Trial Outcomes & Findings for New Breath Actuated MDI Symbicort Compared to Symbicort pMDI and Budesonide pMDI for 12 Weeks Twice a Day (NCT NCT01360021)
NCT ID: NCT01360021
Last Updated: 2014-03-11
Results Overview
Descriptive statistics for post-dose FEV1 (L) by visit; Baseline defined as the last pre-dose value prior to 1st dose of randomized therapy. Trt Avg = Mean of all available valid values after randomization.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
214 participants
Primary outcome timeframe
60 minutes post-dose in clinic visits at baseline, and week 0, 3, 7, 12 and Trt Avg
Results posted on
2014-03-11
Participant Flow
Participant milestones
| Measure |
Symbicort BA MDI
Symbicort BA MDI 2x160/4.5 μg twice daily
|
Symbicort pMDI
Symbicort AC pDMI 2x160/4.5 μg twice daily
|
Budesonide
Budesonide AC pMDI 2x160 μg twice daily
|
|---|---|---|---|
|
Overall Study
STARTED
|
71
|
71
|
72
|
|
Overall Study
COMPLETED
|
63
|
67
|
65
|
|
Overall Study
NOT COMPLETED
|
8
|
4
|
7
|
Reasons for withdrawal
| Measure |
Symbicort BA MDI
Symbicort BA MDI 2x160/4.5 μg twice daily
|
Symbicort pMDI
Symbicort AC pDMI 2x160/4.5 μg twice daily
|
Budesonide
Budesonide AC pMDI 2x160 μg twice daily
|
|---|---|---|---|
|
Overall Study
Eligibility criteria + other
|
2
|
1
|
1
|
|
Overall Study
Protocol Violation
|
0
|
0
|
1
|
|
Overall Study
Withdrawal by Subject
|
4
|
0
|
2
|
|
Overall Study
Adverse Event
|
2
|
3
|
3
|
Baseline Characteristics
New Breath Actuated MDI Symbicort Compared to Symbicort pMDI and Budesonide pMDI for 12 Weeks Twice a Day
Baseline characteristics by cohort
| Measure |
Symbicort BA MDI
n=71 Participants
Symbicort BA MDI 2x160/4.5 μg twice daily
|
Symbicort pMDI
n=71 Participants
Symbicort AC pDMI 2x160/4.5 μg twice daily
|
Budesonide
n=72 Participants
Budesonide AC pMDI 2x160 μg twice daily
|
Total
n=214 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
42.83 Years
STANDARD_DEVIATION 16.156 • n=5 Participants
|
42.62 Years
STANDARD_DEVIATION 16.873 • n=7 Participants
|
42.72 Years
STANDARD_DEVIATION 14.424 • n=5 Participants
|
42.72 Years
STANDARD_DEVIATION 15.770 • n=4 Participants
|
|
Age, Customized
12 - <18 years
|
6 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
21 Participants
n=4 Participants
|
|
Age, Customized
18 - <65 years
|
60 Participants
n=5 Participants
|
56 Participants
n=7 Participants
|
62 Participants
n=5 Participants
|
178 Participants
n=4 Participants
|
|
Age, Customized
65 - <75 years
|
4 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
10 Participants
n=4 Participants
|
|
Age, Customized
>= 75 years
|
1 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
|
Sex: Female, Male
Female
|
37 Participants
n=5 Participants
|
47 Participants
n=7 Participants
|
35 Participants
n=5 Participants
|
119 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
34 Participants
n=5 Participants
|
24 Participants
n=7 Participants
|
37 Participants
n=5 Participants
|
95 Participants
n=4 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Asian
|
4 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Black or African American
|
9 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
27 Participants
n=4 Participants
|
|
Race (NIH/OMB)
White
|
57 Participants
n=5 Participants
|
63 Participants
n=7 Participants
|
57 Participants
n=5 Participants
|
177 Participants
n=4 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
|
Years since asthma diagnosis
|
24.26 Years
STANDARD_DEVIATION 14.891 • n=5 Participants
|
24.12 Years
STANDARD_DEVIATION 15.128 • n=7 Participants
|
24.38 Years
