Trial Outcomes & Findings for An Exploratory Study to Characterise Changes in Airway Inflammation, Symptoms, Lung Function and Reliever Use in Adult Asthma Patients (NCT NCT03924635)

NCT ID: NCT03924635

Last Updated: 2025-01-22

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

42 participants

Primary outcome timeframe

From Day 1 to Day 169 (Treatment period)

Results posted on

2025-01-22

Participant Flow

This study was conducted at six study sites in United Kingdom between 01 August 2019 and 16 December 2022.

Eligible patients from the screening visit entered the 14-day run-in period during which they used 4 devices (1 spirometry sensor, 1 FeNO device, and 2 inhaler sensors) connected to the STIFLE App. The Investigator (or trained study staff) ensured all devices were connected properly and instructed patients on how to use each device and the STIFLE App prior to the run-in period.

Participant milestones

Participant milestones
Measure
SYMBICORT as Maintenance and Reliever Treatment
Patients on ICS (low dose)/LABA prior to study entry received 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 received SYMBICORT (budesonide/formoterol 200/6 μg) × 2 BID for maintenance and PRN for relief.
SYMBICORT as Maintenance, Salbutamol as Reliever Treatment
Patients on ICS (low dose)/LABA prior to study entry received 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 received SYMBICORT (budesonide/formoterol 200/6 μg) × 2 BID for maintenance + salbutamol (100 μg) PRN for relief.
Overall Study
STARTED
18
24
Overall Study
COMPLETED
16
20
Overall Study
NOT COMPLETED
2
4

Reasons for withdrawal

Reasons for withdrawal
Measure
SYMBICORT as Maintenance and Reliever Treatment
Patients on ICS (low dose)/LABA prior to study entry received 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 received SYMBICORT (budesonide/formoterol 200/6 μg) × 2 BID for maintenance and PRN for relief.
SYMBICORT as Maintenance, Salbutamol as Reliever Treatment
Patients on ICS (low dose)/LABA prior to study entry received 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 received SYMBICORT (budesonide/formoterol 200/6 μg) × 2 BID for maintenance + salbutamol (100 μg) PRN for relief.
Overall Study
Withdrawal by Subject
2
4

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
SYMBICORT as Maintenance and Reliever Treatment
n=18 Participants
Patients on ICS (low dose)/LABA prior to study entry received 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 received SYMBICORT (budesonide/formoterol 200/6 μg) × 2 BID for maintenance and PRN for relief.
SYMBICORT as Maintenance, Salbutamol as Reliever Treatment
n=24 Participants
Patients on ICS (low dose)/LABA prior to study entry received 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 received SYMBICORT (budesonide/formoterol 200/6 μg) × 2 BID for maintenance + salbutamol (100 μg) PRN for relief.
Total
n=42 Participants
Total of all reporting groups
Age, Continuous
54.1 Years
STANDARD_DEVIATION 14.6 • n=5 Participants
45.5 Years
STANDARD_DEVIATION 16.0 • n=7 Participants
49.2 Years
STANDARD_DEVIATION 15.8 • n=5 Participants
Sex: Female, Male
Female
12 Participants
n=5 Participants
15 Participants
n=7 Participants
27 Participants
n=5 Participants
Sex: Female, Male
Male
6 Participants
n=5 Participants
9 Participants
n=7 Participants
15 Participants
n=5 Participants
Race/Ethnicity, Customized
Race · American Indian or Alaska Native
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race/Ethnicity, Customized
Race · Asian
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race/Ethnicity, Customized
Race · Native Hawaiian or Other Pacific Islander
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race/Ethnicity, Customized
Race · Black or African American
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race/Ethnicity, Customized
Race · White
17 Participants
n=5 Participants
22 Participants
n=7 Participants
39 Participants
n=5 Participants
Race/Ethnicity, Customized
Race · More than one race
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race/Ethnicity, Customized
Race · Unknown or Not Reported
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race/Ethnicity, Customized
Race · Other
1 Participants
n=5 Participants
2 Participants
n=7 Participants
3 Participants
n=5 Participants

PRIMARY outcome

Timeframe: From Day 1 to Day 169 (Treatment period)

Population: The FAS was defined as all patients randomised who had at least 1 post baseline measurement, irrespective of their protocol adherence and continued participation in the study.

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.

Outcome measures

Outcome measures
Measure
SYMBICORT as Maintenance and Reliever Treatment
n=18 Participants
Patients on ICS (low dose)/LABA prior to study entry received 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 received SYMBICORT (budesonide/formoterol 200/6 μg) × 2 BID for maintenance and PRN for relief.
SYMBICORT as Maintenance, Salbutamol as Reliever Treatment
n=24 Participants
Patients on ICS (low dose)/LABA prior to study entry received 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 received SYMBICORT (budesonide/formoterol 200/6 μg) × 2 BID for maintenance + salbutamol (100 μg) PRN for relief.
Fractional Exhaled Nitric Oxide (FeNO)
8.67 parts per billion (ppb)
Interval 3.25 to 23.97
9.01 parts per billion (ppb)
Interval 2.28 to 18.58

PRIMARY outcome

Timeframe: From Day 1 to Day 169 (Treatment period)

Population: The FAS was defined as all patients randomised who had at least 1 post baseline measurement, irrespective of their protocol adherence and continued participation in the study.

