Trial Outcomes & Findings for Study to Evaluate the Mastery of Inhaler Technique for Budesonide Formoterol (BF) SPIROMAX® as Compared to SYMBICORT® TURBOHALER® as Treatment for Adult Participants With Asthma (NCT NCT02062463)

NCT ID: NCT02062463

Last Updated: 2024-03-22

Results Overview

Device mastery was defined as absence of healthcare professional (HCP)-observed errors by the end of Step 3 of a 6-step standardized device training protocol for empty Spiromax compared to empty Turbohaler. The 6 steps of device training protocol were: Step 1 - Intuitive use; Step 2 - Patient information leaflet; Step 3 - Instructional video; Step 4 - HCP tuition; Step 5 - HCP tuition (1st repeat); Step 6 - HCP tuition (2nd repeat).

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 485 participants
• Primary outcome timeframe: Baseline (Day 1)
• Results posted on: 2024-03-22

Participant Flow

The study was conducted in 2 stages: Stage 1 and 2. In Stage 1, participants were randomly assigned to either empty Spiromax followed by empty Turbohaler or empty Turbohaler followed by empty Spiromax. Stage 2 comprised randomization of eligible participants to the study drugs.

Participant milestones

Measure	Stage 1: Empty Spiromax Followed by Empty Turbohaler Participants were trained on the proper use of empty Spiromax followed by empty Turbohaler devices.	Stage 1: Empty Turbohaler Followed by Empty Spiromax Participants were trained on the proper use of empty Turbohaler followed by empty Spiromax devices.	Stage 2: BF Spiromax Participants who had currently received 800 to 1000 micrograms (μg) beclomethasone-equivalent inhaled corticosteroid (ICS) per day received budesonide/formoterol twice daily using the BF Spiromax 160/4.5 μg device. Therefore, the daily, ex-mouthpiece doses of budesonide and formoterol using BF Spiromax were 640 μg and 18 μg, respectively. Participants who had currently received 1600 to 2000 μg beclomethasone-equivalent ICS per day received budesonide/formoterol twice daily using the BF Spiromax 320/9 μg device. Therefore, the daily, ex-mouthpiece doses of budesonide and formoterol using BF Spiromax were 1280 μg and 36 μg, respectively.	Stage 2: Symbicort Turbohaler Participants who had currently received 800 to 1000 μg beclomethasone-equivalent ICS per day received budesonide/formoterol twice daily using the Symbicort Turbohaler 200/6 μg device. Therefore, the daily, ex-mouthpiece doses of budesonide and formoterol using Symbicort Turbohaler were 800 μg and 24 μg respectively. Participants who had currently received 1600 to 2000 μg beclomethasone-equivalent ICS per day received budesonide/formoterol twice daily using the Symbicort Turbohaler 400/12 μg device. Therefore, the daily, ex-mouthpiece doses of budesonide and formoterol using Symbicort Turbohaler were 1600 μg and 48 μg respectively.
Crossover Stage 1 STARTED	243	242	0	0
Crossover Stage 1 Full Analysis Set	240	241	0	0
Crossover Stage 1 COMPLETED	240	241	0	0
Crossover Stage 1 NOT COMPLETED	3	1	0	0
Stage 2 STARTED	0	0	197	197
Stage 2 Received at Least 1 Dose of Study Drug	0	0	197	197
Stage 2 Full Analysis Set	0	0	151	154
Stage 2 COMPLETED	0	0	144	141
Stage 2 NOT COMPLETED	0	0	53	56

Reasons for withdrawal

Measure	Stage 1: Empty Spiromax Followed by Empty Turbohaler Participants were trained on the proper use of empty Spiromax followed by empty Turbohaler devices.	Stage 1: Empty Turbohaler Followed by Empty Spiromax Participants were trained on the proper use of empty Turbohaler followed by empty Spiromax devices.	Stage 2: BF Spiromax Participants who had currently received 800 to 1000 micrograms (μg) beclomethasone-equivalent inhaled corticosteroid (ICS) per day received budesonide/formoterol twice daily using the BF Spiromax 160/4.5 μg device. Therefore, the daily, ex-mouthpiece doses of budesonide and formoterol using BF Spiromax were 640 μg and 18 μg, respectively. Participants who had currently received 1600 to 2000 μg beclomethasone-equivalent ICS per day received budesonide/formoterol twice daily using the BF Spiromax 320/9 μg device. Therefore, the daily, ex-mouthpiece doses of budesonide and formoterol using BF Spiromax were 1280 μg and 36 μg, respectively.	Stage 2: Symbicort Turbohaler Participants who had currently received 800 to 1000 μg beclomethasone-equivalent ICS per day received budesonide/formoterol twice daily using the Symbicort Turbohaler 200/6 μg device. Therefore, the daily, ex-mouthpiece doses of budesonide and formoterol using Symbicort Turbohaler were 800 μg and 24 μg respectively. Participants who had currently received 1600 to 2000 μg beclomethasone-equivalent ICS per day received budesonide/formoterol twice daily using the Symbicort Turbohaler 400/12 μg device. Therefore, the daily, ex-mouthpiece doses of budesonide and formoterol using Symbicort Turbohaler were 1600 μg and 48 μg respectively.
Crossover Stage 1 Withdrawals during stage 1 were not captured	3	1	0	0
Stage 2 Adverse Event	0	0	12	20
Stage 2 Lack of Efficacy	0	0	3	4
Stage 2 Lost to Follow-up	0	0	20	20
Stage 2 Non-Compliance	0	0	0	1
Stage 2 Other than specified	0	0	3	1
Stage 2 Withdrawal by Subject	0	0	15	10