STANDARD_DEVIATION 15.183 • n=5 Participants
|
24.25 Years
STANDARD_DEVIATION 14.998 • n=4 Participants
|
|
% Predicted FEV1 (Visit 2)
|
67.27 %
STANDARD_DEVIATION 10.048 • n=5 Participants
|
65.02 %
STANDARD_DEVIATION 11.135 • n=7 Participants
|
68.49 %
STANDARD_DEVIATION 9.924 • n=5 Participants
|
66.93 %
STANDARD_DEVIATION 10.434 • n=4 Participants
|
|
% Reversibility in FEV1 (Visit 2)
|
23.93 %
STANDARD_DEVIATION 15.728 • n=5 Participants
|
28.04 %
STANDARD_DEVIATION 14.712 • n=7 Participants
|
23.64 %
STANDARD_DEVIATION 12.692 • n=5 Participants
|
25.20 %
STANDARD_DEVIATION 14.491 • n=4 Participants
|
|
% Reversibility in FEV1 (Visit 3)
|
26.43 %
STANDARD_DEVIATION 16.662 • n=5 Participants
|
28.22 %
STANDARD_DEVIATION 16.118 • n=7 Participants
|
24.88 %
STANDARD_DEVIATION 14.235 • n=5 Participants
|
26.51 %
STANDARD_DEVIATION 15.692 • n=4 Participants
|
|
Baseline % Predicted FEV1 (Visit 4)
|
67.78 %
STANDARD_DEVIATION 11.059 • n=5 Participants
|
67.31 %
STANDARD_DEVIATION 10.683 • n=7 Participants
|
68.27 %
STANDARD_DEVIATION 11.078 • n=5 Participants
|
67.79 %
STANDARD_DEVIATION 10.898 • n=4 Participants
|
PRIMARY outcome
Timeframe: 60 minutes post-dose in clinic visits at baseline, and week 0, 3, 7, 12 and Trt AvgPopulation: Full analysis set: It consist of all randomized patients who received at least one dose of study medication and contributed sufficient data for at least one efficacy endpoint (Primary variable).
Descriptive statistics for post-dose FEV1 (L) by visit; Baseline defined as the last pre-dose value prior to 1st dose of randomized therapy. Trt Avg = Mean of all available valid values after randomization.
Outcome measures
| Measure |
Symbicort BA MDI
n=71 Participants
Symbicort BA MDI 2x160/4.5 μg twice daily
|
Symbicort pMDI
n=71 Participants
Symbicort AC pDMI 2x160/4.5 μg twice daily
|
Budesonide
n=71 Participants
Budesonide AC pMDI 2x160 μg twice daily
|
|---|---|---|---|
|
Forced Expiratory Volume in 1 Second (FEV1) - Post Dose
Baseline
|
2.09 Liter
Geometric Coefficient of Variation 31.46
|
1.97 Liter
Geometric Coefficient of Variation 27.16
|
2.12 Liter
Geometric Coefficient of Variation 26.34
|
|
Forced Expiratory Volume in 1 Second (FEV1) - Post Dose
Week 0
|
2.49 Liter
Geometric Coefficient of Variation 32.14
|
2.35 Liter
Geometric Coefficient of Variation 25.97
|
2.28 Liter
Geometric Coefficient of Variation 27.18
|
|
Forced Expiratory Volume in 1 Second (FEV1) - Post Dose
Week 3
|
2.52 Liter
Geometric Coefficient of Variation 31.98
|
2.34 Liter
Geometric Coefficient of Variation 26.31
|
2.30 Liter
Geometric Coefficient of Variation 30.22
|
|
Forced Expiratory Volume in 1 Second (FEV1) - Post Dose
Week 7
|
2.59 Liter
Geometric Coefficient of Variation 32.17
|
2.35 Liter
Geometric Coefficient of Variation 27.22
|
2.33 Liter
Geometric Coefficient of Variation 29.29
|
|
Forced Expiratory Volume in 1 Second (FEV1) - Post Dose
Week 12
|
2.52 Liter
Geometric Coefficient of Variation 30.71
|
2.39 Liter
Geometric Coefficient of Variation 27.31
|
2.30 Liter
Geometric Coefficient of Variation 28.27
|
|
Forced Expiratory Volume in 1 Second (FEV1) - Post Dose
Treatment Average
|
2.53 Liter
Geometric Coefficient of Variation 30.57
|
2.37 Liter
Geometric Coefficient of Variation 26.33
|
2.30 Liter
Geometric Coefficient of Variation 28.36
|
PRIMARY outcome
Timeframe: Pre AM dose in clinic visits at baseline, and week 3, 7, 12 and Trt AvgPopulation: Full analysis set: It consist of all randomized patients who received at least one dose of study medication and contributed sufficient data for at least one efficacy endpoint (Primary variable).
