Trial Outcomes & Findings for Efficacy and Safety of Fluticasone Propionate(FP)/ Salmeterol Xinafoate (SLM) Hydro Fluoro Alkane (HFA) Metered Dose Inhaler (MDI) in Pediatric Patients With Bronchial Asthma (NCT NCT02113436)

Last Updated: 2017-06-16

Results Overview

The participant's parent or legally acceptable representative made entries asthma symptom experienced by the participant in a patient diary twice daily (day time and night time) in the form of scores on a 4-point rating scale from Baseline (Week -1) until end of TP1 (Week 8). Scores ranged from 0 to 3(0: one, 1: mild, 2: moderate, 3: severe) and maximum score is 6 per day. The Baseline value is a mean value of the last 7 consecutive days during the run-in period (excluding the day of Visit 2 \[Randomization\]). The end of the TP1 value is a mean value of the last 7 consecutive days during the TP1 (excluding the last day of the TP1). Change from Baseline is the difference between the value of the endpoint at the time point of interest and the Baseline value. Participants who completed TP1 and completed their diary were analyzed.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

300 participants

Primary outcome timeframe

Baseline and Week 8

Results posted on

2017-06-16

Participant Flow

Study evaluated the efficacy and safety of fluticasone propionate (FP)/salmeterol xinafoate hydrofluoroalkane (SLM HFA) twice-daily (BID) via metered-dose inhaler (MDI) for 8 weeks in comparison with FP HFA in 6-months to 4-years-old Japanese participants (par.) with infantile bronchial asthma.

Eligible par. at screening entered a 2-week run-in period to receive FP HFA MDI 50 µg, followed by 8-week double-blind treatment period (TP) 1 to receive FP/SLM HFA MDI 50/25 µg or FP HFA MDI 50 µg. In TP2, par. received FP/SLM HFA MDI 50/25 µg for 16 weeks. The total duration of the study was 27 weeks with follow-up.

Participant milestones

Participant milestones
Measure	FP HFA 50 µg In TP1, participants were randomized to receive one or two inhalations of FP HFA 50 µg BID for 8 weeks via a MDI using AeroChamber Plus with face mask. Salbutamol was provided as a rescue medication.	FP/SLM HFA 50/25 µg In TP1, participants were randomized to receive one or two inhalations of FP/SLM HFA 50/25 µg BID for 8 weeks via a MDI using AeroChamber Plus with face mask. Salbutamol was provided as a rescue medication.	FP HFA 50 µg - FP/SLM HFA 50/25 µg 1 or 2 inhalations of FP/SLM HFA MDI 50/25 μg were administered twice daily in TP2 to those participants who received FP HFA MDI 50 μg in TP1.	FP/SLM 50/25 µg - FP/SLM 50/25 µg 1 or 2 inhalations of FP/SLM HFA MDI 50/25 μg were administered twice daily in TP2 to those participants who received FP/SLM HFA MDI 50/25 μg in TP1.
Period 1: 8 Weeks STARTED	150	150	0	0
Period 1: 8 Weeks COMPLETED	142	148	0	0
Period 1: 8 Weeks NOT COMPLETED	8	2	0	0
Period 2: 16 Weeks STARTED	0	0	141	147
Period 2: 16 Weeks COMPLETED	0	0	132	136
Period 2: 16 Weeks NOT COMPLETED	0	0	9	11

