A study to investigate the effects of different dose levels of AZD7594 DPI administered once daily via inhalation over twelve weeks of treatment in asthmatics who are symptomatic on low doses of inhaled corticosteroids compared to patients given placebo. The study will evaluate the efficacy of AZD7594 DPI, how this study drug is absorbed in the blood stream, how safe and tolerable it is for the patients and which doses should be considered as optimal for further investigation.
- Conditions
- AsthmaMedDRA version: 20.0Level: LLTClassification code 10003560Term: Asthma NOSSystem Organ Class: 100000004855Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]
- Registration Number
- EUCTR2017-002483-40-HU
- Lead Sponsor
- AstraZeneca AB
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 714
1. Provision of informed consent prior to any study-specific procedures
2. Men and women 18 to 85 years of age, inclusive
3. Patients 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. Patients 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).
6. Patients 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
8. At Visit 3, patients 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. Patient able to perform acceptable pulmonary function testing for FEV1 according to American Thoracic Society/European Respiratory Society (ATS/ERS) acceptability criteria.
11. Patient 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, patients must provide separate informed consent for the genomic sampling and analysis
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 600
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 114
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
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 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
5. Use of prohibited medications that cannot be stopped during the entire period of the study (starting Visit 1).
6. Patients 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. Patients with implantable cardiac defibrillator and patients with sustained symptomatic ventricular and/or atrial tachyarrhythmia
13. Patients 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. Patients 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. Patient 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. Patient treated with any investigational drug within 30 days (or 5 half-lives, whichever is longer) prior to Visit 1
21. History of or current alcohol or drug abuse (including marijuana), 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)
Exclusion criteria for the pharmacogenomic part of the study:
• Previous allogeneic bone marrow transplant.
• Non-leuk
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To investigate the clinical efficacy of AZD7594 at different dose levels in asthmatics symptomatic on low dose ICS;Secondary Objective: - To describe the (steady state) pharmacokinetics (PK) of AZD7594 in a subset of asthmatics symptomatic on low dose ICS<br>- To describe the pharmacodynamics of AZD7594 by measuring cortisol suppression in a subset of asthmatics symptomatic on low dose ICS<br>- To evaluate the safety and tolerability of AZD7594 in relation to placebo in asthmatics symptomatic on low dose ICS;Primary end point(s): Primary efficacy endpoint:<br>• Change from baseline in trough FEV1 at Week 12;Timepoint(s) of evaluation of this end point: as outlined in section E.5.1
- Secondary Outcome Measures
Name Time Method