Study comparing dual combination of product (budesonide and formoterol) given via two different inhalers. To see which one results in the best effect on breathing.

Study identifier:D5980C00023

ClinicalTrials.gov identifier:NCT04078126

EudraCT identifier:2019-001801-26

CTIS identifier:N/A

Study Complete

Official Title

A Randomized, Open-Label, Two Period Crossover, Chronic Dosing, 1-Week, Pilot Study to Assess the Efficacy and Safety of Budesonide and Formoterol Fumarate Inhalation Aerosol Administered with a Spacer Compared with Symbicort® Turbuhaler® in Subjects with Severe to Very Severe Chronic Obstructive Pulmonary Disease and Low Peak Inspiratory Flow

Medical condition

Chronic obstructive pulmonary disease (COPD)

Phase

Phase 3

Healthy volunteers

Study drug

Sex

All

Actual Enrollment

Study type

Interventional

Age

40 Years - 80 Years

Date

Study Start Date: 10 Sept 2019

Primary Completion Date: 30 Dec 2020

Study Completion Date: 30 Dec 2020

Study design

Allocation: Randomized
Endpoint Classification: -
Intervention Model: Crossover Assignment
Masking: -
Primary Purpose: Treatment

Verification:

Verified 01 Feb 2022 by AstraZeneca

Collaborators

Inclusion and exclusion criteria

Location

Research Site

Gauting, Germany, 82131

Location

Research Site

Landsberg, Germany, 86899

Location

Research Site

Hannover, Germany, D-30173

Location

Research Site

Frankfurt/Main, Germany, 60389

Arms	Assigned Interventions
Experimental: Budesonide and formoterol fumarate (MDI BFF) Subject treated with MDI BFF followed by washout period	Combination Product: BFF Treatment with budesonide and formoterol furmate MDI (metered-dose inhaler)
Active Comparator: Symbicort Turbuhaler Subject treated with Symbicort followed by washout period	Combination Product: Symbicort Turbuhaler Treatment with budesonide and formoterol furmate DPI (dry-powder inhaler)

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 started recruitment in September 2019 with first subject randomized in January 2020. A total of 35 subjects were randomized at 4 study centers. The study completed in Dec 2020.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Subjects were randomized to an open-label, 2 period crossover study comparing Budesonide Formoterol Fumarate (BFF) Metered Dose Inhalation (MDI) administered with a spacer twice daily (BID) with Symbicort Turbuhaler BID. The subjects underwent an intervening two-week washout period where they used Berodual and Budesonide MDI BID.

Reporting Groups

	Description
BFF MDI/Symbicort Turbuhaler	Subject treated with Budesonide Formoterol Fumarate Metered Dose Inhalation followed by washout period and then Symbicort Turbuhaler
Symbicort Turbuhaler/BFF MDI	Subject treated with Symbicort Turbuhaler followed by washout period and then Budesonide Formoterol Fumarate Metered Dose Inhalation

Participant Flow for 3 periods

Period 1: Period 1

	BFF MDI/Symbicort Turbuhaler	Symbicort Turbuhaler/BFF MDI
STARTED	18	17
COMPLETED	18	17
NOT COMPLETED	0	0

Period 2: Washout

	BFF MDI/Symbicort Turbuhaler	Symbicort Turbuhaler/BFF MDI
STARTED	18	17
COMPLETED	18	15
NOT COMPLETED	0	2
Study put on hold due to COVID-19	0	2

Period 3: Period 2

	BFF MDI/Symbicort Turbuhaler	Symbicort Turbuhaler/BFF MDI
STARTED	18	15
COMPLETED	17	14
NOT COMPLETED	1	1
Study put on hold due to COVID-19	1	1

Baseline Characteristics

Analysis Population Description -- Explanation of how the number of participants for analysis was determined.

