A Study in Healthy Volunteers and Patients With Mild Asthma to Investigate the Safety, Anti-inflammatory Effect of Inhaled AZD0449
Condition: Asthma
MeSH terms: Asthma
Study type: Interventional
Phase: Phase 1

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

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

Intervention name(s): AZD0449; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Participants will receive single inhaled AZD0449 nebulizer suspension and single IV dose of AZD0449 solution.; Participants will receive single dose of placebo for AZD0449 (nebulizer suspension).
Allocation: Randomized
Intervention model: Sequential Assignment
Masking: Single (Participant)
Primary purpose: Treatment
Keywords: Inhaled JAK inhibitor