A Multiple Dosing (14 Days) Study to Assess Efficacy and Safety of Three Dose Levels of AZD7594, Given Once Daily by Inhalation, in Patients With Mild to Moderate Asthma
Condition: Asthma; Efficacy; Safety
MeSH terms: Asthma
Intervention: 800 μg AZD7594 once daily; 250 µg AZD7594 once daily; 58 µg AZD7594 once daily; Placebo once daily; Salbutamol
Intervention description: Once daily dosing of 800 µg AZD7594 for 14 days; each dose of AZD7594 inhalation powder will be administered via a dry powder monodose inhaler as 2 hard capsules with 2 inhalations per capsule; Once daily dosing of 800 µg AZD7594 for 14 days; each dose of AZD7594 inhalation powder will be administered via a dry powder monodose inhaler as 2 hard capsules with 2 inhalations per capsule; Once daily dosing of 800 µg AZD7594 for 14 days; each dose of AZD7594 inhalation powder will be administered via a dry powder monodose inhaler as 2 hard capsules with 2 inhalations per capsule; Once daily dosing of Placebo to AZD7594 for 14 days; each dose of Placebo inhalation powder will be administered via a dry powder monodose inhaler as 2 hard capsules with 2 inhalations per capsule; Inhalation as needed
Intervention MeSH terms: Albuterol
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Enrollment: 54.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Mild to moderate asthma; FEV1; efficacy; safety

Summary:

      This study will be a randomised, double-blind, multiple dose (14 days), placebo-controlled,
      multi-center study to assess efficacy and safety of three dose levels of AZD7594, given once
      daily by inhalation, in patients with mild to moderate asthma.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Body mass index of 18 to 35 kg/m2

          -  Men and women 18 to 75 years of age, inclusive

          -  Patients need to be non-smokers or ex-smokers (quit ≥ 6 months before the Visit 1)
             with total smoking history of < 10 pack years

          -  Documented clinical diagnosis of asthma for ≥ 6 months before the Visit 1

          -  Patients on low-dose inhaled corticosteroids (ICS) (equivalent of budesonide ≤ 400 μg
             per day) or low-dose ICS/long-acting β-2 agonist (LABA), or not on any inhaled
             steroids, or patients on montelukast

          -  Patients should be controlled on low dose budesonide during the first 14 ±2 days of
             Run-in Part 1, i.e., they need to have ACQ-5 of ≤ 1.5 at Visit 2.

          -  Prebronchodilator FEV1 at Visit 3 should be between 40% and 90% of predicted (mean of
             2 predose measurements taken 30 minutes apart).

          -  All patients need to have FeNO concentrations of ≥ 25 parts per billion at Visit 3

          -  Demonstrate the ability to use the study inhalation device properly

          -  Women must be of nonchildbearing potential defined as meeting 1 of the following
             criteria:

               -  Permanently or surgically sterilized, including hysterectomy and/or bilateral
                  oophorectomy and/or bilateral salpingectomy

               -  Postmenopausal; aged ≤ 50 years and have been amenorrheic for 12 months or more
                  following cessation of exogenous hormonal treatments and with luteinizing hormone
                  and follicle stimulating hormone levels in the postmenopausal range

               -  Postmenopausal; aged > 50 years and have been amenorrheic for 12 months or more,
                  following cessation of all exogenous hormonal treatments

          -  Male patients should be willing to use a condom to prevent pregnancy and exposure of a
             female partner to AZD7594 and should refrain from donating sperm or fathering a child
             from the first day of dosing until 3 months after the last dose of IMP.

        Exclusion Criteria:

          -  Known or suspected hypersensitivity to the IMPs or excipients, including lactose

          -  Systemic steroid use in the 6 weeks before Visit 1

          -  Any active disease other than asthma

          -  Patients on medium to high-dose ICS (equivalent of budesonide > 400 μg per day) or on
             inhaled anticholinergic combination within the 6 weeks prior to Visit 1

          -  Compliance with the eDiary of at least 80% of the days is expected in both Run-in and
             Treatment Periods. Patients with < 80% eDiary compliance during Run-in Periods would
             not be randomized

          -  Treatment with biologicals such as monoclonal antibodies or chimeric biomolecules
             including omalizumab within 6 months or 5 half-lives before Visit 1, whichever is
             longer

          -  History or clinical suspicion of any clinically relevant disease or disorder which, in
             the opinion of the Investigator, may either put the patient at risk because of
             participation in the study, or influence the results or the patient's ability to
             participate in the study, or any other safety concerns in the opinion of the
             Investigator

          -  ACQ-5 ≥ 3 at any time between Visits 1 and 3

          -  Any contraindication against the use of vagolytic or sympathomimetic drugs as judged
             by the Investigator.

          -  Patients with hepatitis B surface antigen, hepatitis C virus antibody or human
             immunodeficiency virus (HIV)

          -  Donation of blood (≥ 450 mL) within 3 months or donation of plasma within 14 days
             before Visit 1

          -  Pregnant woman or a nursing mother

          -  Suspicion of Gilbert's syndrome

          -  Vulnerable persons (e.g., persons kept in detention)

          -  ACQ-5 of ≥ 3 or daily rescue use of ≥ 12 puffs for ≥ 3 consecutive days during the
             enrollment period

          -  Hypersensitivity to the active substance or to any of the excipients of the Run-in
             medication (i.e., budesonide)