ITT Population - all subjects who were randomized to treatment

Reporting Groups

	Description
Overall Study	Intent-to-Treat (ITT) Population

Baseline Measures

	Overall Study
Number of Participants [units: Participants]	35
Age Continuous ^[1] [units: Years] Mean ± Standard Deviation Mean age (SD), years	65.8 ± 5.5
Sex: Female, Male ^[2] [units: Participants] Distribution of Male/Female Participants
Female	19
Male	16
Race (NIH/OMB) ^[3] [units: Participants] Race for all subjects
American Indian or Alaska Native	0
Asian	0
Native Hawaiian or Other Pacific Islander	0
Black or African American	0
White	35
More than one race	0
Unknown or Not Reported	0

Outcome Measures

1. Primary Outcome Measure: Peak change from baseline in forced expiratory volume in 1 second (FEV1) within 4 hours post-dose following 1 week of treatment [ Time Frame: baseline and 4 hours post dose after 1 week of treatment ]

Measure Type	Primary
Measure Name	Peak change from baseline in forced expiratory volume in 1 second (FEV1) within 4 hours post-dose following 1 week of treatment
Measure Description	Peak change from baseline in FEV1 within 4 hours post-dose was defined as the maximum of the FEV1 assessments within 4 hours post-dosing at each visit minus baseline, provided that there were at least 2 non-missing values during the first 4 hours post dose.
Time Frame	baseline and 4 hours post dose after 1 week of treatment
Safety Issue?

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.
Modified Intent-to-treat (mITT) Population included all patients who were randomized to treatment and received at least one dose of study treatment with post-baseline spirometry data from both treatment periods at Visits 4 and 6. Patients with data judged to be impacted by important protocol deviations were excluded. Patients discontinued and restarted due to the study having been put on hold for the COVID-19 pandemic used the instance of enrollment after they restarted.

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.

Modified Intent-to-treat (mITT) Population included all patients who were randomized to treatment and received at least one dose of study treatment with post-baseline spirometry data from both treatment periods at Visits 4 and 6. Patients with data judged to be impacted by important protocol deviations were excluded. Patients discontinued and restarted due to the study having been put on hold for the COVID-19 pandemic used the instance of enrollment after they restarted.

Reporting Groups

	Description
BFF MDI	Subject treated with Budesonide Formoterol Fumarate Metered Dose Inhalation
Symbicort Turbuhaler	Subject treated with Symbicort Turbuhaler

Measured Values

	BFF MDI	Symbicort Turbuhaler
Number of Participants Analyzed [units:participants]	30	30
Peak change from baseline in forced expiratory volume in 1 second (FEV1) within 4 hours post-dose following 1 week of treatment [units: L] Least Squares Mean (95% Confidence Interval)	0.256 (0.190 to 0.322)	0.274 (0.208 to 0.340)

Statistical Analysis 1 for Peak change from baseline in forced expiratory volume in 1 second (FEV1) within 4 hours post-dose following 1 week of treatment

Groups^[1]	All groups
Method^[3]	ANCOVA
P-Value^[4]	0.3450
Mean Difference (Final Values)^[5]	-0.017
Standard Error of the mean	± 0.0179
95% Confidence Interval	( -0.054 to 0.020 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

2. Secondary Outcome Measure: Area under the curve for change from baseline in FEV1 from area under the curve 0 to 4 hours (AUC0-4 h) following 1 week of treatment [ Time Frame: baseline and 4 hours post dose after 1 week of treatment ]

Measure Type	Secondary
Measure Name	Area under the curve for change from baseline in FEV1 from area under the curve 0 to 4 hours (AUC0-4 h) following 1 week of treatment
Measure Description	FEV1 AUC0-4 was calculated using the trapezoidal rule and was normalized by dividing by the time in hours from dosing to the last measurement included (typically 4 hours).
Time Frame	baseline and 4 hours post dose after 1 week of treatment
Safety Issue?

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 Population included all patients who were randomized to treatment and received at least one dose of study treatment with post-baseline spirometry data from both treatment periods at Visits 4 and 6. Patients with data judged to be impacted by important protocol deviations were excluded. Patients discontinued and restarted due to the study having been put on hold for the COVID-19 pandemic used the instance of enrollment after they restarted.

mITT Population included all patients who were randomized to treatment and received at least one dose of study treatment with post-baseline spirometry data from both treatment periods at Visits 4 and 6. Patients with data judged to be impacted by important protocol deviations were excluded. Patients discontinued and restarted due to the study having been put on hold for the COVID-19 pandemic used the instance of enrollment after they restarted.

