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

A Single-blind, Randomized, Placebo-Controlled 3-Part Study in Healthy Volunteers and Patients With Mild Asthma to Investigate the Safety, Tolerability and Pharmacokinetics of Inhaled AZD0449 Following Single and Multiple Ascending Doses and to Investigate the Anti-Inflammatory Effect of Inhaled AZD0449

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03766399

Enrollment

131

Registered

2018-12-06

Start date

2018-11-30

Completion date

2021-06-24

Last updated

2024-08-23

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Asthma

Keywords

Inhaled JAK inhibitor

Brief summary

This will be a Phase I, first in human (FIH) study consisting of the following parts: Part 1a (SAD), Part 1b (IV Cohort), Part 2 (Multiple ascending dose (MAD), and Part 3 dry-powder inhalation (DPI)/ Proof of mechanism (PoM). Part 1a of the study will be a randomized, single-blind, placebo-controlled, SAD, sequential group design study performed at a single study center. Part 1b, will be an open-label, single-dose, single-cohort study. It will follow a 2-stage design in the way that participants from Part 1a will be selected for the IV Cohort in Part 1b. Part 2 of the study will be a randomized, single-blind, placebo-controlled, MAD, sequential group design and study performed at 3 study centers. Part 3a/b will be a randomized, single-blind, placebo-controlled, DPI/PoM study. The expected duration of each subject in Part 1a of the study is up to 36 days and up to 53 days for subjects participating in Part 1b. The expected duration of each participant in Part 2 is up to 52 days and Part 3 is up to 55 days.

Detailed description

This will be a Phase I, consisting of the following parts: Part 1a, Part 1b, Part 2a/b, Part 3a/b. Part 1a of the study will be a randomized, single-blind, placebo-controlled, SAD, sequential group design study performed at a single study center. Six inhaled dose levels of AZD0449 nebulized suspension are planned to be investigated in 6 cohorts. Depending on emerging safety and PK data, up to 3 additional inhaled dose levels (cohorts), within the pre-specified dose range, may be added at the discretion of the Sponsor. Within each cohort, 6 volunteers will be randomized to receive an inhaled dose of AZD0449 nebulized suspension and 2 volunteers will be randomized to receive inhaled placebo. Intravenous (IV) dosing in Part 1b of the study will be initiated after the completion of cohort 6 in Part 1a or (if Part 1a is completed with less than 6 cohorts) after completion of the last cohort in Part 1a. Part 1b, will be open-label and consist of 2 dose cohorts (IV 0.090 mg and 0.360 mg) and be conducted in 12 healthy volunteers. Six (6) volunteers will be selected for the first IV dose cohort in Part 1b following a 2-stage design. If Part 1b cannot be completed with 6 volunteers from Part 1a or if some of the data are considered not evaluable, up to 6 additional naïve volunteers may be enrolled. A second IV dose cohort in Part 1b will be initiated after the evaluation of the PK and safety results from all cohorts in Part 1a and completion of the first IV dose cohort in Part 1b. The second IV dose cohort will consist of 6 healthy volunteers who have not previously participated in the study (naïve volunteers). Part 2a/b of the study will be a randomized, single-blind, placebo-controlled, MAD, sequential group design study performed at approximately 3 study centers. Part 2a will include cohorts 1 and 2, each comprising of 9 patients with mild asthma. Within each of these cohorts 6 patients will be randomized to receive AZD0449 nebulized suspension and 3 patients randomized to receive placebo. Additional cohorts with 9 patients could be added to study PK, PD and safety for doses lower than 1.2 mg or up to 5 mg. Part 2b will consist of 1 cohort of 8 healthy volunteers; 6 volunteers will be randomized to receive AZD0449 nebulized suspension and 2 volunteers will be randomized to receive placebo. Part 3a/b of the study will be initiated after the completion of Part 2b. Part 3a/b will be a randomized, single-blind, placebo-controlled, DPI/PoM study. Part 3 will be conducted in up to 36 patients with mild asthma (Part 3a) and 8 healthy volunteers (Part 3b, optional). Part 3a will consist of 36 patients, where 18 patients will be randomized to AZD0449 DPI and 18 patients to placebo. An Interim Analysis (IA) will be conducted when 9 patients on each arm have completed the study (50% Part 3a). Should new data on the variability of the FeNO measurements emerge at the IA, the sample size in Part 3a could be changed. If the optional Part 3b is conducted, it will comprise 8 healthy volunteers; 6 volunteers will be randomized to AZD0449 DPI and 2 volunteers to placebo.

Interventions

DRUGAZD0449

Participants will receive single inhaled AZD0449 nebulizer suspension and single IV dose of AZD0449 solution.

DRUGPlacebo

Participants will receive single dose of placebo for AZD0449 (nebulizer suspension).

Study design

Allocation

RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Masking

SINGLE (Subject)

Eligibility

Sex/Gender

ALL

Age

18 Years to 65 Years

Healthy volunteers

Yes

Inclusion criteria

Part 1a/b: 1. Provision of signed and dated, written informed consent before any study specific procedures (applicable for all parts). 2. Healthy male volunteers and healthy female volunteers (for Part 1a and Part 1b first IV cohort, female volunteers must be of non-childbearing potential), aged 18 to 55 years with suitable veins for cannulation or repeated venipuncture. 3. Female patients must not be lactating and must have a negative pregnancy test at the Screening Visit and on admission to the Clinical Unit. Women of non-childbearing potential must fulfill one of the following criteria (Applicable for all parts): 3.1. Postmenopausal defined as amenorrhea for at least 12 months or more following cessation of all exogenous hormonal treatments and follicle-stimulating hormone (FSH) levels in the postmenopausal range. 3.2. Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation. 4. Have a body mass index (BMI) between 18 and 30 kg/m2 inclusive and weigh at least 60 kg. 5. Healthy volunteer has a Forced Expiratory Volume in one second (FEV1) ≥80% of the predicted value regarding age, height, gender and ethnicity at the Screening Visit. 6. Male volunteers and their WOCBP partners should be willing to use highly effective contraception measures and should refrain from donating sperm or fathering a child from the first day of dosing until 3 months after the last dose of IMP. 7. Female volunteers in Part 1b second IV cohort should be willing to use highly effective contraception measures from the first day of dosing until 1 month after the last dose of IMP. 8. Provision of signed, written and dated informed consent for optional genetic research. If a volunteer declines to participate in the genetic component of the study, there will be no penalty or loss of benefit to the volunteer. The volunteer will not be excluded from other aspects of the study described in this protocol. Patients with mild asthma (Part 2a and Part 3a): 1. Male and female (including WOCBP) patients with mild asthma aged 18 to 55 years with suitable veins for cannulation or repeated venipuncture. 2. Patients must be willing to remain in house at the study center for 16 consecutive days (part 2a) or for 30 consecutive days, optional from Day 17 for Germany (part 3a). 3. Have a BMI between 18 and 35 kg/m2 inclusive and weigh at least 50 kg. 4. Physician diagnosed (mild) asthma for at least 6 months prior to screening. 5. Lung function ≥70% predicted for Forced Expiratory Volume in 1 second (FEV1) at the Screening Visit AND at the 12 h timepoint on Day -1, in accordance with the American Thoracic Society (ATS)/European Respiratory Society (ERS) criteria. 6. Have a FeNO of ≥30 ppb at the Screening Visit and at the 12 h timepoint on Day -1. 7. Male patients and their WOCBP partners should be willing to use highly effective contraception measures and should refrain from donating sperm or fathering a child from the first day of dosing until 3 months after the last dose of IMP (applicable for part 2b and 3b). 8. Female patients should be willing to use highly effective contraception measures from the first day of dosing until 1 month after the last dose of IMP. 9. Provision of signed, written and dated informed consent for optional genetic research. If a patient declines to participate in the genetic component of the study, there will be no penalty or loss of benefit to the patient. The patient will not be excluded from other aspects of the study described in this protocol. Healthy volunteers (Part 2b and Part 3b): 1. Healthy male and female (including WOCBP) volunteers aged 18 to 55 years with suitable veins for cannulation or repeated venipuncture. 2. Have a BMI between 18 and 30 kg/m2 inclusive and weigh at least 60 kg. 3. Healthy volunteer has a Forced Expiratory Volume in one second (FEV1) ≥80% of the predicted value regarding age, height, gender and ethnicity at the Screening Visit and at the 12 h timepoint on Day -1, in accordance with the ATS/ERS criteria. 4. Female volunteers should be willing to use highly effective contraception measures from the first day of dosing until 1 month after the last dose of IMP. 5. Provision of signed, written and dated informed consent for optional genetic research. If a healthy volunteer declines to participate in the genetic component of the study, there will be no penalty or loss of benefit to the healthy volunteer. The healthy volunteer will not be excluded from other aspects of the study described in this protocol.

Exclusion criteria

Part 1a/b: 1. History of any clinically important disease or disorder which, in the opinion of the Investigator, may either put the volunteer at risk because of participation in the study, or influence the results or the volunteer's ability to participate in the study. 2. History of any respiratory disorders such as asthma, chronic obstructive pulmonary disease (COPD) or idiopathic pulmonary fibrosis (IPF) (applicable for all parts). 3. Healthy volunteer has an increased risk of infection. 4. History or presence of gastrointestinal, hepatic or renal disease or any other condition known to interfere with absorption, distribution, metabolism or excretion of drugs (applicable to all parts). 5. Any clinically important illness, medical/surgical procedure or trauma within 4 weeks of the first administration of IMP (applicable to all parts). 6. Any laboratory values with the following deviations at the Screening Visit and on admission to the Clinical Unit. Abnormal values may be repeated once at the discretion of the Investigator (applicable to all parts): 6.1. Alanine aminotransferase (ALT) \>upper limit of normal (ULN). 6.2. Aspartate aminotransferase (AST) \>ULN. 6.3. Creatinine \>ULN. 6.4. White blood cell (WBC) count \<LLN (Lower limit of normal). 6.5. Hemoglobin \<LLN. 7. Any clinically important abnormalities in clinical chemistry, hematology or urinalysis results, other than those described under

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants With Adverse Events and Serious Adverse Events	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)]	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.
Maximum Observed Plasma Concentration (Cmax)	Part 1b: Day 1	Cmax of AZD0449 following intravenous administration of a single dose to healthy participants was assessed.
Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUCinf)	Part 1b: Day 1	AUCinf of AZD0449 following intravenous administration of a single dose to healthy participants was assessed.
Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast)	Part 1b: Day 1	AUClast of AZD0449 following intravenous administration of a single dose to healthy participants was assessed.
Area Under the Plasma Concentration Time Curve From Time Zero to 24 Hours After Dosing (AUC(0-24))	Part 1b: Day 1	AUC (0-24) of AZD0449 following intravenous administration of a single dose to healthy participants was assessed.
Time to Reach Peak or Maximum Observed Concentration Following Drug Administration (Tmax)	Part 1b: Day 1	tmax of AZD0449 following intravenous administration of a single dose to healthy participants was assessed.
Terminal Halflife, Estimated as (ln2)/-λz (t½λz )	Part 1b: Day 1	t½λz of AZD0449 following intravenous administration of a single dose to healthy participants was assessed.
Total Body Clearance of Drug From Plasma After Intravascular Administration (CL)	Part 1b: Day 1	CL of AZD0449 following intravenous administration of a single dose of AZD0449 to healthy volunteers was assessed.
Volume of Distribution for Parent Drug at Terminal Phase [Intravenous Administration] (λz)	Part 1b: Day 1	Vz of AZD0449 following intravenous administration of a single dose of AZD0449 to healthy volunteers was assessed.
Terminal Rate Constant, Estimated by Loglinear Leastsquares Regression of the Terminal Part of the -Concentrationtime- Curve (λz)	Part 1b: Day 1	λz of AZD0449 following intravenous administration of a single dose to healthy participants was assessed.
Time of Last Quantifiable Concentration (Tlast)	Part 1b: Day 1	tlast of AZD0449 following intravenous administration of a single dose to healthy participants was assessed.
Dose Normalized Cmax (Cmax/D)	Part 1b: Day 1	Cmax/D of AZD0449 following intravenous administration of a single dose to healthy participants was assessed.

