Trial Outcomes & Findings for A 12-Week Study To Assess The Safety Of Fluticasone Propionate/Salmeterol 100/50 Hydrofluoroalkane (HFA) Versus Fluticasone Propionate 100 HFA In Children With Asthma (NCT NCT00441441)

NCT ID: NCT00441441

Last Updated: 2016-12-16

Results Overview

Adverse Events reported by the Investigator and judged by the Investigator to be possibly related to study drug, categorized by the Medical Dictionary for Regulatory Activities (MeDRA), were reported. ECG, electrocardiogram. QTc (corrected QT interval) and QT represent intervals on an ECG.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 351 participants
• Primary outcome timeframe: Treatment period (weeks 1-12) and Post Treatment (≥1 day after last time study drug)
• Results posted on: 2016-12-16

Participant Flow

A total of 351 participants were enrolled in the study. However, only 350 of these 351 participants comprised the Intent-to-Treat Population, defined as all participants who were randomly assigned to treatment and received >=1 dose of Double-Blind study treatment.

Participant milestones

Measure	Fluticasone Propionate/Salmeterol Hydrofluoroalkane (HFA) Participants who were randomly assigned to Fluticasone Propionate/salmeterol 100/50 micrograms (µg) HFA (2 inhalations of 50/25 µg), twice daily for 12 weeks.	Fluticasone Propionate HFA Participants who were randomly assigned to Fluticasone Propionate 100 µg HFA (2 inhalations of 50 µg), twice daily for 12 weeks.
Overall Study STARTED	173	177
Overall Study COMPLETED	162	163
Overall Study NOT COMPLETED	11	14

Reasons for withdrawal

Measure	Fluticasone Propionate/Salmeterol Hydrofluoroalkane (HFA) Participants who were randomly assigned to Fluticasone Propionate/salmeterol 100/50 micrograms (µg) HFA (2 inhalations of 50/25 µg), twice daily for 12 weeks.	Fluticasone Propionate HFA Participants who were randomly assigned to Fluticasone Propionate 100 µg HFA (2 inhalations of 50 µg), twice daily for 12 weeks.
Overall Study Adverse Event	2	1
Overall Study Protocol Violation	4	6
Overall Study Exacerbation of asthma	1	2
Overall Study Withdrawal by Subject	1	2
Overall Study Other	3	3

Baseline Characteristics

A 12-Week Study To Assess The Safety Of Fluticasone Propionate/Salmeterol 100/50 Hydrofluoroalkane (HFA) Versus Fluticasone Propionate 100 HFA In Children With Asthma

Baseline characteristics by cohort

Measure	Fluticasone Propionate/Salmeterol HFA n=173 Participants Participants who were randomly assigned to Fluticasone Propionate/salmeterol 100/50 micrograms (µg) HFA (2 inhalations of 50/25 µg), twice daily for 12 weeks.	Fluticasone Propionate HFA n=177 Participants Participants who were randomly assigned to Fluticasone Propionate 100 µg HFA (2 inhalations of 50 µg), twice daily for 12 weeks.	Total n=350 Participants Total of all reporting groups
Age, Customized 4-5 years	36 participants n=5 Participants	41 participants n=7 Participants	77 participants n=5 Participants
Age, Customized 6-11 years	137 participants n=5 Participants	136 participants n=7 Participants	273 participants n=5 Participants
Gender Female	66 Participants n=5 Participants	71 Participants n=7 Participants	137 Participants n=5 Participants
Gender Male	107 Participants n=5 Participants	106 Participants n=7 Participants	213 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	70 Participants n=5 Participants	73 Participants n=7 Participants	143 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	103 Participants n=5 Participants	104 Participants n=7 Participants	207 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized White/Caucasian/European Heritage	114 participants n=5 Participants	113 participants n=7 Participants	227 participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	24 participants n=5 Participants	27 participants n=7 Participants	51 participants n=5 Participants
Race/Ethnicity, Customized Central/South Asian Heritage	8 participants n=5 Participants	8 participants n=7 Participants	16 participants n=5 Participants
Race/Ethnicity, Customized African American/African Heritage	7 participants n=5 Participants	8 participants n=7 Participants	15 participants n=5 Participants
Race/Ethnicity, Customized Japanese Heritage	3 participants n=5 Participants	0 participants n=7 Participants	3 participants n=5 Participants
Race/Ethnicity, Customized Arabic/North African Heritage	2 participants n=5 Participants	2 participants n=7 Participants	4 participants n=5 Participants
Race/Ethnicity, Customized South East Asian Heritage	2 participants n=5 Participants	0 participants n=7 Participants	2 participants n=5 Participants
Race/Ethnicity, Customized Mixed Race	13 participants n=5 Participants	19 participants n=7 Participants	32 participants n=5 Participants

PRIMARY outcome

Timeframe: Treatment period (weeks 1-12) and Post Treatment (≥1 day after last time study drug)

Population: Intent-to-Treat (IITT) Population - All participants who were randomized and received at least one dose of double-blind study treatment.

Adverse Events reported by the Investigator and judged by the Investigator to be possibly related to study drug, categorized by the Medical Dictionary for Regulatory Activities (MeDRA), were reported. ECG, electrocardiogram. QTc (corrected QT interval) and QT represent intervals on an ECG.

Outcome measures

Measure	Fluticasone Propionate/Salmeterol HFA n=173 Participants Participants who were randomly assigned to Fluticasone Propionate/salmeterol 100/50 micrograms (µg) HFA (2 inhalations of 50/25 µg), twice daily for 12 weeks.	Fluticasone Propionate HFA n=177 Participants Participants who were randomly assigned to Fluticasone Propionate 100 µg HFA (2 inhalations of 50 µg), twice daily for 12 weeks.	Fluticasone Propionate HFA - Spacer Fluticasone Propionate 100 µg HFA (2 inhalation of 50 µg) twice daily in participants 4-11 years of age for 12 weeks. Participants who also used Spacers	Fluticasone Propionate HFA - No Spacer Fluticasone Propionate 100 µg HFA (2 inhalation of 50 µg) twice daily in participants 4-11 years of age for 12 weeks
Possible Drug-Related Adverse Events Investigations - ECG QTc interval prolonged	9 participants	4 participants	—	—
Possible Drug-Related Adverse Events Investigations - QT interval prolonged	0 participants	2 participants	—	—
Possible Drug-Related Adverse Events Respiratory/thoracic/mediastinal - Dysphonia	2 participants	0 participants	—	—
Possible Drug-Related Adverse Events Participants with any drug-related event	13 participants	16 participants	—	—
Possible Drug-Related Adverse Events Investigations - ECG QT borderline prolonged	1 participants	0 participants	—	—
Possible Drug-Related Adverse Events Investigations - ECG QT interval abnormal	1 participants	0 participants	—	—
Possible Drug-Related Adverse Events Cardiac - Defect conduction intraventricular	2 participants	7 participants	—	—
Possible Drug-Related Adverse Events Cardiac - Conduction disorder	1 participants	1 participants	—	—
Possible Drug-Related Adverse Events Cardiac - Sinus tachycardia	1 participants	0 participants	—	—
Possible Drug-Related Adverse Events Cardiac - Supraventricular ectopics	0 participants	1 participants	—	—
Possible Drug-Related Adverse Events Infections/Infestations - Oral candidiasis	0 participants	1 participants	—	—
Possible Drug-Related Adverse Events Infections/Infest - Oropharyngeal candidiasis	0 participants	1 participants	—	—

PRIMARY outcome

Timeframe: Baseline and Week 12

Population: ITT Population. The number of participants at baseline was 173 and 177, respectively, for the Fluticasone propionate/salmeterol HFA and Fluticasone Propionate (FP) HFA groups. The number of participants at Week 12 was 162 and 160, respectively. Data for 6 participants in the FP treatment arm were either not obtained or not evaluable.

