Trial Outcomes & Findings for A Study in Healthy Volunteers and Patients With Mild Asthma to Investigate the Safety, Anti-inflammatory Effect of Inhaled AZD0449 (NCT NCT03766399)

Last Updated: 2024-08-23

Results Overview

Safety and tolerability of AZD0449 following inhaled administration of single ascending doses to healthy participants, inhaled nebulized administration of multiple ascending doses to healthy participants and patients with mild asthma, and repeated inhaled administration to patients with mild asthma using a DPI was assessed.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

131 participants

Primary outcome timeframe

From screening up to follow-up visit [Part 1 a (6±1 Days post-dose)] [Part 2a (Day 22±1 (10±1 days post-last dose)], Safety Monitoring Period 2b/3a [Day 17 to 27 (15 day post-last dose)]

Results posted on

2024-08-23

Participant Flow

This study was a 3 part study conducted between 30 Nov 2018 and 24 Jun 2021. Part 1 was conducted at a single clinical unit. Part 2 was conducted at 3 clinical units.

Part 1a was a single ascending dose (SAD) study in healthy participants. Part 1b consisted of 2 IV dose cohorts. 6 participants from Part 1a in first IV dose cohort and 6 healthy participants in second IV dose cohort were selected for Part 1b. Part 2 was a multiple ascending dose (MAD) study in patients with mild asthma (Part 2a) and healthy participants (Part 2b). Part 3 included patients with mild asthma (Part 3a) and healthy participants (Part 3b).

Participant milestones

Participant milestones
Measure	Part 1a (SAD) Placebo Randomized healthy participants received Placebo for AZD0449.	Part 1a (SAD) Cohort 1 Randomized healthy participants received a single inhaled dose of AZD0449 0.095 mg nebulized suspension via Jet nebulizer.	Part 1a (SAD) Cohort 2 Randomized healthy participants received a single inhaled dose of AZD0449 0.28 mg nebulized suspension via Jet nebulizer.	Part 1a (SAD) Cohort 3 Randomized healthy participants received a single inhaled dose of AZD0449 0.84 mg nebulized suspension via Jet nebulizer.	Part 1a (SAD) Cohort 4 Randomized healthy participants received a single inhaled dose of AZD0449 1.60 mg nebulized suspension via Jet nebulizer.	Part 1a (SAD) Cohort 5 Randomized healthy participants received a single inhaled dose of AZD0449 3.20 mg nebulized suspension via Jet nebulizer.	Part 1a (SAD) Cohort 6 Randomized healthy participants received a single inhaled dose of AZD0449 5 mg nebulized suspension via Jet nebulizer.	Part 1b (SAD IV) Cohort 1 Randomized healthy participants received a single intravenous (IV) dose of AZD0449 0.090 mg solution.	Part 1b (SAD IV) Cohort 2 Randomized healthy participants received a single IV dose of AZD0449 0.360 mg solution.	Part 2a (MAD) Placebo Randomized patients with mild asthma received Placebo.	Part 2a (MAD) Cohort 1 Randomized patients with mild asthma received a multiple inhaled dose of AZD0449 1.20 mg nebulized suspension via Jet nebulizer.	Part 2a (MAD) Cohort 2 Randomized patients with mild asthma received a multiple inhaled dose of AZD0449 2.50 mg nebulized suspension via Jet nebulizer.	Part 2b (MAD) Placebo Randomized healthy participants received Placebo for AZD0449.	Part 2b (MAD) Cohort 1 Randomized healthy participants received a multiple inhaled of AZD0449 5 mg nebulized suspension via Jet nebulizer.	Part 3a (DPI/PoM) Placebo Randomized patients with mild asthma received Placebo for AZD0449.	Part 3a Dry Powder Inhalation/Proof of Mechanism (DPI/PoM) Randomized patients with mild asthma received a multiple inhaled dose of AZD0449 5 mg DPI.	Part 3b (DPI/Healthy Participants) Placebo Randomized healthy participants received Placebo for AZD0449.	Part 3b (DPI/Healthy Participants) Randomized healthy participants received multiple inhaled dose of AZD0449 5 mg DPI.
Part 1a: SAD (Nebulized Inhalation) STARTED	12	6	6	6	6	6	6	0	0	0	0	0	0	0	0	0	0	0
Part 1a: SAD (Nebulized Inhalation) COMPLETED	12	6	6	6	6	6	6	0	0	0	0	0	0	0	0	0	0	0
Part 1a: SAD (Nebulized Inhalation) NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Part 1b: SAD (Intravenous Dosing) STARTED	0	0	0	0	0	0	0	6	6	0	0	0	0	0	0	0	0	0
Part 1b: SAD (Intravenous Dosing) COMPLETED	0	0	0	0	0	0	0	6	6	0	0	0	0	0	0	0	0	0
Part 1b: SAD (Intravenous Dosing) NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Part 2a: MAD (Nebulized Inhalation) STARTED	0	0	0	0	0	0	0	0	0	6	6	6	0	0	0	0	0	0
Part 2a: MAD (Nebulized Inhalation) COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Part 2a: MAD (Nebulized Inhalation) NOT COMPLETED	0	0	0	0	0	0	0	0	0	6	6	6	0	0	0	0	0	0
Part 2b: MAD (Nebulized Inhalation) STARTED	0	0	0	0	0	0	0	0	0	0	0	0	2	7	0	0	0	0
Part 2b: MAD (Nebulized Inhalation) COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	2	6	0	0	0	0
Part 2b: MAD (Nebulized Inhalation) NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Part 3a: Asthma Patients (DPI) STARTED	0	0	0	0	0	0	0	0	0	0	0	0	0	0	18	18	0	0
Part 3a: Asthma Patients (DPI) COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0	0	18	18	0	0
Part 3a: Asthma Patients (DPI) NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Part 3b: Healthy Participants (DPI) STARTED	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2	6
Part 3b: Healthy Participants (DPI) COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2	6
Part 3b: Healthy Participants (DPI) NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Part 1a (SAD) Placebo Randomized healthy participants received Placebo for AZD0449.	Part 1a (SAD) Cohort 1 Randomized healthy participants received a single inhaled dose of AZD0449 0.095 mg nebulized suspension via Jet nebulizer.	Part 1a (SAD) Cohort 2 Randomized healthy participants received a single inhaled dose of AZD0449 0.28 mg nebulized suspension via Jet nebulizer.	Part 1a (SAD) Cohort 3 Randomized healthy participants received a single inhaled dose of AZD0449 0.84 mg nebulized suspension via Jet nebulizer.	Part 1a (SAD) Cohort 4 Randomized healthy participants received a single inhaled dose of AZD0449 1.60 mg nebulized suspension via Jet nebulizer.	Part 1a (SAD) Cohort 5 Randomized healthy participants received a single inhaled dose of AZD0449 3.20 mg nebulized suspension via Jet nebulizer.	Part 1a (SAD) Cohort 6 Randomized healthy participants received a single inhaled dose of AZD0449 5 mg nebulized suspension via Jet nebulizer.	Part 1b (SAD IV) Cohort 1 Randomized healthy participants received a single intravenous (IV) dose of AZD0449 0.090 mg solution.	Part 1b (SAD IV) Cohort 2 Randomized healthy participants received a single IV dose of AZD0449 0.360 mg solution.	Part 2a (MAD) Placebo Randomized patients with mild asthma received Placebo.	Part 2a (MAD) Cohort 1 Randomized patients with mild asthma received a multiple inhaled dose of AZD0449 1.20 mg nebulized suspension via Jet nebulizer.	Part 2a (MAD) Cohort 2 Randomized patients with mild asthma received a multiple inhaled dose of AZD0449 2.50 mg nebulized suspension via Jet nebulizer.	Part 2b (MAD) Placebo Randomized healthy participants received Placebo for AZD0449.	Part 2b (MAD) Cohort 1 Randomized healthy participants received a multiple inhaled of AZD0449 5 mg nebulized suspension via Jet nebulizer.	Part 3a (DPI/PoM) Placebo Randomized patients with mild asthma received Placebo for AZD0449.	Part 3a Dry Powder Inhalation/Proof of Mechanism (DPI/PoM) Randomized patients with mild asthma received a multiple inhaled dose of AZD0449 5 mg DPI.	Part 3b (DPI/Healthy Participants) Placebo Randomized healthy participants received Placebo for AZD0449.	Part 3b (DPI/Healthy Participants) Randomized healthy participants received multiple inhaled dose of AZD0449 5 mg DPI.
Part 2b: MAD (Nebulized Inhalation) Physician Decision	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0

