Trial Outcomes & Findings for Effects of a Orally Inhaled Fluticasone Furoate on Growth Velocity in Prepubertal, Paediatric Subjects With Asthma Over a Year (NCT NCT02889809)

Last Updated: 2024-01-17

Results Overview

Three reproducible height measurements were taken using a stadiometer at each visit and were recorded to nearest 1/10th of centimeter. Each set of triplicate measurements was averaged to derive one estimated height per participant per visit. Growth velocity was calculated for each participant over double-blind treatment period (up to 52 weeks \[wk\]) by fitting a regression line to averaged height measurements at each visit for that participant during period. Slope of this regression line was participant's growth velocity for double-blind treatment period. Treatment policy estimand was assessed, including all on- and post-treatment data. Baseline was included as covariate which was calculated based on stadiometric height measurements recorded at Visits 1(wk -16), 3(wk-8), and 5(wk0), data from at least two of these visits were used to fit a simple linear regression line against time and the slope of the fitted regression line was the participant's Baseline growth velocity.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

477 participants

Primary outcome timeframe

Up to 52 weeks

Results posted on

2024-01-17

Participant Flow

This was a multicenter, randomized, double-blind, placebo-controlled study to evaluate the effects of a one-year regimen of orally inhaled fluticasone furoate (FF) 50 micrograms (mcg) once daily on growth velocity in prepubertal, pediatric participants with asthma.

Total 477 participants were enrolled in this study.

Participant milestones

Participant milestones
Measure	Placebo Participants received a single-blind placebo inhaler during a 16-week run-in period. After run-in period inhaled placebo was administered once daily (OD) in the morning for 52 weeks during the double-blind treatment period. Participants also received open-label montelukast one tablet orally in the evening (4 milligrams \[mg\] for participants who were 5 years old and 5 mg for participants who were greater than or equal to \[\>=\] 6 years old) as background therapy from the run-in period through to the end of follow-up (8 weeks) period.	FF 50 mcg Participants received received a single-blind placebo inhaler during a 16-week run-in period. After run-in period inhaled FF 50 mcg was administered via ELLIPTA inhaler once daily in the morning for 52 weeks during double-blind treatment period. Participants also received open-label montelukast one tablet orally in the evening (4 mg for participants who were 5 years old and 5 mg for participants who were \>=6 years old) as background therapy from the run-in period through to the end of follow-up (8 weeks) period.
Overall Study STARTED	239	238
Overall Study COMPLETED	196	205
Overall Study NOT COMPLETED	43	33

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received a single-blind placebo inhaler during a 16-week run-in period. After run-in period inhaled placebo was administered once daily (OD) in the morning for 52 weeks during the double-blind treatment period. Participants also received open-label montelukast one tablet orally in the evening (4 milligrams \[mg\] for participants who were 5 years old and 5 mg for participants who were greater than or equal to \[\>=\] 6 years old) as background therapy from the run-in period through to the end of follow-up (8 weeks) period.	FF 50 mcg Participants received received a single-blind placebo inhaler during a 16-week run-in period. After run-in period inhaled FF 50 mcg was administered via ELLIPTA inhaler once daily in the morning for 52 weeks during double-blind treatment period. Participants also received open-label montelukast one tablet orally in the evening (4 mg for participants who were 5 years old and 5 mg for participants who were \>=6 years old) as background therapy from the run-in period through to the end of follow-up (8 weeks) period.
Overall Study Withdrawal by Subject	30	21
Overall Study Lost to Follow-up	1	1
Overall Study Site Closed	12	11

Baseline Characteristics

Effects of a Orally Inhaled Fluticasone Furoate on Growth Velocity in Prepubertal, Paediatric Subjects With Asthma Over a Year

