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

NCT03924635 | Completed Phase 4 Results

• 2 other identifiers: D589BC000182018-003467-64
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 6

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 of inhaled corticosteroids \[(ICS) low or medium\] at study entry

Conditions

Airway Inflammation; Asthma

Keywords

Airway inflammation; Anti-inflammatory reliever; SYMBICORT; Maintenance anti-inflammatory therapy; Reliever medication; Salbutamol

Outcome Measures

Primary Outcomes (5)

• Fractional Exhaled Nitric Oxide (FeNO)

  FeNO was measured by the patient using a FeNO monitoring device (Vivatmo Me). Standard deviation of daily measurement of FeNO were presented for each patient and based on these summary statistics at treatment level were calculated.

  From Day 1 to Day 169 (Treatment period)

• Total Asthma Symptoms Score

  Symptoms scores were calculated using the asthma symptom diary. Asthma symptoms during daytime and night-time were recorded by the patient twice daily in the asthma symptom diary, according to the following scoring system: 0 = no asthma symptoms 1. = you are aware of your asthma symptoms, but you can easily tolerate the symptoms 2. = your asthma is causing you enough discomfort to cause problems with normal activities (or with sleep) 3. = you are unable to do your normal activities (or to sleep) because of your asthma Total asthma symptom scores were reported, which were calculated as the sum of non-missing morning and evening scores. Lower scores indicate no impairment/symptoms, representing increased asthma control. Conversely, higher scores indicate more severe impairment/symptoms, indicating reduced asthma control. Standard deviation of total (daily) asthma symptom scores were presented for each patient and based on these summary statistics at treatment level were calculated.

  From Day 1 to Day 169 (Treatment period)

• Total Reliever Medication Use

  Reliever medication usage was captured in the asthma symptom diary as the number of occasions the reliever inhaler was used. An occasion is defined as 2 puffs for salbutamol or 1 inhalation for SYMBICORT. Standard deviation of total (daily) reliever medication use were presented for each patient and based on these summary statistics at treatment level were calculated.

  From Day 1 to Day 169 (Treatment period)

• Forced Expiratory Volume in 1 Second (FEV1) (Morning and Evening)

  FEV1 was measured by the patient using a spirometry sensor (Spirobank Smart™). Standard deviation of daily measurement of FEV1 were presented for each patient and based on these summary statistics at treatment level were calculated.

  From Day 1 to Day 169 (Treatment period)

• Peak Expiratory Flow (PEF) (Morning and Evening)

  PEF was measured by the patient using a spirometry sensor (Spirobank Smart™). Standard deviation of daily measurement of PEF were presented for each patient and based on these summary statistics at treatment level were calculated.

  From Day 1 to Day 169 (Treatment period)

Secondary Outcomes (2)

• Number of Patients With Secondary Objective Events

  From Day 1 to Day 169 (Treatment period)

• Number of Secondary Objective Events

  From Day 1 to Day 169 (Treatment period)

Study Arms (2)

SYMBICORT as maintenance and reliever treatment

ACTIVE COMPARATOR

Patients on ICS (low dose)/LABA prior to study entry will receive SYMBICORT (budesonide/formoterol 100/6 μg) × 2 twice a day (BID) for maintenance and as needed (PRN) for relief and patients on ICS (medium dose)/LABA prior to study entry will receive SYMBICORT (budesonide/formoterol 200/6 μg) × 2 BID for maintenance and PRN for relief.

Combination Product: SYMBICORT and salbutamol

SYMBICORT as maintenance, salbutamol as reliever treatment

ACTIVE COMPARATOR

Patients on ICS (low dose)/LABA prior to study entry will receive SYMBICORT (budesonide/formoterol 100/6 μg) × 2 BID for maintenance + salbutamol (100 μg) PRN for relief and patients on ICS (medium dose)/LABA prior to study entry will receive SYMBICORT (budesonide/formoterol 200/6 μg) × 2 BID for maintenance + salbutamol (100 μg) PRN for relief.

Combination Product: SYMBICORT and salbutamol

Interventions

SYMBICORT and salbutamol COMBINATION_PRODUCT

SYMBICORT will be given in a TURBOHALER. Salbutamol will be given in a pressurised metered dose inhaler.

Also known as: VENTOLIN (salbutamol), SYMBICORT (budesonide/formoterol)

SYMBICORT as maintenance and reliever treatment; SYMBICORT as maintenance, salbutamol as reliever treatment

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of signed and dated, written Informed Consent Form (ICF) prior to any study-related procedures, sampling, and analyses (at Visit 1).
• Patient must be ≥18 years of age at the time of signing the ICF.
• A physician diagnosis of asthma for a minimum ≥6 months prior to Visit 1.
• Use of ICS (low or medium dose)/LABA for asthma for ≥3 months prior to Visit 1.
• Episode of asthma symptom worsening requiring overuse of reliever (more than the standard for the individual patient) at least once during the last 30 days prior to Visit 1.
• 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.
• Able to perform home FeNO and spirometry assessments and complete the asthma symptom diary on a regular basis during the conduct of the study.
• Male and/or female
• Negative pregnancy test (urine) for female patients of childbearing potential at Visit 1.
• For randomisation at Visit 2, patients should fulfil the following criteria:
• 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.
• At least 80% overall compliance rate for performing FeNO and spirometry assessments and completing the asthma symptom diary during the Run-in Period.

You may not qualify if:

• 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.
• 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.
• Medical history of life- threatening asthma including intubation and intensive care unit admission.
• Medical conditions (other than allergic rhinitis) or medications (other than ICS) that will influence FeNO, as judged by the Investigator.
• 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).
• 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.
• 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.
• Any disease state or procedure that may necessitate the use of oral/systemic corticosteroids during the Treatment Period, other than asthma.
• 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).
• Patients with a history/treatment of malignancy, and which in the Investigator's opinion could compromise the safety of the patient.
• 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.
• 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.
• Alcohol/substance abuse: a history (or suspected history) of alcohol misuse or substance abuse within 2 years prior to Visit 1.
• 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.
• 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.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (6)

Research Site

Bradford, BD9 6RJ, United Kingdom

Location

Research Site

Dundee, DD1 9SY, United Kingdom

Location

Research Site

Nottingham, NG5 1PB, United Kingdom

Location

Research Site

Oxford, United Kingdom

Location

Research Site

Watford, WD18 0HB, United Kingdom

Location

Research Site

Wishaw, ML2 0DP, United Kingdom

Location

Related Links

• Redacted CSR Synopsis

MeSH Terms

Conditions

Asthma

Interventions

Budesonide, Formoterol Fumarate Drug Combination; Albuterol; Budesonide; Formoterol Fumarate

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Drug Combinations; Pharmaceutical Preparations; Phenethylamines; Ethylamines

Results Point of Contact

• Title: Global Clinical Lead
• Organization: AstraZeneca

information.center@astrazeneca.com

1-877-240-9479

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 31, 2019
• First Posted: April 23, 2019
• Study Start: August 1, 2019
• Primary Completion: December 16, 2022
• Study Completion: December 16, 2022
• Last Updated: January 22, 2025
• Results First Posted: January 22, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Locations

GB (6)