Baseline Characteristics

A Study in Healthy Volunteers and Patients With Mild Asthma to Investigate the Safety, Anti-inflammatory Effect of Inhaled AZD0449

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part 1a (SAD) Placebo n=12 Participants Randomized healthy participants received Placebo for AZD0449.	Part 1a (SAD) Cohort 1 n=6 Participants Randomized healthy participants received a single inhaled dose of AZD0449 0.095 mg nebulized suspension via Jet nebulizer.	Part 1a (SAD) Cohort 2 n=6 Participants Randomized healthy participants received a single inhaled dose of AZD0449 0.28 mg nebulized suspension via Jet nebulizer.	Part 1a (SAD) Cohort 3 n=6 Participants Randomized healthy participants received a single inhaled dose of AZD0449 0.84 mg nebulized suspension via Jet nebulizer.	Part 1a (SAD) Cohort 4 n=6 Participants Randomized healthy participants received a single inhaled dose of AZD0449 1.60 mg nebulized suspension via Jet nebulizer.	Part 1a (SAD) Cohort 5 n=6 Participants Randomized healthy participants received a single inhaled dose of AZD0449 3.20 mg nebulized suspension via Jet nebulizer.	Part 1a (SAD) Cohort 6 n=6 Participants Randomized healthy participants received a single inhaled dose of AZD0449 5 mg nebulized suspension via Jet nebulizer.	Part 1b (SAD IV) Cohort 1 n=6 Participants Randomized healthy participants received a single intravenous (IV) dose of AZD0449 0.090 mg solution.	Part 1b (SAD IV) Cohort 2 n=6 Participants Randomized healthy participants received a single IV dose of AZD0449 0.360 mg solution.	Part 2a (MAD) Placebo n=6 Participants Randomized patients with mild asthma received Placebo.	Part 2a (MAD) Cohort 1 n=6 Participants Randomized patients with mild asthma received a multiple inhaled dose of AZD0449 1.20 mg nebulized suspension via Jet nebulizer.	Part 2a (MAD) Cohort 2 n=6 Participants Randomized patients with mild asthma received a multiple inhaled dose of AZD0449 2.50 mg nebulized suspension via Jet nebulizer.	Part 2b (MAD) Cohort 1 n=7 Participants Randomized healthy participants received a multiple inhaled of AZD0449 5 mg nebulized suspension via Jet nebulizer.	Part 2b (MAD) Placebo n=2 Participants Randomized healthy participants received Placebo for AZD0449.	Part 3a (DPI/PoM) n=18 Participants Randomized patients with mild asthma received a multiple inhaled dose of AZD0449 5 mg DPI.	Part 3a (DPI/PoM) Placebo n=18 Participants Randomized patients with mild asthma received Placebo for AZD0449.	Part 3b (DPI/Healthy Participants) Placebo n=2 Participants Randomized healthy participants received Placebo for AZD0449.	Part 3b (DPI/Healthy Participants) n=6 Participants Randomized healthy participants received multiple inhaled dose of AZD0449 5 mg DPI.	Total n=131 Participants Total of all reporting groups
Age, Continuous	31.7 Years STANDARD_DEVIATION 8.1 • n=99 Participants	29.8 Years STANDARD_DEVIATION 6.6 • n=107 Participants	29.3 Years STANDARD_DEVIATION 7.6 • n=206 Participants	36.3 Years STANDARD_DEVIATION 7.7 • n=7 Participants	26.3 Years STANDARD_DEVIATION 5.5 • n=31 Participants	35.8 Years STANDARD_DEVIATION 10.1 • n=30 Participants	30.7 Years STANDARD_DEVIATION 10.4 • n=3 Participants	32.8 Years STANDARD_DEVIATION 7.5 • n=6 Participants	28.5 Years STANDARD_DEVIATION 4.0 • n=114 Participants	37.5 Years STANDARD_DEVIATION 8.5	35.7 Years STANDARD_DEVIATION 13.7 • n=19 Participants	38.7 Years STANDARD_DEVIATION 13.5 • n=4 Participants	41.1 Years STANDARD_DEVIATION 9.4 • n=7 Participants	33.0 Years STANDARD_DEVIATION 11.3 • n=7 Participants	30.0 Years STANDARD_DEVIATION 9.2 • n=3 Participants	30.2 Years STANDARD_DEVIATION 9.1 • n=4 Participants	48.0 Years STANDARD_DEVIATION 4.2 • n=2 Participants	36.8 Years STANDARD_DEVIATION 14.5 • n=102 Participants	32.8 Years STANDARD_DEVIATION 9.8 • n=6 Participants
Sex: Female, Male Female	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants	0 Participants n=30 Participants	0 Participants n=3 Participants	0 Participants n=6 Participants	4 Participants n=114 Participants	0 Participants	0 Participants n=19 Participants	2 Participants n=4 Participants	0 Participants n=7 Participants	0 Participants n=7 Participants	9 Participants n=3 Participants	8 Participants n=4 Participants	0 Participants n=2 Participants	2 Participants n=102 Participants	25 Participants n=6 Participants
Sex: Female, Male Male	12 Participants n=99 Participants	6 Participants n=107 Participants	6 Participants n=206 Participants	6 Participants n=7 Participants	6 Participants n=31 Participants	6 Participants n=30 Participants	6 Participants n=3 Participants	6 Participants n=6 Participants	2 Participants n=114 Participants	6 Participants	6 Participants n=19 Participants	4 Participants n=4 Participants	7 Participants n=7 Participants	2 Participants n=7 Participants	9 Participants n=3 Participants	10 Participants n=4 Participants	2 Participants n=2 Participants	4 Participants n=102 Participants	106 Participants n=6 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	2 Participants n=7 Participants	0 Participants n=31 Participants	0 Participants n=30 Participants	0 Participants n=3 Participants	0 Participants n=6 Participants	0 Participants n=114 Participants	1 Participants	0 Participants n=19 Participants	0 Participants