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Phase 1 Completed N=48 Randomized Single-blind Treatment

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

Source: ClinicalTrials.gov NCT03766399 ↗
Enrolled (actual)
48
Serious AEs
0.0%
Results posted
Aug 2024
Primary outcomePrimary: Number of Participants With Adverse Events and Serious Adverse Events — 3; 2; 2; 3 Participants

Summary

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

Outcome Measures

OutcomeResultp-value
PRIMARY
Number of Participants With Adverse Events and Serious Adverse Events
2; 2; 0; 0; 0; 0
PRIMARY
Maximum Observed Plasma Concentration (Cmax)
0.4360; 1.791; 4.058; 8.646; 19.35; 26.13
PRIMARY
Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUCinf)
1.711; 4.964; 14.60; 35.61; 95.36; 141.2
PRIMARY
Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast)
1.507; 4.608; 13.61; 32.17; 78.27; 121.8
PRIMARY
Area Under the Plasma Concentration Time Curve From Time Zero to 24 Hours After Dosing (AUC(0-24))
1.692; 4.798; 13.09; 29.46; 66.64; 94.029
PRIMARY
Time to Reach Peak or Maximum Observed Concentration Following Drug Administration (Tmax)
1.00; 0.15; 0.10; 0.36; 0.34; 0.50
PRIMARY
Terminal Halflife, Estimated as (ln2)/-λz (t½λz )
3.603; 6.049; 12.51; 24.07; 63.56; 84.26
PRIMARY
Total Body Clearance of Drug From Plasma After Intravascular Administration (CL)
65.38; 57.05
PRIMARY
Volume of Distribution for Parent Drug at Terminal Phase [Intravenous Administration] (λz)
232.0; 248.3
PRIMARY
Terminal Rate Constant, Estimated by Loglinear Leastsquares Regression of the Terminal Part of the -Concentrationtime- Curve (λz)
0.210; 0.105; 0.055; 0.027; 0.013; 0.008
PRIMARY
Time of Last Quantifiable Concentration (Tlast)
10.05; 17.99; 36.02; 48.19; 71.88; 144.41
PRIMARY
Dose Normalized Cmax (Cmax/D)
4.589; 6.396; 4.831; 5.404; 6.047; 5.226
SECONDARY
Number of Participants With Adverse Events and Serious Adverse Events
2; 2; 0; 0; 0; 0
SECONDARY
Maximum Observed Plasma Concentration (Cmax)
0.4360; 1.791; 4.058; 8.646; 19.35; 26.13
SECONDARY
Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUCinf)
1.711; 4.964; 14.60; 35.61; 95.36; 141.2
SECONDARY
Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast)
1.507; 4.608; 13.61; 32.17; 78.27; 121.8
SECONDARY
Area Under the Plasma Concentration Time Curve From Time Zero to 24 Hours After Dosing (AUC(0-24))
1.692; 4.798; 13.09; 29.46; 66.64; 94.029
SECONDARY
Time to Reach Peak or Maximum Observed Concentration Following Drug Administration (Tmax)
1.00; 0.15; 0.10; 0.36; 0.34; 0.50
SECONDARY
Terminal Halflife, Estimated as (ln2)/-λz (t½λz )
3.603; 6.049; 12.51; 24.07; 63.56; 84.26
SECONDARY
Apparent Total Body Clearance of Drug From Plasma After Extravascular Administration (CL/F)
168.5; 162.7; 259.2; 120.1; 93.84; 97.17
SECONDARY
Apparent Volume of Distribution for Parent Drug at Terminal Phase [Extravascular Administration] (Vz/F)
818.1; 1275; 2696; 4180; 8110; 12080
SECONDARY
Terminal Rate Constant, Estimated by Loglinear Leastsquares Regression of the Terminal Part of the -Concentrationtime- Curve (λz)
0.210; 0.105; 0.055; 0.027; 0.013; 0.008
SECONDARY
Time of Last Quantifiable Concentration (Tlast)
10.05; 17.99; 36.02; 48.19; 71.88; 144.41
SECONDARY
Dose Normalized Cmax (Cmax/D)
4.589; 6.396; 4.831; 5.404; 6.047; 5.226
SECONDARY
Change From Baseline in 2 Hours Post-dose Fractional Excretion of Nitric Oxide (FeNO)
-22.6; -22.2; -14.3; -15.0; -12.0 0.9511
SECONDARY
Change From Baseline in 2 Hours Post-dose in FeNO (AUC (0-12))
-299; -274; -200; -213; -162 0.7544

Eligibility 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 ethnicit

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT03766399). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.

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