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=239 Participants Participants received a single-blind placebo inhaler during a 16-week run-in period. After run-in period inhaled placebo was administered once daily (OD) in the morning for 52 weeks during the double-blind treatment period. Participants also received open-label montelukast one tablet orally in the evening (4 milligrams \[mg\] for participants who were 5 years old and 5 mg for participants who were greater than or equal to \[\>=\] 6 years old) as background therapy from the run-in period through to the end of follow-up (8 weeks) period.	FF 50 mcg n=238 Participants Participants received received a single-blind placebo inhaler during a 16-week run-in period. After run-in period inhaled FF 50 mcg was administered via ELLIPTA inhaler once daily in the morning for 52 weeks during double-blind treatment period. Participants also received open-label montelukast one tablet orally in the evening (4 mg for participants who were 5 years old and 5 mg for participants who were \>=6 years old) as background therapy from the run-in period through to the end of follow-up (8 weeks) period.	Total n=477 Participants Total of all reporting groups
Age, Continuous	6.1 Years STANDARD_DEVIATION 1.07 • n=5 Participants	6.3 Years STANDARD_DEVIATION 1.02 • n=7 Participants	6.2 Years STANDARD_DEVIATION 1.05 • n=5 Participants
Sex: Female, Male Female	84 Participants n=5 Participants	94 Participants n=7 Participants	178 Participants n=5 Participants
Sex: Female, Male Male	155 Participants n=5 Participants	144 Participants n=7 Participants	299 Participants n=5 Participants
Race/Ethnicity, Customized African American/African Heritage	13 Participants n=5 Participants	13 Participants n=7 Participants	26 Participants n=5 Participants
Race/Ethnicity, Customized Asian - Central/South Asian Heritage	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Multiple	18 Participants n=5 Participants	20 Participants n=7 Participants	38 Participants n=5 Participants
Race/Ethnicity, Customized White - Arabic/North African Heritage	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Race/Ethnicity, Customized White - Mixed Race	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized White - White/Caucasian/European Heritage	204 Participants n=5 Participants	201 Participants n=7 Participants	405 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 52 weeks

Population: Growth Population comprised of all Intent to Treat (ITT) participants who have stadiometric height assessments from at least three post-randomization, on-treatment clinic visits (i.e., including all available height measurements after Visit 5 \[wk 0\] up to and including Visit 18 \[wk 52\], without exclusion) during the double-blind treatment period.

Outcome measures

Outcome measures
Measure	Placebo n=226 Participants Participants received a single-blind placebo inhaler during a 16-week run-in period. After run-in period inhaled placebo was administered once daily (OD) in the morning for 52 weeks during the double-blind treatment period. Participants also received open-label montelukast one tablet orally in the evening (4 milligrams \[mg\] for participants who were 5 years old and 5 mg for participants who were greater than or equal to \[\>=\] 6 years old) as background therapy from the run-in period through to the end of follow-up (8 weeks) period.	FF 50 mcg n=231 Participants Participants received received a single-blind placebo inhaler during a 16-week run-in period. After run-in period inhaled FF 50 mcg was administered via ELLIPTA inhaler once daily in the morning for 52 weeks during double-blind treatment period. Participants also received open-label montelukast one tablet orally in the evening (4 mg for participants who were 5 years old and 5 mg for participants who were \>=6 years old) as background therapy from the run-in period through to the end of follow-up (8 weeks) period.
Growth Velocity (Centimeter Per Year) Over the Double-blind Treatment Period, as Determined by Stadiometry	6.065 Centimeter per year Standard Error 0.1090	5.905 Centimeter per year Standard Error 0.1078

SECONDARY outcome

Timeframe: Up to 52 weeks

Population: Growth Population

Three reproducible height measurements were taken using stadiometer at each visit\&were recorded to nearest 1/10th of a centimeter.Each set of triplicate measurements was averaged to derive one estimated height per participant per visit.Growth velocity(GV)was calculated for each participant over double-blind treatment(up to 52 weeks)period by fitting regression line to height measurements recorded for that participant during period.Each participant's double-blind(DB) treatment period GV was calculated based on all on \&off treatment height data \&was programmatically compared to data values from Standards from Birth to Maturity for Height,Weight,Height Velocity, established in British Children(1965)\&further updated for North American children(1985)using 3rd percentile value of age closest to participant's age at end of endpoint(i.e.either end of participant's DB treatment period \[Visit18 Wk 52\]/withdrawal from study\[Early Withdrawal Visit\]).Percentage values presented is rounded off.

Outcome measures

Outcome measures
Measure	Placebo n=226 Participants Participants received a single-blind placebo inhaler during a 16-week run-in period. After run-in period inhaled placebo was administered once daily (OD) in the morning for 52 weeks during the double-blind treatment period. Participants also received open-label montelukast one tablet orally in the evening (4 milligrams \[mg\] for participants who were 5 years old and 5 mg for participants who were greater than or equal to \[\>=\] 6 years old) as background therapy from the run-in period through to the end of follow-up (8 weeks) period.	FF 50 mcg n=231 Participants Participants received received a single-blind placebo inhaler during a 16-week run-in period. After run-in period inhaled FF 50 mcg was administered via ELLIPTA inhaler once daily in the morning for 52 weeks during double-blind treatment period. Participants also received open-label montelukast one tablet orally in the evening (4 mg for participants who were 5 years old and 5 mg for participants who were \>=6 years old) as background therapy from the run-in period through to the end of follow-up (8 weeks) period.
Percentage of Participants Below the Third Percentile of Growth Velocity During Double-blind Treatment Period	9 Percentage of participants	7 Percentage of participants

SECONDARY outcome

Timeframe: Baseline and Endpoint (Week 28[Visit 12] up to and including Week 52 [Visit 18])

Population: Growth Population. Only those participants with data available at the specified data points were analyzed.