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.

Outcome measures

Outcome measures
Measure
SYMBICORT as Maintenance and Reliever Treatment
n=18 Participants
Patients on ICS (low dose)/LABA prior to study entry received 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 received SYMBICORT (budesonide/formoterol 200/6 μg) × 2 BID for maintenance and PRN for relief.
SYMBICORT as Maintenance, Salbutamol as Reliever Treatment
n=24 Participants
Patients on ICS (low dose)/LABA prior to study entry received 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 received SYMBICORT (budesonide/formoterol 200/6 μg) × 2 BID for maintenance + salbutamol (100 μg) PRN for relief.
Total Asthma Symptoms Score
0.58 Score on a scale
Interval 0.08 to 1.26
0.83 Score on a scale
Interval 0.0 to 1.47

PRIMARY outcome

Timeframe: From Day 1 to Day 169 (Treatment period)

Population: The FAS was defined as all patients randomised who had at least 1 post baseline measurement, irrespective of their protocol adherence and continued participation in the study.

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.

Outcome measures

Outcome measures
Measure
SYMBICORT as Maintenance and Reliever Treatment
n=18 Participants
Patients on ICS (low dose)/LABA prior to study entry received 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 received SYMBICORT (budesonide/formoterol 200/6 μg) × 2 BID for maintenance and PRN for relief.
SYMBICORT as Maintenance, Salbutamol as Reliever Treatment
n=24 Participants
Patients on ICS (low dose)/LABA prior to study entry received 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 received SYMBICORT (budesonide/formoterol 200/6 μg) × 2 BID for maintenance + salbutamol (100 μg) PRN for relief.
Total Reliever Medication Use
0.75 Number of Occasions
Interval 0.0 to 1.47
1.16 Number of Occasions
Interval 0.31 to 2.75

PRIMARY outcome

Timeframe: From Day 1 to Day 169 (Treatment period)

Population: The FAS was defined as all patients randomised who had at least 1 post baseline measurement, irrespective of their protocol adherence and continued participation in the study.

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.

Outcome measures

Outcome measures
Measure
SYMBICORT as Maintenance and Reliever Treatment
n=18 Participants
Patients on ICS (low dose)/LABA prior to study entry received 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 received SYMBICORT (budesonide/formoterol 200/6 μg) × 2 BID for maintenance and PRN for relief.
SYMBICORT as Maintenance, Salbutamol as Reliever Treatment
n=24 Participants
Patients on ICS (low dose)/LABA prior to study entry received 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 received SYMBICORT (budesonide/formoterol 200/6 μg) × 2 BID for maintenance + salbutamol (100 μg) PRN for relief.
Forced Expiratory Volume in 1 Second (FEV1) (Morning and Evening)
Morning
0.169 Liter (L)
Interval 0.078 to 0.386
0.188 Liter (L)
Interval 0.089 to 0.576
Forced Expiratory Volume in 1 Second (FEV1) (Morning and Evening)
Evening
0.165 Liter (L)
Interval 0.079 to 0.361
0.197 Liter (L)
Interval 0.087 to 0.722

PRIMARY outcome

Timeframe: From Day 1 to Day 169 (Treatment period)

Population: The FAS was defined as all patients randomised who had at least 1 post baseline measurement, irrespective of their protocol adherence and continued participation in the study.

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.

Outcome measures

Outcome measures
Measure
SYMBICORT as Maintenance and Reliever Treatment
n=18 Participants
Patients on ICS (low dose)/LABA prior to study entry received 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 received SYMBICORT (budesonide/formoterol 200/6 μg) × 2 BID for maintenance and PRN for relief.
SYMBICORT as Maintenance, Salbutamol as Reliever Treatment
n=24 Participants
Patients on ICS (low dose)/LABA prior to study entry received 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 received SYMBICORT (budesonide/formoterol 200/6 μg) × 2 BID for maintenance + salbutamol (100 μg) PRN for relief.
Peak Expiratory Flow (PEF) (Morning and Evening)
Morning
30.92 Liter/minute (L/minute)
Interval 16.2 to 59.51
36.28 Liter/minute (L/minute)
Interval 19.89 to 73.16
Peak Expiratory Flow (PEF) (Morning and Evening)
Evening
30.17 Liter/minute (L/minute)
Interval 18.19 to 56.81
35.61 Liter/minute (L/minute)
Interval 22.86 to 79.42

SECONDARY outcome

Timeframe: From Day 1 to Day 169 (Treatment period)

Population: The FAS was defined as all patients randomised who had at least 1 post baseline measurement, irrespective of their protocol adherence and continued participation in the study.