n=4 Participants	0 Participants n=7 Participants	0 Participants n=7 Participants	0 Participants n=3 Participants	2 Participants n=4 Participants	0 Participants n=2 Participants	0 Participants n=102 Participants	5 Participants n=6 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	12 Participants n=99 Participants	6 Participants n=107 Participants	6 Participants n=206 Participants	4 Participants n=7 Participants	6 Participants n=31 Participants	6 Participants n=30 Participants	6 Participants n=3 Participants	6 Participants n=6 Participants	6 Participants n=114 Participants	5 Participants	6 Participants n=19 Participants	6 Participants n=4 Participants	7 Participants n=7 Participants	2 Participants n=7 Participants	18 Participants n=3 Participants	16 Participants n=4 Participants	2 Participants n=2 Participants	6 Participants n=102 Participants	126 Participants n=6 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants	0 Participants n=30 Participants	0 Participants n=3 Participants	0 Participants n=6 Participants	0 Participants n=114 Participants	0 Participants	0 Participants n=19 Participants	0 Participants n=4 Participants	0 Participants n=7 Participants	0 Participants n=7 Participants	0 Participants n=3 Participants	0 Participants n=4 Participants	0 Participants n=2 Participants	0 Participants n=102 Participants	0 Participants n=6 Participants
Race/Ethnicity, Customized White	10 Participants n=99 Participants	4 Participants n=107 Participants	2 Participants n=206 Participants	4 Participants n=7 Participants	4 Participants n=31 Participants	5 Participants n=30 Participants	4 Participants n=3 Participants	3 Participants n=6 Participants	5 Participants n=114 Participants	4 Participants	5 Participants n=19 Participants	5 Participants n=4 Participants	7 Participants n=7 Participants	1 Participants n=7 Participants	13 Participants n=3 Participants	14 Participants n=4 Participants	2 Participants n=2 Participants	5 Participants n=102 Participants	97 Participants n=6 Participants
Race/Ethnicity, Customized Black or African American	0 Participants n=99 Participants	1 Participants n=107 Participants	3 Participants n=206 Participants	1 Participants n=7 Participants	1 Participants n=31 Participants	1 Participants n=30 Participants	1 Participants n=3 Participants	3 Participants n=6 Participants	0 Participants n=114 Participants	0 Participants	1 Participants n=19 Participants	0 Participants n=4 Participants	0 Participants n=7 Participants	0 Participants n=7 Participants	1 Participants n=3 Participants	1 Participants n=4 Participants	0 Participants n=2 Participants	0 Participants n=102 Participants	14 Participants n=6 Participants
Race/Ethnicity, Customized Asian	1 Participants n=99 Participants	1 Participants n=107 Participants	1 Participants n=206 Participants	1 Participants n=7 Participants	1 Participants n=31 Participants	0 Participants n=30 Participants	0 Participants n=3 Participants	0 Participants n=6 Participants	1 Participants n=114 Participants	1 Participants	0 Participants n=19 Participants	1 Participants n=4 Participants	0 Participants n=7 Participants	0 Participants n=7 Participants	2 Participants n=3 Participants	0 Participants n=4 Participants	0 Participants n=2 Participants	1 Participants n=102 Participants	11 Participants n=6 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants	0 Participants n=30 Participants	0 Participants n=3 Participants	0 Participants n=6 Participants	0 Participants n=114 Participants	0 Participants	0 Participants n=19 Participants	0 Participants n=4 Participants	0 Participants n=7 Participants	0 Participants n=7 Participants	0 Participants n=3 Participants	1 Participants n=4 Participants	0 Participants n=2 Participants	0 Participants n=102 Participants	1 Participants n=6 Participants
Race/Ethnicity, Customized American Indian or Alaska native	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants	0 Participants n=30 Participants	0 Participants n=3 Participants	0 Participants n=6 Participants	0 Participants n=114 Participants	0 Participants	0 Participants n=19 Participants	0 Participants n=4 Participants	0 Participants n=7 Participants	0 Participants n=7 Participants	0 Participants n=3 Participants	0 Participants n=4 Participants	0 Participants n=2 Participants	0 Participants n=102 Participants	0 Participants n=6 Participants
Race/Ethnicity, Customized Other	1 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants	0 Participants n=30 Participants	1 Participants n=3 Participants	0 Participants n=6 Participants	0 Participants n=114 Participants	1 Participants	0 Participants n=19 Participants	0 Participants n=4 Participants	0 Participants n=7 Participants	1 Participants n=7 Participants	2 Participants n=3 Participants	2 Participants n=4 Participants	0 Participants n=2 Participants	0 Participants n=102 Participants	8 Participants n=6 Participants

PRIMARY outcome

Timeframe: From screening up to follow-up visit [Part 1 a (6±1 Days post-dose)] [Part 2a (Day 22±1 (10±1 days post-last dose)], Safety Monitoring Period 2b/3a [Day 17 to 27 (15 day post-last dose)]

Population: Safety Analysis Set included all participants and patients who received at least one dose of AZD0449 and for whom any safety post-dose data were available.

