Trial Outcomes & Findings for An Efficacy Study Comparing SYMBICORT® Pressurised Metered Dose Inhaler (pMDI) With Budesonide Hydrofluoroalkanes (HFA) pMDI, in Hispanic Subjects With ICS Dependent Asthma (NCT NCT00419757)

NCT ID: NCT00419757

Last Updated: 2012-08-27

Results Overview

Change from baseline (average of daily records over the 14 days of run-in) to the average of daily records over the treatment period of 12 weeks, with baseline value as covariate.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 558 participants
• Primary outcome timeframe: Baseline (run-in) and throughout 12 weeks
• Results posted on: 2012-08-27

Participant Flow

39 centres in United States enrolled 558 patients with asthma into this study. 308 patients were excluded: 279 for incorrect enrollment/eligibility criteria not fulfilled, 14 for voluntary discontinuations, 2 for development of study specific discontinuation criteria, 2 for adverse events, 10 were lost to follow-up

Male or female, Hispanic (self-reported), ≥12 years

Participant milestones

Measure	Symbicort SYMBICORT® pMDI 160/4.5 μg x 2actuations twice daily	Budesonide Budesonide Hydrofluoroalkane (HFA) pressurised metered dose inhaler (pMDI) 160 μg x 2 actuations twice daily
Overall Study STARTED	127	123
Overall Study COMPLETED	109	102
Overall Study NOT COMPLETED	18	21

Reasons for withdrawal

Measure	Symbicort SYMBICORT® pMDI 160/4.5 μg x 2actuations twice daily	Budesonide Budesonide Hydrofluoroalkane (HFA) pressurised metered dose inhaler (pMDI) 160 μg x 2 actuations twice daily
Overall Study Adverse Event	1	4
Overall Study Lost to Follow-up	1	4
Overall Study Withdrawal by Subject	7	1
Overall Study Protocol Violation	2	3
Overall Study Study specific discontinuation criteria	4	8
Overall Study Multiple reasons	3	1

Baseline Characteristics

An Efficacy Study Comparing SYMBICORT® Pressurised Metered Dose Inhaler (pMDI) With Budesonide Hydrofluoroalkanes (HFA) pMDI, in Hispanic Subjects With ICS Dependent Asthma

Baseline characteristics by cohort

Measure	Symbicort n=127 Participants SYMBICORT® pMDI 160/4.5 μg x 2actuations twice daily	Budesonide n=123 Participants Budesonide Hydrofluoroalkane (HFA) pressurised metered dose inhaler (pMDI) 160 μg x 2 actuations twice daily	Total n=250 Participants Total of all reporting groups
Age Continuous	16.6 Years STANDARD_DEVIATION 39.8 • n=5 Participants	14.9 Years STANDARD_DEVIATION 37.0 • n=7 Participants	15.6 Years STANDARD_DEVIATION 38.4 • n=5 Participants
Sex: Female, Male Female	84 Participants n=5 Participants	80 Participants n=7 Participants	164 Participants n=5 Participants
Sex: Female, Male Male	43 Participants n=5 Participants	43 Participants n=7 Participants	86 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline (run-in) and throughout 12 weeks

Population: Includes all subjects who were randomised, took at least one dose of study medication and contributed sufficient data for the endpoint to be calculated.

Change from baseline (average of daily records over the 14 days of run-in) to the average of daily records over the treatment period of 12 weeks, with baseline value as covariate.

Outcome measures

Measure	Symbicort n=124 Participants SYMBICORT® pMDI 160/4.5 μg x 2actuations twice daily	Budesonide n=119 Participants Budesonide Hydrofluoroalkane (HFA) pressurised metered dose inhaler (pMDI) 160 μg x 2 actuations twice daily
Morning Peak Expiratory Flow (AM PEF)	25.40 Liters/minutes Standard Error 6.0	19.90 Liters/minutes Standard Error 6.5

SECONDARY outcome

Timeframe: 12 weeks

Population: Includes all subjects who were randomised, took at least one dose of study medication and contributed sufficient data for the endpoint to be calculated.

