Last updated on September 2018

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


Brief description of study

This study is a Phase 1, first in human (FiH) study, consisting of 2 parts (Part 1 and Part 2) in healthy male and female participants of non-childbearing potential, performed at a single study center. Part 1 of this study will be a randomized, single-blind, placebo-controlled, single ascending dose (SAD) in healthy male and female participants of non-childbearing potential. Six dose levels of AZD8154 are planned to be investigated. Depending on emerging data, 1 to 2 additional dose levels may be added at the discretion of the Sponsor. Furthermore, one dose level will be repeated using the same formulation of AZD8154 but with a larger particle size (Part 1 only). Part 2 of this study will be a single cohort, open-label, 2-period, study to compare a single inhaled dose of AZD8154 (small particle size) nebuliser suspension with a single IV dose of AZD8154.

Detailed Study Description

This is a phase 1 study to assess the safety, tolerability and pharmacokinetics of AZD8154 following single ascending dose administration in healthy participants. This study will have 2 parts (Part 1 and Part 2). Part 1 of this study consists of six cohorts, each consisting of 8 participants. 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. 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. Part 1 (small particle size cohorts) of the study will comprise of: a screening period of maximum 28 days; a treatment period during which participants will be resident at the clinical unit from the day before Investigational Medicinal Product (IMP) administration (Day -1) until at least 48 hours after IMP administration; discharged on Day 3, and a follow-up visit within 6 1 days after the IMP dose. 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 1 (large particle size cohort) of the study will comprise of: a screening period of maximum 28 days; two treatment periods during which participants will be resident at the clinical unit from the day before IMP administration (Day -1) until at least 48 hours after IMP administration; discharged on Day 3, and a follow-up visit within 6 1 days after the last IMP dose. After completion of dose escalations in Part 1, Part 2 of the study will be initiated. One cohort consisting of 6 participants will be enrolled into Part 2 of the study. All participants 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 subject in a sentinel cohort, no sentinel dosing will be done in the inhaled dosing period. Part 2 of the study will comprise of: a screening period of maximum 28 days; Two treatment periods during which participants will be resident at the clinical unit from the day before IMP administration (Day -1) until at least 48 hours after IMP administration; discharged on Day 3, and a follow-up visit within 6 1 days after last dose of IMP. There will be a minimum washout period of 7 to 14 days between each IMP administration. 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. The diffusing capacity of the lungs for carbon monoxide (DLCO) assessment will be performed in Part 1 of the study. Depending on the emerging data in Part 1, the DLCO assessment may not be performed. Post-dose DLCO will only be performed if a reduction is observed in FEV1 or FVC ( 12%) starting 6 hours after IMP administration.

Clinical Study Identifier: NCT03436316

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