Outcome measures

Outcome measures
Measure	Part 1a (SAD) Placebo n=12 Participants Randomized healthy participants received Placebo for AZD0449.	Part 1a (SAD) Cohort 1 n=6 Participants Randomized healthy participants received a single inhaled dose of AZD0449 0.095 mg nebulized suspension via Jet nebulizer.	Part 1a (SAD) Cohort 2 n=6 Participants Randomized healthy participants received a single inhaled dose of AZD0449 0.28 mg nebulized suspension via Jet nebulizer.	Part 1a (SAD) Cohort 3 n=6 Participants Randomized healthy participants received a single inhaled dose of AZD0449 0.84 mg nebulized suspension via Jet nebulizer.	Part 1a (SAD) Cohort 4 n=6 Participants Randomized healthy participants received a single inhaled dose of AZD0449 1.60 mg nebulized suspension via Jet nebulizer.	Part 1a (SAD) Cohort 5 n=6 Participants Randomized healthy participants received a single inhaled dose of AZD0449 3.20 mg nebulized suspension via Jet nebulizer.	Part 1a (SAD) Cohort 6 n=6 Participants Randomized healthy participants received a single inhaled dose of AZD0449 5 mg nebulized suspension via Jet nebulizer.	Part 2a (MAD) Placebo n=6 Participants Randomized patients with mild asthma received Placebo.	Part 2a (MAD) Cohort 1 n=6 Participants Randomized patients with mild asthma received a multiple inhaled dose of AZD0449 1.20 mg nebulized suspension via Jet nebulizer.	Part 2a (MAD) Cohort 2 n=6 Participants Randomized patients with mild asthma received a multiple inhaled dose of AZD0449 2.50 mg nebulized suspension via Jet nebulizer.	Part 2b (MAD) Placebo n=2 Participants Randomized healthy participants received Placebo for AZD0449.	Part 2b (MAD) Cohort 1 n=7 Participants Randomized healthy participants received a multiple inhaled of AZD0449 5 mg nebulized suspension via Jet nebulizer.	Part 3a (DPI/PoM) Placebo n=18 Participants Randomized patients with mild asthma received Placebo for AZD0449.	Part 3a (DPI/PoM) n=18 Participants Randomized patients with mild asthma received a multiple inhaled dose of AZD0449 5 mg DPI.	Part 3b (DPI/Healthy Participants) Placebo n=2 Participants Randomized healthy participants received Placebo for AZD0449.	Part 3b (DPI/Healthy Participants) n=6 Participants Randomized healthy participants received multiple inhaled dose of AZD0449 5 mg DPI.
Number of Participants With Adverse Events and Serious Adverse Events Any AE leading to withdrawal from study	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Adverse Events and Serious Adverse Events Any AE leading to discontinuation of investigational medicinal product (IMP)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Adverse Events and Serious Adverse Events Any Adverse Event (AE)	3 Participants	2 Participants	2 Participants	3 Participants	3 Participants	3 Participants	1 Participants	4 Participants	5 Participants	3 Participants	2 Participants	6 Participants	15 Participants	14 Participants	0 Participants	3 Participants
Number of Participants With Adverse Events and Serious Adverse Events Any AE with outcome=death	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Adverse Events and Serious Adverse Events Any serious AE (including events with outcome=death)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Part 1b: Day 1

Population: The pharmacokinetic (PK) set consisted of all participants who received at least one dose of AZD0449 and who had evaluable PK data, with no major protocol deviations thought to impact on the analysis of the PK data.

Cmax of AZD0449 following intravenous administration of a single dose to healthy participants was assessed.

Outcome measures

Outcome measures
Measure	Part 1a (SAD) Placebo n=6 Participants Randomized healthy participants received Placebo for AZD0449.	Part 1a (SAD) Cohort 1 n=6 Participants Randomized healthy participants received a single inhaled dose of AZD0449 0.095 mg nebulized suspension via Jet nebulizer.	Part 1a (SAD) Cohort 2 Randomized healthy participants received a single inhaled dose of AZD0449 0.28 mg nebulized suspension via Jet nebulizer.	Part 1a (SAD) Cohort 3 Randomized healthy participants received a single inhaled dose of AZD0449 0.84 mg nebulized suspension via Jet nebulizer.	Part 1a (SAD) Cohort 4 Randomized healthy participants received a single inhaled dose of AZD0449 1.60 mg nebulized suspension via Jet nebulizer.	Part 1a (SAD) Cohort 5 Randomized healthy participants received a single inhaled dose of AZD0449 3.20 mg nebulized suspension via Jet nebulizer.	Part 1a (SAD) Cohort 6 Randomized healthy participants received a single inhaled dose of AZD0449 5 mg nebulized suspension via Jet nebulizer.	Part 2a (MAD) Placebo Randomized patients with mild asthma received Placebo.	Part 2a (MAD) Cohort 1 Randomized patients with mild asthma received a multiple inhaled dose of AZD0449 1.20 mg nebulized suspension via Jet nebulizer.	Part 2a (MAD) Cohort 2 Randomized patients with mild asthma received a multiple inhaled dose of AZD0449 2.50 mg nebulized suspension via Jet nebulizer.	Part 2b (MAD) Placebo Randomized healthy participants received Placebo for AZD0449.	Part 2b (MAD) Cohort 1 Randomized healthy participants received a multiple inhaled of AZD0449 5 mg nebulized suspension via Jet nebulizer.	Part 3a (DPI/PoM) Placebo Randomized patients with mild asthma received Placebo for AZD0449.	Part 3a (DPI/PoM) Randomized patients with mild asthma received a multiple inhaled dose of AZD0449 5 mg DPI.	Part 3b (DPI/Healthy Participants) Placebo Randomized healthy participants received Placebo for AZD0449.	Part 3b (DPI/Healthy Participants) Randomized healthy participants received multiple inhaled dose of AZD0449 5 mg DPI.
Maximum Observed Plasma Concentration (Cmax)	2.053 nanomole/liter (nmol/L) Geometric Coefficient of Variation 15.95	10.31 nanomole/liter (nmol/L) Geometric Coefficient of Variation 17.58	—	—	—	—	—	—	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Part 1b: Day 1

Population: The PK set consisted of all participants who received at least one dose of AZD0449 and who had evaluable PK data, with no major protocol deviations thought to impact on the analysis of the PK data.

AUCinf of AZD0449 following intravenous administration of a single dose to healthy participants was assessed.

