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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03766399




Registration number
NCT03766399
Ethics application status
Date submitted
8/11/2018
Date registered
6/12/2018

Titles & IDs
Public title
A Study in Healthy Volunteers and Patients With Mild Asthma to Investigate the Safety, Anti-inflammatory Effect of Inhaled AZD0449
Scientific title
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
Secondary ID [1] 0 0
2018-003469-32
Secondary ID [2] 0 0
D5371C00001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Asthma 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Asthma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - AZD0449
Treatment: Drugs - Placebo

Experimental: Part 1a (SAD) Cohort 1 - 6 participants will receive inhaled dose 1 of AZD0449 nebulized suspension and 2 participants will receive inhaled placebo.

Experimental: Part 1a (SAD) Cohort 2 - 6 participants will receive inhaled dose 2 of AZD0449 nebulized suspension and 2 participants will receive inhaled placebo.

Experimental: Part 1a (SAD) Cohort 3 - 6 participants will receive inhaled dose 3 of AZD0449 nebulized suspension and 2 participants will receive inhaled placebo.

Experimental: Part 1a (SAD) Cohort 4 - 6 participants will receive inhaled dose 4 of AZD0449 nebulized suspension and 2 participants will receive inhaled placebo.

Placebo comparator: Part 1a (SAD) Cohort 5 - 6 participants will receive inhaled dose 5 of AZD0449 nebulized suspension and 2 participants will receive inhaled placebo.

Experimental: Part 1a (SAD) Cohort 6 - 6 participants will receive inhaled dose 6 of AZD0449 nebulized suspension and 2 participants will receive inhaled placebo.

Experimental: Part 1b (IV cohort 1) - All 6 participants will receive single IV dose of AZD0449 solution.

Experimental: Part 2a (MAD) Cohort 1 - 6 participants will receive inhaled dose 7 of AZD0449 nebulized suspension and 3 participants will receive inhaled placebo.

Experimental: Part 2a (MAD) Cohort 2 - 6 participants will receive inhaled dose 8 of AZD0449 nebulized suspension and 3 participants will receive inhaled placebo.

Experimental: Part 2b (MAD/healthy volunteers) Cohort 3 - 18 healthy volunteers will receive inhaled dose 9 of AZD0449 nebulized suspension and 12 healthy volunteers will receive inhaled placebo.

Experimental: Part 3a (DPI/PoM) - 18 participants will receive inhaled dose 10 of AZD0449 DPI and 6 participants will receive inhaled placebo.

Experimental: Part 1b (IV cohort 2) - 6 healthy volunteers will receive single IV dose of AZD0449 solution.

Experimental: Part 3b (DPI/healthy volunteers) - Part 3b is optional. 8 healthy volunteers; 6 volunteers will receive AZD0449 DPI and 2 volunteers will recieve placebo.


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

Treatment: Drugs: Placebo
Participants will receive single dose of placebo for AZD0449 (nebulizer suspension).