ECGs were transmitted to an independent cardiologist who was responsible for providing interpretation of the ECG as either normal or abnormal (based on personal assessment). The investigator was then responsible for determining the clinical significance of the abnormal ECG in the context of the participants' history and clinical presentation. An abnormal, clinically significant ECG included, but was not limited to: prolonged QT interval, ischemic changes, ventricular hypertrophy, intraventricular conduction abnormalities, and clinically significant arrhythmias. PD, premature discontinuation.

Outcome measures

Measure	Fluticasone Propionate/Salmeterol HFA n=173 Participants Participants who were randomly assigned to Fluticasone Propionate/salmeterol 100/50 micrograms (µg) HFA (2 inhalations of 50/25 µg), twice daily for 12 weeks.	Fluticasone Propionate HFA n=177 Participants Participants who were randomly assigned to Fluticasone Propionate 100 µg HFA (2 inhalations of 50 µg), twice daily for 12 weeks.	Fluticasone Propionate HFA - Spacer Fluticasone Propionate 100 µg HFA (2 inhalation of 50 µg) twice daily in participants 4-11 years of age for 12 weeks. Participants who also used Spacers	Fluticasone Propionate HFA - No Spacer Fluticasone Propionate 100 µg HFA (2 inhalation of 50 µg) twice daily in participants 4-11 years of age for 12 weeks
Investigator Evaluations of Electrocardiogram (ECG) Results Baseline - Normal	145 participants	155 participants	—	—
Investigator Evaluations of Electrocardiogram (ECG) Results Baseline - Abnormal: Not Clinically Significant	27 participants	21 participants	—	—
Investigator Evaluations of Electrocardiogram (ECG) Results Baseline - Abnormal: Clinically Significant	1 participants	0 participants	—	—
Investigator Evaluations of Electrocardiogram (ECG) Results Week 12-Clinically Significant Change-Favorable	2 participants	0 participants	—	—
Investigator Evaluations of Electrocardiogram (ECG) Results Week 12-Clinically Significant Change-Unfavorable	24 participants	18 participants	—	—
Investigator Evaluations of Electrocardiogram (ECG) Results PD-No Change or insignificant Change	7 participants	9 participants	—	—
Investigator Evaluations of Electrocardiogram (ECG) Results PD-Clinically Significant Change-Favorable	0 participants	1 participants	—	—
Investigator Evaluations of Electrocardiogram (ECG) Results PD-Clinically Significant Change-Unfavorable	0 participants	1 participants	—	—
Investigator Evaluations of Electrocardiogram (ECG) Results Week 12-No Change or insignificant Change	136 participants	142 participants	—	—

PRIMARY outcome

Timeframe: Baseline, Week 12

Population: ITT Population. The number of participants at baseline was 173 and 177, respectively, for the Fluticasone propionate/salmeterol HFA and Fluticasone Propionate (FP) HFA groups. The numbers of participants at Week 12 were 162 and 160, respectively. Data for 6 participants in the FP treatment arm were either not obtained or not evaluable.

Post-randomization ECGs categorized by the primary investigator as no change, significant change (favorable), significant change (unfavorable) from the ECG performed at Visit 1 (Baseline) are presented. Significant change (favorable) includes any ECG that improved from baseline, whereas significant change (unfavorable) includes any ECG that worsened from baseline. Clinical significance is determined by the primary investigator.

Outcome measures

Measure	Fluticasone Propionate/Salmeterol HFA n=173 Participants Participants who were randomly assigned to Fluticasone Propionate/salmeterol 100/50 micrograms (µg) HFA (2 inhalations of 50/25 µg), twice daily for 12 weeks.	Fluticasone Propionate HFA n=177 Participants Participants who were randomly assigned to Fluticasone Propionate 100 µg HFA (2 inhalations of 50 µg), twice daily for 12 weeks.	Fluticasone Propionate HFA - Spacer Fluticasone Propionate 100 µg HFA (2 inhalation of 50 µg) twice daily in participants 4-11 years of age for 12 weeks. Participants who also used Spacers	Fluticasone Propionate HFA - No Spacer Fluticasone Propionate 100 µg HFA (2 inhalation of 50 µg) twice daily in participants 4-11 years of age for 12 weeks
Clinically Significant Unfavorable ECGs at Week 12 AEs Reported for ECG findings	22 participants	18 participants	—	—
Clinically Significant Unfavorable ECGs at Week 12 Clinically significant unfavorable ECGs repeated	11 participants	11 participants	—	—
Clinically Significant Unfavorable ECGs at Week 12 Repeated ECGs w/ no change or insignificant change	6 participants	5 participants	—	—
Clinically Significant Unfavorable ECGs at Week 12 Clinically significant unfavorable change	24 participants	18 participants	—	—

PRIMARY outcome

Timeframe: Baseline and Week 12

Population: ITT Population - All subjects who were randomized and received at least one dose of double-blind study treatment.

The range of heart rates for this study was between 49-144 beats per minute

Outcome measures

Measure	Fluticasone Propionate/Salmeterol HFA n=173 Participants Participants who were randomly assigned to Fluticasone Propionate/salmeterol 100/50 micrograms (µg) HFA (2 inhalations of 50/25 µg), twice daily for 12 weeks.	Fluticasone Propionate HFA n=177 Participants Participants who were randomly assigned to Fluticasone Propionate 100 µg HFA (2 inhalations of 50 µg), twice daily for 12 weeks.	Fluticasone Propionate HFA - Spacer Fluticasone Propionate 100 µg HFA (2 inhalation of 50 µg) twice daily in participants 4-11 years of age for 12 weeks. Participants who also used Spacers	Fluticasone Propionate HFA - No Spacer Fluticasone Propionate 100 µg HFA (2 inhalation of 50 µg) twice daily in participants 4-11 years of age for 12 weeks
ECG Measures - Heart Rate Mean Heart Rate - Baseline	84 beats per minute Interval 53.0 to 144.0	82.6 beats per minute Interval 51.0 to 136.0	—	—
ECG Measures - Heart Rate Mean Heart Rate - Week 12	85.5 beats per minute Interval 59.0 to 138.0	81.9 beats per minute Interval 52.0 to 121.0	—	—
ECG Measures - Heart Rate Mean Heart Rate - Premature Discontinuation	73.1 beats per minute Interval 53.0 to 90.0	92.4 beats per minute Interval 49.0 to 130.0	—	—

PRIMARY outcome

Timeframe: Baseline and Week 12

Population: ITT Population - All participants who were randomized and received at least one dose of double-blind study treatment.

