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| ID | Type | Description | Link |
|---|---|---|---|
| 2018-003469-32 | EudraCT Number |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part 1a (SAD) Cohort 1 | Experimental | 6 participants will receive inhaled dose 1 of AZD0449 nebulized suspension and 2 participants will receive inhaled placebo. |
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| Part 1a (SAD) Cohort 2 | Experimental | 6 participants will receive inhaled dose 2 of AZD0449 nebulized suspension and 2 participants will receive inhaled placebo. |
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| Part 1a (SAD) Cohort 3 | Experimental | 6 participants will receive inhaled dose 3 of AZD0449 nebulized suspension and 2 participants will receive inhaled placebo. |
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| Part 1a (SAD) Cohort 4 | Experimental | 6 participants will receive inhaled dose 4 of AZD0449 nebulized suspension and 2 participants will receive inhaled placebo. |
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| Part 1a (SAD) Cohort 5 | Placebo Comparator | 6 participants will receive inhaled dose 5 of AZD0449 nebulized suspension and 2 participants will receive inhaled placebo. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| AZD0449 | Drug | Participants will receive single inhaled AZD0449 nebulizer suspension and single IV dose of AZD0449 solution. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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)] |
| Maximum Observed Plasma Concentration (Cmax) | Cmax of AZD0449 following intravenous administration of a single dose to healthy participants was assessed. | Part 1b: Day 1 |
| 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. | Part 1b: Day 1 |
| 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. | Part 1b: Day 1 |
| 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. | Part 1b: Day 1 |
| Time to Reach Peak or Maximum Observed Concentration Following Drug Administration (Tmax) |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | From screening up to follow-up visit [Part 1b (6±1 Days post-dose)] |
| Maximum Observed Plasma Concentration (Cmax) |
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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 exclusion criteria numbers 3 and 6, as judged by the Investigator (Applicable to all parts). 8. Abnormal vital signs, after 10 minutes supine rest. Abnormal values may be repeated once at the discretion of the Investigator (applicable to all parts). 9. Any clinically important abnormalities in rhythm, conduction or morphology of the resting ECG and any clinically important abnormalities in the 12-lead electrocardiogram (ECG) as considered by the Investigator that may interfere with the interpretation of QTc interval changes, including abnormal ST-T-wave morphology, particularly in the protocol defined primary lead or left ventricular hypertrophy at the Screening Visit and Day -1 (Applicable to all parts). 10. Known or suspected history of drug abuse [within the past 2 years for Part 2a and Part 3a] as judged by the Investigator (Applicable to all parts). 11.Current smokers or those who have smoked or used nicotine products (including e-cigarettes) within the previous 6 months or has smoking history of >5 pack-years (applicable to all parts). 12. History of alcohol abuse or excessive intake of alcohol as judged by the Investigator (in Germany only: excessive intake of alcohol defined as the regular consumption of more than 3 units [24 g] of alcohol per day for men or 2 units [16 g] of alcohol per day for women) (Applicable to all parts). 13. Positive screen for drugs of abuse, cotinine (nicotine) or alcohol at the Screening Visit or on admission to the Clinical Unit (Applicable to all parts). 14. History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity, as judged by the Investigator or history of hypersensitivity to drugs with a similar chemical structure or class to AZD0449 (Applicable to all parts). 15. Use of drugs with enzyme inducing properties such as St John's Wort within 3 weeks before the first administration of IMP (Applicable to all parts). 16. Plasma donation within 1 month of the Screening Visit or any blood donation/blood loss >500 mL during the 3 months before the Screening Visit (Applicable to all parts). 17. Healthy volunteers/patients who have previously received (Applicable to all parts). 18. Involvement of any AstraZeneca or Clinical Unit employee or their close relatives (Applicable to all parts). Patients with mild asthma (Part 2a and Part 3a): 1. History of any clinically important disease other than asthma, or disorder which, in the opinion of the Investigator, may either put the patient at risk because of participation in the study, or influence the results or the patient's ability to participate in the study. 2. Patient has an increased risk of infection. 3. Suspicion of Gilbert's syndrome. 4. Exacerbation of asthma symptoms within 6 months prior to Screening and Day -1 and requiring the use of oral or IV steroids, antibiotics, Accident and Emergency visit, or hospital admission to the Clinical Unit. 5. Female patients who are pregnant, breastfeeding, or are planning a pregnancy during the study period or within 1 month after the last dose of IMP. Healthy volunteers (Part 2b and Part 3b): 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. Female healthy volunteers who are pregnant, breastfeeding, or are planning a pregnancy during the study period or within 1 month after the last dose of IMP.
