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An Exploratory Study to Characterise Changes in Airway Inflammation, Symptoms, Lung Function and Reliever Use in Adult Asthma Patients

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ClinicalTrials.gov Identifier: NCT03924635
Recruitment Status : Recruiting
First Posted : April 23, 2019
Last Update Posted : October 3, 2019
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Brief Summary:
This is a randomised, active-comparator, open-label, parallel-group, multicentre phase IV exploratory study to characterise changes in airway inflammation, symptoms, lung function, and reliever use in asthma patients using SABA (salbutamol) or anti inflammatory reliever (Symbicort®) as reliever medication in addition to Symbicort® as daily asthma controller. Eligible patients diagnosed with asthma at least 6 months prior to the Screening Visit (Visit 1) and fulfilling all of the inclusion criteria and none of the exclusion criteria will continue into the run-in period. At Visit 2, patients will be assessed for randomisation criteria and, if met, will be randomised to receive either Symbicort® as maintenance and reliever treatment or Symbicort® as maintenance treatment and salbutamol as reliever treatment in a 1:1 ratio. Randomisation will be stratified by the patient's ongoing dose (low or medium) of corticosteroids/long-acting β2-agonist (ICS/LABA) at study entry.

Condition or disease Intervention/treatment Phase
Airway Inflammation Asthma Combination Product: Symbicort® and salbutamol Phase 4

Detailed Description:

This is a randomised, active-comparator, open-label, parallel-group, multicentre phase IV exploratory study to characterise changes in airway inflammation, symptoms, lung function, and reliever use in asthma patients using SABA (salbutamol) or anti inflammatory reliever (Symbicort®) as reliever medication in addition to Symbicort® as daily asthma controller. Eligible patients diagnosed with asthma at least 6 months prior to the Screening Visit (Visit 1) and fulfilling all of the inclusion criteria and none of the exclusion criteria will continue into the run-in period. During the run-in period, patients will take their maintenance medication (ie,Symbicort® [100/6 or 200/6 μg, × 2 BID]) and reliever salbutamol [100 μg, PRN]) using the connected inhalers. At Visit 2, patients will be assessed for randomisation criteria and, if met, will be randomised to receive either Symbicort® as maintenance and reliever treatment or Symbicort® as maintenance treatment and salbutamol as reliever treatment in a 1:1 ratio. Randomisation will be stratified by the patient's ongoing dose (low or medium) of inhaled (ICS/LABA) at study entry. This study will include a minimum of 4 clinic visits. Patients will be requested to come to the study site for 4 additional Event Visits (E1 to E4) at approximately 4-day intervals beginning after the first visit if they experience any one of the following 3 criteria: a) A severe exacerbation defined as use of systemic steroids for at least 3 days, emergency room visit, or inpatient hospitalisation due to asthma, b) Symptom worsening criteria based on CompEx evaluation - an asthma worsening identified by a combination of deteriorations in at least 2 variables (decrease in PEF of at least 15% compared with baseline, an increase of reliever medication of at least 1.5 occasions compared with baseline, or an increase in asthma symptoms of at least 1 compare with baseline or the absolute max score [=3]) at least 2 consecutive days, or c) A single day (in 24 hours) with 6 or more occasions of reliever medication use.

The duration of participation in the study will be 26 to 28 weeks (maximum) for each individual patient, including a 2-week run-in period, followed by a 24-week randomised treatment period and an additional follow-up period if the Event Visits fall within the final 2 weeks of the treatment period. The study plans to randomise a minimum of 60 patients to a maximum of 80 patients to achieve at least 54 patients completing the study. The study will be conducted at no less than 2 sites in the United Kingdom (UK). The estimated study duration is approximately 17 months.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A 24-week Randomised Exploratory Open-Label Study Aiming To Characterise Changes In Airway Inflammation, Symptoms, Lung Function, And Reliever Use In Asthma Patients Using SABA(Salbutamol) Or Anti-Inflammatory Reliever (Symbicort®) As Rescue Medication In Addition To Symbicort® As Daily Asthma Controller
Actual Study Start Date : August 1, 2019
Estimated Primary Completion Date : January 4, 2021
Estimated Study Completion Date : January 4, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Asthma

Arm Intervention/treatment
Active Comparator: Symbicort® as maintenance and reliever treatment
Patients on low dose ICS/LABA prior to study entry (per GINA 2018 guidelines) will receive Symbicort® (budesonide/formoterol 100/6 μg) × 2 twice a day (BID) for maintenance and as needed (PRN) for relief and patients on medium dose ICS/LABA prior to study entry (per GINA 2018 guidelines) will receive Symbicort® (budesonide/formoterol 200/6 μg) × 2 BID for maintenance and PRN for relief.
Combination Product: Symbicort® and salbutamol
Salbutamol is a short-acting β-agonist and Symbicort® (fixed dose combination of inhaled corticosteroid plus long-acting β2-agonist) is an anti-inflammatory reliever for asthma. Symbicort® will be given in a Turbohaler®. Salbutamol will be given in a pressurised metered dose inhaler.
Other Names:
  • Ventolin® (salbutamol)
  • Symbicort® (budesonide/formoterol)

