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A Study to Assess the Efficacy and Safety of Multiple Dose Levels of AZD7594 Administered Once Daily by Inhalation in Asthmatic Subjects

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03622112
Recruitment Status : Active, not recruiting
First Posted : August 9, 2018
Last Update Posted : August 28, 2019
Sponsor:
Collaborator:
Parexel
Information provided by (Responsible Party):
AstraZeneca

Brief 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.

Condition or disease Intervention/treatment Phase
Asthma Drug: AZD7594 DPI 55μg/50μg. Drug: AZD7594 DPI 99 µg/90 µg Drug: AZD7594 DPI 198 µg/180 µg Drug: AZD7594 DPI 396 µg/360 µg once daily. Drug: AZD7594 DPI 792 µg/720 µg Drug: Placebo for AZD7594 once daily. Drug: FF 100 µg once daily (open-label) Phase 2

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).


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 808 participants
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.

Primary Purpose: Treatment
Official Title: A Phase 2b Randomised, Double Blind, Placebo-Controlled, Parallel Arm, Multi-Centre Study to Assess Efficacy and Safety of Multiple Dose Levels of AZD7594 DPI Given Once Daily for Twelve Weeks, Compared to Placebo, in Asthmatics Symptomatic on Low Dose ICS
Actual Study Start Date : January 2, 2019
Estimated Primary Completion Date : October 2, 2019
Estimated Study Completion Date : October 2, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Asthma

Arm Intervention/treatment
Experimental: AZD7594 Dose 1
The randomized subjects will receive AZD7594 55 μg/50 μg (nominal/delivered dose), oral inhalation via dry powder inhaler (DPI) once daily.
Drug: AZD7594 DPI 55μg/50μg.
A non-steroidal and selective modulator of the GR.

Experimental: AZD7594 Dose 2
The randomized subjects will receive AZD7594 99 µg/90 µg, oral inhalation via DPI once daily.
Drug: AZD7594 DPI 99 µg/90 µg
A non-steroidal and selective modulator of the GR.

Experimental: AZD7594 Dose 3
The randomized subjects will receive treatment with AZD7594 198 µg/180 µg, oral inhalation via DPI once daily.
Drug: AZD7594 DPI 198 µg/180 µg
A non-steroidal and selective modulator of the GR.

Experimental: AZD7594 Dose 4
The randomized subjects will receive treatment with AZD7594 396 µg/360 µg, oral inhalation via DPI once daily.
Drug: AZD7594 DPI 396 µg/360 µg once daily.
A non-steroidal and selective modulator of the GR.

Experimental: AZD7594 Dose 5
The randomized subjects will receive treatment with AZD7594 792 µg/720 µg, oral inhalation via DPI once daily.
Drug: AZD7594 DPI 792 µg/720 µg
A non-steroidal and selective modulator of the GR.

Placebo Comparator: Placebo
The randomized subjects will receive AZD7594 matching placebo oral inhalation via DPI once daily.
Drug: Placebo for AZD7594 once daily.
Placebo for AZD7594

Active Comparator: Fluticasone Furoate
The randomized subjects will receive treatment with fluticasone furoate (FF) oral inhalation via DPI, 100 µg per nominal dose, once daily (open-label).
Drug: FF 100 µg once daily (open-label)
Fluticasone furoate




Primary Outcome Measures :
  1. Change from baseline in trough FEV1 at week 12 [ Time Frame: At run-in period-Visit 2 (0-7 days after Visit 1), Visit 3 (Day 1), treatment period-Visit 4 (Week 2), Visit 5 (Week 4), Visit 6 (Week 8), and Visit 7 (Week 12) or Early Termination Visit (ETV) ]
    To investigate the clinical efficacy of AZD7594 at different dose levels by assessment of using change in FEV1 between baseline (Visit 3) and week 12, compared to placebo.


