Last updated on May 2019

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


Brief description of study

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 (MAD/PoM), and Part 3 (Bridging). 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 1 cohort from Part 1a will be selected as the IV Cohort in Part 1b. Part 2 of the study will be a randomized, single-blind, placebo-controlled, MAD, sequential group design and PoM study performed at 2 study centers. Part 3 will be a randomized, single-blind, placebo-controlled, single-cohort bridging study performed at a single study center. 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 patient in Part 2 and Part 3 of the study is up to 52 days.

Detailed Study Description

Part 1a of the study with 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 subjects will be randomized to receive an inhaled dose of AZD0449 nebulized suspension and 2 subjects will be randomized to receive inhaled placebo. Dosing for each ascending dose cohort will start with 2 subjects in a sentinel cohort, such that 1 subject will be randomized to receive AZD0449 nebulized suspension and 1 subject will be randomized to receive placebo. In each cohort, subjects will attend a Screening Visit within 28 days before receiving the dose of AZD0449 nebulized suspension or corresponding placebo. For the treatment period, subjects will be admitted to the Clinical Unit on Day -1. On Day 1, subjects will receive a single inhaled dose of AZD0449 nebulized suspension or corresponding placebo. Assessments will be performed, and samples collected from before dosing until at least 60 hours post-dose. Subjects will be discharged from the Clinical Unit after all samples have been collected and assessments have been performed on Day 4. Dosing in Part 1b of the study will only be initiated after the completion of Cohort 6 in Part 1a (SAD), or, if Part 1a is completed with less than 6 cohorts, after completion of the last cohort in Part 1a. The IV Cohort will consist of the 6 subjects that received an inhaled dose of AZD0449 nebulized suspension in Part 1a of the study. Within the IV Cohort, all 6 subjects will receive a single IV dose of AZD0449 solution. Dosing will start with 1 subject in a sentinel cohort. There will be a washout period of at least 2 weeks for the subjects receiving both inhaled dosing in Part 1a and IV dosing in Part 1b. For the IV treatment period, subjects will be admitted to the Clinical Unit on Day -1. On Day 1, subjects will receive a single IV dose of the AZD0449 solution. Assessments will be performed, and samples collected from before dosing until at least 36 hours post-dose. In Part 2 (MAD/PoM) of the study, three dose levels of AZD0449 nebulized suspension are planned to be investigated in 3 cohorts. Cohort 1 and 2 will comprise of 9 patients and within each of these cohorts 6 patients will be randomized to receive AZD0449 nebulized suspension and 3 patients randomized to receive placebo. Cohort 3 will be larger than the other cohorts (30 patients). In Cohort 3, 18 patients will be randomized to receive AZD0449 nebulized suspension and 12 patients randomized to receive placebo. Data from patients receiving placebo in Cohort 1 and Cohort 2 (3 patients per cohort) will be added to data from the 12 placebo patients in Cohort 3. Dosing for each ascending dose cohort will start with 2 patients in a sentinel cohort, such that 1 patient will be randomized to receive AZD0449 nebulized suspension and 1 patient will be randomized to placebo. For the treatment period, subjects will be admitted to the Clinical Unit on Day -2. The first dose will be administered on Day 1. Following this first dose, plasma PK samples will be collected over a period long enough to allow for characterization of the late elimination phase, dosing will only be continued thereafter. Part 3 of the study will only be initiated after the completion of Part 2 (MAD/PoM) of the study. A cohort of the same size and at the same dose level as the PoM cohort in Part 2 will participate in Part 3 of the study. The cohort will comprise of 24 patients, 18 patients will be randomized to receive AZD0449 DPI and 6 patients randomized to receive placebo.

Clinical Study Identifier: NCT03766399

Find a site near you

Start Over

Research Site

Harrow, United Kingdom
  Connect »

Research Site

Manchester, United Kingdom
  Connect »

Recruitment Status: Open


Brief Description Eligibility Contact Research Team


Receive Emails About New Clinical Trials!

Sign up for our FREE service to receive email notifications when clinical trials are posted in the medical category of interest to you.