Active Comparator: Symbicort® as maintenance, salbutamol as reliever treatment
Patients on low dose ICS/LABA prior to study entry (per GINA 2018 guidelines) will receive Symbicort® (budesonide/formoterol 100/6 μg) × 2 BID for maintenance + salbutamol (100 μg) PRN for relief and patients on medium dose ICS/LABA prior to study entry (per GINA 2018 guidelines) will receive Symbicort® (budesonide/formoterol 200/6 μg) × 2 BID for maintenance + salbutamol (100 μg) PRN for relief.
Combination Product: Symbicort® and salbutamol
Salbutamol is a short-acting β-agonist and Symbicort® (fixed dose combination of inhaled corticosteroid plus long-acting β2-agonist) is an anti-inflammatory reliever for asthma. Symbicort® will be given in a Turbohaler®. Salbutamol will be given in a pressurised metered dose inhaler.
Other Names:
  • Ventolin® (salbutamol)
  • Symbicort® (budesonide/formoterol)




Primary Outcome Measures :
  1. Individual patient plots of fractional exhaled Nitric Oxide (FeNO) (morning) [ Time Frame: From Day 1 to Day 168 (Treatment period). ]
    FeNO will be plotted over time for each patient.

  2. Individual patient plots of asthma symptoms (morning and evening) [ Time Frame: From Day 1 to Day 168 (Treatment period) ]
    Symptoms scores will be plotted over time for each patient.

  3. Individual patient plots of occasions of reliever medication use (as needed) [ Time Frame: From Day 1 to Day 168 (Treatment period) ]
    Reliever use will be plotted over time for each patient.

  4. Individual patient plots of forced expiratory volume in 1 second (FEV1) (morning and evening) [ Time Frame: From Day 1 to Day 168 (Treatment period) ]
    FEV1 will be plotted over time for each patient.

  5. Individual patient plots of peak expiratory flow (PEF) (morning and evening) [ Time Frame: From Day 1 to Day 168 (Treatment period) ]
    PEF will be plotted over time for each patient.


Secondary Outcome Measures :
  1. Individual patient plots of FeNO (morning) [ Time Frame: Day -14 to +28 of event (During treatment period only Day 1 to Day 168) ]
    FeNO will be plotted at the time of an event for each patient with an event. Events of interest are severe exacerbation, CompEx (full criteria), a single day (in 24 hours) with 6 or more occasions of reliever medication use, and FeNO >50 ppb.

  2. Individual patient plots of asthma symptoms (morning and evening) [ Time Frame: Day -14 to +28 of event (During treatment period only Day 1 to Day 168) ]
    Symptoms scores will be plotted at the time of an event for each patient with an event. Events of interest are severe exacerbation, CompEx (full criteria), a single day (in 24 hours) with 6 or more occasions of reliever medication use, and FeNO >50 ppb.

  3. Individual patient plots of occasions of reliever medication use (as needed) [ Time Frame: Day -14 to +28 of event (During treatment period only Day 1 to Day 168) ]
    Reliever use will be plotted at the time of an event for each patient with an event. Events of interest are severe exacerbation, CompEx (full criteria), a single day (in 24 hours) with 6 or more occasions of reliever medication use, and FeNO >50 ppb.

  4. Individual patient plots of FEV1 (morning and eveing) [ Time Frame: Day -14 to +28 of event (During treatment period only Day 1 to Day 168) ]
    FEV1 will be plotted at the time of an event for each patient with an event. Events of interest are severe exacerbation, CompEx (full criteria), a single day (in 24 hours) with 6 or more occasions of reliever medication use, and FeNO >50 ppb.

  5. Individual patient plots of PEF (morning and evening) [ Time Frame: Day -14 to +28 of event (During treatment period only Day 1 to Day 168) ]
    PEF will be plotted at the time of an event for each patient with an event. Events of interest are severe exacerbation, CompEx (full criteria), a single day (in 24 hours) with 6 or more occasions of reliever medication use, and FeNO >50 ppb.