Secondary

Measure	Time frame	Description
Change From Baseline in 2 Hours Post-dose Fractional Excretion of Nitric Oxide (FeNO)	At Baseline and Day 12	Assessment of anti-inflammatory effect by evaluating change from baseline in FeNO, 2 hours post-dose of AZD0449 in patients with mild asthma was assessed.
Number of Participants With Adverse Events and Serious Adverse Events	From screening up to follow-up visit [Part 1b (6±1 Days post-dose)]	Safety and tolerability of AZD0449 following intravenous administration of a single dose to healthy participants was assessed.
Change From Baseline in 2 Hours Post-dose in FeNO (AUC (0-12))	At Baseline and Day 12	Assessment of anti-inflammatory effect by evaluating change from baseline in FeNO (AUC (0-12)), 2 hours post-dose of AZD0449 in patients with mild asthma was assessed.
Maximum Observed Plasma Concentration (Cmax)	Part 1a: Day 1, Part 2 and 3: Day 1 and Day 12	Cmax of AZD0449 following inhaled administration of single ascending doses of AZD0449, 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.
Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUCinf)	Part 1a: Day 1, Part 2 and 3: Day 1 and Day 12	AUCinf of AZD0449 following inhaled administration of single ascending doses of AZD0449, 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.
Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast)	Part 1a: Day 1, Part 2 and 3: Day 1 and Day 12	AUClast of AZD0449 following inhaled administration of single ascending doses of AZD0449, 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.
Area Under the Plasma Concentration Time Curve From Time Zero to 24 Hours After Dosing (AUC(0-24))	Part 1a: Day 1, Part 2 and 3: Day 1 and Day 12	AUC (0-24) of AZD0449 following inhaled administration of single ascending doses of AZD0449, inhaled nebulized administration of multiple ascending doses to healthy volunteers and patients with mild asthma, and repeated inhaled administration to patients with mild asthma using a DPI was assessed.
Time to Reach Peak or Maximum Observed Concentration Following Drug Administration (Tmax)	Part 1a: Day 1, Part 2 and 3: Day 1 and Day 12	tmax of AZD0449 following inhaled administration of single ascending doses of AZD0449, intravenous administration of a single dose to healthy volunteers, inhaled nebulized administration of multiple ascending doses to healthy volunteers and patients with mild asthma, and repeated inhaled administration to patients with mild asthma using a DPI was assessed.
Terminal Halflife, Estimated as (ln2)/-λz (t½λz )	Part 1a: Day 1, Part 2 and 3: Day 1 and Day 12	t½λz of AZD0449 following inhaled administration of single ascending doses of AZD0449, inhaled nebulized administration of multiple ascending doses to healthy volunteers and patients with mild asthma, and repeated inhaled administration to patients with mild asthma using a DPI was assessed.
Apparent Total Body Clearance of Drug From Plasma After Extravascular Administration (CL/F)	Part 1a: Day 1, Part 2 and 3: Day 1 and Day 12	CL/F of AZD0449 following inhaled administration of single ascending doses of AZD0449, inhaled nebulized administration of multiple ascending doses to healthy volunteers and patients with mild asthma, and repeated inhaled administration to patients with mild asthma using a DPI was assessed.
Apparent Volume of Distribution for Parent Drug at Terminal Phase [Extravascular Administration] (Vz/F)	Part 1a: Day 1, Part 2 and 3: Day 1 and Day 12	Vz/F of AZD0449 following inhaled administration of single ascending doses of AZD0449, inhaled nebulized administration of multiple ascending doses to healthy volunteers and patients with mild asthma, and repeated inhaled administration to patients with mild asthma using a DPI was assessed.
Terminal Rate Constant, Estimated by Loglinear Leastsquares Regression of the Terminal Part of the -Concentrationtime- Curve (λz)	Part 1a: Day 1, Part 2 and 3: Day 1 and Day 12	λz of AZD0449 following inhaled administration of single ascending doses of AZD0449, inhaled nebulized administration of multiple ascending doses to healthy volunteers and patients with mild asthma, and repeated inhaled administration to patients with mild asthma using a DPI was assessed.
Time of Last Quantifiable Concentration (Tlast)	Part 1a: Day 1, Part 2 and 3: Day 1 and Day 12	tlast of AZD0449 following inhaled administration of single ascending doses of AZD0449, inhaled nebulized administration of multiple ascending doses to healthy volunteers and patients with mild asthma, and repeated inhaled administration to patients with mild asthma using a DPI was assessed.
Dose Normalized Cmax (Cmax/D)	Part 1a: Day 1, Part 2 and 3: Day 1 and Day 12	Cmax/D of AZD0449 following inhaled administration of single ascending doses of AZD0449, inhaled nebulized administration of multiple ascending doses to healthy volunteers and patients with mild asthma, and repeated inhaled administration to patients with mild asthma using a DPI was assessed.

Countries

Germany, New Zealand, United Kingdom

Participant flow

Recruitment details

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.

Pre-assignment details

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).

Participants by arm

Arm	Count
Part 1a (SAD) Placebo Randomized healthy participants received Placebo for AZD0449.	12
Part 1a (SAD) Cohort 1 Randomized healthy participants received a single inhaled dose of AZD0449 0.095 mg nebulized suspension via Jet nebulizer.	6
Part 1a (SAD) Cohort 2 Randomized healthy participants received a single inhaled dose of AZD0449 0.28 mg nebulized suspension via Jet nebulizer.	6
Part 1a (SAD) Cohort 3 Randomized healthy participants received a single inhaled dose of AZD0449 0.84 mg nebulized suspension via Jet nebulizer.	6
Part 1a (SAD) Cohort 4 Randomized healthy participants received a single inhaled dose of AZD0449 1.60 mg nebulized suspension via Jet nebulizer.	6
Part 1a (SAD) Cohort 5 Randomized healthy participants received a single inhaled dose of AZD0449 3.20 mg nebulized suspension via Jet nebulizer.	6
Part 1a (SAD) Cohort 6 Randomized healthy participants received a single inhaled dose of AZD0449 5 mg nebulized suspension via Jet nebulizer.	6
Part 1b (SAD IV) Cohort 1 Randomized healthy participants received a single intravenous (IV) dose of AZD0449 0.090 mg solution.	6
Part 1b (SAD IV) Cohort 2 Randomized healthy participants received a single IV dose of AZD0449 0.360 mg solution.	6
Part 2a (MAD) Placebo Randomized patients with mild asthma received Placebo.	6
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.	6
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.	6
Part 2b (MAD) Cohort 1 Randomized healthy participants received a multiple inhaled of AZD0449 5 mg nebulized suspension via Jet nebulizer.	7
Part 2b (MAD) Placebo Randomized healthy participants received Placebo for AZD0449.	2
Part 3a (DPI/PoM) Randomized patients with mild asthma received a multiple inhaled dose of AZD0449 5 mg DPI.	18
Part 3a (DPI/PoM) Placebo Randomized patients with mild asthma received Placebo for AZD0449.	18
Part 3b (DPI/Healthy Participants) Placebo Randomized healthy participants received Placebo for AZD0449.	2
Part 3b (DPI/Healthy Participants) Randomized healthy participants received multiple inhaled dose of AZD0449 5 mg DPI.	6
Total	131

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003	FG004	FG005	FG006	FG007	FG008	FG009	FG010	FG011	FG012	FG013	FG014	FG015	FG016	FG017
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

