AsthmaPhase 1NCT03766399
A Study in Healthy Volunteers and Patients With Mild Asthma to Investigate the Safety, Anti-inflammatory Effect of Inhaled AZD0449
A Phase 1 study testing AZD0449 in people with Asthma, run by AstraZeneca at 4 sites in 3 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Asthma
- What is being tested?
- AZD0449
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 131 participants
- Where
- 4 sitesin 3 countries
- Study dates
- 30 Nov 2018to 24 Jun 2021
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
4 sites in 3 countries.
4 sites in 3 countries
United Kingdom2 sites
Research Site
Harrow, HA1 3UJ
Research Site
Manchester, M23 9GP
About this study
Official 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
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.
Read the 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.
- Conditions
- Asthma
- Being tested
- AZD0449, Placebo
- Keywords
- Inhaled JAK inhibitor
- Medical subject headings
- Asthma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZD0449Drug
Participants will receive single inhaled AZD0449 nebulizer suspension and single IV dose of AZD0449 solution.
PlaceboDrug
Participants will receive single dose of placebo for AZD0449 (nebulizer suspension).
| Study group | Role | What they receive |
|---|---|---|
| Part 1a (SAD) Cohort 1 | Experimental | 6 participants will receive inhaled dose 1 of AZD0449 nebulized suspension and 2 participants will receive inhaled placebo. Receives: Drug: AZD0449; Drug: Placebo |
| Part 1a (SAD) Cohort 2 | Experimental | 6 participants will receive inhaled dose 2 of AZD0449 nebulized suspension and 2 participants will receive inhaled placebo. Receives: Drug: AZD0449; Drug: Placebo |
| Part 1a (SAD) Cohort 3 | Experimental | 6 participants will receive inhaled dose 3 of AZD0449 nebulized suspension and 2 participants will receive inhaled placebo. Receives: Drug: AZD0449; Drug: Placebo |
| Part 1a (SAD) Cohort 4 | Experimental | 6 participants will receive inhaled dose 4 of AZD0449 nebulized suspension and 2 participants will receive inhaled placebo. Receives: Drug: AZD0449; Drug: Placebo |
| 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. Receives: Drug: AZD0449; Drug: Placebo |
| Part 1a (SAD) Cohort 6 | Experimental | 6 participants will receive inhaled dose 6 of AZD0449 nebulized suspension and 2 participants will receive inhaled placebo. Receives: Drug: AZD0449; Drug: Placebo |
| Part 1b (IV cohort 1) | Experimental | All 6 participants will receive single IV dose of AZD0449 solution. Receives: Drug: AZD0449; Drug: Placebo |
| Part 2a (MAD) Cohort 1 | Experimental | 6 participants will receive inhaled dose 7 of AZD0449 nebulized suspension and 3 participants will receive inhaled placebo. Receives: Drug: AZD0449; Drug: Placebo |
| Part 2a (MAD) Cohort 2 | Experimental | 6 participants will receive inhaled dose 8 of AZD0449 nebulized suspension and 3 participants will receive inhaled placebo. Receives: Drug: AZD0449; Drug: Placebo |
| 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. Receives: Drug: AZD0449; Drug: Placebo |
| Part 3a (DPI/PoM) | Experimental | 18 participants will receive inhaled dose 10 of AZD0449 DPI and 6 participants will receive inhaled placebo. Receives: Drug: AZD0449; Drug: Placebo |
| Part 1b (IV cohort 2) | Experimental | 6 healthy volunteers will receive single IV dose of AZD0449 solution. Receives: Drug: AZD0449; Drug: Placebo |
| 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. Receives: Drug: AZD0449; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Part 1b: Day 1
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Part 1b: Day 1
Secondary outcomes (14)
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.