Growth velocity(GV) quartile(defined as 1st quartile(1Q)=1st-25th percentile,2Q=26th-50th percentile,3Q=51st-75th percentile,4Q=76th-100th percentile) was determined at Baseline\&endpoint.Endpoint was defined as slope of simple linear regression of average stadiometric height recorded at week 28\& upto wk52.Baseline growth velocity was calculated as slope from simple linear regression of average stadiometric height recorded at wk-16,-8\&0.Baseline GV was programmatically compared to reference for standard height data using participant's estimated age at wk0\& age in reference data closest to actual age of participant to determine Baseline GV quartile.Endpoint GV was programmatically compared to reference data using participant's age at endpoint \& age in reference data that was closest to actual age of participant to determine endpoint GV quartile. Any increase/decrease indicates any increase/decrease in quartiles with reference to Baseline. Percentage values presented is rounded off.

Outcome measures

Outcome measures
Measure	Placebo n=216 Participants Participants received a single-blind placebo inhaler during a 16-week run-in period. After run-in period inhaled placebo was administered once daily (OD) in the morning for 52 weeks during the double-blind treatment period. Participants also received open-label montelukast one tablet orally in the evening (4 milligrams \[mg\] for participants who were 5 years old and 5 mg for participants who were greater than or equal to \[\>=\] 6 years old) as background therapy from the run-in period through to the end of follow-up (8 weeks) period.	FF 50 mcg n=223 Participants Participants received received a single-blind placebo inhaler during a 16-week run-in period. After run-in period inhaled FF 50 mcg was administered via ELLIPTA inhaler once daily in the morning for 52 weeks during double-blind treatment period. Participants also received open-label montelukast one tablet orally in the evening (4 mg for participants who were 5 years old and 5 mg for participants who were \>=6 years old) as background therapy from the run-in period through to the end of follow-up (8 weeks) period.
Percentage of Participants With Change in Growth Velocity Quartiles From Baseline to Endpoint Any increase	33 Percentage of Participants	32 Percentage of Participants
Percentage of Participants With Change in Growth Velocity Quartiles From Baseline to Endpoint Any decrease	34 Percentage of Participants	38 Percentage of Participants

SECONDARY outcome

Timeframe: Up to 12 weeks (Visit 8) of double-blind treatment period

Population: Growth Population. Only those participants with data available at the specified data points were analyzed.

Growth velocity was calculated for each participant over double blind period by fitting regression line to height measurements recorded for that participant during period.Slope of this regression line was participant's growth velocity for double-blind treatment period.In order to be included in this analysis,participant must have data from Visit8(Wk 12) stadiometric height assessment.Baseline was included as covariate which was calculated based on stadiometric height measurements recorded at Visits 1(wk -16),3(wk-8),\& 5(wk0),data from at least two of these visits were used to fit simple linear regression line against time\&slope of fitted regression line was participant's Baseline growth velocity.All available height data collected during double-blind treatment period upto Visit8(Wk12) while participant was on randomized double-blind treatment was considered.ANCOVA model was used to estimate mean treatment difference in growth velocity over 1st 12weeks of double-blind treatment period.

Outcome measures

Outcome measures
Measure	Placebo n=210 Participants Participants received a single-blind placebo inhaler during a 16-week run-in period. After run-in period inhaled placebo was administered once daily (OD) in the morning for 52 weeks during the double-blind treatment period. Participants also received open-label montelukast one tablet orally in the evening (4 milligrams \[mg\] for participants who were 5 years old and 5 mg for participants who were greater than or equal to \[\>=\] 6 years old) as background therapy from the run-in period through to the end of follow-up (8 weeks) period.	FF 50 mcg n=211 Participants Participants received received a single-blind placebo inhaler during a 16-week run-in period. After run-in period inhaled FF 50 mcg was administered via ELLIPTA inhaler once daily in the morning for 52 weeks during double-blind treatment period. Participants also received open-label montelukast one tablet orally in the evening (4 mg for participants who were 5 years old and 5 mg for participants who were \>=6 years old) as background therapy from the run-in period through to the end of follow-up (8 weeks) period.
Growth Velocity Over the First 12 Weeks of Double-blind Treatment Period	6.222 Centimeter per year Standard Error 0.1845	6.281 Centimeter per year Standard Error 0.1841

