Trial Outcomes & Findings for Study of Fluticasone Propionate Multidose Dry Powder Inhaler Compared With Fluticasone Propionate/Salmeterol Multidose Dry Powder Inhaler (NCT NCT02980133)

NCT ID: NCT02980133

Last Updated: 2021-11-09

Results Overview

FEV1 was the volume of air exhaled in the first second of a forced expiration as measured by spirometer. The baseline 1-hour trough morning percent predicted FEV1 was defined as the predose trough morning percent predicted FEV1 measurement at the randomization visit (Baseline \[Day 1\]) at the investigational center. The IMP dose was administered right after the predose FEV1 measurement (within a 10 minute window). Participant then performed 1-hour (±10 minutes) postdose lung function assessments on Week 12 at the investigational center.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 841 participants
• Primary outcome timeframe: Baseline, Week 12
• Results posted on: 2021-11-09

Participant Flow

A total of 841 participants with persistent asthma were randomized in a 1:1:1:1 ratio to receive Fp MDPI 25 mcg, Fp MDPI 50 mcg, FS MDPI 50/12.5 mcg, or placebo MDPI. Randomization was stratified by previous therapy (inhaled corticosteroid [ICS] or non-corticosteroid [NCS]).

Participant milestones

Measure	Placebo MDPI Participants received matching placebo via multidose dry powder inhaler (MDPI) for 12 weeks.	Fp MDPI 25 mcg BID Participants received 1 inhalation of 25 micrograms (mcg) fluticasone propionate (Fp) via MDPI twice daily (BID) (total daily dose: 50 mcg) for 12 weeks.	Fp MDPI 50 mcg BID Participants received 1 inhalation of 50 mcg fluticasone propionate via MDPI BID (total daily dose: 100 mcg) for 12 weeks.	FS MDPI 50/12.5 mcg BID Participants received 1 inhalation of 50/12.5 mcg fluticasone propionate/salmeterol (FS) via MDPI BID (total daily dose: 100/25 mcg) for 12 weeks.
Overall Study STARTED	209	211	210	211
Overall Study Received at Least 1 Dose of Study Drug	209	211	208	211
Overall Study COMPLETED	202	206	203	205
Overall Study NOT COMPLETED	7	5	7	6

Reasons for withdrawal

Measure	Placebo MDPI Participants received matching placebo via multidose dry powder inhaler (MDPI) for 12 weeks.	Fp MDPI 25 mcg BID Participants received 1 inhalation of 25 micrograms (mcg) fluticasone propionate (Fp) via MDPI twice daily (BID) (total daily dose: 50 mcg) for 12 weeks.	Fp MDPI 50 mcg BID Participants received 1 inhalation of 50 mcg fluticasone propionate via MDPI BID (total daily dose: 100 mcg) for 12 weeks.	FS MDPI 50/12.5 mcg BID Participants received 1 inhalation of 50/12.5 mcg fluticasone propionate/salmeterol (FS) via MDPI BID (total daily dose: 100/25 mcg) for 12 weeks.
Overall Study Other than specified	1	1	2	2
Overall Study Lost to Follow-up	0	0	1	3
Overall Study Protocol Violation	0	1	0	0
Overall Study Withdrawal by parent/guardian	6	3	3	1
Overall Study Withdrawal by Subject	0	0	1	0

Baseline Characteristics

Here, 'Number analyzed' signifies participants evaluable for this parameter.

Baseline characteristics by cohort

Measure	Placebo MDPI n=209 Participants Participants received matching placebo via MDPI for 12 weeks.	Fp MDPI 25 mcg BID n=211 Participants Participants received 1 inhalation of 25 mcg fluticasone propionate via MDPI BID (total daily dose: 50 mcg) for 12 weeks.	Fp MDPI 50 mcg BID n=210 Participants Participants received 1 inhalation of 50 mcg fluticasone propionate via MDPI BID (total daily dose: 100 mcg) for 12 weeks.	FS MDPI 50/12.5 mcg BID n=211 Participants Participants received 1 inhalation of 50/12.5 mcg fluticasone propionate/salmeterol via MDPI BID (total daily dose: 100/25 mcg) for 12 weeks.	Total n=841 Participants Total of all reporting groups
Race/Ethnicity, Customized Asian	1 Participants n=209 Participants	0 Participants n=211 Participants	2 Participants n=210 Participants	3 Participants n=211 Participants	6 Participants n=841 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=209 Participants	1 Participants n=211 Participants	2 Participants n=210 Participants	0 Participants n=211 Participants	3 Participants n=841 Participants
Age, Continuous	8.5 years STANDARD_DEVIATION 1.98 • n=209 Participants	8.7 years STANDARD_DEVIATION 1.83 • n=211 Participants	8.5 years STANDARD_DEVIATION 1.94 • n=210 Participants	8.4 years STANDARD_DEVIATION 2.05 • n=211 Participants	8.5 years STANDARD_DEVIATION 1.95 • n=841 Participants
Sex: Female, Male Female	79 Participants n=209 Participants	74 Participants n=211 Participants	80 Participants n=210 Participants	91 Participants n=211 Participants	324 Participants n=841 Participants
Sex: Female, Male Male	130 Participants n=209 Participants	137 Participants n=211 Participants	130 Participants n=210 Participants	120 Participants n=211 Participants	517 Participants n=841 Participants
Race/Ethnicity, Customized White	172 Participants n=209 Participants	168 Participants n=211 Participants	171 Participants n=210 Participants	172 Participants n=211 Participants	683 Participants n=841 Participants
Race/Ethnicity, Customized Black or African American	33 Participants n=209 Participants	41 Participants n=211 Participants	32 Participants n=210 Participants	29 Participants n=211 Participants	135 Participants n=841 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	1 Participants n=209 Participants	0 Participants n=211 Participants	0 Participants n=210 Participants	0 Participants n=211 Participants	1 Participants n=841 Participants
Race/Ethnicity, Customized Other	2 Participants n=209 Participants	1 Participants n=211 Participants	3 Participants n=210 Participants	7 Participants n=211 Participants	13 Participants n=841 Participants
At-Home Baseline Percent Predicted Forced Expiratory Volume in 1 Second (FEV1)	68.8 percent predicted of FEV1 STANDARD_DEVIATION 9.70 • n=209 Participants • Here, 'Number analyzed' signifies participants evaluable for this parameter.	69.6 percent predicted of FEV1 STANDARD_DEVIATION 9.68 • n=211 Participants • Here, 'Number analyzed' signifies participants evaluable for this parameter.	69.6 percent predicted of FEV1 STANDARD_DEVIATION 9.47 • n=209 Participants • Here, 'Number analyzed' signifies participants evaluable for this parameter.	69.9 percent predicted of FEV1 STANDARD_DEVIATION 9.15 • n=211 Participants • Here, 'Number analyzed' signifies participants evaluable for this parameter.	69.5 percent predicted of FEV1 STANDARD_DEVIATION 9.49 • n=840 Participants • Here, 'Number analyzed' signifies participants evaluable for this parameter.
In-Clinic Baseline Percent Predicted FEV1	74.9 percent predicted of FEV1 STANDARD_DEVIATION 14.58 • n=209 Participants • Here, 'Number analyzed' signifies participants evaluable for this parameter.	73.0 percent predicted of FEV1 STANDARD_DEVIATION 13.43 • n=211 Participants • Here, 'Number analyzed' signifies participants evaluable for this parameter.	72.9 percent predicted of FEV1 STANDARD_DEVIATION 13.00 • n=209 Participants • Here, 'Number analyzed' signifies participants evaluable for this parameter.	74.1 percent predicted of FEV1 STANDARD_DEVIATION 15.02 • n=211 Participants • Here, 'Number analyzed' signifies participants evaluable for this parameter.	73.7 percent predicted of FEV1 STANDARD_DEVIATION 14.03 • n=840 Participants • Here, 'Number analyzed' signifies participants evaluable for this parameter.

PRIMARY outcome

Timeframe: Baseline, Week 12

Population: ITT analysis set included all randomized participants. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure. Missing data was imputed using MNAR methodology for prematurely discontinue participants or MAR for completers with implausible data.

FEV1 was the volume of air exhaled in the first second of a forced expiration as measured by spirometer. The baseline 1-hour trough morning percent predicted FEV1 was defined as the predose trough morning percent predicted FEV1 measurement at the randomization visit (Baseline [Day 1]) at the investigational center. The IMP dose was administered right after the predose FEV1 measurement (within a 10 minute window). Participant then performed 1-hour (±10 minutes) postdose lung function assessments on Week 12 at the investigational center.