Fridericia's formula QTc interval=QT interval/cubed root of the R-R interval. The Bazett's formula QTc=QT/squared root of the R-R interval.

Outcome measures

Measure	Fluticasone Propionate/Salmeterol HFA n=173 Participants Participants who were randomly assigned to Fluticasone Propionate/salmeterol 100/50 micrograms (µg) HFA (2 inhalations of 50/25 µg), twice daily for 12 weeks.	Fluticasone Propionate HFA n=177 Participants Participants who were randomly assigned to Fluticasone Propionate 100 µg HFA (2 inhalations of 50 µg), twice daily for 12 weeks.	Fluticasone Propionate HFA - Spacer Fluticasone Propionate 100 µg HFA (2 inhalation of 50 µg) twice daily in participants 4-11 years of age for 12 weeks. Participants who also used Spacers	Fluticasone Propionate HFA - No Spacer Fluticasone Propionate 100 µg HFA (2 inhalation of 50 µg) twice daily in participants 4-11 years of age for 12 weeks
ECG Measures - QT Interval Mean QTc Interval (Fridericia)- Baseline	394.5 milliseconds Interval 340.0 to 449.0	390.8 milliseconds Interval 338.0 to 429.0	—	—
ECG Measures - QT Interval Mean QTc Interval (Fridericia) - Week 12	397.5 milliseconds Interval 355.0 to 439.0	393.6 milliseconds Interval 329.0 to 449.0	—	—
ECG Measures - QT Interval Mean QTc Interval (Bazett) - Week 12	420.8 milliseconds Interval 368.0 to 466.0	413.7 milliseconds Interval 351.0 to 477.0	—	—
ECG Measures - QT Interval Premature Discontinuation (Bazett)	403.3 milliseconds Interval 376.0 to 446.0	422.7 milliseconds Interval 378.0 to 454.0	—	—
ECG Measures - QT Interval Premature Discontinuation (Fridericia)	392 milliseconds Interval 359.0 to 417.0	394.8 milliseconds Interval 376.0 to 408.0	—	—
ECG Measures - QT Interval Mean QTc Interval (Bazett) - Baseline	416.3 milliseconds Interval 356.0 to 464.0	411.4 milliseconds Interval 346.0 to 471.0	—	—

PRIMARY outcome

Timeframe: 12-Week Treatment Period

Population: ITT Population - All participants who were randomized and received at least one dose of double-blind study treatment.

Cardiovascular Adverse Events, as categorized by the Medical Dictionary for Regulatory Activities (MeDRA), reported during Treatment Period. The Adverse Events were identified in any ECG interpretation by a central reader (Cardiologist) for any ECG obtained after the first treatment dose and were then reported by the Primary Investigator as an Adverse Event. Please see the category titles for a list of candidate cardiovascular adverse events.

Outcome measures

Measure	Fluticasone Propionate/Salmeterol HFA n=173 Participants Participants who were randomly assigned to Fluticasone Propionate/salmeterol 100/50 micrograms (µg) HFA (2 inhalations of 50/25 µg), twice daily for 12 weeks.	Fluticasone Propionate HFA n=177 Participants Participants who were randomly assigned to Fluticasone Propionate 100 µg HFA (2 inhalations of 50 µg), twice daily for 12 weeks.	Fluticasone Propionate HFA - Spacer Fluticasone Propionate 100 µg HFA (2 inhalation of 50 µg) twice daily in participants 4-11 years of age for 12 weeks. Participants who also used Spacers	Fluticasone Propionate HFA - No Spacer Fluticasone Propionate 100 µg HFA (2 inhalation of 50 µg) twice daily in participants 4-11 years of age for 12 weeks
Cardiovascular Adverse Events Reported During Treatment Period Electrocardiogram (ECG) Change	3 participants	2 participants	—	—
Cardiovascular Adverse Events Reported During Treatment Period ECG Abnormal	1 participants	1 participants	—	—
Cardiovascular Adverse Events Reported During Treatment Period Defect Conduction Intraventricular	4 participants	3 participants	—	—
Cardiovascular Adverse Events Reported During Treatment Period Cardiac Arrhythmia	1 participants	0 participants	—	—
Cardiovascular Adverse Events Reported During Treatment Period Participants with Any Event	98 participants	103 participants	—	—
Cardiovascular Adverse Events Reported During Treatment Period ECG QTc Interval Prolonged	2 participants	1 participants	—	—
Cardiovascular Adverse Events Reported During Treatment Period ECG QT Borderline Prolonged	1 participants	0 participants	—	—
Cardiovascular Adverse Events Reported During Treatment Period Premature Atrial Contraction	1 participants	0 participants	—	—

PRIMARY outcome

Timeframe: 5 Days after Week 12

Population: ITT Population - All participants who were randomized and received at least one dose of double-blind study treatment.

Cardiovascular Adverse Events, as categorized by the Medical Dictionary for Regulatory Activities (MeDRA), reported during Post-treatment period, defined as 1 day after last dose of study drug. The Adverse Events were identified in any ECG interpretation by a central reader (Cardiologist) for any ECG obtained after the first treatment dose and were then reported by the Primary Investigator as an Adverse Event.

Outcome measures

Measure	Fluticasone Propionate/Salmeterol HFA n=173 Participants Participants who were randomly assigned to Fluticasone Propionate/salmeterol 100/50 micrograms (µg) HFA (2 inhalations of 50/25 µg), twice daily for 12 weeks.	Fluticasone Propionate HFA n=177 Participants Participants who were randomly assigned to Fluticasone Propionate 100 µg HFA (2 inhalations of 50 µg), twice daily for 12 weeks.	Fluticasone Propionate HFA - Spacer Fluticasone Propionate 100 µg HFA (2 inhalation of 50 µg) twice daily in participants 4-11 years of age for 12 weeks. Participants who also used Spacers	Fluticasone Propionate HFA - No Spacer Fluticasone Propionate 100 µg HFA (2 inhalation of 50 µg) twice daily in participants 4-11 years of age for 12 weeks
Cardiovascular Adverse Events Reported During the Post-Treatment Period Participants with Any Event	19 participants	19 participants	—	—
Cardiovascular Adverse Events Reported During the Post-Treatment Period ECG QTc interval prolonged	11 participants	5 participants	—	—
Cardiovascular Adverse Events Reported During the Post-Treatment Period ECG QT interval Abnormal	1 participants	0 participants	—	—
Cardiovascular Adverse Events Reported During the Post-Treatment Period Defect Conduction Intraventricular	2 participants	7 participants	—	—
Cardiovascular Adverse Events Reported During the Post-Treatment Period Conduction disorder	1 participants	1 participants	—	—
Cardiovascular Adverse Events Reported During the Post-Treatment Period Sinus Tachycardia	1 participants	0 participants	—	—
Cardiovascular Adverse Events Reported During the Post-Treatment Period Supraventricular Ectopics	0 participants	1 participants	—	—
Cardiovascular Adverse Events Reported During the Post-Treatment Period QT interval prolonged	1 participants	2 participants	—	—

PRIMARY outcome

Timeframe: Treatment period (weeks 1-12)

Population: ITT Population - All participants who were randomized and received at least one dose of double-blind study treatment.