SECONDARY outcome

Timeframe: Baseline (Week 0 [Visit 5]) and up to Endpoint (Week 52 [Visit 18])

Population: Growth Population. Only those participants with data available at the specified data points were analyzed

Each participant's SDS for each of three required stadiometric height measurements was calculated as:(observed height measurement-standard median height for age at Visit \[week-16\]) divided by (/) (\[standard 95th height percentile for age at visit-standard 5th height percentile for age at visit\]/\[2\*1.645\]).Standard median, 95th percentile, \& 5th percentile values were obtained from standard tables (Guidance for Industry Orally Inhaled \& Intranasal Corticosteroid). SDS for each height stadiometric measurement at each visit was calculated using percentiles from standard tables \& averaged for each participant before being summarized by treatment group. A reduction in SDS over time indicates growth deceleration \& an increase in SDS over time means growth acceleration.Baseline was defined as height SD score at Visit 5 (week 0). Endpoint was defined as height SD score at Visit 18 (week52) (on- \& off-treatment data). Change from Baseline was calculated as Endpoint value minus Baseline value.

Outcome measures

Outcome measures
Measure	Placebo n=196 Participants Participants received a single-blind placebo inhaler during a 16-week run-in period. After run-in period inhaled placebo was administered once daily (OD) in the morning for 52 weeks during the double-blind treatment period. Participants also received open-label montelukast one tablet orally in the evening (4 milligrams \[mg\] for participants who were 5 years old and 5 mg for participants who were greater than or equal to \[\>=\] 6 years old) as background therapy from the run-in period through to the end of follow-up (8 weeks) period.	FF 50 mcg n=202 Participants Participants received received a single-blind placebo inhaler during a 16-week run-in period. After run-in period inhaled FF 50 mcg was administered via ELLIPTA inhaler once daily in the morning for 52 weeks during double-blind treatment period. Participants also received open-label montelukast one tablet orally in the evening (4 mg for participants who were 5 years old and 5 mg for participants who were \>=6 years old) as background therapy from the run-in period through to the end of follow-up (8 weeks) period.
Change in Height Standard Deviation Scores (SDS) From Baseline to Endpoint	-0.02 Standard Deviation Score Standard Deviation 0.281	-0.04 Standard Deviation Score Standard Deviation 0.281

SECONDARY outcome

Timeframe: Up to 76 weeks

Population: Intent-to-Treat Population comprised of all randomized participants who received at least one dose of study treatment.

An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A SAE is defined as any untoward medical occurrence that, at any dose which results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, other situations as per investigator's judgement.

Outcome measures

Outcome measures
Measure	Placebo n=239 Participants Participants received a single-blind placebo inhaler during a 16-week run-in period. After run-in period inhaled placebo was administered once daily (OD) in the morning for 52 weeks during the double-blind treatment period. Participants also received open-label montelukast one tablet orally in the evening (4 milligrams \[mg\] for participants who were 5 years old and 5 mg for participants who were greater than or equal to \[\>=\] 6 years old) as background therapy from the run-in period through to the end of follow-up (8 weeks) period.	FF 50 mcg n=238 Participants Participants received received a single-blind placebo inhaler during a 16-week run-in period. After run-in period inhaled FF 50 mcg was administered via ELLIPTA inhaler once daily in the morning for 52 weeks during double-blind treatment period. Participants also received open-label montelukast one tablet orally in the evening (4 mg for participants who were 5 years old and 5 mg for participants who were \>=6 years old) as background therapy from the run-in period through to the end of follow-up (8 weeks) period.
Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) Any SAEs	8 Participants	6 Participants
Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) Any Non-serious AEs	105 Participants	99 Participants

SECONDARY outcome

Timeframe: Up to 52 weeks

Population: Intent-to-Treat Population.

An exacerbation is defined as deterioration of asthma requiring the use of systemic corticosteroids (tablets, suspension, or injection) for at least 3 days or a single depot corticosteroid injection, or an in-patient hospitalization or emergency department (ED) visit due to asthma that required systemic corticosteroids. Number of participants with on-treatment asthma exacerbations during double-blind treatment period is presented.

Outcome measures

Outcome measures
Measure	Placebo n=239 Participants Participants received a single-blind placebo inhaler during a 16-week run-in period. After run-in period inhaled placebo was administered once daily (OD) in the morning for 52 weeks during the double-blind treatment period. Participants also received open-label montelukast one tablet orally in the evening (4 milligrams \[mg\] for participants who were 5 years old and 5 mg for participants who were greater than or equal to \[\>=\] 6 years old) as background therapy from the run-in period through to the end of follow-up (8 weeks) period.	FF 50 mcg n=238 Participants Participants received received a single-blind placebo inhaler during a 16-week run-in period. After run-in period inhaled FF 50 mcg was administered via ELLIPTA inhaler once daily in the morning for 52 weeks during double-blind treatment period. Participants also received open-label montelukast one tablet orally in the evening (4 mg for participants who were 5 years old and 5 mg for participants who were \>=6 years old) as background therapy from the run-in period through to the end of follow-up (8 weeks) period.
Number of Participants With On-treatment Asthma Exacerbations Over Double-blind Treatment Period	22 Participants	7 Participants

Adverse Events

Placebo

Serious events: 8 serious events

Other events: 105 other events

Deaths: 0 deaths

FF 50 mcg

Serious events: 6 serious events

Other events: 99 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=239 participants at risk Participants received a single-blind placebo inhaler during a 16-week run-in period. After run-in period inhaled placebo was administered once daily (OD) in the morning for 52 weeks during the double-blind treatment period. Participants also received open-label montelukast one tablet orally in the evening (4 milligrams \[mg\] for participants who were 5 years old and 5 mg for participants who were greater than or equal to \[\>=\] 6 years old) as background therapy from the run-in period through to the end of follow-up (8 weeks) period.	FF 50 mcg n=238 participants at risk Participants received received a single-blind placebo inhaler during a 16-week run-in period. After run-in period inhaled FF 50 mcg was administered via ELLIPTA inhaler once daily in the morning for 52 weeks during double-blind treatment period. Participants also received open-label montelukast one tablet orally in the evening (4 mg for participants who were 5 years old and 5 mg for participants who were \>=6 years old) as background therapy from the run-in period through to the end of follow-up (8 weeks) period.
Gastrointestinal disorders Faecaloma	0.00% 0/239 • All cause mortality, non-serious adverse events (AEs) and serious AEs were collected up to 76 weeks All-cause mortality, non-serious AEs and SAEs were collected in Intent-to-Treat Population which comprised of all randomized participants who received at least one dose of study treatment.	0.42% 1/238 • Number of events 1 • All cause mortality, non-serious adverse events (AEs) and serious AEs were collected up to 76 weeks All-cause mortality, non-serious AEs and SAEs were collected in Intent-to-Treat Population which comprised of all randomized participants who received at least one dose of study treatment.
Infections and infestations Adenoviral haemorrhagic cystitis	0.00% 0/239 • All cause mortality, non-serious adverse events (AEs) and serious AEs were collected up to 76 weeks All-cause mortality, non-serious AEs and SAEs were collected in Intent-to-Treat Population which comprised of all randomized participants who received at least one dose of study treatment.	0.42% 1/238 • Number of events 1 • All cause mortality, non-serious adverse events (AEs) and serious AEs were collected up to 76 weeks All-cause mortality, non-serious AEs and SAEs were collected in Intent-to-Treat Population which comprised of all randomized participants who received at least one dose of study treatment.
Infections and infestations Appendicitis	0.00% 0/239 • All cause mortality, non-serious adverse events (AEs) and serious AEs were collected up to 76 weeks All-cause mortality, non-serious AEs and SAEs were collected in Intent-to-Treat Population which comprised of all randomized participants who received at least one dose of study treatment.	0.42% 1/238 • Number of events 1 • All cause mortality, non-serious adverse events (AEs) and serious AEs were collected up to 76 weeks All-cause mortality, non-serious AEs and SAEs were collected in Intent-to-Treat Population which comprised of all randomized participants who received at least one dose of study treatment.
Infections and infestations Bronchitis	0.00% 0/239 • All cause mortality, non-serious adverse events (AEs) and serious AEs were collected up to 76 weeks All-cause mortality, non-serious AEs and SAEs were collected in Intent-to-Treat Population which comprised of all randomized participants who received at least one dose of study treatment.	0.42% 1/238 • Number of events 1 • All cause mortality, non-serious adverse events (AEs) and serious AEs were collected up to 76 weeks All-cause mortality, non-serious AEs and SAEs were collected in Intent-to-Treat Population which comprised of all randomized participants who received at least one dose of study treatment.
Infections and infestations Gastroenteritis norovirus	0.42% 1/239 • Number of events 1 • All cause mortality, non-serious adverse events (AEs) and serious AEs were collected up to 76 weeks All-cause mortality, non-serious AEs and SAEs were collected in Intent-to-Treat Population which comprised of all randomized participants who received at least one dose of study treatment.	0.00% 0/238 • All cause mortality, non-serious adverse events (AEs) and serious AEs were collected up to 76 weeks All-cause mortality, non-serious AEs and SAEs were collected in Intent-to-Treat Population which comprised of all randomized participants who received at least one dose of study treatment.
Infections and infestations Pneumonia	0.42% 1/239 • Number of events 1 • All cause mortality, non-serious adverse events (AEs) and serious AEs were collected up to 76 weeks All-cause mortality, non-serious AEs and SAEs were collected in Intent-to-Treat Population which comprised of all randomized participants who received at least one dose of study treatment.	0.42% 1/238 • Number of events 1 • All cause mortality, non-serious adverse events (AEs) and serious AEs were collected up to 76 weeks All-cause mortality, non-serious AEs and SAEs were collected in Intent-to-Treat Population which comprised of all randomized participants who received at least one dose of study treatment.
Infections and infestations Tonsillitis	0.00% 0/239 • All cause mortality, non-serious adverse events (AEs) and serious AEs were collected up to 76 weeks All-cause mortality, non-serious AEs and SAEs were collected in Intent-to-Treat Population which comprised of all randomized participants who received at least one dose of study treatment.	0.42% 1/238 • Number of events 1 • All cause mortality, non-serious adverse events (AEs) and serious AEs were collected up to 76 weeks All-cause mortality, non-serious AEs and SAEs were collected in Intent-to-Treat Population which comprised of all randomized participants who received at least one dose of study treatment.
Infections and infestations Urinary tract infection	0.42% 1/239 • Number of events 1 • All cause mortality, non-serious adverse events (AEs) and serious AEs were collected up to 76 weeks All-cause mortality, non-serious AEs and SAEs were collected in Intent-to-Treat Population which comprised of all randomized participants who received at least one dose of study treatment.	0.00% 0/238 • All cause mortality, non-serious adverse events (AEs) and serious AEs were collected up to 76 weeks All-cause mortality, non-serious AEs and SAEs were collected in Intent-to-Treat Population which comprised of all randomized participants who received at least one dose of study treatment.
Injury, poisoning and procedural complications Fracture	0.42% 1/239 • Number of events 1 • All cause mortality, non-serious adverse events (AEs) and serious AEs were collected up to 76 weeks All-cause mortality, non-serious AEs and SAEs were collected in Intent-to-Treat Population which comprised of all randomized participants who received at least one dose of study treatment.	0.00% 0/238 • All cause mortality, non-serious adverse events (AEs) and serious AEs were collected up to 76 weeks All-cause mortality, non-serious AEs and SAEs were collected in Intent-to-Treat Population which comprised of all randomized participants who received at least one dose of study treatment.
Metabolism and nutrition disorders Diabetes mellitus	0.42% 1/239 • Number of events 1 • All cause mortality, non-serious adverse events (AEs) and serious AEs were collected up to 76 weeks All-cause mortality, non-serious AEs and SAEs were collected in Intent-to-Treat Population which comprised of all randomized participants who received at least one dose of study treatment.	0.00% 0/238 • All cause mortality, non-serious adverse events (AEs) and serious AEs were collected up to 76 weeks All-cause mortality, non-serious AEs and SAEs were collected in Intent-to-Treat Population which comprised of all randomized participants who received at least one dose of study treatment.
Renal and urinary disorders Haematuria	0.00% 0/239 • All cause mortality, non-serious adverse events (AEs) and serious AEs were collected up to 76 weeks All-cause mortality, non-serious AEs and SAEs were collected in Intent-to-Treat Population which comprised of all randomized participants who received at least one dose of study treatment.	0.42% 1/238 • Number of events 1 • All cause mortality, non-serious adverse events (AEs) and serious AEs were collected up to 76 weeks All-cause mortality, non-serious AEs and SAEs were collected in Intent-to-Treat Population which comprised of all randomized participants who received at least one dose of study treatment.
Reproductive system and breast disorders Testicular appendage torsion	0.42% 1/239 • Number of events 1 • All cause mortality, non-serious adverse events (AEs) and serious AEs were collected up to 76 weeks All-cause mortality, non-serious AEs and SAEs were collected in Intent-to-Treat Population which comprised of all randomized participants who received at least one dose of study treatment.	0.00% 0/238 • All cause mortality, non-serious adverse events (AEs) and serious AEs were collected up to 76 weeks All-cause mortality, non-serious AEs and SAEs were collected in Intent-to-Treat Population which comprised of all randomized participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Asthma	0.84% 2/239 • Number of events 2 • All cause mortality, non-serious adverse events (AEs) and serious AEs were collected up to 76 weeks All-cause mortality, non-serious AEs and SAEs were collected in Intent-to-Treat Population which comprised of all randomized participants who received at least one dose of study treatment.	0.00% 0/238 • All cause mortality, non-serious adverse events (AEs) and serious AEs were collected up to 76 weeks All-cause mortality, non-serious AEs and SAEs were collected in Intent-to-Treat Population which comprised of all randomized participants who received at least one dose of study treatment.