Outcome measures

Measure	Fp MDPI 25 mcg BID n=211 Participants Participants received 1 inhalation of 25 mcg fluticasone propionate via MDPI BID (total daily dose: 50 mcg) for 12 weeks.	Fp MDPI 50 mcg BID n=209 Participants Participants received 1 inhalation of 50 mcg fluticasone propionate via MDPI BID (total daily dose: 100 mcg) for 12 weeks.	FS MDPI 50/12.5 mcg BID n=211 Participants Participants received 1 inhalation of 50/12.5 mcg fluticasone propionate/salmeterol via MDPI BID (total daily dose: 100/25 mcg) for 12 weeks.	FS MDPI 50/12.5 mcg BID Participants received 1 inhalation of 50/12.5 mcg fluticasone propionate/salmeterol via MDPI BID (total daily dose: 100/25 mcg) for 12 weeks.
For FS MDPI Versus Fp MDPI: Change From Baseline in 1-Hour Postdose Percent Predicted Morning Forced Expiratory Volume in 1 Second (FEV1) at Week 12	16.8 percent predicted of FEV1 Standard Error 1.32	16.4 percent predicted of FEV1 Standard Error 1.32	18.2 percent predicted of FEV1 Standard Error 1.29	—

PRIMARY outcome

Timeframe: Baseline, Week 12

Population: ITT analysis set included all randomized participants. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure. Missing data was imputed using missing not at random (MNAR) methodology for prematurely discontinue participants or missing at random (MAR) for completers with implausible data.

FEV1 was the volume of air exhaled in the first second of a forced expiration as measured by spirometer. Baseline trough morning percent predicted FEV1 was defined as the average value of recorded (nonmissing) morning assessments 5 out of the last 7 days prior to randomization. The first day before randomization consisted of the electronic patient diary entry at home on the morning of the randomization visit (Baseline [Day 1]) and the first day postrandomization consisted of the electronic patient diary entry at home on the morning of the day after the randomization visit (Baseline [Day 1]). For postdose weekly average of trough morning percent predicted FEV1 measurements, the values were the averages based on the available data for that week. The averages were calculated as the sum of morning FEV1 values divided by the number of nonmissing assessments.

Outcome measures

Measure	Fp MDPI 25 mcg BID n=209 Participants Participants received 1 inhalation of 25 mcg fluticasone propionate via MDPI BID (total daily dose: 50 mcg) for 12 weeks.	Fp MDPI 50 mcg BID n=211 Participants Participants received 1 inhalation of 50 mcg fluticasone propionate via MDPI BID (total daily dose: 100 mcg) for 12 weeks.	FS MDPI 50/12.5 mcg BID n=209 Participants Participants received 1 inhalation of 50/12.5 mcg fluticasone propionate/salmeterol via MDPI BID (total daily dose: 100/25 mcg) for 12 weeks.	FS MDPI 50/12.5 mcg BID Participants received 1 inhalation of 50/12.5 mcg fluticasone propionate/salmeterol via MDPI BID (total daily dose: 100/25 mcg) for 12 weeks.
For Fp MDPI Versus Placebo: Change From Baseline in Weekly Average of the Percent Predicted Trough Morning FEV1 at Week 12	7.3 percent predicted of FEV1 Standard Error 1.10	13.3 percent predicted of FEV1 Standard Error 1.09	14.2 percent predicted of FEV1 Standard Error 1.10	—

SECONDARY outcome

Timeframe: Baseline, Week 1 to 12

Population: ITT analysis set included all randomized participants. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.

PEF is defined as the maximum airflow during a forced expiration beginning with the lungs fully inflated. Morning PEF was determined in the morning, before administration of IMP or rescue medications. Baseline trough morning PEF was defined as the average value of recorded (nonmissing) morning assessments 5 out of the last 7 days prior to randomization. The first day before randomization consisted of the electronic patient diary entry at home on the morning of the randomization visit (Baseline [Day 1]) and the first day postrandomization consisted of the electronic patient diary entry at home on the morning of the day after the randomization visit (Baseline [Day 1]). For postdose weekly average of trough morning PEF measurements, the values were the averages based on the available data for that week. The averages were calculated as the sum of morning PEF values divided by the number of nonmissing assessments.