Characteristic	Part 1a (SAD) Cohort 1	Part 1a (SAD) Placebo	Total	Part 3b (DPI/Healthy Participants)	Part 3b (DPI/Healthy Participants) Placebo	Part 3a (DPI/PoM) Placebo	Part 3a (DPI/PoM)	Part 2b (MAD) Placebo	Part 2b (MAD) Cohort 1	Part 2a (MAD) Cohort 2	Part 2a (MAD) Cohort 1	Part 2a (MAD) Placebo	Part 1b (SAD IV) Cohort 2	Part 1b (SAD IV) Cohort 1	Part 1a (SAD) Cohort 6	Part 1a (SAD) Cohort 5	Part 1a (SAD) Cohort 4	Part 1a (SAD) Cohort 3	Part 1a (SAD) Cohort 2
Age, Continuous	29.8 Years STANDARD_DEVIATION 6.6	31.7 Years STANDARD_DEVIATION 8.1	32.8 Years STANDARD_DEVIATION 9.8	36.8 Years STANDARD_DEVIATION 14.5	48.0 Years STANDARD_DEVIATION 4.2	30.2 Years STANDARD_DEVIATION 9.1	30.0 Years STANDARD_DEVIATION 9.2	33.0 Years STANDARD_DEVIATION 11.3	41.1 Years STANDARD_DEVIATION 9.4	38.7 Years STANDARD_DEVIATION 13.5	35.7 Years STANDARD_DEVIATION 13.7	37.5 Years STANDARD_DEVIATION 8.5	28.5 Years STANDARD_DEVIATION 4	32.8 Years STANDARD_DEVIATION 7.5	30.7 Years STANDARD_DEVIATION 10.4	35.8 Years STANDARD_DEVIATION 10.1	26.3 Years STANDARD_DEVIATION 5.5	36.3 Years STANDARD_DEVIATION 7.7	29.3 Years STANDARD_DEVIATION 7.6
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants	0 Participants	5 Participants	0 Participants	0 Participants	2 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	2 Participants	0 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	6 Participants	12 Participants	126 Participants	6 Participants	2 Participants	16 Participants	18 Participants	2 Participants	7 Participants	6 Participants	6 Participants	5 Participants	6 Participants	6 Participants	6 Participants	6 Participants	6 Participants	4 Participants	6 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	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	0 Participants	0 Participants	0 Participants
Race/Ethnicity, Customized American Indian or Alaska native	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	0 Participants	0 Participants	0 Participants
Race/Ethnicity, Customized Asian	1 Participants	1 Participants	11 Participants	1 Participants	0 Participants	0 Participants	2 Participants	0 Participants	0 Participants	1 Participants	0 Participants	1 Participants	1 Participants	0 Participants	0 Participants	0 Participants	1 Participants	1 Participants	1 Participants
Race/Ethnicity, Customized Black or African American	1 Participants	0 Participants	14 Participants	0 Participants	0 Participants	1 Participants	1 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	3 Participants	1 Participants	1 Participants	1 Participants	1 Participants	3 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	1 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
Race/Ethnicity, Customized Other	0 Participants	1 Participants	8 Participants	0 Participants	0 Participants	2 Participants	2 Participants	1 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race/Ethnicity, Customized White	4 Participants	10 Participants	97 Participants	5 Participants	2 Participants	14 Participants	13 Participants	1 Participants	7 Participants	5 Participants	5 Participants	4 Participants	5 Participants	3 Participants	4 Participants	5 Participants	4 Participants	4 Participants	2 Participants
Sex: Female, Male Female	0 Participants	0 Participants	25 Participants	2 Participants	0 Participants	8 Participants	9 Participants	0 Participants	0 Participants	2 Participants	0 Participants	0 Participants	4 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Sex: Female, Male Male	6 Participants	12 Participants	106 Participants	4 Participants	2 Participants	10 Participants	9 Participants	2 Participants	7 Participants	4 Participants	6 Participants	6 Participants	2 Participants	6 Participants	6 Participants	6 Participants	6 Participants	6 Participants	6 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk	EG005 affected / at risk	EG006 affected / at risk	EG007 affected / at risk	EG008 affected / at risk	EG009 affected / at risk	EG010 affected / at risk	EG011 affected / at risk	EG012 affected / at risk	EG013 affected / at risk	EG014 affected / at risk	EG015 affected / at risk	EG016 affected / at risk	EG017 affected / at risk
deaths Total, all-cause mortality	0 / 12	0 / 6	0 / 6	0 / 6	0 / 6	0 / 6	0 / 6	0 / 6	0 / 6	0 / 6	0 / 6	0 / 6	0 / 2	0 / 7	0 / 18	0 / 18	0 / 2	0 / 6
other Total, other adverse events	3 / 12	2 / 6	2 / 6	3 / 6	3 / 6	3 / 6	1 / 6	2 / 6	2 / 6	4 / 6	5 / 6	3 / 6	2 / 2	6 / 7	15 / 18	14 / 18	0 / 2	3 / 6
serious Total, serious adverse events	0 / 12	0 / 6	0 / 6	0 / 6	0 / 6	0 / 6	0 / 6	0 / 6	0 / 6	0 / 6	0 / 6	0 / 6	0 / 2	0 / 7	0 / 18	0 / 18	0 / 2	0 / 6

Outcome results

Primary

Area Under the Plasma Concentration Time Curve From Time Zero to 24 Hours After Dosing (AUC(0-24))

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

Time frame: 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.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Part 1a (SAD) Placebo	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
Part 1a (SAD) Cohort 1	Area Under the Plasma Concentration Time Curve From Time Zero to 24 Hours After Dosing (AUC(0-24))	17.03 hournanomole/L (hnmol/L)	Geometric Coefficient of Variation 20.18

Primary

Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUCinf)

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

Time frame: Part 1b: Day 1

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Part 1a (SAD) Placebo	Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUCinf)	3.697 h*nmol/L	Geometric Coefficient of Variation 14.27
Part 1a (SAD) Cohort 1	Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUCinf)	17.10 h*nmol/L	Geometric Coefficient of Variation 21.01

Primary

Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast)

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

Time frame: Part 1b: Day 1

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Part 1a (SAD) Placebo	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
Part 1a (SAD) Cohort 1	Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast)	16.94 h*nmol/L	Geometric Coefficient of Variation 20.39

Primary

Dose Normalized Cmax (Cmax/D)

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

Time frame: Part 1b: Day 1

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Part 1a (SAD) Placebo	Dose Normalized Cmax (Cmax/D)	22.81 (nmol/L)/milligram (mg)	Geometric Coefficient of Variation 15.95
Part 1a (SAD) Cohort 1	Dose Normalized Cmax (Cmax/D)	28.65 (nmol/L)/milligram (mg)	Geometric Coefficient of Variation 17.58

Primary

Maximum Observed Plasma Concentration (Cmax)

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

Time frame: 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.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Part 1a (SAD) Placebo	Maximum Observed Plasma Concentration (Cmax)	2.053 nanomole/liter (nmol/L)	Geometric Coefficient of Variation 15.95
Part 1a (SAD) Cohort 1	Maximum Observed Plasma Concentration (Cmax)	10.31 nanomole/liter (nmol/L)	Geometric Coefficient of Variation 17.58

Primary

Number of Participants With Adverse Events and Serious Adverse Events

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.

Time frame: 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.