Other adverse events

Other adverse events
Measure	Placebo n=239 participants at risk Participants received a single-blind placebo inhaler during a 16-week run-in period. After run-in period inhaled placebo was administered once daily (OD) in the morning for 52 weeks during the double-blind treatment period. Participants also received open-label montelukast one tablet orally in the evening (4 milligrams \[mg\] for participants who were 5 years old and 5 mg for participants who were greater than or equal to \[\>=\] 6 years old) as background therapy from the run-in period through to the end of follow-up (8 weeks) period.	FF 50 mcg n=238 participants at risk Participants received received a single-blind placebo inhaler during a 16-week run-in period. After run-in period inhaled FF 50 mcg was administered via ELLIPTA inhaler once daily in the morning for 52 weeks during double-blind treatment period. Participants also received open-label montelukast one tablet orally in the evening (4 mg for participants who were 5 years old and 5 mg for participants who were \>=6 years old) as background therapy from the run-in period through to the end of follow-up (8 weeks) period.
General disorders Pyrexia	7.5% 18/239 • Number of events 23 • All cause mortality, non-serious adverse events (AEs) and serious AEs were collected up to 76 weeks All-cause mortality, non-serious AEs and SAEs were collected in Intent-to-Treat Population which comprised of all randomized participants who received at least one dose of study treatment.	5.5% 13/238 • Number of events 15 • All cause mortality, non-serious adverse events (AEs) and serious AEs were collected up to 76 weeks All-cause mortality, non-serious AEs and SAEs were collected in Intent-to-Treat Population which comprised of all randomized participants who received at least one dose of study treatment.
Infections and infestations Bronchitis	5.0% 12/239 • Number of events 13 • All cause mortality, non-serious adverse events (AEs) and serious AEs were collected up to 76 weeks All-cause mortality, non-serious AEs and SAEs were collected in Intent-to-Treat Population which comprised of all randomized participants who received at least one dose of study treatment.	3.8% 9/238 • Number of events 11 • All cause mortality, non-serious adverse events (AEs) and serious AEs were collected up to 76 weeks All-cause mortality, non-serious AEs and SAEs were collected in Intent-to-Treat Population which comprised of all randomized participants who received at least one dose of study treatment.
Infections and infestations Influenza	2.9% 7/239 • Number of events 8 • All cause mortality, non-serious adverse events (AEs) and serious AEs were collected up to 76 weeks All-cause mortality, non-serious AEs and SAEs were collected in Intent-to-Treat Population which comprised of all randomized participants who received at least one dose of study treatment.	4.6% 11/238 • Number of events 11 • All cause mortality, non-serious adverse events (AEs) and serious AEs were collected up to 76 weeks All-cause mortality, non-serious AEs and SAEs were collected in Intent-to-Treat Population which comprised of all randomized participants who received at least one dose of study treatment.
Infections and infestations Nasopharyngitis	10.5% 25/239 • Number of events 31 • All cause mortality, non-serious adverse events (AEs) and serious AEs were collected up to 76 weeks All-cause mortality, non-serious AEs and SAEs were collected in Intent-to-Treat Population which comprised of all randomized participants who received at least one dose of study treatment.	9.7% 23/238 • Number of events 26 • All cause mortality, non-serious adverse events (AEs) and serious AEs were collected up to 76 weeks All-cause mortality, non-serious AEs and SAEs were collected in Intent-to-Treat Population which comprised of all randomized participants who received at least one dose of study treatment.
Infections and infestations Pharyngitis	3.8% 9/239 • Number of events 10 • All cause mortality, non-serious adverse events (AEs) and serious AEs were collected up to 76 weeks All-cause mortality, non-serious AEs and SAEs were collected in Intent-to-Treat Population which comprised of all randomized participants who received at least one dose of study treatment.	1.3% 3/238 • Number of events 3 • All cause mortality, non-serious adverse events (AEs) and serious AEs were collected up to 76 weeks All-cause mortality, non-serious AEs and SAEs were collected in Intent-to-Treat Population which comprised of all randomized participants who received at least one dose of study treatment.
