A Study to Assess the Efficacy and Safety of Multiple Dose Levels of AZD7594 Administered Once Daily by Inhalation in Asthmatic Subjects
Condition: Asthma
MeSH terms: Asthma
Study type: Interventional
Phase: Phase 2

Summary: 
      This study will assess the efficacy and safety of multiple dose levels of AZD7594
      administered once daily (QD) by inhalation in a 12-week treatment period on asthma subjects.
      The activity will be assessed by comparing AZD7594 to placebo. The comparison between active
      comparator (FF) and placebo will be used for bench marking. The efficacy is assessed by the
      evaluation of change in trough forced expiratory volume in 1 second (FEV1). The aim is to
      develop AZD7594 as a once daily inhaled non-steroidal selective GR modulator (SGRM), which
      may ultimately lead to better disease control of both chronic obstructive pulmonary disease
      (COPD) and asthma through improved efficacy and compliance. The overall rationale for
      developing a once daily AZD7594 in a dry powder inhaler (DPI) is to provide a safe and
      effective future treatment option for both asthma and COPD subjects.
    

Detailed description: 
      This is a randomised, placebo-controlled, double-blind multi center (8 countries: Europe,
      United States [US], South Africa, and Japan) study conducted on 714 subjects (102 subject per
      arm) with asthma symptomatic on low dose inhaled corticosteroids (ICS). The study consists of
      3 periods:

        -  Run-in period (21-28 days; visits 1 to 3)

        -  Treatment period (12-week; Visits 4 to 7)

        -  Follow-up (1-week; visit 8).

      The Run-in period consist of 3 visits: Screening visit (1), reversibility visit (2) and
      randomization visit (3). All subjects will sign an informed consent form (ICF) prior to
      participating in any study-specific procedures. Subjects found to be eligible at Visit 1
      (Screening Visit) will discontinue all asthma medications and switch to low dose budesonide
      (200 μg twice a day [BID] in Europe and 180 μg BID in US) and rescue medication will be taken
      as needed. Subjects on long-acting beta agonist (LABA), fixed dose combination ICS/LABA
      treatment or a long-acting muscarinic antagonist (LAMA) will return for Visit 2 between 2 to
      7 days after Visit 1 to have a sufficient wash-out time of their asthma medications. If
      reversibility criteria are met at Visit 2, subjects will proceed to Visit 3 (Randomization
      will occur within 21 to 28 days of Visit 1). At Visit 3, subjects who remain symptomatic
      while on low dose budesonide will be randomized in an overall ratio of 1:1:1:1:1:1:1 to one
      of 7 possible treatments and will receive inhalation powder via oral route:

        -  AZD7594 DPI 55μg [nominal strength]/50 μg [delivered dose] (QD)

        -  AZD7594 DPI 99 μg/90 μg QD

        -  AZD7594 DPI 198 μg/180 μg QD

        -  AZD7594 DPI 396 μg/360 μg QD

        -  AZD7594 DPI 792 μg/720 μg QD

        -  Placebo for AZD7594 QD

        -  FF 100 μg QD (open-label) The follow-up will be done by telephone contact within 7 to 10
           days after Visit 7 or last investigational product (IP) intake.

      The total duration of the study will be between 113 to 135 days for each individual subject
      and is planned to run approximately 12 months (it should not exceed 18 months).
    

Intervention name(s): AZD7594 DPI 55μg/50μg.; AZD7594 DPI 99 µg/90 µg; AZD7594 DPI 198 µg/180 µg; AZD7594 DPI 396 µg/360 µg once daily.; AZD7594 DPI 792 µg/720 µg; Placebo for AZD7594 once daily.; FF 100 µg once daily (open-label)
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug; Drug
Intervention description(s): A non-steroidal and selective modulator of the GR.; A non-steroidal and selective modulator of the GR.; A non-steroidal and selective modulator of the GR.; A non-steroidal and selective modulator of the GR.; A non-steroidal and selective modulator of the GR.; Placebo for AZD7594; Fluticasone furoate
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Primary purpose: Treatment
Keywords: Inhaled non-steroidal glucocorticoid receptor modulator; Asthma; Inhaled corticosteroids.; Glucocorticoid receptor (GA) agonists.; Chronic obstructive pulmonary disease.; Short-acting B2 agonist.; Fluticasone furoate.