Reasons for withdrawal

Reasons for withdrawal
Measure	FP HFA 50 µg In TP1, participants were randomized to receive one or two inhalations of FP HFA 50 µg BID for 8 weeks via a MDI using AeroChamber Plus with face mask. Salbutamol was provided as a rescue medication.	FP/SLM HFA 50/25 µg In TP1, participants were randomized to receive one or two inhalations of FP/SLM HFA 50/25 µg BID for 8 weeks via a MDI using AeroChamber Plus with face mask. Salbutamol was provided as a rescue medication.	FP HFA 50 µg - FP/SLM HFA 50/25 µg 1 or 2 inhalations of FP/SLM HFA MDI 50/25 μg were administered twice daily in TP2 to those participants who received FP HFA MDI 50 μg in TP1.	FP/SLM 50/25 µg - FP/SLM 50/25 µg 1 or 2 inhalations of FP/SLM HFA MDI 50/25 μg were administered twice daily in TP2 to those participants who received FP/SLM HFA MDI 50/25 μg in TP1.
Period 1: 8 Weeks Adverse Event	1	0	0	0
Period 1: 8 Weeks Protocol Violation	1	0	0	0
Period 1: 8 Weeks Par. Reached Stopping Criteria	5	2	0	0
Period 1: 8 Weeks Withdrawal by Subject	1	0	0	0
Period 2: 16 Weeks Adverse Event	0	0	4	5
Period 2: 16 Weeks Par. Reached Stopping Criteria	0	0	2	5
Period 2: 16 Weeks Physician Decision	0	0	2	0
Period 2: 16 Weeks Withdrawal by Subject	0	0	1	1

Baseline Characteristics

Efficacy and Safety of Fluticasone Propionate(FP)/ Salmeterol Xinafoate (SLM) Hydro Fluoro Alkane (HFA) Metered Dose Inhaler (MDI) in Pediatric Patients With Bronchial Asthma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	FP HFA 50 µg n=150 Participants In TP1, participants were randomized to receive one or two inhalations of FP HFA 50 µg BID for 8 weeks via a MDI using AeroChamber Plus with face mask. Salbutamol was provided as a rescue medication.	FP/SLM HFA 50/25 µg n=150 Participants In TP1, participants were randomized to receive one or two inhalations of FP/SLM HFA 50/25 µg BID for 8 weeks via a MDI using AeroChamber Plus with face mask. Salbutamol was provided as a rescue medication.	Total n=300 Participants Total of all reporting groups
Age, Continuous Overall Study	38.4 Months STANDARD_DEVIATION 14.10 • n=93 Participants	40.5 Months STANDARD_DEVIATION 14.07 • n=4 Participants	39.5 Months STANDARD_DEVIATION 14.11 • n=27 Participants
Sex: Female, Male Female	60 Participants n=93 Participants	55 Participants n=4 Participants	115 Participants n=27 Participants
Sex: Female, Male Male	90 Participants n=93 Participants	95 Participants n=4 Participants	185 Participants n=27 Participants
Race/Ethnicity, Customized Asian - Japanese Heritage	150 Participants n=93 Participants	150 Participants n=4 Participants	300 Participants n=27 Participants

PRIMARY outcome

Timeframe: Baseline and Week 8

Population: ITT Population: all randomized par. who received at least one dose of study medication.

Outcome measures

Outcome measures
Measure	FP HFA 50 µg n=142 Participants In TP1, participants were randomized to receive one or two inhalations of FP HFA 50 µg BID for 8 weeks via a MDI using AeroChamber Plus with face mask. Salbutamol was provided as a rescue medication.	FP/SLM HFA 50/25 µg n=148 Participants In TP1, participants were randomized to receive one or two inhalations of FP/SLM HFA 50/25 µg BID for 8 weeks via a MDI using AeroChamber Plus with face mask. Salbutamol was provided as a rescue medication.
Mean Change From Baseline in Total Asthma Symptom Score (Daytime Plus Night Time) at the End of the Treatment Period 1 (TP1)	-3.01 Scores on a scale Standard Error 0.545	-3.97 Scores on a scale Standard Error 0.534

SECONDARY outcome

Timeframe: Baseline and Week 8

Population: ITT Population

The participant's parent or legally acceptable representative recorded asthma symptoms experienced by the participant during the night in a patient diary in the form of scores on a 4-point rating scale from Baseline (Week -1) until end of TP1 (Week 8). Scores ranged from 0 to 3(0: one, 1: mild, 2: moderate, 3: severe) and maximum score is 3 per day. Change from Baseline in the asthma symptom scores at night time at the end of TP1 was analyzed. The Baseline value is a mean value of the last 7 consecutive days during the run-in period (excluding the day of Visit 2 \[Randomization\]). The end of the TP1 value is a mean value of the last 7 consecutive days during the TP1 (excluding the last day of the TP1). Change from Baseline is the difference between the value of the endpoint at the time point of interest and the Baseline value. Participants who completed TP1 and completed their diary were analyzed.

Outcome measures

Outcome measures
Measure	FP HFA 50 µg n=142 Participants In TP1, participants were randomized to receive one or two inhalations of FP HFA 50 µg BID for 8 weeks via a MDI using AeroChamber Plus with face mask. Salbutamol was provided as a rescue medication.	FP/SLM HFA 50/25 µg n=148 Participants In TP1, participants were randomized to receive one or two inhalations of FP/SLM HFA 50/25 µg BID for 8 weeks via a MDI using AeroChamber Plus with face mask. Salbutamol was provided as a rescue medication.
Mean Change From Baseline in Night-time Asthma Symptoms Score at the End of Treatment Period 1 (TP1)	-1.61 Scores on a scale Standard Error 0.292	-2.10 Scores on a scale Standard Error 0.286

SECONDARY outcome

Timeframe: Baseline and Week 8

Population: ITT Population.

The participant's parent or legally acceptable representative recorded asthma symptoms experienced by the participant during the day in a patient diary in the form of scores on a 4-point rating scale from Baseline (Week -1) until end of TP1 (Week 8). Scores ranged from 0 to 3(0: one, 1: mild, 2: moderate, 3: severe) and maximum score is 3 per day. Change from Baseline in the asthma symptom scores at day time at the end of TP1 was analyzed. The Baseline value is a mean value of the last 7 consecutive days during the run-in period (excluding the day of Visit 2 \[Randomization\]). The end of the TP1 value is a mean value of the last 7 consecutive days during the TP1 (excluding the last day of the TP1). Change from Baseline is the difference between the value of the endpoint at the time point of interest and the Baseline value. Participants who completed TP1 and completed their diary were analyzed.

Outcome measures

Outcome measures
Measure	FP HFA 50 µg n=142 Participants In TP1, participants were randomized to receive one or two inhalations of FP HFA 50 µg BID for 8 weeks via a MDI using AeroChamber Plus with face mask. Salbutamol was provided as a rescue medication.	FP/SLM HFA 50/25 µg n=148 Participants In TP1, participants were randomized to receive one or two inhalations of FP/SLM HFA 50/25 µg BID for 8 weeks via a MDI using AeroChamber Plus with face mask. Salbutamol was provided as a rescue medication.
Mean Change From Baseline in Daytime Asthma Symptoms Score at the End of Treatment Period 1 (TP1)	-1.39 Scores on a scale Standard Error 0.287	-1.87 Scores on a scale Standard Error 0.281

SECONDARY outcome

Timeframe: Up to 8 weeks

Population: ITT Population

The definition of exacerbations was amended during the study. \<Original\> An exacerbation is defined as deterioration of asthma requiring the use of systemic corticosteroids (oral, parenteral, or depot) for at least 3 days or an in-patient hospitalization or emergency department visit due to asthma that required systemic corticosteroids. \<Amendment\> An asthma exacerbation is defined as deterioration of asthma requiring the use of prednisone or hydrocortisone equivalent systemic corticosteroids for at least 3 days, or requiring the use of dexamethasone or betametasone equivalent systemic corticosteroids (oral, intravenous or intramuscular), or requiring the use of systemic depot corticosteroids once, or an in-patient hospitalization that required treatment for respiratory symptom with wheezing, or emergency department visit due to asthma that required intravenous systemic corticosteroids.

Outcome measures

Outcome measures
Measure	FP HFA 50 µg n=147 Participants In TP1, participants were randomized to receive one or two inhalations of FP HFA 50 µg BID for 8 weeks via a MDI using AeroChamber Plus with face mask. Salbutamol was provided as a rescue medication.	FP/SLM HFA 50/25 µg n=150 Participants In TP1, participants were randomized to receive one or two inhalations of FP/SLM HFA 50/25 µg BID for 8 weeks via a MDI using AeroChamber Plus with face mask. Salbutamol was provided as a rescue medication.
Number of Participants With at Least One Asthma Exacerbation in Treatment Period 1 (TP1)	8 Participants	4 Participants

SECONDARY outcome

Timeframe: Baseline and Week 8

Population: ITT Population

Severity and control statuses based on Japanese pediatric guideline for the treatment and management of asthma (JPGL) can be assessed according to JPAC. Theoretically range of JPAC score was 0 (poor control) to 18 (complete control) point. JPAC questionnaire was recorded at Baseline (Week -2) and Week 8 by the participant's parent or legally acceptable representative who knew the participant's asthma for the last month. Change from Baseline is the difference between the value of the endpoint at the time point of interest and the Baseline value. Participants who completed TP1 were analyzed.

Outcome measures

Outcome measures
Measure	FP HFA 50 µg n=142 Participants In TP1, participants were randomized to receive one or two inhalations of FP HFA 50 µg BID for 8 weeks via a MDI using AeroChamber Plus with face mask. Salbutamol was provided as a rescue medication.	FP/SLM HFA 50/25 µg n=148 Participants In TP1, participants were randomized to receive one or two inhalations of FP/SLM HFA 50/25 µg BID for 8 weeks via a MDI using AeroChamber Plus with face mask. Salbutamol was provided as a rescue medication.
Mean Change From Baseline in Japanese Pediatric Asthma Control Program (JPAC) Score at the End of Treatment Period 1 (TP1)	-0.3 Scores on a scale Standard Error 0.25	0.4 Scores on a scale Standard Error 0.24

SECONDARY outcome

Timeframe: Baseline and Week 8

Population: ITT Population

The number of inhalations of rescue salbutamol inhalation aerosol (medication used to relieve symptoms immediately) used during the day and night was recorded by the participant's parent or legally acceptable representative twice daily in a patient diary from Baseline (Week -1) until Week 8. A 24-hour period in which a participant's responses to both the morning and evening assessments indicated no use of rescue medication was considered as rescue free. Participants who were rescue free for 24-hour periods during the 8 weeks in TP1 were assessed. The Baseline value was derived from the last 7 days of the patient diary prior to the randomization of the participant. Change from Baseline is the difference between the value of the endpoint at the time point of interest and the Baseline value. Participants who completed TP1 and completed their diary were analyzed.

Outcome measures

Outcome measures
Measure	FP HFA 50 µg n=142 Participants In TP1, participants were randomized to receive one or two inhalations of FP HFA 50 µg BID for 8 weeks via a MDI using AeroChamber Plus with face mask. Salbutamol was provided as a rescue medication.	FP/SLM HFA 50/25 µg n=148 Participants In TP1, participants were randomized to receive one or two inhalations of FP/SLM HFA 50/25 µg BID for 8 weeks via a MDI using AeroChamber Plus with face mask. Salbutamol was provided as a rescue medication.
Mean Change From Baseline in Use of Rescue Medication (Number of Occasions Used During a 24-hour Period) in Treatment Period 1 (TP1)	0.07 Occasions per 24 hours Standard Error 0.048	0.01 Occasions per 24 hours Standard Error 0.047

SECONDARY outcome

Timeframe: Baseline and Week 8

Population: ITT Population

The number of inhalations of rescue salbutamol inhalation aerosol (medication used to relieve symptoms immediately) used during the day and night was recorded by the participant's parent or legally acceptable representative twice daily in a patient diary. A 24-hour period in which a participant's responses to both the morning and evening assessments indicated no use of rescue medication was considered as rescue free. Participants who were rescue free for 24-hour periods during the 8-week Treatment Period were assessed. The Baseline value was derived from the last 7 days of the patient diary prior to the randomization of the participant. Change from Baseline is the difference between the value of the endpoint at the time point of interest and the Baseline value. Participants who completed TP1 and completed their diary were analyzed.

