Trial Outcomes & Findings for A Multiple Dosing (14 Days) Study to Assess Efficacy and Safety of Three Dose Levels of AZD7594, Given Once Daily by Inhalation, in Patients With Mild to Moderate Asthma (NCT NCT02479412)

Last Updated: 2018-02-15

Results Overview

Comparison of the efficacy of AZD7594 in terms of change from baseline in morning trough forced expiratory volume in 1 second (FEV1) on Day 15 (defined as the average of the values at 23:00 and 23:30 hours after last dose of investigational medicinal product \[IMP\] on Day 14) with placebo

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

54 participants

Primary outcome timeframe

On Day 1 (pre-dose) and on Day 15 in each period

Results posted on

2018-02-15

Participant Flow

The study was conducted in Germany (9 centers) and Bulgaria (1 center). A total of 54 participants with mild to moderate asthma were randomized after screening, and received study treatment (AZD7594 or placebo) given over 3 Treatment Periods in an incomplete block crossover design.

The study consisted of a 2-part run-in period, 3 treatment periods separated by intervening wash-out periods, and a final period of safety follow-up .

Participant milestones

Participant milestones
Measure	Sequence 1 (Placebo + AZD7594 58 μg + AZD7594 250 μg) Participants received Placebo in Treatment Period 1 (1st intervention - 14 days), AZD7594 58 μg in Treatment Period 2 (2nd intervention - 14 days) and AZD7594 250 μg treatment in Period 3 (3rd intervention - 14 days). After treatment periods 1 and 2, participants had an intervening wash-out period of 21 days.	Sequence 2 (Placebo + AZD7594 250 μg + AZD7594 800 μg) Participants received Placebo in Treatment Period 1 (1st intervention - 14 days), AZD7594 250 μg in Treatment Period 2 (2nd intervention - 14 days) and AZD7594 800 μg in Treatment Period 3 (3rd intervention - 14 days). After treatment periods 1 and 2, participants had an intervening wash-out period of 21 days.	Sequence 3 (Placebo + AZD7594 800 µg + AZD7594 58 µg) Participants received Placebo in Treatment Period 1 (1st intervention - 14 days), AZD7594 800 μg in Treatment Period 2 (2nd intervention - 14 days) and AZD7594 58 μg in Treatment Period 3 (3rd intervention - 14 days). After treatment periods 1 and 2, participants had an intervening wash-out period of 21 days.	Sequence 4 (AZD7594 58 μg + Placebo + AZD7594 800 μg) Participants received AZD7594 58 μg in Treatment Period 1 (1st intervention - 14 days), Placebo in Treatment Period 2 (2nd intervention - 14 days) and AZD7594 800 μg in Treatment Period 3 (3rd intervention - 14 days). After treatment periods 1 and 2, participants had an intervening wash-out period of 21 days.	Sequence 5 (AZD7594 58 µg + AZD7594 800 µg + Placebo) Participants received AZD7594 58 μg in Treatment Period 1 (1st intervention - 14 days), AZD7594 800 μg in Treatment Period 2 (2nd intervention - 14 days) and Placebo in Treatment Period 3 (3rd intervention - 14 days). After treatment periods 1 and 2, participants had an intervening wash-out period of 21 days.	Sequence 6 (AZD7594 250 μg + Placebo + AZD7594 58 μg) Participants received AZD7594 250 μg in Treatment Period 1 (1st intervention - 14 days), Placebo in Treatment Period 2 (2nd intervention - 14 days) and AZD7594 58 μg in Treatment Period 3 (3rd intervention - 14 days). After treatment periods 1 and 2, participants had an intervening wash-out period of 21 days.	Sequence 7 (AZD7594 250 μg + AZD7594 58 μg + Placebo) Participants received AZD7594 250 μg in Treatment Period 1 (1st intervention - 14 days), AZD7594 58 μg in Treatment Period 2 (2nd intervention - 14 days) and Placebo in Treatment Period 3 (3rd intervention- 14 days). After treatment periods 1 and 2, participants had an intervening wash-out period of 21 days.	Sequence 8 (AZD7594 800 μg + Placebo + AZD7594 250 μg) Participants received AZD7594 800 μg in Treatment Period 1 (1st intervention - 14 days), Placebo in Treatment Period 2 (2nd intervention - 14 days) and AZD7594 250 μg Treatment Period 3 (3rd intervention - 14 days). After treatment periods 1 and 2, participants had an intervening wash-out period of 21 days.	Sequence 9 (AZD7594 800 μg + AZD7594 250 μg + Placebo) Participant received AZD7594 800 μg in Treatment Period 1 (1st intervention 14 days), AZD7594 250 μg in Treatment Period 2 (2nd intervention - 14 days) and Placebo in Treatment Period 3 (3rd intervention - 14 days). After treatment periods 1 and 2, participants had an intervening wash-out period of 21 days.
Overall Study STARTED	6	6	6	7	6	5	6	5	7
Overall Study COMPLETED	6	6	4	6	5	5	6	4	6
Overall Study NOT COMPLETED	0	0	2	1	1	0	0	1	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Sequence 3 (Placebo + AZD7594 800 µg + AZD7594 58 µg) Participants received Placebo in Treatment Period 1 (1st intervention - 14 days), AZD7594 800 μg in Treatment Period 2 (2nd intervention - 14 days) and AZD7594 58 μg in Treatment Period 3 (3rd intervention - 14 days). After treatment periods 1 and 2, participants had an intervening wash-out period of 21 days.	Sequence 4 (AZD7594 58 μg + Placebo + AZD7594 800 μg) Participants received AZD7594 58 μg in Treatment Period 1 (1st intervention - 14 days), Placebo in Treatment Period 2 (2nd intervention - 14 days) and AZD7594 800 μg in Treatment Period 3 (3rd intervention - 14 days). After treatment periods 1 and 2, participants had an intervening wash-out period of 21 days.	Sequence 5 (AZD7594 58 µg + AZD7594 800 µg + Placebo) Participants received AZD7594 58 μg in Treatment Period 1 (1st intervention - 14 days), AZD7594 800 μg in Treatment Period 2 (2nd intervention - 14 days) and Placebo in Treatment Period 3 (3rd intervention - 14 days). After treatment periods 1 and 2, participants had an intervening wash-out period of 21 days.	Sequence 8 (AZD7594 800 μg + Placebo + AZD7594 250 μg) Participants received AZD7594 800 μg in Treatment Period 1 (1st intervention - 14 days), Placebo in Treatment Period 2 (2nd intervention - 14 days) and AZD7594 250 μg Treatment Period 3 (3rd intervention - 14 days). After treatment periods 1 and 2, participants had an intervening wash-out period of 21 days.	Sequence 9 (AZD7594 800 μg + AZD7594 250 μg + Placebo) Participant received AZD7594 800 μg in Treatment Period 1 (1st intervention 14 days), AZD7594 250 μg in Treatment Period 2 (2nd intervention - 14 days) and Placebo in Treatment Period 3 (3rd intervention - 14 days). After treatment periods 1 and 2, participants had an intervening wash-out period of 21 days.
Overall Study Adverse Event	1	0	0	0	0
Overall Study Study-specific withdrawal criteria	1	1	0	1	1
Overall Study Randomization to wrong PK sampling group	0	0	1	0	0

