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    Summary
    EudraCT Number:2016-004140-10
    Sponsor's Protocol Code Number:D6540C00001
    National Competent Authority:Poland - Office for Medicinal Products
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2017-08-21
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedPoland - Office for Medicinal Products
    A.2EudraCT number2016-004140-10
    A.3Full title of the trial
    A randomised, double-blind, placebo- and active-controlled, parallel-arm, multicentre study to assess efficacy, pharmacokinetics, safety and tolerability of multiple dose levels of abediterol administered once daily for four weeks, in patients with asthma symptomatic on inhaled corticosteroids
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A study to investigate the effects of different dose levels of abediterol administered once daily during four weeks to patients with symptomatic asthma on inhaled corticosteroids compared to patients given an open label comparator or placebo. The study will evaluate the efficacy of abediterol, how this study drug is absorbed in the blood stream and how safe and tolerable it is for the patients.
    A.4.1Sponsor's protocol code numberD6540C00001
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorAstraZeneca AB
    B.1.3.4CountrySweden
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportAstraZeneca AB
    B.4.2CountrySweden
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationAstraZeneca AB
    B.5.2Functional name of contact pointClinical Trial Information Desk
    B.5.3 Address:
    B.5.3.1Street AddressKarlebyhus Astraallén
    B.5.3.2Town/ citySödertälje
    B.5.3.3Post codeSE-151 85
    B.5.3.4CountrySweden
    B.5.6E-mailinformation.center@astrazeneca.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameAbediterol
    D.3.2Product code AZD0548
    D.3.4Pharmaceutical form Inhalation powder
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPInhalation use
    Oral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNAbediterol
    D.3.9.1CAS number 1044516-17-7
    D.3.9.2Current sponsor codeAZD0548
    D.3.9.3Other descriptive nameAbediterol napadisylate
    D.3.9.4EV Substance CodeSUB169367
    D.3.10 Strength
    D.3.10.1Concentration unit µg microgram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number0.156
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameAbediterol
    D.3.2Product code AZD0548
    D.3.4Pharmaceutical form Inhalation powder
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPInhalation use
    Oral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNAbediterol
    D.3.9.1CAS number 1044516-17-7
    D.3.9.2Current sponsor codeAZD0548
    D.3.9.3Other descriptive nameAbediterol napadisylate
    D.3.9.4EV Substance CodeSUB169367
    D.3.10 Strength
    D.3.10.1Concentration unit µg microgram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number0.313
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 3
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameAbediterol
    D.3.2Product code AZD0548
    D.3.4Pharmaceutical form Inhalation powder
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPInhalation use
    Oral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNAbediterol
    D.3.9.1CAS number 1044516-17-7
    D.3.9.2Current sponsor codeAZD0548
    D.3.9.3Other descriptive nameAbediterol napadisylate
    D.3.9.4EV Substance CodeSUB169367
    D.3.10 Strength
    D.3.10.1Concentration unit µg microgram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number0.625
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 4
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameAbediterol
    D.3.2Product code AZD0548
    D.3.4Pharmaceutical form Inhalation powder
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPInhalation use
    Oral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNAbediterol
    D.3.9.1CAS number 1044516-17-7
    D.3.9.2Current sponsor codeAZD0548
    D.3.9.3Other descriptive nameAbediterol napadisylate
    D.3.9.4EV Substance CodeSUB169367
    D.3.10 Strength
    D.3.10.1Concentration unit µg microgram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number1.25
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 5
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameAbediterol
    D.3.2Product code AZD0548
    D.3.4Pharmaceutical form Inhalation powder
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPInhalation use
    Oral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNAbediterol
    D.3.9.1CAS number 1044516-17-7
    D.3.9.2Current sponsor codeAZD0548
    D.3.9.3Other descriptive nameAbediterol napadisylate
    D.3.9.4EV Substance CodeSUB169367
    D.3.10 Strength
    D.3.10.1Concentration unit µg microgram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number2.5
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 6
    D.1.2 and D.1.3IMP RoleComparator
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Serevent Accuhaler
    D.2.1.1.2Name of the Marketing Authorisation holderGlaxo Wellcome UK Ltd. - Stockley Park West, Uxbridge, Middlesex, UB11 1BT
    D.2.1.2Country which granted the Marketing AuthorisationUnited Kingdom
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameSerevent Accuhaler containing 50 micrograms of salmeterol (as xinafoate)
    D.3.4Pharmaceutical form Inhalation powder, pre-dispensed
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPInhalation use
    Oral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNSalmeterol
    D.3.9.1CAS number 94749-08-3
    D.3.9.3Other descriptive nameSALMETEROL XINAFOATE
    D.3.9.4EV Substance CodeSUB04314MIG
    D.3.10 Strength
    D.3.10.1Concentration unit µg microgram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number50
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboInhalation powder
    D.8.4Route of administration of the placeboInhalation use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    This study will be performed in men and non-pregnant, non-lactating women, all between 12 and 95 years of age with asthma symptomatic on ICS and fulfilling the reversibility criterion (improvement of FEV1≥12% and 200 mL after administration of salbutamol/albuterol) at Visit 2.