Outcome measures

Outcome measures
Measure	Part 1a (SAD) Placebo n=6 Participants Randomized healthy participants received Placebo for AZD0449.	Part 1a (SAD) Cohort 1 n=6 Participants Randomized healthy participants received a single inhaled dose of AZD0449 0.095 mg nebulized suspension via Jet nebulizer.	Part 1a (SAD) Cohort 2 Randomized healthy participants received a single inhaled dose of AZD0449 0.28 mg nebulized suspension via Jet nebulizer.	Part 1a (SAD) Cohort 3 Randomized healthy participants received a single inhaled dose of AZD0449 0.84 mg nebulized suspension via Jet nebulizer.	Part 1a (SAD) Cohort 4 Randomized healthy participants received a single inhaled dose of AZD0449 1.60 mg nebulized suspension via Jet nebulizer.	Part 1a (SAD) Cohort 5 Randomized healthy participants received a single inhaled dose of AZD0449 3.20 mg nebulized suspension via Jet nebulizer.	Part 1a (SAD) Cohort 6 Randomized healthy participants received a single inhaled dose of AZD0449 5 mg nebulized suspension via Jet nebulizer.	Part 2a (MAD) Placebo Randomized patients with mild asthma received Placebo.	Part 2a (MAD) Cohort 1 Randomized patients with mild asthma received a multiple inhaled dose of AZD0449 1.20 mg nebulized suspension via Jet nebulizer.	Part 2a (MAD) Cohort 2 Randomized patients with mild asthma received a multiple inhaled dose of AZD0449 2.50 mg nebulized suspension via Jet nebulizer.	Part 2b (MAD) Placebo Randomized healthy participants received Placebo for AZD0449.	Part 2b (MAD) Cohort 1 Randomized healthy participants received a multiple inhaled of AZD0449 5 mg nebulized suspension via Jet nebulizer.	Part 3a (DPI/PoM) Placebo Randomized patients with mild asthma received Placebo for AZD0449.	Part 3a (DPI/PoM) Randomized patients with mild asthma received a multiple inhaled dose of AZD0449 5 mg DPI.	Part 3b (DPI/Healthy Participants) Placebo Randomized healthy participants received Placebo for AZD0449.	Part 3b (DPI/Healthy Participants) Randomized healthy participants received multiple inhaled dose of AZD0449 5 mg DPI.
Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUCinf)	3.697 h*nmol/L Geometric Coefficient of Variation 14.27	17.10 h*nmol/L Geometric Coefficient of Variation 21.01	—	—	—	—	—	—	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Part 1b: Day 1

AUClast of AZD0449 following intravenous administration of a single dose to healthy participants was assessed.

Outcome measures

Outcome measures
Measure	Part 1a (SAD) Placebo n=6 Participants Randomized healthy participants received Placebo for AZD0449.	Part 1a (SAD) Cohort 1 n=6 Participants Randomized healthy participants received a single inhaled dose of AZD0449 0.095 mg nebulized suspension via Jet nebulizer.	Part 1a (SAD) Cohort 2 Randomized healthy participants received a single inhaled dose of AZD0449 0.28 mg nebulized suspension via Jet nebulizer.	Part 1a (SAD) Cohort 3 Randomized healthy participants received a single inhaled dose of AZD0449 0.84 mg nebulized suspension via Jet nebulizer.	Part 1a (SAD) Cohort 4 Randomized healthy participants received a single inhaled dose of AZD0449 1.60 mg nebulized suspension via Jet nebulizer.	Part 1a (SAD) Cohort 5 Randomized healthy participants received a single inhaled dose of AZD0449 3.20 mg nebulized suspension via Jet nebulizer.	Part 1a (SAD) Cohort 6 Randomized healthy participants received a single inhaled dose of AZD0449 5 mg nebulized suspension via Jet nebulizer.	Part 2a (MAD) Placebo Randomized patients with mild asthma received Placebo.	Part 2a (MAD) Cohort 1 Randomized patients with mild asthma received a multiple inhaled dose of AZD0449 1.20 mg nebulized suspension via Jet nebulizer.	Part 2a (MAD) Cohort 2 Randomized patients with mild asthma received a multiple inhaled dose of AZD0449 2.50 mg nebulized suspension via Jet nebulizer.	Part 2b (MAD) Placebo Randomized healthy participants received Placebo for AZD0449.	Part 2b (MAD) Cohort 1 Randomized healthy participants received a multiple inhaled of AZD0449 5 mg nebulized suspension via Jet nebulizer.	Part 3a (DPI/PoM) Placebo Randomized patients with mild asthma received Placebo for AZD0449.	Part 3a (DPI/PoM) Randomized patients with mild asthma received a multiple inhaled dose of AZD0449 5 mg DPI.	Part 3b (DPI/Healthy Participants) Placebo Randomized healthy participants received Placebo for AZD0449.	Part 3b (DPI/Healthy Participants) Randomized healthy participants received multiple inhaled dose of AZD0449 5 mg DPI.
Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast)	3.567 h*nmol/L Geometric Coefficient of Variation 15.07	16.94 h*nmol/L Geometric Coefficient of Variation 20.39	—	—	—	—	—	—	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Part 1b: Day 1

AUC (0-24) of AZD0449 following intravenous administration of a single dose to healthy participants was assessed.

Outcome measures

Outcome measures
Measure	Part 1a (SAD) Placebo n=6 Participants Randomized healthy participants received Placebo for AZD0449.	Part 1a (SAD) Cohort 1 n=6 Participants Randomized healthy participants received a single inhaled dose of AZD0449 0.095 mg nebulized suspension via Jet nebulizer.	Part 1a (SAD) Cohort 2 Randomized healthy participants received a single inhaled dose of AZD0449 0.28 mg nebulized suspension via Jet nebulizer.	Part 1a (SAD) Cohort 3 Randomized healthy participants received a single inhaled dose of AZD0449 0.84 mg nebulized suspension via Jet nebulizer.	Part 1a (SAD) Cohort 4 Randomized healthy participants received a single inhaled dose of AZD0449 1.60 mg nebulized suspension via Jet nebulizer.	Part 1a (SAD) Cohort 5 Randomized healthy participants received a single inhaled dose of AZD0449 3.20 mg nebulized suspension via Jet nebulizer.	Part 1a (SAD) Cohort 6 Randomized healthy participants received a single inhaled dose of AZD0449 5 mg nebulized suspension via Jet nebulizer.	Part 2a (MAD) Placebo Randomized patients with mild asthma received Placebo.	Part 2a (MAD) Cohort 1 Randomized patients with mild asthma received a multiple inhaled dose of AZD0449 1.20 mg nebulized suspension via Jet nebulizer.	Part 2a (MAD) Cohort 2 Randomized patients with mild asthma received a multiple inhaled dose of AZD0449 2.50 mg nebulized suspension via Jet nebulizer.	Part 2b (MAD) Placebo Randomized healthy participants received Placebo for AZD0449.	Part 2b (MAD) Cohort 1 Randomized healthy participants received a multiple inhaled of AZD0449 5 mg nebulized suspension via Jet nebulizer.	Part 3a (DPI/PoM) Placebo Randomized patients with mild asthma received Placebo for AZD0449.	Part 3a (DPI/PoM) Randomized patients with mild asthma received a multiple inhaled dose of AZD0449 5 mg DPI.	Part 3b (DPI/Healthy Participants) Placebo Randomized healthy participants received Placebo for AZD0449.	Part 3b (DPI/Healthy Participants) Randomized healthy participants received multiple inhaled dose of AZD0449 5 mg DPI.
Area Under the Plasma Concentration Time Curve From Time Zero to 24 Hours After Dosing (AUC(0-24))	3.692 hournanomole/L (hnmol/L) Geometric Coefficient of Variation 14.31	17.03 hournanomole/L (hnmol/L) Geometric Coefficient of Variation 20.18	—	—	—	—	—	—	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Part 1b: Day 1

tmax of AZD0449 following intravenous administration of a single dose to healthy participants was assessed.