Arm	Measure	Group	Value (NUMBER)
Part 1a (SAD) Placebo	Number of Participants With Adverse Events and Serious Adverse Events	Any serious AE (including events with outcome=death)	0 Participants
Part 1a (SAD) Placebo	Number of Participants With Adverse Events and Serious Adverse Events	Any Adverse Event (AE)	3 Participants
Part 1a (SAD) Placebo	Number of Participants With Adverse Events and Serious Adverse Events	Any AE with outcome=death	0 Participants
Part 1a (SAD) Placebo	Number of Participants With Adverse Events and Serious Adverse Events	Any AE leading to discontinuation of investigational medicinal product (IMP)	0 Participants
Part 1a (SAD) Placebo	Number of Participants With Adverse Events and Serious Adverse Events	Any AE leading to withdrawal from study	0 Participants
Part 1a (SAD) Cohort 1	Number of Participants With Adverse Events and Serious Adverse Events	Any AE leading to discontinuation of investigational medicinal product (IMP)	0 Participants
Part 1a (SAD) Cohort 1	Number of Participants With Adverse Events and Serious Adverse Events	Any Adverse Event (AE)	2 Participants
Part 1a (SAD) Cohort 1	Number of Participants With Adverse Events and Serious Adverse Events	Any AE leading to withdrawal from study	0 Participants
Part 1a (SAD) Cohort 1	Number of Participants With Adverse Events and Serious Adverse Events	Any AE with outcome=death	0 Participants
Part 1a (SAD) Cohort 1	Number of Participants With Adverse Events and Serious Adverse Events	Any serious AE (including events with outcome=death)	0 Participants
Part 1a (SAD) Cohort 2	Number of Participants With Adverse Events and Serious Adverse Events	Any AE leading to discontinuation of investigational medicinal product (IMP)	0 Participants
Part 1a (SAD) Cohort 2	Number of Participants With Adverse Events and Serious Adverse Events	Any serious AE (including events with outcome=death)	0 Participants
Part 1a (SAD) Cohort 2	Number of Participants With Adverse Events and Serious Adverse Events	Any AE leading to withdrawal from study	0 Participants
Part 1a (SAD) Cohort 2	Number of Participants With Adverse Events and Serious Adverse Events	Any Adverse Event (AE)	2 Participants
Part 1a (SAD) Cohort 2	Number of Participants With Adverse Events and Serious Adverse Events	Any AE with outcome=death	0 Participants
Part 1a (SAD) Cohort 3	Number of Participants With Adverse Events and Serious Adverse Events	Any AE leading to discontinuation of investigational medicinal product (IMP)	0 Participants
Part 1a (SAD) Cohort 3	Number of Participants With Adverse Events and Serious Adverse Events	Any AE with outcome=death	0 Participants
Part 1a (SAD) Cohort 3	Number of Participants With Adverse Events and Serious Adverse Events	Any serious AE (including events with outcome=death)	0 Participants
Part 1a (SAD) Cohort 3	Number of Participants With Adverse Events and Serious Adverse Events	Any AE leading to withdrawal from study	0 Participants
Part 1a (SAD) Cohort 3	Number of Participants With Adverse Events and Serious Adverse Events	Any Adverse Event (AE)	3 Participants
Part 1a (SAD) Cohort 4	Number of Participants With Adverse Events and Serious Adverse Events	Any AE with outcome=death	0 Participants
Part 1a (SAD) Cohort 4	Number of Participants With Adverse Events and Serious Adverse Events	Any AE leading to withdrawal from study	0 Participants
Part 1a (SAD) Cohort 4	Number of Participants With Adverse Events and Serious Adverse Events	Any AE leading to discontinuation of investigational medicinal product (IMP)	0 Participants
Part 1a (SAD) Cohort 4	Number of Participants With Adverse Events and Serious Adverse Events	Any serious AE (including events with outcome=death)	0 Participants
Part 1a (SAD) Cohort 4	Number of Participants With Adverse Events and Serious Adverse Events	Any Adverse Event (AE)	3 Participants
Part 1a (SAD) Cohort 5	Number of Participants With Adverse Events and Serious Adverse Events	Any AE leading to withdrawal from study	0 Participants
Part 1a (SAD) Cohort 5	Number of Participants With Adverse Events and Serious Adverse Events	Any Adverse Event (AE)	3 Participants
Part 1a (SAD) Cohort 5	Number of Participants With Adverse Events and Serious Adverse Events	Any serious AE (including events with outcome=death)	0 Participants
Part 1a (SAD) Cohort 5	Number of Participants With Adverse Events and Serious Adverse Events	Any AE with outcome=death	0 Participants
Part 1a (SAD) Cohort 5	Number of Participants With Adverse Events and Serious Adverse Events	Any AE leading to discontinuation of investigational medicinal product (IMP)	0 Participants
Part 1a (SAD) Cohort 6	Number of Participants With Adverse Events and Serious Adverse Events	Any serious AE (including events with outcome=death)	0 Participants
Part 1a (SAD) Cohort 6	Number of Participants With Adverse Events and Serious Adverse Events	Any AE with outcome=death	0 Participants
Part 1a (SAD) Cohort 6	Number of Participants With Adverse Events and Serious Adverse Events	Any AE leading to discontinuation of investigational medicinal product (IMP)	0 Participants
Part 1a (SAD) Cohort 6	Number of Participants With Adverse Events and Serious Adverse Events	Any Adverse Event (AE)	1 Participants
Part 1a (SAD) Cohort 6	Number of Participants With Adverse Events and Serious Adverse Events	Any AE leading to withdrawal from study	0 Participants
Part 2a (MAD) Placebo	Number of Participants With Adverse Events and Serious Adverse Events	Any Adverse Event (AE)	4 Participants
Part 2a (MAD) Placebo	Number of Participants With Adverse Events and Serious Adverse Events	Any AE leading to discontinuation of investigational medicinal product (IMP)	0 Participants
Part 2a (MAD) Placebo	Number of Participants With Adverse Events and Serious Adverse Events	Any AE with outcome=death	0 Participants
Part 2a (MAD) Placebo	Number of Participants With Adverse Events and Serious Adverse Events	Any AE leading to withdrawal from study	0 Participants
Part 2a (MAD) Placebo	Number of Participants With Adverse Events and Serious Adverse Events	Any serious AE (including events with outcome=death)	0 Participants
Part 2a (MAD) Cohort 1	Number of Participants With Adverse Events and Serious Adverse Events	Any AE leading to discontinuation of investigational medicinal product (IMP)	0 Participants
Part 2a (MAD) Cohort 1	Number of Participants With Adverse Events and Serious Adverse Events	Any Adverse Event (AE)	5 Participants
Part 2a (MAD) Cohort 1	Number of Participants With Adverse Events and Serious Adverse Events	Any serious AE (including events with outcome=death)	0 Participants
Part 2a (MAD) Cohort 1	Number of Participants With Adverse Events and Serious Adverse Events	Any AE with outcome=death	0 Participants
Part 2a (MAD) Cohort 1	Number of Participants With Adverse Events and Serious Adverse Events	Any AE leading to withdrawal from study	0 Participants
Part 2a (MAD) Cohort 2	Number of Participants With Adverse Events and Serious Adverse Events	Any Adverse Event (AE)	3 Participants
Part 2a (MAD) Cohort 2	Number of Participants With Adverse Events and Serious Adverse Events	Any AE leading to discontinuation of investigational medicinal product (IMP)	0 Participants
Part 2a (MAD) Cohort 2	Number of Participants With Adverse Events and Serious Adverse Events	Any AE with outcome=death	0 Participants
Part 2a (MAD) Cohort 2	Number of Participants With Adverse Events and Serious Adverse Events	Any serious AE (including events with outcome=death)	0 Participants
Part 2a (MAD) Cohort 2	Number of Participants With Adverse Events and Serious Adverse Events	Any AE leading to withdrawal from study	0 Participants
Part 2b (MAD) Placebo	Number of Participants With Adverse Events and Serious Adverse Events	Any AE leading to withdrawal from study	0 Participants
Part 2b (MAD) Placebo	Number of Participants With Adverse Events and Serious Adverse Events	Any AE with outcome=death	0 Participants
Part 2b (MAD) Placebo	Number of Participants With Adverse Events and Serious Adverse Events	Any serious AE (including events with outcome=death)	0 Participants
Part 2b (MAD) Placebo	Number of Participants With Adverse Events and Serious Adverse Events	Any AE leading to discontinuation of investigational medicinal product (IMP)	0 Participants
Part 2b (MAD) Placebo	Number of Participants With Adverse Events and Serious Adverse Events	Any Adverse Event (AE)	2 Participants
Part 2b (MAD) Cohort 1	Number of Participants With Adverse Events and Serious Adverse Events	Any AE leading to withdrawal from study	1 Participants
Part 2b (MAD) Cohort 1	Number of Participants With Adverse Events and Serious Adverse Events	Any AE with outcome=death	0 Participants
Part 2b (MAD) Cohort 1	Number of Participants With Adverse Events and Serious Adverse Events	Any serious AE (including events with outcome=death)	0 Participants
Part 2b (MAD) Cohort 1	Number of Participants With Adverse Events and Serious Adverse Events	Any Adverse Event (AE)	6 Participants
Part 2b (MAD) Cohort 1	Number of Participants With Adverse Events and Serious Adverse Events	Any AE leading to discontinuation of investigational medicinal product (IMP)	1 Participants
Part 3a (DPI/PoM) Placebo	Number of Participants With Adverse Events and Serious Adverse Events	Any AE with outcome=death	0 Participants
Part 3a (DPI/PoM) Placebo	Number of Participants With Adverse Events and Serious Adverse Events	Any serious AE (including events with outcome=death)	0 Participants
Part 3a (DPI/PoM) Placebo	Number of Participants With Adverse Events and Serious Adverse Events	Any AE leading to withdrawal from study	0 Participants
Part 3a (DPI/PoM) Placebo	Number of Participants With Adverse Events and Serious Adverse Events	Any Adverse Event (AE)	15 Participants
Part 3a (DPI/PoM) Placebo	Number of Participants With Adverse Events and Serious Adverse Events	Any AE leading to discontinuation of investigational medicinal product (IMP)	0 Participants
Part 3a (DPI/PoM)	Number of Participants With Adverse Events and Serious Adverse Events	Any Adverse Event (AE)	14 Participants
Part 3a (DPI/PoM)	Number of Participants With Adverse Events and Serious Adverse Events	Any serious AE (including events with outcome=death)	0 Participants
Part 3a (DPI/PoM)	Number of Participants With Adverse Events and Serious Adverse Events	Any AE with outcome=death	0 Participants
Part 3a (DPI/PoM)	Number of Participants With Adverse Events and Serious Adverse Events	Any AE leading to discontinuation of investigational medicinal product (IMP)	0 Participants
Part 3a (DPI/PoM)	Number of Participants With Adverse Events and Serious Adverse Events	Any AE leading to withdrawal from study	0 Participants
Part 3b (DPI/Healthy Participants) Placebo	Number of Participants With Adverse Events and Serious Adverse Events	Any AE with outcome=death	0 Participants
Part 3b (DPI/Healthy Participants) Placebo	Number of Participants With Adverse Events and Serious Adverse Events	Any AE leading to withdrawal from study	0 Participants
Part 3b (DPI/Healthy Participants) Placebo	Number of Participants With Adverse Events and Serious Adverse Events	Any AE leading to discontinuation of investigational medicinal product (IMP)	0 Participants
Part 3b (DPI/Healthy Participants) Placebo	Number of Participants With Adverse Events and Serious Adverse Events	Any Adverse Event (AE)	0 Participants
Part 3b (DPI/Healthy Participants) Placebo	Number of Participants With Adverse Events and Serious Adverse Events	Any serious AE (including events with outcome=death)	0 Participants
Part 3b (DPI/Healthy Participants)	Number of Participants With Adverse Events and Serious Adverse Events	Any Adverse Event (AE)	3 Participants
Part 3b (DPI/Healthy Participants)	Number of Participants With Adverse Events and Serious Adverse Events	Any AE leading to withdrawal from study	0 Participants
Part 3b (DPI/Healthy Participants)	Number of Participants With Adverse Events and Serious Adverse Events	Any AE leading to discontinuation of investigational medicinal product (IMP)	0 Participants
Part 3b (DPI/Healthy Participants)	Number of Participants With Adverse Events and Serious Adverse Events	Any serious AE (including events with outcome=death)	0 Participants
Part 3b (DPI/Healthy Participants)	Number of Participants With Adverse Events and Serious Adverse Events	Any AE with outcome=death	0 Participants

Primary

Terminal Halflife, Estimated as (ln2)/-λz (t½λz )

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

Time frame: Part 1b: Day 1

Arm	Measure	Value (MEAN)	Dispersion
Part 1a (SAD) Placebo	Terminal Halflife, Estimated as (ln2)/-λz (t½λz )	2.463 Hours	Standard Deviation 0.5698
Part 1a (SAD) Cohort 1	Terminal Halflife, Estimated as (ln2)/-λz (t½λz )	3.370 Hours	Standard Deviation 2.453

Primary

Terminal Rate Constant, Estimated by Loglinear Leastsquares Regression of the Terminal Part of the -Concentrationtime- Curve (λz)

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

Time frame: Part 1b: Day 1

Arm	Measure	Value (MEDIAN)
Part 1a (SAD) Placebo	Terminal Rate Constant, Estimated by Loglinear Leastsquares Regression of the Terminal Part of the -Concentrationtime- Curve (λz)	0.285 Hours
Part 1a (SAD) Cohort 1	Terminal Rate Constant, Estimated by Loglinear Leastsquares Regression of the Terminal Part of the -Concentrationtime- Curve (λz)	0.298 Hours

Primary

Time of Last Quantifiable Concentration (Tlast)

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

Time frame: Part 1b: Day 1

Arm	Measure	Value (MEDIAN)
Part 1a (SAD) Placebo	Time of Last Quantifiable Concentration (Tlast)	9.98 Hours
Part 1a (SAD) Cohort 1	Time of Last Quantifiable Concentration (Tlast)	15.00 Hours

Primary

Time to Reach Peak or Maximum Observed Concentration Following Drug Administration (Tmax)

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

Time frame: Part 1b: Day 1

Arm	Measure	Value (MEDIAN)
Part 1a (SAD) Placebo	Time to Reach Peak or Maximum Observed Concentration Following Drug Administration (Tmax)	1.00 Hours
Part 1a (SAD) Cohort 1	Time to Reach Peak or Maximum Observed Concentration Following Drug Administration (Tmax)	0.69 Hours

Primary

Total Body Clearance of Drug From Plasma After Intravascular Administration (CL)

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

Time frame: Part 1b: Day 1

Arm	Measure	Value (MEAN)	Dispersion
Part 1a (SAD) Placebo	Total Body Clearance of Drug From Plasma After Intravascular Administration (CL)	65.38 Liter/hour (L/h)	Standard Deviation 9.099
Part 1a (SAD) Cohort 1	Total Body Clearance of Drug From Plasma After Intravascular Administration (CL)	57.05 Liter/hour (L/h)	Standard Deviation 10.86

Primary

Volume of Distribution for Parent Drug at Terminal Phase [Intravenous Administration] (λz)

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

Time frame: Part 1b: Day 1

Arm	Measure	Value (MEAN)	Dispersion
Part 1a (SAD) Placebo	Volume of Distribution for Parent Drug at Terminal Phase [Intravenous Administration] (λz)	232.0 Liter	Standard Deviation 62.16
Part 1a (SAD) Cohort 1	Volume of Distribution for Parent Drug at Terminal Phase [Intravenous Administration] (λz)	248.3 Liter	Standard Deviation 109

Secondary

Apparent Total Body Clearance of Drug From Plasma After Extravascular Administration (CL/F)

CL/F of AZD0449 following inhaled administration of single ascending doses of AZD0449, inhaled nebulized administration of multiple ascending doses to healthy volunteers and patients with mild asthma, and repeated inhaled administration to patients with mild asthma using a DPI was assessed.

Time frame: Part 1a: Day 1, Part 2 and 3: Day 1 and Day 12

Population: The PK set consisted of all participants and patients 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.