    E.1.1.1Medical condition in easily understood language
    Asthma (an illness that causes breathing difficulty) that is not fully controlled, so that episodes of breathing difficulty are still occurring despite the use of other available treatments.
    E.1.1.2Therapeutic area Diseases [C] - Respiratory Tract Diseases [C08]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10003560
    E.1.2Term Asthma NOS
    E.1.2System Organ Class 100000015470
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The primary objective is to investigate the efficacy of abediterol once daily after 4 weeks of treatment as measured by change from baseline in trough FEV1 on Day 29
    E.2.2Secondary objectives of the trial
    - To investigate the efficacy of abediterol as measured by changes in other spirometry parameters after 4 weeks of treatment in patients with asthma
    - To investigate the efficacy of abediterol in patient reported outcomes after 4 weeks of treatment in patients with asthma
    - To investigate the onset of action of abediterol
    - To characterize the dose-response curve
    - To investigate PK parameters of abediterol in a subset of patients
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    A subset of approximately 206 patients will undergo PK
    assessments. All patients from Japan and all adolescents will be included in the PK sub-study.
    E.3Principal inclusion criteria
    1. Patient or patient’s parents/legal guardians who provided written informed consent (assent for underage patients) prior to any study-specific procedures.
    2. Men and non-pregnant, non-lactating women between 12 and 95 years of age, inclusive.
    3. Non-smoker or former smoker who quit ≥6 months prior to Visit 1 and have a total smoking history of ≤10 pack-years.
    4. Patient with documented clinical diagnosis of asthma for ≥6 months before Visit 1 according to GINA guidelines.
    5. Patient with normal or controlled blood pressure (defined as systolic blood pressure [SBP] between 90 and 150 mm Hg, and diastolic blood pressure [DBP] between 40 and 90 mm Hg) at Screening, measured after resting in the supine position for 5 min. Patients stable on anti-hypertensive can be included.
    6. Patient with no relevant clinical laboratory findings at Screening (Visits 1 or 2) as judged by the Investigator.
    7. Patient on stable dose of ICSs or ICS/LABA FDC, for at least 1 month prior to Visit 1, at the doses approved in the country of enrolment.
    8. Patient with a compliance with their ICS with inhalation treatment during Run-in Period of at least 75%, as measured with the eDiary.
    9. Patient with pre-bronchodilator FEV1at Visit 2 ≥40% and ≤90% of predicted (mean of 2 pre-bronchodilator measurements taken 30 min apart).
    10. Patient who fulfils reversibility criteria to salbutamol/albuterol at Visit 2, with reversibility as defined per the 2005 American Thoracic Society (ATS)/European Respiratory Society (ERS) criteria, ie, ≥12% and ≥200 mL after administration of 4 puffs of salbutamol/albuterol.
