Adverse Event" defined in the clinical study protocol were regarded as SAEs.	14.3% 1/7 • Number of events 1 • Serious adverse events (SAEs) were recorded from the signing of informed consent and adverse events (AEs) were recorded from randomization until the final follow-up visit. An AE is an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. AEs which met the "Definitions of Serious Adverse Event" defined in the clinical study protocol were regarded as SAEs.	0.00% 0/6 • Serious adverse events (SAEs) were recorded from the signing of informed consent and adverse events (AEs) were recorded from randomization until the final follow-up visit. An AE is an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. AEs which met the "Definitions of Serious Adverse Event" defined in the clinical study protocol were regarded as SAEs.	4.8% 1/21 • Number of events 1 • Serious adverse events (SAEs) were recorded from the signing of informed consent and adverse events (AEs) were recorded from randomization until the final follow-up visit. An AE is an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. AEs which met the "Definitions of Serious Adverse Event" defined in the clinical study protocol were regarded as SAEs.	3.7% 1/27 • Number of events 1 • Serious adverse events (SAEs) were recorded from the signing of informed consent and adverse events (AEs) were recorded from randomization until the final follow-up visit. An AE is an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. AEs which met the "Definitions of Serious Adverse Event" defined in the clinical study protocol were regarded as SAEs.

Additional Information

AZD7594 Global Clinical Leader

AstraZeneca AB

Phone: +46317761000

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee All clinical study findings and documents will be regarded as confidential. The investigator and members of his/her research team must not disclose such information without prior written approval from the sponsor.
Publication restrictions are in place

Restriction type: OTHER