Asthma MedDRA version: 20.0 Level: LLT Classification code 10003560 Term: Asthma NOS System Organ Class: 100000004855
Conditions
Interventions
Product Name: AZD7594
Product Code: AZD7594
Pharmaceutical Form: Inhalation powder
INN or Proposed INN: AZD7594
CAS Number: 1196509-60-0
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion 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. 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 with moderate asthma 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 at either -45 or -15 minutes pre-dose 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 (pharmacogenomic sampling is not applicable to German sites) 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
Exclusion criteria
Exclusion criteria: 1. Known or suspected hypersensitivity (including history of paradoxical bronchospasm) 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 (e.g. severe diabetes, renal or hepatic impairment, and paradoxical bronchospasm) 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 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. Positive drug screening result that cannot be justified by patient’s medical history and its relevant treatment (over-the-counter prod
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate the clinical efficacy of AZD7594 at different dose levels in asthmatics symptomatic on low dose ICS; Primary end point(s): Primary efficacy endpoint: • 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 Objective: - To describe the (steady state) pharmacokinetics (PK) of AZD7594 in a subset of asthmatics symptomatic on low dose ICS - To describe the pharmacodynamics of AZD7594 by measuring cortisol suppression in a subset of asthmatics symptomatic on low dose ICS - To evaluate the safety and tolerability of AZD7594 in relation to placebo in asthmatics symptomatic on low dose ICS | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary efficacy endpoints: • Change from baseline in trough FEV1 at Weeks 2, 4, 8, and average over the treatment period • Change from baseline in FENO at Weeks 2, 4, 8, 12, and average over the treatment period • Change from baseline in trough FVC at Week 12 and average over the treatment period • Change from baseline in ACQ-5 at Week 12 and average over the treatment period • Change from baseline in average morning PEF over the treatment period • Change from baseline in average evening PEF over the treatment period • Change from baseline in average daily use of rescue medication over the treatment period • Change from baseline in percent night-time awakening days over the treatment period • Change from baseline in average daily asthma symptom score over the treatment period • Change from baseline in percent asthma control days over the treatment period • Change from baseline in percent rescue-free days over the treatment period • Change from baseline in percent symptom-free days over the treatment period • Time to first CompEx event, time to recurrent CompEx event, and CompEx event rate PK endpoint: • AZD7594 plasma concentration and (steady state) PK parameters (Css,max, Css,min, tss,max, AUClast, AUCt, Css, avg, Css,max /D, and AUCt/D and %Fluctuation) will be derived PD endpoint: • Area under the plasma cortisol concentration-time curve from zero to 24 hours after dosing (AUEC(0-24)), compared to placebo Adverse event endpoint: • Adverse events (AEs)/Serious adverse events (SAEs)/Discontinuation of IP due to AE (DAEs) Vital signs Clinical chemistry/haematology parameters Electrocardiogram | — |
Countries
Bulgaria, Germany, Hungary, Japan, Poland, South Africa, Ukraine, United States
Contacts
Public ContactInformation Center
AstraZeneca AB
Outcome results
None listed