Outcome measures

Outcome measures
Measure	FP HFA 50 µg n=142 Participants In TP1, participants were randomized to receive one or two inhalations of FP HFA 50 µg BID for 8 weeks via a MDI using AeroChamber Plus with face mask. Salbutamol was provided as a rescue medication.	FP/SLM HFA 50/25 µg n=148 Participants In TP1, participants were randomized to receive one or two inhalations of FP/SLM HFA 50/25 µg BID for 8 weeks via a MDI using AeroChamber Plus with face mask. Salbutamol was provided as a rescue medication.
Mean Change From Baseline in Use of Rescue Medication (Percentage of Days With Rescue-free 24-hour Period) at the End of Treatment Period 1 (TP1)	-2.9 Percentage of days Standard Error 2.16	-0.3 Percentage of days Standard Error 2.11

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: ITT Population

The participant's parent or legally acceptable representative recorded asthma symptoms experienced by the participant in a patient diary twice daily (daytime and night time) in the form of scores on a 4-point rating scale from Baseline (Week -1) until end of TP2 (Week 24). Scores ranged from 0 (none) to 3 (severe) and maximum score is 6 per day. Change from Baseline in the asthma symptom scores at daytime plus night time at the end of TP2 was analyzed. The Baseline value is a mean value of the last 7 consecutive days during the run-in period (excluding the day of Visit 2 \[Randomization\]).The end of the TP2 value is a mean value of the last 7 consecutive days during the TP2 (excluding the last day of the TP2). Change from Baseline is the difference between the value of the endpoint at the time point of interest and the Baseline value. Participants who received at least one dose of open-label medication in the TP2 were analyzed.

Outcome measures

Outcome measures
Measure	FP HFA 50 µg n=141 Participants In TP1, participants were randomized to receive one or two inhalations of FP HFA 50 µg BID for 8 weeks via a MDI using AeroChamber Plus with face mask. Salbutamol was provided as a rescue medication.	FP/SLM HFA 50/25 µg n=147 Participants In TP1, participants were randomized to receive one or two inhalations of FP/SLM HFA 50/25 µg BID for 8 weeks via a MDI using AeroChamber Plus with face mask. Salbutamol was provided as a rescue medication.
Mean Change From Baseline in Total Asthma Symptom Score (Daytime Plus Night Time) at the End of the Treatment Period 2 (TP2)	-5.29 Scores on a scale Standard Deviation 6.422	-6.10 Scores on a scale Standard Deviation 7.665

Adverse Events

Period 1 - FP HFA 50 µg

Serious events: 5 serious events

Other events: 109 other events

Deaths: 0 deaths

Period 1 - FP/SLM HFA 50/25 µg

Serious events: 1 serious events

Other events: 111 other events

Deaths: 0 deaths

Period 2 - FP/SLM HFA 50/25 μg

Serious events: 20 serious events

Other events: 262 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Publication restrictions are in place

Restriction type: OTHER

Measure	Period 1 - FP HFA 50 µg n=150 participants at risk In TP1, participants were randomized to receive one or two inhalations of FP HFA 50 µg BID for 8 weeks via a MDI using AeroChamber Plus with face mask. Salbutamol was provided as a rescue medication.	Period 1 - FP/SLM HFA 50/25 µg n=150 participants at risk In TP1, participants were randomized to receive one or two inhalations of FP/SLM HFA 50/25 µg BID for 8 weeks via a MDI using AeroChamber Plus with face mask. Salbutamol was provided as a rescue medication.	Period 2 - FP/SLM HFA 50/25 μg n=288 participants at risk 1 or 2 inhalations of FP/SLM HFA MDI 50/25 μg were administered twice daily in TP2 to those participants who received FP HFA MDI 50 μg or FP/SLM HFA MDI 50/25 µg in TP1.
Respiratory, thoracic and mediastinal disorders Asthma	2.7% 4/150 • All on-treatment serious adverse events (SAEs) and non-serious AEs were collected for 25 weeks in Treatment Period 1 and Treatment Period 2 On-treatment AEs and SAEs are reported for the ITT Population.	0.00% 0/150 • All on-treatment serious adverse events (SAEs) and non-serious AEs were collected for 25 weeks in Treatment Period 1 and Treatment Period 2 On-treatment AEs and SAEs are reported for the ITT Population.	2.8% 8/288 • All on-treatment serious adverse events (SAEs) and non-serious AEs were collected for 25 weeks in Treatment Period 1 and Treatment Period 2 On-treatment AEs and SAEs are reported for the ITT Population.
Infections and infestations Bronchitis	0.00% 0/150 • All on-treatment serious adverse events (SAEs) and non-serious AEs were collected for 25 weeks in Treatment Period 1 and Treatment Period 2 On-treatment AEs and SAEs are reported for the ITT Population.	0.67% 1/150 • All on-treatment serious adverse events (SAEs) and non-serious AEs were collected for 25 weeks in Treatment Period 1 and Treatment Period 2 On-treatment AEs and SAEs are reported for the ITT Population.	0.35% 1/288 • All on-treatment serious adverse events (SAEs) and non-serious AEs were collected for 25 weeks in Treatment Period 1 and Treatment Period 2 On-treatment AEs and SAEs are reported for the ITT Population.
Infections and infestations Gastroenteritis	0.67% 1/150 • All on-treatment serious adverse events (SAEs) and non-serious AEs were collected for 25 weeks in Treatment Period 1 and Treatment Period 2 On-treatment AEs and SAEs are reported for the ITT Population.	0.00% 0/150 • All on-treatment serious adverse events (SAEs) and non-serious AEs were collected for 25 weeks in Treatment Period 1 and Treatment Period 2 On-treatment AEs and SAEs are reported for the ITT Population.	0.35% 1/288 • All on-treatment serious adverse events (SAEs) and non-serious AEs were collected for 25 weeks in Treatment Period 1 and Treatment Period 2 On-treatment AEs and SAEs are reported for the ITT Population.
Infections and infestations Upper respiratory tract infection	0.67% 1/150 • All on-treatment serious adverse events (SAEs) and non-serious AEs were collected for 25 weeks in Treatment Period 1 and Treatment Period 2 On-treatment AEs and SAEs are reported for the ITT Population.	0.00% 0/150 • All on-treatment serious adverse events (SAEs) and non-serious AEs were collected for 25 weeks in Treatment Period 1 and Treatment Period 2 On-treatment AEs and SAEs are reported for the ITT Population.	0.00% 0/288 • All on-treatment serious adverse events (SAEs) and non-serious AEs were collected for 25 weeks in Treatment Period 1 and Treatment Period 2 On-treatment AEs and SAEs are reported for the ITT Population.
Infections and infestations Pneumonia	0.00% 0/150 • All on-treatment serious adverse events (SAEs) and non-serious AEs were collected for 25 weeks in Treatment Period 1 and Treatment Period 2 On-treatment AEs and SAEs are reported for the ITT Population.	0.00% 0/150 • All on-treatment serious adverse events (SAEs) and non-serious AEs were collected for 25 weeks in Treatment Period 1 and Treatment Period 2 On-treatment AEs and SAEs are reported for the ITT Population.	2.4% 7/288 • All on-treatment serious adverse events (SAEs) and non-serious AEs were collected for 25 weeks in Treatment Period 1 and Treatment Period 2 On-treatment AEs and SAEs are reported for the ITT Population.