Descriptive statistics for predose FEV1(L) by visit; Baseline defined as the last pre-dose value prior to 1st dose of randomized therapy. Trt Avg = Mean of all available valid values after randomization.
Outcome measures
| Measure |
Symbicort BA MDI
n=71 Participants
Symbicort BA MDI 2x160/4.5 μg twice daily
|
Symbicort pMDI
n=71 Participants
Symbicort AC pDMI 2x160/4.5 μg twice daily
|
Budesonide
n=71 Participants
Budesonide AC pMDI 2x160 μg twice daily
|
|---|---|---|---|
|
Forced Expiratory Volume in 1 Second (FEV1) - Pre Dose
Baseline
|
2.09 Liters
Geometric Coefficient of Variation 31.46
|
1.97 Liters
Geometric Coefficient of Variation 27.16
|
2.12 Liters
Geometric Coefficient of Variation 26.34
|
|
Forced Expiratory Volume in 1 Second (FEV1) - Pre Dose
Week 3
|
2.32 Liters
Geometric Coefficient of Variation 32.79
|
2.12 Liters
Geometric Coefficient of Variation 28.29
|
2.22 Liters
Geometric Coefficient of Variation 31.21
|
|
Forced Expiratory Volume in 1 Second (FEV1) - Pre Dose
Week 7
|
2.40 Liters
Geometric Coefficient of Variation 32.86
|
2.11 Liters
Geometric Coefficient of Variation 29.96
|
2.25 Liters
Geometric Coefficient of Variation 29.01
|
|
Forced Expiratory Volume in 1 Second (FEV1) - Pre Dose
Week 12
|
2.34 Liters
Geometric Coefficient of Variation 30.84
|
2.17 Liters
Geometric Coefficient of Variation 31.29
|
2.23 Liters
Geometric Coefficient of Variation 30.15
|
|
Forced Expiratory Volume in 1 Second (FEV1) - Pre Dose
Average of treatment period
|
2.34 Liters
Geometric Coefficient of Variation 30.15
|
2.15 Liters
Geometric Coefficient of Variation 29.15
|
2.23 Liters
Geometric Coefficient of Variation 29.36
|
SECONDARY outcome
Timeframe: Recorded morning upon rising and evening before sleep for 14 weeksPopulation: Full analysis set: It consist of all randomized patients who received at least one dose of study medication and contributed sufficient data for at least one efficacy endpoint (Primary variable).
Outcome measures
| Measure |
Symbicort BA MDI
n=71 Participants
Symbicort BA MDI 2x160/4.5 μg twice daily
|
Symbicort pMDI
n=71 Participants
Symbicort AC pDMI 2x160/4.5 μg twice daily
|
Budesonide
n=71 Participants
Budesonide AC pMDI 2x160 μg twice daily
|
|---|---|---|---|
|
Peak Expiratory Flow
Morning Peak expiratory flow (Baseline)
|
357.95 L/Min
Standard Deviation 100.59
|
335.70 L/Min
Standard Deviation 102.99
|
360.46 L/Min
Standard Deviation 103.09
|
|
Peak Expiratory Flow
Evening Peak expiratory flow (Baseline)
|
364.61 L/Min
Standard Deviation 103.62
|
347.86 L/Min
Standard Deviation 110.80
|
367.64 L/Min
Standard Deviation 102.73
|
|
Peak Expiratory Flow
Evening Peak expiratory flow (Treatment Average)
|
379.96 L/Min
Standard Deviation 104.72
|
362.99 L/Min
Standard Deviation 112.63
|
348.94 L/Min
Standard Deviation 97.94
|
|
Peak Expiratory Flow
Morning Peak expiratory flow (Treatment Average)
|
376.28 L/Min
Standard Deviation 106.76
|
353.69 L/Min
Standard Deviation 108.72
|
343.59 L/Min
Standard Deviation 98.12
|
SECONDARY outcome
Timeframe: Recorded between 6:00 - 11:00 AM from previous 12 hours and 6:00 -11:00 PM from previous 12 hours for 14 weeksPopulation: Full analysis set: It consist of all randomized patients who received at least one dose of study medication and contributed sufficient data for at least one efficacy endpoint (Primary variable).
The total score is calculated as sum of the morning and evening scores of each day and the treatment period mean score is defined as the mean of all total score recorded during the 12-week treatment period. Trt Avg=Mean total score of double-blind period values.(day/night score ranges from 0 to 3; 0=no asthma symptoms; 3= unable to do normal activities (or to sleep) due to asthma). Higher score represents worse outcome.
Outcome measures
| Measure |
Symbicort BA MDI
n=71 Participants
Symbicort BA MDI 2x160/4.5 μg twice daily
|
Symbicort pMDI
n=71 Participants
Symbicort AC pDMI 2x160/4.5 μg twice daily
|
Budesonide
n=71 Participants
Budesonide AC pMDI 2x160 μg twice daily
|
|---|---|---|---|
|
Asthma Symptoms Score (Total)
Baseline
|
2.04 Asthma score on a scale of 0 to 3
Standard Deviation 0.98
|
1.92 Asthma score on a scale of 0 to 3
Standard Deviation 0.72
|
2.12 Asthma score on a scale of 0 to 3
Standard Deviation 0.88
|
|
Asthma Symptoms Score (Total)
Treatment Average (Trt Avg)
|
1.68 Asthma score on a scale of 0 to 3
Standard Deviation 1.10
|
1.45 Asthma score on a scale of 0 to 3
Standard Deviation 0.91
|
2.02 Asthma score on a scale of 0 to 3
Standard Deviation 0.96
|
SECONDARY outcome
Timeframe: Recorded 6:00 - 11:00 AM for 14 weeksPopulation: Full analysis set: It consist of all randomized patients who received at least one dose of study medication and contributed sufficient data for at least one efficacy endpoint (Primary variable).
The percentage of days with no awakenings due to asthma. Baseline= Mean % awakening-free nights during run-in period ; Trt Avg=Mean % awakening-free nights during double-blind period.
Outcome measures
| Measure |
Symbicort BA MDI
n=71 Participants
Symbicort BA MDI 2x160/4.5 μg twice daily
|
Symbicort pMDI
n=71 Participants
Symbicort AC pDMI 2x160/4.5 μg twice daily
|
Budesonide
n=71 Participants
Budesonide AC pMDI 2x160 μg twice daily
|
|---|---|---|---|
|
Night-time Awakenings Due to Asthma Symptoms(% Awakening-free Nights)
Baseline
|
78.54 Percentage of days with no awakenings
Standard Deviation 28.97
|
78.76 Percentage of days with no awakenings
Standard Deviation 29.76
|
81.59 Percentage of days with no awakenings
Standard Deviation 25.32
|
|
Night-time Awakenings Due to Asthma Symptoms(% Awakening-free Nights)
Treatment Average (Trt Avg)
|
83.73 Percentage of days with no awakenings
Standard Deviation 30.90
|
89.93 Percentage of days with no awakenings
Standard Deviation 21.40
|
84.62 Percentage of days with no awakenings
Standard Deviation 26.31
|
SECONDARY outcome
Timeframe: Recorded between 6:00 - 11:00 AM from previous 12 hours and 6:00 -11:00 PM from previous 12 hours for 14 weeksPopulation: Full analysis set: It consist of all randomized patients who received at least one dose of study medication and contributed sufficient data for at least one efficacy endpoint (Primary variable).
Total daily rescue medication use is calculated as the sum of morning and evening use each day and averaged over the 12 weeks treatment periods to calculate the treatment period mean. Baseline= Mean rescue medication used during run-in period ; Trt Avg=Mean rescue medication used during double-blind period.
Outcome measures
| Measure |
Symbicort BA MDI
n=71 Participants
Symbicort BA MDI 2x160/4.5 μg twice daily
|
Symbicort pMDI
n=71 Participants
Symbicort AC pDMI 2x160/4.5 μg twice daily
|
Budesonide
n=71 Participants
Budesonide AC pMDI 2x160 μg twice daily
|
|---|---|---|---|
|
Use of Rescue Medication Day and Night (Total Daily Rescue Medication Use)
Baseline
|
2.55 Inhalations/24 hrs
Standard Deviation 2.48
|
2.19 Inhalations/24 hrs
Standard Deviation 1.75
|
2.65 Inhalations/24 hrs
Standard Deviation 2.36
|
|
Use of Rescue Medication Day and Night (Total Daily Rescue Medication Use)
Treatment Average (Trt Avg)
|
1.81 Inhalations/24 hrs
Standard Deviation 2.67
|
1.26 Inhalations/24 hrs
Standard Deviation 1.60
|
2.34 Inhalations/24 hrs
Standard Deviation 2.38
|
Adverse Events
Budesonide
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Symbicort BA MDI
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Symbicort pMDI
Serious events: 1 serious events
Other events: 7 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Budesonide
n=71 participants at risk
|
Symbicort BA MDI
n=71 participants at risk
|
Symbicort pMDI
n=71 participants at risk
|
|---|---|---|---|
|
Infections and infestations
APPENDICITIS
|
0.00%
0/71
'Number of participants in the safety analysis set is (71 for all the group)as 1 patients from the Budesonide group has not taken any dose of the IP, so not included in the Safety population'
|
0.00%
0/71
'Number of participants in the safety analysis set is (71 for all the group)as 1 patients from the Budesonide group has not taken any dose of the IP, so not included in the Safety population'
|
1.4%
1/71 • Number of events 1
'Number of participants in the safety analysis set is (71 for all the group)as 1 patients from the Budesonide group has not taken any dose of the IP, so not included in the Safety population'
|
Other adverse events
| Measure |
Budesonide
n=71 participants at risk
|
Symbicort BA MDI
n=71 participants at risk
|
Symbicort pMDI
n=71 participants at risk
|
|---|---|---|---|
|
Infections and infestations
VIRAL UPPER RESPIRATORY TRACT INFECTION
|
4.2%
3/71 • Number of events 3
'Number of participants in the safety analysis set is (71 for all the group)as 1 patients from the Budesonide group has not taken any dose of the IP, so not included in the Safety population'
|
2.8%
2/71 • Number of events 2
'Number of participants in the safety analysis set is (71 for all the group)as 1 patients from the Budesonide group has not taken any dose of the IP, so not included in the Safety population'
|
9.9%
7/71 • Number of events 7
'Number of participants in the safety analysis set is (71 for all the group)as 1 patients from the Budesonide group has not taken any dose of the IP, so not included in the Safety population'
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than less than or equal to 180 days from the date of AZ's request to allow for the filing of a patent app or the taking of such measures as AZ deems appropriate to establish and preserve its proprietary rights in teh material being submitted.
- Publication restrictions are in place
Restriction type: OTHER