The Primary Investigator determined the severity of the exacerbation based on the participant's clinical presentation and the investigator's understanding of the disease, the participant, and his or her clinical experiences. The severity of the exacerbation was not defined in the protocol. Mild: Usually treated at home. Prompt relief with inhaled short-acting beta2 agonist. Possible short course of oral systemic corticosteroids. Moderate: Usually requires office or emergency department visit. Relief with frequent inhaled short-acting beta2 agonist. Oral systemic corticosteroids; some symptoms last for 1-2 days after treatment begins. Severe: Usually requires emergency department visit and likely hospitalization. Partial relief with frequent inhaled short-acting beta2 agonist. Oral systemic corticosteroids; some symptoms last for more than 3 days after treatment begins. Adjunctive therapies are helpful.

Outcome measures

Measure	Fluticasone Propionate/Salmeterol HFA n=173 Participants Participants who were randomly assigned to Fluticasone Propionate/salmeterol 100/50 micrograms (µg) HFA (2 inhalations of 50/25 µg), twice daily for 12 weeks.	Fluticasone Propionate HFA n=177 Participants Participants who were randomly assigned to Fluticasone Propionate 100 µg HFA (2 inhalations of 50 µg), twice daily for 12 weeks.	Fluticasone Propionate HFA - Spacer Fluticasone Propionate 100 µg HFA (2 inhalation of 50 µg) twice daily in participants 4-11 years of age for 12 weeks. Participants who also used Spacers	Fluticasone Propionate HFA - No Spacer Fluticasone Propionate 100 µg HFA (2 inhalation of 50 µg) twice daily in participants 4-11 years of age for 12 weeks
Asthma Exacerbations: Worsening of Asthma Requiring Emergency Intervention, Hospitalization, or Treatment With Asthma Medications Prohibited by the Protocols Participants with any asthma exacerbation	1 participants	3 participants	—	—
Asthma Exacerbations: Worsening of Asthma Requiring Emergency Intervention, Hospitalization, or Treatment With Asthma Medications Prohibited by the Protocols Severity - Mild	1 participants	2 participants	—	—
Asthma Exacerbations: Worsening of Asthma Requiring Emergency Intervention, Hospitalization, or Treatment With Asthma Medications Prohibited by the Protocols Severity - Moderate/Severe	0 participants	1 participants	—	—
Asthma Exacerbations: Worsening of Asthma Requiring Emergency Intervention, Hospitalization, or Treatment With Asthma Medications Prohibited by the Protocols Withdrawal due to Asthma Exacerbation	1 participants	2 participants	—	—

PRIMARY outcome

Timeframe: Baseline and week 12

Population: Cortisol Population - all participants not excluded due to the following reasons: missing data, use of protocol-specified corticosteroids (prior to screening), collection time outside of 24 ± 2 hours, use of inhaled cortical steroid (ICS) during treatment, and who stopped study medication \>1 day prior to start of post-baseline urine collection.

"Abnormal high cortisol excretion" and "Abnormal low cortisol excretion" are defined as above the upper limit of normal and below the lower limit of normal, respectively. The normal range for cortisol levels vary by age and gender. An abnormality is defined as a value of 24-hour urinary cortisol excretion that is outside the normal range. The normal range for 24-hour urinary cortisol excretion was provided by the central laboratory.

Outcome measures

Measure	Fluticasone Propionate/Salmeterol HFA n=147 Participants Participants who were randomly assigned to Fluticasone Propionate/salmeterol 100/50 micrograms (µg) HFA (2 inhalations of 50/25 µg), twice daily for 12 weeks.	Fluticasone Propionate HFA n=144 Participants Participants who were randomly assigned to Fluticasone Propionate 100 µg HFA (2 inhalations of 50 µg), twice daily for 12 weeks.	Fluticasone Propionate HFA - Spacer Fluticasone Propionate 100 µg HFA (2 inhalation of 50 µg) twice daily in participants 4-11 years of age for 12 weeks. Participants who also used Spacers	Fluticasone Propionate HFA - No Spacer Fluticasone Propionate 100 µg HFA (2 inhalation of 50 µg) twice daily in participants 4-11 years of age for 12 weeks
Number of Participants With the Indicated Levels of 24-hour Urinary Cortisol Excretion Baseline - Abnormal high cortisol excretion, n	13 participants	17 participants	—	—
Number of Participants With the Indicated Levels of 24-hour Urinary Cortisol Excretion Baseline - Abnormal low cortisol excretion, n	1 participants	0 participants	—	—
Number of Participants With the Indicated Levels of 24-hour Urinary Cortisol Excretion Week 12 - Abnormal high cortisol excretion, n	13 participants	8 participants	—	—
Number of Participants With the Indicated Levels of 24-hour Urinary Cortisol Excretion Week 12 - Abnormal low cortisol excretion, n	2 participants	0 participants	—	—

PRIMARY outcome

Timeframe: Baseline and Week 12

Population: Cortisol Population

Normal range for Cortisol levels vary by age and gender. Geometric mean is the product of the values taken to the Nth root, where N is the number of values in the set of values.

Outcome measures

Measure	Fluticasone Propionate/Salmeterol HFA n=147 Participants Participants who were randomly assigned to Fluticasone Propionate/salmeterol 100/50 micrograms (µg) HFA (2 inhalations of 50/25 µg), twice daily for 12 weeks.	Fluticasone Propionate HFA n=144 Participants Participants who were randomly assigned to Fluticasone Propionate 100 µg HFA (2 inhalations of 50 µg), twice daily for 12 weeks.	Fluticasone Propionate HFA - Spacer Fluticasone Propionate 100 µg HFA (2 inhalation of 50 µg) twice daily in participants 4-11 years of age for 12 weeks. Participants who also used Spacers	Fluticasone Propionate HFA - No Spacer Fluticasone Propionate 100 µg HFA (2 inhalation of 50 µg) twice daily in participants 4-11 years of age for 12 weeks
Geometric Mean Values of 24-hour Urinary Cortisol Excretion at Baseline and Week 12 Baseline - Geometric Mean	32.71 Nanomoles per 24 hours (nmol/24 hrs) Interval 2.7 to 156.2	30.88 Nanomoles per 24 hours (nmol/24 hrs) Interval 4.2 to 891.6	—	—
Geometric Mean Values of 24-hour Urinary Cortisol Excretion at Baseline and Week 12 Week 12 - Geometric Mean	25.03 Nanomoles per 24 hours (nmol/24 hrs) Interval 1.7 to 152.6	23.17 Nanomoles per 24 hours (nmol/24 hrs) Interval 5.3 to 145.8	—	—

PRIMARY outcome

Timeframe: Baseline and Week 12

Population: Cortisol Population

Normal range for Cortisol levels vary by age and gender. The data provided are a direct calculation of the Week 12 geometric mean divided by the baseline value, nanomoles per 24 hours (nmol/24 hrs).