Arm	Measure	Group	Value (MEAN)	Dispersion
Part 1a (SAD) Placebo	Apparent Total Body Clearance of Drug From Plasma After Extravascular Administration (CL/F)	Day 1	168.5 liter/hour (L/h)	Standard Deviation 101.9
Part 1a (SAD) Cohort 1	Apparent Total Body Clearance of Drug From Plasma After Extravascular Administration (CL/F)	Day 1	162.7 liter/hour (L/h)	Standard Deviation 73.35
Part 1a (SAD) Cohort 2	Apparent Total Body Clearance of Drug From Plasma After Extravascular Administration (CL/F)	Day 1	259.2 liter/hour (L/h)	Standard Deviation 360.3
Part 1a (SAD) Cohort 3	Apparent Total Body Clearance of Drug From Plasma After Extravascular Administration (CL/F)	Day 1	120.1 liter/hour (L/h)	Standard Deviation 10.39
Part 1a (SAD) Cohort 4	Apparent Total Body Clearance of Drug From Plasma After Extravascular Administration (CL/F)	Day 1	93.84 liter/hour (L/h)	Standard Deviation 35.34
Part 1a (SAD) Cohort 5	Apparent Total Body Clearance of Drug From Plasma After Extravascular Administration (CL/F)	Day 1	97.17 liter/hour (L/h)	Standard Deviation 26.31
Part 1a (SAD) Cohort 6	Apparent Total Body Clearance of Drug From Plasma After Extravascular Administration (CL/F)	Day 12	121.9 liter/hour (L/h)	Standard Deviation 44.38
Part 1a (SAD) Cohort 6	Apparent Total Body Clearance of Drug From Plasma After Extravascular Administration (CL/F)	Day 1	128.0 liter/hour (L/h)	Standard Deviation 21.67
Part 2a (MAD) Placebo	Apparent Total Body Clearance of Drug From Plasma After Extravascular Administration (CL/F)	Day 1	117.9 liter/hour (L/h)	Standard Deviation 26.32
Part 2a (MAD) Placebo	Apparent Total Body Clearance of Drug From Plasma After Extravascular Administration (CL/F)	Day 12	88.89 liter/hour (L/h)	Standard Deviation 28.36
Part 2a (MAD) Cohort 1	Apparent Total Body Clearance of Drug From Plasma After Extravascular Administration (CL/F)	Day 12	85.35 liter/hour (L/h)	Standard Deviation 29.74
Part 2a (MAD) Cohort 1	Apparent Total Body Clearance of Drug From Plasma After Extravascular Administration (CL/F)	Day 1	113.0 liter/hour (L/h)	Standard Deviation 37.98
Part 2a (MAD) Cohort 2	Apparent Total Body Clearance of Drug From Plasma After Extravascular Administration (CL/F)	Day 1	175.1 liter/hour (L/h)	Standard Deviation 87.78
Part 2a (MAD) Cohort 2	Apparent Total Body Clearance of Drug From Plasma After Extravascular Administration (CL/F)	Day 12	118.4 liter/hour (L/h)	Standard Deviation 66.81
Part 2b (MAD) Placebo	Apparent Total Body Clearance of Drug From Plasma After Extravascular Administration (CL/F)	Day 1	141.9 liter/hour (L/h)	Standard Deviation 41.92
Part 2b (MAD) Placebo	Apparent Total Body Clearance of Drug From Plasma After Extravascular Administration (CL/F)	Day 12	84.21 liter/hour (L/h)	Standard Deviation 28.88

Secondary

Apparent Volume of Distribution for Parent Drug at Terminal Phase [Extravascular Administration] (Vz/F)

Vz/F of AZD0449 following inhaled administration of single ascending doses of AZD0449, inhaled nebulized administration of multiple ascending doses to healthy volunteers and patients with mild asthma, and repeated inhaled administration to patients with mild asthma using a DPI was assessed.

Time frame: Part 1a: Day 1, Part 2 and 3: Day 1 and Day 12

Arm	Measure	Group	Value (MEAN)	Dispersion
Part 1a (SAD) Placebo	Apparent Volume of Distribution for Parent Drug at Terminal Phase [Extravascular Administration] (Vz/F)	Day 1	818.1 Liter	Standard Deviation 430.3
Part 1a (SAD) Cohort 1	Apparent Volume of Distribution for Parent Drug at Terminal Phase [Extravascular Administration] (Vz/F)	Day 1	1275 Liter	Standard Deviation 456.2
Part 1a (SAD) Cohort 2	Apparent Volume of Distribution for Parent Drug at Terminal Phase [Extravascular Administration] (Vz/F)	Day 1	2696 Liter	Standard Deviation 1301
Part 1a (SAD) Cohort 3	Apparent Volume of Distribution for Parent Drug at Terminal Phase [Extravascular Administration] (Vz/F)	Day 1	4180 Liter	Standard Deviation 620.1
Part 1a (SAD) Cohort 4	Apparent Volume of Distribution for Parent Drug at Terminal Phase [Extravascular Administration] (Vz/F)	Day 1	8110 Liter	Standard Deviation 3100
Part 1a (SAD) Cohort 5	Apparent Volume of Distribution for Parent Drug at Terminal Phase [Extravascular Administration] (Vz/F)	Day 1	12080 Liter	Standard Deviation 4962
Part 1a (SAD) Cohort 6	Apparent Volume of Distribution for Parent Drug at Terminal Phase [Extravascular Administration] (Vz/F)	Day 12	20620 Liter	Standard Deviation 18120
Part 1a (SAD) Cohort 6	Apparent Volume of Distribution for Parent Drug at Terminal Phase [Extravascular Administration] (Vz/F)	Day 1	3294 Liter	Standard Deviation 779.9
Part 2a (MAD) Placebo	Apparent Volume of Distribution for Parent Drug at Terminal Phase [Extravascular Administration] (Vz/F)	Day 1	3030 Liter	Standard Deviation 1666
Part 2a (MAD) Placebo	Apparent Volume of Distribution for Parent Drug at Terminal Phase [Extravascular Administration] (Vz/F)	Day 12	15970 Liter	Standard Deviation 11290
Part 2a (MAD) Cohort 1	Apparent Volume of Distribution for Parent Drug at Terminal Phase [Extravascular Administration] (Vz/F)	Day 1	2542 Liter	Standard Deviation 1340
Part 2a (MAD) Cohort 1	Apparent Volume of Distribution for Parent Drug at Terminal Phase [Extravascular Administration] (Vz/F)	Day 12	20470 Liter	Standard Deviation 13390
Part 2a (MAD) Cohort 2	Apparent Volume of Distribution for Parent Drug at Terminal Phase [Extravascular Administration] (Vz/F)	Day 1	3692 Liter	Standard Deviation 2537
Part 2a (MAD) Cohort 2	Apparent Volume of Distribution for Parent Drug at Terminal Phase [Extravascular Administration] (Vz/F)	Day 12	23520 Liter	Standard Deviation 20930
Part 2b (MAD) Placebo	Apparent Volume of Distribution for Parent Drug at Terminal Phase [Extravascular Administration] (Vz/F)	Day 12	15060 Liter	Standard Deviation 3134
Part 2b (MAD) Placebo	Apparent Volume of Distribution for Parent Drug at Terminal Phase [Extravascular Administration] (Vz/F)	Day 1	2977 Liter	Standard Deviation 1280

Secondary

Area Under the Plasma Concentration Time Curve From Time Zero to 24 Hours After Dosing (AUC(0-24))

AUC (0-24) of AZD0449 following inhaled administration of single ascending doses of AZD0449, inhaled nebulized administration of multiple ascending doses to healthy volunteers and patients with mild asthma, and repeated inhaled administration to patients with mild asthma using a DPI was assessed.

Time frame: Part 1a: Day 1, Part 2 and 3: Day 1 and Day 12

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Part 1a (SAD) Placebo	Area Under the Plasma Concentration Time Curve From Time Zero to 24 Hours After Dosing (AUC(0-24))	Day 1	1.692 hournanomole/L (hnmol/L)	Geometric Coefficient of Variation 58.94
Part 1a (SAD) Cohort 1	Area Under the Plasma Concentration Time Curve From Time Zero to 24 Hours After Dosing (AUC(0-24))	Day 1	4.798 hournanomole/L (hnmol/L)	Geometric Coefficient of Variation 43.67
Part 1a (SAD) Cohort 2	Area Under the Plasma Concentration Time Curve From Time Zero to 24 Hours After Dosing (AUC(0-24))	Day 1	13.09 hournanomole/L (hnmol/L)	Geometric Coefficient of Variation 118
Part 1a (SAD) Cohort 3	Area Under the Plasma Concentration Time Curve From Time Zero to 24 Hours After Dosing (AUC(0-24))	Day 1	29.46 hournanomole/L (hnmol/L)	Geometric Coefficient of Variation 11.16
Part 1a (SAD) Cohort 4	Area Under the Plasma Concentration Time Curve From Time Zero to 24 Hours After Dosing (AUC(0-24))	Day 1	66.64 hournanomole/L (hnmol/L)	Geometric Coefficient of Variation 27.05
Part 1a (SAD) Cohort 5	Area Under the Plasma Concentration Time Curve From Time Zero to 24 Hours After Dosing (AUC(0-24))	Day 1	94.029 hournanomole/L (hnmol/L)	Geometric Coefficient of Variation 35.49
Part 1a (SAD) Cohort 6	Area Under the Plasma Concentration Time Curve From Time Zero to 24 Hours After Dosing (AUC(0-24))	Day 12	27.39 hournanomole/L (hnmol/L)	Geometric Coefficient of Variation 31.38
Part 1a (SAD) Cohort 6	Area Under the Plasma Concentration Time Curve From Time Zero to 24 Hours After Dosing (AUC(0-24))	Day 1	21.67 hournanomole/L (hnmol/L)	Geometric Coefficient of Variation 13.03
Part 2a (MAD) Placebo	Area Under the Plasma Concentration Time Curve From Time Zero to 24 Hours After Dosing (AUC(0-24))	Day 1	50.07 hournanomole/L (hnmol/L)	Geometric Coefficient of Variation 24.64
Part 2a (MAD) Placebo	Area Under the Plasma Concentration Time Curve From Time Zero to 24 Hours After Dosing (AUC(0-24))	Day 12	78.12 hournanomole/L (hnmol/L)	Geometric Coefficient of Variation 32.39
Part 2a (MAD) Cohort 1	Area Under the Plasma Concentration Time Curve From Time Zero to 24 Hours After Dosing (AUC(0-24))	Day 1	112.3 hournanomole/L (hnmol/L)	Geometric Coefficient of Variation 50.33
Part 2a (MAD) Cohort 1	Area Under the Plasma Concentration Time Curve From Time Zero to 24 Hours After Dosing (AUC(0-24))	Day 12	166.4 hournanomole/L (hnmol/L)	Geometric Coefficient of Variation 43.85
Part 2a (MAD) Cohort 2	Area Under the Plasma Concentration Time Curve From Time Zero to 24 Hours After Dosing (AUC(0-24))	Day 1	69.00 hournanomole/L (hnmol/L)	Geometric Coefficient of Variation 38.24
Part 2a (MAD) Cohort 2	Area Under the Plasma Concentration Time Curve From Time Zero to 24 Hours After Dosing (AUC(0-24))	Day 12	125.6 hournanomole/L (hnmol/L)	Geometric Coefficient of Variation 48.14
Part 2b (MAD) Placebo	Area Under the Plasma Concentration Time Curve From Time Zero to 24 Hours After Dosing (AUC(0-24))	Day 12	167.9 hournanomole/L (hnmol/L)	Geometric Coefficient of Variation 41.54
Part 2b (MAD) Placebo	Area Under the Plasma Concentration Time Curve From Time Zero to 24 Hours After Dosing (AUC(0-24))	Day 1	80.87 hournanomole/L (hnmol/L)	Geometric Coefficient of Variation 31.67

Secondary

Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUCinf)

AUCinf of AZD0449 following inhaled administration of single ascending doses of AZD0449, 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.