Outcome measures

Outcome measures
Measure	Part 1a (SAD) Placebo n=6 Participants Randomized healthy participants received Placebo for AZD0449.	Part 1a (SAD) Cohort 1 n=6 Participants Randomized healthy participants received a single inhaled dose of AZD0449 0.095 mg nebulized suspension via Jet nebulizer.	Part 1a (SAD) Cohort 2 Randomized healthy participants received a single inhaled dose of AZD0449 0.28 mg nebulized suspension via Jet nebulizer.	Part 1a (SAD) Cohort 3 Randomized healthy participants received a single inhaled dose of AZD0449 0.84 mg nebulized suspension via Jet nebulizer.	Part 1a (SAD) Cohort 4 Randomized healthy participants received a single inhaled dose of AZD0449 1.60 mg nebulized suspension via Jet nebulizer.	Part 1a (SAD) Cohort 5 Randomized healthy participants received a single inhaled dose of AZD0449 3.20 mg nebulized suspension via Jet nebulizer.	Part 1a (SAD) Cohort 6 Randomized healthy participants received a single inhaled dose of AZD0449 5 mg nebulized suspension via Jet nebulizer.	Part 2a (MAD) Placebo Randomized patients with mild asthma received Placebo.	Part 2a (MAD) Cohort 1 Randomized patients with mild asthma received a multiple inhaled dose of AZD0449 1.20 mg nebulized suspension via Jet nebulizer.	Part 2a (MAD) Cohort 2 Randomized patients with mild asthma received a multiple inhaled dose of AZD0449 2.50 mg nebulized suspension via Jet nebulizer.	Part 2b (MAD) Placebo Randomized healthy participants received Placebo for AZD0449.	Part 2b (MAD) Cohort 1 Randomized healthy participants received a multiple inhaled of AZD0449 5 mg nebulized suspension via Jet nebulizer.	Part 3a (DPI/PoM) Placebo Randomized patients with mild asthma received Placebo for AZD0449.	Part 3a (DPI/PoM) Randomized patients with mild asthma received a multiple inhaled dose of AZD0449 5 mg DPI.	Part 3b (DPI/Healthy Participants) Placebo Randomized healthy participants received Placebo for AZD0449.	Part 3b (DPI/Healthy Participants) Randomized healthy participants received multiple inhaled dose of AZD0449 5 mg DPI.
Time to Reach Peak or Maximum Observed Concentration Following Drug Administration (Tmax)	1.00 Hours Interval 0.73 to 1.0	0.69 Hours Interval 0.43 to 0.82	—	—	—	—	—	—	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Part 1b: Day 1

t½λz of AZD0449 following intravenous administration of a single dose to healthy participants was assessed.

Outcome measures

Outcome measures
Measure	Part 1a (SAD) Placebo n=6 Participants Randomized healthy participants received Placebo for AZD0449.	Part 1a (SAD) Cohort 1 n=6 Participants Randomized healthy participants received a single inhaled dose of AZD0449 0.095 mg nebulized suspension via Jet nebulizer.	Part 1a (SAD) Cohort 2 Randomized healthy participants received a single inhaled dose of AZD0449 0.28 mg nebulized suspension via Jet nebulizer.	Part 1a (SAD) Cohort 3 Randomized healthy participants received a single inhaled dose of AZD0449 0.84 mg nebulized suspension via Jet nebulizer.	Part 1a (SAD) Cohort 4 Randomized healthy participants received a single inhaled dose of AZD0449 1.60 mg nebulized suspension via Jet nebulizer.	Part 1a (SAD) Cohort 5 Randomized healthy participants received a single inhaled dose of AZD0449 3.20 mg nebulized suspension via Jet nebulizer.	Part 1a (SAD) Cohort 6 Randomized healthy participants received a single inhaled dose of AZD0449 5 mg nebulized suspension via Jet nebulizer.	Part 2a (MAD) Placebo Randomized patients with mild asthma received Placebo.	Part 2a (MAD) Cohort 1 Randomized patients with mild asthma received a multiple inhaled dose of AZD0449 1.20 mg nebulized suspension via Jet nebulizer.	Part 2a (MAD) Cohort 2 Randomized patients with mild asthma received a multiple inhaled dose of AZD0449 2.50 mg nebulized suspension via Jet nebulizer.	Part 2b (MAD) Placebo Randomized healthy participants received Placebo for AZD0449.	Part 2b (MAD) Cohort 1 Randomized healthy participants received a multiple inhaled of AZD0449 5 mg nebulized suspension via Jet nebulizer.	Part 3a (DPI/PoM) Placebo Randomized patients with mild asthma received Placebo for AZD0449.	Part 3a (DPI/PoM) Randomized patients with mild asthma received a multiple inhaled dose of AZD0449 5 mg DPI.	Part 3b (DPI/Healthy Participants) Placebo Randomized healthy participants received Placebo for AZD0449.	Part 3b (DPI/Healthy Participants) Randomized healthy participants received multiple inhaled dose of AZD0449 5 mg DPI.
Terminal Halflife, Estimated as (ln2)/-λz (t½λz )	2.463 Hours Standard Deviation 0.5698	3.370 Hours Standard Deviation 2.453	—	—	—	—	—	—	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Part 1b: Day 1

CL of AZD0449 following intravenous administration of a single dose of AZD0449 to healthy volunteers was assessed.

