Phase4/Symbicort® versus Pulmicort Flexhaler® in African Americans - Titan

Study identifier:D589BL00003

ClinicalTrials.gov identifier:N/A

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

A 12-wk, rand., double-blind, double dummy, multi-ctr., phase IV study comparing efficacy and safety of SYMBICORT® pMDI 160/4.5 ug x 2 actuations twice daily versus Pulmicort® (budesonide inhalation powder DPI) 180 ug x 2 inhalations twice daily, in adult and adolescent African American subjects with asthma

Medical condition

asthma

Phase

Phase 4

Healthy volunteers

Study drug

Budesonide / formoterol fumarate (SYMBICORT), Budesonide

Sex

All

Actual Enrollment

311

Study type

Interventional

Age

12 Years +

Date

Study Start Date: 01 Jun 2008

Primary Completion Date: 01 Sept 2009

Study Completion Date: 01 Sept 2009

Study design

Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind
Primary Purpose: Treatment

Verification:

Verified 01 Oct 2012 by AstraZeneca Pharmaceuticals

Collaborators

Inclusion and exclusion criteria

Location

Research Site

Hagerstown, MD, United States

Location

Research Site

Waco, TX, United States

Location

Research Site

Decatur, GA, United States

Location

Research Site

Blue Bell, PA, United States

Location

Research Site

San Antonio, TX, United States

Location

Research Site

Inverness, FL, United States

Location

Research Site

Colorado Springs, CO, United States

Location

Research Site

Emporia, VA, United States

Arms	Assigned Interventions
Experimental: 1	Drug: Budesonide / formoterol fumarate (SYMBICORT) 160/4.5 μg x 2 actuations twice daily (bid) Other Name: SYMBICORT
Active Comparator: 2	Drug: Budesonide inhalation powder 180 μg x 2 inhalations bid (PULMICORT) Other Name: PULMICORT

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
First participant enrolled on 05 June 2008, last participant last visit on 10 September 2009.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
10 subjects were excluded from the FAS: 9 who received the incorrect study medication and 1 who was randomized to receive SYMBICORT pMDI, but never received study medication. Therefore, 153 subjects (from 156 randomized to Symbicort) and 148 (from 155 randomized to Budesonide) were included in the FAS used to present baseline characteristics.

Reporting Groups

	Description
Symbicort	Symbicort pressurized metered dose inhaler (pMDI) 160/4.5 mcg x 2 actuations, twice daily.
Budesonide	Budesonide inhalation dry powder inhaler (DPI) 180 mcg x 2 inhalations, twice daily.

Participant Flow: Overall Study

	Symbicort	Budesonide
STARTED	156^[1]	155^[2]
COMPLETED	118^[3]	102^[4]
NOT COMPLETED	38	53
Adverse Event	1	0
Withdrawal by Subject	7	7
Lost to Follow-up	3	4
Incorrect enrollment	5	7
Developed study discontinuation criteria	18	28
Severe noncompliance to protocol	3	3
Termination due to lab results	1	0
Didn't follow study medication dosage	0	2
Withdrew consent	0	1
Incorrectly Discontinued	0	1

[1]	Randomized
[2]	Randomized
[3]	Completed participants based on randomized population (156) minus discontinued participants (38).
[4]	Completed participants based on randomized population (155) minus discontinued participants (53).

Baseline Characteristics

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

Reporting Groups

	Description
Symbicort	Symbicort pressurized metered dose inhaler (pMDI) 160/4.5 mcg x 2 actuations, twice daily.
Budesonide	Budesonide inhalation dry powder inhaler (DPI) 180 mcg x 2 inhalations, twice daily.

Baseline Measures

	Symbicort	Budesonide	Total
Number of Participants [units: Participants]	153	148	301
Age Continuous [units: Years] Mean ± Standard Deviation	38.6 ± 13.8	39.8 ± 15.4	39.2 ± 14.6
Gender, Male/Female [units: Participants]
Female	109	87	196
Male	44	61	105

Outcome Measures

1. Primary Outcome Measure: Change from baseline in pre-dose forced expiratory volume in 1 second (FEV1) averaged over treatment period [ Time Frame: Baseline to 12 weeks ]

Measure Type	Primary
Measure Name	Change from baseline in pre-dose forced expiratory volume in 1 second (FEV1) averaged over treatment period
Measure Description	Mean change from baseline (Visit 3) value to average value recorded at visits during treatment period
Time Frame	Baseline to 12 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.
Full analysis set (FAS) was performed and was based on data from all subjects who were randomized, took at least 1 dose of study medication, and contributed sufficient data for calculation of this outcome Measure.

Reporting Groups

	Description
Symbicort	Symbicort pressurized metered dose inhaler (pMDI) 160/4.5 mcg x 2 actuations, twice daily.
Budesonide	Budesonide inhalation dry powder inhaler (DPI) 180 mcg x 2 inhalations, twice daily.

Measured Values

	Symbicort	Budesonide
Number of Participants Analyzed [units:participants]	150	143
Change from baseline in pre-dose forced expiratory volume in 1 second (FEV1) averaged over treatment period [units: Liters] Mean (Standard Deviation)	0.16 (0.31)	0.07 (0.26)

No statistical analysis provided for Change from baseline in pre-dose forced expiratory volume in 1 second (FEV1) averaged over treatment period

2. Secondary Outcome Measure: Change from baseline in morning peak expiratory flow (AM PEF) averaged over the treatment period [ Time Frame: Baseline to 12 weeks ]

Measure Type	Secondary
Measure Name	Change from baseline in morning peak expiratory flow (AM PEF) averaged over the treatment period
Measure Description	Mean change from baseline (Visit 3) value to average value recorded at visits during treatment period
Time Frame	Baseline to 12 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.
Full analysis set (FAS) was performed and was based on data from all subjects who were randomized, took at least 1 dose of study medication, and contributed sufficient data for calculation of this outcome Measure.

Reporting Groups

	Description
Symbicort	Symbicort pressurized metered dose inhaler (pMDI) 160/4.5 mcg x 2 actuations, twice daily.
Budesonide	Budesonide inhalation dry powder inhaler (DPI) 180 mcg x 2 inhalations, twice daily.

Measured Values

	Symbicort	Budesonide
Number of Participants Analyzed [units:participants]	149	139
Change from baseline in morning peak expiratory flow (AM PEF) averaged over the treatment period [units: Liters/minute] Mean (Standard Deviation)	25.34 (43.70)	7.53 (32.41)

No statistical analysis provided for Change from baseline in morning peak expiratory flow (AM PEF) averaged over the treatment period

3. Secondary Outcome Measure: Change from baseline in evening peak expiratory flow (PM PEF) averaged over the treatment period [ Time Frame: Baseline to 12 weeks ]

Measure Type	Secondary
Measure Name	Change from baseline in evening peak expiratory flow (PM PEF) averaged over the treatment period
Measure Description	Mean change from baseline (Visit 3) value to average value recorded at visits during treatment period
Time Frame	Baseline to 12 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.
Full analysis set (FAS) was performed and was based on data from all subjects who were randomized, took at least 1 dose of study medication, and contributed sufficient data for calculation of this outcome Measure.

Reporting Groups

	Description
Symbicort	Symbicort pressurized metered dose inhaler (pMDI) 160/4.5 mcg x 2 actuations, twice daily.
Budesonide	Budesonide inhalation dry powder inhaler (DPI) 180 mcg x 2 inhalations, twice daily.

Measured Values

	Symbicort	Budesonide
Number of Participants Analyzed [units:participants]	149	141
Change from baseline in evening peak expiratory flow (PM PEF) averaged over the treatment period [units: Liters/minute] Mean (Standard Deviation)	21.61 (40.75)	7.67 (48.97)

No statistical analysis provided for Change from baseline in evening peak expiratory flow (PM PEF) averaged over the treatment period

4. Secondary Outcome Measure: Change from baseline in pre-dose forced vital capacity (FVC) averaged over the treatment period [ Time Frame: Baseline to 12 weeks ]

Measure Type	Secondary
Measure Name	Change from baseline in pre-dose forced vital capacity (FVC) averaged over the treatment period
Measure Description	Mean change from baseline (Visit 3) value to average value recorded at visits during treatment period
Time Frame	Baseline to 12 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.
Full analysis set (FAS) was performed and was based on data from all subjects who were randomized, took at least 1 dose of study medication, and contributed sufficient data for calculation of this outcome Measure.

Reporting Groups

	Description
Symbicort	Symbicort pressurized metered dose inhaler (pMDI) 160/4.5 mcg x 2 actuations, twice daily.
Budesonide	Budesonide inhalation dry powder inhaler (DPI) 180 mcg x 2 inhalations, twice daily.

Measured Values

	Symbicort	Budesonide
Number of Participants Analyzed [units:participants]	150	143
Change from baseline in pre-dose forced vital capacity (FVC) averaged over the treatment period [units: Liters] Mean (Standard Deviation)	0.14 (0.32)	0.07 (0.27)

No statistical analysis provided for Change from baseline in pre-dose forced vital capacity (FVC) averaged over the treatment period

5. Secondary Outcome Measure: Change From Baseline in Pre-dose Forced Expiratory Flow (FEF 25-75%) Averaged Over the Treatment Period [ Time Frame: Baseline to 12 weeks ]

Measure Type	Secondary
Measure Name	Change From Baseline in Pre-dose Forced Expiratory Flow (FEF 25-75%) Averaged Over the Treatment Period
Measure Description	Mean change of the FEF (25-75%) value at the baseline (Visit 3) compared to average value of the FEF (25-75%) recorded at visits during treatment period (to week 12). The mean change was calculated.
Time Frame	Baseline to 12 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.
Full analysis set (FAS) was performed and was based on data from all subjects who were randomized, took at least 1 dose of study medication, and contributed sufficient data for calculation of this outcome Measure.

Reporting Groups

	Description
Symbicort	Symbicort pressurized metered dose inhaler (pMDI) 160/4.5 mcg x 2 actuations, twice daily.
Budesonide	Budesonide inhalation dry powder inhaler (DPI) 180 mcg x 2 inhalations, twice daily.

Measured Values

	Symbicort	Budesonide
Number of Participants Analyzed [units:participants]	150	143
Change From Baseline in Pre-dose Forced Expiratory Flow (FEF 25-75%) Averaged Over the Treatment Period [units: Liters/second] Mean (Standard Deviation)	0.21 (0.47)	0.12 (0.47)

No statistical analysis provided for Change From Baseline in Pre-dose Forced Expiratory Flow (FEF 25-75%) Averaged Over the Treatment Period

6. Secondary Outcome Measure: Number of first predefined asthma events by inhaled corticosteroid (ICS) dose at entry [ Time Frame: 12 weeks ]

Measure Type	Secondary
Measure Name	Number of first predefined asthma events by inhaled corticosteroid (ICS) dose at entry
Measure Description	Total number of participants with any first predefined asthma event (decrease in FEV1 ≥ 20%,or to <40% of predicted normal value,12 puffs of albuterol pMDI per day on 3 or more days, decrease in morning PEF ≥ 20% on 3 or more days, use of rescue medication for 2 or more nights, emergency treatment, hospitalization, use of other asthma medication)
Time Frame	12 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.

Reporting Groups

	Description
Symbicort	Symbicort pressurized metered dose inhaler (pMDI) 160/4.5 mcg x 2 actuations, twice daily.
Budesonide	Budesonide inhalation dry powder inhaler (DPI) 180 mcg x 2 inhalations, twice daily.

Measured Values

	Symbicort	Budesonide
Number of Participants Analyzed [units:participants]	153	148
Number of first predefined asthma events by inhaled corticosteroid (ICS) dose at entry [units: Participants]	57	67

No statistical analysis provided for Number of first predefined asthma events by inhaled corticosteroid (ICS) dose at entry

7. Secondary Outcome Measure: Number of withdrawals due to a predefined asthma event [ Time Frame: 12 weeks ]

Measure Type	Secondary
Measure Name	Number of withdrawals due to a predefined asthma event
Measure Description	Total number of participants who withdrew due to a predefined asthma event (decrease in FEV1 ≥ 20%,or to <40% of predicted normal value,12 puffs of albuterol pMDI per day on 3 or more days, decrease in morning PEF ≥ 20% on 3 or more days, use of rescue medication for 2 or more nights, emergency treatment, hospitalization, use of other asthma meds)
Time Frame	12 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.

Reporting Groups

	Description
Symbicort	Symbicort pressurized metered dose inhaler (pMDI) 160/4.5 mcg x 2 actuations, twice daily.
Budesonide	Budesonide inhalation dry powder inhaler (DPI) 180 mcg x 2 inhalations, twice daily.

Measured Values

	Symbicort	Budesonide
Number of Participants Analyzed [units:participants]	153	148
Number of withdrawals due to a predefined asthma event [units: Participants]	18	28

No statistical analysis provided for Number of withdrawals due to a predefined asthma event

8. Secondary Outcome Measure: Change from baseline in total average daily asthma symptom score averaged over the treatment period [ Time Frame: Baseline to 12 weeks ]

Measure Type	Secondary
Measure Name	Change from baseline in total average daily asthma symptom score averaged over the treatment period
Measure Description	Diary assessment of total asthma symptoms score (treatment average) by Inhaled Corticosteroid (ICS) dose at entry. Asthma symptoms are cough, wheeze and shortness of breath. Each symptom is usually rated from 0-3: 0-no symptoms, 1-mild, 2-moderate and 3-severe. Change from baseline (Visit 3) mean value to average value recorded at visits during treatment period
Time Frame	Baseline to 12 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.
Full analysis set (FAS) was performed and was based on data from all subjects who were randomized, took at least 1 dose of study medication, and contributed sufficient data for calculation of this outcome Measure.

Reporting Groups

	Description
Symbicort	Symbicort pressurized metered dose inhaler (pMDI) 160/4.5 mcg x 2 actuations, twice daily.
Budesonide	Budesonide inhalation dry powder inhaler (DPI) 180 mcg x 2 inhalations, twice daily.

Measured Values

	Symbicort	Budesonide
Number of Participants Analyzed [units:participants]	149	142
Change from baseline in total average daily asthma symptom score averaged over the treatment period [units: Scores on a scale] Mean (Standard Deviation)	-0.35 (0.42)	-0.23 (0.40)

No statistical analysis provided for Change from baseline in total average daily asthma symptom score averaged over the treatment period

9. Secondary Outcome Measure: Change from baseline in nighttime asthma symptom score averaged over the treatment period [ Time Frame: Baseline to 12 weeks ]

Measure Type	Secondary
Measure Name	Change from baseline in nighttime asthma symptom score averaged over the treatment period
Measure Description	Diary assessment of nighttime asthma symptoms score (treatment average) by ICS dose at entry. Asthma symptoms are cough, wheeze and shortness of breath. Each symptom is usually rated from 0-3: 0-no symptoms, 1-mild, 2-moderate and 3-severe. Change from baseline (Visit 3) mean value to average value recorded at visits during treatment period; full analysis set (FAS)
Time Frame	Baseline to 12 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.
Full analysis set (FAS) was performed and was based on data from all subjects who were randomized, took at least 1 dose of study medication, and contributed sufficient data for calculation of this outcome Measure.

Reporting Groups

	Description
Symbicort	Symbicort pressurized metered dose inhaler (pMDI) 160/4.5 mcg x 2 actuations, twice daily.
Budesonide	Budesonide inhalation dry powder inhaler (DPI) 180 mcg x 2 inhalations, twice daily.

Measured Values

	Symbicort	Budesonide
Number of Participants Analyzed [units:participants]	151	146
Change from baseline in nighttime asthma symptom score averaged over the treatment period [units: Scores on a scale] Mean (Standard Deviation)	-0.38 (0.47)	-0.26 (0.42)

No statistical analysis provided for Change from baseline in nighttime asthma symptom score averaged over the treatment period

10. Secondary Outcome Measure: Change from baseline in daytime asthma symptom score averaged over the treatment period [ Time Frame: Baseline to 12 weeks ]

Measure Type	Secondary
Measure Name	Change from baseline in daytime asthma symptom score averaged over the treatment period
Measure Description	Diary assessment of daytime asthma symptoms score (treatment average) by ICS dose at entry. Asthma symptoms are cough, wheeze and shortness of breath. Each symptom is usually rated from 0-3: 0-no symptoms, 1-mild, 2-moderate and 3-severe. Change from baseline (Visit 3) mean value to average value recorded at visits during treatment period; full analysis set (FAS)
Time Frame	Baseline to 12 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.
Full analysis set (FAS) was performed and was based on data from all subjects who were randomized, took at least 1 dose of study medication, and contributed sufficient data for calculation of this outcome Measure.

Reporting Groups

	Description
Symbicort	Symbicort pressurized metered dose inhaler (pMDI) 160/4.5 mcg x 2 actuations, twice daily.
Budesonide	Budesonide inhalation dry powder inhaler (DPI) 180 mcg x 2 inhalations, twice daily.

Measured Values

	Symbicort	Budesonide
Number of Participants Analyzed [units:participants]	150	143
Change from baseline in daytime asthma symptom score averaged over the treatment period [units: Scores on a scale] Mean (Standard Deviation)	-0.33 (0.45)	-0.24 (0.45)

No statistical analysis provided for Change from baseline in daytime asthma symptom score averaged over the treatment period

11. Secondary Outcome Measure: Change from baseline in awakening-free nights averaged over the treatment period [ Time Frame: Baseline to 12 weeks ]

Measure Type	Secondary
Measure Name	Change from baseline in awakening-free nights averaged over the treatment period
Measure Description	Diary assessment of number of nights free from awakenings due to asthma; mean change from baseline (Visit 3) value to average value recorded at visits during treatment period
Time Frame	Baseline to 12 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.
Full analysis set (FAS) was performed and was based on data from all subjects who were randomized, took at least 1 dose of study medication, and contributed sufficient data for calculation of this outcome Measure.

Reporting Groups

	Description
Symbicort	Symbicort pressurized metered dose inhaler (pMDI) 160/4.5 mcg x 2 actuations, twice daily.
Budesonide	Budesonide inhalation dry powder inhaler (DPI) 180 mcg x 2 inhalations, twice daily.

Measured Values

	Symbicort	Budesonide
Number of Participants Analyzed [units:participants]	150	143
Change from baseline in awakening-free nights averaged over the treatment period [units: Number of nights] Mean (Standard Deviation)	17.51 (26.51)	11.85 (25.92)

No statistical analysis provided for Change from baseline in awakening-free nights averaged over the treatment period

12. Secondary Outcome Measure: Change from baseline to the average in total rescue medication use averaged over the treatment period [ Time Frame: Baseline to 12 weeks ]

Measure Type	Secondary
Measure Name	Change from baseline to the average in total rescue medication use averaged over the treatment period
Measure Description	Diary assessment of total daily puffs of rescue medication used for asthma symptoms relief; mean change from baseline (Visit 3) value to average value recorded at visits during treatment period
Time Frame	Baseline to 12 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.
Full analysis set (FAS) was performed and was based on data from all subjects who were randomized, took at least 1 dose of study medication, and contributed sufficient data for calculation of this outcome Measure.

Reporting Groups

	Description
Symbicort	Symbicort pressurized metered dose inhaler (pMDI) 160/4.5 mcg x 2 actuations, twice daily.
Budesonide	Budesonide inhalation dry powder inhaler (DPI) 180 mcg x 2 inhalations, twice daily.

Measured Values

	Symbicort	Budesonide
Number of Participants Analyzed [units:participants]	150	144
Change from baseline to the average in total rescue medication use averaged over the treatment period [units: Puffs/day] Mean (Standard Deviation)	-1.27 (1.81)	-0.62 (1.68)

No statistical analysis provided for Change from baseline to the average in total rescue medication use averaged over the treatment period

13. Secondary Outcome Measure: Change from baseline to the average in nighttime rescue medication use averaged over the treatment period [ Time Frame: Baseline to 12 weeks ]

Measure Type	Secondary
Measure Name	Change from baseline to the average in nighttime rescue medication use averaged over the treatment period
Measure Description	Diary assessment of total nighttime puffs of rescue medication used for asthma symptoms relief; mean change from baseline (Visit 3) value to average value recorded at visits during treatment period
Time Frame	Baseline to 12 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.
Full analysis set (FAS) was performed and was based on data from all subjects who were randomized, took at least 1 dose of study medication, and contributed sufficient data for calculation of this outcome Measure.

Reporting Groups

	Description
Symbicort	Symbicort pressurized metered dose inhaler (pMDI) 160/4.5 mcg x 2 actuations, twice daily.
Budesonide	Budesonide inhalation dry powder inhaler (DPI) 180 mcg x 2 inhalations, twice daily.

Measured Values

	Symbicort	Budesonide
Number of Participants Analyzed [units:participants]	150	144
Change from baseline to the average in nighttime rescue medication use averaged over the treatment period [units: Puffs/day] Mean (Standard Deviation)	-0.79 (1.07)	-0.35 (0.93)

No statistical analysis provided for Change from baseline to the average in nighttime rescue medication use averaged over the treatment period

14. Secondary Outcome Measure: Change from baseline to the average in daytime medication use averaged over the treatment period [ Time Frame: Baseline to 12 weeks ]

Measure Type	Secondary
Measure Name	Change from baseline to the average in daytime medication use averaged over the treatment period
Measure Description	Diary assessment of total daytime puffs of rescue medication used for asthma symptoms relief; mean change from baseline (Visit 3) value to average value recorded at visits during treatment period
Time Frame	Baseline to 12 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.
Full analysis set (FAS) was performed and was based on data from all subjects who were randomized, took at least 1 dose of study medication, and contributed sufficient data for calculation of this outcome Measure.

Reporting Groups

	Description
Symbicort	Symbicort pressurized metered dose inhaler (pMDI) 160/4.5 mcg x 2 actuations, twice daily.
Budesonide	Budesonide inhalation dry powder inhaler (DPI) 180 mcg x 2 inhalations, twice daily.

Measured Values

	Symbicort	Budesonide
Number of Participants Analyzed [units:participants]	150	144
Change from baseline to the average in daytime medication use averaged over the treatment period [units: Puffs/day] Mean (Standard Deviation)	-0.48 (0.93)	-0.27 (0.92)

No statistical analysis provided for Change from baseline to the average in daytime medication use averaged over the treatment period

15. Secondary Outcome Measure: Change from baseline to the average in rescue medication-free days averaged over the treatment period [ Time Frame: Baseline to 12 weeks ]

Measure Type	Secondary
Measure Name	Change from baseline to the average in rescue medication-free days averaged over the treatment period
Measure Description	Diary assessment of total (percent) days free from rescue medication use for asthma symptoms relief; mean change from baseline (Visit 3) value to average value recorded at visits during treatment period
Time Frame	Baseline to 12 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.
Full analysis set (FAS) was performed and was based on data from all subjects who were randomized, took at least 1 dose of study medication, and contributed sufficient data for calculation of this outcome Measure.

Reporting Groups

	Description
Symbicort	Symbicort pressurized metered dose inhaler (pMDI) 160/4.5 mcg x 2 actuations, twice daily.
Budesonide	Budesonide inhalation dry powder inhaler (DPI) 180 mcg x 2 inhalations, twice daily.

Measured Values

	Symbicort	Budesonide
Number of Participants Analyzed [units:participants]	150	144
Change from baseline to the average in rescue medication-free days averaged over the treatment period [units: percentage of days] Mean (Standard Deviation)	29.31 (34.13)	17.70 (35.39)

No statistical analysis provided for Change from baseline to the average in rescue medication-free days averaged over the treatment period

16. Secondary Outcome Measure: Change from baseline in asthma symptom-free days averaged over the treatment period [ Time Frame: Baseline to 12 weeks ]

Measure Type	Secondary
Measure Name	Change from baseline in asthma symptom-free days averaged over the treatment period
Measure Description	Diary assessment of number (percent) of days free from asthma symptoms by ICS dose at entry; mean change from baseline (Visit 3) value to average value recorded at visits during treatment period
Time Frame	Baseline to 12 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.
Full analysis set (FAS) was performed and was based on data from all subjects who were randomized, took at least 1 dose of study medication, and contributed sufficient data for calculation of this outcome Measure.

Reporting Groups

	Description
Symbicort	Symbicort pressurized metered dose inhaler (pMDI) 160/4.5 mcg x 2 actuations, twice daily.
Budesonide	Budesonide inhalation dry powder inhaler (DPI) 180 mcg x 2 inhalations, twice daily.

Measured Values

	Symbicort	Budesonide
Number of Participants Analyzed [units:participants]	151	146
Change from baseline in asthma symptom-free days averaged over the treatment period [units: percentage of days] Mean (Standard Deviation)	23.99 (29.82)	17.55 (28.58)

No statistical analysis provided for Change from baseline in asthma symptom-free days averaged over the treatment period

17. Secondary Outcome Measure: Change from baseline to the average for asthma-control days averaged over the treatment period [ Time Frame: Baseline to 12 weeks ]

Measure Type	Secondary
Measure Name	Change from baseline to the average for asthma-control days averaged over the treatment period
Measure Description	Diary assessment of number (percent) of asthma-control days (defined as days that were free of symptoms and nighttime and daytime rescue medication use); mean change from baseline (Visit 3) value to average value recorded at visits during treatment period
Time Frame	Baseline to 12 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.
Full analysis set (FAS) was performed and was based on data from all subjects who were randomized, took at least 1 dose of study medication, and contributed sufficient data for calculation of this outcome Measure.

Reporting Groups

	Description
Symbicort	Symbicort pressurized metered dose inhaler (pMDI) 160/4.5 mcg x 2 actuations, twice daily.
Budesonide	Budesonide inhalation dry powder inhaler (DPI) 180 mcg x 2 inhalations, twice daily.

Measured Values

	Symbicort	Budesonide
Number of Participants Analyzed [units:participants]	151	147
Change from baseline to the average for asthma-control days averaged over the treatment period [units: percentage of days] Mean (Standard Deviation)	21.89 (29.48)	15.12 (26.80)

No statistical analysis provided for Change from baseline to the average for asthma-control days averaged over the treatment period

18. Secondary Outcome Measure: Perception of onset of medication effect at last week of treatment assessed by number of participants who agreed with Item 2 on the Onset of Effect Questionnaire (OEQ) [ Time Frame: 12 week ]

Measure Type	Secondary
Measure Name	Perception of onset of medication effect at last week of treatment assessed by number of participants who agreed with Item 2 on the Onset of Effect Questionnaire (OEQ)
Measure Description	Diary assessment of participants age 12 years and older and 18 years and older who agreed with OEQ Item 2 at last week of treatment - During the past week, you could feel your medication begin to work right away
Time Frame	12 week
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.

Reporting Groups

	Description
Symbicort	Symbicort pressurized metered dose inhaler (pMDI) 160/4.5 mcg x 2 actuations, twice daily.
Budesonide	Budesonide inhalation dry powder inhaler (DPI) 180 mcg x 2 inhalations, twice daily.

Measured Values

	Symbicort	Budesonide
Number of Participants Analyzed [units:participants]	144	136
Perception of onset of medication effect at last week of treatment assessed by number of participants who agreed with Item 2 on the Onset of Effect Questionnaire (OEQ) [units: Participants]
12 years and older	123	112
18 years and older	109	95

No statistical analysis provided for Perception of onset of medication effect at last week of treatment assessed by number of participants who agreed with Item 2 on the Onset of Effect Questionnaire (OEQ)

19. Secondary Outcome Measure: Change from baseline to end of treatment in overall score on the Asthma Quality of Life Questionnaire-Standardized (AQLQ[S]) [ Time Frame: Baseline to 12 weeks ]

Measure Type	Secondary
Measure Name	Change from baseline to end of treatment in overall score on the Asthma Quality of Life Questionnaire-Standardized (AQLQ[S])
Measure Description	Mean change in overall score at end of treatment for participants age 17 years and older (scores ranged from 1 to 7, with higher scores indicating better quality of life); mean change from baseline (Visit 3) value to average value recorded at visits during treatment period
Time Frame	Baseline to 12 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.
Full analysis set (FAS) was performed and was based on data from all subjects who were randomized, took at least 1 dose of study medication, and contributed sufficient data for calculation of this outcome Measure.

Reporting Groups

	Description
Symbicort	Symbicort pressurized metered dose inhaler (pMDI) 160/4.5 mcg x 2 actuations, twice daily.
Budesonide	Budesonide inhalation dry powder inhaler (DPI) 180 mcg x 2 inhalations, twice daily.

Measured Values

	Symbicort	Budesonide
Number of Participants Analyzed [units:participants]	125	123
Change from baseline to end of treatment in overall score on the Asthma Quality of Life Questionnaire-Standardized (AQLQ[S]) [units: Scores on a scale] Mean (Standard Deviation)	0.55 (0.96)	0.33 (1.07)

No statistical analysis provided for Change from baseline to end of treatment in overall score on the Asthma Quality of Life Questionnaire-Standardized (AQLQ[S])

20. Secondary Outcome Measure: Proportion of participants who reported on the Asthma Control Test (ACT) that their asthma was controlled at the last week of treatment [ Time Frame: 12 weeks ]

Measure Type	Secondary
Measure Name	Proportion of participants who reported on the Asthma Control Test (ACT) that their asthma was controlled at the last week of treatment
Measure Description	There are 5 questions in the survey, and each question has 5 responses (total score for each question can range from 1 to 5). To score the survey, responses to the 5 questions are added to yield a total score that ranges from 5 (poor control of asthma control) to 25 (complete control of asthma). Score of 20 or higher was indicative of well-controlled asthma.
Time Frame	12 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.

Reporting Groups

	Description
Symbicort	Symbicort pressurized metered dose inhaler (pMDI) 160/4.5 mcg x 2 actuations, twice daily.
Budesonide	Budesonide inhalation dry powder inhaler (DPI) 180 mcg x 2 inhalations, twice daily.

Measured Values

	Symbicort	Budesonide
Number of Participants Analyzed [units:participants]	143	139
Proportion of participants who reported on the Asthma Control Test (ACT) that their asthma was controlled at the last week of treatment [units: Proportion of Participants]	0.524	0.518

No statistical analysis provided for Proportion of participants who reported on the Asthma Control Test (ACT) that their asthma was controlled at the last week of treatment

21. Secondary Outcome Measure: Change from baseline to last week of treatment in scores on the Asthma Impact Survey (AIS) [ Time Frame: Baseline to 12 weeks ]

Measure Type	Secondary
Measure Name	Change from baseline to last week of treatment in scores on the Asthma Impact Survey (AIS)
Measure Description	There are 6 questions in the survey, and each question has 5 responses (total score for each question can range from 6 to 13). Responses to the 6 questions were added to yield a total score that ranged from 36 to 78. Scoring is based on a norm-based method. Higher AIS scores indicated more asthma impact and poorer quality of life; mean change from baseline (Visit 3) value to average value recorded at visits during treatment period.
Time Frame	Baseline to 12 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.

Reporting Groups

	Description
Symbicort	Symbicort pressurized metered dose inhaler (pMDI) 160/4.5 mcg x 2 actuations, twice daily.
Budesonide	Budesonide inhalation dry powder inhaler (DPI) 180 mcg x 2 inhalations, twice daily.

Measured Values

	Symbicort	Budesonide
Number of Participants Analyzed [units:participants]	128	124
Change from baseline to last week of treatment in scores on the Asthma Impact Survey (AIS) [units: Scores on a scale] Mean (Standard Deviation)	-4.05 (6.79)	-2.72 (9.75)

No statistical analysis provided for Change from baseline to last week of treatment in scores on the Asthma Impact Survey (AIS)

22. Secondary Outcome Measure: Perception of onset of medication effect at last week of treatment assessed by number of participants who agreed with Item 5 on the Onset of Effect Questionnaire (OEQ) [ Time Frame: 12 week ]

Measure Type	Secondary
Measure Name	Perception of onset of medication effect at last week of treatment assessed by number of participants who agreed with Item 5 on the Onset of Effect Questionnaire (OEQ)
Measure Description	Diary assessment of participants age 12 years and older and 18 years and older who agreed with OEQ Item 5 at last week of treatment - During the past week, you were satisfied with how quickly you felt your study medication began to work.
Time Frame	12 week
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.

Reporting Groups

	Description
Symbicort	Symbicort pressurized metered dose inhaler (pMDI) 160/4.5 mcg x 2 actuations, twice daily.
Budesonide	Budesonide inhalation dry powder inhaler (DPI) 180 mcg x 2 inhalations, twice daily.

Measured Values

	Symbicort	Budesonide
Number of Participants Analyzed [units:participants]	144	136
Perception of onset of medication effect at last week of treatment assessed by number of participants who agreed with Item 5 on the Onset of Effect Questionnaire (OEQ) [units: Participants]
12 years and older	112	99
18 years and older	100	81

No statistical analysis provided for Perception of onset of medication effect at last week of treatment assessed by number of participants who agreed with Item 5 on the Onset of Effect Questionnaire (OEQ)

23. Secondary Outcome Measure: Perception of onset of medication effect at first week of treatment assessed by number of participants who agreed with Item 2 on the Onset of Effect Questionnaire (OEQ) [ Time Frame: 1 week ]

Measure Type	Secondary
Measure Name	Perception of onset of medication effect at first week of treatment assessed by number of participants who agreed with Item 2 on the Onset of Effect Questionnaire (OEQ)
Measure Description	Diary assessment of participants age 12 years and older and 18 years and older who agreed with OEQ Item 2 at first week of treatment - During the past week, you could feel your medication begin to work right away
Time Frame	1 week
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.

Reporting Groups

	Description
Symbicort	Symbicort pressurized metered dose inhaler (pMDI) 160/4.5 mcg x 2 actuations, twice daily.
Budesonide	Budesonide inhalation dry powder inhaler (DPI) 180 mcg x 2 inhalations, twice daily.

Measured Values

	Symbicort	Budesonide
Number of Participants Analyzed [units:participants]	256	234
Perception of onset of medication effect at first week of treatment assessed by number of participants who agreed with Item 2 on the Onset of Effect Questionnaire (OEQ) [units: Participants]
12 years and older	113	95
18 years and older	101	81

No statistical analysis provided for Perception of onset of medication effect at first week of treatment assessed by number of participants who agreed with Item 2 on the Onset of Effect Questionnaire (OEQ)

24. Secondary Outcome Measure: Perception of onset of medication effect at first week of treatment assessed by number of participants who agreed with Item 5 on the Onset of Effect Questionnaire (OEQ) [ Time Frame: 1 week ]

Measure Type	Secondary
Measure Name	Perception of onset of medication effect at first week of treatment assessed by number of participants who agreed with Item 5 on the Onset of Effect Questionnaire (OEQ)
Measure Description	Diary assessment of participants age 12 years and older and 18 years and older who agreed with OEQ Item 5 at first week of treatment - During the past week, you were satisfied with how quickly you felt your study medication began to work.
Time Frame	1 week
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.

Reporting Groups

	Description
Symbicort	Symbicort pressurized metered dose inhaler (pMDI) 160/4.5 mcg x 2 actuations, twice daily.
Budesonide	Budesonide inhalation dry powder inhaler (DPI) 180 mcg x 2 inhalations, twice daily.

Measured Values

	Symbicort	Budesonide
Number of Participants Analyzed [units:participants]	256	234
Perception of onset of medication effect at first week of treatment assessed by number of participants who agreed with Item 5 on the Onset of Effect Questionnaire (OEQ) [units: Participants]
12 years and older	96	83
18 years and older	86	70

No statistical analysis provided for Perception of onset of medication effect at first week of treatment assessed by number of participants who agreed with Item 5 on the Onset of Effect Questionnaire (OEQ)

Serious Adverse Events

Time Frame	No text entered.
Additional Description	No text entered.

Reporting Groups

	Description
Symbicort	Symbicort pressurized metered dose inhaler (pMDI) 160/4.5 mcg x 2 actuations, twice daily.
Budesonide	Budesonide inhalation dry powder inhaler (DPI) 180 mcg x 2 inhalations, twice daily.

Serious Adverse Events

Symbicort

Budesonide

Total, serious adverse events

# participants affected / at risk

1/156 (0.64%)

2/155 (1.29%)

General disorders

Pyrexia¹,^†

# participants affected / at risk

0/156 (0.00%)

1/155 (0.65%)

Reproductive system and breast disorders

Ovarian Cyst Ruptured¹,^†

# participants affected / at risk

1/156 (0.64%)

0/155 (0.00%)

Respiratory, thoracic and mediastinal disorders

Asthma¹,^†

# participants affected / at risk

0/156 (0.00%)

1/155 (0.65%)

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 10.0
2	Term from vocabulary,

Other Adverse Events

Time Frame	No text entered.
Additional Description	No text entered.

Frequency Threshold

Threshold above which other adverse events are reported	5%

Reporting Groups

	Description
Symbicort	Symbicort pressurized metered dose inhaler (pMDI) 160/4.5 mcg x 2 actuations, twice daily.
Budesonide	Budesonide inhalation dry powder inhaler (DPI) 180 mcg x 2 inhalations, twice daily.

Other Adverse Events

Symbicort

Budesonide

Total, other (not including serious) adverse events

# participants affected / at risk

18/156 (11.54%)

12/155 (7.74%)

Infections and infestations

Nasopharyngitis¹,^†

# participants affected / at risk

8/156 (5.13%)

4/155 (2.58%)

Nervous system disorders

Headache¹,^†

# participants affected / at risk

10/156 (6.41%)

8/155 (5.16%)

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 10.0
2	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: If Sponsor does not publish within 2 years after study completion, PI is permitted to publish, with confidential information removed from manuscript. Sponsor will have opportunity to review and approve publication at least 60 days pior to being submitted/disclosed. Sponsor can request, in writing, an additional 90 day 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
No text entered.

Results Point of Contact

Name/Title:	Gerard Lynch
Organization:	AstraZeneca
E-mail:	[email protected]

Documents available

https://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_6111&studyid=394&filename=CSR-D589BL00003.pdf
Download
CSR-D589BL00003.pdf
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information

800-236-9933

information.center@astrazeneca.com

Investigators

Principal Investigator

Ubaldo Martin

AstraZeneca

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

https://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_6111&studyid=394&filename=CSR-D589BL00003.pdf

CSR-D589BL00003.pdf

Trial Results Summaries