Infections and infestations Respiratory tract infection viral	1.7% 4/239 • Number of events 7 • All cause mortality, non-serious adverse events (AEs) and serious AEs were collected up to 76 weeks All-cause mortality, non-serious AEs and SAEs were collected in Intent-to-Treat Population which comprised of all randomized participants who received at least one dose of study treatment.	4.2% 10/238 • Number of events 11 • All cause mortality, non-serious adverse events (AEs) and serious AEs were collected up to 76 weeks All-cause mortality, non-serious AEs and SAEs were collected in Intent-to-Treat Population which comprised of all randomized participants who received at least one dose of study treatment.
Infections and infestations Rhinitis	7.5% 18/239 • Number of events 26 • All cause mortality, non-serious adverse events (AEs) and serious AEs were collected up to 76 weeks All-cause mortality, non-serious AEs and SAEs were collected in Intent-to-Treat Population which comprised of all randomized participants who received at least one dose of study treatment.	6.7% 16/238 • Number of events 18 • All cause mortality, non-serious adverse events (AEs) and serious AEs were collected up to 76 weeks All-cause mortality, non-serious AEs and SAEs were collected in Intent-to-Treat Population which comprised of all randomized participants who received at least one dose of study treatment.
Infections and infestations Upper respiratory tract infection	13.8% 33/239 • Number of events 57 • All cause mortality, non-serious adverse events (AEs) and serious AEs were collected up to 76 weeks All-cause mortality, non-serious AEs and SAEs were collected in Intent-to-Treat Population which comprised of all randomized participants who received at least one dose of study treatment.	12.2% 29/238 • Number of events 63 • All cause mortality, non-serious adverse events (AEs) and serious AEs were collected up to 76 weeks All-cause mortality, non-serious AEs and SAEs were collected in Intent-to-Treat Population which comprised of all randomized participants who received at least one dose of study treatment.
Nervous system disorders Headache	5.0% 12/239 • Number of events 24 • All cause mortality, non-serious adverse events (AEs) and serious AEs were collected up to 76 weeks All-cause mortality, non-serious AEs and SAEs were collected in Intent-to-Treat Population which comprised of all randomized participants who received at least one dose of study treatment.	4.2% 10/238 • Number of events 17 • All cause mortality, non-serious adverse events (AEs) and serious AEs were collected up to 76 weeks All-cause mortality, non-serious AEs and SAEs were collected in Intent-to-Treat Population which comprised of all randomized participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Cough	6.3% 15/239 • Number of events 23 • All cause mortality, non-serious adverse events (AEs) and serious AEs were collected up to 76 weeks All-cause mortality, non-serious AEs and SAEs were collected in Intent-to-Treat Population which comprised of all randomized participants who received at least one dose of study treatment.	5.0% 12/238 • Number of events 15 • All cause mortality, non-serious adverse events (AEs) and serious AEs were collected up to 76 weeks All-cause mortality, non-serious AEs and SAEs were collected in Intent-to-Treat Population which comprised of all randomized participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	3.8% 9/239 • Number of events 11 • All cause mortality, non-serious adverse events (AEs) and serious AEs were collected up to 76 weeks All-cause mortality, non-serious AEs and SAEs were collected in Intent-to-Treat Population which comprised of all randomized participants who received at least one dose of study treatment.	3.4% 8/238 • Number of events 9 • All cause mortality, non-serious adverse events (AEs) and serious AEs were collected up to 76 weeks All-cause mortality, non-serious AEs and SAEs were collected in Intent-to-Treat Population which comprised of all randomized participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	3.3% 8/239 • Number of events 10 • All cause mortality, non-serious adverse events (AEs) and serious AEs were collected up to 76 weeks All-cause mortality, non-serious AEs and SAEs were collected in Intent-to-Treat Population which comprised of all randomized participants who received at least one dose of study treatment.	1.3% 3/238 • Number of events 3 • All cause mortality, non-serious adverse events (AEs) and serious AEs were collected up to 76 weeks All-cause mortality, non-serious AEs and SAEs were collected in Intent-to-Treat Population which comprised of all randomized participants who received at least one dose of study treatment.

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