The number of patients with inflammatory, asthma symptoms, lung function, and reliever use profile surrounding an event were assessed. Events of interest were Severe exacerbation (SevEx), composite surrogate endpoint for severe exacerbations of asthma (CompEx), and a single day (in 24 hours) with 6 or more occasions of reliever medication use. CompEx is an extended definition of asthma exacerbations combining diary-based event with traditionally defined severe exacerbations. Severe exacerbation are the events leading to one or more of the following; ≥ 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.

Outcome measures

Outcome measures
Measure
SYMBICORT as Maintenance and Reliever Treatment
n=18 Participants
Patients on ICS (low dose)/LABA prior to study entry received 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 received SYMBICORT (budesonide/formoterol 200/6 μg) × 2 BID for maintenance and PRN for relief.
SYMBICORT as Maintenance, Salbutamol as Reliever Treatment
n=24 Participants
Patients on ICS (low dose)/LABA prior to study entry received 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 received SYMBICORT (budesonide/formoterol 200/6 μg) × 2 BID for maintenance + salbutamol (100 μg) PRN for relief.
Number of Patients With Secondary Objective Events
SevEx events
2 Participants
7 Participants
Number of Patients With Secondary Objective Events
A single day (in 24 hours) with 6 or more occasions of reliever medication use
3 Participants
9 Participants
Number of Patients With Secondary Objective Events
CompEx events
4 Participants
12 Participants

SECONDARY outcome

Timeframe: From Day 1 to Day 169 (Treatment period)

Population: The FAS was defined as all patients randomised who had at least 1 post baseline measurement, irrespective of their protocol adherence and continued participation in the study.

The inflammatory, asthma symptoms, lung function, and reliever use profile surrounding an event were assessed. Events of interest were Severe exacerbation (SevEx), composite surrogate endpoint for severe exacerbations of asthma (CompEx), and a single day (in 24 hours) with 6 or more occasions of reliever medication use. CompEx is an extended definition of asthma exacerbations combining diary-based event with traditionally defined severe exacerbations. Severe exacerbation are the events leading to one or more of the following; ≥ 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.

Outcome measures

Outcome measures
Measure
SYMBICORT as Maintenance and Reliever Treatment
n=18 Participants
Patients on ICS (low dose)/LABA prior to study entry received 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 received SYMBICORT (budesonide/formoterol 200/6 μg) × 2 BID for maintenance and PRN for relief.
SYMBICORT as Maintenance, Salbutamol as Reliever Treatment
n=24 Participants
Patients on ICS (low dose)/LABA prior to study entry received 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 received SYMBICORT (budesonide/formoterol 200/6 μg) × 2 BID for maintenance + salbutamol (100 μg) PRN for relief.
Number of Secondary Objective Events
SevEx events
2 Number of events
8 Number of events
Number of Secondary Objective Events
CompEx events
8 Number of events
15 Number of events
Number of Secondary Objective Events
A single day (in 24 hours) with 6 or more occasions of reliever medication use
3 Number of events
18 Number of events

Adverse Events

SYMBICORT as Maintenance and Reliever Treatment

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

SYMBICORT as Maintenance, Salbutamol as Reliever Treatment

Serious events: 1 serious events
Other events: 0 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
SYMBICORT as Maintenance and Reliever Treatment
n=18 participants at risk
Patients on ICS (low dose)/LABA prior to study entry received 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 received SYMBICORT (budesonide/formoterol 200/6 μg) × 2 BID for maintenance and PRN for relief.
SYMBICORT as Maintenance, Salbutamol as Reliever Treatment
n=24 participants at risk
Patients on ICS (low dose)/LABA prior to study entry received 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 received SYMBICORT (budesonide/formoterol 200/6 μg) × 2 BID for maintenance + salbutamol (100 μg) PRN for relief.
Infections and infestations
Central nervous system infection
0.00%
0/18 • From Run-in period (Day -14 to -1) up to premature discontinuation visit and last Event Visit (Day 169)
4.2%
1/24 • Number of events 1 • From Run-in period (Day -14 to -1) up to premature discontinuation visit and last Event Visit (Day 169)

Other adverse events

Adverse event data not reported

Additional Information

Global Clinical Lead

AstraZeneca

Phone: 1-877-240-9479

Results disclosure agreements

  • Principal investigator is a sponsor employee This document contains trade secrets and confidential commercial information, disclosure of which is prohibited without providing advance notice to AstraZeneca and opportunity to object.
  • Publication restrictions are in place

Restriction type: OTHER