Baseline Characteristics

Study to Evaluate the Mastery of Inhaler Technique for Budesonide Formoterol (BF) SPIROMAX® as Compared to SYMBICORT® TURBOHALER® as Treatment for Adult Participants With Asthma

Baseline characteristics by cohort

Measure	Empty Spiromax Followed by Empty Turbohaler n=243 Participants Participants were trained on the proper use of empty Spiromax followed by empty Turbohaler devices.	Empty Turbohaler Followed by Empty Spiromax n=242 Participants Participants were trained on the proper use of empty Turbohaler followed by empty Spiromax devices.	Total n=485 Participants Total of all reporting groups
Age, Continuous	54.4 years STANDARD_DEVIATION 13.8 • n=5 Participants	53.1 years STANDARD_DEVIATION 14.2 • n=7 Participants	53.8 years STANDARD_DEVIATION 14.0 • n=5 Participants
Sex: Female, Male Female	152 Participants n=5 Participants	134 Participants n=7 Participants	286 Participants n=5 Participants
Sex: Female, Male Male	91 Participants n=5 Participants	108 Participants n=7 Participants	199 Participants n=5 Participants
Race/Ethnicity, Customized White	238 Participants n=5 Participants	235 Participants n=7 Participants	473 Participants n=5 Participants
Race/Ethnicity, Customized Black	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race/Ethnicity, Customized Asian	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Race/Ethnicity, Customized Other	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline (Day 1)

Population: Full analysis set (FAS) for Stage 1 included all randomized participants who completed assessments on both study devices (empty Turbohaler and empty Spiromax), permitting a paired analysis of results.

Device mastery was defined as absence of healthcare professional (HCP)-observed errors by the end of Step 3 of a 6-step standardized device training protocol for empty Spiromax compared to empty Turbohaler. The 6 steps of device training protocol were: Step 1 - Intuitive use; Step 2 - Patient information leaflet; Step 3 - Instructional video; Step 4 - HCP tuition; Step 5 - HCP tuition (1st repeat); Step 6 - HCP tuition (2nd repeat).

Outcome measures

Measure	Stage 1: Empty Spiromax n=481 Participants Participants were trained on the proper use of empty Spiromax.	Stage 1: Empty Turbohaler n=481 Participants Participants were trained on the proper use of empty Turbohaler.
Stage 1: Percentage of Participants Achieving Device Mastery	94.4 percentage of participants	86.9 percentage of participants

PRIMARY outcome

Timeframe: Baseline up to Week 12

Population: FAS for Stage 2 included all randomized participants who returned for assessment of maintenance of inhaler technique at Week 12, and who had at least 10 weeks (inclusive) of device use of the inhaler (treatment) to which they were randomly assigned.

Maintenance of device mastery was defined as absence of HCP-observed errors after 12 weeks of device use.

Outcome measures

Measure	Stage 1: Empty Spiromax n=151 Participants Participants were trained on the proper use of empty Spiromax.	Stage 1: Empty Turbohaler n=154 Participants Participants were trained on the proper use of empty Turbohaler.
Stage 2: Percentage of Participants Maintaining Device Mastery	58.9 percentage of participants	53.2 percentage of participants

SECONDARY outcome

Timeframe: Day 1

Population: FAS for Stage 1 included all randomized participants who completed assessments on both study devices (empty Turbohaler and empty Spiromax), permitting a paired analysis of results.

The number of participants achieving device mastery by Step 1 (no training/intuitive use) of the device training process. Device mastery was defined as the absence of nurse-observed errors by the end of Step 3 of a 6-step standardized device training protocol for each device. The 6 training steps were as follows: Step 1, intuitive use; Step 2, patient device information leaflet; Step 3, instructional video; Step 4, nurse tuition; Step 5, nurse tuition (1st repeat); Step 6, nurse tuition (2nd repeat). After each training step an assessment of device use was carried out by the nurse using a pre-defined list of inhaler errors.

Outcome measures

Measure	Stage 1: Empty Spiromax n=481 Participants Participants were trained on the proper use of empty Spiromax.	Stage 1: Empty Turbohaler n=481 Participants Participants were trained on the proper use of empty Turbohaler.
Stage 1: Percentage of Participants Achieving Device Mastery by Step 1	33.3 Percentage of participants	11.4 Percentage of participants

SECONDARY outcome

Timeframe: Day 1

Population: FAS for Stage 1 included all randomized participants who completed assessments on both study devices (empty Turbohaler and empty Spiromax), permitting a paired analysis of results.