Outcome measures

Measure	Fluticasone Propionate/Salmeterol HFA n=147 Participants Participants who were randomly assigned to Fluticasone Propionate/salmeterol 100/50 micrograms (µg) HFA (2 inhalations of 50/25 µg), twice daily for 12 weeks.	Fluticasone Propionate HFA n=144 Participants Participants who were randomly assigned to Fluticasone Propionate 100 µg HFA (2 inhalations of 50 µg), twice daily for 12 weeks.	Fluticasone Propionate HFA - Spacer Fluticasone Propionate 100 µg HFA (2 inhalation of 50 µg) twice daily in participants 4-11 years of age for 12 weeks. Participants who also used Spacers	Fluticasone Propionate HFA - No Spacer Fluticasone Propionate 100 µg HFA (2 inhalation of 50 µg) twice daily in participants 4-11 years of age for 12 weeks
Geometric Mean Ratio for Week12:Baseline for 24-hour Urinary Cortisol Excretion	0.77 ratio	0.75 ratio	—	—

PRIMARY outcome

Timeframe: Baseline and Week 12

Population: Cortisol Population

AeroChamber Plus spacers were provided for participants who demonstrated the inability to coordinate the use of an Meter Dose Inhaler at Visit 1. AeroChamber Plus spacer delivers 22% more medication than the original AeroChamber and is available in three mask sizes and without a mask. "Abnormal high cortisol excretion" and "Abnormal low cortisol excretion" are defined as above the upper limit of normal and below the lower limit of normal, respectively. An abnormality is defined as a value of 24-hour urinary cortisol excretion that is outside the normal range. The normal range for 24-hour urinary cortisol excretion was provided by the central laboratory.

Outcome measures

Measure	Fluticasone Propionate/Salmeterol HFA n=115 Participants Participants who were randomly assigned to Fluticasone Propionate/salmeterol 100/50 micrograms (µg) HFA (2 inhalations of 50/25 µg), twice daily for 12 weeks.	Fluticasone Propionate HFA n=32 Participants Participants who were randomly assigned to Fluticasone Propionate 100 µg HFA (2 inhalations of 50 µg), twice daily for 12 weeks.	Fluticasone Propionate HFA - Spacer n=113 Participants Fluticasone Propionate 100 µg HFA (2 inhalation of 50 µg) twice daily in participants 4-11 years of age for 12 weeks. Participants who also used Spacers	Fluticasone Propionate HFA - No Spacer n=31 Participants Fluticasone Propionate 100 µg HFA (2 inhalation of 50 µg) twice daily in participants 4-11 years of age for 12 weeks
Number of Participants With the Indicated Levels of 24 Hour Urinary Cortisol Excretion by Spacer Use Baseline - Abnormal high cortisol excretion	12 participants	1 participants	14 participants	3 participants
Number of Participants With the Indicated Levels of 24 Hour Urinary Cortisol Excretion by Spacer Use Baseline - Abnormal low cortisol excretion	0 participants	1 participants	0 participants	0 participants
Number of Participants With the Indicated Levels of 24 Hour Urinary Cortisol Excretion by Spacer Use Week 12 - Abnormal high cortisol excretion	10 participants	3 participants	7 participants	1 participants
Number of Participants With the Indicated Levels of 24 Hour Urinary Cortisol Excretion by Spacer Use Week 12 - Abnormal low cortisol excretion	2 participants	0 participants	0 participants	0 participants

PRIMARY outcome

Timeframe: Baseline and Week 12

Population: Cortisol Population

AeroChamber Plus spacers were provided for participants who demonstrated the inability to coordinate the use of an Meter Dose Inhaler at Visit 1. AeroChamber Plus spacer delivers 22% more medication than the original AeroChamber and is available in three mask sizes and without a mask. Geometric mean is the product of the values taken to the Nth root, where N is the number of values in the set of values.

Outcome measures

Measure	Fluticasone Propionate/Salmeterol HFA n=115 Participants Participants who were randomly assigned to Fluticasone Propionate/salmeterol 100/50 micrograms (µg) HFA (2 inhalations of 50/25 µg), twice daily for 12 weeks.	Fluticasone Propionate HFA n=32 Participants Participants who were randomly assigned to Fluticasone Propionate 100 µg HFA (2 inhalations of 50 µg), twice daily for 12 weeks.	Fluticasone Propionate HFA - Spacer n=113 Participants Fluticasone Propionate 100 µg HFA (2 inhalation of 50 µg) twice daily in participants 4-11 years of age for 12 weeks. Participants who also used Spacers	Fluticasone Propionate HFA - No Spacer n=31 Participants Fluticasone Propionate 100 µg HFA (2 inhalation of 50 µg) twice daily in participants 4-11 years of age for 12 weeks
Geometric Mean Values of 24 Hour Urinary Cortisol Excretion by Spacer Use at Baseline and Week 12 Baseline - Geometric Mean	31.89 Nanomoles per 24 hours (nmol/24 hrs) Interval 3.6 to 156.2	35.84 Nanomoles per 24 hours (nmol/24 hrs) Interval 2.7 to 143.3	30.61 Nanomoles per 24 hours (nmol/24 hrs) Interval 4.2 to 891.6	31.89 Nanomoles per 24 hours (nmol/24 hrs) Interval 7.9 to 335.0
Geometric Mean Values of 24 Hour Urinary Cortisol Excretion by Spacer Use at Baseline and Week 12 Week 12 - Geometric Mean	23.37 Nanomoles per 24 hours (nmol/24 hrs) Interval 1.7 to 143.3	32.05 Nanomoles per 24 hours (nmol/24 hrs) Interval 4.6 to 152.6	23.20 Nanomoles per 24 hours (nmol/24 hrs) Interval 5.3 to 103.2	23.06 Nanomoles per 24 hours (nmol/24 hrs) Interval 5.4 to 145.8

PRIMARY outcome

Timeframe: Baseline and Week 12

Population: Cortisol Population

AeroChamber Plus spacers were provided for participants who demonstrated the inability to coordinate the use of an Meter Dose Inhaler at Visit 1. AeroChamber Plus spacer delivers 22% more medication than the original AeroChamber and is available in three mask sizes and without a mask. The data provided are a direct calculation of the Week 12 geometric mean divided by the baseline value, nanomoles per 24 hours (nmol/24 hrs).