Outcome measures

Outcome measures
Measure	Part 1a (SAD) Placebo n=6 Participants Randomized healthy participants received Placebo for AZD0449.	Part 1a (SAD) Cohort 1 n=6 Participants Randomized healthy participants received a single inhaled dose of AZD0449 0.095 mg nebulized suspension via Jet nebulizer.	Part 1a (SAD) Cohort 2 Randomized healthy participants received a single inhaled dose of AZD0449 0.28 mg nebulized suspension via Jet nebulizer.	Part 1a (SAD) Cohort 3 Randomized healthy participants received a single inhaled dose of AZD0449 0.84 mg nebulized suspension via Jet nebulizer.	Part 1a (SAD) Cohort 4 Randomized healthy participants received a single inhaled dose of AZD0449 1.60 mg nebulized suspension via Jet nebulizer.	Part 1a (SAD) Cohort 5 Randomized healthy participants received a single inhaled dose of AZD0449 3.20 mg nebulized suspension via Jet nebulizer.	Part 1a (SAD) Cohort 6 Randomized healthy participants received a single inhaled dose of AZD0449 5 mg nebulized suspension via Jet nebulizer.	Part 2a (MAD) Placebo Randomized patients with mild asthma received Placebo.	Part 2a (MAD) Cohort 1 Randomized patients with mild asthma received a multiple inhaled dose of AZD0449 1.20 mg nebulized suspension via Jet nebulizer.	Part 2a (MAD) Cohort 2 Randomized patients with mild asthma received a multiple inhaled dose of AZD0449 2.50 mg nebulized suspension via Jet nebulizer.	Part 2b (MAD) Placebo Randomized healthy participants received Placebo for AZD0449.	Part 2b (MAD) Cohort 1 Randomized healthy participants received a multiple inhaled of AZD0449 5 mg nebulized suspension via Jet nebulizer.	Part 3a (DPI/PoM) Placebo Randomized patients with mild asthma received Placebo for AZD0449.	Part 3a (DPI/PoM) Randomized patients with mild asthma received a multiple inhaled dose of AZD0449 5 mg DPI.	Part 3b (DPI/Healthy Participants) Placebo Randomized healthy participants received Placebo for AZD0449.	Part 3b (DPI/Healthy Participants) Randomized healthy participants received multiple inhaled dose of AZD0449 5 mg DPI.
Total Body Clearance of Drug From Plasma After Intravascular Administration (CL)	65.38 Liter/hour (L/h) Standard Deviation 9.099	57.05 Liter/hour (L/h) Standard Deviation 10.86	—	—	—	—	—	—	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Part 1b: Day 1

Vz of AZD0449 following intravenous administration of a single dose of AZD0449 to healthy volunteers was assessed.

Outcome measures

Outcome measures
Measure	Part 1a (SAD) Placebo n=6 Participants Randomized healthy participants received Placebo for AZD0449.	Part 1a (SAD) Cohort 1 n=6 Participants Randomized healthy participants received a single inhaled dose of AZD0449 0.095 mg nebulized suspension via Jet nebulizer.	Part 1a (SAD) Cohort 2 Randomized healthy participants received a single inhaled dose of AZD0449 0.28 mg nebulized suspension via Jet nebulizer.	Part 1a (SAD) Cohort 3 Randomized healthy participants received a single inhaled dose of AZD0449 0.84 mg nebulized suspension via Jet nebulizer.	Part 1a (SAD) Cohort 4 Randomized healthy participants received a single inhaled dose of AZD0449 1.60 mg nebulized suspension via Jet nebulizer.	Part 1a (SAD) Cohort 5 Randomized healthy participants received a single inhaled dose of AZD0449 3.20 mg nebulized suspension via Jet nebulizer.	Part 1a (SAD) Cohort 6 Randomized healthy participants received a single inhaled dose of AZD0449 5 mg nebulized suspension via Jet nebulizer.	Part 2a (MAD) Placebo Randomized patients with mild asthma received Placebo.	Part 2a (MAD) Cohort 1 Randomized patients with mild asthma received a multiple inhaled dose of AZD0449 1.20 mg nebulized suspension via Jet nebulizer.	Part 2a (MAD) Cohort 2 Randomized patients with mild asthma received a multiple inhaled dose of AZD0449 2.50 mg nebulized suspension via Jet nebulizer.	Part 2b (MAD) Placebo Randomized healthy participants received Placebo for AZD0449.	Part 2b (MAD) Cohort 1 Randomized healthy participants received a multiple inhaled of AZD0449 5 mg nebulized suspension via Jet nebulizer.	Part 3a (DPI/PoM) Placebo Randomized patients with mild asthma received Placebo for AZD0449.	Part 3a (DPI/PoM) Randomized patients with mild asthma received a multiple inhaled dose of AZD0449 5 mg DPI.	Part 3b (DPI/Healthy Participants) Placebo Randomized healthy participants received Placebo for AZD0449.	Part 3b (DPI/Healthy Participants) Randomized healthy participants received multiple inhaled dose of AZD0449 5 mg DPI.
Volume of Distribution for Parent Drug at Terminal Phase [Intravenous Administration] (λz)	232.0 Liter Standard Deviation 62.16	248.3 Liter Standard Deviation 109.0	—	—	—	—	—	—	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Part 1b: Day 1

λz of AZD0449 following intravenous administration of a single dose to healthy participants was assessed.

Outcome measures

Outcome measures
Measure	Part 1a (SAD) Placebo n=6 Participants Randomized healthy participants received Placebo for AZD0449.	Part 1a (SAD) Cohort 1 n=6 Participants Randomized healthy participants received a single inhaled dose of AZD0449 0.095 mg nebulized suspension via Jet nebulizer.	Part 1a (SAD) Cohort 2 Randomized healthy participants received a single inhaled dose of AZD0449 0.28 mg nebulized suspension via Jet nebulizer.	Part 1a (SAD) Cohort 3 Randomized healthy participants received a single inhaled dose of AZD0449 0.84 mg nebulized suspension via Jet nebulizer.	Part 1a (SAD) Cohort 4 Randomized healthy participants received a single inhaled dose of AZD0449 1.60 mg nebulized suspension via Jet nebulizer.	Part 1a (SAD) Cohort 5 Randomized healthy participants received a single inhaled dose of AZD0449 3.20 mg nebulized suspension via Jet nebulizer.	Part 1a (SAD) Cohort 6 Randomized healthy participants received a single inhaled dose of AZD0449 5 mg nebulized suspension via Jet nebulizer.	Part 2a (MAD) Placebo Randomized patients with mild asthma received Placebo.	Part 2a (MAD) Cohort 1 Randomized patients with mild asthma received a multiple inhaled dose of AZD0449 1.20 mg nebulized suspension via Jet nebulizer.	Part 2a (MAD) Cohort 2 Randomized patients with mild asthma received a multiple inhaled dose of AZD0449 2.50 mg nebulized suspension via Jet nebulizer.	Part 2b (MAD) Placebo Randomized healthy participants received Placebo for AZD0449.	Part 2b (MAD) Cohort 1 Randomized healthy participants received a multiple inhaled of AZD0449 5 mg nebulized suspension via Jet nebulizer.	Part 3a (DPI/PoM) Placebo Randomized patients with mild asthma received Placebo for AZD0449.	Part 3a (DPI/PoM) Randomized patients with mild asthma received a multiple inhaled dose of AZD0449 5 mg DPI.	Part 3b (DPI/Healthy Participants) Placebo Randomized healthy participants received Placebo for AZD0449.	Part 3b (DPI/Healthy Participants) Randomized healthy participants received multiple inhaled dose of AZD0449 5 mg DPI.
Terminal Rate Constant, Estimated by Loglinear Leastsquares Regression of the Terminal Part of the -Concentrationtime- Curve (λz)	0.285 Hours Interval 0.217 to 0.376	0.298 Hours Interval 0.084 to 0.371	—	—	—	—	—	—	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Part 1b: Day 1