    11. Patient with an asthma symptom score >0 as recorded on eDiary on at least 3 out of the last 7 days of Run-in Period.
    12. Patient who demonstrates the ability to use the study inhalation device properly.
    13. Patient able to perform acceptable pulmonary function testing for FEV1according to ATS/ERS acceptability criteria.
    14. Negative pregnancy test (serum pregnancy test at Screening) for female patients.
    15. Female patients must be 1 year post-menopausal, surgically sterile, or must be able to adhere to the conditions of contraceptive requirements as described in the protocol. Male patients must be surgically sterile or must be able to adhere to the conditions of contraceptive requirements as described in the protocol.
    16. Patients willing not to donate blood during the study and for 3 months following their last dose of IP for patients participating in the PK sub-study and for 8 weeks for other patients.
    17. Patient willing and able to follow study directions and restrictions.
    E.4Principal exclusion criteria
    1. Patient has known or suspected hypersensitivity to the IP or excipients, including lactose (Note: lactose intolerance is not an exclusion)
    2. Patient who has used systemic steroid in the 6 weeks before Visit 1
    3. Patient with a history of hospitalisation due to asthma in the 6 months prior to Visit 1 or a history of intubation because of asthma ever in their lifetime
    4. Patient with any active pulmonary disease other than asthma
    5. Patient non-compliant with study procedures in the Run-in Period – as judged by the Investigator
    6. 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
    7. Patient treated with any investigational drug within 30 days (or 6 half-lives, whichever is longer) prior to Visit 1
    8. Patient on treatment with strong cytochrome P450 (CYP)3A4 inhibitors such as ketoconazole or itraconazole or CYP3A4 inducers such as rifampin at Visit 1 or within 14 days prior to administration of IP
    9. Patient with a history, laboratory abnormality, or clinical suspicion of any clinically relevant disease or disorder, including uncontrolled hypertension or uncontrolled diabetes, 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.
    10. Patient with diagnosis of any kind of chronic hepatitis or know human immunodeficiency virus (HIV) infections at the time of enrolment.
    11. Patient with any active malignancy or treatment thereof within the five years prior to enrolment
    12. Patient with any clinically important abnormalities in rhythm, conduction, or morphology of the screening 12-lead ECG as judged by the Investigator on the screening ECG
    13. Patient with prolonged QT interval using Fridericia’s correction ≥450 msec on the screening ECG or family history of long QT syndrome
    14. Patient with PR(PQ) interval prolongation (>240 msec), intermittent second or third degree atrio-ventricular (AV) block or AV dissociation on the screening ECG manually read
    15. Patient with implantable cardiac defibrillator and patients with sustained symptomatic ventricular and/or atrial tachyarrhythmia
    16. Patient with any contraindication against the use of sympathomimetic drugs as judged by the Investigator
    17. Patient 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
    18. Patient with a history of hospitalisation within 12 months caused by heart failure or a diagnosis of heart failure higher than New York Heart Association Class II
    19. Patient with suspected poor capability to follow instructions of the study, as judged by the Investigator
    20. Patient with previous participation or prior screen failure in the current study
    21. Patient with a history of or current alcohol or drug abuse (including marijuana), as judged by the Investigator
    22. Patient with planned in-patient surgery, major dental procedure or hospitalisation during the study
    23. Patient involved in the planning and/or conduct of the study (applies to both AstraZeneca staff, contract research organisation (CRO) staff and/or staff at the study site)
    24. Vulnerable persons (eg, persons kept in detention)
    25. Patient with daily rescue medication use of ≥12 puffs for ≥3 consecutive days or an exacerbation or a change in the dose of ICS during the Run-in Period
    26. Patient who intend to use any concomitant medication not permitted by this protocol
    27. Patients who received live attenuated vaccine within 30 days prior to Visit 1 or who received inactivated vaccine within 7 days prior to Visit 1
    E.5 End points
    E.5.1Primary end point(s)
    Change from baseline (pre-dose, Visit 3) in morning trough FEV1 on Day 29 (Visit 7) (defined as the average of the FEV1 values at 23:15 and 23:45 hours after IP administration on Day 28)