The number of participants achieving device mastery by Step 2 (patient device information leaflet) of the device training process. Device mastery was defined as the absence of nurse-observed errors by the end of Step 3 of a 6-step standardized device training protocol for each device. The 6 training steps were as follows: Step 1, intuitive use; Step 2, patient device information leaflet; Step 3, instructional video; Step 4, nurse tuition; Step 5, nurse tuition (1st repeat); Step 6, nurse tuition (2nd repeat). After each training step an assessment of device use was carried out by the nurse using a pre-defined list of inhaler errors.

Outcome measures

Measure	Stage 1: Empty Spiromax n=481 Participants Participants were trained on the proper use of empty Spiromax.	Stage 1: Empty Turbohaler n=481 Participants Participants were trained on the proper use of empty Turbohaler.
Stage 1: Percentage of Participants Achieving Device Mastery by Step 2	80.2 Percentage of participants	64.0 Percentage of participants

SECONDARY outcome

Timeframe: Baseline (Day 1)

Population: FAS for Stage 1 included all randomized participants who completed assessments on both study devices (empty Turbohaler and empty Spiromax), permitting a paired analysis of results.

Outcome measures

Measure	Stage 1: Empty Spiromax n=481 Participants Participants were trained on the proper use of empty Spiromax.	Stage 1: Empty Turbohaler n=481 Participants Participants were trained on the proper use of empty Turbohaler.
Stage 1: Number of Steps Taken to Achieve Device Mastery	1 steps Interval 0.0 to 12.0	2 steps Interval 0.0 to 15.0

SECONDARY outcome

Timeframe: Day 1

Population: FAS for Stage 1 included all randomized participants who completed assessments on both study devices (empty Turbohaler and empty Spiromax), permitting a paired analysis of results.

Outcome measures

Measure	Stage 1: Empty Spiromax n=481 Participants Participants were trained on the proper use of empty Spiromax.	Stage 1: Empty Turbohaler n=481 Participants Participants were trained on the proper use of empty Turbohaler.
Stage 1: Number of Nurse-Observed Errors	1.91 Errors Standard Deviation 0.89	2.36 Errors Standard Deviation 0.92

SECONDARY outcome

Timeframe: Baseline (Day 1)

Population: FAS for Stage 1 included all randomized participants who completed assessments on both study devices (empty Turbohaler and empty Spiromax), permitting a paired analysis of results. Here 'overall number of participants analyzed' = participants evaluable for this outcome measure.

The PASAPQ is a multi-item measure of inhalation device satisfaction and preference designed specifically for participants with asthma and chronic obstructive pulmonary disease. The PASAPQ includes a total of 14 device satisfaction items, including an overall satisfaction item. The total score was the sum of the 13 items related to performance and convenience domains (7 items for performance domain: Questions 1-5, 10-11, and 6 items for convenience domain: Questions 6-9, 12-13). Each PASAPQ item had response options ranging from 1 (very dissatisfied) to 7 (very satisfied). To calculate the total score, the items within each domain were first summed and then transformed to a 0 (least) or 100 (most) point scale, with higher scores indicating greater satisfaction.

Outcome measures

Measure	Stage 1: Empty Spiromax n=477 Participants Participants were trained on the proper use of empty Spiromax.	Stage 1: Empty Turbohaler n=477 Participants Participants were trained on the proper use of empty Turbohaler.
Stage 1: Patient Satisfaction and Preference Questionnaire (PASAPQ) Total Score	89.80 units on a scale Interval 18.37 to 100.0	85.71 units on a scale Interval 14.29 to 100.0

SECONDARY outcome

Timeframe: Baseline up to Week 12

Population: FAS for Stage 2 included all randomized participants who returned for assessment of maintenance of inhaler technique at Week 12, and who had at least 10 weeks (inclusive) of device use of the inhaler (treatment) to which they were randomly assigned.

Composite score calculated as the sum of nurse observed errors and technology-observed errors.

Outcome measures

Measure	Stage 1: Empty Spiromax n=151 Participants Participants were trained on the proper use of empty Spiromax.	Stage 1: Empty Turbohaler n=154 Participants Participants were trained on the proper use of empty Turbohaler.
Composite Endpoint: Stage 2: Total Number of Observed Errors (Nurse and Technology [Vitalograph Pneumotrac Spirometer])	0.50 errors Standard Deviation 0.68	0.82 errors Standard Deviation 1.10

SECONDARY outcome

Timeframe: Week 12

Population: FAS for Stage 2 included all randomized participants who returned for assessment of maintenance of inhaler technique at Week 12, and who had at least 10 weeks (inclusive) of device use of the inhaler (treatment) to which they were randomly assigned.

Outcome measures

Measure	Stage 1: Empty Spiromax n=151 Participants Participants were trained on the proper use of empty Spiromax.	Stage 1: Empty Turbohaler n=154 Participants Participants were trained on the proper use of empty Turbohaler.
Stage 2: Number of Technology-Observed Errors (Vitalograph Pneumotrac Spirometer)	0.01 Errors Standard Deviation 0.08	0.01 Errors Standard Deviation 0.08

SECONDARY outcome

Timeframe: Baseline up to Week 12

Population: FAS for Stage 2 included all randomized participants who returned for assessment of maintenance of inhaler technique at Week 12, and who had at least 10 weeks (inclusive) of device use of the inhaler (treatment) to which they were randomly assigned.