Reporting Groups

	Description
BFF MDI	Subject treated with Budesonide Formoterol Fumarate Metered Dose Inhalation
Symbicort Turbuhaler	Subject treated with Symbicort Turbuhaler

Measured Values

	BFF MDI	Symbicort Turbuhaler
Number of Participants Analyzed [units:participants]	30	30
Area under the curve for change from baseline in FEV1 from area under the curve 0 to 4 hours (AUC0-4 h) following 1 week of treatment [units: L] Least Squares Mean (95% Confidence Interval)	0.194 (0.133 to 0.254)	0.210 (0.149 to 0.271)

Statistical Analysis 1 for Area under the curve for change from baseline in FEV1 from area under the curve 0 to 4 hours (AUC0-4 h) following 1 week of treatment

Groups^[1]	All groups
Method^[3]	ANCOVA
P-Value^[4]	0.3675
Mean Difference (Final Values)^[5]	-0.017
Standard Error of the mean	± 0.0183
95% Confidence Interval	( -0.054 to 0.021 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

3. Secondary Outcome Measure: Change from baseline in pre-dose FEV1 following 1 week of treatment [ Time Frame: baseline and after 1 week of treatment ]

Measure Type	Secondary
Measure Name	Change from baseline in pre-dose FEV1 following 1 week of treatment
Measure Description	Change from baseline in pre-dose FEV1 following 1 week of treatment was defined as the 45-minute pre-dose value following 1 week of treatment minus baseline.
Time Frame	baseline and after 1 week of treatment
Safety Issue?

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 Population included all patients who were randomized to treatment and received at least one dose of study treatment with post-baseline spirometry data from both treatment periods at Visits 4 and 6. Patients with data judged to be impacted by important protocol deviations were excluded. Patients discontinued and restarted due to the study having been put on hold for the COVID-19 pandemic used the instance of enrollment after they restarted.

Reporting Groups

	Description
BFF MDI	Subject treated with Budesonide Formoterol Fumarate Metered Dose Inhalation
Symbicort Turbuhaler	Subject treated with Symbicort Turbuhaler

Measured Values

	BFF MDI	Symbicort Turbuhaler
Number of Participants Analyzed [units:participants]	30	30
Change from baseline in pre-dose FEV1 following 1 week of treatment [units: L] Least Squares Mean (95% Confidence Interval)	0.081 (0.030 to 0.131)	0.087 (0.037 to 0.137)

Statistical Analysis 1 for Change from baseline in pre-dose FEV1 following 1 week of treatment

Groups^[1]	All groups
Method^[3]	ANCOVA
P-Value^[4]	0.7563
Mean Difference (Final Values)^[5]	-0.006
Standard Error of the mean	± 0.0199
95% Confidence Interval	( -0.047 to 0.034 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

4. Secondary Outcome Measure: Change from baseline in 2-hour post-dose inspiratory capacity (IC) following 1 week of treatment [ Time Frame: baseline and 2 hours post dose after 1 week of treatment ]

Measure Type	Secondary
Measure Name	Change from baseline in 2-hour post-dose inspiratory capacity (IC) following 1 week of treatment
Measure Description	Change from baseline in 2-hour post-dose IC following 1 week of treatment was defined as the 2-hour post-dose assessment of IC following 1 week of treatment minus baseline IC.
Time Frame	baseline and 2 hours post dose after 1 week of treatment
Safety Issue?

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 Population included all patients who were randomized to treatment and received at least one dose of study treatment with post-baseline spirometry data from both treatment periods at Visits 4 and 6. Patients with data judged to be impacted by important protocol deviations were excluded. Patients discontinued and restarted due to the study having been put on hold for the COVID-19 pandemic used the instance of enrollment after they restarted.

Reporting Groups

	Description
BFF MDI	Subject treated with Budesonide Formoterol Fumarate Metered Dose Inhalation
Symbicort Turbuhaler	Subject treated with Symbicort Turbuhaler

Measured Values

	BFF MDI	Symbicort Turbuhaler
Number of Participants Analyzed [units:participants]	30	30
Change from baseline in 2-hour post-dose inspiratory capacity (IC) following 1 week of treatment [units: L] Least Squares Mean (95% Confidence Interval)	0.379 (0.242 to 0.517)	0.411 (0.275 to 0.548)

Statistical Analysis 1 for Change from baseline in 2-hour post-dose inspiratory capacity (IC) following 1 week of treatment

Groups^[1]	All groups
Method^[3]	ANCOVA
P-Value^[4]	0.5419
Mean Difference (Final Values)^[5]	-0.032
Standard Error of the mean	± 0.0521
95% Confidence Interval	( -0.139 to 0.075 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

5. Secondary Outcome Measure: Change from baseline in pre-dose peak inspiratory flow (PIF; InCheck device set to no resistance) following 1 week of treatment [ Time Frame: baseline and after 1 week of treatment ]

Measure Type	Secondary
Measure Name	Change from baseline in pre-dose peak inspiratory flow (PIF; InCheck device set to no resistance) following 1 week of treatment
Measure Description	Change from baseline in pre-dose PIF (InCheck device set to no resistance) following 1 week of treatment was defined as the pre-dose PIF (InCheck device set to no resistance) following 1 week of treatment minus baseline PIF. (The InCheck Inspiratory Flow Measurement Device is an inhalation airflow meter that may be set to various resistances similar to marketed inhaler products. For this measurement, the device was set to no resistance.)
Time Frame	baseline and after 1 week of treatment
Safety Issue?

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 Population included all patients who were randomized to treatment and received at least one dose of study treatment with post-baseline spirometry data from both treatment periods at Visits 4 and 6. Patients with data judged to be impacted by important protocol deviations were excluded. Patients discontinued and restarted due to the study having been put on hold for the COVID-19 pandemic used the instance of enrollment after they restarted.

Reporting Groups

	Description
BFF MDI	Subject treated with Budesonide Formoterol Fumarate Metered Dose Inhalation
Symbicort Turbuhaler	Subject treated with Symbicort Turbuhaler

Measured Values

	BFF MDI	Symbicort Turbuhaler
Number of Participants Analyzed [units:participants]	30	30
Change from baseline in pre-dose peak inspiratory flow (PIF; InCheck device set to no resistance) following 1 week of treatment [units: L/min] Least Squares Mean (95% Confidence Interval)	1.50 (-2.26 to 5.27)	5.11 (1.34 to 8.88)

Statistical Analysis 1 for Change from baseline in pre-dose peak inspiratory flow (PIF; InCheck device set to no resistance) following 1 week of treatment

Groups^[1]	All groups
Method^[3]	ANCOVA
P-Value^[4]	0.1337
Mean Difference (Final Values)^[5]	-3.60
Standard Error of the mean	± 2.334
95% Confidence Interval	( -8.39 to 1.18 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

6. Secondary Outcome Measure: Change from baseline in pre-dose PIF (resistance set equal to Turbuhaler S) following 1 week of treatment [ Time Frame: baseline and after 1 week of treatment ]

Measure Type	Secondary
Measure Name	Change from baseline in pre-dose PIF (resistance set equal to Turbuhaler S) following 1 week of treatment
Measure Description	Change from baseline in pre-dose PIF (resistance set equal to Turbuhaler S) following 1 week of treatment was defined as the pre-dose PIF (resistance set equal to Turbuhaler S) following 1 week of treatment minus baseline PIF. (The InCheck Inspiratory Flow Measurement Device is an inhalation airflow meter that may be set to various resistances similar to marketed inhaler products. For this measurement, the device was set to resistance equal to the product Turbuhaler S.)
Time Frame	baseline and after 1 week of treatment
Safety Issue?

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 Population included all patients who were randomized to treatment and received at least one dose of study treatment with post-baseline spirometry data from both treatment periods at Visits 4 and 6. Patients with data judged to be impacted by important protocol deviations were excluded. Patients discontinued and restarted due to the study having been put on hold for the COVID-19 pandemic used the instance of enrollment after they restarted.

Reporting Groups

	Description
BFF MDI	Subject treated with Budesonide Formoterol Fumarate Metered Dose Inhalation
Symbicort Turbuhaler	Subject treated with Symbicort Turbuhaler

Measured Values

	BFF MDI	Symbicort Turbuhaler
Number of Participants Analyzed [units:participants]	30	30
Change from baseline in pre-dose PIF (resistance set equal to Turbuhaler S) following 1 week of treatment [units: L/min] Least Squares Mean (95% Confidence Interval)	1.13 (-0.78 to 3.03)	3.82 (1.91 to 5.72)

Statistical Analysis 1 for Change from baseline in pre-dose PIF (resistance set equal to Turbuhaler S) following 1 week of treatment

Groups^[1]	All groups
Method^[3]	ANCOVA
P-Value^[4]	0.0431
Mean Difference (Final Values)^[5]	-2.69
Standard Error of the mean	± 1.269
95% Confidence Interval	( -5.29 to -0.09 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

7. Secondary Outcome Measure: Change from baseline in pre-dose PIF (resistance set equal to ELLIPTA) following 1 week of treatment [ Time Frame: baseline and after 1 week of treatment ]

Measure Type	Secondary
Measure Name	Change from baseline in pre-dose PIF (resistance set equal to ELLIPTA) following 1 week of treatment
Measure Description	Change from baseline in pre-dose PIF (resistance set equal to ELLIPTA) following 1 week of treatment was defined as the pre-dose PIF (resistance set equal to ELLIPTA) following 1 week of treatment minus baseline PIF. (The InCheck Inspiratory Flow Measurement Device is an inhalation airflow meter that may be set to various resistances similar to marketed inhaler products. For this measurement, the device was set to resistance equal to the product ELLIPTA.)
Time Frame	baseline and after 1 week of treatment
Safety Issue?

Population Description

Reporting Groups

	Description
BFF MDI	Subject treated with Budesonide Formoterol Fumarate Metered Dose Inhalation
Symbicort Turbuhaler	Subject treated with Symbicort Turbuhaler

Measured Values

	BFF MDI	Symbicort Turbuhaler
Number of Participants Analyzed [units:participants]	30	30
Change from baseline in pre-dose PIF (resistance set equal to ELLIPTA) following 1 week of treatment [units: L/min] Least Squares Mean (95% Confidence Interval)	1.21 (-1.15 to 3.56)	2.74 (0.39 to 5.09)

Statistical Analysis 1 for Change from baseline in pre-dose PIF (resistance set equal to ELLIPTA) following 1 week of treatment

Groups^[1]	All groups
Method^[3]	ANCOVA
P-Value^[4]	0.3625
Mean Difference (Final Values)^[5]	-1.53
Standard Error of the mean	± 1.667
95% Confidence Interval	( -4.87 to 1.81 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

8. Secondary Outcome Measure: Change from baseline in 2-hour post-dose FEV1 following the first dose [ Time Frame: baseline and 2 hours post dose after the first dose of treatment ]

Measure Type	Secondary
Measure Name	Change from baseline in 2-hour post-dose FEV1 following the first dose
Measure Description	Change from baseline in 2-hour post-dose FEV1 following the 1st dose of treatment was defined as the 2-hour post-dose assessment of FEV1 following the 1st dose of treatment (Visit 3 or 5) minus baseline FEV1.
Time Frame	baseline and 2 hours post dose after the first dose of treatment
Safety Issue?

Population Description

Reporting Groups

	Description
BFF MDI	Subject treated with Budesonide Formoterol Fumarate Metered Dose Inhalation
Symbicort Turbuhaler	Subject treated with Symbicort Turbuhaler

Measured Values

	BFF MDI	Symbicort Turbuhaler
Number of Participants Analyzed [units:participants]	30	30
Change from baseline in 2-hour post-dose FEV1 following the first dose [units: L] Least Squares Mean (95% Confidence Interval)	0.136 (0.100 to 0.173)	0.093 (0.057 to 0.130)

Statistical Analysis 1 for Change from baseline in 2-hour post-dose FEV1 following the first dose

Groups^[1]	All groups
Method^[3]	ANCOVA
P-Value^[4]	0.0375
Mean Difference (Final Values)^[5]	0.043
Standard Error of the mean	± 0.0198
95% Confidence Interval	( 0.003 to 0.084 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

9. Secondary Outcome Measure: Change from baseline in 2-hour post-dose IC following the first dose [ Time Frame: baseline and 2 hours post dose after the first dose of treatment ]

Measure Type	Secondary
Measure Name	Change from baseline in 2-hour post-dose IC following the first dose
Measure Description	Change from baseline in 2-hour post-dose IC following the 1st dose of treatment was defined as the 2-hour post-dose assessment of IC following the 1st dose of treatment (Visit 3 or 5) minus baseline IC.
Time Frame	baseline and 2 hours post dose after the first dose of treatment
Safety Issue?

Population Description

Reporting Groups

	Description
BFF MDI	Subject treated with Budesonide Formoterol Fumarate Metered Dose Inhalation
Symbicort Turbuhaler	Subject treated with Symbicort Turbuhaler

Measured Values

	BFF MDI	Symbicort Turbuhaler
Number of Participants Analyzed [units:participants]	28	30
Change from baseline in 2-hour post-dose IC following the first dose [units: L] Least Squares Mean (95% Confidence Interval)	0.264 (0.164 to 0.363)	0.258 (0.161 to 0.356)

Statistical Analysis 1 for Change from baseline in 2-hour post-dose IC following the first dose

Groups^[1]	All groups
Method^[3]	ANCOVA
P-Value^[4]	0.9089
Mean Difference (Final Values)^[5]	0.005
Standard Error of the mean	± 0.0443
95% Confidence Interval	( -0.086 to 0.096 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

Serious Adverse Events

Time Frame	Non-serious adverse events were monitored/assessed from Randomization throughout the Treatment Period and including the washout and follow-up periods, a maximum of 6 weeks. Serious adverse events were recorded from the time of signing of the informed consent, through Run-in, Treatment Period, including washout, and follow-up period, a maximum of 9 weeks.
Additional Description	The Safety Population was defined as all subjects who were randomized to treatment and received at least one dose of study treatment. Subjects were analyzed according to the treatment actually received.

Reporting Groups

	Description
BFF MDI	Subject treated with Budesonide Formoterol Fumarate Metered Dose Inhalation
Symbicort Turbuhaler	Subject treated with Symbicort Turbuhaler

Serious Adverse Events

	BFF MDI	Symbicort Turbuhaler
Total, serious adverse events
# participants affected / at risk	0/33 (0.00%)	0/35 (0.00%)

Other Adverse Events

Time Frame	Non-serious adverse events were monitored/assessed from Randomization throughout the Treatment Period and including the washout and follow-up periods, a maximum of 6 weeks. Serious adverse events were recorded from the time of signing of the informed consent, through Run-in, Treatment Period, including washout, and follow-up period, a maximum of 9 weeks.
Additional Description	The Safety Population was defined as all subjects who were randomized to treatment and received at least one dose of study treatment. Subjects were analyzed according to the treatment actually received.

Frequency Threshold

Threshold above which other adverse events are reported	2%

Reporting Groups

	Description
BFF MDI	Subject treated with Budesonide Formoterol Fumarate Metered Dose Inhalation
Symbicort Turbuhaler	Subject treated with Symbicort Turbuhaler

Other Adverse Events

BFF MDI

Symbicort Turbuhaler

Total, other (not including serious) adverse events

# participants affected / at risk

1/33 (3.03%)

1/35 (2.86%)

Cardiac disorders

Angina pectoris^†

# participants affected / at risk

1/33 (3.03%)

0/35 (0.00%)

# events

Gastrointestinal disorders

Abdominal discomfort^†

# participants affected / at risk

0/33 (0.00%)

1/35 (2.86%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary,

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:

	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.
	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.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description:

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
No text entered.

Results Point of Contact

Name/Title:	AstraZeneca AB
Organization:	AstraZeneca AB
Phone	877-240-9479 Ext: 1
E-mail:	[email protected]

Documents available

The CSP redacted.
Download
the SAP redacted.
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

information.center@astrazeneca.com

Investigators

Principal Investigator

Bärbel Huber

2601

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

Research Site

Research Site

Research Site

The CSP redacted.

the SAP redacted.

Trial Results Summaries