Baseline Characteristics

A Multiple Dosing (14 Days) Study to Assess Efficacy and Safety of Three Dose Levels of AZD7594, Given Once Daily by Inhalation, in Patients With Mild to Moderate Asthma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sequence 1 (Placebo + AZD7594 58 μg + AZD7594 250 μg) n=6 Participants Participants received Placebo in Treatment Period 1 (1st intervention - 14 days), AZD7594 58 μg in Treatment Period 2 (2nd intervention - 14 days) and AZD7594 250 μg treatment in Period 3 (3rd intervention - 14 days). After treatment periods 1 and 2, participants had an intervening wash-out period of 21 days.	Sequence 2 (Placebo + AZD7594 250 μg + AZD7594 800 μg) n=6 Participants Participants received Placebo in Treatment Period 1 (1st intervention - 14 days), AZD7594 250 μg in Treatment Period 2 (2nd intervention - 14 days) and AZD7594 800 μg in Treatment Period 3 (3rd intervention - 14 days). After treatment periods 1 and 2, participants had an intervening wash-out period of 21 days.	Sequence 3 (Placebo + AZD7594 800 µg + AZD7594 58 µg) n=6 Participants Participants received Placebo in Treatment Period 1 (1st intervention - 14 days), AZD7594 800 μg in Treatment Period 2 (2nd intervention - 14 days) and AZD7594 58 μg in Treatment Period 3 (3rd intervention - 14 days). After treatment periods 1 and 2, participants had an intervening wash-out period of 21 days.	Sequence 4 (AZD7594 58 μg + Placebo + AZD7594 800 μg) n=7 Participants Participants received AZD7594 58 μg in Treatment Period 1 (1st intervention - 14 days), Placebo in Treatment Period 2 (2nd intervention - 14 days) and AZD7594 800 μg in Treatment Period 3 (3rd intervention - 14 days). After treatment periods 1 and 2, participants had an intervening wash-out period of 21 days.	Sequence 5 (AZD7594 58 µg + AZD7594 800 µg + Placebo) n=6 Participants Participants received AZD7594 58 μg in Treatment Period 1 (1st intervention - 14 days), AZD7594 800 μg in Treatment Period 2 (2nd intervention - 14 days) and Placebo in Treatment Period 3 (3rd intervention - 14 days). After treatment periods 1 and 2, participants had an intervening wash-out period of 21 days.	Sequence 6 (AZD7594 250 μg + Placebo + AZD7594 58 μg) n=5 Participants Participants received AZD7594 250 μg in Treatment Period 1 (1st intervention - 14 days), Placebo in Treatment Period 2 (2nd intervention - 14 days) and AZD7594 58 μg in Treatment Period 3 (3rd intervention - 14 days). After treatment periods 1 and 2, participants had an intervening wash-out period of 21 days.	Sequence 7 (AZD7594 250 μg + AZD7594 58 μg + Placebo) n=6 Participants Participants received AZD7594 250 μg in Treatment Period 1 (1st intervention - 14 days), AZD7594 58 μg in Treatment Period 2 (2nd intervention - 14 days) and Placebo in Treatment Period 3 (3rd intervention- 14 days). After treatment periods 1 and 2, participants had an intervening wash-out period of 21 days.	Sequence 8 (AZD7594 800 μg + Placebo + AZD7594 250 μg) n=5 Participants Participants received AZD7594 800 μg in Treatment Period 1 (1st intervention - 14 days), Placebo in Treatment Period 2 (2nd intervention - 14 days) and AZD7594 250 μg Treatment Period 3 (3rd intervention - 14 days). After treatment periods 1 and 2, participants had an intervening wash-out period of 21 days.	Sequence 9 (AZD7594 800 μg + AZD7594 250 μg + Placebo) n=7 Participants Participant received AZD7594 800 μg in Treatment Period 1 (1st intervention 14 days), AZD7594 250 μg in Treatment Period 2 (2nd intervention - 14 days) and Placebo in Treatment Period 3 (3rd intervention - 14 days). After treatment periods 1 and 2, participants had an intervening wash-out period of 21 days.	Total n=54 Participants Total of all reporting groups
Age, Continuous Age (years)	49 Years STANDARD_DEVIATION 14 • n=5 Participants	50 Years STANDARD_DEVIATION 10 • n=7 Participants	56 Years STANDARD_DEVIATION 10 • n=5 Participants	50 Years STANDARD_DEVIATION 17 • n=4 Participants	49 Years STANDARD_DEVIATION 7 • n=21 Participants	55 Years STANDARD_DEVIATION 9 • n=8 Participants	48 Years STANDARD_DEVIATION 14 • n=8 Participants	55 Years STANDARD_DEVIATION 14 • n=24 Participants	46 Years STANDARD_DEVIATION 13 • n=42 Participants	51 Years STANDARD_DEVIATION 12 • n=42 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	0 Participants n=4 Participants	3 Participants n=21 Participants	2 Participants n=8 Participants	0 Participants n=8 Participants	1 Participants n=24 Participants	1 Participants n=42 Participants	10 Participants n=42 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	6 Participants n=7 Participants	4 Participants n=5 Participants	7 Participants n=4 Participants	3 Participants n=21 Participants	3 Participants n=8 Participants	6 Participants n=8 Participants	4 Participants n=24 Participants	6 Participants n=42 Participants	44 Participants n=42 Participants

PRIMARY outcome

Timeframe: On Day 1 (pre-dose) and on Day 15 in each period

Population: All randomized participants who received at least one dose of randomized study drug, were included in the full analysis set (FAS), following the principle of intent to treat (ITT). Participants were included in the analysis according to the treatment to which they were randomized.

Outcome measures

Outcome measures
Measure	AZD7594 n=33 Participants AZD7594 DPI once daily	Placebo n=51 Participants Placebo for AZD7594 DPI once daily	AZD7594 250 μg AZD7594 DPI once daily - 2 capsules of 125 μg	AZD7594 800 μg AZD7594 DPI once daily - 2 capsules of 400 μg
Efficacy of AZD7594 by Assessment of the Change From Baseline in Morning Trough Forced Expiratory Volume in 1 Second (FEV1) on Day 15 AZD7594 58 µg vs. PBO	0.08639 Liters Interval -0.0165 to 0.1893	0.05948 Liters Interval -0.02453 to 0.1435	—	—
Efficacy of AZD7594 by Assessment of the Change From Baseline in Morning Trough Forced Expiratory Volume in 1 Second (FEV1) on Day 15 AZD7594 250 µg vs.PBO	0.1355 Liters Interval 0.03283 to 0.2382	0.05948 Liters Interval -0.02453 to 0.1435	—	—
Efficacy of AZD7594 by Assessment of the Change From Baseline in Morning Trough Forced Expiratory Volume in 1 Second (FEV1) on Day 15 AZD7594 800 µg vs.PBO	0.2072 Liters Interval 0.1041 to 0.3104	0.05948 Liters Interval -0.02453 to 0.1435	—	—

SECONDARY outcome

Timeframe: On Day 1 (pre-dose) and on Day 8 in each period

Population: All randomized participants who received at least one dose of randomized study drug, were included in the FAS, following the principle of ITT. Participants were included in the analysis according to the treatment to which they were randomized.