Secondary Outcome Measures :
  1. Change from baseline in trough FEV1 at weeks 2, 4, 8 and average over the treatment period [ Time Frame: At run-in period-Visit 2 (0-7 days after Visit 1), Visit 3 (Day 1), treatment period-Visit 4 (Week 2), Visit 5 (Week 4), Visit 6 (Week 8), and Visit 7 (Week 12) or ETV ]
    To investigate the clinical efficacy of AZD7594 at different dose levels at each study visit using change in trough FEV1 from baseline (Visit 3) compared to placebo.

  2. Change from baseline in fractional exhaled nitric oxide (FENO) at Weeks 2, 4, 8, 12, and average over the treatment period [ Time Frame: At run-in period-Visit 1 (21-28 days before visit 3), Visit 2 (0-7 days after Visit 1), Visit 3 (Day 1), treatment period-Visit 4 (Week 2), Visit 5 (Week 4), Visit 6 (Week 8), and Visit 7 (Week 12) or ETV ]
    To investigate the clinical efficacy of AZD7594 at different dose levels at each study visit using change from baseline (Visit 3) in FENO compared to placebo. The concentration of FENO will be measured in units of parts per billion (ppb).

  3. Change from baseline in trough forced vital capacity (FVC) at Week 12 and average over the treatment period [ Time Frame: At run-in period-Visit 2 (0-7 days after Visit 1), Visit 3 (Day 1), treatment period-Visit 4 (Week 2), Visit 5 (Week 4), Visit 6 (Week 8), and Visit 7 (Week 12) or ETV ]
    To investigate the clinical efficacy of AZD7594 at different dose levels in terms of change from baseline (Visit 3) in trough FVC compared to placebo.

  4. Change from baseline in Asthma Control Questionnaire (ACQ) -5 at Week 12 and average over the treatment period [ Time Frame: At run-in period-Visit 1 (21-28 days before visit 3), Visit 2 (0-7 days after Visit 1), Visit 3 (Day 1), treatment period-Visit 4 (Week 2), Visit 5 (Week 4), Visit 6 (Week 8), and Visit 7 (Week 12) or ETV ]
    To investigate the clinical efficacy of AZD7594 at different dose levels in terms of change from baseline (Visit 3) in Asthma Control Questionnaire-5 during treatment period compared to placebo. The validated ACQ-5 measures both the adequacy of asthma control and changes in asthma control. The questionnaire has 5 items; each item is scored on a scale of 0 to 6, where higher scores represent more severe impairment/symptoms.

  5. Change from baseline in average morning Peak Expiratory Flow (PEF) over the treatment period [ Time Frame: At run-in period-Visit 1 (21-28 days before visit 3), Visit 2 (0-7 days after Visit 1), Visit 3 (Day 1), treatment period-Visit 4 (Week 2), Visit 5 (Week 4), Visit 6 (Week 8), and Visit 7 (Week 12) ]
    To investigate the clinical efficacy of AZD7594 in terms of change from baseline in average morning PEF over the treatment period at different dose levels and versus placebo. Baseline is defined as mean peak flow over the last week of the run-in period (before Visit 3).

  6. Change from baseline in average evening PEF over the treatment period [ Time Frame: At run-in period-Visit 1 (21-28 days before visit 3), Visit 2 (0-7 days after Visit 1), Visit 3 (Day 1), treatment period-Visit 4 (Week 2), Visit 5 (Week 4), Visit 6 (Week 8), and Visit 7 (Week 12) ]
    To investigate the clinical efficacy of AZD7594 in terms of change from baseline in average morning PEF over the treatment period at different dose levels and versus placebo. Baseline is defined as mean peak flow over the last week of the run-in period (before Visit 3).

  7. Change from baseline in average daily use of rescue medication over the treatment period [ Time Frame: At run-in period-Visit 1 (21-28 days before visit 3), Visit 2 (0-7 days after Visit 1), Visit 3 (Day 1), treatment period-Visit 4 (Week 2), Visit 5 (Week 4), Visit 6 (Week 8), and Visit 7 (Week 12) ]
    To investigate the clinical efficacy of AZD7594 will be assessed in terms of change from baseline in average daily use of SABA (as measured each morning and evening) during treatment period at different dose levels and versus placebo.

