Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
This study randomized subjects at 244 study centers in 7 countries, from June 2016 and November 2017. The study period was scheduled to take up to approximately 30 weeks for each individual subject from the time of screening through the follow-up period.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Subjects were randomized in a 3:3:3:1:1 ratio to BFF 320/9.6, BFF 160/9.6, FF 9.6, BD 320, and Symbicort.

Reporting Groups

  Description
BFF MDI 320/9.6 μg Budesonide Formoterol Fumarate Metered Dose Inhalation 320/9.6 μg
BFF MDI 160/9.6 μg Budesonide Formoterol Fumarate Metered Dose Inhalation 160/9.6 μg
FF MDI 9.6 μg Formoterol Fumarate Metered Dose Inhalation 9.6 μg
BD MDI 320 μg Budesonide Metered Dose Inhalation 320 μg
Symbicort TBH 400/12 μg Symbicort Turbuhaler 400/12 μg

Participant Flow:   Overall Study

  BFF MDI 320/9.6 μg BFF MDI 160/9.6 μg FF MDI 9.6 μg BD MDI 320 μg Symbicort TBH 400/12 μg
 STARTED  655 637 644 206 219
 COMPLETED  576 567 554 169 190
 NOT COMPLETED  79 70 90 37 29
  Adverse Event   27 22 17 13 12
  Withdrawal by Subject   21 20 24 13 10
  Lack of Efficacy   16 15 32 8 2
  Lost to Follow-up   6 3 5 2 2
  Physician Decision   3 2 3 1 2
  Protocol disc criteria   3 3 4 0 0
  Protocol Violation   0 4 4 0 1
  Administrative Reasons   3 1 1 0 0

Baseline Characteristics

Analysis Population Description -- Explanation of how the number of participants for analysis was determined.
The Modified Intent-To-Treat (mITT) Population is a subset of the ITT Population, and is defined as all subjects with post-randomization data obtained prior to discontinuation from treatment. The Intent-To-Treat (ITT) Population is defined as all subjects who were randomized to treatment and received any amount of the study treatment.

Reporting Groups

Description
BFF MDI 320/9.6 μg Budesonide Formoterol Fumarate Metered Dose Inhalation 320/9.6 μg
BFF MDI 160/9.6 μg Budesonide Formoterol Fumarate Metered Dose Inhalation 160/9.6 μg
FF MDI 9.6 μg Formoterol Fumarate Metered Dose Inhalation 9.6 μg
BD MDI 320 μg Budesonide Metered Dose Inhalation 320 μg
Symbicort TBH 400/12 μg Symbicort Turbuhaler 400/12 μg

Baseline Measures

  BFF MDI 320/9.6 μg BFF MDI 160/9.6 μg FF MDI 9.6 μg BD MDI 320 μg Symbicort TBH 400/12 μg Total
Number of Participants
[units: Participants] 		664 649 648 209 219 2389
Age Continuous
[units: Years]
Mean ± Standard Deviation		 64.2 ± 7.7 64.3 ± 7.6 64.1 ± 8.0 64.2 ± 7.4 65.3 ± 7.0 64.3 ± 7.7
Sex: Female, Male
[units: Participants]

Values listed are mITT population
            
Female 253 260 261 81 78 933
Male 402 377 383 125 141 1428
Ethnicity (NIH/OMB)
[units: Participants]

Values listed are mITT population
            
Hispanic or Latino 16 18 21 8 6 69
Not Hispanic or Latino 637 616 623 198 212 2286
Unknown or Not Reported 2 3 0 0 1 6
Race (NIH/OMB)
[units: Participants]

Values listed are mITT population
            
American Indian or Alaska Native 2 2 2 0 0 6
Asian 1 1 0 0 1 3
Native Hawaiian or Other Pacific Islander 0 0 0 0 0 0
Black or African American 19 15 20 9 8 71
White 633 619 622 197 210 2281
More than one race 0 0 0 0 0 0
Unknown or Not Reported 0 0 0 0 0 0

Outcome Measures

1. Primary Outcome Measure: Change from baseline in morning pre-dose trough FEV1 at Week 24 (BFF MDI versus FF MDI)   [ Time Frame: at Week 24 ]

Measure Type Primary
Measure Name Change from baseline in morning pre-dose trough FEV1 at Week 24 (BFF MDI versus FF MDI)
Measure Description Change from baseline in morning pre-dose trough FEV1 (Forced expiratory volume in 1 second) at Week 24 (BFF MDI versus FF MDI)
Time Frame at Week 24
Safety Issue? No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
mITT

Reporting Groups

  Description
BFF MDI 320/9.6 μg Budesonide Formoterol Fumarate Metered Dose Inhalation 320/9.6 μg
BFF MDI 160/9.6 μg Budesonide Formoterol Fumarate Metered Dose Inhalation 160/9.6 μg
FF MDI 9.6 μg Formoterol Fumarate Metered Dose Inhalation 9.6 μg

Measured Values

  BFF MDI 320/9.6 μg BFF MDI 160/9.6 μg FF MDI 9.6 μg
Number of Participants Analyzed
[units:participants]
 571 564 550
Change from baseline in morning pre-dose trough FEV1 at Week 24 (BFF MDI versus FF MDI)
[units: Liter]
Least Squares Mean (95% Confidence Interval) 		0.036 (0.019 to 0.053) 0.017 (0.000 to 0.034) -0.003 (-0.020 to 0.015)

No statistical analysis provided for Change from baseline in morning pre-dose trough FEV1 at Week 24 (BFF MDI versus FF MDI)

2. Primary Outcome Measure: Change from baseline in FEV1 AUC0-4 (BFF MDI vs BD MDI)   [ Time Frame: at Week 24 ]

Measure Type Primary
Measure Name Change from baseline in FEV1 AUC0-4 (BFF MDI vs BD MDI)
Measure Description Change from baseline in FEV1 (Forced Expiratory Volume) AUC0-4 (Area under the curve from 0 to 4 hours) (BFF MDI vs BD MDI)
Time Frame at Week 24
Safety Issue? No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
mITT

Reporting Groups

  Description
BFF MDI 320/9.6 μg Budesonide Formoterol Fumarate Metered Dose Inhalation 320/9.6 μg
BFF MDI 160/9.6 μg Budesonide Formoterol Fumarate Metered Dose Inhalation 160/9.6 μg
FF MDI 9.6 ug Formoterol Fumarate Metered Dose Inhalation 9.6 μg
BD MDI 320 ug Budesonide Metered Dose Inhalation 320 μg
Symbicort TBH 400/12 ug Symbicort Turbuhaler 400/12 ug

Measured Values

  BFF MDI 320/9.6 μg BFF MDI 160/9.6 μg FF MDI 9.6 ug BD MDI 320 ug Symbicort TBH 400/12 ug
Number of Participants Analyzed
[units:participants]
 571 565 549 168 189
Change from baseline in FEV1 AUC0-4 (BFF MDI vs BD MDI)
[units: Liter]
Least Squares Mean (95% Confidence Interval) 		0.194 (0.177 to 0.212) 0.179 (0.161 to 0.197) 0.161 (0.143 to 0.179) 0.022 (-0.011 to 0.054) 0.187 (0.157 to 0.218)

No statistical analysis provided for Change from baseline in FEV1 AUC0-4 (BFF MDI vs BD MDI)

3. Secondary Outcome Measure: Time to first moderate or severe COPD exacerbation (BFF MDI vs FF MDI).   [ Time Frame: over 24 Weeks (timepoints of 4, 12 & 20 weeks) ]

Measure Type Secondary
Measure Name Time to first moderate or severe COPD exacerbation (BFF MDI vs FF MDI).
Measure Description Time to first moderate or severe COPD (Chronic Obstructive Pulmonary Disease) exacerbation (BFF MDI vs FF MDI).
Time Frame over 24 Weeks (timepoints of 4, 12 & 20 weeks)
Safety Issue? No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
mITT

