A Study to Evaluate the Safety, Tolerability and Absorption to the Blood After Administration of Single and Multiple Doses of AZD8154 in Healthy Participants.

This is a phase 1 study to assess the safety, tolerability and pharmacokinetics of AZD8154 following single and multiple ascending dose administration in healthy participants. This study will have 3 parts (Part 1, Part 2, and Part 3). Part 1 consists of six cohorts, each consisting of 8 participants. Depending on emerging PK and adverse event (AE) data, 1 to 2 additional inhaled dose levels, within the pre-specified dose range, may be added at the discretion of the Sponsor. One dose level cohort selected based on emerging data will be repeated using the same formulation of AZD8154 but with a larger particle size. The selected cohort (e.g., Cohort 5), referred to as the "Large Particle Size Cohort", will be dosed at the same dose level with a larger particle size after a minimum washout period of 7 to 14 days between each dose administration. Small Particle Size Cohorts: Within each cohort, 6 participants will be randomized to receive an inhaled dose of AZD8154 (small particle size) and 2 participants will be randomized to receive inhaled placebo. Dosing for each ascending dose cohort will proceed with 2 participants in a sentinel cohort, such that 1 participant will be randomized to receive placebo and 1 participant will be randomized to receive AZD8154 (small particle size). Large Particle Size Cohort: For the selected Large Particle Size Cohort, the 6 participants that received AZD8154 (small particle size) will return for a second Treatment Period after a minimum washout period of 7 to 14 days. All 6 participants will receive an inhaled dose of AZD8154 (large particle size), at the same dose level that they received AZD8154 (small particle size) in Treatment Period 1. The duration of the washout period is based on the predicted half-life of AZD8154 and was selected to diminish the impact of carry-over effects from the first Treatment Period. Part 2: Part 2 of this study will be a single cohort. One cohort consisting of 6 participants will be enrolled into Part 2 of the study. All subjects will receive AZD8154 IV in Treatment Period 1 and then after washout, receive inhaled AZD8154 (small particle size) in Treatment Period 2. Intravenous dosing will proceed with 1 participant in a sentinel cohort, no sentinel dosing will be done in the inhaled dosing period. Part 3: Three cohorts (MAD Cohort 1 to Cohort 3), each consisting of 8 participants, will participate in Part 3 of the study. Within each cohort, 6 participants will be randomized to receive an inhaled dose of AZD8154 and 2 participants will be randomized to receive inhaled placebo. Dosing for each ascending dose cohort will proceed with 2 participants in a sentinel cohort, such that 1 participant will be randomized to receive placebo and 1 participant will be randomized to receive AZD8154. In Part 3, participants will be randomized to receive an inhaled dose of AZD8154 nebuliser suspension or placebo. Three (3) inhaled dose levels of AZD8154 that are administered once daily are planned to be investigated. Based upon emerging PK and safety data in MAD Cohorts 1 to 3, up to 2 additional inhaled dose levels, within the pre-specified dose range, may also be added at the discretion of the Sponsor.