Asthma Events, defined as any of: decrease in lung function (FEV1 or AM PEF), use of rescue medication over maximum allowed per day, night awakening requiring use of rescue medication, exacerbation of asthma requiring medical assistance, use of not allowed asthma medication

Outcome measures

Measure	Symbicort n=127 Participants SYMBICORT® pMDI 160/4.5 μg x 2actuations twice daily	Budesonide n=123 Participants Budesonide Hydrofluoroalkane (HFA) pressurised metered dose inhaler (pMDI) 160 μg x 2 actuations twice daily
Percentage of Participants With Pre-defined Asthma Events	25.20 Percentage of Participants	31.70 Percentage of Participants

SECONDARY outcome

Timeframe: 12 weeks

Population: Includes all subjects who were randomised, took at least one dose of study medication and contributed sufficient data for the endpoint to be calculated.

Percentage of participants with "Withdrawals Due to Pre-defined Asthma Events" as recorded in CRF. Includes all subjects who were randomised, took at least one dose of study medication and contributed sufficient data for the endpoint to be calculated.

Outcome measures

Measure	Symbicort n=96 Participants SYMBICORT® pMDI 160/4.5 μg x 2actuations twice daily	Budesonide n=92 Participants Budesonide Hydrofluoroalkane (HFA) pressurised metered dose inhaler (pMDI) 160 μg x 2 actuations twice daily
Percentage of Participants With "Withdrawals Due to Pre-defined Asthma Events"	2.10 Percentage of Participants	6.50 Percentage of Participants

SECONDARY outcome

Timeframe: Baseline, 2, 6 and 12 weeks

Population: Includes all subjects who were randomised, took at least one dose of study medication and contributed sufficient data for the endpoint to be calculated.

Changes in pre-dose FEV1 from baseline to the average value over the treatment period, with baseline value as covariate. Includes all subjects who were randomised, took at least one dose of study medication and contributed sufficient data for the endpoint to be calculated.

Outcome measures

Measure	Symbicort n=124 Participants SYMBICORT® pMDI 160/4.5 μg x 2actuations twice daily	Budesonide n=122 Participants Budesonide Hydrofluoroalkane (HFA) pressurised metered dose inhaler (pMDI) 160 μg x 2 actuations twice daily
Changes Pre-dose Forced Expiratory Volume in 1 Second (FEV1)	0.16 Liters Standard Error 0.03	0.11 Liters Standard Error 0.03

SECONDARY outcome

Timeframe: Baseline (run-in) and throughout 12 weeks

Population: Includes all subjects who were randomised, took at least one dose of study medication and contributed sufficient data for the endpoint to be calculated.

Change from baseline (average of daily records over the 14 days of run-in) to the average of daily records over the treatment period of 12 weeks with baseline as covariate. Includes all subjects who were randomised, took at least one dose of study medication and contributed sufficient data for the endpoint to be calculated.

Outcome measures

Measure	Symbicort n=124 Participants SYMBICORT® pMDI 160/4.5 μg x 2actuations twice daily	Budesonide n=119 Participants Budesonide Hydrofluoroalkane (HFA) pressurised metered dose inhaler (pMDI) 160 μg x 2 actuations twice daily
Change From Baseline in a Evening Peak Expiratory Flow (PM PEF)	20.60 Liters/minutes Standard Error 6.2	15.80 Liters/minutes Standard Error 6.7

SECONDARY outcome

Timeframe: Baseline (run-in) and throughout 12 weeks

Population: Includes all subjects who were randomised, took at least one dose of study medication and contributed sufficient data for the endpoint to be calculated.

Change from baseline in average of daily scores for nighttime asthma over 12 weeks of treatment, with baseline value as covariate.

Daily scale:

• 0 = No symptoms
• 1 = Mild symptoms
• 2 = Moderate symptoms
• 3 = Severe symptoms

Outcome measures

Measure	Symbicort n=125 Participants SYMBICORT® pMDI 160/4.5 μg x 2actuations twice daily	Budesonide n=119 Participants Budesonide Hydrofluoroalkane (HFA) pressurised metered dose inhaler (pMDI) 160 μg x 2 actuations twice daily
Change in Nighttime Asthma Symptom Score From Baseline Through 12 Weeks	-0.40 Units on a scale Standard Error 0.01	-0.30 Units on a scale Standard Error 0.01

SECONDARY outcome

Timeframe: Baseline (run-in) and throughout 12 weeks

Population: Includes all subjects who were randomised, took at least one dose of study medication and contributed sufficient data for the endpoint to be calculated.

Change from baseline in average of daily scores for daytime asthma over 12 weeks of treatment, with baseline value as covariate.

Daily scale:

• 0 = No symptoms
• 1 = Mild symptoms
• 2 = Moderate symptoms
• 3 = Severe symptoms

Outcome measures

Measure	Symbicort n=125 Participants SYMBICORT® pMDI 160/4.5 μg x 2actuations twice daily	Budesonide n=119 Participants Budesonide Hydrofluoroalkane (HFA) pressurised metered dose inhaler (pMDI) 160 μg x 2 actuations twice daily
Change in Daytime Asthma Symptom Score From Baseline Through 12 Weeks	-0.40 Units on a scale Standard Error 0.01	-0.30 Units on a scale Standard Error 0.01

SECONDARY outcome

Timeframe: Baseline (run-in) and throughout 12 weeks

Population: Includes all subjects who were randomised, took at least one dose of study medication and contributed sufficient data for the endpoint to be calculated.

Change from baseline in percentage of nights with awakenings due to asthma over 12 weeks of treatment, with baseline value as covariate.

Outcome measures

Measure	Symbicort n=125 Participants SYMBICORT® pMDI 160/4.5 μg x 2actuations twice daily	Budesonide n=119 Participants Budesonide Hydrofluoroalkane (HFA) pressurised metered dose inhaler (pMDI) 160 μg x 2 actuations twice daily
Change in Asthma Related Awakenings Free Nights, From Baseline Through 12 Weeks	5.40 Percentage of nights Standard Error 1.7	5.50 Percentage of nights Standard Error 1.9

SECONDARY outcome

Timeframe: Baseline (run-in) and throughout 12 weeks

Population: Includes all subjects who were randomised, took at least one dose of study medication and contributed sufficient data for the endpoint to be calculated.

Change from baseline in rescue medication use over 12 weeks of treatment with baseline value as covariate. Includes all subjects who were randomised, took at least one dose of study medication and contributed sufficient data for the endpoint to be calculated.

Outcome measures

Measure	Symbicort n=125 Participants SYMBICORT® pMDI 160/4.5 μg x 2actuations twice daily	Budesonide n=119 Participants Budesonide Hydrofluoroalkane (HFA) pressurised metered dose inhaler (pMDI) 160 μg x 2 actuations twice daily
Change From Baseline in Rescue Medication Use Over 12 Weeks of Treatment	-0.80 puffs/day Standard Error 0.20	-0.60 puffs/day Standard Error 0.20

SECONDARY outcome

Timeframe: Baseline (run-in) and throughout 12 weeks

Population: Includes all subjects who were randomised, took at least one dose of study medication and contributed sufficient data for the endpoint to be calculated.

Change from baseline in percentage of rescue-free days over 12 weeks of treatment, with baseline value as covariate. Includes all subjects who were randomised, took at least one dose of study medication and contributed sufficient data for the endpoint to be calculated.

Outcome measures

Measure	Symbicort n=125 Participants SYMBICORT® pMDI 160/4.5 μg x 2actuations twice daily	Budesonide n=119 Participants Budesonide Hydrofluoroalkane (HFA) pressurised metered dose inhaler (pMDI) 160 μg x 2 actuations twice daily
Change From Baseline in Rescue-free Days Over 12 Weeks of Treatment	19.70 Percentage of days Standard Error 3.30	17.70 Percentage of days Standard Error 3.50

SECONDARY outcome

Timeframe: Baseline (run-in) and throughout 12 weeks

Population: Includes all subjects who were randomised, took at least one dose of study medication and contributed sufficient data for the endpoint to be calculated.