Outcome measures

Measure	Fluticasone Propionate/Salmeterol HFA n=115 Participants Participants who were randomly assigned to Fluticasone Propionate/salmeterol 100/50 micrograms (µg) HFA (2 inhalations of 50/25 µg), twice daily for 12 weeks.	Fluticasone Propionate HFA n=32 Participants Participants who were randomly assigned to Fluticasone Propionate 100 µg HFA (2 inhalations of 50 µg), twice daily for 12 weeks.	Fluticasone Propionate HFA - Spacer n=113 Participants Fluticasone Propionate 100 µg HFA (2 inhalation of 50 µg) twice daily in participants 4-11 years of age for 12 weeks. Participants who also used Spacers	Fluticasone Propionate HFA - No Spacer n=31 Participants Fluticasone Propionate 100 µg HFA (2 inhalation of 50 µg) twice daily in participants 4-11 years of age for 12 weeks
Geometric Mean Ratio for Week12: Baseline for 24 Hour Urinary Cortisol Excretion by Spacer Use	0.73 ratio	0.89 ratio	0.76 ratio	0.72 ratio

SECONDARY outcome

Timeframe: Baseline and week 12

Population: Subset of ITT Population: Participants who were 6-11 years of age (population not necessarily selected to show efficacy differences). Total numbers of participants analyzed for the Fluticasone propionate (FP)/salmeterol HFA and FP groups, respectively, were 137 and 136 at baseline; 126 and 124 at Week 12, and 6 and 7 at premature discontinuation.

FEV1 (Forced Expiratory Volume in 1 second) is the volume of air that can be forced out in one second, after taking a deep breath. FEV1 is measured using a spirometer and obtaining "best effort" from 3 to 8 measurements. Week 12 is the measure taken at Week 12.

Outcome measures

Measure	Fluticasone Propionate/Salmeterol HFA n=137 Participants Participants who were randomly assigned to Fluticasone Propionate/salmeterol 100/50 micrograms (µg) HFA (2 inhalations of 50/25 µg), twice daily for 12 weeks.	Fluticasone Propionate HFA n=136 Participants Participants who were randomly assigned to Fluticasone Propionate 100 µg HFA (2 inhalations of 50 µg), twice daily for 12 weeks.	Fluticasone Propionate HFA - Spacer Fluticasone Propionate 100 µg HFA (2 inhalation of 50 µg) twice daily in participants 4-11 years of age for 12 weeks. Participants who also used Spacers	Fluticasone Propionate HFA - No Spacer Fluticasone Propionate 100 µg HFA (2 inhalation of 50 µg) twice daily in participants 4-11 years of age for 12 weeks
Clinic Morning (AM) Forced Expiratory Volume in Participants 6-11 Years Week 12 - Mean FEV1	1.91 Liters per second (L/sec) Standard Error 0.038	1.82 Liters per second (L/sec) Standard Error 0.036	—	—
Clinic Morning (AM) Forced Expiratory Volume in Participants 6-11 Years Week 12 - Mean Change from baseline	0.24 Liters per second (L/sec) Standard Error 0.023	0.18 Liters per second (L/sec) Standard Error 0.023	—	—
Clinic Morning (AM) Forced Expiratory Volume in Participants 6-11 Years Premature discontinuation - Mean FEV1	1.81 Liters per second (L/sec) Standard Error 0.14	1.70 Liters per second (L/sec) Standard Error 0.212	—	—
Clinic Morning (AM) Forced Expiratory Volume in Participants 6-11 Years Premature discontin. - Mean Change from baseline	0.03 Liters per second (L/sec) Standard Error 0.09	-0.07 Liters per second (L/sec) Standard Error 0.120	—	—
Clinic Morning (AM) Forced Expiratory Volume in Participants 6-11 Years Baseline - Mean FEV1	1.67 Liters per second (L/sec) Standard Error 0.035	1.64 Liters per second (L/sec) Standard Error 0.035	—	—

SECONDARY outcome

Timeframe: Baseline and 12-Week Treatment Period

Population: Participants from the ITT Population (not necessarily selected to show efficacy differences). Total numbers of participants analyzed for the Fluticasone propionate (FP)/salmeterol HFA and FP groups, respectively, were 173 and 175 at baseline; 173 and 174 at Weeks 1-12; and 171 and 173 for the last 7 days on treatment.

The peak expiratory flow (PEF) rate measures how fast a person can exhale air. It is used to compare to normal flow rates to predict obstruction and disease. The average PEF for a child or adolescent whose height is 43 inches is 147 Liters/minute (L/min), whose height is 66 inches is 454 L/min. Triplicate measurements taken for the best effort recorded.

Outcome measures

Measure	Fluticasone Propionate/Salmeterol HFA n=173 Participants Participants who were randomly assigned to Fluticasone Propionate/salmeterol 100/50 micrograms (µg) HFA (2 inhalations of 50/25 µg), twice daily for 12 weeks.	Fluticasone Propionate HFA n=177 Participants Participants who were randomly assigned to Fluticasone Propionate 100 µg HFA (2 inhalations of 50 µg), twice daily for 12 weeks.	Fluticasone Propionate HFA - Spacer Fluticasone Propionate 100 µg HFA (2 inhalation of 50 µg) twice daily in participants 4-11 years of age for 12 weeks. Participants who also used Spacers	Fluticasone Propionate HFA - No Spacer Fluticasone Propionate 100 µg HFA (2 inhalation of 50 µg) twice daily in participants 4-11 years of age for 12 weeks
AM Peak Expiratory Flow Baseline - Mean AM PEF	213 Liters/minute (L/min) Standard Error 4.83	203 Liters/minute (L/min) Standard Error 4.37	—	—
AM Peak Expiratory Flow Weeks 1-12 - Mean AM PEF	233 Liters/minute (L/min) Standard Error 5.07	220 Liters/minute (L/min) Standard Error 4.43	—	—
AM Peak Expiratory Flow Weeks 1-12 - Mean Change from Baseline	20.2 Liters/minute (L/min) Standard Error 2.04	17.4 Liters/minute (L/min) Standard Error 1.86	—	—
AM Peak Expiratory Flow Last 7 Days on Treatment - Mean AM PEF	238 Liters/minute (L/min) Standard Error 5.39	226 Liters/minute (L/min) Standard Error 4.73	—	—
AM Peak Expiratory Flow Last 7 Days on Treatment-Mean Change from Baseline	25.3 Liters/minute (L/min) Standard Error 2.58	23.3 Liters/minute (L/min) Standard Error 2.47	—	—

SECONDARY outcome

Timeframe: Baseline and 12-Week Treatment Period

Population: Participants from the ITT population (not necessarily selected to show efficacy differences). Total numbers of participants analyzed for the Fluticasone propionate (FP)/salmeterol HFA and FP groups, respectively, were 173 and 175 at baseline; 172 and 174 at Weeks 1-12; and 167 and 170 for the last 7 days on treatment.

Each morning prior dosing or PEF, self-scored based on past 24 hours: 0=No symptoms, 1=Symptoms for one short period, 2=Symptoms for two or more short periods, 3=Frequent Symptoms which did not affect activities of daily living (ADL), 4=Frequent.