Outcome measures

Measure	Fp MDPI 25 mcg BID n=208 Participants Participants received 1 inhalation of 25 mcg fluticasone propionate via MDPI BID (total daily dose: 50 mcg) for 12 weeks.	Fp MDPI 50 mcg BID n=210 Participants Participants received 1 inhalation of 50 mcg fluticasone propionate via MDPI BID (total daily dose: 100 mcg) for 12 weeks.	FS MDPI 50/12.5 mcg BID n=208 Participants Participants received 1 inhalation of 50/12.5 mcg fluticasone propionate/salmeterol via MDPI BID (total daily dose: 100/25 mcg) for 12 weeks.	FS MDPI 50/12.5 mcg BID n=211 Participants Participants received 1 inhalation of 50/12.5 mcg fluticasone propionate/salmeterol via MDPI BID (total daily dose: 100/25 mcg) for 12 weeks.
Change From Baseline in the Weekly Average of Daily Trough Morning (Predose and Pre-Rescue Bronchodilator) Peak Expiratory Flow (PEF) Over the 12 Week Treatment Period	12.3 liters/minute Standard Error 2.65	28.9 liters/minute Standard Error 2.62	26.3 liters/minute Standard Error 2.64	32.0 liters/minute Standard Error 2.61

SECONDARY outcome

Timeframe: Baseline, Week 1 to 12

Population: ITT analysis set included all randomized participants. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.

Participants recorded the number of inhalations of rescue medication (albuterol/salbutamol HFA MDI) each morning and evening in the electronic patient diary. An entry of 0 inhalations indicated no rescue medication was needed. To calculate the total daily use of albuterol/salbutamol inhalation aerosol (number of inhalations), the electronic patient diary entry on randomization visit (Baseline [Day 1]) was defined as the first day of analysis. The weekly average of the total daily inhalations was the average based on the available data for that week. The average was calculated as the sum of total daily inhalations over the 7 days for each analysis week divided by the number of nonmissing assessments. LS mean and standard error (SE) were obtained using mixed model for repeated measures (MMRM).

Outcome measures

Measure	Fp MDPI 25 mcg BID n=208 Participants Participants received 1 inhalation of 25 mcg fluticasone propionate via MDPI BID (total daily dose: 50 mcg) for 12 weeks.	Fp MDPI 50 mcg BID n=210 Participants Participants received 1 inhalation of 50 mcg fluticasone propionate via MDPI BID (total daily dose: 100 mcg) for 12 weeks.	FS MDPI 50/12.5 mcg BID n=209 Participants Participants received 1 inhalation of 50/12.5 mcg fluticasone propionate/salmeterol via MDPI BID (total daily dose: 100/25 mcg) for 12 weeks.	FS MDPI 50/12.5 mcg BID n=211 Participants Participants received 1 inhalation of 50/12.5 mcg fluticasone propionate/salmeterol via MDPI BID (total daily dose: 100/25 mcg) for 12 weeks.
Change From Baseline in the Weekly Average of Total Daily (24 Hour) Use of Albuterol/Salbutamol Inhalation Aerosol (Number of Inhalations) Over Weeks 1 Through 12	-0.2 inhalations Standard Error 0.05	-0.4 inhalations Standard Error 0.05	-0.5 inhalations Standard Error 0.05	-0.4 inhalations Standard Error 0.05

SECONDARY outcome

Timeframe: Baseline, Week 1 to 12

Population: ITT analysis set included all randomized participants. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.

Asthma symptom scores were recorded in the patient diary. Each participant assessed the symptoms of cough, wheeze, shortness of breath, and chest tightness and entered a single score that was inclusive of all symptoms. Daytime Symptom Score (determined in the evening) ranged from 0=No symptoms during the day to 5=Symptoms so severe that I could not go to work or perform normal daily activities. Nighttime Symptom Score (determined in the morning) ranged from 0=No symptoms during the night to 4=Symptoms so severe that I did not sleep at all. The total daily asthma symptom score was the average of the daytime and nighttime scores. The total daily asthma symptom score ranged from 0 - 9 with 0=no symptoms during the day or night and 9=severe symptoms both day and night. The weekly average was calculated as the sum of total daily asthma symptom scores over the 7 days for each analysis week divided by the number of nonmissing assessments. LS mean and SE were obtained using MMRM.