Measured: From screening up to follow-up visit [Part 1b (6±1 Days post-dose)]
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: At Baseline and Day 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Dec 2018
- Study start30 Nov 2018
- Primary completion24 Jun 2021
- Study completion24 Jun 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for AsthmaStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 131 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Dave Singh, Principal investigator, The Medicines Evaluation Unit
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03766399
- Sponsor's protocol ID
- D5371C00001
- Other IDs
- 2018-003469-32, 2018
- Status last verified
- Mar 2024
- First submitted
- 8 Nov 2018
- Last updated
- 23 Aug 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Study at a glance
From the registry record, last updated by the sponsor on 23 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT03766399
- Acronym / sponsor ID
- D5371C00001
- Conditions
- Asthma
- Keywords
- Inhaled JAK inhibitor
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 131 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- 30 Nov 2018 (actual)
- Primary completion
- 24 Jun 2021 (actual)
- Study completion
- 24 Jun 2021 (actual)
- First posted
- 6 Dec 2018 (actual)
- Results
- Posted 23 Aug 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Single blind (participant)
- Number of arms
- 13
| Arm | Type | Receives |
|---|---|---|
| Part 1a (SAD) Cohort 1 | Experimental | Drug: AZD0449, Drug: Placebo6 participants will receive inhaled dose 1 of AZD0449 nebulized suspension and 2 participants will receive inhaled placebo. |
| Part 1a (SAD) Cohort 2 | Experimental | Drug: AZD0449, Drug: Placebo6 participants will receive inhaled dose 2 of AZD0449 nebulized suspension and 2 participants will receive inhaled placebo. |
| Part 1a (SAD) Cohort 3 | Experimental | Drug: AZD0449, Drug: Placebo6 participants will receive inhaled dose 3 of AZD0449 nebulized suspension and 2 participants will receive inhaled placebo. |
| Part 1a (SAD) Cohort 4 | Experimental | Drug: AZD0449, Drug: Placebo6 participants will receive inhaled dose 4 of AZD0449 nebulized suspension and 2 participants will receive inhaled placebo. |
| Part 1a (SAD) Cohort 5 | Placebo comparator | Drug: AZD0449, Drug: Placebo6 participants will receive inhaled dose 5 of AZD0449 nebulized suspension and 2 participants will receive inhaled placebo. |
| Part 1a (SAD) Cohort 6 | Experimental | Drug: AZD0449, Drug: Placebo6 participants will receive inhaled dose 6 of AZD0449 nebulized suspension and 2 participants will receive inhaled placebo. |
| Part 1b (IV cohort 1) | Experimental | Drug: AZD0449, Drug: PlaceboAll 6 participants will receive single IV dose of AZD0449 solution. |
| Part 2a (MAD) Cohort 1 | Experimental | Drug: AZD0449, Drug: Placebo6 participants will receive inhaled dose 7 of AZD0449 nebulized suspension and 3 participants will receive inhaled placebo. |
| Part 2a (MAD) Cohort 2 | Experimental | Drug: AZD0449, Drug: Placebo6 participants will receive inhaled dose 8 of AZD0449 nebulized suspension and 3 participants will receive inhaled placebo. |
| Part 2b (MAD/healthy volunteers) Cohort 3 | Experimental | Drug: AZD0449, Drug: Placebo18 healthy volunteers will receive inhaled dose 9 of AZD0449 nebulized suspension and 12 healthy volunteers will receive inhaled placebo. |
| Part 3a (DPI/PoM) | Experimental | Drug: AZD0449, Drug: Placebo18 participants will receive inhaled dose 10 of AZD0449 DPI and 6 participants will receive inhaled placebo. |
| Part 1b (IV cohort 2) | Experimental | Drug: AZD0449, Drug: Placebo6 healthy volunteers will receive single IV dose of AZD0449 solution. |
| Part 3b (DPI/healthy volunteers) | Experimental | Drug: AZD0449, Drug: PlaceboPart 3b is optional. 8 healthy volunteers; 6 volunteers will receive AZD0449 DPI and 2 volunteers will recieve placebo. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 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.