The efficacy of AZD7594 was assessed in terms of change from baseline in fractional exhaled nitric oxide (FeNO) on Day 8

Outcome measures

Outcome measures
Measure	AZD7594 n=33 Participants AZD7594 DPI once daily	Placebo n=52 Participants Placebo for AZD7594 DPI once daily	AZD7594 250 μg AZD7594 DPI once daily - 2 capsules of 125 μg	AZD7594 800 μg AZD7594 DPI once daily - 2 capsules of 400 μg
Efficacy of AZD7594 by Assessment of the Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) on Day 8 AZD7594 58 (Participant count=32) µg vs. PBO	-9.153 Parts per billion (ppb) Interval -15.08 to -3.23	-4.296 Parts per billion (ppb) Interval -9.046 to 0.4536	—	—
Efficacy of AZD7594 by Assessment of the Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) on Day 8 AZD7594 250 µg (Participant count=33) vs. PBO	-14.71 Parts per billion (ppb) Interval -20.56 to -8.862	-4.296 Parts per billion (ppb) Interval -9.046 to 0.4536	—	—
Efficacy of AZD7594 by Assessment of the Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) on Day 8 AZD7594 800 µg (Participant count=32) vs. PBO	-19.04 Parts per billion (ppb) Interval -24.99 to -13.1	-4.296 Parts per billion (ppb) Interval -9.046 to 0.4536	—	—

SECONDARY outcome

Timeframe: On Day 1 (pre-dose) and on Day 15 in each period

The efficacy of AZD7594 was assessed in terms of change from baseline in fractional exhaled nitric oxide (FeNO) on Day 15

Outcome measures

Outcome measures
Measure	AZD7594 n=33 Participants AZD7594 DPI once daily	Placebo n=51 Participants Placebo for AZD7594 DPI once daily	AZD7594 250 μg AZD7594 DPI once daily - 2 capsules of 125 μg	AZD7594 800 μg AZD7594 DPI once daily - 2 capsules of 400 μg
Efficacy of AZD7594 by Assessment of the Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) on Day 15 AZD7594 250 µg (Participant count=33) vs. PBO	-14.81 Parts per billion (ppb) Interval -22.96 to -6.657	-0.5488 Parts per billion (ppb) Interval -6.723 to 5.626	—	—
Efficacy of AZD7594 by Assessment of the Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) on Day 15 AZD7594 58 µg (Participant count=32) vs. PBO	-14.40 Parts per billion (ppb) Interval -22.67 to -6.129	-0.5488 Parts per billion (ppb) Interval -6.723 to 5.626	—	—
Efficacy of AZD7594 by Assessment of the Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) on Day 15 AZD7594 800 µg (Participant count=32) vs. PBO	-20.44 Parts per billion (ppb) Interval -28.72 to -12.17	-0.5488 Parts per billion (ppb) Interval -6.723 to 5.626	—	—

SECONDARY outcome

Timeframe: On Day 1 (pre-dose) and on Day 8 (pre-dose) in each period

The efficacy of AZD7594 was assessed in terms of change from baseline in morning trough forced expiratory volume in 1 second (FEV1) on Day 8 (defined as the average of the values at 23:00 and 23:30 hours after last dose of investigational medicinal product \[IMP\] on Day 7)

Outcome measures

Outcome measures
Measure	AZD7594 n=33 Participants AZD7594 DPI once daily	Placebo n=52 Participants Placebo for AZD7594 DPI once daily	AZD7594 250 μg AZD7594 DPI once daily - 2 capsules of 125 μg	AZD7594 800 μg AZD7594 DPI once daily - 2 capsules of 400 μg
Efficacy of AZD7594 by Assessment of the Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) on Day 8 AZD7594 58 μg vs. PBO	0.1016 Liters Interval -0.00007235 to 0.2033	0.07112 Liters Interval -0.009222 to 0.1515	—	—
Efficacy of AZD7594 by Assessment of the Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) on Day 8 AZD7594 250 μg vs. PBO	0.08856 Liters Interval -0.01295 to 0.1901	0.07112 Liters Interval -0.009222 to 0.1515	—	—
Efficacy of AZD7594 by Assessment of the Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) on Day 8 AZD7594 800 μg vs. PBO	0.2272 Liters Interval 0.1252 to 0.3293	0.07112 Liters Interval -0.009222 to 0.1515	—	—

SECONDARY outcome

Timeframe: On Day 1 (pre-dose) and on Day 15 (pre-dose) in each period

The efficacy of AZD7594 was assessed in terms of change from baseline in morning trough forced vital capacity (FVC) on Day 15 (defined as the average of the values at 23:00 and 23:30 hours after last dose of investigational medicinal product \[IMP\] on Day 14)

Outcome measures

Outcome measures
Measure	AZD7594 n=33 Participants AZD7594 DPI once daily	Placebo n=51 Participants Placebo for AZD7594 DPI once daily	AZD7594 250 μg AZD7594 DPI once daily - 2 capsules of 125 μg	AZD7594 800 μg AZD7594 DPI once daily - 2 capsules of 400 μg
Efficacy of AZD7594 by Assessment of the Change From Baseline in Trough Forced Vital Capacity (FVC) on Day 15 AZD7594 58 μg vs. PBO	0.04186 Liters Interval -0.06673 to 0.1505	0.07653 Liters Interval -0.01626 to 0.1693	—	—
Efficacy of AZD7594 by Assessment of the Change From Baseline in Trough Forced Vital Capacity (FVC) on Day 15 AZD7594 250 μg vs. PBO	0.1047 Liters Interval -0.003607 to 0.2131	0.07653 Liters Interval -0.01626 to 0.1693	—	—
Efficacy of AZD7594 by Assessment of the Change From Baseline in Trough Forced Vital Capacity (FVC) on Day 15 AZD7594 800 μg vs. PBO	0.1382 Liters Interval 0.02938 to 0.2471	0.0765 Liters Interval -0.01626 to 0.1693	—	—

SECONDARY outcome

Timeframe: On Day 1 (pre-dose) and on Day 8 (pre-dose) in each period

The efficacy of AZD7594 was assessed in terms of change from baseline in morning trough forced vital capacity (FVC) on Day 8 (defined as the average of the values at 23:00 and 23:30 hours after last dose of investigational medicinal product \[IMP\] on Day 7)

Outcome measures

Outcome measures
Measure	AZD7594 n=33 Participants AZD7594 DPI once daily	Placebo n=52 Participants Placebo for AZD7594 DPI once daily	AZD7594 250 μg AZD7594 DPI once daily - 2 capsules of 125 μg	AZD7594 800 μg AZD7594 DPI once daily - 2 capsules of 400 μg
Efficacy of AZD7594 by Assessment of the Change From Baseline in Trough Forced Vital Capacity (FVC) on Day 8 AZD7594 58 μg vs. PBO	0.06179 Liters Interval -0.04132 to 0.1649	0.08441 Liters Interval 0.001635 to 0.1672	—	—
Efficacy of AZD7594 by Assessment of the Change From Baseline in Trough Forced Vital Capacity (FVC) on Day 8 AZD7594 250 μg vs. PBO	0.08410 Liters Interval -0.01877 to 0.187	0.08441 Liters Interval 0.001635 to 0.1672	—	—
Efficacy of AZD7594 by Assessment of the Change From Baseline in Trough Forced Vital Capacity (FVC) on Day 8 AZD7594 800 μg vs. PBO	0.1527 Liters Interval 0.04929 to 0.2562	0.08441 Liters Interval 0.001635 to 0.1672	—	—

SECONDARY outcome

Timeframe: Every morning at pre-dose from Day 1 to Day 15

The efficacy of AZD7594 was assessed in terms of change from baseline in morning peak expiratory flow (mPEF) before administration of the investigational medicinal product (IMP) in each treatment period. The first PEF measurement was on the evening of Visit 1. Every morning and every evening after Visit 1, patients were required to perform 3 maneuvers for PEF assessment. The highest value from among the 3 assessments was marked as mPEF with the date and time of the measurement. The final PEF assessment was done on the morning of Visit 11 (Day 15 of Treatment Period 3).