Total number of device handling errors included HCP observed errors and technology observed errors.

Outcome measures

Measure	Stage 1: Empty Spiromax n=151 Participants Participants were trained on the proper use of empty Spiromax.	Stage 1: Empty Turbohaler n=154 Participants Participants were trained on the proper use of empty Turbohaler.
Stage 2: Total Number of Handling Errors	0.50 errors Standard Deviation 0.68	0.82 errors Standard Deviation 1.10

SECONDARY outcome

Timeframe: Baseline (Day 1), Week 12

Population: FAS for Stage 2 included all randomized participants who returned for assessment of maintenance of inhaler technique at Week 12, and who had at least 10 weeks (inclusive) of device use of the inhaler (treatment) to which they were randomly assigned.

The difference in the number of handling errors identified after participant training using the patient device information leaflet at stage 1 and after 12 weeks of treatment (end of stage 2).

Outcome measures

Measure	Stage 1: Empty Spiromax n=151 Participants Participants were trained on the proper use of empty Spiromax.	Stage 1: Empty Turbohaler n=154 Participants Participants were trained on the proper use of empty Turbohaler.
Stage 2: Change in Handling Errors From Stage 1 to Stage 2	-0.95 Errors Standard Deviation 1.72	-2.01 Errors Standard Deviation 2.52

SECONDARY outcome

Timeframe: Baseline up to Week 12

Population: FAS for Stage 2 included all randomized participants who returned for assessment of maintenance of inhaler technique at Week 12, and who had at least 10 weeks (inclusive) of device use of the inhaler (treatment) to which they were randomly assigned.

Treatment adherence was categorized (as less than or equal to 50%, 51%-70%, 71%-99%, and 100%) and compared across treatment groups using a chi-square test.

Outcome measures

Measure	Stage 1: Empty Spiromax n=151 Participants Participants were trained on the proper use of empty Spiromax.	Stage 1: Empty Turbohaler n=154 Participants Participants were trained on the proper use of empty Turbohaler.
Stage 2: Number of Participants In Pre-specified Treatment Adherence Categories (Assessed by Device Dose Counters) ≤50%	60 Participants	61 Participants
Stage 2: Number of Participants In Pre-specified Treatment Adherence Categories (Assessed by Device Dose Counters) 51-70%	19 Participants	16 Participants
Stage 2: Number of Participants In Pre-specified Treatment Adherence Categories (Assessed by Device Dose Counters) 71-99%	70 Participants	71 Participants
Stage 2: Number of Participants In Pre-specified Treatment Adherence Categories (Assessed by Device Dose Counters) 100%	2 Participants	6 Participants

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, and 12

Population: FAS for Stage 2 included all randomized participants who returned for assessment of maintenance of inhaler technique at Week 12, and who had at least 10 weeks (inclusive) of device use of the inhaler (treatment) to which they were randomly assigned. Here 'overall number of participants analyzed' = participants evaluable for this outcome measure.

The ACQ is a 7-item, validated tool for assessing asthma control (Juniper et al 1999). Thinking about their asthma for the last 7 days, participants were asked to evaluate their asthma against 5 symptom items and a rescue bronchodilator use question using a 7-point scale (0=no impairment and 6=maximum impairment). Spirometry data were used to grade the percent predicted forced expiratory volume in 1 second (FEV1) on a 7-point scale (0 to 6). The score is the mean of the first 6 questions (excluding the FEV1 question), generating a value from 0 (totally controlled) to 6 (severely uncontrolled). A negative change from Baseline indicates improvement.

Outcome measures

Measure	Stage 1: Empty Spiromax n=142 Participants Participants were trained on the proper use of empty Spiromax.	Stage 1: Empty Turbohaler n=147 Participants Participants were trained on the proper use of empty Turbohaler.
Stage 2: Change From Baseline in 6-Item Asthma Control Questionnaire (ACQ) (Excluding Forced Expiratory Volume in 1 Second [FEV1] Question) Score at Weeks 4, 8, and 12 Change at Week 4	-0.22 units on a scale Standard Deviation 0.83	-0.33 units on a scale Standard Deviation 0.81
Stage 2: Change From Baseline in 6-Item Asthma Control Questionnaire (ACQ) (Excluding Forced Expiratory Volume in 1 Second [FEV1] Question) Score at Weeks 4, 8, and 12 Change at Week 8	-0.20 units on a scale Standard Deviation 0.98	-0.30 units on a scale Standard Deviation 1.04
Stage 2: Change From Baseline in 6-Item Asthma Control Questionnaire (ACQ) (Excluding Forced Expiratory Volume in 1 Second [FEV1] Question) Score at Weeks 4, 8, and 12 Change at Week 12	-0.22 units on a scale Standard Deviation 0.95	-0.36 units on a scale Standard Deviation 1.05

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: FAS for Stage 2 included all randomized participants who returned for assessment of maintenance of inhaler technique at Week 12, and who had at least 10 weeks (inclusive) of device use of the inhaler (treatment) to which they were randomly assigned. Here 'overall number of participants analyzed' = participants evaluable for this outcome measure.

