A Study to Evaluate the Safety, Tolerability and Absorption to the Blood After Administration of Single and Multiple Doses of AZD8154 in Healthy Participants.
Condition: Asthma
Study type: Interventional
Phase: Phase 1

Summary: 
      This study is a Phase 1, first in human (FiH) study, consisting of 3 parts (Part 1, Part 2,
      and Part 3) 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. Part 3 will be a single
      blind placebo controlled, multiple ascending doses (MAD) sequential design study in healthy
      male and/or female subjects of non childbearing potential conducted at a single center. Part
      3:Three (3) inhaled dose levels of AZD8154 are planned to be investigated. Depending on the
      emerging data, up to 2 additional inhaled dose levels may be added at the discretion of the
      Sponsor.
    

Detailed description: 
      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.
    

Intervention name(s): AZD8154
Intervention type(s): Drug
Intervention description(s): SAD Part 1; 6 cohorts which receive single dosing. One cohort is invited back for large particle administration. Part 2; 1 cohort which receives IV dose and then inhaled administration of AZD8154. MAD Part 3; 3 cohorts will receive inhaled multiple dosing. Additional doses are provisional and could be adjusted based on the emerging data from the previous dose by the safety review committee (SRC).
Allocation: Randomized
Intervention model: Sequential Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Phosphoinositide 3-kinase (PI3K) inhibitor; First-in-human (FiH) study