Outcome measures

Outcome measures
Measure	AZD7594 n=33 Participants AZD7594 DPI once daily	Placebo n=52 Participants Placebo for AZD7594 DPI once daily	AZD7594 250 μg AZD7594 DPI once daily - 2 capsules of 125 μg	AZD7594 800 μg AZD7594 DPI once daily - 2 capsules of 400 μg
Efficacy of AZD7594 by Assessment of the Change From Baseline in Morning Peak Expiratory Flow (mPEF) Before Administration Over the Treatment Period AZD7594 58 μg vs. PBO	10.42 L/min Interval -1.909 to 22.74	0.08136 L/min Interval -10.5 to 10.66	—	—
Efficacy of AZD7594 by Assessment of the Change From Baseline in Morning Peak Expiratory Flow (mPEF) Before Administration Over the Treatment Period AZD7594 250 μg vs. PBO	5.334 L/min Interval -6.975 to 17.64	0.08136 L/min Interval -10.5 to 10.66	—	—
Efficacy of AZD7594 by Assessment of the Change From Baseline in Morning Peak Expiratory Flow (mPEF) Before Administration Over the Treatment Period AZD7594 800 μg vs. PBO	12.60 L/min Interval 0.2402 to 24.96	0.08136 L/min Interval -10.5 to 10.66	—	—

SECONDARY outcome

Timeframe: Every evening from Day 1 to Day 14 in each period

The efficacy of AZD7594 was assessed in terms of change from baseline in evening peak expiratory flow (ePEF) in each treatment period. The first PEF measurement was on the evening of Visit 1. Every morning and every evening after Visit 1, patients were required to perform 3 maneuvers for PEF assessment. The highest value from among the 3 assessments was marked as ePEF together with the date and time of the measurement. The final PEF assessment was done on the morning of Visit 11 (Day 15 of Treatment Period 3).

Outcome measures

Outcome measures
Measure	AZD7594 n=33 Participants AZD7594 DPI once daily	Placebo n=51 Participants Placebo for AZD7594 DPI once daily	AZD7594 250 μg AZD7594 DPI once daily - 2 capsules of 125 μg	AZD7594 800 μg AZD7594 DPI once daily - 2 capsules of 400 μg
Efficacy of AZD7594 by Assessment of the Change From Baseline in Evening Peak Expiratory Flow (ePEF) Before Administration Over the Treatment Period AZD7594 58 μg vs. PBO	7.475 L/min Interval -4.426 to 19.38	-8.257 L/min Interval -18.71 to 2.193	—	—
Efficacy of AZD7594 by Assessment of the Change From Baseline in Evening Peak Expiratory Flow (ePEF) Before Administration Over the Treatment Period AZD7594 250 μg vs. PBO	6.040 L/min Interval -5.839 to 17.92	-8.257 L/min Interval -18.71 to 2.193	—	—
Efficacy of AZD7594 by Assessment of the Change From Baseline in Evening Peak Expiratory Flow (ePEF) Before Administration Over the Treatment Period AZD7594 800 μg vs. PBO	11.65 L/min Interval -0.2692 to 23.58	-8.257 L/min Interval -18.71 to 2.193	—	—

SECONDARY outcome

Timeframe: Every day from Day 1 to Day 15 (from evening of Day 1 to morning of Day 15)

The efficacy of AZD7594 was assessed in terms of change from baseline in average daily use of salbutamol (each morning and evening) in each treatment period.

Outcome measures

Outcome measures
Measure	AZD7594 n=33 Participants AZD7594 DPI once daily	Placebo n=51 Participants Placebo for AZD7594 DPI once daily	AZD7594 250 μg AZD7594 DPI once daily - 2 capsules of 125 μg	AZD7594 800 μg AZD7594 DPI once daily - 2 capsules of 400 μg
Efficacy of AZD7594 by Assessment of the Change From Baseline in Average Daily Use of Rescue Salbutamol Over the Treatment Period AZD7594 58 μg vs. PBO	-0.6776 Number of inhalations per day Interval -1.071 to -0.2841	-0.3340 Number of inhalations per day Interval -0.6733 to 0.005227	—	—
Efficacy of AZD7594 by Assessment of the Change From Baseline in Average Daily Use of Rescue Salbutamol Over the Treatment Period AZD7594 250 μg vs. PBO	-0.8193 Number of inhalations per day Interval -1.212 to -0.4267	-0.3340 Number of inhalations per day Interval -0.6733 to 0.005227	—	—
Efficacy of AZD7594 by Assessment of the Change From Baseline in Average Daily Use of Rescue Salbutamol Over the Treatment Period AZD7594 800 μg vs. PBO	-1.137 Number of inhalations per day Interval -1.531 to -0.7422	-0.3340 Number of inhalations per day Interval -0.6733 to 0.005227	—	—

SECONDARY outcome

Timeframe: At baseline and on Day 15 in each period

The efficacy of AZD7594 was assessed in terms of change from baseline to Day 15 in Asthma Control Questionnaire-5 in each treatment period. Five questions were asked and each question was scored on a scale of 0 to 6, where a higher score represents a more severe impairment/symptom. The ACQ-5 score at a given visit was defined as the average of the scores given for each of the questions, calculated as ACQ-5 score = Sum of 5 scores/5.

Outcome measures

Outcome measures
Measure	AZD7594 n=33 Participants AZD7594 DPI once daily	Placebo n=52 Participants Placebo for AZD7594 DPI once daily	AZD7594 250 μg AZD7594 DPI once daily - 2 capsules of 125 μg	AZD7594 800 μg AZD7594 DPI once daily - 2 capsules of 400 μg
Efficacy of AZD7594 by Assessment of the Change From Baseline to Day 15 in Asthma Control Questionnaire-5 AZD7594 58 μg vs. PBO	-0.2929 Unit on a scale Interval -0.4744 to -0.1113	0.01428 Unit on a scale Interval -0.1281 to 0.1567	—	—
Efficacy of AZD7594 by Assessment of the Change From Baseline to Day 15 in Asthma Control Questionnaire-5 AZD7594 250 μg vs. PBO	-0.1681 Unit on a scale Interval -0.3496 to 0.01335	0.1428 Unit on a scale Interval -0.1281 to 0.1567	—	—
Efficacy of AZD7594 by Assessment of the Change From Baseline to Day 15 in Asthma Control Questionnaire-5 AZD7594 800 μg vs. PBO	-0.4158 Unit on a scale Interval -0.5975 to -0.2342	0.01428 Unit on a scale Interval -0.1281 to 0.1567	—	—

SECONDARY outcome

Timeframe: At baseline and on Day 8 in each period

The efficacy of AZD7594 was assessed in terms of change from baseline to Day 15 in Asthma Control Questionnaire-5 in each treatment period. Five questions were asked and each question was scored on a scale of 0 to 6, where a lower score represents a more severe impairment/symptom. The ACQ-5 score at a given visit was defined as the average of the scores given for each of the questions, calculated as ACQ-5 score = Sum of 5 scores/5.