The ACQ is a 7-item, validated tool for assessing asthma control (Juniper et al 1999). Thinking about their asthma for the last 7 days, participants were asked to evaluate their asthma against 5 symptom items and a rescue bronchodilator use question using a 7-point scale (0=no impairment and 6=maximum impairment). Spirometry data were used to grade the percent predicted FEV1 on a 7-point scale (0 to 6). The ACQ score is the mean of the 7 questions, generating a value from 0 (totally controlled) to 6 (severely uncontrolled). A negative change from Baseline indicates improvement.

Outcome measures

Measure	Stage 1: Empty Spiromax n=145 Participants Participants were trained on the proper use of empty Spiromax.	Stage 1: Empty Turbohaler n=149 Participants Participants were trained on the proper use of empty Turbohaler.
Stage 2: Change From Baseline in 7-Item ACQ	-0.20 units on a scale Standard Deviation 0.78	-0.31 units on a scale Standard Deviation 0.92

SECONDARY outcome

Timeframe: Baseline up to Week 12

Population: FAS for Stage 2 included all randomized participants who returned for assessment of maintenance of inhaler technique at Week 12, and who had at least 10 weeks (inclusive) of device use of the inhaler (treatment) to which they were randomly assigned.

Time to treatment failure was defined as change of asthma treatment or treatment for an asthma exacerbation or lower respiratory tract infection.

Outcome measures

Measure	Stage 1: Empty Spiromax n=151 Participants Participants were trained on the proper use of empty Spiromax.	Stage 1: Empty Turbohaler n=154 Participants Participants were trained on the proper use of empty Turbohaler.
Stage 2: Time to First Treatment Failure	76.38 days Standard Deviation 21.42	73.95 days Standard Deviation 24.27

SECONDARY outcome

Timeframe: Week 12

Population: FAS for Stage 2 included all randomized participants who returned for assessment of maintenance of inhaler technique at Week 12, and who had at least 10 weeks (inclusive) of device use of the inhaler (treatment) to which they were randomly assigned.

Severe asthma exacerbation was defined as a hospitalization or emergency room attendance for asthma, or an acute course of oral corticosteroids (OCS).

Outcome measures

Measure	Stage 1: Empty Spiromax n=151 Participants Participants were trained on the proper use of empty Spiromax.	Stage 1: Empty Turbohaler n=154 Participants Participants were trained on the proper use of empty Turbohaler.
Stage 2: Number of Participants With Severe Asthma Exacerbations 0 asthma exacerbation	139 Participants	136 Participants
Stage 2: Number of Participants With Severe Asthma Exacerbations 1 asthma exacerbation	11 Participants	17 Participants
Stage 2: Number of Participants With Severe Asthma Exacerbations 2 asthma exacerbation	1 Participants	1 Participants
Stage 2: Number of Participants With Severe Asthma Exacerbations ≥3 asthma exacerbations	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline Up to Week 12

Population: FAS for Stage 2 included all randomized participants who returned for assessment of maintenance of inhaler technique at Week 12, and who had at least 10 weeks (inclusive) of device use of the inhaler (treatment) to which they were randomly assigned. Here 'overall number of participants analyzed' = participants evaluable for this outcome measure.

The impact of maintaining device mastery on time to treatment failure (defined as change of asthma treatment or treatment for an asthma exacerbation or lower respiratory tract infection) was assessed by comparing the time to treatment failure for participants with and without device mastery. Device mastery was defined as the absence of nurse-observed errors by the end of Step 3 of a 6-step standardized device training protocol for each device.

Outcome measures

Measure	Stage 1: Empty Spiromax n=151 Participants Participants were trained on the proper use of empty Spiromax.	Stage 1: Empty Turbohaler n=154 Participants Participants were trained on the proper use of empty Turbohaler.
Stage 2: Impact of Maintaining Device Mastery on Time to Treatment Failure Device mastery = Yes	72.99 Days Standard Deviation 22.38	75.93 Days Standard Deviation 22.59
Stage 2: Impact of Maintaining Device Mastery on Time to Treatment Failure Device mastery = No	81.24 Days Standard Deviation 19.11	71.69 Days Standard Deviation 26.03

SECONDARY outcome

Timeframe: Baseline Up to Week 12

Population: FAS for Stage 2 included all randomized participants who returned for assessment of maintenance of inhaler technique at Week 12, and who had at least 10 weeks (inclusive) of device use of the inhaler (treatment) to which they were randomly assigned. Here 'overall number of participants analyzed' = participants evaluable for this outcome measure.

The impact of maintaining device mastery on asthma control was assessed by comparing the 7-item ACQ scores for participants with and without device mastery. The ACQ is a 7-item, validated tool for assessing asthma control (Juniper et al 1999). Thinking about their asthma for the last 7 days, participants were asked to evaluate their asthma against 5 symptom items and a rescue bronchodilator use question using a 7-point scale (0=no impairment and 6=maximum impairment). Spirometry data were used to grade the percent predicted FEV1 on a 7-point scale (0 to 6). The ACQ score is the mean of the 7 questions, generating a value from 0 (totally controlled) to 6 (severely uncontrolled). Device mastery was defined as the absence of nurse-observed errors by the end of Step 3 of a 6-step standardized device training protocol for each device.