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| Name | Affiliation | Role |
|---|---|---|
| Dave Singh | The Medicines Evaluation Unit | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | Berlin | 14050 | Germany | |||
| Research Site |
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| Label | URL |
|---|---|
| Related Info | View source |
| Related Info | View source |
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Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
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AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
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).
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.
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| ID | Title | Description |
|---|---|---|
| FG000 | Part 1a (SAD) Placebo | Randomized healthy participants received Placebo for AZD0449. |
| FG001 | Part 1a (SAD) Cohort 1 | Randomized healthy participants received a single inhaled dose of AZD0449 0.095 mg nebulized suspension via Jet nebulizer. |
| FG002 | Part 1a (SAD) Cohort 2 | Randomized healthy participants received a single inhaled dose of AZD0449 0.28 mg nebulized suspension via Jet nebulizer. |
| FG003 | Part 1a (SAD) Cohort 3 | Randomized healthy participants received a single inhaled dose of AZD0449 0.84 mg nebulized suspension via Jet nebulizer. |
| FG004 | Part 1a (SAD) Cohort 4 | Randomized healthy participants received a single inhaled dose of AZD0449 1.60 mg nebulized suspension via Jet nebulizer. |
| FG005 | Part 1a (SAD) Cohort 5 | Randomized healthy participants received a single inhaled dose of AZD0449 3.20 mg nebulized suspension via Jet nebulizer. |
| FG006 | Part 1a (SAD) Cohort 6 | Randomized healthy participants received a single inhaled dose of AZD0449 5 mg nebulized suspension via Jet nebulizer. |
| FG007 | Part 1b (SAD IV) Cohort 1 | Randomized healthy participants received a single intravenous (IV) dose of AZD0449 0.090 mg solution. |
| FG008 | Part 1b (SAD IV) Cohort 2 | Randomized healthy participants received a single IV dose of AZD0449 0.360 mg solution. |
| FG009 | Part 2a (MAD) Placebo | Randomized patients with mild asthma received Placebo. |
| FG010 | 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. |
| FG011 | 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. |
| FG012 | Part 2b (MAD) Placebo | Randomized healthy participants received Placebo for AZD0449. |
| FG013 | Part 2b (MAD) Cohort 1 | Randomized healthy participants received a multiple inhaled of AZD0449 5 mg nebulized suspension via Jet nebulizer. |
| FG014 | Part 3a (DPI/PoM) Placebo | Randomized patients with mild asthma received Placebo for AZD0449. |
| FG015 | 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. |
| FG016 | Part 3b (DPI/Healthy Participants) Placebo | Randomized healthy participants received Placebo for AZD0449. |
| FG017 | Part 3b (DPI/Healthy Participants) | Randomized healthy participants received multiple inhaled dose of AZD0449 5 mg DPI. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Part 1a: SAD (Nebulized Inhalation) |
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| Part 1b: SAD (Intravenous Dosing) |
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| Part 2a: MAD (Nebulized Inhalation) |
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| Part 2b: MAD (Nebulized Inhalation) |
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| Part 3a: Asthma Patients (DPI) |
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| Part 3b: Healthy Participants (DPI) |
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| ID | Title | Description |
|---|---|---|
| BG000 | Part 1a (SAD) Placebo | Randomized healthy participants received Placebo for AZD0449. |
| BG001 | Part 1a (SAD) Cohort 1 | Randomized healthy participants received a single inhaled dose of AZD0449 0.095 mg nebulized suspension via Jet nebulizer. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | 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. | Posted | Number | Participants | 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)] |
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From screening up to follow-up visit [Part 1 a/b (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)].