Change from baseline in percentage of symptom-free days over 12 weeks of treatment, with baseline value as covariate. Includes all subjects who were randomised, took at least one dose of study medication and contributed sufficient data for the endpoint to be calculated.

Outcome measures

Measure	Symbicort n=125 Participants SYMBICORT® pMDI 160/4.5 μg x 2actuations twice daily	Budesonide n=119 Participants Budesonide Hydrofluoroalkane (HFA) pressurised metered dose inhaler (pMDI) 160 μg x 2 actuations twice daily
Change From Baseline in Symptom-free Days Over 12 Weeks of Treatment	24.40 Percentage of days Standard Error 3.30	21.00 Percentage of days Standard Error 3.50

SECONDARY outcome

Timeframe: Baseline and week 12

Population: Includes all subjects who were randomised, took at least one dose of study medication and contributed sufficient data for the endpoint to be calculated.

The assessment was made using a 5-point Likert scale with 1=much better, 2=somewhat better, 3=comparable, 4=somewhat worse, and 5=much worse transformed to a binary variable with points 1 and 2 combined as "Yes" and points 3, 4, 5 as "No". Percent of Participants that gave positive responses.

Outcome measures

Measure	Symbicort n=125 Participants SYMBICORT® pMDI 160/4.5 μg x 2actuations twice daily	Budesonide n=119 Participants Budesonide Hydrofluoroalkane (HFA) pressurised metered dose inhaler (pMDI) 160 μg x 2 actuations twice daily
Subject Global Assessment	88.70 Percent of Participants	86.30 Percent of Participants

SECONDARY outcome

Timeframe: Baseline and week 12

Population: Includes all subjects who were randomised, took at least one dose of study medication and contributed sufficient data for the endpoint to be calculated.

The assessment was made using a 5-point scale with 1=much better, 2=somewhat better, 3=comparable, 4=somewhat worse, and 5=much worse transformed to a binary variable with points 1and 2 combined as "Yes" and points 3, 4, 5 as "No". Percent of Participants that gave positive responses.

Outcome measures

Measure	Symbicort n=125 Participants SYMBICORT® pMDI 160/4.5 μg x 2actuations twice daily	Budesonide n=119 Participants Budesonide Hydrofluoroalkane (HFA) pressurised metered dose inhaler (pMDI) 160 μg x 2 actuations twice daily
Physician Global Assessment	92.00 Perscentage of Participants	84.60 Perscentage of Participants

SECONDARY outcome

Timeframe: Week 12

Population: Only subjects 18 years and older, who were randomised, took at least one dose of study medication and contributed sufficient data for the endpoint to be calculated.

Mean scores (6-points scale, where 1-means the most positive opinion and 6-the most negative opinion) were calculated for items in domain. 6-point response options were scored on a 0±100 scale, where 100 represented the highest level of satisfaction and 0 the lowest level of satisfaction.

Outcome measures

Measure	Symbicort n=104 Participants SYMBICORT® pMDI 160/4.5 μg x 2actuations twice daily	Budesonide n=100 Participants Budesonide Hydrofluoroalkane (HFA) pressurised metered dose inhaler (pMDI) 160 μg x 2 actuations twice daily
Patient Satisfaction With Asthma Medication (PSAM) in Term of Domain: Control Relief Index	87.20 Units on a scale Standard Error 1.97	82.50 Units on a scale Standard Error 2.08

SECONDARY outcome

Timeframe: Week 12

Population: Only subjects 18 years and older, who were randomised, took at least one dose of study medication and contributed sufficient data for the endpoint to be calculated.

Mean scores (6 or 5-points scale, where 1-means the most positive opinion and 5/6-the most negative opinion) were calculated for items in domain. 6-point response options were scored on a 0±100 scale, where 100 represented the highest level of satisfaction and 0 the lowest level of satisfaction.