Reporting Groups

  Description
BFF MDI 320/9.6 μg Budesonide Formoterol Fumarate Metered Dose Inhalation 320/9.6 μg
BFF MDI 160/9.6 μg Budesonide Formoterol Fumarate Metered Dose Inhalation 160/9.6 μg
FF MDI 9.6 μg Formoterol Fumarate Metered Dose Inhalation 9.6 μg
BD MDI 320 μg Budesonide Metered Dose Inhalation 320 μg
Symbicort TBH 400/12 ug Symbicort Turbuhaler 400/12 ug

Measured Values

  BFF MDI 320/9.6 μg BFF MDI 160/9.6 μg FF MDI 9.6 μg BD MDI 320 μg Symbicort TBH 400/12 ug
Number of Participants Analyzed
[units:participants]
 655 637 644 206 219
Time to first moderate or severe COPD exacerbation (BFF MDI vs FF MDI).
[units: Percentage of Participants]
Number (95% Confidence Interval) 		         
Percentage of Subjects to Exacerbate at 4 Weeks 3.2 (2.1 to 4.9) 3.3 (2.2 to 5.1) 5.5 (4.0 to 7.6) 7.0 (4.2 to 11.5) 1.8 (0.7 to 4.8)
Percentage of Subjects to Exacerbate at 12 Weeks 9.8 (7.7 to 12.4) 9.9 (7.8 to 12.5) 15.0 (12.4 to 18.1) 14.9 (10.6 to 20.7) 8.6 (5.5 to 13.3)
Percentage of Subjects to Exacerbate at 20 Weeks 14.4 (11.9 to 17.4) 18.5 (15.6 to 21.8) 20.5 (17.5 to 23.9) 17.7 (13.0 to 23.9) 13.1 (9.2 to 18.6)

No statistical analysis provided for Time to first moderate or severe COPD exacerbation (BFF MDI vs FF MDI).

4. Secondary Outcome Measure: Percentage of subjects achieving an MCID (Minimal clinically important difference) of 4 units or more in SGRQ at Week 24   [ Time Frame: at Week 24 ]

Measure Type Secondary
Measure Name Percentage of subjects achieving an MCID (Minimal clinically important difference) of 4 units or more in SGRQ at Week 24
Measure Description The SGRQ (St. George’s Respiratory Questionnaire) is a disease-specific questionnaire, self-completed by participants, used to evaluate the effect of BFF MDI, FF MDI, BD MDI, & Symbicort TBH on health-related quality of life as compared to placebo in subjects with COPD. The scores range from 0 (minimum, best possible health status) to 100 (maximum, worst possible health status). The SGRQ contains 76 items grouped into three domains (symptoms, activity and impacts). Change from Baseline at a particular visit was calculated as the SGRQ total score at that visit minus Baseline. Change from Baseline in total score of -4 units or lower is considered as clinically meaningful improvement in quality of life.
Time Frame at Week 24
Safety Issue? No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
mITT

Reporting Groups

  Description
BFF MDI 320/9.6 μg Budesonide Formoterol Fumarate Metered Dose Inhalation 320/9.6 μg
BFF MDI 160/9.6 μg Budesonide Formoterol Fumarate Metered Dose Inhalation 160/9.6 μg
FF MDI 9.6 μg Formoterol Fumarate Metered Dose Inhalation 9.6 μg
BD MDI 320 μg Budesonide Metered Dose Inhalation 320 μg
Symbicort TBH 400/12 μg Symbicort Turbuhaler 400/12 μg

Measured Values

  BFF MDI 320/9.6 μg BFF MDI 160/9.6 μg FF MDI 9.6 μg BD MDI 320 μg Symbicort TBH 400/12 μg
Number of Participants Analyzed
[units:participants]
 649 635 640 204 217
Percentage of subjects achieving an MCID (Minimal clinically important difference) of 4 units or more in SGRQ at Week 24
[units: Percentage of Subjects]
 48.12 47.22 41.59 43.62 53.78

No statistical analysis provided for Percentage of subjects achieving an MCID (Minimal clinically important difference) of 4 units or more in SGRQ at Week 24

5. Secondary Outcome Measure: Change from baseline in morning pre-dose trough FEV1 at Week 24 (BFF MDI vs BD MDI)   [ Time Frame: at Week 24 ]

Measure Type Secondary
Measure Name Change from baseline in morning pre-dose trough FEV1 at Week 24 (BFF MDI vs BD MDI)
Measure Description Change from baseline in morning pre-dose trough FEV1(Forced Expiratory Volume in 1 second) at Week 24 (BFF MDI vs BD MDI)
Time Frame at Week 24
Safety Issue? No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
mITT

Reporting Groups

  Description
BFF MDI 320/9.6 μg Budesonide Formoterol Fumarate Metered Dose Inhalation 320/9.6 μg
BFF MDI 160/9.6 μg Budesonide Formoterol Fumarate Metered Dose Inhalation 160/9.6 μg
FF MDI 9.6 μg Formoterol Fumarate Metered Dose Inhalation 9.6 μg
BD MDI 320 μg Budesonide Metered Dose Inhalation 320 μg
Symbicort TBH 400/12 μg Symbicort Turbuhaler 400/12 μg

Measured Values

  BFF MDI 320/9.6 μg BFF MDI 160/9.6 μg FF MDI 9.6 μg BD MDI 320 μg Symbicort TBH 400/12 μg
Number of Participants Analyzed
[units:participants]
 571 564 550 168 189
Change from baseline in morning pre-dose trough FEV1 at Week 24 (BFF MDI vs BD MDI)
[units: Liter]
Least Squares Mean (95% Confidence Interval) 		0.036 (0.019 to 0.053) 0.017 (0.000 to 0.034) -0.003 (-0.020 to 0.015) -0.028 (-0.060 to 0.003) 0.039 (0.009 to 0.069)

No statistical analysis provided for Change from baseline in morning pre-dose trough FEV1 at Week 24 (BFF MDI vs BD MDI)

6. Secondary Outcome Measure: Peak change from baseline in FEV1 at Week 24 (BFF MDI vs BD MDI)   [ Time Frame: at Week 24 ]

Measure Type Secondary
Measure Name Peak change from baseline in FEV1 at Week 24 (BFF MDI vs BD MDI)
Measure Description Peak change from baseline in FEV1 (Forced Expiratory Volume in 1 second) at Week 24 (BFF MDI vs BD MDI)
Time Frame at Week 24
Safety Issue? No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
mITT

Reporting Groups

  Description
BFF MDI 320/9.6 μg Budesonide Formoterol Fumarate Metered Dose Inhalation 320/9.6 μg
BFF MDI 160/9.6 μg Budesonide Formoterol Fumarate Metered Dose Inhalation 160/9.6 μg
FF MDI 9.6 μg Formoterol Fumarate Metered Dose Inhalation 9.6 μg
BD MDI 320 μg Budesonide Metered Dose Inhalation 320 μg
Symbicort TBH 400/12 μg Symbicort Turbuhaler 400/12 μg

Measured Values

  BFF MDI 320/9.6 μg BFF MDI 160/9.6 μg FF MDI 9.6 μg BD MDI 320 μg Symbicort TBH 400/12 μg
Number of Participants Analyzed
[units:participants]
 571 565 549 168 189
Peak change from baseline in FEV1 at Week 24 (BFF MDI vs BD MDI)
[units: Liter]
Least Squares Mean (95% Confidence Interval) 		0.272 (0.254 to 0.291) 0.258 (0.239 to 0.276) 0.243 (0.224 to 0.261) 0.116 (0.082 to 0.150) 0.267 (0.253 to 0.299)

No statistical analysis provided for Peak change from baseline in FEV1 at Week 24 (BFF MDI vs BD MDI)

7. Secondary Outcome Measure: Change from baseline in average daily rescue Ventolin HFA use over 24 weeks (BFF MDI vs BD MDI)   [ Time Frame: over 24 Weeks ]

Measure Type Secondary
Measure Name Change from baseline in average daily rescue Ventolin HFA use over 24 weeks (BFF MDI vs BD MDI)
Measure Description Change from baseline in average daily rescue Ventolin HFA use over 24 weeks (BFF MDI vs BD MDI)
Time Frame over 24 Weeks
Safety Issue? No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
mITT

Reporting Groups

  Description
BFF MDI 320/9.6 μg Budesonide Formoterol Fumarate Metered Dose Inhalation 320/9.6 μg
BFF MDI 160/9.6 μg Budesonide Formoterol Fumarate Metered Dose Inhalation 160/9.6 μg
FF MDI 9.6 μg Formoterol Fumarate Metered Dose Inhalation 9.6 μg
BD MDI 320 μg Budesonide Metered Dose Inhalation 320 μg
Symbicort TBH 400/12 μg Symbicort Turbuhaler 400/12 μg

Measured Values

  BFF MDI 320/9.6 μg BFF MDI 160/9.6 μg FF MDI 9.6 μg BD MDI 320 μg Symbicort TBH 400/12 μg
Number of Participants Analyzed
[units:participants]
 654 636 641 206 218
Change from baseline in average daily rescue Ventolin HFA use over 24 weeks (BFF MDI vs BD MDI)
[units: Puffs per day]
Least Squares Mean (95% Confidence Interval) 		-1.3 (-1.5 to -1.1) -1.3 (-1.4 to -1.1) -1.1 (-1.2 to -0.9) -0.6 (-0.9 to -0.3) -1.2 (-1.5 to -0.9)

No statistical analysis provided for Change from baseline in average daily rescue Ventolin HFA use over 24 weeks (BFF MDI vs BD MDI)

8. Secondary Outcome Measure: Time to onset of action on Day 1 - 5 Minutes (BFF MDI vs BD MDI)   [ Time Frame: Day 1 - 5 Minutes ]

Measure Type Secondary
Measure Name Time to onset of action on Day 1 - 5 Minutes (BFF MDI vs BD MDI)
Measure Description Time to onset of action on Day 1 (BFF MDI vs BD MDI). Change from baseline at 5 Minutes.
Time Frame Day 1 - 5 Minutes
Safety Issue? No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
mITT

Reporting Groups

  Description
BFF MDI 320/9.6 μg Budesonide Formoterol Fumarate Metered Dose Inhalation 320/9.6 μg
BFF MDI 160/9.6 μg Budesonide Formoterol Fumarate Metered Dose Inhalation 160/9.6 μg
FF MDI 9.6 μg Formoterol Fumarate Metered Dose Inhalation 9.6 μg
BD MDI 320 μg Budesonide Metered Dose Inhalation 320 μg
Symbicort TBH 400/12 μg Symbicort Turbuhaler 400/12 μg

Measured Values

  BFF MDI 320/9.6 μg BFF MDI 160/9.6 μg FF MDI 9.6 μg BD MDI 320 μg Symbicort TBH 400/12 μg
Number of Participants Analyzed
[units:participants]
 535 536 534 171 173
Time to onset of action on Day 1 - 5 Minutes (BFF MDI vs BD MDI)
[units: Liter]
Least Squares Mean (95% Confidence Interval) 		0.157 (0.148 to 0.166) 0.151 (0.142 to 0.161) 0.160 (0.150 to 0.169) 0.025 (0.009 to 0.041) 0.131 (0.115 to 0.148)

No statistical analysis provided for Time to onset of action on Day 1 - 5 Minutes (BFF MDI vs BD MDI)

9. Secondary Outcome Measure: Time to onset of action on Day 1 - 15 Minutes (BFF MDI vs BD MDI)   [ Time Frame: Day 1 - 15 Minutes ]

Measure Type Secondary
Measure Name Time to onset of action on Day 1 - 15 Minutes (BFF MDI vs BD MDI)
Measure Description Time to onset of action on Day 1- 15 Minutes (BFF MDI vs BD MDI). Change from baseline at 15 Minutes.
Time Frame Day 1 - 15 Minutes
Safety Issue? No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
mITT

Reporting Groups

  Description
BFF MDI 320/9.6 μg Budesonide Formoterol Fumarate Metered Dose Inhalation 320/9.6 μg
BFF MDI 160/9.6 μg Budesonide Formoterol Fumarate Metered Dose Inhalation 160/9.6 μg
FF MDI 9.6 μg Formoterol Fumarate Metered Dose Inhalation 9.6 μg
BD MDI 320 μg Budesonide Metered Dose Inhalation 320 μg
Symbicort TBH 400/12 μg Symbicort Turbuhaler 400/12 μg

Measured Values

  BFF MDI 320/9.6 μg BFF MDI 160/9.6 μg FF MDI 9.6 μg BD MDI 320 μg Symbicort TBH 400/12 μg
Number of Participants Analyzed
[units:participants]
 624 615 612 203 211
Time to onset of action on Day 1 - 15 Minutes (BFF MDI vs BD MDI)
[units: Liter]
Least Squares Mean (95% Confidence Interval) 		0.190 (0.180 to 0.200) 0.186 (0.176 to 0.196) 0.201 (0.191 to 0.211) 0.040 (0.022 to 0.058) 0.167 (0.149 to 0.184)

No statistical analysis provided for Time to onset of action on Day 1 - 15 Minutes (BFF MDI vs BD MDI)

10. Secondary Outcome Measure: Time to onset of action on Day 1 - 30 Minutes (BFF MDI vs BD MDI)   [ Time Frame: Day 1 - 30 Minutes ]

Measure Type Secondary
Measure Name Time to onset of action on Day 1 - 30 Minutes (BFF MDI vs BD MDI)
Measure Description Time to onset of action on Day 1 (BFF MDI vs BD MDI). Change from baseline at 30 Minutes.
Time Frame Day 1 - 30 Minutes
Safety Issue? No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
mITT

Reporting Groups

  Description
BFF MDI 320/9.6 μg Budesonide Formoterol Fumarate Metered Dose Inhalation 320/9.6 μg
BFF MDI 160/9.6 μg Budesonide Formoterol Fumarate Metered Dose Inhalation 160/9.6 μg
FF MDI 9.6 μg Formoterol Fumarate Metered Dose Inhalation 9.6 μg
BD MDI 320 μg Budesonide Metered Dose Inhalation 320 μg
Symbicort TBH 400/12 μg Symbicort Turbuhaler 400/12 μg

Measured Values

  BFF MDI 320/9.6 μg BFF MDI 160/9.6 μg FF MDI 9.6 μg BD MDI 320 μg Symbicort TBH 400/12 μg
Number of Participants Analyzed
[units:participants]
 648 627 638 203 214
Time to onset of action on Day 1 - 30 Minutes (BFF MDI vs BD MDI)
[units: Liter]
Least Squares Mean (95% Confidence Interval) 		0.207 (0.196 to 0.217) 0.207 (0.196 to 0.218) 0.215 (0.205 to 0.226) 0.047 (0.028 to 0.066) 0.190 (0.172 to 0.209)

No statistical analysis provided for Time to onset of action on Day 1 - 30 Minutes (BFF MDI vs BD MDI)

11. Secondary Outcome Measure: Time to onset of action on Day 1 - 1 Hour (BFF MDI vs BD MDI)   [ Time Frame: Day 1 - 1 Hour ]

Measure Type Secondary
Measure Name Time to onset of action on Day 1 - 1 Hour (BFF MDI vs BD MDI)
Measure Description Time to onset of action on Day 1 (BFF MDI vs BD MDI). Change from baseline at 1 hour.
Time Frame Day 1 - 1 Hour
Safety Issue? No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
mITT

Reporting Groups

  Description
BFF MDI 320/9.6 μg Budesonide Formoterol Fumarate Metered Dose Inhalation 320/9.6 μg
BFF MDI 160/9.6 μg Budesonide Formoterol Fumarate Metered Dose Inhalation 160/9.6 μg
FF MDI 9.6 μg Formoterol Fumarate Metered Dose Inhalation 9.6 μg
BD MDI 320 μg Budesonide Metered Dose Inhalation 320 μg
Symbicort TBH 400/12 μg Symbicort Turbuhaler 400/12 μg

Measured Values

  BFF MDI 320/9.6 μg BFF MDI 160/9.6 μg FF MDI 9.6 μg BD MDI 320 μg Symbicort TBH 400/12 μg
Number of Participants Analyzed
[units:participants]
 649 628 640 204 215
Time to onset of action on Day 1 - 1 Hour (BFF MDI vs BD MDI)
[units: Liter]
Least Squares Mean (95% Confidence Interval) 		0.225 (0.213 to 0.236) 0.221 (0.210 to 0.233) 0.236 (0.225 to 0.248) 0.053 (0.033 to 0.073) 0.211 (0.191 to 0.231)

No statistical analysis provided for Time to onset of action on Day 1 - 1 Hour (BFF MDI vs BD MDI)

12. Secondary Outcome Measure: Time to onset of action on Day 1 - 2 Hours (BFF MDI vs BD MDI)   [ Time Frame: Day 1 - 2 Hours ]

Measure Type Secondary
Measure Name Time to onset of action on Day 1 - 2 Hours (BFF MDI vs BD MDI)
Measure Description Time to onset of action on Day 1 (BFF MDI vs BD MDI). Change from baseline at 2 hours.
Time Frame Day 1 - 2 Hours
Safety Issue? No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
mITT

Reporting Groups

  Description
BFF MDI 320/9.6 μg Budesonide Formoterol Fumarate Metered Dose Inhalation 320/9.6 μg
BFF MDI 160/9.6 μg Budesonide Formoterol Fumarate Metered Dose Inhalation 160/9.6 μg
FF MDI 9.6 μg Formoterol Fumarate Metered Dose Inhalation 9.6 μg
BD MDI 320 μg Budesonide Metered Dose Inhalation 320 μg
Symbicort TBH 400/12 μg Symbicort Turbuhaler 400/12 μg

Measured Values

  BFF MDI 320/9.6 μg BFF MDI 160/9.6 μg FF MDI 9.6 μg BD MDI 320 μg Symbicort TBH 400/12 μg
Number of Participants Analyzed
[units:participants]
 649 629 636 205 217
Time to onset of action on Day 1 - 2 Hours (BFF MDI vs BD MDI)
[units: Liter]
Least Squares Mean (95% Confidence Interval) 		0.253 (0.241 to 0.265) 0.234 (0.222 to 0.247) 0.244 (0.231 to 0.256) 0.063 (0.042 to 0.085) 0.221 (0.200 to 0.243)

No statistical analysis provided for Time to onset of action on Day 1 - 2 Hours (BFF MDI vs BD MDI)

13. Secondary Outcome Measure: Time to onset of action on Day 1 - 4 Hours (BFF MDI vs BD MDI)   [ Time Frame: Day 1 - 4 Hours ]

Measure Type Secondary
Measure Name Time to onset of action on Day 1 - 4 Hours (BFF MDI vs BD MDI)
Measure Description Time to onset of action on Day 1 (BFF MDI vs BD MDI). Change from baseline at 4 hours.
Time Frame Day 1 - 4 Hours
Safety Issue? No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
mITT

Reporting Groups

  Description
BFF MDI 320/9.6 μg Budesonide Formoterol Fumarate Metered Dose Inhalation 320/9.6 μg
BFF MDI 160/9.6 μg Budesonide Formoterol Fumarate Metered Dose Inhalation 160/9.6 μg
FF MDI 9.6 μg Formoterol Fumarate Metered Dose Inhalation 9.6 μg
BD MDI 320 μg Budesonide Metered Dose Inhalation 320 μg
Symbicort TBH 400/12 μg Symbicort Turbuhaler 400/12 μg

Measured Values

  BFF MDI 320/9.6 μg BFF MDI 160/9.6 μg FF MDI 9.6 μg BD MDI 320 μg Symbicort TBH 400/12 μg
Number of Participants Analyzed
[units:participants]
 651 630 634 201 217
Time to onset of action on Day 1 - 4 Hours (BFF MDI vs BD MDI)
[units: Liter]
Least Squares Mean (95% Confidence Interval) 		0.230 (0.216 to 0.243) 0.215 (0.202 to 0.229) 0.212 (0.199 to 0.226) 0.073 (0.049 to 0.097) 0.209 (0.186 to 0.232)

No statistical analysis provided for Time to onset of action on Day 1 - 4 Hours (BFF MDI vs BD MDI)

14. Other Pre-specified Outcome Measure: Substudy: 12-hour PFT endpoint FEV1 AUC0-12   [ Time Frame: at Week 12 ]

Measure Type Other Pre-specified
Measure Name Substudy: 12-hour PFT endpoint FEV1 AUC0-12
Measure Description Substudy: 12-hour PFT (Pulmonary Function Test) endpoint FEV1 (Forced Expiratory Volume) AUC0-12 (Area under the Curve 0-12)
Time Frame at Week 12
Safety Issue? No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
mITT

Reporting Groups

  Description
BFF MDI 320/9.6 μg Budesonide Formoterol Fumarate Metered Dose Inhalation 320/9.6 μg
BFF MDI 160/9.6 μg Budesonide Formoterol Fumarate Metered Dose Inhalation 160/9.6 μg
FF MDI 9.6 μg Formoterol Fumarate Metered Dose Inhalation 9.6 μg
BD MDI 320 μg Budesonide Metered Dose Inhalation 320 μg

Measured Values

  BFF MDI 320/9.6 μg BFF MDI 160/9.6 μg FF MDI 9.6 μg BD MDI 320 μg
Number of Participants Analyzed
[units:participants]
 160 167 189 47
Substudy: 12-hour PFT endpoint FEV1 AUC0-12
[units: Liter]
Least Squares Mean (95% Confidence Interval) 		0.135 (0.107 to 0.163) 0.124 (0.097 to 0.152) 0.117 (0.089 to 0.145) 0.024 (-0.028 to 0.075)

No statistical analysis provided for Substudy: 12-hour PFT endpoint FEV1 AUC0-12

Serious Adverse Events

Time Frame Adverse events were collected from the time the subject signed informed consent throughout the treatment period and up to 14 days following the last dose of study drug
Additional Description Serious Adverse Events were collected from the time the subject signed informed consent throughout the treatment period and up to approximately 30 weeks, which includes screening and follow up (14 days after last dose of study drug). 

Reporting Groups

  Description
BFF MDI 320/9.6 μg Budesonide Formoterol Fumarate Metered Dose Inhalation 320/9.6 μg
BFF MDI 160/9.6 μg Budesonide Formoterol Fumarate Metered Dose Inhalation 160/9.6 μg
FF MDI 9.6 μg Formoterol Fumarate Metered Dose Inhalation 9.6 μg
BD MDI 320 μg Budesonide Metered Dose Inhalation 320 μg
Symbicort TBH 400/12 μg Symbicort Turbuhaler 400/12 μg

Serious Adverse Events

  BFF MDI 320/9.6 μg BFF MDI 160/9.6 μg FF MDI 9.6 μg BD MDI 320 μg Symbicort TBH 400/12 μg
Total, serious adverse events          
# participants affected / at risk 42/655 (6.41%) 45/637 (7.06%) 72/644 (11.18%) 15/206 (7.28%) 20/219 (9.13%)
Respiratory, thoracic and mediastinal disorders          
Chronic obstructive pulmonary disease1, †          
# participants affected / at risk 15/655 (2.29%) 10/637 (1.57%) 29/644 (4.50%) 2/206 (0.97%) 6/219 (2.74%)
# events 16 10 35 2 6
Respiratory, thoracic and mediastinal disorders          
Acute respiratory failure1, †          
# participants affected / at risk 2/655 (0.31%) 2/637 (0.31%) 4/644 (0.62%) 0/206 (0.00%) 1/219 (0.46%)
# events 2 2 4 0 1
Respiratory, thoracic and mediastinal disorders          
Pulmonary embolism1, †          
# participants affected / at risk 1/655 (0.15%) 0/637 (0.00%) 1/644 (0.16%) 0/206 (0.00%) 0/219 (0.00%)
# events 1 0 1 0 0
Respiratory, thoracic and mediastinal disorders          
Respiratory failure1, †          
# participants affected / at risk 0/655 (0.00%) 0/637 (0.00%) 1/644 (0.16%) 0/206 (0.00%) 1/219 (0.46%)
# events 0 0 1 0 1
Respiratory, thoracic and mediastinal disorders          
Pleural effusion1, †          
# participants affected / at risk 0/655 (0.00%) 0/637 (0.00%) 1/644 (0.16%) 0/206 (0.00%) 0/219 (0.00%)
# events 0 0 1 0 0
Cardiac disorders          
Atrial fibrillation1, †          
# participants affected / at risk 1/655 (0.15%) 5/637 (0.78%) 2/644 (0.31%) 1/206 (0.49%) 0/219 (0.00%)
# events 1 5 2 1 0
Cardiac disorders          
Cardiac failure congestive1, †          
# participants affected / at risk 1/655 (0.15%) 1/637 (0.16%) 1/644 (0.16%) 2/206 (0.97%) 1/219 (0.46%)
# events 1 1 2 2 1
Cardiac disorders          
Acute myocardial infarction1, †          
# participants affected / at risk 0/655 (0.00%) 2/637 (0.31%) 2/644 (0.31%) 0/206 (0.00%) 0/219 (0.00%)
# events 0 2 2 0 0
Cardiac disorders          
Angina pectoris1, †          
# participants affected / at risk 1/655 (0.15%) 2/637 (0.31%) 1/644 (0.16%) 0/206 (0.00%) 0/219 (0.00%)
# events 1 2 1 0 0
Cardiac disorders          
Angina unstable1, †          
# participants affected / at risk 0/655 (0.00%) 2/637 (0.31%) 1/644 (0.16%) 0/206 (0.00%) 0/219 (0.00%)
# events 0 2 1 0 0
Cardiac disorders          
Atrial flutter1, †          
# participants affected / at risk 1/655 (0.15%) 0/637 (0.00%) 1/644 (0.16%) 1/206 (0.49%) 0/219 (0.00%)
# events 1 0 1 1 0
Cardiac disorders          
Cardiac failure1, †          
# participants affected / at risk 2/655 (0.31%) 0/637 (0.00%) 1/644 (0.16%) 0/206 (0.00%) 0/219 (0.00%)
# events 2 0 1 0 0
Cardiac disorders          
Cardiac failure chronic1, †          
# participants affected / at risk 0/655 (0.00%) 2/637 (0.31%) 1/644 (0.16%) 0/206 (0.00%) 0/219 (0.00%)
# events 0 2 1 0 0
Cardiac disorders          
Myocardial ischaemia1, †          
# participants affected / at risk 0/655 (0.00%) 0/637 (0.00%) 1/644 (0.16%) 1/206 (0.49%) 0/219 (0.00%)
# events 0 0 2 1 0
Cardiac disorders          
Atrioventricular block complete1, †          
# participants affected / at risk 0/655 (0.00%) 1/637 (0.16%) 0/644 (0.00%) 1/206 (0.49%) 0/219 (0.00%)
# events 0 1 0 1 0
Cardiac disorders          
Cardiac arrest1, †          
# participants affected / at risk 1/655 (0.15%) 1/637 (0.16%) 0/644 (0.00%) 0/206 (0.00%) 0/219 (0.00%)
# events 1 1 0 0 0
Cardiac disorders          
Coronary artery disease1, †          
# participants affected / at risk 0/655 (0.00%) 1/637 (0.16%) 1/644 (0.16%) 0/206 (0.00%) 0/219 (0.00%)
# events 0 1 1 0 0
Cardiac disorders          
Arteriosclerosis coronary artery1, †          
# participants affected / at risk 0/655 (0.00%) 1/637 (0.16%) 0/644 (0.00%) 0/206 (0.00%) 0/219 (0.00%)
# events 0 1 0 0 0
Cardiac disorders          
Congestive cardiomyopathy1, †          
# participants affected / at risk 0/655 (0.00%) 1/637 (0.16%) 0/644 (0.00%) 0/206 (0.00%) 0/219 (0.00%)
# events 0 1 0 0 0
Cardiac disorders          
Coronary artery stenosis1, †          
# participants affected / at risk 0/655 (0.00%) 0/637 (0.00%) 0/644 (0.00%) 1/206 (0.49%) 0/219 (0.00%)
# events 0 0 0 1 0
Cardiac disorders          
Myocardial infarction1, †          
# participants affected / at risk 0/655 (0.00%) 0/637 (0.00%) 0/644 (0.00%) 1/206 (0.49%) 0/219 (0.00%)
# events 0 0 0 1 0
Infections and infestations          
Pneumonia1, †          
# participants affected / at risk 4/655 (0.61%) 5/637 (0.78%) 6/644 (0.93%) 0/206 (0.00%) 3/219 (1.37%)
# events 4 5 7 0 3
Infections and infestations          
Abdominal hernia gangrenous1, †          
# participants affected / at risk 0/655 (0.00%) 0/637 (0.00%) 0/644 (0.00%) 0/206 (0.00%) 1/219 (0.46%)
# events 0 0 0 0 1
Infections and infestations          
Breast abscess1, †          
# participants affected / at risk 0/655 (0.00%) 0/637 (0.00%) 1/644 (0.16%) 0/206 (0.00%) 0/219 (0.00%)
# events 0 0 1 0 0
Infections and infestations          
Cellulitis1, †          
# participants affected / at risk 0/655 (0.00%) 0/637 (0.00%) 1/644 (0.16%) 0/206 (0.00%) 0/219 (0.00%)
# events 0 0 1 0 0
Infections and infestations          
Clostridium difficile colitis1, †          
# participants affected / at risk 0/655 (0.00%) 0/637 (0.00%) 1/644 (0.16%) 0/206 (0.00%) 0/219 (0.00%)
# events 0 0 1 0 0
Infections and infestations          
Sepsis1, †          
# participants affected / at risk 0/655 (0.00%) 0/637 (0.00%) 0/644 (0.00%) 0/206 (0.00%) 1/219 (0.46%)
# events 0 0 0 0 1
Infections and infestations          
Staphylococcal infection1, †          
# participants affected / at risk 0/655 (0.00%) 1/637 (0.16%) 0/644 (0.00%) 0/206 (0.00%) 0/219 (0.00%)
# events 0 1 0 0 0
Infections and infestations          
Tooth abscess1, †          
# participants affected / at risk 0/655 (0.00%) 1/637 (0.16%) 0/644 (0.00%) 0/206 (0.00%) 0/219 (0.00%)
# events 0 1 0 0 0
Nervous system disorders          
Ischaemic stroke1, †          
# participants affected / at risk 0/655 (0.00%) 1/637 (0.16%) 2/644 (0.31%) 0/206 (0.00%) 1/219 (0.46%)
# events 0 1 2 0 1
Nervous system disorders          
Cerebrovascular accident1, †          
# participants affected / at risk 1/655 (0.15%) 0/637 (0.00%) 1/644 (0.16%) 0/206 (0.00%) 1/219 (0.46%)
# events 1 0 1 0 1
Nervous system disorders          
Transient ischaemic attack1, †          
# participants affected / at risk 0/655 (0.00%) 1/637 (0.16%) 1/644 (0.16%) 0/206 (0.00%) 0/219 (0.00%)
# events 0 1 1 0 0
Nervous system disorders          
Carotid artery stenosis1, †          
# participants affected / at risk 0/655 (0.00%) 0/637 (0.00%) 1/644 (0.16%) 0/206 (0.00%) 0/219 (0.00%)
# events 0 0 1 0 0
Nervous system disorders          
Embolic stroke1, †          
# participants affected / at risk 0/655 (0.00%) 0/637 (0.00%) 0/644 (0.00%) 1/206 (0.49%) 0/219 (0.00%)
# events 0 0 0 1 0
Nervous system disorders          
Epilepsy1, †          
# participants affected / at risk 0/655 (0.00%) 1/637 (0.16%) 0/644 (0.00%) 0/206 (0.00%) 0/219 (0.00%)
# events 0 1 0 0 0
Nervous system disorders          
Hypoaesthesia1, †          
# participants affected / at risk 0/655 (0.00%) 1/637 (0.16%) 0/644 (0.00%) 0/206 (0.00%) 0/219 (0.00%)
# events 0 1 0 0 0
Nervous system disorders          
Intracranial aneurysm1, †          
# participants affected / at risk 0/655 (0.00%) 1/637 (0.16%) 0/644 (0.00%) 0/206 (0.00%) 0/219 (0.00%)
# events 0 1 0 0 0
Nervous system disorders          
Syncope2, †          
# participants affected / at risk 0/655 (0.00%) 0/637 (0.00%) 1/644 (0.16%) 0/206 (0.00%) 0/219 (0.00%)
# events 0 0 1 0 0
Gastrointestinal disorders          
Small intestinal obstruction1, †          
# participants affected / at risk 0/655 (0.00%) 1/637 (0.16%) 2/644 (0.31%) 0/206 (0.00%) 0/219 (0.00%)
# events 0 1 2 0 0
Gastrointestinal disorders          
Pancreatitis acute1, †          
# participants affected / at risk 0/655 (0.00%) 0/637 (0.00%) 0/644 (0.00%) 0/206 (0.00%) 2/219 (0.91%)
# events 0 0 0 0 2
Gastrointestinal disorders          
Abdominal pain1, †          
# participants affected / at risk 1/655 (0.15%) 0/637 (0.00%) 0/644 (0.00%) 0/206 (0.00%) 0/219 (0.00%)
# events 1 0 0 0 0
Gastrointestinal disorders          
Colitis ischaemic2, †          
# participants affected / at risk 0/655 (0.00%) 0/637 (0.00%) 1/644 (0.16%) 0/206 (0.00%) 0/219 (0.00%)
# events 0 0 1 0 0
Gastrointestinal disorders          
Diverticulum intestinal1, †          
# participants affected / at risk 0/655 (0.00%) 1/637 (0.16%) 0/644 (0.00%) 0/206 (0.00%) 0/219 (0.00%)
# events 0 1 0 0 0
Gastrointestinal disorders          
Gastrointestinal ulcer1, †          
# participants affected / at risk 0/655 (0.00%) 0/637 (0.00%) 1/644 (0.16%) 0/206 (0.00%) 0/219 (0.00%)
# events 0 0 1 0 0
Gastrointestinal disorders          
Hiatus hernia1, †          
# participants affected / at risk 1/655 (0.15%) 0/637 (0.00%) 0/644 (0.00%) 0/206 (0.00%) 0/219 (0.00%)
# events 1 0 0 0 0
Gastrointestinal disorders          
Inflammatory bowel disease1, †          
# participants affected / at risk 1/655 (0.15%) 0/637 (0.00%) 0/644 (0.00%) 0/206 (0.00%) 0/219 (0.00%)
# events 1 0 0 0 0
Gastrointestinal disorders          
Inguinal hernia1, †          
# participants affected / at risk 0/655 (0.00%) 0/637 (0.00%) 0/644 (0.00%) 1/206 (0.49%) 0/219 (0.00%)
# events 0 0 0 1 0
Gastrointestinal disorders          
Pancreatitis1, †          
# participants affected / at risk 0/655 (0.00%) 1/637 (0.16%) 0/644 (0.00%) 0/206 (0.00%) 0/219 (0.00%)
# events 0 1 0 0 0
Gastrointestinal disorders          
Strangulated umbilical hernia1, †          
# participants affected / at risk 0/655 (0.00%) 0/637 (0.00%) 0/644 (0.00%) 1/206 (0.49%) 0/219 (0.00%)
# events 0 0 0 1 0
Gastrointestinal disorders          
Upper gastrointestinal haemorrhage1, †          
# participants affected / at risk 0/655 (0.00%) 1/637 (0.16%) 0/644 (0.00%) 0/206 (0.00%) 0/219 (0.00%)
# events 0 1 0 0 0
Injury, poisoning and procedural complications          
Hip fracture1, †          
# participants affected / at risk 0/655 (0.00%) 1/637 (0.16%) 0/644 (0.00%) 0/206 (0.00%) 1/219 (0.46%)
# events 0 1 0 0 1
Injury, poisoning and procedural complications          
Acetabulum fracture1, †          
# participants affected / at risk 0/655 (0.00%) 0/637 (0.00%) 0/644 (0.00%) 0/206 (0.00%) 1/219 (0.46%)
# events 0 0 0 0 1
Injury, poisoning and procedural complications          
Dural tear1, †          
# participants affected / at risk 0/655 (0.00%) 0/637 (0.00%) 1/644 (0.16%) 0/206 (0.00%) 0/219 (0.00%)
# events 0 0 1 0 0
Injury, poisoning and procedural complications          
Femur fracture1, †          
# participants affected / at risk 1/655 (0.15%) 0/637 (0.00%) 0/644 (0.00%) 0/206 (0.00%) 0/219 (0.00%)
# events 1 0 0 0 0
Injury, poisoning and procedural complications          
Forearm fracture1, †          
# participants affected / at risk 0/655 (0.00%) 0/637 (0.00%) 0/644 (0.00%) 0/206 (0.00%) 1/219 (0.46%)
# events 0 0 0 0 1
Injury, poisoning and procedural complications          
Lower limb fracture1, †          
# participants affected / at risk 1/655 (0.15%) 0/637 (0.00%) 0/644 (0.00%) 0/206 (0.00%) 0/219 (0.00%)
# events 1 0 0 0 0
Injury, poisoning and procedural complications          
Radius fracture1, †          
# participants affected / at risk 0/655 (0.00%) 0/637 (0.00%) 0/644 (0.00%) 1/206 (0.49%) 0/219 (0.00%)
# events 0 0 0 1 0
Injury, poisoning and procedural complications          
Rib fracture1, †          
# participants affected / at risk 1/655 (0.15%) 0/637 (0.00%) 0/644 (0.00%) 0/206 (0.00%) 0/219 (0.00%)
# events 1 0 0 0 0
Injury, poisoning and procedural complications          
Thermal burn1, †          
# participants affected / at risk 0/655 (0.00%) 0/637 (0.00%) 0/644 (0.00%) 0/206 (0.00%) 1/219 (0.46%)
# events 0 0 0 0 1
Injury, poisoning and procedural complications          
Upper limb fracture1, †          
# participants affected / at risk 0/655 (0.00%) 0/637 (0.00%) 1/644 (0.16%) 0/206 (0.00%) 0/219 (0.00%)
# events 0 0 1 0 0
Injury, poisoning and procedural complications          
Vascular pseudoaneurysm1, †          
# participants affected / at risk 1/655 (0.15%) 0/637 (0.00%) 0/644 (0.00%) 0/206 (0.00%) 0/219 (0.00%)
# events 1 0 0 0 0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)          
Adenocarcinoma of colon1, †          
# participants affected / at risk 0/655 (0.00%) 0/637 (0.00%) 0/644 (0.00%) 1/206 (0.49%) 0/219 (0.00%)
# events 0 0 0 1 0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)          
Brain cancer metastatic1, †          
# participants affected / at risk 0/655 (0.00%) 1/637 (0.16%) 0/644 (0.00%) 0/206 (0.00%) 0/219 (0.00%)
# events 0 1 0 0 0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)          
Breast cancer male1, †          
# participants affected / at risk 0/655 (0.00%) 0/637 (0.00%) 1/644 (0.16%) 0/206 (0.00%) 0/219 (0.00%)
# events 0 0 1 0 0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)          
Bronchial carcinoma1, †          
# participants affected / at risk 0/655 (0.00%) 0/637 (0.00%) 0/644 (0.00%) 1/206 (0.49%) 0/219 (0.00%)
# events 0 0 0 1 0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)          
Gastric neoplasm1, †          
# participants affected / at risk 0/655 (0.00%) 0/637 (0.00%) 1/644 (0.16%) 0/206 (0.00%) 0/219 (0.00%)
# events 0 0 1 0 0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)          
Lung neoplasm malignant1, †          
# participants affected / at risk 0/655 (0.00%) 0/637 (0.00%) 1/644 (0.16%) 0/206 (0.00%) 0/219 (0.00%)
# events 0 0 1 0 0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)          
Mesothelioma1, †          
# participants affected / at risk 1/655 (0.15%) 0/637 (0.00%) 0/644 (0.00%) 0/206 (0.00%) 0/219 (0.00%)
# events 1 0 0 0 0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)          
Metastases to liver1, †          
# participants affected / at risk 0/655 (0.00%) 0/637 (0.00%) 0/644 (0.00%) 1/206 (0.49%) 0/219 (0.00%)
# events 0 0 0 1 0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)          
Metastatic carcinoma of the bladder1, †          
# participants affected / at risk 0/655 (0.00%) 0/637 (0.00%) 1/644 (0.16%) 0/206 (0.00%) 0/219 (0.00%)
# events 0 0 1 0 0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)          
Non-small cell lung cancer1, †          
# participants affected / at risk 0/655 (0.00%) 1/637 (0.16%) 0/644 (0.00%) 0/206 (0.00%) 0/219 (0.00%)
# events 0 1 0 0 0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)          
Pancreatic carcinoma metastatic1, †          
# participants affected / at risk 1/655 (0.15%) 0/637 (0.00%) 0/644 (0.00%) 0/206 (0.00%) 0/219 (0.00%)
# events 1 0 0 0 0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)          
Prostate cancer1, †          
# participants affected / at risk 1/655 (0.15%) 0/637 (0.00%) 0/644 (0.00%) 0/206 (0.00%) 0/219 (0.00%)
# events 1 0 0 0 0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)          
Transitional cell carcinoma1, †          
# participants affected / at risk 0/655 (0.00%) 0/637 (0.00%) 0/644 (0.00%) 0/206 (0.00%) 1/219 (0.46%)
# events 0 0 0 0 1
Hepatobiliary disorders          
Cholecystitis1, †          
# participants affected / at risk 1/655 (0.15%) 0/637 (0.00%) 1/644 (0.16%) 1/206 (0.49%) 0/219 (0.00%)
# events 1 0 1 1 0
Hepatobiliary disorders          
Bile duct stone1, †          
# participants affected / at risk 1/655 (0.15%) 0/637 (0.00%) 1/644 (0.16%) 0/206 (0.00%) 0/219 (0.00%)
# events 1 0 1 0 0
Hepatobiliary disorders          
Cholelithiasis1, †          
# participants affected / at risk 0/655 (0.00%) 0/637 (0.00%) 1/644 (0.16%) 0/206 (0.00%) 1/219 (0.46%)
# events 0 0 1 0 1
Hepatobiliary disorders          
Cholecystitis acute1, †          
# participants affected / at risk 0/655 (0.00%) 0/637 (0.00%) 1/644 (0.16%) 0/206 (0.00%) 0/219 (0.00%)
# events 0 0 1 0 0
Musculoskeletal and connective tissue disorders          
Osteoarthritis1, †          
# participants affected / at risk 1/655 (0.15%) 0/637 (0.00%) 1/644 (0.16%) 0/206 (0.00%) 0/219 (0.00%)
# events 1 0 1 0 0
Musculoskeletal and connective tissue disorders          
Arthralgia1, †          
# participants affected / at risk 0/655 (0.00%) 1/637 (0.16%) 0/644 (0.00%) 0/206 (0.00%) 0/219 (0.00%)
# events 0 2 0 0 0
Musculoskeletal and connective tissue disorders          
Arthritis1, †          
# participants affected / at risk 0/655 (0.00%) 0/637 (0.00%) 1/644 (0.16%) 0/206 (0.00%) 0/219 (0.00%)
# events 0 0 1 0 0
Musculoskeletal and connective tissue disorders          
Bursitis1, †          
# participants affected / at risk 0/655 (0.00%) 0/637 (0.00%) 0/644 (0.00%) 0/206 (0.00%) 1/219 (0.46%)
# events 0 0 0 0 1
Musculoskeletal and connective tissue disorders          
Musculoskeletal chest pain1, †          
# participants affected / at risk 1/655 (0.15%) 0/637 (0.00%) 0/644 (0.00%) 0/206 (0.00%) 0/219 (0.00%)
# events 1 0 0 0 0
Musculoskeletal and connective tissue disorders          
Tendonitis1, †          
# participants affected / at risk 1/655 (0.15%) 0/637 (0.00%) 0/644 (0.00%) 0/206 (0.00%) 0/219 (0.00%)
# events 1 0 0 0 0
Vascular disorders          
Arteriosclerosis1, †          
# participants affected / at risk 0/655 (0.00%) 0/637 (0.00%) 1/644 (0.16%) 0/206 (0.00%) 0/219 (0.00%)
# events 0 0 1 0 0
Vascular disorders          
Haematoma1, †          
# participants affected / at risk 0/655 (0.00%) 0/637 (0.00%) 1/644 (0.16%) 0/206 (0.00%) 0/219 (0.00%)
# events 0 0 1 0 0
Vascular disorders          
Hypertensive emergency1, †          
# participants affected / at risk 0/655 (0.00%) 1/637 (0.16%) 0/644 (0.00%) 0/206 (0.00%) 0/219 (0.00%)
# events 0 1 0 0 0
Vascular disorders          
Peripheral artery thrombosis1, †          
# participants affected / at risk 0/655 (0.00%) 1/637 (0.16%) 0/644 (0.00%) 0/206 (0.00%) 0/219 (0.00%)
# events 0 1 0 0 0
Vascular disorders          
Peripheral ischaemia1, †          
# participants affected / at risk 0/655 (0.00%) 0/637 (0.00%) 1/644 (0.16%) 0/206 (0.00%) 0/219 (0.00%)
# events 0 0 1 0 0
Vascular disorders          
Thrombophlebitis superficial1, †          
# participants affected / at risk 0/655 (0.00%) 0/637 (0.00%) 1/644 (0.16%) 0/206 (0.00%) 0/219 (0.00%)
# events 0 0 1 0 0
General disorders          
Chest discomfort1, †          
# participants affected / at risk 1/655 (0.15%) 0/637 (0.00%) 0/644 (0.00%) 0/206 (0.00%) 0/219 (0.00%)
# events 1 0 0 0 0
General disorders          
Chest pain1, †          
# participants affected / at risk 1/655 (0.15%) 0/637 (0.00%) 0/644 (0.00%) 0/206 (0.00%) 0/219 (0.00%)
# events 1 0 0 0 0
General disorders          
Death1, †          
# participants affected / at risk 0/655 (0.00%) 0/637 (0.00%) 0/644 (0.00%) 0/206 (0.00%) 1/219 (0.46%)
# events 0 0 0 0 1
General disorders          
Incarcerated hernia1, †          
# participants affected / at risk 0/655 (0.00%) 0/637 (0.00%) 1/644 (0.16%) 0/206 (0.00%) 0/219 (0.00%)
# events 0 0 1 0 0
General disorders          
Sudden cardiac death1, †          
# participants affected / at risk 0/655 (0.00%) 0/637 (0.00%) 1/644 (0.16%) 0/206 (0.00%) 0/219 (0.00%)
# events 0 0 1 0 0
Metabolism and nutrition disorders          
Cachexia1, †          
# participants affected / at risk 0/655 (0.00%) 0/637 (0.00%) 0/644 (0.00%) 0/206 (0.00%) 1/219 (0.46%)
# events 0 0 0 0 1
Metabolism and nutrition disorders          
Diabetes mellitus1, †          
# participants affected / at risk 0/655 (0.00%) 0/637 (0.00%) 1/644 (0.16%) 0/206 (0.00%) 0/219 (0.00%)
# events 0 0 1 0 0
Metabolism and nutrition disorders          
Diabetes with hyperosmolarity1, †          
# participants affected / at risk 1/655 (0.15%) 0/637 (0.00%) 0/644 (0.00%) 0/206 (0.00%) 0/219 (0.00%)
# events 1 0 0 0 0
Metabolism and nutrition disorders          
Electrolyte imbalance1, †          
# participants affected / at risk 0/655 (0.00%) 0/637 (0.00%) 1/644 (0.16%) 0/206 (0.00%) 0/219 (0.00%)
# events 0 0 1 0 0
Metabolism and nutrition disorders          
Gout1, †          
# participants affected / at risk 0/655 (0.00%) 0/637 (0.00%) 1/644 (0.16%) 0/206 (0.00%) 0/219 (0.00%)
# events 0 0 1 0 0
Renal and urinary disorders          
Acute kidney injury1, †          
# participants affected / at risk 1/655 (0.15%) 0/637 (0.00%) 0/644 (0.00%) 0/206 (0.00%) 0/219 (0.00%)
# events 1 0 0 0 0
Renal and urinary disorders          
Chronic kidney disease1, †          
# participants affected / at risk 0/655 (0.00%) 0/637 (0.00%) 1/644 (0.16%) 0/206 (0.00%) 0/219 (0.00%)
# events 0 0 1 0 0
Renal and urinary disorders          
Hypertonic bladder1, †          
# participants affected / at risk 1/655 (0.15%) 0/637 (0.00%) 0/644 (0.00%) 0/206 (0.00%) 0/219 (0.00%)
# events 1 0 0 0 0
Renal and urinary disorders          
Renal tubular necrosis1, †          
# participants affected / at risk 0/655 (0.00%) 0/637 (0.00%) 1/644 (0.16%) 0/206 (0.00%) 0/219 (0.00%)
# events 0 0 1 0 0
Eye disorders          
Cataract1, †          
# participants affected / at risk 0/655 (0.00%) 1/637 (0.16%) 1/644 (0.16%) 0/206 (0.00%) 0/219 (0.00%)
# events 0 1 1 0 0
Product Issues          
Device battery issue1, †          
# participants affected / at risk 0/655 (0.00%) 0/637 (0.00%) 1/644 (0.16%) 0/206 (0.00%) 0/219 (0.00%)
# events 0 0 1 0 0
Psychiatric disorders          
Mental status changes1, †          
# participants affected / at risk 0/655 (0.00%) 1/637 (0.16%) 0/644 (0.00%) 0/206 (0.00%) 0/219 (0.00%)
# events 0 1 0 0 0
Reproductive system and breast disorders          
Prostatic haemorrhage1, †          
# participants affected / at risk 1/655 (0.15%) 0/637 (0.00%) 0/644 (0.00%) 0/206 (0.00%) 0/219 (0.00%)
# events 1 0 0 0 0
Injury, poisoning and procedural complications          
Skull fractured base1, †          
# participants affected / at risk 0/655 (0.00%) 0/637 (0.00%) 1/644 (0.16%) 0/206 (0.00%) 0/219 (0.00%)
# events 0 0 1 0 0
Renal and urinary disorders          
Renal cyst1, †          
# participants affected / at risk 1/655 (0.15%) 0/637 (0.00%) 0/644 (0.00%) 0/206 (0.00%) 0/219 (0.00%)
# events 1 0 0 0 0
† Events were collected by systematic assessment
1 Term from vocabulary,  MedDRA
2 Term from vocabulary,  MedDRa

Other Adverse Events

Time Frame Adverse events were collected from the time the subject signed informed consent throughout the treatment period and up to 14 days following the last dose of study drug
Additional Description Serious Adverse Events were collected from the time the subject signed informed consent throughout the treatment period and up to approximately 30 weeks, which includes screening and follow up (14 days after last dose of study drug). 

Frequency Threshold

Threshold above which other adverse events are reported 2%

Reporting Groups

  Description
BFF MDI 320/9.6 μg Budesonide Formoterol Fumarate Metered Dose Inhalation 320/9.6 μg
BFF MDI 160/9.6 μg Budesonide Formoterol Fumarate Metered Dose Inhalation 160/9.6 μg
FF MDI 9.6 μg Formoterol Fumarate Metered Dose Inhalation 9.6 μg
BD MDI 320 μg Budesonide Metered Dose Inhalation 320 μg
Symbicort TBH 400/12 μg Symbicort Turbuhaler 400/12 μg

Other Adverse Events

  BFF MDI 320/9.6 μg BFF MDI 160/9.6 μg FF MDI 9.6 μg BD MDI 320 μg Symbicort TBH 400/12 μg
Total, other (not including serious) adverse events          
# participants affected / at risk 240/655 (36.64%) 201/637 (31.55%) 219/644 (34.01%) 75/206 (36.41%) 57/219 (26.03%)
Infections and infestations          
Nasopharyngitis1, †          
# participants affected / at risk 40/655 (6.11%) 40/637 (6.28%) 43/644 (6.68%) 17/206 (8.25%) 14/219 (6.39%)
# events 46 44 46 18 18
Infections and infestations          
Upper respiratory tract infection1, †          
# participants affected / at risk 25/655 (3.82%) 21/637 (3.30%) 20/644 (3.11%) 5/206 (2.43%) 3/219 (1.37%)
# events 27 24 20 7 3
Infections and infestations          
Chronic obstructive pulmonary disease1, †          
# participants affected / at risk 16/655 (2.44%) 10/637 (1.57%) 30/644 (4.66%) 2/206 (0.97%) 6/219 (2.74%)
# events 17 10 36 2 6
Vascular disorders          
Hypertension1, †          
# participants affected / at risk 14/655 (2.14%) 22/637 (3.45%) 15/644 (2.33%) 5/206 (2.43%) 4/219 (1.83%)
# events 14 22 15 5 5
Musculoskeletal and connective tissue disorders          
Back pain1, †          
# participants affected / at risk 18/655 (2.75%) 13/637 (2.04%) 18/644 (2.80%) 3/206 (1.46%) 2/219 (0.91%)
# events 21 14 19 3 2
Nervous system disorders          
Headache1, †          
# participants affected / at risk 19/655 (2.90%) 8/637 (1.26%) 15/644 (2.33%) 3/206 (1.46%) 1/219 (0.46%)
# events 27 10 15 4 3
Respiratory, thoracic and mediastinal disorders          
Cough1, †          
# participants affected / at risk 7/655 (1.07%) 15/637 (2.35%) 15/644 (2.33%) 7/206 (3.40%) 0/219 (0.00%)
# events 8 15 15 7 0
Infections and infestations          
Oral candidiasis1, †          
# participants affected / at risk 17/655 (2.60%) 14/637 (2.20%) 5/644 (0.78%) 3/206 (1.46%) 3/219 (1.37%)
# events 18 15 6 3 3
Respiratory, thoracic and mediastinal disorders          
Dyspnoea1, †          
# participants affected / at risk 12/655 (1.83%) 11/637 (1.73%) 9/644 (1.40%) 7/206 (3.40%) 3/219 (1.37%)
# events 12 11 9 7 3
Infections and infestations          
Bronchitis1, †          
# participants affected / at risk 16/655 (2.44%) 7/637 (1.10%) 10/644 (1.55%) 4/206 (1.94%) 2/219 (0.91%)
# events 17 8 10 4 2
Infections and infestations          
Sinusitis1, †          
# participants affected / at risk 10/655 (1.53%) 9/637 (1.41%) 12/644 (1.86%) 2/206 (0.97%) 5/219 (2.28%)
# events 12 10 13 2 5
Gastrointestinal disorders          
Diarrhoea1, †          
# participants affected / at risk 9/655 (1.37%) 9/637 (1.41%) 9/644 (1.40%) 5/206 (2.43%) 3/219 (1.37%)
# events 9 9 9 6 3
Respiratory, thoracic and mediastinal disorders          
Dysphonia2, †          
# participants affected / at risk 16/655 (2.44%) 13/637 (2.04%) 3/644 (0.47%) 2/206 (0.97%) 1/219 (0.46%)
# events 16 13 3 2 1
Musculoskeletal and connective tissue disorders          
Muscle spasms1, †          
# participants affected / at risk 14/655 (2.14%) 6/637 (0.94%) 6/644 (0.93%) 0/206 (0.00%) 8/219 (3.65%)
# events 15 6 7 0 8
Psychiatric disorders          
Anxiety1, †          
# participants affected / at risk 6/655 (0.92%) 2/637 (0.31%) 4/644 (0.62%) 5/206 (2.43%) 1/219 (0.46%)
# events 6 2 4 5 1
General disorders          
Fatigue1, †          
# participants affected / at risk 1/655 (0.15%) 1/637 (0.16%) 5/644 (0.78%) 5/206 (2.43%) 1/219 (0.46%)
# events 1 1 5 5 1
† Events were collected by systematic assessment
1 Term from vocabulary,  MedDRA
2 Term from vocabulary,  medDRA

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that 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 or equal to 180 days . The sponsor cannot require changes to the communication and cannot extend the embargo.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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Results Point of Contact

Name/Title: Paul M. Dorinsky, MD
Organization: Pearl Therapeutics, a Member of the AstraZeneca Group
Phone 650-305-2600 
E-mail: [email protected]
.