  8. Change from baseline in percent night-time awakening days over the treatment period [ Time Frame: At run-in period-Visit 1 (21-28 days before visit 3), Visit 2 (0-7 days after Visit 1), Visit 3 (Day 1), treatment period-Visit 4 (Week 2), Visit 5 (Week 4), Visit 6 (Week 8), and Visit 7 (Week 12) or ETV ]
    To investigate the clinical efficacy of AZD7594 in terms of change in percent of night-time awakenings compared to baseline ( last 7 days of Run-in period) over the treatment period. Subjects will record every morning if they had any awakening because of asthma during the last night at different dose levels and versus placebo.

  9. Change from baseline in average daily asthma symptom score over the treatment period [ Time Frame: At run-in period-Visit 1 (21-28 days before visit 3), Visit 2 (0-7 days after Visit 1), Visit 3 (Day 1), treatment period-Visit 4 (Week 2), Visit 5 (Week 4), Visit 6 (Week 8), and Visit 7 (Week 12) or ETV ]
    To investigate the clinical efficacy of AZD7594 in terms of change in average daily Asthma Symptom Score over the treatment period, compared to baseline (last 7 days of Run-in period). Subjects will record the severity of Asthma Symptoms during night-time and day-time each morning and evening at different dose levels and versus placebo. Asthma Symptom Score is a scale of 0 to 3, where higher scores represent more severe impairment/symptoms.

  10. Change from baseline in percent asthma control days over the treatment period [ Time Frame: At run-in period-Visit 1 (21-28 days before visit 3), Visit 2 (0-7 days after Visit 1), Visit 3 (Day 1), treatment period-Visit 4 (Week 2), Visit 5 (Week 4), Visit 6 (Week 8), and Visit 7 (Week 12) or ETV ]
    To investigate the clinical efficacy of AZD7594 in terms of amount of asthma control days over the treatment period at different dose levels and versus placebo.

  11. Change from baseline in percent rescue-free days over the treatment period [ Time Frame: At run-in period-Visit 1 (21-28 days before visit 3), Visit 2 (0-7 days after Visit 1), Visit 3 (Day 1), treatment period-Visit 4 (Week 2), Visit 5 (Week 4), Visit 6 (Week 8), and Visit 7 (Week 12) or ETV. ]
    To investigate the clinical efficacy of AZD7594 in terms of change from baseline in percent rescue-free days over the treatment period at different dose levels and versus placebo.

  12. Change from baseline in percent symptom-free days over the treatment period [ Time Frame: At run-in period-Visit 1 (21-28 days before visit 3), Visit 2 (0-7 days after Visit 1), Visit 3 (Day 1), treatment period-Visit 4 (Week 2), Visit 5 (Week 4), Visit 6 (Week 8), and Visit 7 (Week 12) or ETV ]
    To investigate the clinical efficacy of AZD7594 in terms of change from baseline in percent symptom-free days over the treatment period at different dose levels and versus placebo.

  13. Time to first CompEx (composite endpoint for severe exacerbations of asthma) event [ Time Frame: At run-in period-Visit 1 (21-28 days before visit 3), Visit 2 (0-7 days after Visit 1), Visit 3 (Day 1), treatment period-Visit 4 (Week 2), Visit 5 (Week 4), Visit 6 (Week 8), and Visit 7 (Week 12) or ETV ]
    To investigate the clinical efficacy of AZD7594 in terms of time to first CompEx event at different dose levels and versus placebo.

  14. Time to recurrent CompEx event [ Time Frame: At run-in period-Visit 1 (21-28 days before visit 3), Visit 2 (0-7 days after Visit 1), Visit 3 (Day 1), treatment period-Visit 4 (Week 2), Visit 5 (Week 4), Visit 6 (Week 8), and Visit 7 (Week 12) or ETV ]
    To investigate the clinical efficacy of AZD7594 in terms of time to recurrent CompEx event at different dose levels and versus placebo.