Infections and infestations Herpangina	0.00% 0/150 • All on-treatment serious adverse events (SAEs) and non-serious AEs were collected for 25 weeks in Treatment Period 1 and Treatment Period 2 On-treatment AEs and SAEs are reported for the ITT Population.	0.00% 0/150 • All on-treatment serious adverse events (SAEs) and non-serious AEs were collected for 25 weeks in Treatment Period 1 and Treatment Period 2 On-treatment AEs and SAEs are reported for the ITT Population.	0.35% 1/288 • All on-treatment serious adverse events (SAEs) and non-serious AEs were collected for 25 weeks in Treatment Period 1 and Treatment Period 2 On-treatment AEs and SAEs are reported for the ITT Population.
Infections and infestations Otitis media acute	0.00% 0/150 • All on-treatment serious adverse events (SAEs) and non-serious AEs were collected for 25 weeks in Treatment Period 1 and Treatment Period 2 On-treatment AEs and SAEs are reported for the ITT Population.	0.00% 0/150 • All on-treatment serious adverse events (SAEs) and non-serious AEs were collected for 25 weeks in Treatment Period 1 and Treatment Period 2 On-treatment AEs and SAEs are reported for the ITT Population.	0.35% 1/288 • All on-treatment serious adverse events (SAEs) and non-serious AEs were collected for 25 weeks in Treatment Period 1 and Treatment Period 2 On-treatment AEs and SAEs are reported for the ITT Population.
Infections and infestations Pneumonia bacterial	0.00% 0/150 • All on-treatment serious adverse events (SAEs) and non-serious AEs were collected for 25 weeks in Treatment Period 1 and Treatment Period 2 On-treatment AEs and SAEs are reported for the ITT Population.	0.00% 0/150 • All on-treatment serious adverse events (SAEs) and non-serious AEs were collected for 25 weeks in Treatment Period 1 and Treatment Period 2 On-treatment AEs and SAEs are reported for the ITT Population.	0.35% 1/288 • All on-treatment serious adverse events (SAEs) and non-serious AEs were collected for 25 weeks in Treatment Period 1 and Treatment Period 2 On-treatment AEs and SAEs are reported for the ITT Population.
Infections and infestations Pseudocroup	0.00% 0/150 • All on-treatment serious adverse events (SAEs) and non-serious AEs were collected for 25 weeks in Treatment Period 1 and Treatment Period 2 On-treatment AEs and SAEs are reported for the ITT Population.	0.00% 0/150 • All on-treatment serious adverse events (SAEs) and non-serious AEs were collected for 25 weeks in Treatment Period 1 and Treatment Period 2 On-treatment AEs and SAEs are reported for the ITT Population.	0.35% 1/288 • All on-treatment serious adverse events (SAEs) and non-serious AEs were collected for 25 weeks in Treatment Period 1 and Treatment Period 2 On-treatment AEs and SAEs are reported for the ITT Population.
Infections and infestations Tracheobronchitis mycoplasmal	0.00% 0/150 • All on-treatment serious adverse events (SAEs) and non-serious AEs were collected for 25 weeks in Treatment Period 1 and Treatment Period 2 On-treatment AEs and SAEs are reported for the ITT Population.	0.00% 0/150 • All on-treatment serious adverse events (SAEs) and non-serious AEs were collected for 25 weeks in Treatment Period 1 and Treatment Period 2 On-treatment AEs and SAEs are reported for the ITT Population.	0.35% 1/288 • All on-treatment serious adverse events (SAEs) and non-serious AEs were collected for 25 weeks in Treatment Period 1 and Treatment Period 2 On-treatment AEs and SAEs are reported for the ITT Population.
