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
Intervention: 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 description: 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
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Masking description: All double-blind medication kits will have similar appearance regardless of the IP (AZD7594 or placebo) contained in a DPI device and will be labelled using a unique medication identification number (Kit ID) that is linked to a treatment arm. IVRS/IWRS will assign the study medication to be dispensed to each subjects at Visit 3.
Supplies of budesonide, FF and SABA (salbutamol/albuterol) will be open-label.
Enrollment: 808.0
Sex: All
Minimum age: 18 Years
Maximum age: 85 Years
Healthy volunteers: No
Keywords: Inhaled non-steroidal glucocorticoid receptor modulator; Asthma; Inhaled corticosteroids.; Glucocorticoid receptor (GA) agonists.; Chronic obstructive pulmonary disease.; Short-acting B2 agonist.; Fluticasone furoate.

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.
    

Eligibility criteria:

        Inclusion criteria

        1. Provision of informed consent prior to any study-specific procedures 2. Men and women 18
        to 85 years of age, inclusive, with body mass index (BMI)≤35 3. Subjects need to be
        non-smokers or ex-smokers (have quit e cigarettes or other inhaled tobacco products ≥6
        months before Visit 1) with a total smoking history of less than 10 pack-years (not
        applicable for e cigarettes) 4. Documented clinical diagnosis of asthma for ≥6 months
        before Visit 1 5. Subjects on stable medium to high dose ICS (equivalent of budesonide >400
        μg/day) or low to medium dose ICS/LABA for at least 4 weeks prior to screening (Visit 1)
        (Appendix A, GINA, 2018) 6. Subjects must demonstrate reversibility to inhaled
        bronchodilators at Visit 2 (a ≥12% and ≥200 mL improvement in FEV1 after administration of
        a 4 puffs of salbutamol/albuterol) 7. Pre-bronchodilator FEV1 at Visit 3 between 40% and
        90% predicted at either -45 or -15 minutes pre-dose 8. At Visit 3, subjects need to be
        symptomatic on low dose ICS as evidenced by combined daily asthma mean symptom score of >1
        over the previous 7 days or SABA use on ≥3 of the last 7 days during the Run-in Period 9.
        Demonstrate the ability to use the study inhalation device properly 10. Subject able to
        perform acceptable pulmonary function testing for FEV1 according to American Thoracic
        Society/European Respiratory Society (ATS/ERS) acceptability criteria 11. Subject is
        willing and able to follow study procedures and restrictions. Women of child bearing
        potential (WOCBP) should be stable on their chosen method of highly effective birth control
        for a minimum of 3 months prior to Visit 1, and willing to use that for the entire duration
        of the study (from the time they sign the informed consent), and for 1 month after the last
        dose of IP 12. For optional inclusion in the Gx component of the study, subjects must
        provide separate informed consent for the genomic sampling and analysis Exclusion criteria

          1. Known or suspected hypersensitivity to any of the IPs, including budesonide, or
             excipients, including lactose

          2. Systemic steroid use within the 6 weeks before Visit 1

          3. Concomitant chronic respiratory disease (including current sleep apnea)

          4. History or clinical suspicion of any clinically relevant or active disease or disorder
             which, in the opinion of the Investigator, may either put the subject at risk because
             of participation in the study, or influence the results or the subject's ability to
             participate in the study, or any other safety concerns in the opinion of the
             Investigator

          5. Use of prohibited medications that cannot be stopped during the entire period of the
             study (starting Visit 1).

          6. Subjects with <80% eDiary compliance during Run in Period at Visit 3

          7. ACQ-5 of ≥3 at Visit 1, Visit 2, or Visit 3

          8. Daily rescue use of SABA ≥12 puffs for ≥3 consecutive days at any time during Run-in
             Period, before randomisation

          9. Any clinically important abnormalities in rhythm, conduction or morphology of the
             digital ECG at rest and any abnormalities in the digital ECG (at Visit 1 or Visit 3)
             that, as considered by the Investigator, may interfere with the interpretation of QT
             interval corrected (QTc) interval changes

         10. Prolonged QT interval corrected using Fridericia's formula (QTcF) ≥450 msec based on
             ECG at Visit 1 or Visit 3; or family history of long QT syndrome

         11. PR (PQ) interval prolongation (>240 msec), intermittent second or third degree
             atrial-ventricular (AV) block or AV dissociation at Visit 1 or Visit 3

         12. Subjects with implantable cardiac defibrillator and subjects with sustained
             symptomatic ventricular and/or atrial tachyarrhythmia

         13. Subjects with unstable angina pectoris or stable angina pectoris classified higher
             than Canadian Cardiovascular Society Class II, or a myocardial infarction or stroke
             within 6 months before Visit 1

         14. History of hospitalisation within 12 months before Visit 1 caused by heart failure or
             a diagnosis of heart failure higher than New York Heart Association Class II

         15. Subjects who are positive for hepatitis B surface antigen (HBsAg), hepatitis C virus
             (HCV) antibody or human immunodeficiency virus (HIV) at Visit 1

         16. Donation of blood (≥ 450 mL) within 3 months or donation of plasma within 14 days
             before Visit 1

         17. Suspected poor capability to follow instructions of the study, as judged by the
             Investigator

         18. Previous participation or prior screen failure in the current study, or participation
             in any other research study within 1 month prior to Visit 1

         19. Subject under treatment with biologicals such as monoclonal antibodies or chimeric
             biomolecules including omalizumab, mepolizumab, and reslizumab within 6 months or 5
             half-lives before Visit 1, whichever is longer

         20. Subject treated with any investigational drug within 30 days (or 5 half-lives,
             whichever is longer) prior to Visit 1

         21. Positive drug screening result that cannot be justified by subject's medical history
             and its relevant treatment (over-the-counter product or a valid prescription), or
             history of or current alcohol or drug abuse (including marijuana and
             marijuana-containing valid prescriptions), as judged by the Investigator

         22. Planned in-patient surgery, major dental procedure or hospitalisation during the study

         23. Pregnant woman or lactating woman

         24. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca
             staff, contract research organisation staff and/or staff at the study centre)

         25. Suspicion of Gilbert's syndrome

         26. Vulnerable persons (eg, persons kept in detention)