Key exclusion criteria (1 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AZD0449Participants will receive single inhaled AZD0449 nebulizer suspension and single IV dose of AZD0449 solution. | Drug | Part 1a (SAD) Cohort 1, Part 1a (SAD) Cohort 2, Part 1a (SAD) Cohort 3, Part 1a (SAD) Cohort 4, Part 1a (SAD) Cohort 5, Part 1a (SAD) Cohort 6, Part 1b (IV cohort 1), Part 1b (IV cohort 2), Part 2a (MAD) Cohort 1, Part 2a (MAD) Cohort 2, Part 2b (MAD/healthy volunteers) Cohort 3, Part 3a (DPI/PoM), Part 3b (DPI/healthy volunteers) |
| PlaceboParticipants will receive single dose of placebo for AZD0449 (nebulizer suspension). | Drug | Part 1a (SAD) Cohort 1, Part 1a (SAD) Cohort 2, Part 1a (SAD) Cohort 3, Part 1a (SAD) Cohort 4, Part 1a (SAD) Cohort 5, Part 1a (SAD) Cohort 6, Part 1b (IV cohort 1), Part 1b (IV cohort 2), Part 2a (MAD) Cohort 1, Part 2a (MAD) Cohort 2, Part 2b (MAD/healthy volunteers) Cohort 3, Part 3a (DPI/PoM), Part 3b (DPI/healthy volunteers) |
Primary outcome
Number of Participants With Adverse Events and Serious Adverse Events
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)]
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)
Time frame: 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)
Time frame: 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)
Time frame: 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))
Time frame: 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)
Time frame: 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 )
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: Part 1b: Day 1
tlast of AZD0449 following intravenous administration of a single dose to healthy participants was assessed.
Dose Normalized Cmax (Cmax/D)
Time frame: Part 1b: Day 1
Cmax/D of AZD0449 following intravenous administration of a single dose to healthy participants was assessed.
14 secondary outcomes
Number of Participants With Adverse Events and Serious Adverse Events
Time frame: From screening up to follow-up visit [Part 1b (6±1 Days post-dose)]
Maximum Observed Plasma Concentration (Cmax)
Time frame: 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)
Time frame: 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)
Time frame: 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))
Time frame: 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)
Time frame: Part 1a: Day 1, Part 2 and 3: Day 1 and Day 12
Terminal Halflife, Estimated as (ln2)/-λz (t½λz )
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: Part 1a: Day 1, Part 2 and 3: Day 1 and Day 12
Time of Last Quantifiable Concentration (Tlast)
Time frame: Part 1a: Day 1, Part 2 and 3: Day 1 and Day 12
Dose Normalized Cmax (Cmax/D)
Time frame: 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)
Time frame: At Baseline and Day 12
Change From Baseline in 2 Hours Post-dose in FeNO (AUC (0-12))
Time frame: At Baseline and Day 12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Aug 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Related InfoLink provided by the sponsor.
- Related InfoLink provided by the sponsor.
- Related InfoLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. 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.
Related trials for Asthma
RecruitingPhase 1
Pilot Study to Identify the Mediators and Inflammatory Cell Surface Receptors Involved in Allergic Airway Inflammation
Asthma
RecruitingPhase 1
A Study to Compare the Relative Potency of Salbutamol Administered Via Metered Dose Inhalers (MDI) Containing Propellants HFA-152a to HFA-134a in Mild Asthmatics Aged 18 to 65 Inclusive
Asthma, Mild Asthma
RecruitingPhase 3
A Study Assessing the Effect of Dupilumab on Inducing Clinical Remission in Asthma
Asthma Control
Active, not recruitingPhase 2/3
Local Antibiotic Delivery for Community Acquired Pneumonia
Community Acquired Pneumonia (CAP)
RecruitingPhase 2
A Study to Learn About the Study Medicine Called PF-07275315 in People With Moderate-To-Severe Asthma
Asthma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dave Singh principal investigator
The Medicines Evaluation Unit
4 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AZD0449 in people with Asthma, run by AstraZeneca at 4 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United Kingdom, Germany, New Zealand. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Aug 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Adverse Events and Serious Adverse Events (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)]). The study lists 12 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Aug 2024.