Outcome measures

Measure	Fp MDPI 25 mcg BID n=208 Participants Participants received 1 inhalation of 25 mcg fluticasone propionate via MDPI BID (total daily dose: 50 mcg) for 12 weeks.	Fp MDPI 50 mcg BID n=210 Participants Participants received 1 inhalation of 50 mcg fluticasone propionate via MDPI BID (total daily dose: 100 mcg) for 12 weeks.	FS MDPI 50/12.5 mcg BID n=209 Participants Participants received 1 inhalation of 50/12.5 mcg fluticasone propionate/salmeterol via MDPI BID (total daily dose: 100/25 mcg) for 12 weeks.	FS MDPI 50/12.5 mcg BID n=211 Participants Participants received 1 inhalation of 50/12.5 mcg fluticasone propionate/salmeterol via MDPI BID (total daily dose: 100/25 mcg) for 12 weeks.
Change From Baseline in the Weekly Average of the Total Daily Asthma Symptom Score Over Weeks 1 Through 12	-0.1 units on a scale Standard Error 0.02	-0.2 units on a scale Standard Error 0.02	-0.2 units on a scale Standard Error 0.02	-0.2 units on a scale Standard Error 0.02

SECONDARY outcome

Timeframe: Baseline, Week 1 to 12

Population: ITT analysis set included all randomized participants. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.

C-ACT was a simple, participant-completed tool used for the assessment of overall asthma control. The first 4 items of the test were completed by the participant, while the last 3 items were completed by the participant's parents/legal guardians/caregivers. A total sum score based upon responses to all items was calculated to provide an overall measure of asthma control. The derived C-ACT score ranging from 0 to 27. These scores spanned the continuum of poor control of asthma (score ≤5) to complete control of asthma (score ≥25), with a cut off score of 19 indicating participants with poorly controlled asthma. LS mean and SE were obtained using MMRM.

Outcome measures

Measure	Fp MDPI 25 mcg BID n=204 Participants Participants received 1 inhalation of 25 mcg fluticasone propionate via MDPI BID (total daily dose: 50 mcg) for 12 weeks.	Fp MDPI 50 mcg BID n=208 Participants Participants received 1 inhalation of 50 mcg fluticasone propionate via MDPI BID (total daily dose: 100 mcg) for 12 weeks.	FS MDPI 50/12.5 mcg BID n=205 Participants Participants received 1 inhalation of 50/12.5 mcg fluticasone propionate/salmeterol via MDPI BID (total daily dose: 100/25 mcg) for 12 weeks.	FS MDPI 50/12.5 mcg BID n=209 Participants Participants received 1 inhalation of 50/12.5 mcg fluticasone propionate/salmeterol via MDPI BID (total daily dose: 100/25 mcg) for 12 weeks.
Change From Baseline in Asthma Control (Measured by Childhood Asthma Control Test [C-ACT] Score) Over the 12 Week Treatment Period	4.5 units on a scale Standard Error 0.21	5.1 units on a scale Standard Error 0.21	5.5 units on a scale Standard Error 0.21	5.4 units on a scale Standard Error 0.21

SECONDARY outcome

Timeframe: Baseline up to Week 12

Population: ITT analysis set included all randomized participants. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.

The time to first onset of effect, defined as the first decrease from baseline in daily rescue medication use, was calculated based on the number of inhalations of rescue medication (albuterol/salbutamol hydrofluoroalkane metered-dose inhaler [HFA MDI] [90 mcg ex actuator] or equivalent) recorded by the participant each morning and evening in the patient diary built into the handheld device.

Outcome measures

Measure	Fp MDPI 25 mcg BID n=208 Participants Participants received 1 inhalation of 25 mcg fluticasone propionate via MDPI BID (total daily dose: 50 mcg) for 12 weeks.	Fp MDPI 50 mcg BID n=210 Participants Participants received 1 inhalation of 50 mcg fluticasone propionate via MDPI BID (total daily dose: 100 mcg) for 12 weeks.	FS MDPI 50/12.5 mcg BID n=208 Participants Participants received 1 inhalation of 50/12.5 mcg fluticasone propionate/salmeterol via MDPI BID (total daily dose: 100/25 mcg) for 12 weeks.	FS MDPI 50/12.5 mcg BID n=211 Participants Participants received 1 inhalation of 50/12.5 mcg fluticasone propionate/salmeterol via MDPI BID (total daily dose: 100/25 mcg) for 12 weeks.
Time to First Onset of Effect	20.0 days Interval 5.0 to Due to smaller number of participants with an event, upper limit of 95% confidence interval (CI) could not be calculated.	NA days Interval 3.0 to Due to smaller number of participants with an event, median and upper limit of 95% CI could not be calculated.	2.0 days Interval 2.0 to 2.0	6.0 days Interval 2.0 to Due to smaller number of participants with an event, upper limit of 95% CI could not be calculated.

SECONDARY outcome

Timeframe: Baseline up to Week 12

Population: ITT analysis set included all randomized participants. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.

Outcome measures

Measure	Fp MDPI 25 mcg BID n=208 Participants Participants received 1 inhalation of 25 mcg fluticasone propionate via MDPI BID (total daily dose: 50 mcg) for 12 weeks.	Fp MDPI 50 mcg BID n=210 Participants Participants received 1 inhalation of 50 mcg fluticasone propionate via MDPI BID (total daily dose: 100 mcg) for 12 weeks.	FS MDPI 50/12.5 mcg BID n=208 Participants Participants received 1 inhalation of 50/12.5 mcg fluticasone propionate/salmeterol via MDPI BID (total daily dose: 100/25 mcg) for 12 weeks.	FS MDPI 50/12.5 mcg BID n=211 Participants Participants received 1 inhalation of 50/12.5 mcg fluticasone propionate/salmeterol via MDPI BID (total daily dose: 100/25 mcg) for 12 weeks.
Percentage of Participants Who Discontinued From Investigational Medicinal Product (IMP) for Asthma Exacerbation During the 12 Week Treatment Period	6 percentage of participants	2 percentage of participants	1 percentage of participants	2 percentage of participants

Adverse Events

Placebo MDPI

Serious events: 1 serious events

Other events: 11 other events

Deaths: 0 deaths

Fp MDPI 25 mcg BID

Serious events: 2 serious events

Other events: 8 other events

Deaths: 0 deaths

Fp MDPI 50 mcg BID

Serious events: 1 serious events

Other events: 11 other events

Deaths: 0 deaths

FS MDPI 50/12.5 mcg BID

Serious events: 4 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo MDPI n=209 participants at risk Participants received matching placebo via MDPI for 12 weeks.	Fp MDPI 25 mcg BID n=211 participants at risk Participants received 1 inhalation of 25 mcg fluticasone propionate via MDPI BID (total daily dose: 50 mcg) for 12 weeks.	Fp MDPI 50 mcg BID n=208 participants at risk Participants received 1 inhalation of 50 mcg fluticasone propionate via MDPI BID (total daily dose: 100 mcg) for 12 weeks.	FS MDPI 50/12.5 mcg BID n=211 participants at risk Participants received 1 inhalation of 50/12.5 mcg fluticasone propionate/salmeterol via MDPI BID (total daily dose: 100/25 mcg) for 12 weeks.
Blood and lymphatic system disorders Lymphadenitis	0.00% 0/209 • Baseline up to Week 13 Safety analysis set included all randomized participants who received at least 1 dose of IMP.	0.00% 0/211 • Baseline up to Week 13 Safety analysis set included all randomized participants who received at least 1 dose of IMP.	0.00% 0/208 • Baseline up to Week 13 Safety analysis set included all randomized participants who received at least 1 dose of IMP.	0.47% 1/211 • Number of events 1 • Baseline up to Week 13 Safety analysis set included all randomized participants who received at least 1 dose of IMP.
General disorders Pyrexia	0.00% 0/209 • Baseline up to Week 13 Safety analysis set included all randomized participants who received at least 1 dose of IMP.	0.00% 0/211 • Baseline up to Week 13 Safety analysis set included all randomized participants who received at least 1 dose of IMP.	0.00% 0/208 • Baseline up to Week 13 Safety analysis set included all randomized participants who received at least 1 dose of IMP.	0.47% 1/211 • Number of events 1 • Baseline up to Week 13 Safety analysis set included all randomized participants who received at least 1 dose of IMP.
Infections and infestations Pneumonia mycoplasmal	0.00% 0/209 • Baseline up to Week 13 Safety analysis set included all randomized participants who received at least 1 dose of IMP.	0.47% 1/211 • Number of events 1 • Baseline up to Week 13 Safety analysis set included all randomized participants who received at least 1 dose of IMP.	0.00% 0/208 • Baseline up to Week 13 Safety analysis set included all randomized participants who received at least 1 dose of IMP.	0.00% 0/211 • Baseline up to Week 13 Safety analysis set included all randomized participants who received at least 1 dose of IMP.
Infections and infestations Respiratory tract infection viral	0.48% 1/209 • Number of events 1 • Baseline up to Week 13 Safety analysis set included all randomized participants who received at least 1 dose of IMP.	0.00% 0/211 • Baseline up to Week 13 Safety analysis set included all randomized participants who received at least 1 dose of IMP.	0.00% 0/208 • Baseline up to Week 13 Safety analysis set included all randomized participants who received at least 1 dose of IMP.	0.00% 0/211 • Baseline up to Week 13 Safety analysis set included all randomized participants who received at least 1 dose of IMP.
Nervous system disorders Headache	0.00% 0/209 • Baseline up to Week 13 Safety analysis set included all randomized participants who received at least 1 dose of IMP.	0.00% 0/211 • Baseline up to Week 13 Safety analysis set included all randomized participants who received at least 1 dose of IMP.	0.00% 0/208 • Baseline up to Week 13 Safety analysis set included all randomized participants who received at least 1 dose of IMP.	0.47% 1/211 • Number of events 1 • Baseline up to Week 13 Safety analysis set included all randomized participants who received at least 1 dose of IMP.
Nervous system disorders Partial seizures	0.00% 0/209 • Baseline up to Week 13 Safety analysis set included all randomized participants who received at least 1 dose of IMP.	0.00% 0/211 • Baseline up to Week 13 Safety analysis set included all randomized participants who received at least 1 dose of IMP.	0.00% 0/208 • Baseline up to Week 13 Safety analysis set included all randomized participants who received at least 1 dose of IMP.	0.47% 1/211 • Number of events 1 • Baseline up to Week 13 Safety analysis set included all randomized participants who received at least 1 dose of IMP.
Psychiatric disorders Disruptive mood dysregulation disorder	0.00% 0/209 • Baseline up to Week 13 Safety analysis set included all randomized participants who received at least 1 dose of IMP.	0.00% 0/211 • Baseline up to Week 13 Safety analysis set included all randomized participants who received at least 1 dose of IMP.	0.48% 1/208 • Number of events 1 • Baseline up to Week 13 Safety analysis set included all randomized participants who received at least 1 dose of IMP.	0.00% 0/211 • Baseline up to Week 13 Safety analysis set included all randomized participants who received at least 1 dose of IMP.
Respiratory, thoracic and mediastinal disorders Asthma	0.48% 1/209 • Number of events 1 • Baseline up to Week 13 Safety analysis set included all randomized participants who received at least 1 dose of IMP.	0.47% 1/211 • Number of events 1 • Baseline up to Week 13 Safety analysis set included all randomized participants who received at least 1 dose of IMP.	0.00% 0/208 • Baseline up to Week 13 Safety analysis set included all randomized participants who received at least 1 dose of IMP.	0.00% 0/211 • Baseline up to Week 13 Safety analysis set included all randomized participants who received at least 1 dose of IMP.

Other adverse events

Measure	Placebo MDPI n=209 participants at risk Participants received matching placebo via MDPI for 12 weeks.	Fp MDPI 25 mcg BID n=211 participants at risk Participants received 1 inhalation of 25 mcg fluticasone propionate via MDPI BID (total daily dose: 50 mcg) for 12 weeks.	Fp MDPI 50 mcg BID n=208 participants at risk Participants received 1 inhalation of 50 mcg fluticasone propionate via MDPI BID (total daily dose: 100 mcg) for 12 weeks.	FS MDPI 50/12.5 mcg BID n=211 participants at risk Participants received 1 inhalation of 50/12.5 mcg fluticasone propionate/salmeterol via MDPI BID (total daily dose: 100/25 mcg) for 12 weeks.
Infections and infestations Nasopharyngitis	5.3% 11/209 • Number of events 12 • Baseline up to Week 13 Safety analysis set included all randomized participants who received at least 1 dose of IMP.	3.8% 8/211 • Number of events 9 • Baseline up to Week 13 Safety analysis set included all randomized participants who received at least 1 dose of IMP.	5.3% 11/208 • Number of events 11 • Baseline up to Week 13 Safety analysis set included all randomized participants who received at least 1 dose of IMP.	4.3% 9/211 • Number of events 9 • Baseline up to Week 13 Safety analysis set included all randomized participants who received at least 1 dose of IMP.

Additional Information

Director, Clinical Research

Teva Branded Pharmaceutical Products, R&D Inc.

Phone: 1-888-483-8279

Email: USMedInfo@tevapharm.com

Results disclosure agreements

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