  15. Annualized CompEx event rate [ Time Frame: At run-in period-Visit 1 (21-28 days before visit 3), Visit 2 (0-7 days after Visit 1), Visit 3 (Day 1), treatment period-Visit 4 (Week 2), Visit 5 (Week 4), Visit 6 (Week 8), and Visit 7 (Week 12) or ETV ]
    To investigate the clinical efficacy of AZD7594 in terms of CompEx event rate at different dose levels and versus placebo.

  16. Observed maximum concentration at steady state (Css,max) of AZD7594 [ Time Frame: At Visit 7 (Week 12) ]
    To describe the PK of AZD7594, Css,max will be assessed after administration of multiple oral inhalation doses of AZD7594 in a subset of subjects.

  17. Observed minimum concentration (Css,min) at the end of the dosing interval of AZD7594 [ Time Frame: At Visits 5 (Week 4) and 7 (Week 12) ]
    To describe the PK of AZD7594, Css,min will be assessed after administration of multiple oral inhalation doses of AZD7594 in a subset of subjects.

  18. Time to maximum concentration at steady state (Tss,max) of AZD7594 [ Time Frame: At Visit 7 (Week 12) ]
    To describe the PK of AZD7594, Tss,max will be assessed after administration of multiple oral inhalation doses of AZD7594 in a subset of subjects.

  19. Area under the plasma concentration-curve from time zero to the time of last quantifiable analyte (AUClast) of AZD7594 [ Time Frame: At Visit 7 (Week 12) ]
    To describe the PK of AZD7594, AUClast will be assessed after administration of multiple oral inhalation doses of AZD7594 in a subset of subjects.

  20. Area under the plasma concentration-curve within a dosing interval (AUCt) of AZD7594 [ Time Frame: At Visit 7 (Week 12) ]
    To describe the PK of AZD7594, AUCt will be assessed after administration of multiple oral inhalation doses of AZD7594 in a subset of subjects.

  21. Average plasma concentration during a dosing interval at steady state AUCτ/24 (Css, avg) of AZD7594 [ Time Frame: At Visit 7 (Week 12) ]
    To describe the PK of AZD7594, Css, avg will be assessed after administration of multiple oral inhalation doses of AZD7594 estimated as AUCτ/24 in a subset of subjects.

  22. Dose normalised Css,max (Css,max/D) of AZD7594 [ Time Frame: At Visit 7 (Week 12) ]
    To describe the PK of AZD7594, Css,max/D will be assessed after administration of multiple oral inhalation doses of AZD7594 in a subset of subjects.

  23. Dose normalised AUCτ (AUCτ/D) of AZD7594 [ Time Frame: At Visit 7 (Week 12) ]
    To describe the PK of AZD7594, AUCτ/D will be assessed after administration of multiple oral inhalation doses of AZD7594 in a subset of subjects.

  24. Percentage of fluctuation over one dosing interval at steady state of AZD7594 [ Time Frame: At Visit 7 (Week 12) ]
    To describe the PK of AZD7594, %fluctuation will be assessed after administration of multiple oral inhalation doses of AZD7594 in a subset of subjects.

  25. Area under the plasma cortisol concentration-time curve from zero to 24 hours after dosing (AUEC(0-24)) of AZD7594 [ Time Frame: At Visit 7 (Week 12) ]
    To describe the pharmacodynamics of AZD7594 cortisol suppression will be estimated, in a subset of subjects, and compared to placebo.

  26. Number of subjects with treatment-emergent adverse events (TEAEs) [ Time Frame: At run-in period-Visit 1 (21-28 days before visit 3), Visit 2 (0-7 days after Visit 1), Visit 3 (Day 1), treatment period-Visit 4 (Week 2), Visit 5 (Week 4), Visit 6 (Week 8), Visit 7 (Week 12) or ETV and follow up-Visit 8 (7-10 days after Visit 7) ]
    To evaluate the safety and tolerability, adverse events will be collected from the time of signature of informed consent through the follow-up visit, in order to evaluate the safety and tolerability of AZD7594.