Outcome measures

Measure	Stage 1: Empty Spiromax n=145 Participants Participants were trained on the proper use of empty Spiromax.	Stage 1: Empty Turbohaler n=149 Participants Participants were trained on the proper use of empty Turbohaler.
Stage 2: Impact of Maintaining Device Mastery on Asthma Control Questionnaire Score Device mastery = Yes	1.25 Units on a scale Standard Deviation 1.05	1.35 Units on a scale Standard Deviation 0.95
Stage 2: Impact of Maintaining Device Mastery on Asthma Control Questionnaire Score Device mastery = No	1.46 Units on a scale Standard Deviation 0.97	1.37 Units on a scale Standard Deviation 0.97

SECONDARY outcome

Timeframe: Baseline up to Week 12

Population: The safety population for stage 2 included all participants randomly assigned to treatment who received at least 1 dose of study drug.

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both SAEs and non-serious AEs. A summary of other non-serious AEs and all SAEs, regardless of causality is located in the 'Reported AE section'.

Outcome measures

Measure	Stage 1: Empty Spiromax n=197 Participants Participants were trained on the proper use of empty Spiromax.	Stage 1: Empty Turbohaler n=197 Participants Participants were trained on the proper use of empty Turbohaler.
Number of Participants With Adverse Events (AEs)	113 Participants	119 Participants