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Part 1a (SAD) Placebo | Randomized healthy participants received Placebo for AZD0449. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Dizziness | Nervous system disorders | MedDRA version 24.0 | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Global Clinical Head | AstraZeneca Clinical Study Information Center | +1-877-240-94 79 | information.center@astrazeneca.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Feb 4, 2021 | May 23, 2022 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Nov 5, 2021 | Mar 28, 2024 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D001249 | Asthma |
| ID | Term |
|---|---|
| D001982 | Bronchial Diseases |
| D012140 | Respiratory Tract Diseases |
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
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| Part 1a (SAD) Cohort 6 | Experimental | 6 participants will receive inhaled dose 6 of AZD0449 nebulized suspension and 2 participants will receive inhaled placebo. |
|
| Part 1b (IV cohort 1) | Experimental | All 6 participants will receive single IV dose of AZD0449 solution. |
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| Part 2a (MAD) Cohort 1 | Experimental | 6 participants will receive inhaled dose 7 of AZD0449 nebulized suspension and 3 participants will receive inhaled placebo. |
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| Part 2a (MAD) Cohort 2 | Experimental | 6 participants will receive inhaled dose 8 of AZD0449 nebulized suspension and 3 participants will receive inhaled placebo. |
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| Part 2b (MAD/healthy volunteers) Cohort 3 | Experimental | 18 healthy volunteers will receive inhaled dose 9 of AZD0449 nebulized suspension and 12 healthy volunteers will receive inhaled placebo. |
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| Part 3a (DPI/PoM) | Experimental | 18 participants will receive inhaled dose 10 of AZD0449 DPI and 6 participants will receive inhaled placebo. |
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| Part 1b (IV cohort 2) | Experimental | 6 healthy volunteers will receive single IV dose of AZD0449 solution. |
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| Part 3b (DPI/healthy volunteers) | Experimental | Part 3b is optional. 8 healthy volunteers; 6 volunteers will receive AZD0449 DPI and 2 volunteers will recieve placebo. |
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| Placebo | Drug | Participants will receive single dose of placebo for AZD0449 (nebulizer suspension). |
|
tmax of AZD0449 following intravenous administration of a single dose to healthy participants was assessed. |
| Part 1b: Day 1 |
| Terminal Halflife, Estimated as (ln2)/-λz (t½λz ) | t½λz of AZD0449 following intravenous administration of a single dose to healthy participants was assessed. | Part 1b: Day 1 |
| 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. | Part 1b: Day 1 |
| 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. | Part 1b: Day 1 |
| 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. | Part 1b: Day 1 |
| Time of Last Quantifiable Concentration (Tlast) | tlast of AZD0449 following intravenous administration of a single dose to healthy participants was assessed. | Part 1b: Day 1 |
| Dose Normalized Cmax (Cmax/D) | Cmax/D of AZD0449 following intravenous administration of a single dose to healthy participants was assessed. | Part 1b: Day 1 |
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. |
| Part 1a: Day 1, Part 2 and 3: Day 1 and Day 12 |
| 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. | Part 1a: Day 1, Part 2 and 3: Day 1 and Day 12 |
| 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. | Part 1a: Day 1, Part 2 and 3: Day 1 and Day 12 |
| 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. | Part 1a: Day 1, Part 2 and 3: Day 1 and Day 12 |
| 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. | Part 1a: Day 1, Part 2 and 3: Day 1 and Day 12 |
| 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. | Part 1a: Day 1, Part 2 and 3: Day 1 and Day 12 |
| 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. | Part 1a: Day 1, Part 2 and 3: Day 1 and Day 12 |
| 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. | Part 1a: Day 1, Part 2 and 3: Day 1 and Day 12 |
| 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. | Part 1a: Day 1, Part 2 and 3: Day 1 and Day 12 |
| 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. | Part 1a: Day 1, Part 2 and 3: Day 1 and Day 12 |
| 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. | Part 1a: Day 1, Part 2 and 3: Day 1 and Day 12 |
| 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. | At Baseline and Day 12 |
| 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. | At Baseline and Day 12 |
| Wellington |
| 6021 |
| New Zealand |
| Research Site | Harrow | HA1 3UJ | United Kingdom |
| Research Site | Manchester | M23 9GP | United Kingdom |
| Related Info | View source |
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| BG002 | Part 1a (SAD) Cohort 2 | Randomized healthy participants received a single inhaled dose of AZD0449 0.28 mg nebulized suspension via Jet nebulizer. |
| BG003 | Part 1a (SAD) Cohort 3 | Randomized healthy participants received a single inhaled dose of AZD0449 0.84 mg nebulized suspension via Jet nebulizer. |
| BG004 | Part 1a (SAD) Cohort 4 | Randomized healthy participants received a single inhaled dose of AZD0449 1.60 mg nebulized suspension via Jet nebulizer. |
| BG005 | Part 1a (SAD) Cohort 5 | Randomized healthy participants received a single inhaled dose of AZD0449 3.20 mg nebulized suspension via Jet nebulizer. |
| BG006 | Part 1a (SAD) Cohort 6 | Randomized healthy participants received a single inhaled dose of AZD0449 5 mg nebulized suspension via Jet nebulizer. |
| BG007 | Part 1b (SAD IV) Cohort 1 | Randomized healthy participants received a single intravenous (IV) dose of AZD0449 0.090 mg solution. |
| BG008 | Part 1b (SAD IV) Cohort 2 | Randomized healthy participants received a single IV dose of AZD0449 0.360 mg solution. |
| BG009 | Part 2a (MAD) Placebo | Randomized patients with mild asthma received Placebo. |
| BG010 | 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. |
| BG011 | 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. |
| BG012 | Part 2b (MAD) Cohort 1 | Randomized healthy participants received a multiple inhaled of AZD0449 5 mg nebulized suspension via Jet nebulizer. |
| BG013 | Part 2b (MAD) Placebo | Randomized healthy participants received Placebo for AZD0449. |
| BG014 | Part 3a (DPI/PoM) | Randomized patients with mild asthma received a multiple inhaled dose of AZD0449 5 mg DPI. |
| BG015 | Part 3a (DPI/PoM) Placebo | Randomized patients with mild asthma received Placebo for AZD0449. |
| BG016 | Part 3b (DPI/Healthy Participants) Placebo | Randomized healthy participants received Placebo for AZD0449. |
| BG017 | Part 3b (DPI/Healthy Participants) | Randomized healthy participants received multiple inhaled dose of AZD0449 5 mg DPI. |
| BG018 | Total | Total of all reporting groups |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| OG001 | Part 1a (SAD) Cohort 1 | Randomized healthy participants received a single inhaled dose of AZD0449 0.095 mg nebulized suspension via Jet nebulizer. |
| OG002 | Part 1a (SAD) Cohort 2 | Randomized healthy participants received a single inhaled dose of AZD0449 0.28 mg nebulized suspension via Jet nebulizer. |
| OG003 | Part 1a (SAD) Cohort 3 | Randomized healthy participants received a single inhaled dose of AZD0449 0.84 mg nebulized suspension via Jet nebulizer. |
| OG004 | Part 1a (SAD) Cohort 4 | Randomized healthy participants received a single inhaled dose of AZD0449 1.60 mg nebulized suspension via Jet nebulizer. |
| OG005 | Part 1a (SAD) Cohort 5 | Randomized healthy participants received a single inhaled dose of AZD0449 3.20 mg nebulized suspension via Jet nebulizer. |
| OG006 | Part 1a (SAD) Cohort 6 | Randomized healthy participants received a single inhaled dose of AZD0449 5 mg nebulized suspension via Jet nebulizer. |
| OG007 | Part 2a (MAD) Placebo | Randomized patients with mild asthma received Placebo. |
| OG008 | 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. |
| OG009 | 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. |
| OG010 | Part 2b (MAD) Placebo | Randomized healthy participants received Placebo for AZD0449. |
| OG011 | Part 2b (MAD) Cohort 1 | Randomized healthy participants received a multiple inhaled of AZD0449 5 mg nebulized suspension via Jet nebulizer. |
| OG012 | Part 3a (DPI/PoM) Placebo | Randomized patients with mild asthma received Placebo for AZD0449. |
| OG013 | Part 3a (DPI/PoM) | Randomized patients with mild asthma received a multiple inhaled dose of AZD0449 5 mg DPI. |
| OG014 | Part 3b (DPI/Healthy Participants) Placebo | Randomized healthy participants received Placebo for AZD0449. |
| OG015 | Part 3b (DPI/Healthy Participants) | Randomized healthy participants received multiple inhaled dose of AZD0449 5 mg DPI. |
|
|
| Primary | Maximum Observed Plasma Concentration (Cmax) | Cmax of AZD0449 following intravenous administration of a single dose to healthy participants was assessed. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanomole/liter (nmol/L) | Part 1b: Day 1 |
|
|
|
| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*nmol/L | Part 1b: Day 1 |
|
|
|
| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*nmol/L | Part 1b: Day 1 |
|
|
|
| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | hour*nanomole/L (h*nmol/L) | Part 1b: Day 1 |
|
|
|
| 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. | 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. | Posted | Median | Full Range | Hours | Part 1b: Day 1 |
|
|
|
| Primary | Terminal Halflife, Estimated as (ln2)/-λz (t½λz ) | t½λz of AZD0449 following intravenous administration of a single dose to healthy participants was assessed. | 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. | Posted | Mean | Standard Deviation | Hours | Part 1b: Day 1 |
|
|
|
| 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. | 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. | Posted | Mean | Standard Deviation | Liter/hour (L/h) | Part 1b: Day 1 |
|
|
|
| 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. | 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. | Posted | Mean | Standard Deviation | Liter | Part 1b: Day 1 |
|
|
|
| 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. | 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. | Posted | Median | Full Range | Hours | Part 1b: Day 1 |
|
|
|
| Primary | Time of Last Quantifiable Concentration (Tlast) | tlast of AZD0449 following intravenous administration of a single dose to healthy participants was assessed. | 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. | Posted | Median | Full Range | Hours | Part 1b: Day 1 |
|
|
|
| Primary | Dose Normalized Cmax (Cmax/D) | Cmax/D of AZD0449 following intravenous administration of a single dose to healthy participants was assessed. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | (nmol/L)/milligram (mg) | Part 1b: Day 1 |
|
|
|
| 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. | Safety Analysis Set included all participants who received at least one dose of AZD0449 and for whom any safety post-dose data were available. | Posted | Number | Participants | From screening up to follow-up visit [Part 1b (6±1 Days post-dose)] |
|
|
|
| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanomole/liter (nmol/L) | Part 1a: Day 1, Part 2 and 3: Day 1 and Day 12 |
|
|
|
| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*nmol/L | Part 1a: Day 1, Part 2 and 3: Day 1 and Day 12 |
|
|
|
| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*nmol/L | Part 1a: Day 1, Part 2 and 3: Day 1 and Day 12 |
|
|
|
| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | hour*nanomole/L (h*nmol/L) | Part 1a: Day 1, Part 2 and 3: Day 1 and Day 12 |
|
|
|
| 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. | 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. | Posted | Median | Full Range | Hours | Part 1a: Day 1, Part 2 and 3: Day 1 and Day 12 |
|
|
|
| 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. | 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. | Posted | Mean | Standard Deviation | Hours | Part 1a: Day 1, Part 2 and 3: Day 1 and Day 12 |
|
|
|
| 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. | 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. | Posted | Mean | Standard Deviation | liter/hour (L/h) | Part 1a: Day 1, Part 2 and 3: Day 1 and Day 12 |
|
|
|
| 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. | 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. | Posted | Mean | Standard Deviation | Liter | Part 1a: Day 1, Part 2 and 3: Day 1 and Day 12 |
|
|
|
| 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. | 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. | Posted | Median | Full Range | Hours | Part 1a: Day 1, Part 2 and 3: Day 1 and Day 12 |
|
|
|
| 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. | 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. | Posted | Median | Full Range | Hours | Part 1a: Day 1, Part 2 and 3: Day 1 and Day 12 |
|
|
|
| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | (nmol/L)/milligram (mg) | Part 1a: Day 1, Part 2 and 3: Day 1 and Day 12 |
|
|
|
| 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. | 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. | Posted | Least Squares Mean | 90% Confidence Interval | parts per billion (ppb) | At Baseline and Day 12 |
|
|
|
|
| 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. | 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. | Posted | Least Squares Mean | 90% Confidence Interval | parts per billion (ppb) | At Baseline and Day 12 |
|
|
|
|
| 0 |
| 12 |
| 0 |
| 12 |
| 3 |
| 12 |
| EG001 | Part 1a (SAD) Cohort 1 | Randomized healthy participants received a single inhaled dose of AZD0449 0.095 mg nebulized suspension via Jet nebulizer. | 0 | 6 | 0 | 6 | 2 | 6 |
| EG002 | Part 1a (SAD) Cohort 2 | Randomized healthy participants received a single inhaled dose of AZD0449 0.28 mg nebulized suspension via Jet nebulizer. | 0 | 6 | 0 | 6 | 2 | 6 |
| EG003 | Part 1a (SAD) Cohort 3 | Randomized healthy participants received a single inhaled dose of AZD0449 0.84 mg nebulized suspension via Jet nebulizer. | 0 | 6 | 0 | 6 | 3 | 6 |
| EG004 | Part 1a (SAD) Cohort 4 | Randomized healthy participants received a single inhaled dose of AZD0449 1.60 mg nebulized suspension via Jet nebulizer. | 0 | 6 | 0 | 6 | 3 | 6 |
| EG005 | Part 1a (SAD) Cohort 5 | Randomized healthy participants received a single inhaled dose of AZD0449 3.20 mg nebulized suspension via Jet nebulizer. | 0 | 6 | 0 | 6 | 3 | 6 |
| EG006 | Part 1a (SAD) Cohort 6 | Randomized healthy participants received a single inhaled dose of AZD0449 5 mg nebulized suspension via Jet nebulizer. | 0 | 6 | 0 | 6 | 1 | 6 |
| EG007 | Part 1b (SAD IV) Cohort 1 | Randomized healthy participants received a single intravenous (IV) dose of AZD0449 0.090 mg solution. | 0 | 6 | 0 | 6 | 2 | 6 |
| EG008 | Part 1b (SAD IV) Cohort 2 | Randomized healthy participants received a single IV dose of AZD0449 0.360 mg solution. | 0 | 6 | 0 | 6 | 2 | 6 |
| EG009 | Part 2a (MAD) Placebo | Randomized patients with mild asthma received Placebo. | 0 | 6 | 0 | 6 | 4 | 6 |
| EG010 | 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. | 0 | 6 | 0 | 6 | 5 | 6 |
| EG011 | 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. | 0 | 6 | 0 | 6 | 3 | 6 |
| EG012 | Part 2b (MAD) Placebo | Randomized healthy participants received Placebo for AZD0449. | 0 | 2 | 0 | 2 | 2 | 2 |
| EG013 | Part 2b (MAD) Cohort 1 | Randomized healthy participants received a multiple inhaled of AZD0449 5 mg nebulized suspension via Jet nebulizer. | 0 | 7 | 0 | 7 | 6 | 7 |
| EG014 | Part 3a (DPI/PoM) Placebo | Randomized patients with mild asthma received Placebo for AZD0449. | 0 | 18 | 0 | 18 | 15 | 18 |
| EG015 | Part 3a (DPI/PoM) | Randomized patients with mild asthma received a multiple inhaled dose of AZD0449 5 mg DPI. | 0 | 18 | 0 | 18 | 14 | 18 |
| EG016 | Part 3b (DPI/Healthy Participants) Placebo | Randomized healthy participants received Placebo for AZD0449. | 0 | 2 | 0 | 2 | 0 | 2 |
| EG017 | Part 3b (DPI/Healthy Participants) | Randomized healthy participants received multiple inhaled dose of AZD0449 5 mg DPI. | 0 | 6 | 0 | 6 | 3 | 6 |
| Dysgeusia | Nervous system disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Presyncope | Nervous system disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Somnolence | Nervous system disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Dry throat | Respiratory, thoracic and mediastinal disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Abdominal discomfort | Gastrointestinal disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Abdominal distension | Gastrointestinal disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Dermatitis contact | Skin and subcutaneous tissue disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Rash erythematous | Skin and subcutaneous tissue disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Lymphadenopathy | Blood and lymphatic system disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Ear discomfort | Ear and labyrinth disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Herpes zoster | Infections and infestations | MedDRA version 24.0 | Non-systematic Assessment |
|
| SARS-CoV-2 antibody test positive | Investigations | MedDRA version 24.0 | Non-systematic Assessment |
|
| Catheter site pain | General disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Abnormal dreams | Psychiatric disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Hiccups | Respiratory, thoracic and mediastinal disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Oropharyngeal discomfort | Respiratory, thoracic and mediastinal disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Wheezing | Respiratory, thoracic and mediastinal disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Dizziness postural | Nervous system disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Paraesthesia | Nervous system disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Eructation | Gastrointestinal disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Palpitations | Cardiac disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Chest discomfort | General disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Facial pain | General disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Fatigue | General disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Hordeolum | Infections and infestations | MedDRA version 24.0 | Non-systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA version 24.0 | Non-systematic Assessment |
|
| Rhinitis | Infections and infestations | MedDRA version 24.0 | Non-systematic Assessment |
|
| Injury | Injury, poisoning and procedural complications | MedDRA version 24.0 | Non-systematic Assessment |
|
| Forced expiratory volume decreased | Investigations | MedDRA version 24.0 | Non-systematic Assessment |
|
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Muscle twitching | Musculoskeletal and connective tissue disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Skin irritation | Skin and subcutaneous tissue disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Aphthous ulcer | Gastrointestinal disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Arthropod bite | Injury, poisoning and procedural complications | MedDRA version 24.0 | Non-systematic Assessment |
|
| Electrocardiogram T wave abnormal | Investigations | MedDRA version 24.0 | Non-systematic Assessment |
|
| Burning sensation mucosal | Nervous system disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Taste disorder | Nervous system disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Testis discomfort | Reproductive system and breast disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Sneezing | Respiratory, thoracic and mediastinal disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Catarrh | Respiratory, thoracic and mediastinal disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Mouth ulceration | Gastrointestinal disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Application site rash | General disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Application site dermatitis | General disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Application site irritation | General disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Catheter site rash | General disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Infusion site pain | General disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Chest pain | General disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Infusion site rash | General disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Migraine | Nervous system disorders | MedDRA version 24.0 | Non-systematic Assessment |
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| Syncope | Nervous system disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Hyperventilation | Respiratory, thoracic and mediastinal disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Dermatitis | Skin and subcutaneous tissue disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Skin fissures | Skin and subcutaneous tissue disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Macule | Skin and subcutaneous tissue disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Contusion | Injury, poisoning and procedural complications | MedDRA version 24.0 | Non-systematic Assessment |
|
| Nasal injury | Injury, poisoning and procedural complications | MedDRA version 24.0 | Non-systematic Assessment |
|
| Muscle strain | Injury, poisoning and procedural complications | MedDRA version 24.0 | Non-systematic Assessment |
|
| Skin laceration | Injury, poisoning and procedural complications | MedDRA version 24.0 | Non-systematic Assessment |
|
| Animal scratch | Injury, poisoning and procedural complications | MedDRA version 24.0 | Non-systematic Assessment |
|
| Lip injury | Injury, poisoning and procedural complications | MedDRA version 24.0 | Non-systematic Assessment |
|
| Skin abrasion | Injury, poisoning and procedural complications | MedDRA version 24.0 | Non-systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Allergy to arthropod bite | Immune system disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Depressed mood | Psychiatric disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Tachycardia | Cardiac disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| External ear inflammation | Ear and labyrinth disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Vertigo positional | Ear and labyrinth disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Photopsia | Eye disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Melanocytic naevus | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA version 24.0 | Non-systematic Assessment |
|
No unpublished information may be disclosed without prior written approval from AstraZeneca AB.
| D012130 |
| Respiratory Hypersensitivity |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
| Any serious AE (including events with outcome=death) |
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| Any AE leading to withdrawal from study |
|
| Any AE leading to discontinuation of investigational medicinal product (IMP) |
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| Linear Mixed Model |
| 0.2849 |
| LS means difference |
| -7.87 |
| 2-Sided |
| 90 |
| -20.3 |
| 4.59 |
| Other |
| Comparison of Part 2a (MAD) Cohort 1 Vs Part 2a (MAD) Placebo | Linear Mixed Model | 0.2595 | LS means difference | -8.31 | 2-Sided | 90 | -20.8 | 4.14 | Other |
| Comparison of Part 3a (DPI/PoM) Vs Part 3a (DPI/PoM) Placebo | Linear Mixed Model | 0.3604 | LS means difference | -3.04 | 2-Sided | 90 | -8.60 | 2.51 | Other |
| Linear Mixed Model |
| 0.3750 |
| LS means difference |
| -73.3 |
| 2-Sided |
| 90 |
| -214 |
| 67.6 |
| Other |
| Comparison of Part 2a (MAD) Cohort 1 Vs Part 2a (MAD) Placebo | Linear Mixed Model | 0.2377 | LS means difference | -98.7 | 2-Sided | 90 | -240 | 42.3 | Other |
| Comparison of Part 3a (DPI/PoM) Vs Part 3a (DPI/PoM) Placebo | Linear Mixed Model | 0.1105 | LS means difference | -50.4 | 2-Sided | 90 | -102 | 1.61 | Other |