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With Adverse Events and Serious Adverse Events
Timepoint [1] 0 0
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)]
Primary outcome [2] 0 0
Maximum Observed Plasma Concentration (Cmax)
Timepoint [2] 0 0
Part 1b: Day 1
Primary outcome [3] 0 0
Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUCinf)
Timepoint [3] 0 0
Part 1b: Day 1
Primary outcome [4] 0 0
Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast)
Timepoint [4] 0 0
Part 1b: Day 1
Primary outcome [5] 0 0
Area Under the Plasma Concentration Time Curve From Time Zero to 24 Hours After Dosing (AUC(0-24))
Timepoint [5] 0 0
Part 1b: Day 1
Primary outcome [6] 0 0
Time to Reach Peak or Maximum Observed Concentration Following Drug Administration (Tmax)
Timepoint [6] 0 0
Part 1b: Day 1
Primary outcome [7] 0 0
Terminal Halflife, Estimated as (ln2)/-?z (t½?z )
Timepoint [7] 0 0
Part 1b: Day 1
Primary outcome [8] 0 0
Total Body Clearance of Drug From Plasma After Intravascular Administration (CL)
Timepoint [8] 0 0
Part 1b: Day 1
Primary outcome [9] 0 0
Volume of Distribution for Parent Drug at Terminal Phase [Intravenous Administration] (?z)
Timepoint [9] 0 0
Part 1b: Day 1
Primary outcome [10] 0 0
Terminal Rate Constant, Estimated by Loglinear Leastsquares Regression of the Terminal Part of the -Concentrationtime- Curve (?z)
Timepoint [10] 0 0
Part 1b: Day 1
Primary outcome [11] 0 0
Time of Last Quantifiable Concentration (Tlast)
Timepoint [11] 0 0
Part 1b: Day 1
Primary outcome [12] 0 0
Dose Normalized Cmax (Cmax/D)
Timepoint [12] 0 0
Part 1b: Day 1
Secondary outcome [1] 0 0
Number of Participants With Adverse Events and Serious Adverse Events
Timepoint [1] 0 0
From screening up to follow-up visit [Part 1b (6±1 Days post-dose)]
Secondary outcome [2] 0 0
Maximum Observed Plasma Concentration (Cmax)
Timepoint [2] 0 0
Part 1a: Day 1, Part 2 and 3: Day 1 and Day 12
Secondary outcome [3] 0 0
Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUCinf)
Timepoint [3] 0 0
Part 1a: Day 1, Part 2 and 3: Day 1 and Day 12
Secondary outcome [4] 0 0
Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast)
Timepoint [4] 0 0
Part 1a: Day 1, Part 2 and 3: Day 1 and Day 12
Secondary outcome [5] 0 0
Area Under the Plasma Concentration Time Curve From Time Zero to 24 Hours After Dosing (AUC(0-24))
Timepoint [5] 0 0
Part 1a: Day 1, Part 2 and 3: Day 1 and Day 12
Secondary outcome [6] 0 0
Time to Reach Peak or Maximum Observed Concentration Following Drug Administration (Tmax)
Timepoint [6] 0 0
Part 1a: Day 1, Part 2 and 3: Day 1 and Day 12
Secondary outcome [7] 0 0
Terminal Halflife, Estimated as (ln2)/-?z (t½?z )
Timepoint [7] 0 0
Part 1a: Day 1, Part 2 and 3: Day 1 and Day 12
Secondary outcome [8] 0 0
Apparent Total Body Clearance of Drug From Plasma After Extravascular Administration (CL/F)
Timepoint [8] 0 0
Part 1a: Day 1, Part 2 and 3: Day 1 and Day 12
Secondary outcome [9] 0 0
Apparent Volume of Distribution for Parent Drug at Terminal Phase [Extravascular Administration] (Vz/F)
Timepoint [9] 0 0
Part 1a: Day 1, Part 2 and 3: Day 1 and Day 12
Secondary outcome [10] 0 0
Terminal Rate Constant, Estimated by Loglinear Leastsquares Regression of the Terminal Part of the -Concentrationtime- Curve (?z)
Timepoint [10] 0 0
Part 1a: Day 1, Part 2 and 3: Day 1 and Day 12
Secondary outcome [11] 0 0
Time of Last Quantifiable Concentration (Tlast)
Timepoint [11] 0 0
Part 1a: Day 1, Part 2 and 3: Day 1 and Day 12
Secondary outcome [12] 0 0
Dose Normalized Cmax (Cmax/D)
Timepoint [12] 0 0
Part 1a: Day 1, Part 2 and 3: Day 1 and Day 12
Secondary outcome [13] 0 0
Change From Baseline in 2 Hours Post-dose Fractional Excretion of Nitric Oxide (FeNO)
Timepoint [13] 0 0
At Baseline and Day 12
Secondary outcome [14] 0 0
Change From Baseline in 2 Hours Post-dose in FeNO (AUC (0-12))
Timepoint [14] 0 0
At Baseline and Day 12

Eligibility
Key inclusion criteria
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.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
Germany
State/province [1] 0 0
Berlin
Country [2] 0 0
New Zealand
State/province [2] 0 0
Wellington
Country [3] 0 0
United Kingdom
State/province [3] 0 0
Harrow
Country [4] 0 0
United Kingdom
State/province [4] 0 0
Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
AstraZeneca
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Dave Singh
Address 0 0
The Medicines Evaluation Unit
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
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.
When will data be available (start and end dates)?
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.
Available to whom?
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.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://astrazenecagroup-dt.pharmacm.com/DT/Home


What supporting documents are/will be available?

Results publications and other study-related documents

No documents have been uploaded by study researchers.