  27. Number of subjects with abnormal findings in Electrocardiography (ECG) [ Time Frame: At run-in period-Visit 1 (21-28 days before visit 3), Visit 2 (0-7 days after Visit 1), Visit 3 (Day 1), treatment period-Visit 4 (Week 2), Visit 5 (Week 4), Visit 6 (Week 8), and Visit 7 (Week 12) or ETV ]
    To assess any clinically significant abnormalities in the cardiovascular system functioning using standard digital ECG evaluations. Standard digital ECG evaluations will be recorded after approximately 5 minutes resting and before blood sampling or blood testing.

  28. Laboratory assessments of clinical chemistry [ Time Frame: At run-in period-Visit 1 (21-28 days before visit 3), Visit 2 (0-7 days after Visit 1), Visit 3 (Day 1), treatment period-Visit 4 (Week 2), Visit 5 (Week 4), Visit 6 (Week 8), and Visit 7 (Week 12) or ETV ]
    To evaluate safety and tolerability by assessment of electrolytes (sodium, potassium, calcium, phosphate and dehydroepiandrosterone sulphate), enzymes (alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase [AST]), substrates (Glucose, cholesterol, triglycerides, creatinine, bilirubin, albumin, CRP, and osteocalcin), endocrinology (T4, free T4 and TSH to be collected at V1 and 7), human immunodeficiency virus (HIV), surface antigen of the hepatitis B virus (HBsAg) and antibodies to Hepatitis C virus (HCV) will be collected at Visit 1.

  29. Laboratory assessments of hematology [ Time Frame: At run-in period-Visit 1 (21-28 days before visit 3), Visit 2 (0-7 days after Visit 1), Visit 3 (Day 1), treatment period-Visit 4 (Week 2), Visit 5 (Week 4), Visit 6 (Week 8), and Visit 7 (Week 12) or ETV ]
    To evaluate safety and tolerability by assessment of Haematocrit, haemoglobin, erythrocytes (red blood cells), thrombocytes (platelets) count, reticulocytes, leucocytes (white blood cells) count, leucocytes differential blood count (neutrophils, lymphocytes, monocytes, eosinophils and basophils), MCV and MCH.

  30. Assessments of blood pressure [ Time Frame: At run-in period-Visit 1 (21-28 days before visit 3), Visit 2 (0-7 days after Visit 1), Visit 3 (Day 1), treatment period-Visit 4 (Week 2), Visit 5 (Week 4), Visit 6 (Week 8), and Visit 7 (Week 12) or ETV ]
    To evaluate safety and tolerability by assessment of systolic and diastolic blood pressure.

  31. Assessments of heart rate [ Time Frame: At run-in period-Visit 1 (21-28 days before visit 3), Visit 2 (0-7 days after Visit 1), Visit 3 (Day 1), treatment period-Visit 4 (Week 2), Visit 5 (Week 4), Visit 6 (Week 8), and Visit 7 (Week 12) or ETV ]
    To evaluate safety and tolerability by assessment of heart rate.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03622112


  Show 91 Study Locations
Sponsors and Collaborators
AstraZeneca
Parexel
Investigators
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Principal Investigator: Kai Michael Beeh, Dr med Insaf - Institut für Atemwegsforschung GmbH, D65187, Germany.

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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT03622112     History of Changes
Other Study ID Numbers: D3741C00007
First Posted: August 9, 2018    Key Record Dates
Last Update Posted: August 28, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by AstraZeneca:
Inhaled non-steroidal glucocorticoid receptor modulator
Asthma
Inhaled corticosteroids.
Glucocorticoid receptor (GA) agonists.
Chronic obstructive pulmonary disease.
Short-acting B2 agonist.
Fluticasone furoate.
Additional relevant MeSH terms:
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Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Fluticasone
Glucocorticoids
Anti-Inflammatory Agents
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Dermatologic Agents
Anti-Allergic Agents
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists