BAI: New Breath Actuated MDI Symbicort Compared to Symbicort pMDI and Budesonide pMDI for 12 Weeks Twice a Day
Sponsor
AstraZeneca (Industry)
Overall Status
Completed
CT.gov ID
NCT01360021
Collaborator
(none)
214
41
3
9
5.2
0.6
Study Details
Study Description
Brief Summary
This is a comparison of the efficacy of the Symbicort breath actuated dose inhaler to the Symbicort pressured meter dose inhaler after 12 weeks of a twice a day dose.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
214 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Care Provider, Investigator)
Primary Purpose:
Treatment
Official Title:
A 12-week, Double-blind, Randomized, Multi-centre, Parallel-group Study Evaluating the Efficacy Safety, and Patient Use (User Study) of Symbicort® (Budesonide/Formoterol) Breath Actuated Metered Dose Inhaler (BA MDI) 2x160/4.5 μg Twice Daily Compared With Symbicort (Budesonide/Formoterol) AC (Actuation Counter) pMDI® 2x160/4.5 μg Twice Daily and Budesonide AC pMDI 2x160 μg Twice Daily in Adult and Adolescent Asthmatics
Study Start Date
:
Nov 1, 2011
Actual Primary Completion Date
:
Aug 1, 2012
Actual Study Completion Date
:
Aug 1, 2012
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: 1 Symbicort/inhaler Symbicort BA MDI 2x160/4.5 μg twice daily |
Drug: Symbicort
Breath actuated metered dose inhaler
|
| Active Comparator: Symbicort/inhaler Symbicort AC pDMI 2x160/4.5 μg twice daily |
Drug: Symbicort
Actuation counter pressured metered dose inhaler
|
| Active Comparator: Budesonide/inhaler Budesonide AC pMDI 2x160 μg twice daily |
Drug: Budesonide
Actuation counter pressured metered dose inhaler
|
Outcome Measures
Primary Outcome Measures
- Forced Expiratory Volume in 1 Second (FEV1) - Post Dose [60 minutes post-dose in clinic visits at baseline, and week 0, 3, 7, 12 and Trt Avg]
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.
- Forced Expiratory Volume in 1 Second (FEV1) - Pre Dose [Pre AM dose in clinic visits at baseline, and week 3, 7, 12 and Trt Avg]
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.
Secondary Outcome Measures
- Peak Expiratory Flow [Recorded morning upon rising and evening before sleep for 14 weeks]
- Asthma Symptoms Score (Total) [Recorded between 6:00 - 11:00 AM from previous 12 hours and 6:00 -11:00 PM from previous 12 hours for 14 weeks]
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.
- Night-time Awakenings Due to Asthma Symptoms(% Awakening-free Nights) [Recorded 6:00 - 11:00 AM for 14 weeks]
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.
- Use of Rescue Medication Day and Night (Total Daily Rescue Medication Use) [Recorded between 6:00 - 11:00 AM from previous 12 hours and 6:00 -11:00 PM from previous 12 hours for 14 weeks]
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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
12 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Male or female 12 years and above
-
Clinical diagnosis of asthma according to the American Thoracic Society definition at least 6 months
-
Pre-bronchodilator FEV1 ≥ 45% and ≤ 85% of predicted normal
-
Patients with reversible airway obstruction
-
Documented daily use of inhaled corticosteroids for ≥ 3 months
Exclusion Criteria:
-
History of life-threatening asthma, defined for this protocol as an asthma episode that required intubation and/or was associated with hypercapnea, respiratory arrest or hypoxic seizures during the 2 years prior to Visit 2
-
Hospitalized during previous 6 months for asthma
-
Required emergency treatment more than once during previous 6 months for an asthma-related condition
-
Intake of oral, rectal or parenteral glucocorticosteroid within 30 days of enrolment
-
Respiratory infection affecting the asthma within 30 days
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Research Site | Huntington Beach | California | United States | |
| 2 | Research Site | Long Beach | California | United States | |
| 3 | Research Site | Los Angeles | California | United States | |
| 4 | Research Site | Orange | California | United States | |
| 5 | Research Site | Rancho Mirage | California | United States | |
| 6 | Research Site | Riverside | California | United States | |
| 7 | Research Site | Sacramento | California | United States | |
| 8 | Research Site | San Diego | California | United States | |
| 9 | Research Site | San Jose | California | United States | |
| 10 | Research Site | Tallahassee | Florida | United States | |
| 11 | Research Site | Savannah | Georgia | United States | |
| 12 | Research Site | River Forest | Illinois | United States | |
| 13 | Research Site | Louisville | Kentucky | United States | |
| 14 | Research Site | Metairie | Louisiana | United States | |
| 15 | Research Site | Bangor | Maine | United States | |
| 16 | Research Site | Wheaton | Maryland | United States | |
| 17 | Research Site | North Dartmouth | Massachusetts | United States | |
| 18 | Research Site | Columbia | Missouri | United States | |
| 19 | Research Site | Rolla | Missouri | United States | |
| 20 | Research Site | Skillman | New Jersey | United States | |
| 21 | Research Site | North Syracuse | New York | United States | |
| 22 | Research Site | Rochester | New York | United States | |
| 23 | Research Site | Cincinnati | Ohio | United States | |
| 24 | Research Site | Collegeville | Pennsylvania | United States | |
| 25 | Research Site | Lincoln | Rhode Island | United States | |
| 26 | Research Site | Charleston | South Carolina | United States | |
| 27 | Research Site | Spartanburg | South Carolina | United States | |
| 28 | Research Site | Dallas | Texas | United States | |
| 29 | Research Site | Tacoma | Washington | United States | |
| 30 | Research Site | Greenfield | Wisconsin | United States | |
| 31 | Research Site | Madison | Wisconsin | United States | |
| 32 | Research Site | Ruse | Bulgaria | ||
| 33 | Research Site | Sevlievo | Bulgaria | ||
| 34 | Research Site | Sofia | Bulgaria | ||
| 35 | Research Site | Varna | Bulgaria | ||
| 36 | Research Site | Balassagyarmat | Hungary | ||
| 37 | Research Site | Budapest | Hungary | ||
| 38 | Research Site | Salgotarjan | Hungary | ||
| 39 | Research Site | Szazhalombatta | Hungary | ||
| 40 | Research Site | Ekaterinburg | Russia | Russian Federation | |
| 41 | Research Site | Moscow | Russia | Russian Federation |
Sponsors and Collaborators
- AstraZeneca
Investigators
- Study Director: Goran Eckerwall, MD, AstraZeneca R&D, Mölndal
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01360021
Other Study ID Numbers:
- D589OC00003
First Posted:
May 25, 2011
Last Update Posted:
Mar 11, 2014
Last Verified:
Jan 1, 2014
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Symbicort BA MDI | Symbicort pMDI | Budesonide |
|---|---|---|---|
| Arm/Group Description | Symbicort BA MDI 2x160/4.5 μg twice daily | Symbicort AC pDMI 2x160/4.5 μg twice daily | Budesonide AC pMDI 2x160 μg twice daily |
| Period Title: Overall Study | |||
| STARTED | 71 | 71 | 72 |
| COMPLETED | 63 | 67 | 65 |
| NOT COMPLETED | 8 | 4 | 7 |
Baseline Characteristics
| Arm/Group Title | Symbicort BA MDI | Symbicort pMDI | Budesonide | Total |
|---|---|---|---|---|
| Arm/Group Description | Symbicort BA MDI 2x160/4.5 μg twice daily | Symbicort AC pDMI 2x160/4.5 μg twice daily | Budesonide AC pMDI 2x160 μg twice daily | Total of all reporting groups |
| Overall Participants | 71 | 71 | 72 | 214 |
| Age (Years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [Years] |
42.83
(16.156)
|
42.62
(16.873)
|
42.72
(14.424)
|
42.72
(15.770)
|
| Age, Customized (Number) [Number] | ||||
| 12 - <18 years |
6
8.5%
|
8
11.3%
|
7
9.7%
|
21
9.8%
|
| 18 - <65 years |
60
84.5%
|
56
78.9%
|
62
86.1%
|
178
83.2%
|
| 65 - <75 years |
4
5.6%
|
4
5.6%
|
2
2.8%
|
10
4.7%
|
| >= 75 years |
1
1.4%
|
3
4.2%
|
1
1.4%
|
5
2.3%
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
37
52.1%
|
47
66.2%
|
35
48.6%
|
119
55.6%
|
| Male |
34
47.9%
|
24
33.8%
|
37
51.4%
|
95
44.4%
|
| Race (NIH/OMB) (Count of Participants) | ||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Asian |
4
5.6%
|
1
1.4%
|
1
1.4%
|
6
2.8%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
1
1.4%
|
1
0.5%
|
| Black or African American |
9
12.7%
|
7
9.9%
|
11
15.3%
|
27
12.6%
|
| White |
57
80.3%
|
63
88.7%
|
57
79.2%
|
177
82.7%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
1
1.4%
|
0
0%
|
2
2.8%
|
3
1.4%
|
| Years since asthma diagnosis (Years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [Years] |
24.26
(14.891)
|
24.12
(15.128)
|
24.38
(15.183)
|
24.25
(14.998)
|
| % Predicted FEV1 (Visit 2) (%) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [%] |
67.27
(10.048)
|
65.02
(11.135)
|
68.49
(9.924)
|
66.93
(10.434)
|
| % Reversibility in FEV1 (Visit 2) (%) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [%] |
23.93
(15.728)
|
28.04
(14.712)
|
23.64
(12.692)
|
25.20
(14.491)
|
| % Reversibility in FEV1 (Visit 3) (%) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [%] |
26.43
(16.662)
|
28.22
(16.118)
|
24.88
(14.235)
|
26.51
(15.692)
|
| Baseline % Predicted FEV1 (Visit 4) (%) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [%] |
67.78
(11.059)
|
67.31
(10.683)
|
68.27
(11.078)
|
67.79
(10.898)
|
Outcome Measures
| Title | Forced Expiratory Volume in 1 Second (FEV1) - Post Dose |
|---|---|
| Description | 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. |
| Time Frame | 60 minutes post-dose in clinic visits at baseline, and week 0, 3, 7, 12 and Trt Avg |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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). |
| Arm/Group Title | Symbicort BA MDI | Symbicort pMDI | Budesonide |
|---|---|---|---|
| Arm/Group Description | Symbicort BA MDI 2x160/4.5 μg twice daily | Symbicort AC pDMI 2x160/4.5 μg twice daily | Budesonide AC pMDI 2x160 μg twice daily |
| Measure Participants | 71 | 71 | 71 |
| Baseline |
2.09
(31.46)
|
1.97
(27.16)
|
2.12
(26.34)
|
| Week 0 |
2.49
(32.14)
|
2.35
(25.97)
|
2.28
(27.18)
|
| Week 3 |
2.52
(31.98)
|
2.34
(26.31)
|
2.30
(30.22)
|
| Week 7 |
2.59
(32.17)
|
2.35
(27.22)
|
2.33
(29.29)
|
| Week 12 |
2.52
(30.71)
|
2.39
(27.31)
|
2.30
(28.27)
|
| Treatment Average |
2.53
(30.57)
|
2.37
(26.33)
|
2.30
(28.36)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Symbicort pMDI, Budesonide |
|---|---|---|
| Comments | The comparison of Symbicort AC pMDI 2x160/4.5 µg bid with budesonide AC pMDI 2x160 µg bid for post dose FEV1 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ANCOVA model on the log transformed outcome variable with treatment and country as factor, and log transformed baseline FEV1 (pre-dose) as covariate. | |
| Method of Estimation | Estimation Parameter | Estimated Geometic Mean Ratio |
| Estimated Value | 1.10 | |
| Confidence Interval |
(2-Sided) 95% 1.06 to 1.14 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Symbicort AC pMDI 2x160/4.5 µg bid vs Budesonide AC pMDI 2x160 µg bid | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Symbicort BA MDI, Symbicort pMDI |
|---|---|---|
| Comments | The comparisons of Symbicort BA MDI 2x160/4.5 µg bid with Symbicort AC pMDI 2x160/4.5 µg bid for post dose FEV1. | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | Assuming a standard deviation of 0.2 (for pre dose FEV1) on the log-scale and 60 patients/arm, the width of the confidence interval will extend 0.072 from the point estimate on the log-scale. The lower and upper limits of the CI for the ratio of effects will thus be obtained by multiplying the estimated ratio by 0.931 and 1.075, respectively. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Estimated Geometric Mean Ratio |
| Estimated Value | 1.01 | |
| Confidence Interval |
(2-Sided) 95% 0.97 to 1.05 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The comparisons was used to assess therapeutic equivalence of Symbicort AC pMDI and Symbicort BA MDI. Assay sensitivity was demonstrated before proceeding to assess therapeutic equivalence of the 2 Symbicort products. | |
| Title | Forced Expiratory Volume in 1 Second (FEV1) - Pre Dose |
|---|---|
| Description | 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. |
| Time Frame | Pre AM dose in clinic visits at baseline, and week 3, 7, 12 and Trt Avg |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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). |
| Arm/Group Title | Symbicort BA MDI | Symbicort pMDI | Budesonide |
|---|---|---|---|
| Arm/Group Description | Symbicort BA MDI 2x160/4.5 μg twice daily | Symbicort AC pDMI 2x160/4.5 μg twice daily | Budesonide AC pMDI 2x160 μg twice daily |
| Measure Participants | 71 | 71 | 71 |
| Baseline |
2.09
(31.46)
|
1.97
(27.16)
|
2.12
(26.34)
|
| Week 3 |
2.32
(32.79)
|
2.12
(28.29)
|
2.22
(31.21)
|
| Week 7 |
2.40
(32.86)
|
2.11
(29.96)
|
2.25
(29.01)
|
| Week 12 |
2.34
(30.84)
|
2.17
(31.29)
|
2.23
(30.15)
|
| Average of treatment period |
2.34
(30.15)
|
2.15
(29.15)
|
2.23
(29.36)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Symbicort BA MDI, Symbicort pMDI |
|---|---|---|
| Comments | The comparisons of Symbicort BA MDI 2x160/4.5 µg bid with Symbicort AC pMDI 2x160/4.5 µg bid, for pre-dose FEV1. | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | Assuming a standard deviation of 0.2 (for pre dose FEV1) on the log-scale and 60 patients/arm, the width of the confidence interval will extend 0.072 from the point estimate on the log-scale. The lower and upper limits of the CI for the ratio of effects will thus be obtained by multiplying the estimated ratio by 0.931 and 1.075, respectively. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Estimated Geometric Mean Ratio |
| Estimated Value | 1.03 | |
| Confidence Interval |
(2-Sided) 95% 0.99 to 1.08 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The comparisons was used to assess therapeutic equivalence of Symbicort AC pMDI and Symbicort BA MDI. Assay sensitivity was demonstrated before proceeding to assess therapeutic equivalence of the 2 Symbicort products. | |
| Title | Peak Expiratory Flow |
|---|---|
| Description | |
| Time Frame | Recorded morning upon rising and evening before sleep for 14 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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). |
| Arm/Group Title | Symbicort BA MDI | Symbicort pMDI | Budesonide |
|---|---|---|---|
| Arm/Group Description | Symbicort BA MDI 2x160/4.5 μg twice daily | Symbicort AC pDMI 2x160/4.5 μg twice daily | Budesonide AC pMDI 2x160 μg twice daily |
| Measure Participants | 71 | 71 | 71 |
| Morning Peak expiratory flow (Baseline) |
357.95
(100.59)
|
335.70
(102.99)
|
360.46
(103.09)
|
| Evening Peak expiratory flow (Baseline) |
364.61
(103.62)
|
347.86
(110.80)
|
367.64
(102.73)
|
| Evening Peak expiratory flow (Treatment Average) |
379.96
(104.72)
|
362.99
(112.63)
|
348.94
(97.94)
|
| Morning Peak expiratory flow (Treatment Average) |
376.28
(106.76)
|
353.69
(108.72)
|
343.59
(98.12)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Symbicort BA MDI, Symbicort pMDI |
|---|---|---|
| Comments | Morning peak expiratory flow (mPEF): Comparing mean changes from baseline to the average of the double-blind treatment period between Symbicort BA MDI 2x160/4.5 μg bid and Symbicort AC pMDI 2x160/4.5 µg bid | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | No adjustment were be made for multiplicity for these supportive variables and nominal p-values were reported. | |
| Statistical Test of Hypothesis | p-Value | 0.825 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ANCOVA model includes treatment and country as a factor and baseline value as covariate. | |
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | 1.49 | |
| Confidence Interval |
(2-Sided) 95% -11.81 to 14.80 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 6.75 |
|
| Estimation Comments | Secondary efficacy variables were analyzed as continuous data, comparing mean changes from baseline to the average of the double-blind treatment period between treatments. No adjustment were made for multiplicity and nominal p-values were reported. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Symbicort pMDI, Budesonide |
|---|---|---|
| Comments | Morning peak expiratory flow (mPEF): Comparing mean changes from baseline to the average of the double-blind treatment period between Symbicort AC pMDI 2x160/4.5 µg bid minus Budesonide AC pMDI 2x160 µg bid | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ANCOVA model includes treatment and country as a factor and baseline value as covariate. | |
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | 33.52 | |
| Confidence Interval |
(2-Sided) 95% 20.11 to 46.93 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 6.80 |
|
| Estimation Comments | Secondary efficacy variables were analyzed as continuous data, comparing mean changes from baseline to the average of the double-blind treatment period between treatments. No adjustment were made for multiplicity and nominal p-values were reported. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Symbicort BA MDI, Symbicort pMDI |
|---|---|---|
| Comments | Evening peak expiratory flow (ePEF): Comparing mean changes from baseline to the average of the double-blind treatment period between Symbicort BA MDI 2x160/4.5 μg bid and Symbicort AC pMDI 2x160/4.5 µg bid. | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | No adjustment were made for multiplicity for these supportive variables and nominal p-values were reported. | |
| Statistical Test of Hypothesis | p-Value | 0.810 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ANCOVA model includes treatment and country as a factor and baseline value as covariate. | |
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | 1.48 | |
| Confidence Interval |
(2-Sided) 95% -10.66 to 13.61 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 6.15 |
|
| Estimation Comments | Secondary efficacy variables were analyzed as continuous data, comparing mean changes from baseline to the average of the double-blind treatment period between treatments. No adjustment were made for multiplicity and nominal p-values were reported. | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Symbicort pMDI, Budesonide |
|---|---|---|
| Comments | Evening peak expiratory flow (ePEF): Comparing mean changes from baseline to the average of the double-blind treatment period between Symbicort AC pMDI 2x160/4.5 µg bid and Budesonide AC pMDI 2x160 µg bid. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ANCOVA model includes treatment and country as a factor and baseline value as covariate. | |
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | 32.25 | |
| Confidence Interval |
(2-Sided) 95% 20.01 to 44.49 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 6.21 |
|
| Estimation Comments | Secondary efficacy variables were analyzed as continuous data, comparing mean changes from baseline to the average of the double-blind treatment period between treatments. No adjustment were made for multiplicity and nominal p-values were reported. | |
| Title | Asthma Symptoms Score (Total) |
|---|---|
| Description | 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. |
| Time Frame | Recorded between 6:00 - 11:00 AM from previous 12 hours and 6:00 -11:00 PM from previous 12 hours for 14 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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). |
| Arm/Group Title | Symbicort BA MDI | Symbicort pMDI | Budesonide |
|---|---|---|---|
| Arm/Group Description | Symbicort BA MDI 2x160/4.5 μg twice daily | Symbicort AC pDMI 2x160/4.5 μg twice daily | Budesonide AC pMDI 2x160 μg twice daily |
| Measure Participants | 71 | 71 | 71 |
| Baseline |
2.04
(0.98)
|
1.92
(0.72)
|
2.12
(0.88)
|
| Treatment Average (Trt Avg) |
1.68
(1.10)
|
1.45
(0.91)
|
2.02
(0.96)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Symbicort BA MDI, Symbicort pMDI |
|---|---|---|
| Comments | Comparing mean changes from baseline to the average of the double-blind treatment period between Symbicort BA MDI 2x160/4.5 μg bid and Symbicort AC pMDI 2x160/4.5 µg bid. | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | No adjustment were made for multiplicity for these supportive variables and nominal p-values were reported. | |
| Statistical Test of Hypothesis | p-Value | 0.272 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ANCOVA model includes treatment and country as a factor and baseline value as covariate. | |
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | 0.13 | |
| Confidence Interval |
(2-Sided) 95% -0.10 to 0.35 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.11 |
|
| Estimation Comments | ||
| Title | Night-time Awakenings Due to Asthma Symptoms(% Awakening-free Nights) |
|---|---|
| Description | 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. |
| Time Frame | Recorded 6:00 - 11:00 AM for 14 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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). |
| Arm/Group Title | Symbicort BA MDI | Symbicort pMDI | Budesonide |
|---|---|---|---|
| Arm/Group Description | Symbicort BA MDI 2x160/4.5 μg twice daily | Symbicort AC pDMI 2x160/4.5 μg twice daily | Budesonide AC pMDI 2x160 μg twice daily |
| Measure Participants | 71 | 71 | 71 |
| Baseline |
78.54
(28.97)
|
78.76
(29.76)
|
81.59
(25.32)
|
| Treatment Average (Trt Avg) |
83.73
(30.90)
|
89.93
(21.40)
|
84.62
(26.31)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Symbicort BA MDI, Symbicort pMDI |
|---|---|---|
| Comments | Comparing mean changes from baseline to the average of the double-blind treatment period between Symbicort BA MDI 2x160/4.5 μg bid and Symbicort AC pMDI 2x160/4.5 µg bid. | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | No adjustment were made for multiplicity for these supportive variables and nominal p-values were reported. | |
| Statistical Test of Hypothesis | p-Value | 0.025 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ANCOVA model includes treatment and country as a factor and baseline value as covariate. | |
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | -6.10 | |
| Confidence Interval |
(2-Sided) 95% -11.41 to -0.79 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 2.69 |
|
| Estimation Comments | ||
| Title | Use of Rescue Medication Day and Night (Total Daily Rescue Medication Use) |
|---|---|
| Description | 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. |
| Time Frame | Recorded between 6:00 - 11:00 AM from previous 12 hours and 6:00 -11:00 PM from previous 12 hours for 14 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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). |
| Arm/Group Title | Symbicort BA MDI | Symbicort pMDI | Budesonide |
|---|---|---|---|
| Arm/Group Description | Symbicort BA MDI 2x160/4.5 μg twice daily | Symbicort AC pDMI 2x160/4.5 μg twice daily | Budesonide AC pMDI 2x160 μg twice daily |
| Measure Participants | 71 | 71 | 71 |
| Baseline |
2.55
(2.48)
|
2.19
(1.75)
|
2.65
(2.36)
|
| Treatment Average (Trt Avg) |
1.81
(2.67)
|
1.26
(1.60)
|
2.34
(2.38)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Symbicort BA MDI, Symbicort pMDI |
|---|---|---|
| Comments | Comparing mean changes from baseline to the average of the double-blind treatment period between BAI Symbicort BA MDI 2x160/4.5 μg bid and pMDI Symbicort AC pMDI 2x160/4.5 µg bid. | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | No adjustment were made for multiplicity for these supportive variables and nominal p-values were reported. | |
| Statistical Test of Hypothesis | p-Value | 0.258 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ANCOVA model includes treatment and country as a factor and baseline value as covariate. | |
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | 0.26 | |
| Confidence Interval |
(2-Sided) 95% -0.19 to 0.71 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.23 |
|
| Estimation Comments | ||
Adverse Events
| Time Frame | ||||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | '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' | |||||
| Arm/Group Title | Budesonide | Symbicort BA MDI | Symbicort pMDI | |||
| Arm/Group Description | ||||||
All Cause Mortality |
||||||
| Budesonide | Symbicort BA MDI | Symbicort pMDI | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | |||
Serious Adverse Events |
||||||
| Budesonide | Symbicort BA MDI | Symbicort pMDI | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/71 (0%) | 0/71 (0%) | 1/71 (1.4%) | |||
| Infections and infestations | ||||||
| APPENDICITIS | 0/71 (0%) | 0 | 0/71 (0%) | 0 | 1/71 (1.4%) | 1 |
Other (Not Including Serious) Adverse Events |
||||||
| Budesonide | Symbicort BA MDI | Symbicort pMDI | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/71 (4.2%) | 2/71 (2.8%) | 7/71 (9.9%) | |||
| Infections and infestations | ||||||
| VIRAL UPPER RESPIRATORY TRACT INFECTION | 3/71 (4.2%) | 3 | 2/71 (2.8%) | 2 | 7/71 (9.9%) | 7 |
Limitations/Caveats
No. 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.
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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.
Results Point of Contact
| Name/Title | Goran Eckerwall, MD |
|---|---|
| Organization | Astrazeneca |
| Phone | |
| aztrial_results_posting@astrazeneca.com |
Responsible Party:
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01360021
Other Study ID Numbers:
- D589OC00003
First Posted:
May 25, 2011
Last Update Posted:
Mar 11, 2014
Last Verified:
Jan 1, 2014