Outcome measures

Outcome measures
Measure	AZD7594 n=33 Participants AZD7594 DPI once daily	Placebo n=52 Participants Placebo for AZD7594 DPI once daily	AZD7594 250 μg AZD7594 DPI once daily - 2 capsules of 125 μg	AZD7594 800 μg AZD7594 DPI once daily - 2 capsules of 400 μg
Efficacy of AZD7594 by Assessment of the Change From Baseline to Day 8 in Asthma Control Questionnaire-5 AZD7594 58 μg vs. PBO	-0.2724 Unit on a scale Interval -0.4309 to -0.1138	-0.1072 Unit on a scale Interval -0.232 to 0.01748	—	—
Efficacy of AZD7594 by Assessment of the Change From Baseline to Day 8 in Asthma Control Questionnaire-5 AZD7594 250 μg vs. PBO	-0.1980 Unit on a scale Interval -0.3565 to -0.03952	-0.1072 Unit on a scale Interval -0.232 to 0.01748	—	—
Efficacy of AZD7594 by Assessment of the Change From Baseline to Day 8 in Asthma Control Questionnaire-5 AZD7594 800 μg vs. PBO	-0.3604 Unit on a scale Interval -0.5191 to -0.2017	-0.1072 Unit on a scale Interval -0.232 to 0.01748	—	—

SECONDARY outcome

Timeframe: At baseline and from Day 2 to Day 15 in each period

The efficacy of AZD7594 was assessed in terms of change in nighttime awakenings in each treatment period. The patients were asked to answer 'Yes' or 'No' to the question of "Did your asthma cause you to wake up last night?". If yes, the number and percentage of days that had a night-time awakening were determined for each of the study periods.

Outcome measures

Outcome measures
Measure	AZD7594 n=33 Participants AZD7594 DPI once daily	Placebo n=52 Participants Placebo for AZD7594 DPI once daily	AZD7594 250 μg AZD7594 DPI once daily - 2 capsules of 125 μg	AZD7594 800 μg AZD7594 DPI once daily - 2 capsules of 400 μg
Efficacy of AZD7594 by Assessment of Night-time Awakenings AZD7594 58 μg vs. PBO	-0.4120 Number of nighttime awakenings Interval -0.7229 to -0.101	0.006541 Number of nighttime awakenings Interval -0.2509 to 0.264	—	—
Efficacy of AZD7594 by Assessment of Night-time Awakenings AZD7594 250 μg vs. PBO	-0.1729 Number of nighttime awakenings Interval -0.4833 to 0.1376	0.006541 Number of nighttime awakenings Interval -0.2509 to 0.264	—	—
Efficacy of AZD7594 by Assessment of Night-time Awakenings AZD7594 800 μg vs. PBO	-0.7595 Number of nighttime awakenings Interval -1.071 to -0.4479	0.006541 Number of nighttime awakenings Interval -0.2509 to 0.264	—	—

SECONDARY outcome

Timeframe: At baseline and from Day 1 to Day 14 in each period

The efficacy of AZD7594 was assessed in terms of change in daily symptom score from baseline to average of treatment period post dose (Day 1-14) in each treatment period. Severity scores for asthma symptoms were recorded twice daily, once in the morning and once in the evening with the scoring system of 0-no asthma symptoms, 1-toleratable asthma symptoms, 2-discomfort asthma symptoms with normal activities (or with sleep) and 3-asthma symptoms with impaired normal activities (or to sleep).

Outcome measures

Outcome measures
Measure	AZD7594 n=33 Participants AZD7594 DPI once daily	Placebo n=51 Participants Placebo for AZD7594 DPI once daily	AZD7594 250 μg AZD7594 DPI once daily - 2 capsules of 125 μg	AZD7594 800 μg AZD7594 DPI once daily - 2 capsules of 400 μg
Efficacy of AZD7594 by Assessment of Daily Symptom Score AZD7594 58 μg vs. PBO	-0.1190 Unit on a scale Interval -0.219 to -0.01903	-0.01229 Unit on a scale Interval -0.09729 to 0.0727	—	—
Efficacy of AZD7594 by Assessment of Daily Symptom Score AZD7594 250 μg vs. PBO	-0.09435 Unit on a scale Interval -0.1941 to 0.005411	-0.01229 Unit on a scale Interval -0.09729 to 0.0727	—	—
Efficacy of AZD7594 by Assessment of Daily Symptom Score AZD7594 800 μg vs. PBO	-0.2150 Unit on a scale Interval -0.3151 to -0.1149	-0.01229 Unit on a scale Interval -0.09729 to 0.0727	—	—

SECONDARY outcome

Timeframe: At baseline and from Day 1 to Day 14 post-dose in each period

The efficacy of AZD7594 was assessed in terms of amount of asthma control days in each treatment period. An asthma control day was defined as a day with asthma symptom score = 0, a night with no awakenings due to asthma symptoms and a day with no use of rescue medication. A given calendar day was defined as an asthma control day if it fulfills the criteria for a symptom-free day and for a rescue medication-free day

Outcome measures

Outcome measures
Measure	AZD7594 n=33 Participants AZD7594 DPI once daily	Placebo n=51 Participants Placebo for AZD7594 DPI once daily	AZD7594 250 μg AZD7594 DPI once daily - 2 capsules of 125 μg	AZD7594 800 μg AZD7594 DPI once daily - 2 capsules of 400 μg
Efficacy of AZD7594 by Assessment of Asthma Control Days AZD7594 58 μg vs. PBO	0.9502 Asthma control days Interval 0.3166 to 1.584	0.2773 Asthma control days Interval -0.2745 to 0.829	—	—
Efficacy of AZD7594 by Assessment of Asthma Control Days AZD7594 250 μg vs. PBO	0.705 Asthma control days Interval 0.07299 to 1.338	0.2773 Asthma control days Interval -0.2745 to 0.829	—	—
Efficacy of AZD7594 by Assessment of Asthma Control Days AZD7594 800 μg vs. PBO	1.219 Asthma control days Interval 0.5843 to 1.853	0.2773 Asthma control days Interval -0.2745 to 0.829	—	—

SECONDARY outcome

Timeframe: From Screening to Follow-up (these two examinations are up to 165 days apart)

Population: The safety analysis set (SAF) included all randomized participants who received at least one dose of randomized study drug during the treatment periods of the study. This analysis set was classified by actual treatment received. If no participants received incorrect treatment then the SAF was identical to the FAS.

Assessment of safety and tolerability of three dose levels of AZD7594 in participants with mild to moderate asthma. IP referred to investigational product.

Outcome measures

Outcome measures
Measure	AZD7594 n=52 Participants AZD7594 DPI once daily	Placebo n=34 Participants Placebo for AZD7594 DPI once daily	AZD7594 250 μg n=34 Participants AZD7594 DPI once daily - 2 capsules of 125 μg	AZD7594 800 μg n=34 Participants AZD7594 DPI once daily - 2 capsules of 400 μg
Number of Participants With Adverse Events Any AE	17 Number of participants	13 Number of participants	9 Number of participants	12 Number of participants
Number of Participants With Adverse Events AE causally related to IP	3 Number of participants	1 Number of participants	1 Number of participants	2 Number of participants
Number of Participants With Adverse Events Any AE with an outcome of death	0 Number of participants	0 Number of participants	0 Number of participants	0 Number of participants
Number of Participants With Adverse Events Any SAE (including events with outcome of death)	0 Number of participants	0 Number of participants	0 Number of participants	0 Number of participants
Number of Participants With Adverse Events Any AE leading to discontinuation of IP	1 Number of participants	0 Number of participants	0 Number of participants	0 Number of participants

SECONDARY outcome

Timeframe: On Day 1 in each period (in participants with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, and 4 h post-dose)

Population: The PK analysis set (PKS) included the subset of all randomized participants for whom 24-hour PK sampling was performed on Day 14, for whom the primary PK parameters (Cmax , AUC(0-4), Cmax,ss, AUC(0-24)) were calculated in at least one treatment period, and who had no major protocol deviations considered to impact the analysis of the PK data.

Comparison of Cmax (maximum observed plasma concentration) of AZD7594 on Day 1 of each treatment period; up to 6 samples were collected in each period (i.e. in participants with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, and 4 h post-dose)

Outcome measures

Outcome measures
Measure	AZD7594 n=9 Participants AZD7594 DPI once daily	Placebo n=9 Participants Placebo for AZD7594 DPI once daily	AZD7594 250 μg n=8 Participants AZD7594 DPI once daily - 2 capsules of 125 μg	AZD7594 800 μg AZD7594 DPI once daily - 2 capsules of 400 μg
Rate and Extent of Absorption of Three Dose Levels of AZD7594 by Assessment of Cmax of AZD7594	36.40 pmol/L Geometric Coefficient of Variation 32.80	92.02 pmol/L Geometric Coefficient of Variation 34.17	169.7 pmol/L Geometric Coefficient of Variation 43.21	—

SECONDARY outcome

Timeframe: On Day 1 in each period (in participants with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, and 4 h post-dose)

Population: The subset of all randomized participants; 24-hour PK sampling was performed on Day 14, the primary PK parameters (Cmax , AUC(0-4), Cmax,ss, AUC(0-24)) were calculated in at least one treatment period, and who had no major protocol deviations considered to impact the analysis of the PK data.

Comparison of AUC(0-4) (Area under the plasma concentration-time curve from time zero to 4 hours after administration) of AZD7594 on Day 1 of each treatment period; up to 6 samples were collected in each period (i.e. in participants with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, and 4 h post-dose).

Outcome measures

Outcome measures
Measure	AZD7594 n=9 Participants AZD7594 DPI once daily	Placebo n=9 Participants Placebo for AZD7594 DPI once daily	AZD7594 250 μg n=8 Participants AZD7594 DPI once daily - 2 capsules of 125 μg	AZD7594 800 μg AZD7594 DPI once daily - 2 capsules of 400 μg
Rate and Extent of Absorption of Three Dose Levels of AZD7594 by Assessment of AUC(0-4) of AZD7594	85.02 h*pmol/L Geometric Coefficient of Variation 8.21	188.4 h*pmol/L Geometric Coefficient of Variation 30.58	371.1 h*pmol/L Geometric Coefficient of Variation 31.55	—

SECONDARY outcome

Timeframe: On Day 14 in each period (in participants with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, 4, 8, 12, 16 and 24 h post-dose)

Population: PKS included the subset of all randomized participants for whom 24-hour PK sampling was performed on Day 14, for whom the primary PK parameters (Cmax , AUC(0-4), Cmax,ss, AUC(0-24)) were calculated in at least one treatment period, and who had no major protocol deviations considered to impact the analysis of the PK data.

Comparison of Cmax,ss (observed maximum plasma concentration at steady state) of AZD7594 on Day 14 of each treatment period; up to 10 samples were collected in each period (i.e. in participants with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, 4, 8, 12, 16 and 24 h post-dose)

Outcome measures

Outcome measures
Measure	AZD7594 n=9 Participants AZD7594 DPI once daily	Placebo n=9 Participants Placebo for AZD7594 DPI once daily	AZD7594 250 μg n=8 Participants AZD7594 DPI once daily - 2 capsules of 125 μg	AZD7594 800 μg AZD7594 DPI once daily - 2 capsules of 400 μg
Rate and Extent of Absorption of Three Dose Levels of AZD7594 Following Multiple Dose Administration by Assessment of Cmax,ss of AZD7594	54.97 pmol/L Geometric Coefficient of Variation 19.70	158.7 pmol/L Geometric Coefficient of Variation 35.01	421.6 pmol/L Geometric Coefficient of Variation 37.26	—

SECONDARY outcome

Timeframe: On Day 14 in each period (in participants with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, 4, 8, 12, 16 and 24 h post-dose)

Comparison of AUC(0-24) (Area under the plasma concentration-time curve from time zero to 24 hours after administration) of AZD7594 on Day 14 of each treatment period; up to 10 samples were collected in each period (i.e. in participants with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, 4, 8, 12, 16 and 24 h post-dose)

Outcome measures

Outcome measures
Measure	AZD7594 n=9 Participants AZD7594 DPI once daily	Placebo n=9 Participants Placebo for AZD7594 DPI once daily	AZD7594 250 μg n=8 Participants AZD7594 DPI once daily - 2 capsules of 125 μg	AZD7594 800 μg AZD7594 DPI once daily - 2 capsules of 400 μg
Rate and Extent of Absorption of Three Dose Levels of AZD7594 Following Multiple Dose Administration by Assessment of AUC(0-24) of AZD7594	467.1 h*pmol/L Geometric Coefficient of Variation 17.91	1725 h*pmol/L Geometric Coefficient of Variation 44.33	4894 h*pmol/L Geometric Coefficient of Variation 52.48	—

SECONDARY outcome

Timeframe: On Day 1 and Day 14 in each period (in participants with intensive pharmacokinetic assessments, on Day 1 at pre-dose and 15 and 30 minutes, and 1, 2 and 4 h post-dose, on Day 14 at pre-dose and 15 and 30 minutes, and 1, 2, 4, 8, 12, 16 and 24 h post-dose)

Comparison of AUC(0-last) (Area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration (Day 1 and Day 14)) of AZD7594 (i.e. in participants with intensive pharmacokinetic assessments)

Outcome measures

Outcome measures
Measure	AZD7594 n=9 Participants AZD7594 DPI once daily	Placebo n=9 Participants Placebo for AZD7594 DPI once daily	AZD7594 250 μg n=8 Participants AZD7594 DPI once daily - 2 capsules of 125 μg	AZD7594 800 μg AZD7594 DPI once daily - 2 capsules of 400 μg
Rate and Extent of Absorption of Three Dose Levels of AZD7594 Following Multiple Dose Administration by Assessment of AUC(0-last) of AZD7594 Day 1	56.85 h*pmol/L Geometric Coefficient of Variation 45.40	188.5 h*pmol/L Geometric Coefficient of Variation 30.57	371.8 h*pmol/L Geometric Coefficient of Variation 31.63	—
Rate and Extent of Absorption of Three Dose Levels of AZD7594 Following Multiple Dose Administration by Assessment of AUC(0-last) of AZD7594 Day 14	467.3 h*pmol/L Geometric Coefficient of Variation 17.93	1728 h*pmol/L Geometric Coefficient of Variation 44.36	4897 h*pmol/L Geometric Coefficient of Variation 52.48	—

SECONDARY outcome

Timeframe: On Day 1 in each period (in participants with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, and 4 h post-dose)

Comparison of tmax (time to reach maximum plasma concentration) of AZD7594 on Day 1 of each treatment period; up to 6 samples were collected in each period (i.e. in participants with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, and 4 h post-dose)

Outcome measures

Outcome measures
Measure	AZD7594 n=9 Participants AZD7594 DPI once daily	Placebo n=9 Participants Placebo for AZD7594 DPI once daily	AZD7594 250 μg n=8 Participants AZD7594 DPI once daily - 2 capsules of 125 μg	AZD7594 800 μg AZD7594 DPI once daily - 2 capsules of 400 μg
Rate and Extent of Absorption of Three Dose Levels of AZD7594 by Assessment of Tmax of AZD7594	0.25 Hour Interval 0.23 to 0.27	0.25 Hour Interval 0.25 to 0.5	0.25 Hour Interval 0.25 to 0.55	—

SECONDARY outcome

Timeframe: On Day 14 in each period (in participants with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, 4, 8, 12, 16 and 24 h post-dose)

Comparison of tmax,ss (time to reach maximum plasma concentration at steady state) of AZD7594 on Day 14 of each treatment period; up to 10 samples were collected in each period (i.e. in participants with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, 4, 8, 12, 16 and 24 h post-dose)

Outcome measures

Outcome measures
Measure	AZD7594 n=9 Participants AZD7594 DPI once daily	Placebo n=9 Participants Placebo for AZD7594 DPI once daily	AZD7594 250 μg n=8 Participants AZD7594 DPI once daily - 2 capsules of 125 μg	AZD7594 800 μg AZD7594 DPI once daily - 2 capsules of 400 μg
Rate and Extent of Absorption of Three Dose Levels of AZD7594 Following Multiple Dose Administration by Assessment of Tmax,ss of AZD7594	0.25 Hour Interval 0.25 to 0.5	0.25 Hour Interval 0.23 to 0.27	0.25 Hour Interval 0.25 to 0.98	—

SECONDARY outcome

Timeframe: On Day 14 in each period (in participants with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, 4, 8, 12, 16 and 24 h post-dose)

Comparison of Cavg,ss (average plasma concentration during a dosing interval at steady state) of AZD7594 on Day 14 of each treatment period; up to 10 samples were collected in each period (i.e. in participants with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, 4, 8, 12, 16 and 24 h post-dose)

Outcome measures

Outcome measures
Measure	AZD7594 n=9 Participants AZD7594 DPI once daily	Placebo n=9 Participants Placebo for AZD7594 DPI once daily	AZD7594 250 μg n=8 Participants AZD7594 DPI once daily - 2 capsules of 125 μg	AZD7594 800 μg AZD7594 DPI once daily - 2 capsules of 400 μg
Rate and Extent of Absorption of Three Dose Levels of AZD7594 Following Multiple Dose Administration by Assessment of Cavg,ss of AZD7594	19.48 pmol/L Geometric Coefficient of Variation 17.93	71.89 pmol/L Geometric Coefficient of Variation 44.33	203.9 pmol/L Geometric Coefficient of Variation 52.55	—

SECONDARY outcome

Timeframe: On Day 1 in each period

Comparison of Cmax/D (dose-normalized Cmax) of AZD7594

Outcome measures

Outcome measures
Measure	AZD7594 n=9 Participants AZD7594 DPI once daily	Placebo n=9 Participants Placebo for AZD7594 DPI once daily	AZD7594 250 μg n=8 Participants AZD7594 DPI once daily - 2 capsules of 125 μg	AZD7594 800 μg AZD7594 DPI once daily - 2 capsules of 400 μg
Rate and Extent of Absorption of Three Dose Levels of AZD7594 Following Multiple Dose Administration by Assessment of Cmax/D of AZD7594	380.8 pmol/L/μmol Geometric Coefficient of Variation 32.80	223.4 pmol/L/μmol Geometric Coefficient of Variation 34.17	128.5 pmol/L/μmol Geometric Coefficient of Variation 43.21	—

SECONDARY outcome

Timeframe: On Day 14 in each period

Comparison of AUC(0-24)/D (dose-normalized AUC(0-24)) of AZD7594

Outcome measures

Outcome measures
Measure	AZD7594 n=9 Participants AZD7594 DPI once daily	Placebo n=9 Participants Placebo for AZD7594 DPI once daily	AZD7594 250 μg n=8 Participants AZD7594 DPI once daily - 2 capsules of 125 μg	AZD7594 800 μg AZD7594 DPI once daily - 2 capsules of 400 μg
Rate and Extent of Absorption of Three Dose Levels of AZD7594 Following Multiple Dose Administration by Assessment of AUC(0-24)/D of AZD7594	4886 h*pmol/L/ μmol Geometric Coefficient of Variation 17.91 • Interval 3977.0 to 4944.0	4188 h*pmol/L/ μmol Geometric Coefficient of Variation 44.33	3708 h*pmol/L/ μmol Geometric Coefficient of Variation 52.48	—

SECONDARY outcome

Timeframe: On Day 14 at pre-dose in each period

Population: The subset of all randomized participants, 24-hour PK sampling was performed on Day 14, primary PK parameters (Cmax , AUC(0-4), Cmax,ss, AUC(0-24)) were calculated in at least one treatment period, and who had no major protocol deviations considered to impact the analysis of the PK data. Cmin was not determined for AZD7594 58 μg

Comparison of steady-state minimum (pre-dose) concentration (Cmin) of AZD7594 in each treatment period

Outcome measures

Outcome measures
Measure	AZD7594 n=9 Participants AZD7594 DPI once daily	Placebo n=9 Participants Placebo for AZD7594 DPI once daily	AZD7594 250 μg n=8 Participants AZD7594 DPI once daily - 2 capsules of 125 μg	AZD7594 800 μg AZD7594 DPI once daily - 2 capsules of 400 μg
Rate and Extent of Absorption of Three Dose Levels of AZD7594 Following Multiple Dose Administration by Assessment of Cmin of AZD7594	NA pmol/L Geometric Coefficient of Variation NA Not applicable for AZD7594 58 μg. Will be reported in the separate population PK report	55.95 pmol/L Geometric Coefficient of Variation 51.74	191.6 pmol/L Geometric Coefficient of Variation 68.27	—

Adverse Events

Placebo (PBO)

Serious events: 0 serious events

Other events: 17 other events

Deaths: 0 deaths

AZD7594 58 μg

Serious events: 0 serious events

Other events: 13 other events

Deaths: 0 deaths

AZD7594 250 μg

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

AZD7594 800 μg

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Global Clinical Leader

AstraZeneca AB

Phone: +46 31 7761000

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee If a publication (e.g., in a scientific journal) based on the results of this study is envisaged, approval from AstraZeneca will be obtained and a draft manuscript will be submitted to AstraZeneca for scrutiny and comment. The choice of conduit will be mutually agreed.
Publication restrictions are in place

Restriction type: OTHER

Measure	Placebo (PBO) n=52 participants at risk Placebo for AZD7594 DPI once daily	AZD7594 58 μg n=34 participants at risk AZD7594 DPI once daily - 2 capsules of 29 μg	AZD7594 250 μg n=34 participants at risk AZD7594 DPI once daily - 2 capsules of 125 μg	AZD7594 800 μg n=34 participants at risk AZD7594 DPI once daily - 2 capsules of 400 μg
Infections and infestations Nasopharyngitis	15.4% 8/52 • From Screening to Follow-up (these two examinations are up to 165 days apart)	11.8% 4/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)	5.9% 2/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)	11.8% 4/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)
Infections and infestations Gastroenteritis	0.00% 0/52 • From Screening to Follow-up (these two examinations are up to 165 days apart)	8.8% 3/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)	0.00% 0/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)	0.00% 0/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)
Infections and infestations Gastrointestinal infection	0.00% 0/52 • From Screening to Follow-up (these two examinations are up to 165 days apart)	0.00% 0/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)	2.9% 1/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)	0.00% 0/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)
Infections and infestations Hordeolum	0.00% 0/52 • From Screening to Follow-up (these two examinations are up to 165 days apart)	0.00% 0/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)	2.9% 1/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)	0.00% 0/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)
Infections and infestations Rhinitis	0.00% 0/52 • From Screening to Follow-up (these two examinations are up to 165 days apart)	0.00% 0/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)	2.9% 1/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)	0.00% 0/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)
Infections and infestations Sinusitis	1.9% 1/52 • From Screening to Follow-up (these two examinations are up to 165 days apart)	0.00% 0/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)	0.00% 0/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)	0.00% 0/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)
Nervous system disorders Headache	0.00% 0/52 • From Screening to Follow-up (these two examinations are up to 165 days apart)	0.00% 0/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)	8.8% 3/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)	5.9% 2/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)
Nervous system disorders Migraine	0.00% 0/52 • From Screening to Follow-up (these two examinations are up to 165 days apart)	2.9% 1/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)	0.00% 0/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)	2.9% 1/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)
Respiratory, thoracic and mediastinal disorders Cough	1.9% 1/52 • From Screening to Follow-up (these two examinations are up to 165 days apart)	5.9% 2/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)	0.00% 0/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)	0.00% 0/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/52 • From Screening to Follow-up (these two examinations are up to 165 days apart)	2.9% 1/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)	2.9% 1/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)	0.00% 0/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)
Respiratory, thoracic and mediastinal disorders Asthma	1.9% 1/52 • From Screening to Follow-up (these two examinations are up to 165 days apart)	0.00% 0/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)	2.9% 1/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)	0.00% 0/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/52 • From Screening to Follow-up (these two examinations are up to 165 days apart)	0.00% 0/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)	0.00% 0/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)	2.9% 1/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)
Respiratory, thoracic and mediastinal disorders Respiratory distress	0.00% 0/52 • From Screening to Follow-up (these two examinations are up to 165 days apart)	0.00% 0/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)	0.00% 0/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)	2.9% 1/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)
Respiratory, thoracic and mediastinal disorders Sputum increased	1.9% 1/52 • From Screening to Follow-up (these two examinations are up to 165 days apart)	2.9% 1/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)	0.00% 0/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)	0.00% 0/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)
Respiratory, thoracic and mediastinal disorders Dyspnoea	3.8% 2/52 • From Screening to Follow-up (these two examinations are up to 165 days apart)	0.00% 0/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)	0.00% 0/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)	0.00% 0/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)
Respiratory, thoracic and mediastinal disorders Nasal inflammation	1.9% 1/52 • From Screening to Follow-up (these two examinations are up to 165 days apart)	0.00% 0/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)	0.00% 0/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)	0.00% 0/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)
Respiratory, thoracic and mediastinal disorders Productive cough	1.9% 1/52 • From Screening to Follow-up (these two examinations are up to 165 days apart)	0.00% 0/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)	0.00% 0/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)	0.00% 0/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)
Gastrointestinal disorders Diarrhoea	0.00% 0/52 • From Screening to Follow-up (these two examinations are up to 165 days apart)	0.00% 0/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)	0.00% 0/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)	8.8% 3/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)
Gastrointestinal disorders Abdominal discomfort	0.00% 0/52 • From Screening to Follow-up (these two examinations are up to 165 days apart)	2.9% 1/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)	0.00% 0/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)	0.00% 0/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)
Gastrointestinal disorders Dental caries	0.00% 0/52 • From Screening to Follow-up (these two examinations are up to 165 days apart)	2.9% 1/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)	0.00% 0/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)	0.00% 0/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)
Gastrointestinal disorders Abdominal pain upper	1.9% 1/52 • From Screening to Follow-up (these two examinations are up to 165 days apart)	0.00% 0/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)	0.00% 0/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)	0.00% 0/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)
Gastrointestinal disorders Gingival bleeding	1.9% 1/52 • From Screening to Follow-up (these two examinations are up to 165 days apart)	0.00% 0/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)	0.00% 0/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)	0.00% 0/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)
Gastrointestinal disorders Toothache	1.9% 1/52 • From Screening to Follow-up (these two examinations are up to 165 days apart)	0.00% 0/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)	0.00% 0/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)	0.00% 0/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)
Gastrointestinal disorders Vomiting	1.9% 1/52 • From Screening to Follow-up (these two examinations are up to 165 days apart)	0.00% 0/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)	0.00% 0/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)	0.00% 0/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/52 • From Screening to Follow-up (these two examinations are up to 165 days apart)	2.9% 1/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)	0.00% 0/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)	0.00% 0/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/52 • From Screening to Follow-up (these two examinations are up to 165 days apart)	0.00% 0/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)	0.00% 0/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)	2.9% 1/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/52 • From Screening to Follow-up (these two examinations are up to 165 days apart)	2.9% 1/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)	0.00% 0/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)	0.00% 0/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)
Investigations Blood lactate dehydrogenase increased	0.00% 0/52 • From Screening to Follow-up (these two examinations are up to 165 days apart)	0.00% 0/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)	0.00% 0/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)	2.9% 1/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)
Investigations Hepatic enzyme increased	1.9% 1/52 • From Screening to Follow-up (these two examinations are up to 165 days apart)	0.00% 0/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)	2.9% 1/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)	0.00% 0/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)
Hepatobiliary disorders Hepatosplenomegaly	0.00% 0/52 • From Screening to Follow-up (these two examinations are up to 165 days apart)	0.00% 0/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)	0.00% 0/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)	2.9% 1/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)
Injury, poisoning and procedural complications Contusion	0.00% 0/52 • From Screening to Follow-up (these two examinations are up to 165 days apart)	0.00% 0/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)	2.9% 1/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)	0.00% 0/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/52 • From Screening to Follow-up (these two examinations are up to 165 days apart)	2.9% 1/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)	0.00% 0/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)	0.00% 0/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)
Skin and subcutaneous tissue disorders Eczema	1.9% 1/52 • From Screening to Follow-up (these two examinations are up to 165 days apart)	0.00% 0/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)	0.00% 0/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)	0.00% 0/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)
Blood and lymphatic system disorders Anaemia vitamin B12 deficiency	1.9% 1/52 • From Screening to Follow-up (these two examinations are up to 165 days apart)	0.00% 0/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)	0.00% 0/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)	0.00% 0/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)
Eye disorders Eye irritation	1.9% 1/52 • From Screening to Follow-up (these two examinations are up to 165 days apart)	0.00% 0/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)	0.00% 0/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)	0.00% 0/34 • From Screening to Follow-up (these two examinations are up to 165 days apart)