Infections and infestations Viral pharyngitis	0.00% 0/150 • All on-treatment serious adverse events (SAEs) and non-serious AEs were collected for 25 weeks in Treatment Period 1 and Treatment Period 2 On-treatment AEs and SAEs are reported for the ITT Population.	0.00% 0/150 • All on-treatment serious adverse events (SAEs) and non-serious AEs were collected for 25 weeks in Treatment Period 1 and Treatment Period 2 On-treatment AEs and SAEs are reported for the ITT Population.	0.35% 1/288 • All on-treatment serious adverse events (SAEs) and non-serious AEs were collected for 25 weeks in Treatment Period 1 and Treatment Period 2 On-treatment AEs and SAEs are reported for the ITT Population.
Injury, poisoning and procedural complications Skull fracture	0.00% 0/150 • All on-treatment serious adverse events (SAEs) and non-serious AEs were collected for 25 weeks in Treatment Period 1 and Treatment Period 2 On-treatment AEs and SAEs are reported for the ITT Population.	0.00% 0/150 • All on-treatment serious adverse events (SAEs) and non-serious AEs were collected for 25 weeks in Treatment Period 1 and Treatment Period 2 On-treatment AEs and SAEs are reported for the ITT Population.	0.35% 1/288 • All on-treatment serious adverse events (SAEs) and non-serious AEs were collected for 25 weeks in Treatment Period 1 and Treatment Period 2 On-treatment AEs and SAEs are reported for the ITT Population.
Injury, poisoning and procedural complications Skull fractured base	0.00% 0/150 • All on-treatment serious adverse events (SAEs) and non-serious AEs were collected for 25 weeks in Treatment Period 1 and Treatment Period 2 On-treatment AEs and SAEs are reported for the ITT Population.	0.00% 0/150 • All on-treatment serious adverse events (SAEs) and non-serious AEs were collected for 25 weeks in Treatment Period 1 and Treatment Period 2 On-treatment AEs and SAEs are reported for the ITT Population.	0.35% 1/288 • All on-treatment serious adverse events (SAEs) and non-serious AEs were collected for 25 weeks in Treatment Period 1 and Treatment Period 2 On-treatment AEs and SAEs are reported for the ITT Population.
Injury, poisoning and procedural complications Subdural haemorrhage	0.00% 0/150 • All on-treatment serious adverse events (SAEs) and non-serious AEs were collected for 25 weeks in Treatment Period 1 and Treatment Period 2 On-treatment AEs and SAEs are reported for the ITT Population.	0.00% 0/150 • All on-treatment serious adverse events (SAEs) and non-serious AEs were collected for 25 weeks in Treatment Period 1 and Treatment Period 2 On-treatment AEs and SAEs are reported for the ITT Population.	0.35% 1/288 • All on-treatment serious adverse events (SAEs) and non-serious AEs were collected for 25 weeks in Treatment Period 1 and Treatment Period 2 On-treatment AEs and SAEs are reported for the ITT Population.
Nervous system disorders Febrile convulsion	0.00% 0/150 • All on-treatment serious adverse events (SAEs) and non-serious AEs were collected for 25 weeks in Treatment Period 1 and Treatment Period 2 On-treatment AEs and SAEs are reported for the ITT Population.	0.00% 0/150 • All on-treatment serious adverse events (SAEs) and non-serious AEs were collected for 25 weeks in Treatment Period 1 and Treatment Period 2 On-treatment AEs and SAEs are reported for the ITT Population.	0.35% 1/288 • All on-treatment serious adverse events (SAEs) and non-serious AEs were collected for 25 weeks in Treatment Period 1 and Treatment Period 2 On-treatment AEs and SAEs are reported for the ITT Population.
Skin and subcutaneous tissue disorders Henoch-Schonlein purpura	0.00% 0/150 • All on-treatment serious adverse events (SAEs) and non-serious AEs were collected for 25 weeks in Treatment Period 1 and Treatment Period 2 On-treatment AEs and SAEs are reported for the ITT Population.	0.00% 0/150 • All on-treatment serious adverse events (SAEs) and non-serious AEs were collected for 25 weeks in Treatment Period 1 and Treatment Period 2 On-treatment AEs and SAEs are reported for the ITT Population.	0.35% 1/288 • All on-treatment serious adverse events (SAEs) and non-serious AEs were collected for 25 weeks in Treatment Period 1 and Treatment Period 2 On-treatment AEs and SAEs are reported for the ITT Population.