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 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Provision of signed and dated, written Informed Consent Form (ICF) prior to any study-related procedures, sampling, and analyses (at Visit 1).
  2. Patient must be ≥18 years of age at the time of signing the ICF.
  3. A physician diagnosis of asthma for a minimum ≥6 months prior to Visit 1.
  4. Use of low or medium dose ICS/LABA (GINA 2018 guidelines1) for asthma for ≥3 months prior to Visit 1.
  5. Episode of asthma symptom worsening requiring over use of reliever (more than the standard for the individual patient) at least once during the last 30 days prior to Visit 1.
  6. The patient must be able to read speak, and understand local language; and be able to, in the Investigator's judgment, comply with the study protocol.
  7. Able to perform home FeNO and spirometry assessments and complete the asthma symptom diary on a regular basis during the conduct of the study.
  8. Asthma exacerbation history: patient reported history of one (or more) severe asthma exacerbation requiring treatment with systemic corticosteroids (intramuscular, intravenous, or oral) in the 12 months prior to Visit 1.
  9. Male and/or female
  10. Negative pregnancy test (urine) for female patients of childbearing potential at Visit 1.
  11. For randomisation at Visit 2, patients should fulfil the following criteria:

    1. Symptoms requiring reliever medication use for a minimum of 2 to a maximum 8 days out of the last 10 days of the run-in period.
    2. At least 80% overall compliance rate for performing FeNO and spirometry assessments and completing the asthma symptom diary during the run-in period.

Exclusion Criteria:

  1. Any significant disease or disorder, or evidence of drug/substance abuse which in the Investigator's opinion would pose a risk to patient safety, interfere with the conduct of study, have an impact on the study results, or make it undesirable for the patient to participate in the study.
  2. Any asthma worsening requiring change in asthma treatment other than the patient's prescribed reliever medication (Symbicort® as Maintenance and Reliever Therapy [SMART] therapy, SABA, and/or short-acting anticholinergic agent) within 30 days prior to Visit 1.
  3. Medical history of life- threatening asthma including intubation and intensive care unit admission.
  4. Medical conditions (other than allergic rhinitis) or medications (other than ICS) that will influence FeNO, as judged by the Investigator.
  5. Concurrent respiratory disease: presence of a known pre-existing, clinically important lung condition other than asthma (eg, cystic fibrosis, idiopathic pulmonary fibrosis, pulmonary arterial hypertension).
  6. Acute upper or lower respiratory infections requiring antibiotics or antiviral medication within 30 days prior to the date informed consent is obtained (Visit 1) or during the screening/run-in period.
  7. A severe asthma exacerbation (defined by an exacerbation resulting in ≥3 days of oral corticosteroids [or one depot intramuscular injection of a glucocorticosteroid], an urgent care or emergency room visit that results in systemic corticosteroids, or an inpatient hospitalisation due to asthma) within 30 days prior to screening.
  8. Any disease state or procedure that may necessitate the use of oral/systemic corticosteroids during the treatment period, other than asthma.
  9. Malignancy: a current malignancy or previous history of cancer in remission for less than 12 months prior to Visit 1 (patients that had localised carcinoma of the skin which was resected for cure will not be excluded).
  10. Patients with a history/treatment of malignancy, and which in the Investigator's opinion could compromise the safety of the patient.
  11. Other concurrent medical conditions: patients who have known, pre-existing, clinically significant endocrine, autoimmune, metabolic, neurological, renal, gastrointestinal, hepatic, haematological or any other system abnormalities that are uncontrolled with standard treatment.
  12. Current smokers. Previous smokers are allowed to be included provided that they stopped smoking >12 months prior to Visit 1 AND have a smoking history of ≤10 pack years.
  13. Alcohol/substance abuse: a history (or suspected history) of alcohol misuse or substance abuse within 2 years prior to Visit 1.
  14. Participation in another clinical study with any marketed or investigational biologic drug within 4 months or 5 half-lives (whichever is longer) prior to Visit 1.
  15. Participation in another clinical study with a non-biologic investigational product or new formulation of a marketed non-biologic drug during the last 30 days prior to Visit 1.
  16. Patients with a known hypersensitivity to the study drugs or any of the excipients of the products.
  17. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
  18. Previous randomisation in the present study.
  19. For women only - currently pregnant (confirmed with positive pregnancy test), breast-feeding or planned pregnancy during the study. Fertile women not using acceptable contraceptive measures, as judged by the Investigator. Periodic abstinence, spermicides only, and the lactational amenorrhoea method are not acceptable methods of contraception.
  20. Planned hospitalisation during the study that would interfere with study objectives as judged by the Investigator.

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): NCT03924635


Contacts
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Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com

Locations
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United Kingdom
Research Site Recruiting
Dundee, United Kingdom, DD1 9SY
Research Site Recruiting
Nottingham, United Kingdom, NG5 1PB
Research Site Recruiting
Oxford, United Kingdom, OX3 7FZ
Sponsors and Collaborators
AstraZeneca

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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT03924635     History of Changes
Other Study ID Numbers: D589BC00018
First Posted: April 23, 2019    Key Record Dates
Last Update Posted: October 3, 2019
Last Verified: September 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by AstraZeneca:
Airway inflammation
Anti-inflammatory reliever
Symbicort
Maintenance anti-inflammatory therapy
Reliever medication
Salbutamol
Additional relevant MeSH terms:
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Asthma
Inflammation
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Pathologic Processes
Budesonide
Albuterol
Formoterol Fumarate
Budesonide, Formoterol Fumarate Drug Combination
Anti-Inflammatory Agents
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents