Trial Outcomes & Findings for Symbicort Rapihaler Therapeutic Equivalence Study (NCT NCT00536731)

Results Overview

Change in the Morning PEF from baseline (calculated as a mean using all available data for the 10 last days of run-in period) to week 6 (calculated as a mean using all available data after randomisation). No imputation of missing data was performed

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

742 participants

Primary outcome timeframe

Baseline to 6 weeks

Results posted on

2012-08-15

Participant Flow

898 subjects enrolled; 156 not randomised: 94 incorrect enrolment, 9 adverse events, 18 voluntary discontinuations, 1 lost to follow-up, 1use of not allowed medication, 1 non-compliant

Participant milestones

Participant milestones
Measure	Symbicort pMDI Symbicort®pMDI® 40/2.25 μg 2 Actuations Twice Daily	Symbicort Turbuhaler Symbicort Turbuhaler® 80/4.5 μg 1 Inhalation Twice Daily	Pulmicort Turbuhaler Pulmicort®Turbuhaler® 100 μg 1 Inhalation Twice Daily
Overall Study STARTED	253	246	243
Overall Study COMPLETED	249	241	238
Overall Study NOT COMPLETED	4	5	5

Reasons for withdrawal

Reasons for withdrawal
Measure	Symbicort pMDI Symbicort®pMDI® 40/2.25 μg 2 Actuations Twice Daily	Symbicort Turbuhaler Symbicort Turbuhaler® 80/4.5 μg 1 Inhalation Twice Daily	Pulmicort Turbuhaler Pulmicort®Turbuhaler® 100 μg 1 Inhalation Twice Daily
Overall Study Adverse Event	3	2	3
Overall Study Withdrawal by Subject	0	2	0
Overall Study Intake of prohibited conc. medication	0	0	1
Overall Study Safety reasons	0	0	1
Overall Study Other	1	1	0

Baseline Characteristics

Symbicort Rapihaler Therapeutic Equivalence Study

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Symbicort pMDI n=253 Participants Symbicort®pMDI® 40/2.25 μg 2 Actuations Twice Daily	Symbicort Turbuhaler n=246 Participants Symbicort Turbuhaler® 80/4.5 μg 1 Inhalation Twice Daily	Pulmicort Turbuhaler n=243 Participants Pulmicort®Turbuhaler® 100 μg 1 Inhalation Twice Daily	Total n=742 Participants Total of all reporting groups
Age Continuous	41 years n=5 Participants	42 years n=7 Participants	39 years n=5 Participants	41 years n=4 Participants
Sex: Female, Male Female	152 Participants n=5 Participants	142 Participants n=7 Participants	131 Participants n=5 Participants	425 Participants n=4 Participants
Sex: Female, Male Male	101 Participants n=5 Participants	104 Participants n=7 Participants	112 Participants n=5 Participants	317 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline to 6 weeks

Change in the Morning PEF from baseline (calculated as a mean using all available data for the 10 last days of run-in period) to week 6 (calculated as a mean using all available data after randomisation). No imputation of missing data was performed

Outcome measures

Outcome measures
Measure	Symbicort pMDI n=253 Participants Symbicort®pMDI® 40/2.25 μg 2 Actuations Twice Daily	Symbicort Turbuhaler n=245 Participants Symbicort Turbuhaler® 80/4.5 μg 1 Inhalation Twice Daily	Pulmicort Turbuhaler n=243 Participants Pulmicort®Turbuhaler® 100 μg 1 Inhalation Twice Daily
Morning Peak Expiratory Flow (PEF)	12.88 Liters/min Standard Deviation 24.6	13.78 Liters/min Standard Deviation 29.7	4.59 Liters/min Standard Deviation 27.9

SECONDARY outcome

Timeframe: Baseline to 6 weeks

Change in the Evening PEF from baseline (calculated as a mean using all available data for the 10 last days of run-in period) to week 6 (calculated as a mean using all available data after randomisation). No imputation of missing data was performed

Outcome measures

Outcome measures
Measure	Symbicort pMDI n=253 Participants Symbicort®pMDI® 40/2.25 μg 2 Actuations Twice Daily	Symbicort Turbuhaler n=245 Participants Symbicort Turbuhaler® 80/4.5 μg 1 Inhalation Twice Daily	Pulmicort Turbuhaler n=243 Participants Pulmicort®Turbuhaler® 100 μg 1 Inhalation Twice Daily
Evening Peak Expiratory Flow (PEF)	12.34 Liters/min Standard Deviation 24.3	10.80 Liters/min Standard Deviation 29.1	1.43 Liters/min Standard Deviation 25.7

SECONDARY outcome

Timeframe: Baseline to 6 weeks

Change in the Asthma Symptom Score (Night) from baseline (calculated as a mean using all available data for the 10 last days of run-in period) to week 6 (calculated as a mean using all available data after randomization, with run-in values as covariate). No imputation of missing data was performed. Daily scale:0 = No symptoms; 1 = Mild symptoms; 2 = Moderate symptoms; 3 = Severe symptoms.

Outcome measures

Outcome measures
Measure	Symbicort pMDI n=253 Participants Symbicort®pMDI® 40/2.25 μg 2 Actuations Twice Daily	Symbicort Turbuhaler n=245 Participants Symbicort Turbuhaler® 80/4.5 μg 1 Inhalation Twice Daily	Pulmicort Turbuhaler n=243 Participants Pulmicort®Turbuhaler® 100 μg 1 Inhalation Twice Daily
Asthma Symptom Score, Night	-0.24 Units on a scale Standard Deviation 0.41	-0.27 Units on a scale Standard Deviation 0.41	-0.15 Units on a scale Standard Deviation 0.39

SECONDARY outcome

Timeframe: Baseline to 6 weeks

Change in the Asthma Symptom Score (Day) from baseline (calculated as a mean using all available data for the 10 last days of run-in period) to week 6 (calculated as a mean using all available data after randomization, with run-in values as covariate). No imputation of missing data was performed. Daily scale:0 = No symptoms; 1 = Mild symptoms; 2 = Moderate symptoms; 3 = Severe symptoms.

Outcome measures

Outcome measures
Measure	Symbicort pMDI n=253 Participants Symbicort®pMDI® 40/2.25 μg 2 Actuations Twice Daily	Symbicort Turbuhaler n=245 Participants Symbicort Turbuhaler® 80/4.5 μg 1 Inhalation Twice Daily	Pulmicort Turbuhaler n=243 Participants Pulmicort®Turbuhaler® 100 μg 1 Inhalation Twice Daily
Asthma Symptom Score, Day	-0.21 Units on a scale Standard Deviation 0.38	-0.24 Units on a scale Standard Deviation 0.40	-0.15 Units on a scale Standard Deviation 0.40

SECONDARY outcome

Timeframe: Baseline to 6 weeks

Change in the Asthma Symptom Score (Total) from baseline (calculated as a mean using all available data for the 10 last days of run-in period) to week 6 (calculated as a mean using all available data after randomization, with run-in values as covariate). No imputation of missing data was performed. Daily scale:0 = No symptoms; 1 = Mild symptoms; 2 = Moderate symptoms; 3 = Severe symptoms.

Outcome measures

Outcome measures
Measure	Symbicort pMDI n=253 Participants Symbicort®pMDI® 40/2.25 μg 2 Actuations Twice Daily	Symbicort Turbuhaler n=245 Participants Symbicort Turbuhaler® 80/4.5 μg 1 Inhalation Twice Daily	Pulmicort Turbuhaler n=243 Participants Pulmicort®Turbuhaler® 100 μg 1 Inhalation Twice Daily
Asthma Symptom Score, Total	-0.45 Units on a scale Standard Deviation 0.73	-0.51 Units on a scale Standard Deviation 0.75	-0.30 Units on a scale Standard Deviation 0.73

SECONDARY outcome

Timeframe: Baseline and 6 weeks

Change in the Percentage of Nights With Awakenings Due to Asthma from baseline (calculated as a mean using all available data for the 10 last days of run-in period) to week 6 (calculated as a mean using all available data after randomization, with run-in values as covariate). No imputation of missing data was performed. The participants answered "Yes" or "No" whether she/he woke up during the night due to asthma.

Outcome measures

Outcome measures
Measure	Symbicort pMDI n=253 Participants Symbicort®pMDI® 40/2.25 μg 2 Actuations Twice Daily	Symbicort Turbuhaler n=245 Participants Symbicort Turbuhaler® 80/4.5 μg 1 Inhalation Twice Daily	Pulmicort Turbuhaler n=243 Participants Pulmicort®Turbuhaler® 100 μg 1 Inhalation Twice Daily
Percentage of Nights With Awakenings Due to Asthma	-14.0 Percentage of night Standard Deviation 24.1	-14.0 Percentage of night Standard Deviation 26.4	-8.3 Percentage of night Standard Deviation 25.5

SECONDARY outcome

Timeframe: Baseline to 6 weeks

Change in the Use of Rescue Medication (Night) from baseline (calculated as a mean using all available data for the 10 last days of run-in period) to week 6 (calculated as a mean using all available data after randomization, with run-in values as covariate). No imputation of missing data was performed

Outcome measures

Outcome measures
Measure	Symbicort pMDI n=253 Participants Symbicort®pMDI® 40/2.25 μg 2 Actuations Twice Daily	Symbicort Turbuhaler n=245 Participants Symbicort Turbuhaler® 80/4.5 μg 1 Inhalation Twice Daily	Pulmicort Turbuhaler n=243 Participants Pulmicort®Turbuhaler® 100 μg 1 Inhalation Twice Daily
Use of Rescue Medication, Night	-0.41 Inhalations Standard Deviation 0.64	-0.39 Inhalations Standard Deviation 0.76	-0.19 Inhalations Standard Deviation 0.67

SECONDARY outcome

Timeframe: Baseline to 6 weeks

Change in the Use of Rescue Medication (Day) from baseline (calculated as a mean using all available data for the 10 last days of run-in period) to week 6 (calculated as a mean using all available data after randomization, with run-in values as covariate). No imputation of missing data was performed

Outcome measures

Outcome measures
Measure	Symbicort pMDI n=253 Participants Symbicort®pMDI® 40/2.25 μg 2 Actuations Twice Daily	Symbicort Turbuhaler n=245 Participants Symbicort Turbuhaler® 80/4.5 μg 1 Inhalation Twice Daily	Pulmicort Turbuhaler n=243 Participants Pulmicort®Turbuhaler® 100 μg 1 Inhalation Twice Daily
Use of Rescue Medication, Day	-0.21 Inhalations Standard Deviation 0.39	-0.20 Inhalations Standard Deviation 0.47	-0.13 Inhalations Standard Deviation 0.56

SECONDARY outcome

Timeframe: Baseline to 6 weeks

Change in the Use of Rescue Medication (Total) from baseline (calculated as a mean using all available data for the 10 last days of run-in period) to week 6 (calculated as a mean using all available data after randomization, with run-in values as covariate). No imputation of missing data was performed

Outcome measures

Outcome measures
Measure	Symbicort pMDI n=253 Participants Symbicort®pMDI® 40/2.25 μg 2 Actuations Twice Daily	Symbicort Turbuhaler n=245 Participants Symbicort Turbuhaler® 80/4.5 μg 1 Inhalation Twice Daily	Pulmicort Turbuhaler n=243 Participants Pulmicort®Turbuhaler® 100 μg 1 Inhalation Twice Daily
Use of Rescue Medication, Total	-0.62 Inhalations Standard Deviation 0.89	-0.58 Inhalations Standard Deviation 1.09	-0.32 Inhalations Standard Deviation 1.12

SECONDARY outcome

Timeframe: Baseline to 6 weeks

Change in the Percentage of Symptom-free Days from baseline (calculated as a mean using all available data for the 10 last days of run-in period) to week 6 (calculated as a mean using all available data after randomization, with run-in values as covariate). No imputation of missing data was performed. Symptom-free Day: no symptoms (asthma symptom score=0) night and day, and no awakenings due to asthma.

Outcome measures

Outcome measures
Measure	Symbicort pMDI n=253 Participants Symbicort®pMDI® 40/2.25 μg 2 Actuations Twice Daily	Symbicort Turbuhaler n=245 Participants Symbicort Turbuhaler® 80/4.5 μg 1 Inhalation Twice Daily	Pulmicort Turbuhaler n=243 Participants Pulmicort®Turbuhaler® 100 μg 1 Inhalation Twice Daily
Percentage of Symptom-free Days	12.5 Percentage of days Standard Deviation 23.7	15.3 Percentage of days Standard Deviation 24.5	9.1 Percentage of days Standard Deviation 21.2

SECONDARY outcome

Timeframe: Baseline to 6 weeks

Change in the Percentage of Symptom Control Days from baseline (calculated as a mean using all available data for the 10 last days of run-in period) to week 6 (calculated as a mean using all available data after randomization, with run-in values as covariate). No imputation of missing data was performed. Asthma Control Day: no symptoms (asthma symptom score=0) night and day, no awakenings due to asthma, no rescue medication.

Outcome measures

Outcome measures
Measure	Symbicort pMDI n=253 Participants Symbicort®pMDI® 40/2.25 μg 2 Actuations Twice Daily	Symbicort Turbuhaler n=245 Participants Symbicort Turbuhaler® 80/4.5 μg 1 Inhalation Twice Daily	Pulmicort Turbuhaler n=243 Participants Pulmicort®Turbuhaler® 100 μg 1 Inhalation Twice Daily
Percentage of Asthma Control Days	12.7 Percentage of days Standard Deviation 23.6	15.1 Percentage of days Standard Deviation 24.4	9.1 Percentage of days Standard Deviation 21.2

SECONDARY outcome

Timeframe: Baseline to 6 weeks

Change in the Percentage of Rescue Free Days from baseline (calculated as a mean using all available data for the 10 last days of run-in period) to week 6 (calculated as a mean using all available data after randomization, with run-in values as covariate). No imputation of missing data was performed. Rescue-free Day defined as day and night with no use of rescue medication.

Outcome measures

Outcome measures
Measure	Symbicort pMDI n=253 Participants Symbicort®pMDI® 40/2.25 μg 2 Actuations Twice Daily	Symbicort Turbuhaler n=245 Participants Symbicort Turbuhaler® 80/4.5 μg 1 Inhalation Twice Daily	Pulmicort Turbuhaler n=243 Participants Pulmicort®Turbuhaler® 100 μg 1 Inhalation Twice Daily
Percentage of Rescue Free Days	24.0 Percentage of days Standard Deviation 30.9	26.2 Percentage of days Standard Deviation 30.7	17.2 Percentage of days Standard Deviation 28.4

SECONDARY outcome

Timeframe: Baseline to 6 weeks

Change in the FEV1from baseline to week 6 (calculated as a mean using all available data after randomization)

Outcome measures

Outcome measures
Measure	Symbicort pMDI n=253 Participants Symbicort®pMDI® 40/2.25 μg 2 Actuations Twice Daily	Symbicort Turbuhaler n=243 Participants Symbicort Turbuhaler® 80/4.5 μg 1 Inhalation Twice Daily	Pulmicort Turbuhaler n=242 Participants Pulmicort®Turbuhaler® 100 μg 1 Inhalation Twice Daily
Forced Expiratory Volume in 1 Second (FEV1)	0.095 Liters Standard Deviation 0.328	0.147 Liters Standard Deviation 0.364	0.112 Liters Standard Deviation 0.326

Adverse Events

Symbicort pMDI

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Symbicort Turbuhaler

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

Pulmicort Turbuhaler

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Symbicort pMDI n=253 participants at risk Symbicort pMDI	Symbicort Turbuhaler n=246 participants at risk Symbicort Turbuhaler	Pulmicort Turbuhaler n=243 participants at risk Pulmicort Turbuhaler
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/253	0.41% 1/246	0.41% 1/243

Other adverse events

Adverse event data not reported

Additional Information

Gerard Lynch

AstraZeneca

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place