Safety, Tolerability, & Pharmacokinetics Study of Single & Multiple Inhaled Doses of Imatinib Inhalation Solution
Condition: Pulmonary Arterial Hypertension
MeSH terms: Respiratory Aspiration; Pulmonary Arterial Hypertension
Study type: Interventional
Phase: Phase 1

Summary: 
      This is a randomised, double-blind, placebo-controlled, dose escalation study to evaluate the
      safety, tolerability, and PK of single and multiple inhaled doses of imatinib inhalation
      solution (AER-901) in healthy adult volunteers. This study consists of 3 parts and an
      optional fourth part.
    

Detailed description: 
      This is a randomised, double-blind, placebo-controlled, dose escalation study to evaluate the
      safety, tolerability, and PK of single and multiple inhaled doses of imatinib inhalation
      solution (AER-901) in healthy adult volunteers. This study consists of 3 parts and an
      optional fourth part:

        -  Part A: double-blind, placebo-controlled, single ascending dose (SAD).

        -  Part B: double-blind, placebo-controlled, multiple ascending dose (MAD).

        -  Part C (optional): open-label, single-dose, crossover. The decision to proceed with Part
           C will be made by the Sponsor after reviewing unblinded safety and PK data from Part D
           of the study.

        -  Part D: double-blind, placebo-controlled, 5 mg single dose (SD) followed by a twice
           daily (BID) 5 mg dose (total daily dose of 10 mg) of AER-901 in a propylene glycol
           formulation vs. placebo.

      Oversight for the study will be provided by an SRC composed of the Principal Investigator
      (PI), the Sponsor's Medical Monitor (MM) and an independent MM. The decision to progress from
      Cohort A1 to Cohort A2 will be based on safety and tolerability data and not PK data from
      Cohort A1. However, the decision to progress from Cohort A2 to Cohort A3 will be based on
      review of safety and tolerability data from Cohort A2 and PK data from Cohort A1 by the SRC.
      A similar sequence will follow for subsequent progression decisions by the SRC for the
      cohorts in Part A and Part B of the study.

      All parts of the study (A, B, C, and D) will include a 28-day Screening period, a Treatment
      period, and a Follow-up period. Parts C and D include an additional treatment period and a
      Washout period between the 2 treatment periods.

      Throughout this Study Protocol, timings for post-dose assessments for spirometry, ECG, blood
      and urine samples for PK analysis are stated in relation to completion of the most recent
      dose of IP.
    

Intervention name(s): AER-901 Solution for Nebulization; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Part A: participants will be enrolled into 1 of up to 5 sequential cohorts (A1 to A5). Inhaled AER-901 doses of 5, 10, 20, 40, and 80mg are planned.
Part B: participants will be enrolled into 1 of up to 3 cohorts (B1 to B3).
Cohorts B2 and B3 will commence following Part D of the study and following SRC review of safety, tolerability, and PK data. A decision to dose with either a propylene glycol formulation or a sterile water formulation will be made by the SRC at the time of the review of the Part D data.
Part D has a three-part design (Treatment Periods 1 & 2 separated by a Washout period) and will compare placebo to a single-dose of AER-901 (5 mg/mL QD) followed by two doses of AER-901.
Each cohort will consist of 8 participants (6 receiving AER 901 and 2 receiving placebo).; 0.45% sterile saline for injection delivered via the FOX MOBILE device.
Other intervention name(s): AER-901; Placebo for Nebulization
Allocation: Randomized
Intervention model: Sequential Assignment
Intervention model description: This is a randomised, double-blind, placebo-controlled, dose escalation study to evaluate the safety, tolerability, and PK of single and multiple inhaled doses of imatinib inhalation solution (AER-901) in healthy adult volunteers. This study consists of 3 parts and an optional fourth part:
Part A: double-blind, placebo-controlled, single ascending dose (SAD).
Part B: double-blind, placebo-controlled, multiple ascending dose (MAD).
Part C (optional): open-label, single-dose, crossover. The decision to proceed with Part C will be made by the Sponsor after reviewing unblinded safety and PK data from Part D of the study.
Part D: double-blind, placebo-controlled, 5 mg single dose (SD) followed by a twice daily (BID) 5 mg dose (total daily dose of 10 mg) of AER-901 in a propylene glycol formulation vs. placebo.
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Basic Science
Keywords: Healthy Subjects; Imatinib; AER-901; PAH; Imatinib mesylate; inhalation; inhaled; nebulization; FOX Mobile; inhaler; Gleevec