Time frame: Part 1a: Day 1, Part 2 and 3: Day 1 and Day 12

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Part 1a (SAD) Placebo	Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUCinf)	Day 1	1.711 h*nmol/L	Geometric Coefficient of Variation 58.87
Part 1a (SAD) Cohort 1	Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUCinf)	Day 1	4.964 h*nmol/L	Geometric Coefficient of Variation 45.39
Part 1a (SAD) Cohort 2	Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUCinf)	Day 1	14.60 h*nmol/L	Geometric Coefficient of Variation 127.6
Part 1a (SAD) Cohort 3	Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUCinf)	Day 1	35.61 h*nmol/L	Geometric Coefficient of Variation 8.706
Part 1a (SAD) Cohort 4	Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUCinf)	Day 1	95.36 h*nmol/L	Geometric Coefficient of Variation 33.47
Part 1a (SAD) Cohort 5	Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUCinf)	Day 1	141.2 h*nmol/L	Geometric Coefficient of Variation 27.16
Part 1a (SAD) Cohort 6	Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUCinf)	Day 12	84.73 h*nmol/L	Geometric Coefficient of Variation 22.26
Part 1a (SAD) Cohort 6	Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUCinf)	Day 1	25.27 h*nmol/L	Geometric Coefficient of Variation 16.74
Part 2a (MAD) Placebo	Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUCinf)	Day 1	57.82 h*nmol/L	Geometric Coefficient of Variation 24.77
Part 2a (MAD) Placebo	Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUCinf)	Day 12	230.0 h*nmol/L	Geometric Coefficient of Variation 22.39
Part 2a (MAD) Cohort 1	Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUCinf)	Day 12	615.8 h*nmol/L	Geometric Coefficient of Variation 44.26
Part 2a (MAD) Cohort 1	Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUCinf)	Day 1	126.8 h*nmol/L	Geometric Coefficient of Variation 48.59
Part 2a (MAD) Cohort 2	Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUCinf)	Day 1	82.44 h*nmol/L	Geometric Coefficient of Variation 39.54
Part 2a (MAD) Cohort 2	Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUCinf)	Day 12	399.1 h*nmol/L	Geometric Coefficient of Variation 46.09
Part 2b (MAD) Placebo	Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUCinf)	Day 1	97.31 h*nmol/L	Geometric Coefficient of Variation 30.03
Part 2b (MAD) Placebo	Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUCinf)	Day 12	658.9 h*nmol/L	Geometric Coefficient of Variation 65.34

Secondary

Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast)

AUClast of AZD0449 following inhaled administration of single ascending doses of AZD0449, 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.

Time frame: Part 1a: Day 1, Part 2 and 3: Day 1 and Day 12

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Part 1a (SAD) Placebo	Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast)	Day 1	1.507 h*nmol/L	Geometric Coefficient of Variation 64.24
Part 1a (SAD) Cohort 1	Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast)	Day 1	4.608 h*nmol/L	Geometric Coefficient of Variation 48.35
Part 1a (SAD) Cohort 2	Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast)	Day 1	13.61 h*nmol/L	Geometric Coefficient of Variation 127.2
Part 1a (SAD) Cohort 3	Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast)	Day 1	32.17 h*nmol/L	Geometric Coefficient of Variation 10.01
Part 1a (SAD) Cohort 4	Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast)	Day 1	78.27 h*nmol/L	Geometric Coefficient of Variation 28.58
Part 1a (SAD) Cohort 5	Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast)	Day 1	121.8 h*nmol/L	Geometric Coefficient of Variation 31.83
Part 1a (SAD) Cohort 6	Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast)	Day 1	22.95 h*nmol/L	Geometric Coefficient of Variation 13.65
Part 1a (SAD) Cohort 6	Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast)	Day 12	61.90 h*nmol/L	Geometric Coefficient of Variation 30.97
Part 2a (MAD) Placebo	Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast)	Day 1	52.67 h*nmol/L	Geometric Coefficient of Variation 24.68
Part 2a (MAD) Placebo	Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast)	Day 12	182.8 h*nmol/L	Geometric Coefficient of Variation 29.08
Part 2a (MAD) Cohort 1	Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast)	Day 1	118.3 h*nmol/L	Geometric Coefficient of Variation 49.99
Part 2a (MAD) Cohort 1	Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast)	Day 12	509.6 h*nmol/L	Geometric Coefficient of Variation 48.5
Part 2a (MAD) Cohort 2	Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast)	Day 12	355.6 h*nmol/L	Geometric Coefficient of Variation 48.27
Part 2a (MAD) Cohort 2	Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast)	Day 1	74.54 h*nmol/L	Geometric Coefficient of Variation 38.78
Part 2b (MAD) Placebo	Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast)	Day 12	570.5 h*nmol/L	Geometric Coefficient of Variation 57
Part 2b (MAD) Placebo	Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast)	Day 1	87.87 h*nmol/L	Geometric Coefficient of Variation 31.91

Secondary

Change From Baseline in 2 Hours Post-dose Fractional Excretion of Nitric Oxide (FeNO)

Assessment of anti-inflammatory effect by evaluating change from baseline in FeNO, 2 hours post-dose of AZD0449 in patients with mild asthma was assessed.

Time frame: At Baseline and Day 12

Population: The Full Analysis Set (FAS) consisted of all participants randomized into the study who have received at least 1 dose of IMP and having at least one 2-hour post-dose FeNO assessment after the first IMP intake.

Arm	Measure	Value (LEAST_SQUARES_MEAN)
Part 1a (SAD) Placebo	Change From Baseline in 2 Hours Post-dose Fractional Excretion of Nitric Oxide (FeNO)	-22.6 parts per billion (ppb)
Part 1a (SAD) Cohort 1	Change From Baseline in 2 Hours Post-dose Fractional Excretion of Nitric Oxide (FeNO)	-22.2 parts per billion (ppb)
Part 1a (SAD) Cohort 2	Change From Baseline in 2 Hours Post-dose Fractional Excretion of Nitric Oxide (FeNO)	-14.3 parts per billion (ppb)
Part 1a (SAD) Cohort 3	Change From Baseline in 2 Hours Post-dose Fractional Excretion of Nitric Oxide (FeNO)	-15.0 parts per billion (ppb)
Part 1a (SAD) Cohort 4	Change From Baseline in 2 Hours Post-dose Fractional Excretion of Nitric Oxide (FeNO)	-12.0 parts per billion (ppb)

Comparison: Comparison of Part 2a (MAD) Cohort 1 Vs Part 2a (MAD) Cohort 2p-value: 0.951190% CI: [-12.9, 12]Linear Mixed Model

Comparison: Comparison of Part 2a (MAD) Cohort 2 Vs Part 2a (MAD) Placebop-value: 0.284990% CI: [-20.3, 4.59]Linear Mixed Model

Comparison: Comparison of Part 2a (MAD) Cohort 1 Vs Part 2a (MAD) Placebop-value: 0.259590% CI: [-20.8, 4.14]Linear Mixed Model

Comparison: Comparison of Part 3a (DPI/PoM) Vs Part 3a (DPI/PoM) Placebop-value: 0.360490% CI: [-8.6, 2.51]Linear Mixed Model

Secondary

Change From Baseline in 2 Hours Post-dose in FeNO (AUC (0-12))

Assessment of anti-inflammatory effect by evaluating change from baseline in FeNO (AUC (0-12)), 2 hours post-dose of AZD0449 in patients with mild asthma was assessed.

Time frame: At Baseline and Day 12

Arm	Measure	Value (LEAST_SQUARES_MEAN)
Part 1a (SAD) Placebo	Change From Baseline in 2 Hours Post-dose in FeNO (AUC (0-12))	-299 parts per billion (ppb)
Part 1a (SAD) Cohort 1	Change From Baseline in 2 Hours Post-dose in FeNO (AUC (0-12))	-274 parts per billion (ppb)
Part 1a (SAD) Cohort 2	Change From Baseline in 2 Hours Post-dose in FeNO (AUC (0-12))	-200 parts per billion (ppb)
Part 1a (SAD) Cohort 3	Change From Baseline in 2 Hours Post-dose in FeNO (AUC (0-12))	-213 parts per billion (ppb)
Part 1a (SAD) Cohort 4	Change From Baseline in 2 Hours Post-dose in FeNO (AUC (0-12))	-162 parts per billion (ppb)

Comparison: Comparison of Part 2a (MAD) Cohort 1 Vs Part 2a (MAD) Cohort 2p-value: 0.754490% CI: [-166, 115]Linear Mixed Model

Comparison: Comparison of Part 2a (MAD) Cohort 2 Vs Part 2a (MAD) Placebop-value: 0.37590% CI: [-214, 67.6]Linear Mixed Model

Comparison: Comparison of Part 2a (MAD) Cohort 1 Vs Part 2a (MAD) Placebop-value: 0.237790% CI: [-240, 42.3]Linear Mixed Model

Comparison: Comparison of Part 3a (DPI/PoM) Vs Part 3a (DPI/PoM) Placebop-value: 0.110590% CI: [-102, 1.61]Linear Mixed Model

Secondary

Dose Normalized Cmax (Cmax/D)

Cmax/D of AZD0449 following inhaled administration of single ascending doses of AZD0449, inhaled nebulized administration of multiple ascending doses to healthy volunteers and patients with mild asthma, and repeated inhaled administration to patients with mild asthma using a DPI was assessed.