Outcome measures

Measure	Fluticasone Propionate/Salmeterol HFA n=177 Participants Participants who were randomly assigned to Fluticasone Propionate/salmeterol 100/50 micrograms (µg) HFA (2 inhalations of 50/25 µg), twice daily for 12 weeks.	Fluticasone Propionate HFA n=173 Participants Participants who were randomly assigned to Fluticasone Propionate 100 µg HFA (2 inhalations of 50 µg), twice daily for 12 weeks.	Fluticasone Propionate HFA - Spacer Fluticasone Propionate 100 µg HFA (2 inhalation of 50 µg) twice daily in participants 4-11 years of age for 12 weeks. Participants who also used Spacers	Fluticasone Propionate HFA - No Spacer Fluticasone Propionate 100 µg HFA (2 inhalation of 50 µg) twice daily in participants 4-11 years of age for 12 weeks
Asthma Symptom Scores Baseline - Mean Score	1.3 Score in scale Standard Error 0.06	1.4 Score in scale Standard Error 0.06	—	—
Asthma Symptom Scores Weeks 1-12 - Mean Score	0.9 Score in scale Standard Error 0.06	0.8 Score in scale Standard Error 0.05	—	—
Asthma Symptom Scores Weeks 1-12 - Mean change from baseline	-0.4 Score in scale Standard Error 0.06	-0.6 Score in scale Standard Error 0.06	—	—
Asthma Symptom Scores Last 7 Days on Treatment - Mean Score	0.8 Score in scale Standard Error 0.07	0.8 Score in scale Standard Error 0.07	—	—
Asthma Symptom Scores Last 7 Days on Treat. - Mean change from baseline	-0.5 Score in scale Standard Error 0.07	-0.6 Score in scale Standard Error 0.08	—	—

SECONDARY outcome

Timeframe: Baseline and 12-Week Treatment Period

Population: Participants from the ITT population (not necessarily selected to show efficacy differences). Total numbers of participants analyzed for the Fluticasone propionate (FP)/salmeterol HFA and FP groups, respectively, were 173 and 175 at baseline; 172 and 174 at Weeks 1-12; and 167 and 170 for the last 7 days on treatment.

Percentage of number of days without asthma symptoms based on Asthma Symptom Scores. Each morning prior to dosing or PEF, asthma symptoms were self-scored based on the past 24 hours: 0=no symptoms, 1=symptoms for one short period, 2=symptoms for two or more short periods, 3=frequent symptoms that did not affect activities of daily living (ADL), 4=frequent .

Outcome measures

Measure	Fluticasone Propionate/Salmeterol HFA n=173 Participants Participants who were randomly assigned to Fluticasone Propionate/salmeterol 100/50 micrograms (µg) HFA (2 inhalations of 50/25 µg), twice daily for 12 weeks.	Fluticasone Propionate HFA n=177 Participants Participants who were randomly assigned to Fluticasone Propionate 100 µg HFA (2 inhalations of 50 µg), twice daily for 12 weeks.	Fluticasone Propionate HFA - Spacer Fluticasone Propionate 100 µg HFA (2 inhalation of 50 µg) twice daily in participants 4-11 years of age for 12 weeks. Participants who also used Spacers	Fluticasone Propionate HFA - No Spacer Fluticasone Propionate 100 µg HFA (2 inhalation of 50 µg) twice daily in participants 4-11 years of age for 12 weeks
Percentage of Symptom Free Days Last 7 Days on Treat. - Mean change from baseline	32.1 Percentage of days Standard Error 3.32	34.9 Percentage of days Standard Error 3.43	—	—
Percentage of Symptom Free Days Baseline - Mean Percent	20.0 Percentage of days Standard Error 2.02	18.4 Percentage of days Standard Error 2.00	—	—
Percentage of Symptom Free Days Weeks 1-12 - Mean Percent	46.7 Percentage of days Standard Error 2.77	48.7 Percentage of days Standard Error 2.80	—	—
Percentage of Symptom Free Days Weeks 1-12 - Mean change from baseline	26.8 Percentage of days Standard Error 2.47	30.5 Percentage of days Standard Error 2.62	—	—
Percentage of Symptom Free Days Last 7 Days on Treatment - Mean Percent	51.9 Percentage of days Standard Error 3.51	53.4 Percentage of days Standard Error 3.44	—	—

SECONDARY outcome

Timeframe: Baseline and 12-Week Treatment Period

Population: Participants from the ITT population (not necessarily selected to show efficacy differences). Total numbers of participants analyzed for the Fluticasone propionate (FP)/salmeterol HFA and FP groups, respectively, were 168 and 174 at baseline; 166 and 172 at Weeks 1-12; and 157 and 165 for the last 7 days on treatment.

Albuterol inhalation aerosol was used as a rescue or prophylactic and recorded daily by subject or caregiver. The number of puffs of albuterol over the previous 24 hour period prior to dosing was recorded.

Outcome measures

Measure	Fluticasone Propionate/Salmeterol HFA n=173 Participants Participants who were randomly assigned to Fluticasone Propionate/salmeterol 100/50 micrograms (µg) HFA (2 inhalations of 50/25 µg), twice daily for 12 weeks.	Fluticasone Propionate HFA n=177 Participants Participants who were randomly assigned to Fluticasone Propionate 100 µg HFA (2 inhalations of 50 µg), twice daily for 12 weeks.	Fluticasone Propionate HFA - Spacer Fluticasone Propionate 100 µg HFA (2 inhalation of 50 µg) twice daily in participants 4-11 years of age for 12 weeks. Participants who also used Spacers	Fluticasone Propionate HFA - No Spacer Fluticasone Propionate 100 µg HFA (2 inhalation of 50 µg) twice daily in participants 4-11 years of age for 12 weeks
Albuterol Use Baseline - Mean number of puffs	1.5 Number of puffs per 24 hours Standard Error 0.12	1.8 Number of puffs per 24 hours Standard Error 0.19	—	—
Albuterol Use Weeks 1-12 - Mean number of puffs	1.0 Number of puffs per 24 hours Standard Error 0.09	0.9 Number of puffs per 24 hours Standard Error 0.09	—	—
Albuterol Use Weeks 1-12 - Mean change from baseline	-0.6 Number of puffs per 24 hours Standard Error 0.12	-1.0 Number of puffs per 24 hours Standard Error 0.16	—	—
Albuterol Use Last 7 Days on Treatment - Mean number of puffs	0.7 Number of puffs per 24 hours Standard Error 0.11	0.7 Number of puffs per 24 hours Standard Error 0.11	—	—
Albuterol Use Last 7 Days on Treat. - Mean change from baseline	0.15 Number of puffs per 24 hours Standard Error 0.8	-1.2 Number of puffs per 24 hours Standard Error 0.19	—	—

SECONDARY outcome

Timeframe: Baseline and 12-Week Treatment Period

Population: Participants from the ITT population (not necessarily selected to show efficacy differences). Total numbers of participants analyzed for the Fluticasone propionate (FP)/salmeterol HFA and FP groups, respectively, were 168 and 174 at baseline; 166 and 172 at Weeks 1-12; and 157 and 165 for the last 7 days on treatment.

Percentage of days when Albuterol use was unnecessary based on daily record and symptom free days.