tlast of AZD0449 following intravenous administration of a single dose to healthy participants was assessed.

Outcome measures

Outcome measures
Measure	Part 1a (SAD) Placebo n=6 Participants Randomized healthy participants received Placebo for AZD0449.	Part 1a (SAD) Cohort 1 n=6 Participants Randomized healthy participants received a single inhaled dose of AZD0449 0.095 mg nebulized suspension via Jet nebulizer.	Part 1a (SAD) Cohort 2 Randomized healthy participants received a single inhaled dose of AZD0449 0.28 mg nebulized suspension via Jet nebulizer.	Part 1a (SAD) Cohort 3 Randomized healthy participants received a single inhaled dose of AZD0449 0.84 mg nebulized suspension via Jet nebulizer.	Part 1a (SAD) Cohort 4 Randomized healthy participants received a single inhaled dose of AZD0449 1.60 mg nebulized suspension via Jet nebulizer.	Part 1a (SAD) Cohort 5 Randomized healthy participants received a single inhaled dose of AZD0449 3.20 mg nebulized suspension via Jet nebulizer.	Part 1a (SAD) Cohort 6 Randomized healthy participants received a single inhaled dose of AZD0449 5 mg nebulized suspension via Jet nebulizer.	Part 2a (MAD) Placebo Randomized patients with mild asthma received Placebo.	Part 2a (MAD) Cohort 1 Randomized patients with mild asthma received a multiple inhaled dose of AZD0449 1.20 mg nebulized suspension via Jet nebulizer.	Part 2a (MAD) Cohort 2 Randomized patients with mild asthma received a multiple inhaled dose of AZD0449 2.50 mg nebulized suspension via Jet nebulizer.	Part 2b (MAD) Placebo Randomized healthy participants received Placebo for AZD0449.	Part 2b (MAD) Cohort 1 Randomized healthy participants received a multiple inhaled of AZD0449 5 mg nebulized suspension via Jet nebulizer.	Part 3a (DPI/PoM) Placebo Randomized patients with mild asthma received Placebo for AZD0449.	Part 3a (DPI/PoM) Randomized patients with mild asthma received a multiple inhaled dose of AZD0449 5 mg DPI.	Part 3b (DPI/Healthy Participants) Placebo Randomized healthy participants received Placebo for AZD0449.	Part 3b (DPI/Healthy Participants) Randomized healthy participants received multiple inhaled dose of AZD0449 5 mg DPI.
Time of Last Quantifiable Concentration (Tlast)	9.98 Hours Interval 7.98 to 10.03	15.00 Hours Interval 11.98 to 24.03	—	—	—	—	—	—	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Part 1b: Day 1

Cmax/D of AZD0449 following intravenous administration of a single dose to healthy participants was assessed.

Outcome measures

Outcome measures
Measure	Part 1a (SAD) Placebo n=6 Participants Randomized healthy participants received Placebo for AZD0449.	Part 1a (SAD) Cohort 1 n=6 Participants Randomized healthy participants received a single inhaled dose of AZD0449 0.095 mg nebulized suspension via Jet nebulizer.	Part 1a (SAD) Cohort 2 Randomized healthy participants received a single inhaled dose of AZD0449 0.28 mg nebulized suspension via Jet nebulizer.	Part 1a (SAD) Cohort 3 Randomized healthy participants received a single inhaled dose of AZD0449 0.84 mg nebulized suspension via Jet nebulizer.	Part 1a (SAD) Cohort 4 Randomized healthy participants received a single inhaled dose of AZD0449 1.60 mg nebulized suspension via Jet nebulizer.	Part 1a (SAD) Cohort 5 Randomized healthy participants received a single inhaled dose of AZD0449 3.20 mg nebulized suspension via Jet nebulizer.	Part 1a (SAD) Cohort 6 Randomized healthy participants received a single inhaled dose of AZD0449 5 mg nebulized suspension via Jet nebulizer.	Part 2a (MAD) Placebo Randomized patients with mild asthma received Placebo.	Part 2a (MAD) Cohort 1 Randomized patients with mild asthma received a multiple inhaled dose of AZD0449 1.20 mg nebulized suspension via Jet nebulizer.	Part 2a (MAD) Cohort 2 Randomized patients with mild asthma received a multiple inhaled dose of AZD0449 2.50 mg nebulized suspension via Jet nebulizer.	Part 2b (MAD) Placebo Randomized healthy participants received Placebo for AZD0449.	Part 2b (MAD) Cohort 1 Randomized healthy participants received a multiple inhaled of AZD0449 5 mg nebulized suspension via Jet nebulizer.	Part 3a (DPI/PoM) Placebo Randomized patients with mild asthma received Placebo for AZD0449.	Part 3a (DPI/PoM) Randomized patients with mild asthma received a multiple inhaled dose of AZD0449 5 mg DPI.	Part 3b (DPI/Healthy Participants) Placebo Randomized healthy participants received Placebo for AZD0449.	Part 3b (DPI/Healthy Participants) Randomized healthy participants received multiple inhaled dose of AZD0449 5 mg DPI.
Dose Normalized Cmax (Cmax/D)	22.81 (nmol/L)/milligram (mg) Geometric Coefficient of Variation 15.95	28.65 (nmol/L)/milligram (mg) Geometric Coefficient of Variation 17.58	—	—	—	—	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: From screening up to follow-up visit [Part 1b (6±1 Days post-dose)]

Population: Safety Analysis Set included all participants who received at least one dose of AZD0449 and for whom any safety post-dose data were available.

Safety and tolerability of AZD0449 following intravenous administration of a single dose to healthy participants was assessed.