Time frame: Part 1a: Day 1, Part 2 and 3: Day 1 and Day 12

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Part 1a (SAD) Placebo	Dose Normalized Cmax (Cmax/D)	Day 1	4.589 (nmol/L)/milligram (mg)	Geometric Coefficient of Variation 54.69
Part 1a (SAD) Cohort 1	Dose Normalized Cmax (Cmax/D)	Day 1	6.396 (nmol/L)/milligram (mg)	Geometric Coefficient of Variation 26.72
Part 1a (SAD) Cohort 2	Dose Normalized Cmax (Cmax/D)	Day 1	4.831 (nmol/L)/milligram (mg)	Geometric Coefficient of Variation 68.59
Part 1a (SAD) Cohort 3	Dose Normalized Cmax (Cmax/D)	Day 1	5.404 (nmol/L)/milligram (mg)	Geometric Coefficient of Variation 37.45
Part 1a (SAD) Cohort 4	Dose Normalized Cmax (Cmax/D)	Day 1	6.047 (nmol/L)/milligram (mg)	Geometric Coefficient of Variation 20.56
Part 1a (SAD) Cohort 5	Dose Normalized Cmax (Cmax/D)	Day 1	5.226 (nmol/L)/milligram (mg)	Geometric Coefficient of Variation 48.72
Part 1a (SAD) Cohort 6	Dose Normalized Cmax (Cmax/D)	Day 1	3.897 (nmol/L)/milligram (mg)	Geometric Coefficient of Variation 18.64
Part 1a (SAD) Cohort 6	Dose Normalized Cmax (Cmax/D)	Day 12	3.897 (nmol/L)/milligram (mg)	Geometric Coefficient of Variation 39.84
Part 2a (MAD) Placebo	Dose Normalized Cmax (Cmax/D)	Day 12	5.248 (nmol/L)/milligram (mg)	Geometric Coefficient of Variation 24.59
Part 2a (MAD) Placebo	Dose Normalized Cmax (Cmax/D)	Day 1	4.837 (nmol/L)/milligram (mg)	Geometric Coefficient of Variation 32.95
Part 2a (MAD) Cohort 1	Dose Normalized Cmax (Cmax/D)	Day 12	6.730 (nmol/L)/milligram (mg)	Geometric Coefficient of Variation 39.61
Part 2a (MAD) Cohort 1	Dose Normalized Cmax (Cmax/D)	Day 1	6.775 (nmol/L)/milligram (mg)	Geometric Coefficient of Variation 39.92
Part 2a (MAD) Cohort 2	Dose Normalized Cmax (Cmax/D)	Day 1	2.468 (nmol/L)/milligram (mg)	Geometric Coefficient of Variation 35.66
Part 2a (MAD) Cohort 2	Dose Normalized Cmax (Cmax/D)	Day 12	3.265 (nmol/L)/milligram (mg)	Geometric Coefficient of Variation 42.77
Part 2b (MAD) Placebo	Dose Normalized Cmax (Cmax/D)	Day 1	2.582 (nmol/L)/milligram (mg)	Geometric Coefficient of Variation 29.36
Part 2b (MAD) Placebo	Dose Normalized Cmax (Cmax/D)	Day 12	3.811 (nmol/L)/milligram (mg)	Geometric Coefficient of Variation 39.71

Secondary

Maximum Observed Plasma Concentration (Cmax)

Cmax of AZD0449 following inhaled administration of single ascending doses of AZD0449, 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.

Time frame: Part 1a: Day 1, Part 2 and 3: Day 1 and Day 12

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Part 1a (SAD) Placebo	Maximum Observed Plasma Concentration (Cmax)	Day 1	0.4360 nanomole/liter (nmol/L)	Geometric Coefficient of Variation 54.69
Part 1a (SAD) Placebo	Maximum Observed Plasma Concentration (Cmax)	Day 12	NA nanomole/liter (nmol/L)	—
Part 1a (SAD) Cohort 1	Maximum Observed Plasma Concentration (Cmax)	Day 12	NA nanomole/liter (nmol/L)	—
Part 1a (SAD) Cohort 1	Maximum Observed Plasma Concentration (Cmax)	Day 1	1.791 nanomole/liter (nmol/L)	Geometric Coefficient of Variation 26.72
Part 1a (SAD) Cohort 2	Maximum Observed Plasma Concentration (Cmax)	Day 1	4.058 nanomole/liter (nmol/L)	Geometric Coefficient of Variation 68.59
Part 1a (SAD) Cohort 2	Maximum Observed Plasma Concentration (Cmax)	Day 12	NA nanomole/liter (nmol/L)	—
Part 1a (SAD) Cohort 3	Maximum Observed Plasma Concentration (Cmax)	Day 12	NA nanomole/liter (nmol/L)	—
Part 1a (SAD) Cohort 3	Maximum Observed Plasma Concentration (Cmax)	Day 1	8.646 nanomole/liter (nmol/L)	Geometric Coefficient of Variation 37.45
Part 1a (SAD) Cohort 4	Maximum Observed Plasma Concentration (Cmax)	Day 1	19.35 nanomole/liter (nmol/L)	Geometric Coefficient of Variation 20.56
Part 1a (SAD) Cohort 4	Maximum Observed Plasma Concentration (Cmax)	Day 12	NA nanomole/liter (nmol/L)	—
Part 1a (SAD) Cohort 5	Maximum Observed Plasma Concentration (Cmax)	Day 12	NA nanomole/liter (nmol/L)	—
Part 1a (SAD) Cohort 5	Maximum Observed Plasma Concentration (Cmax)	Day 1	26.13 nanomole/liter (nmol/L)	Geometric Coefficient of Variation 48.72
Part 1a (SAD) Cohort 6	Maximum Observed Plasma Concentration (Cmax)	Day 12	4.676 nanomole/liter (nmol/L)	Geometric Coefficient of Variation 39.84
Part 1a (SAD) Cohort 6	Maximum Observed Plasma Concentration (Cmax)	Day 1	4.676 nanomole/liter (nmol/L)	Geometric Coefficient of Variation 18.64
Part 2a (MAD) Placebo	Maximum Observed Plasma Concentration (Cmax)	Day 12	13.12 nanomole/liter (nmol/L)	Geometric Coefficient of Variation 24.59
Part 2a (MAD) Placebo	Maximum Observed Plasma Concentration (Cmax)	Day 1	12.09 nanomole/liter (nmol/L)	Geometric Coefficient of Variation 32.95
Part 2a (MAD) Cohort 1	Maximum Observed Plasma Concentration (Cmax)	Day 1	33.87 nanomole/liter (nmol/L)	Geometric Coefficient of Variation 39.92
Part 2a (MAD) Cohort 1	Maximum Observed Plasma Concentration (Cmax)	Day 12	33.65 nanomole/liter (nmol/L)	Geometric Coefficient of Variation 39.61
Part 2a (MAD) Cohort 2	Maximum Observed Plasma Concentration (Cmax)	Day 1	12.34 nanomole/liter (nmol/L)	Geometric Coefficient of Variation 35.66
Part 2a (MAD) Cohort 2	Maximum Observed Plasma Concentration (Cmax)	Day 12	16.32 nanomole/liter (nmol/L)	Geometric Coefficient of Variation 42.77
Part 2b (MAD) Placebo	Maximum Observed Plasma Concentration (Cmax)	Day 12	19.05 nanomole/liter (nmol/L)	Geometric Coefficient of Variation 39.71
Part 2b (MAD) Placebo	Maximum Observed Plasma Concentration (Cmax)	Day 1	12.91 nanomole/liter (nmol/L)	Geometric Coefficient of Variation 29.36

Secondary

Number of Participants With Adverse Events and Serious Adverse Events

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

Time frame: 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.

Arm	Measure	Group	Value (NUMBER)
Part 1a (SAD) Placebo	Number of Participants With Adverse Events and Serious Adverse Events	Any AE with outcome=death	0 Participants
Part 1a (SAD) Placebo	Number of Participants With Adverse Events and Serious Adverse Events	Any AE leading to withdrawal from study	0 Participants
Part 1a (SAD) Placebo	Number of Participants With Adverse Events and Serious Adverse Events	Any serious AE (including events with outcome=death)	0 Participants
Part 1a (SAD) Placebo	Number of Participants With Adverse Events and Serious Adverse Events	Any AE leading to discontinuation of investigational medicinal product (IMP)	0 Participants
Part 1a (SAD) Placebo	Number of Participants With Adverse Events and Serious Adverse Events	Any Adverse Event (AE)	2 Participants
Part 1a (SAD) Cohort 1	Number of Participants With Adverse Events and Serious Adverse Events	Any AE leading to discontinuation of investigational medicinal product (IMP)	0 Participants
Part 1a (SAD) Cohort 1	Number of Participants With Adverse Events and Serious Adverse Events	Any Adverse Event (AE)	2 Participants
Part 1a (SAD) Cohort 1	Number of Participants With Adverse Events and Serious Adverse Events	Any AE with outcome=death	0 Participants
Part 1a (SAD) Cohort 1	Number of Participants With Adverse Events and Serious Adverse Events	Any serious AE (including events with outcome=death)	0 Participants
Part 1a (SAD) Cohort 1	Number of Participants With Adverse Events and Serious Adverse Events	Any AE leading to withdrawal from study	0 Participants

Secondary

Terminal Halflife, Estimated as (ln2)/-λz (t½λz )

t½λz of AZD0449 following inhaled administration of single ascending doses of AZD0449, inhaled nebulized administration of multiple ascending doses to healthy volunteers and patients with mild asthma, and repeated inhaled administration to patients with mild asthma using a DPI was assessed.

Time frame: Part 1a: Day 1, Part 2 and 3: Day 1 and Day 12

Arm	Measure	Group	Value (MEAN)	Dispersion
Part 1a (SAD) Placebo	Terminal Halflife, Estimated as (ln2)/-λz (t½λz )	Day 1	3.603 Hours	Standard Deviation 1.281
Part 1a (SAD) Cohort 1	Terminal Halflife, Estimated as (ln2)/-λz (t½λz )	Day 1	6.049 Hours	Standard Deviation 2.481
Part 1a (SAD) Cohort 2	Terminal Halflife, Estimated as (ln2)/-λz (t½λz )	Day 1	12.51 Hours	Standard Deviation 5.169
Part 1a (SAD) Cohort 3	Terminal Halflife, Estimated as (ln2)/-λz (t½λz )	Day 1	24.07 Hours	Standard Deviation 2.592
Part 1a (SAD) Cohort 4	Terminal Halflife, Estimated as (ln2)/-λz (t½λz )	Day 1	63.56 Hours	Standard Deviation 30.66
Part 1a (SAD) Cohort 5	Terminal Halflife, Estimated as (ln2)/-λz (t½λz )	Day 1	84.26 Hours	Standard Deviation 23.19
Part 1a (SAD) Cohort 6	Terminal Halflife, Estimated as (ln2)/-λz (t½λz )	Day 12	104.9 Hours	Standard Deviation 43.78
Part 1a (SAD) Cohort 6	Terminal Halflife, Estimated as (ln2)/-λz (t½λz )	Day 1	18.43 Hours	Standard Deviation 6.029
Part 2a (MAD) Placebo	Terminal Halflife, Estimated as (ln2)/-λz (t½λz )	Day 12	115.2 Hours	Standard Deviation 42.21
Part 2a (MAD) Placebo	Terminal Halflife, Estimated as (ln2)/-λz (t½λz )	Day 1	18.35 Hours	Standard Deviation 9.705
Part 2a (MAD) Cohort 1	Terminal Halflife, Estimated as (ln2)/-λz (t½λz )	Day 1	14.94 Hours	Standard Deviation 3.707
Part 2a (MAD) Cohort 1	Terminal Halflife, Estimated as (ln2)/-λz (t½λz )	Day 12	160.0 Hours	Standard Deviation 63.96
Part 2a (MAD) Cohort 2	Terminal Halflife, Estimated as (ln2)/-λz (t½λz )	Day 1	14.93 Hours	Standard Deviation 8.198
Part 2a (MAD) Cohort 2	Terminal Halflife, Estimated as (ln2)/-λz (t½λz )	Day 12	124.4 Hours	Standard Deviation 53.54
Part 2b (MAD) Placebo	Terminal Halflife, Estimated as (ln2)/-λz (t½λz )	Day 12	132.5 Hours	Standard Deviation 33.23
Part 2b (MAD) Placebo	Terminal Halflife, Estimated as (ln2)/-λz (t½λz )	Day 1	14.09 Hours	Standard Deviation 2.7171