    E.5.1.1Timepoint(s) of evaluation of this end point
    FEV1 values at 23:15 and 23:45 hours after IP administration on Day 28
    E.5.2Secondary end point(s)
    • Changes from baseline (pre-dose, Visit 3) in peak FEV1, FEV1 area under the curve from time 0 to 6 hours (AUC(0-6)), FEV1AUC(0-12), FEV1 AUC(0-24), peak forced vital capacity (FVC), trough FVC, FVC AUC(0-6), FVC AUC(0-24) on Day 29
    • Change from baseline (pre-dose, Visit 3) in trough FEV1, peak FEV1, FEV1(AUC(0-6)), FEV1 AUC(0-12), FEV1AUC(0-24), peak FVC, FVC AUC(0-6), FVC AUC(0-12), and FVC AUC(0-24), after first dose (on Day 1)
    • Change from baseline in trough FEV1, peak FEV1, peak FVC, trough FVC, over the whole treatment period (from Day 8 to Day 29)
    • Percentage of patients achieving an increase of 200 mL and 12% in FEV1from baseline at each time point of Day 1 and Day 29
    • Percentage of patients achieving an increase from baseline in peak and trough FEV1, of 12% and 200 mL on Day 29

    • Change from baseline (last 2 weeks of Run-in Period) in daily symptoms, use of daily rescue medication, morning peak expiratory flow (mPEF), evening peak expiratory flow (ePEF), nocturnal awakenings over the 29-day treatment period
    • Change from baseline (last week of Run-in Period) in Asthma Control Questionnaire (ACQ) on Day 29
    • Change from baseline (pre-dose, Visit 3) in EuroQoL health-related quality of life, 5 dimensions questionnaire (EQ-5D) on Day 29

    • Change from baseline in FEV1at each time point on Day 1 and Day 29
    • Time to achieve 200 mL and 12% improvement in FEV1 from baseline on Day 1

    • Emax model fit to trough FEV1and peak FEV1

    • Day 1: maximum plasma concentration (Cmax), time to reach maximum plasma concentration (tmax), terminal rate constant (λz), terminal half-life (t1/2λz), area under the plasma concentration-curve from time 0 to the time of last quantifiable concentration (AUClast), AUC(0-6), AUC(0-12), AUC(0-24), Cmax/D, AUC(0-6)/D, and AUC(0-24)/D
    • Day 29: Cmax, tmax, λz, t1/2λz, AUClast, AUC(0-6), AUC(0-12), AUC(0-24), average plasma concentration during a dosing interval (Cavg), Cmax/D, AUC(0-24)/D, accumulation ratio for Cmax (Rac[Cmax]), accumulation ratio for AUC(0-24)
    (Rac[AUC(0-24)]), Rac[AUC(0-6)], and Fluctuation index during a dosing interval (%Fluctuation)
    E.5.2.1Timepoint(s) of evaluation of this end point
    as specified in Sections 2.2 and 4.2 of the protocol; Most of secondary endpoints will be measured at Day 8, 15, 22 and 29 main ones on Day 29 only
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response Yes
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) Yes
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial7
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned5
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA29
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Bulgaria
    Germany
    Hungary
    Japan
    Poland
    South Africa
    Ukraine
    United States
    E.8.7Trial has a data monitoring committee No
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    The end of the study is defined as ‘the last visit of the last patient undergoing the study’. For this study, last visit corresponds to the follow-up contact.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years0
    E.8.9.1In the Member State concerned months8
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years0
    E.8.9.2In all countries concerned by the trial months11
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 Yes
    F.1.1Number of subjects for this age range: 60
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) Yes
    F.1.1.6.1Number of subjects for this age range: 60
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 455
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 85
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally Yes
    F.3.3.6.1Details of subjects incapable of giving consent
    Adolescents: Patient must be willing and able to follow study directions. Patients or parents/legal guardians provided written informed consent (assent for underage patients), in Japan required for all subjects <20 years.
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state100
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 350
    F.4.2.2In the whole clinical trial 600
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    There are no plans to provide study treatment after termination of the study. Patients can return to their usual medication after completion of the study.
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2017-09-27
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2017-09-20
    P. End of Trial
    P.End of Trial StatusCompleted
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