Adverse Events

Stage 2: BF Spiromax

Serious events: 3 serious events

Other events: 27 other events

Deaths: 0 deaths

Stage 2: Symbicort Turbohaler

Serious events: 7 serious events

Other events: 39 other events

Deaths: 0 deaths

Serious adverse events

Measure	Stage 2: BF Spiromax n=197 participants at risk Participants who had currently received 800 to 1000 μg beclometasone-equivalent ICS per day received budesonide/formoterol twice daily using the BF Spiromax 160/4.5 μg device. Therefore, the daily, ex-mouthpiece doses of budesonide and formoterol using BF Spiromax were 640 μg and 18 μg, respectively. Participants who had currently received 1600 to 2000 μg beclometasone-equivalent ICS per day received budesonide/formoterol twice daily using the BF Spiromax 320/9 μg device. Therefore, the daily, ex-mouthpiece doses of budesonide and formoterol using BF Spiromax were 1280 μg and 36 μg, respectively.	Stage 2: Symbicort Turbohaler n=197 participants at risk Participants who had currently received 800 to 1000 μg beclometasone-equivalent ICS per day received budesonide/formoterol twice daily using the Symbicort Turbohaler 200/6 μg device. Therefore, the daily, ex-mouthpiece doses of budesonide and formoterol using Symbicort Turbohaler were 800 μg and 24 μg respectively. Participants who had currently received 1600 to 2000 μg beclometasone-equivalent ICS per day received budesonide/formoterol twice daily using the Symbicort Turbohaler 400/12 μg device. Therefore, the daily, ex-mouthpiece doses of budesonide and formoterol using Symbicort Turbohaler were 1600 μg and 48 μg respectively.
Cardiac disorders Angina pectoris	0.51% 1/197 • Number of events 1 • Baseline up to Week 12 Per planned analysis no adverse events were collected or reported during Stage 1. For the purpose of adverse event recording, the study period was defined for each participant as the time period from randomization of treatment in stage 2 through the end of the treatment period. The safety population for stage 2 included all participants randomly assigned to treatment who received at least 1 dose of study drug.	0.00% 0/197 • Baseline up to Week 12 Per planned analysis no adverse events were collected or reported during Stage 1. For the purpose of adverse event recording, the study period was defined for each participant as the time period from randomization of treatment in stage 2 through the end of the treatment period. The safety population for stage 2 included all participants randomly assigned to treatment who received at least 1 dose of study drug.
Cardiac disorders Atrial flutter	0.00% 0/197 • Baseline up to Week 12 Per planned analysis no adverse events were collected or reported during Stage 1. For the purpose of adverse event recording, the study period was defined for each participant as the time period from randomization of treatment in stage 2 through the end of the treatment period. The safety population for stage 2 included all participants randomly assigned to treatment who received at least 1 dose of study drug.	0.51% 1/197 • Number of events 1 • Baseline up to Week 12 Per planned analysis no adverse events were collected or reported during Stage 1. For the purpose of adverse event recording, the study period was defined for each participant as the time period from randomization of treatment in stage 2 through the end of the treatment period. The safety population for stage 2 included all participants randomly assigned to treatment who received at least 1 dose of study drug.
Cardiac disorders Atrioventricular block	0.00% 0/197 • Baseline up to Week 12 Per planned analysis no adverse events were collected or reported during Stage 1. For the purpose of adverse event recording, the study period was defined for each participant as the time period from randomization of treatment in stage 2 through the end of the treatment period. The safety population for stage 2 included all participants randomly assigned to treatment who received at least 1 dose of study drug.	0.51% 1/197 • Number of events 1 • Baseline up to Week 12 Per planned analysis no adverse events were collected or reported during Stage 1. For the purpose of adverse event recording, the study period was defined for each participant as the time period from randomization of treatment in stage 2 through the end of the treatment period. The safety population for stage 2 included all participants randomly assigned to treatment who received at least 1 dose of study drug.
General disorders Chest pain	0.00% 0/197 • Baseline up to Week 12 Per planned analysis no adverse events were collected or reported during Stage 1. For the purpose of adverse event recording, the study period was defined for each participant as the time period from randomization of treatment in stage 2 through the end of the treatment period. The safety population for stage 2 included all participants randomly assigned to treatment who received at least 1 dose of study drug.	1.0% 2/197 • Number of events 2 • Baseline up to Week 12 Per planned analysis no adverse events were collected or reported during Stage 1. For the purpose of adverse event recording, the study period was defined for each participant as the time period from randomization of treatment in stage 2 through the end of the treatment period. The safety population for stage 2 included all participants randomly assigned to treatment who received at least 1 dose of study drug.
Infections and infestations Lower respiratory tract infection	0.51% 1/197 • Number of events 1 • Baseline up to Week 12 Per planned analysis no adverse events were collected or reported during Stage 1. For the purpose of adverse event recording, the study period was defined for each participant as the time period from randomization of treatment in stage 2 through the end of the treatment period. The safety population for stage 2 included all participants randomly assigned to treatment who received at least 1 dose of study drug.	0.51% 1/197 • Number of events 1 • Baseline up to Week 12 Per planned analysis no adverse events were collected or reported during Stage 1. For the purpose of adverse event recording, the study period was defined for each participant as the time period from randomization of treatment in stage 2 through the end of the treatment period. The safety population for stage 2 included all participants randomly assigned to treatment who received at least 1 dose of study drug.
Infections and infestations Postoperative wound infection	0.51% 1/197 • Number of events 1 • Baseline up to Week 12 Per planned analysis no adverse events were collected or reported during Stage 1. For the purpose of adverse event recording, the study period was defined for each participant as the time period from randomization of treatment in stage 2 through the end of the treatment period. The safety population for stage 2 included all participants randomly assigned to treatment who received at least 1 dose of study drug.	0.00% 0/197 • Baseline up to Week 12 Per planned analysis no adverse events were collected or reported during Stage 1. For the purpose of adverse event recording, the study period was defined for each participant as the time period from randomization of treatment in stage 2 through the end of the treatment period. The safety population for stage 2 included all participants randomly assigned to treatment who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Thermal burn	0.00% 0/197 • Baseline up to Week 12 Per planned analysis no adverse events were collected or reported during Stage 1. For the purpose of adverse event recording, the study period was defined for each participant as the time period from randomization of treatment in stage 2 through the end of the treatment period. The safety population for stage 2 included all participants randomly assigned to treatment who received at least 1 dose of study drug.	0.51% 1/197 • Number of events 1 • Baseline up to Week 12 Per planned analysis no adverse events were collected or reported during Stage 1. For the purpose of adverse event recording, the study period was defined for each participant as the time period from randomization of treatment in stage 2 through the end of the treatment period. The safety population for stage 2 included all participants randomly assigned to treatment who received at least 1 dose of study drug.
Renal and urinary disorders Renal failure acute	0.00% 0/197 • Baseline up to Week 12 Per planned analysis no adverse events were collected or reported during Stage 1. For the purpose of adverse event recording, the study period was defined for each participant as the time period from randomization of treatment in stage 2 through the end of the treatment period. The safety population for stage 2 included all participants randomly assigned to treatment who received at least 1 dose of study drug.	0.51% 1/197 • Number of events 1 • Baseline up to Week 12 Per planned analysis no adverse events were collected or reported during Stage 1. For the purpose of adverse event recording, the study period was defined for each participant as the time period from randomization of treatment in stage 2 through the end of the treatment period. The safety population for stage 2 included all participants randomly assigned to treatment who received at least 1 dose of study drug.
Reproductive system and breast disorders Ovarian mass	0.00% 0/197 • Baseline up to Week 12 Per planned analysis no adverse events were collected or reported during Stage 1. For the purpose of adverse event recording, the study period was defined for each participant as the time period from randomization of treatment in stage 2 through the end of the treatment period. The safety population for stage 2 included all participants randomly assigned to treatment who received at least 1 dose of study drug.	0.51% 1/197 • Number of events 1 • Baseline up to Week 12 Per planned analysis no adverse events were collected or reported during Stage 1. For the purpose of adverse event recording, the study period was defined for each participant as the time period from randomization of treatment in stage 2 through the end of the treatment period. The safety population for stage 2 included all participants randomly assigned to treatment who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Asthma	0.51% 1/197 • Number of events 1 • Baseline up to Week 12 Per planned analysis no adverse events were collected or reported during Stage 1. For the purpose of adverse event recording, the study period was defined for each participant as the time period from randomization of treatment in stage 2 through the end of the treatment period. The safety population for stage 2 included all participants randomly assigned to treatment who received at least 1 dose of study drug.	0.00% 0/197 • Baseline up to Week 12 Per planned analysis no adverse events were collected or reported during Stage 1. For the purpose of adverse event recording, the study period was defined for each participant as the time period from randomization of treatment in stage 2 through the end of the treatment period. The safety population for stage 2 included all participants randomly assigned to treatment who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/197 • Baseline up to Week 12 Per planned analysis no adverse events were collected or reported during Stage 1. For the purpose of adverse event recording, the study period was defined for each participant as the time period from randomization of treatment in stage 2 through the end of the treatment period. The safety population for stage 2 included all participants randomly assigned to treatment who received at least 1 dose of study drug.	0.51% 1/197 • Number of events 1 • Baseline up to Week 12 Per planned analysis no adverse events were collected or reported during Stage 1. For the purpose of adverse event recording, the study period was defined for each participant as the time period from randomization of treatment in stage 2 through the end of the treatment period. The safety population for stage 2 included all participants randomly assigned to treatment who received at least 1 dose of study drug.
Vascular disorders Hypotension	0.00% 0/197 • Baseline up to Week 12 Per planned analysis no adverse events were collected or reported during Stage 1. For the purpose of adverse event recording, the study period was defined for each participant as the time period from randomization of treatment in stage 2 through the end of the treatment period. The safety population for stage 2 included all participants randomly assigned to treatment who received at least 1 dose of study drug.	0.51% 1/197 • Number of events 1 • Baseline up to Week 12 Per planned analysis no adverse events were collected or reported during Stage 1. For the purpose of adverse event recording, the study period was defined for each participant as the time period from randomization of treatment in stage 2 through the end of the treatment period. The safety population for stage 2 included all participants randomly assigned to treatment who received at least 1 dose of study drug.