Outcome measures

Measure	Symbicort n=104 Participants SYMBICORT® pMDI 160/4.5 μg x 2actuations twice daily	Budesonide n=100 Participants Budesonide Hydrofluoroalkane (HFA) pressurised metered dose inhaler (pMDI) 160 μg x 2 actuations twice daily
Patient Satisfaction With Asthma Medication (PSAM) in Term of Domain: Overall Perception of Medication	90.67 Units on a scale Standard Error 1.79	86.66 Units on a scale Standard Error 1.89

SECONDARY outcome

Timeframe: Week 12

Population: Only subjects 18 years and older, who were randomised, took at least one dose of study medication and contributed sufficient data for the endpoint to be calculated.

Mean scores (5-points scale, where 1-means the most positive opinion and 5-the most negative opinion) were calculated for items in domain. 6-point response options were scored on a 0±100 scale, where 100 represented the highest level of satisfaction and 0 the lowest level of satisfaction.

Outcome measures

Measure	Symbicort n=104 Participants SYMBICORT® pMDI 160/4.5 μg x 2actuations twice daily	Budesonide n=100 Participants Budesonide Hydrofluoroalkane (HFA) pressurised metered dose inhaler (pMDI) 160 μg x 2 actuations twice daily
Patient Satisfaction With Asthma Medication (PSAM) in Term of Domain: Comparison With Other Medications	88.45 Units on a scale Standard Error 2.34	80.60 Units on a scale Standard Error 2.47

Adverse Events

Symbicort

Serious events: 4 serious events

Other events: 69 other events

Deaths: 0 deaths

Budesonide

Serious events: 0 serious events

Other events: 48 other events

Deaths: 0 deaths

Serious adverse events

Measure	Symbicort n=127 participants at risk SYMBICORT® pMDI 160/4.5 μg x 2 actuations twice daily	Budesonide n=123 participants at risk budesonide HFA pMDI 160 μg x 2 actuations twice daily
Gastrointestinal disorders Gastrointestinal Hemorrhage	0.79% 1/127	0.00% 0/123
Infections and infestations Cellulitis	0.79% 1/127	0.00% 0/123
Hepatobiliary disorders Cholecystitis	0.79% 1/127	0.00% 0/123
Respiratory, thoracic and mediastinal disorders Status Asthmaticus	0.79% 1/127	0.00% 0/123

Other adverse events

Measure	Symbicort n=127 participants at risk SYMBICORT® pMDI 160/4.5 μg x 2 actuations twice daily	Budesonide n=123 participants at risk budesonide HFA pMDI 160 μg x 2 actuations twice daily
Musculoskeletal and connective tissue disorders Arthralgia	2.4% 3/127	4.1% 5/123
Musculoskeletal and connective tissue disorders Back Pain	3.9% 5/127	2.4% 3/123
Infections and infestations Bronchitis	2.4% 3/127	0.00% 0/123
Respiratory, thoracic and mediastinal disorders Cough	3.1% 4/127	5.7% 7/123
Reproductive system and breast disorders Dysmenorrhoea	2.4% 3/127	0.00% 0/123
Ear and labyrinth disorders Ear Pain	2.4% 3/127	0.00% 0/123
Nervous system disorders Headache	15.0% 19/127	11.4% 14/123
Infections and infestations Influenza	2.4% 3/127	0.00% 0/123
Respiratory, thoracic and mediastinal disorders Nasal Congestion	6.3% 8/127	0.00% 0/123
Infections and infestations Nasopharyngitis	5.5% 7/127	0.00% 0/123
General disorders Pain	2.4% 3/127	0.00% 0/123
Infections and infestations Pharyngitis Streptococcal	2.4% 3/127	0.00% 0/123
Respiratory, thoracic and mediastinal disorders Pharyngolaryngeal Pain	0.00% 0/127	2.4% 3/123
General disorders Pyrexia	2.4% 3/127	0.00% 0/123
Infections and infestations Sinusitis	0.00% 0/127	2.4% 3/123
Gastrointestinal disorders Toothache	0.00% 0/127	2.4% 3/123
Infections and infestations Upper Respiratory Tract Infection	0.00% 0/127	3.3% 4/123
Infections and infestations Viral Upper Respiratory Tract Infection	5.5% 7/127	4.9% 6/123

Additional Information

Gerard Lynch

AstraZeneca

Email: aztrial_results_posting@astrazeneca.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place