Secondary

Terminal Rate Constant, Estimated by Loglinear Leastsquares Regression of the Terminal Part of the -Concentrationtime- Curve (λz)

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

Time frame: Part 1a: Day 1, Part 2 and 3: Day 1 and Day 12

Arm	Measure	Group	Value (MEDIAN)
Part 1a (SAD) Placebo	Terminal Rate Constant, Estimated by Loglinear Leastsquares Regression of the Terminal Part of the -Concentrationtime- Curve (λz)	Day 1	0.210 Hours
Part 1a (SAD) Cohort 1	Terminal Rate Constant, Estimated by Loglinear Leastsquares Regression of the Terminal Part of the -Concentrationtime- Curve (λz)	Day 1	0.105 Hours
Part 1a (SAD) Cohort 2	Terminal Rate Constant, Estimated by Loglinear Leastsquares Regression of the Terminal Part of the -Concentrationtime- Curve (λz)	Day 1	0.055 Hours
Part 1a (SAD) Cohort 3	Terminal Rate Constant, Estimated by Loglinear Leastsquares Regression of the Terminal Part of the -Concentrationtime- Curve (λz)	Day 1	0.027 Hours
Part 1a (SAD) Cohort 4	Terminal Rate Constant, Estimated by Loglinear Leastsquares Regression of the Terminal Part of the -Concentrationtime- Curve (λz)	Day 1	0.013 Hours
Part 1a (SAD) Cohort 5	Terminal Rate Constant, Estimated by Loglinear Leastsquares Regression of the Terminal Part of the -Concentrationtime- Curve (λz)	Day 1	0.008 Hours
Part 1a (SAD) Cohort 6	Terminal Rate Constant, Estimated by Loglinear Leastsquares Regression of the Terminal Part of the -Concentrationtime- Curve (λz)	Day 12	0.008 Hours
Part 1a (SAD) Cohort 6	Terminal Rate Constant, Estimated by Loglinear Leastsquares Regression of the Terminal Part of the -Concentrationtime- Curve (λz)	Day 1	0.041 Hours
Part 2a (MAD) Placebo	Terminal Rate Constant, Estimated by Loglinear Leastsquares Regression of the Terminal Part of the -Concentrationtime- Curve (λz)	Day 1	0.038 Hours
Part 2a (MAD) Placebo	Terminal Rate Constant, Estimated by Loglinear Leastsquares Regression of the Terminal Part of the -Concentrationtime- Curve (λz)	Day 12	0.006 Hours
Part 2a (MAD) Cohort 1	Terminal Rate Constant, Estimated by Loglinear Leastsquares Regression of the Terminal Part of the -Concentrationtime- Curve (λz)	Day 1	0.053 Hours
Part 2a (MAD) Cohort 1	Terminal Rate Constant, Estimated by Loglinear Leastsquares Regression of the Terminal Part of the -Concentrationtime- Curve (λz)	Day 12	0.004 Hours
Part 2a (MAD) Cohort 2	Terminal Rate Constant, Estimated by Loglinear Leastsquares Regression of the Terminal Part of the -Concentrationtime- Curve (λz)	Day 1	0.057 Hours
Part 2a (MAD) Cohort 2	Terminal Rate Constant, Estimated by Loglinear Leastsquares Regression of the Terminal Part of the -Concentrationtime- Curve (λz)	Day 12	0.005 Hours
Part 2b (MAD) Placebo	Terminal Rate Constant, Estimated by Loglinear Leastsquares Regression of the Terminal Part of the -Concentrationtime- Curve (λz)	Day 12	0.005 Hours
Part 2b (MAD) Placebo	Terminal Rate Constant, Estimated by Loglinear Leastsquares Regression of the Terminal Part of the -Concentrationtime- Curve (λz)	Day 1	0.048 Hours

Secondary

Time of Last Quantifiable Concentration (Tlast)

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

Time frame: Part 1a: Day 1, Part 2 and 3: Day 1 and Day 12

Arm	Measure	Group	Value (MEDIAN)
Part 1a (SAD) Placebo	Time of Last Quantifiable Concentration (Tlast)	Day 1	10.05 Hours
Part 1a (SAD) Cohort 1	Time of Last Quantifiable Concentration (Tlast)	Day 1	17.99 Hours
Part 1a (SAD) Cohort 2	Time of Last Quantifiable Concentration (Tlast)	Day 1	36.02 Hours
Part 1a (SAD) Cohort 3	Time of Last Quantifiable Concentration (Tlast)	Day 1	48.19 Hours
Part 1a (SAD) Cohort 4	Time of Last Quantifiable Concentration (Tlast)	Day 1	71.88 Hours
Part 1a (SAD) Cohort 5	Time of Last Quantifiable Concentration (Tlast)	Day 1	144.41 Hours
Part 1a (SAD) Cohort 6	Time of Last Quantifiable Concentration (Tlast)	Day 12	168.03 Hours
Part 1a (SAD) Cohort 6	Time of Last Quantifiable Concentration (Tlast)	Day 1	36.02 Hours
Part 2a (MAD) Placebo	Time of Last Quantifiable Concentration (Tlast)	Day 12	228.38 Hours
Part 2a (MAD) Placebo	Time of Last Quantifiable Concentration (Tlast)	Day 1	36.00 Hours
Part 2a (MAD) Cohort 1	Time of Last Quantifiable Concentration (Tlast)	Day 12	359.96 Hours
Part 2a (MAD) Cohort 1	Time of Last Quantifiable Concentration (Tlast)	Day 1	35.95 Hours
Part 2a (MAD) Cohort 2	Time of Last Quantifiable Concentration (Tlast)	Day 12	359.99 Hours
Part 2a (MAD) Cohort 2	Time of Last Quantifiable Concentration (Tlast)	Day 1	36.02 Hours
Part 2b (MAD) Placebo	Time of Last Quantifiable Concentration (Tlast)	Day 1	36.02 Hours
Part 2b (MAD) Placebo	Time of Last Quantifiable Concentration (Tlast)	Day 12	360.00 Hours

Secondary

Time to Reach Peak or Maximum Observed Concentration Following Drug Administration (Tmax)

tmax of AZD0449 following inhaled administration of single ascending doses of AZD0449, intravenous administration of a single dose to healthy volunteers, inhaled nebulized administration of multiple ascending doses to healthy volunteers and patients with mild asthma, and repeated inhaled administration to patients with mild asthma using a DPI was assessed.

Time frame: Part 1a: Day 1, Part 2 and 3: Day 1 and Day 12

Arm	Measure	Group	Value (MEDIAN)
Part 1a (SAD) Placebo	Time to Reach Peak or Maximum Observed Concentration Following Drug Administration (Tmax)	Day 1	1.00 Hours
Part 1a (SAD) Cohort 1	Time to Reach Peak or Maximum Observed Concentration Following Drug Administration (Tmax)	Day 1	0.15 Hours
Part 1a (SAD) Cohort 2	Time to Reach Peak or Maximum Observed Concentration Following Drug Administration (Tmax)	Day 1	0.10 Hours
Part 1a (SAD) Cohort 3	Time to Reach Peak or Maximum Observed Concentration Following Drug Administration (Tmax)	Day 1	0.36 Hours
Part 1a (SAD) Cohort 4	Time to Reach Peak or Maximum Observed Concentration Following Drug Administration (Tmax)	Day 1	0.34 Hours
Part 1a (SAD) Cohort 5	Time to Reach Peak or Maximum Observed Concentration Following Drug Administration (Tmax)	Day 1	0.50 Hours
Part 1a (SAD) Cohort 6	Time to Reach Peak or Maximum Observed Concentration Following Drug Administration (Tmax)	Day 12	1.00 Hours
Part 1a (SAD) Cohort 6	Time to Reach Peak or Maximum Observed Concentration Following Drug Administration (Tmax)	Day 1	0.20 Hours
Part 2a (MAD) Placebo	Time to Reach Peak or Maximum Observed Concentration Following Drug Administration (Tmax)	Day 1	2.01 Hours
Part 2a (MAD) Placebo	Time to Reach Peak or Maximum Observed Concentration Following Drug Administration (Tmax)	Day 12	0.23 Hours
Part 2a (MAD) Cohort 1	Time to Reach Peak or Maximum Observed Concentration Following Drug Administration (Tmax)	Day 12	0.51 Hours
Part 2a (MAD) Cohort 1	Time to Reach Peak or Maximum Observed Concentration Following Drug Administration (Tmax)	Day 1	0.43 Hours
Part 2a (MAD) Cohort 2	Time to Reach Peak or Maximum Observed Concentration Following Drug Administration (Tmax)	Day 1	1.25 Hours
Part 2a (MAD) Cohort 2	Time to Reach Peak or Maximum Observed Concentration Following Drug Administration (Tmax)	Day 12	1.58 Hours
Part 2b (MAD) Placebo	Time to Reach Peak or Maximum Observed Concentration Following Drug Administration (Tmax)	Day 1	2.00 Hours
Part 2b (MAD) Placebo	Time to Reach Peak or Maximum Observed Concentration Following Drug Administration (Tmax)	Day 12	1.04 Hours

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026

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

Conditions

Keywords

Brief summary

Detailed description

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Recruitment details

Pre-assignment details

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

Area Under the Plasma Concentration Time Curve From Time Zero to 24 Hours After Dosing (AUC(0-24))

Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUCinf)

Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast)

Dose Normalized Cmax (Cmax/D)

Maximum Observed Plasma Concentration (Cmax)

Number of Participants With Adverse Events and Serious Adverse Events

Terminal Halflife, Estimated as (ln2)/-λz (t½λz )

Terminal Rate Constant, Estimated by Loglinear Leastsquares Regression of the Terminal Part of the -Concentrationtime- Curve (λz)

Time of Last Quantifiable Concentration (Tlast)

Time to Reach Peak or Maximum Observed Concentration Following Drug Administration (Tmax)

Total Body Clearance of Drug From Plasma After Intravascular Administration (CL)

Volume of Distribution for Parent Drug at Terminal Phase [Intravenous Administration] (λz)

Apparent Total Body Clearance of Drug From Plasma After Extravascular Administration (CL/F)

Apparent Volume of Distribution for Parent Drug at Terminal Phase [Extravascular Administration] (Vz/F)

Area Under the Plasma Concentration Time Curve From Time Zero to 24 Hours After Dosing (AUC(0-24))

Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUCinf)

Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast)

Change From Baseline in 2 Hours Post-dose Fractional Excretion of Nitric Oxide (FeNO)

Change From Baseline in 2 Hours Post-dose in FeNO (AUC (0-12))

Dose Normalized Cmax (Cmax/D)

Maximum Observed Plasma Concentration (Cmax)

Number of Participants With Adverse Events and Serious Adverse Events

Terminal Halflife, Estimated as (ln2)/-λz (t½λz )

Terminal Rate Constant, Estimated by Loglinear Leastsquares Regression of the Terminal Part of the -Concentrationtime- Curve (λz)

Time of Last Quantifiable Concentration (Tlast)

Time to Reach Peak or Maximum Observed Concentration Following Drug Administration (Tmax)