Other adverse events

Measure	Stage 2: BF Spiromax n=197 participants at risk Participants who had currently received 800 to 1000 μg beclometasone-equivalent ICS per day received budesonide/formoterol twice daily using the BF Spiromax 160/4.5 μg device. Therefore, the daily, ex-mouthpiece doses of budesonide and formoterol using BF Spiromax were 640 μg and 18 μg, respectively. Participants who had currently received 1600 to 2000 μg beclometasone-equivalent ICS per day received budesonide/formoterol twice daily using the BF Spiromax 320/9 μg device. Therefore, the daily, ex-mouthpiece doses of budesonide and formoterol using BF Spiromax were 1280 μg and 36 μg, respectively.	Stage 2: Symbicort Turbohaler n=197 participants at risk Participants who had currently received 800 to 1000 μg beclometasone-equivalent ICS per day received budesonide/formoterol twice daily using the Symbicort Turbohaler 200/6 μg device. Therefore, the daily, ex-mouthpiece doses of budesonide and formoterol using Symbicort Turbohaler were 800 μg and 24 μg respectively. Participants who had currently received 1600 to 2000 μg beclometasone-equivalent ICS per day received budesonide/formoterol twice daily using the Symbicort Turbohaler 400/12 μg device. Therefore, the daily, ex-mouthpiece doses of budesonide and formoterol using Symbicort Turbohaler were 1600 μg and 48 μg respectively.
Infections and infestations Lower respiratory tract infection	8.1% 16/197 • Number of events 16 • Baseline up to Week 12 Per planned analysis no adverse events were collected or reported during Stage 1. For the purpose of adverse event recording, the study period was defined for each participant as the time period from randomization of treatment in stage 2 through the end of the treatment period. The safety population for stage 2 included all participants randomly assigned to treatment who received at least 1 dose of study drug.	14.7% 29/197 • Number of events 29 • Baseline up to Week 12 Per planned analysis no adverse events were collected or reported during Stage 1. For the purpose of adverse event recording, the study period was defined for each participant as the time period from randomization of treatment in stage 2 through the end of the treatment period. The safety population for stage 2 included all participants randomly assigned to treatment who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Cough	5.6% 11/197 • Number of events 11 • Baseline up to Week 12 Per planned analysis no adverse events were collected or reported during Stage 1. For the purpose of adverse event recording, the study period was defined for each participant as the time period from randomization of treatment in stage 2 through the end of the treatment period. The safety population for stage 2 included all participants randomly assigned to treatment who received at least 1 dose of study drug.	6.1% 12/197 • Number of events 12 • Baseline up to Week 12 Per planned analysis no adverse events were collected or reported during Stage 1. For the purpose of adverse event recording, the study period was defined for each participant as the time period from randomization of treatment in stage 2 through the end of the treatment period. The safety population for stage 2 included all participants randomly assigned to treatment who received at least 1 dose of study drug.

Additional Information

Director, Clinical Research

Teva Branded Pharmaceutical Products R&D, Inc.

Phone: 1-888-483-8279

Email: USMedInfo@tevapharm.com

Results disclosure agreements

• Principal investigator is a sponsor employee Sponsor has the right 60 days before submission for publication to review/provide comments. If the Sponsor's review shows that potentially patentable subject matter would be disclosed, publication or public disclosure shall be delayed for up to 90 additional days in order for the Sponsor, or Sponsor's designees, to file the necessary patent applications. In multicenter trials, each PI will postpone single center publications until after disclosure or publication of multicenter data.
• Publication restrictions are in place

Restriction type: OTHER