Outcome measures

Measure	Fluticasone Propionate/Salmeterol HFA n=173 Participants Participants who were randomly assigned to Fluticasone Propionate/salmeterol 100/50 micrograms (µg) HFA (2 inhalations of 50/25 µg), twice daily for 12 weeks.	Fluticasone Propionate HFA n=177 Participants Participants who were randomly assigned to Fluticasone Propionate 100 µg HFA (2 inhalations of 50 µg), twice daily for 12 weeks.	Fluticasone Propionate HFA - Spacer Fluticasone Propionate 100 µg HFA (2 inhalation of 50 µg) twice daily in participants 4-11 years of age for 12 weeks. Participants who also used Spacers	Fluticasone Propionate HFA - No Spacer Fluticasone Propionate 100 µg HFA (2 inhalation of 50 µg) twice daily in participants 4-11 years of age for 12 weeks
Percent of Albuterol-free Days Baseline - Mean percent rescue free	43.7 Percentage of days Standard Error 2.85	42.5 Percentage of days Standard Error 3.04	—	—
Percent of Albuterol-free Days Weeks 1-12 - Mean percent rescue free	67.1 Percentage of days Standard Error 2.46	70.0 Percentage of days Standard Error 2.40	—	—
Percent of Albuterol-free Days Weeks 1-12 - Mean change from baseline	23.6 Percentage of days Standard Error 2.79	28.3 Percentage of days Standard Error 2.93	—	—
Percent of Albuterol-free Days Last 7 Days on Treat. - Mean percent rescue free	75.4 Percentage of days Standard Error 2.96	75.8 Percentage of days Standard Error 2.98	—	—
Percent of Albuterol-free Days Last 7 Days on Treat. - Mean change from baseline	30.4 Percentage of days Standard Error 3.50	32.8 Percentage of days Standard Error 3.58	—	—

POST_HOC outcome

Timeframe: Baseline and Week 12

Population: Cortisol Population

A post-hoc analysis excluding participants with urine cortisol baseline values of >200 nanomoles/24 hours. Geometric mean is the product of the values taken to the Nth root, where N is the number of values in the set of values.

Outcome measures

Measure	Fluticasone Propionate/Salmeterol HFA n=147 Participants Participants who were randomly assigned to Fluticasone Propionate/salmeterol 100/50 micrograms (µg) HFA (2 inhalations of 50/25 µg), twice daily for 12 weeks.	Fluticasone Propionate HFA n=140 Participants Participants who were randomly assigned to Fluticasone Propionate 100 µg HFA (2 inhalations of 50 µg), twice daily for 12 weeks.	Fluticasone Propionate HFA - Spacer Fluticasone Propionate 100 µg HFA (2 inhalation of 50 µg) twice daily in participants 4-11 years of age for 12 weeks. Participants who also used Spacers	Fluticasone Propionate HFA - No Spacer Fluticasone Propionate 100 µg HFA (2 inhalation of 50 µg) twice daily in participants 4-11 years of age for 12 weeks
Geometric Mean Values of 24-hour Urinary Cortisol Excretion at Baseline and Week 12 Baseline - Geometric Mean	32.71 Nanamoles per 24 hours (nmol/24 hrs) Interval 2.7 to 156.2	28.39 Nanamoles per 24 hours (nmol/24 hrs) Interval 4.2 to 146.9	—	—
Geometric Mean Values of 24-hour Urinary Cortisol Excretion at Baseline and Week 12 Week 12 - Geometric Mean	25.03 Nanamoles per 24 hours (nmol/24 hrs) Interval 1.7 to 152.6	22.80 Nanamoles per 24 hours (nmol/24 hrs) Interval 5.3 to 145.8	—	—

POST_HOC outcome

Timeframe: Baseline and Week 12

Population: Cortisol Population

A post-hoc analysis excluding participants with urine cortisol baseline values of >200 nmol/24 hrs. The data provided are a direct calculation of the Week 12 geometric mean divided by the baseline value, nanomoles per 24 hours (nmol/24 hrs) .

Outcome measures

Measure	Fluticasone Propionate/Salmeterol HFA n=147 Participants Participants who were randomly assigned to Fluticasone Propionate/salmeterol 100/50 micrograms (µg) HFA (2 inhalations of 50/25 µg), twice daily for 12 weeks.	Fluticasone Propionate HFA n=140 Participants Participants who were randomly assigned to Fluticasone Propionate 100 µg HFA (2 inhalations of 50 µg), twice daily for 12 weeks.	Fluticasone Propionate HFA - Spacer Fluticasone Propionate 100 µg HFA (2 inhalation of 50 µg) twice daily in participants 4-11 years of age for 12 weeks. Participants who also used Spacers	Fluticasone Propionate HFA - No Spacer Fluticasone Propionate 100 µg HFA (2 inhalation of 50 µg) twice daily in participants 4-11 years of age for 12 weeks
Geometric Mean Ratio for Baseline:Week12 24-hour Urinary Cortisol Excretion	0.77 ratio	0.80 ratio	—	—

POST_HOC outcome

Timeframe: Baseline and Week 12

Population: Cortisol Population

AeroChamber Plus spacers were provided for participants who demonstrated the inability to coordinate the use of an Meter Dose Inhaler at Visit 1. AeroChamber Plus spacer delivers 22% more medication than the original AeroChamber and is available in three mask sizes and without a mask. Geometric mean is the product of the values taken to the Nth root, where N is the number of values in the set of values.

Outcome measures

Measure	Fluticasone Propionate/Salmeterol HFA n=58 Participants Participants who were randomly assigned to Fluticasone Propionate/salmeterol 100/50 micrograms (µg) HFA (2 inhalations of 50/25 µg), twice daily for 12 weeks.	Fluticasone Propionate HFA n=202 Participants Participants who were randomly assigned to Fluticasone Propionate 100 µg HFA (2 inhalations of 50 µg), twice daily for 12 weeks.	Fluticasone Propionate HFA - Spacer Fluticasone Propionate 100 µg HFA (2 inhalation of 50 µg) twice daily in participants 4-11 years of age for 12 weeks. Participants who also used Spacers	Fluticasone Propionate HFA - No Spacer Fluticasone Propionate 100 µg HFA (2 inhalation of 50 µg) twice daily in participants 4-11 years of age for 12 weeks
Geometric Mean Values of 24-hour Urinary Cortisol Excretion by Spacer Use Excluding Participants With Abnormal Urinary Cortisol Excretion Values at Baseline From the Cortisol Population at Baseline and Week 12 Baseline - Geometric Mean	31.88 Nanomoles per 24 hr (nmoles/24 hr) Interval 7.9 to 81.7	27.08 Nanomoles per 24 hr (nmoles/24 hr) Interval 3.6 to 166.3	—	—
Geometric Mean Values of 24-hour Urinary Cortisol Excretion by Spacer Use Excluding Participants With Abnormal Urinary Cortisol Excretion Values at Baseline From the Cortisol Population at Baseline and Week 12 Week 12 - Geometric Mean	27.85 Nanomoles per 24 hr (nmoles/24 hr) Interval 5.4 to 152.6	22.38 Nanomoles per 24 hr (nmoles/24 hr) Interval 1.7 to 143.3	—	—

POST_HOC outcome

Timeframe: Baseline and Week 12

Population: Cortisol Population

AeroChamber Plus spacers were provided for participants who demonstrated the inability to coordinate the use of an Meter Dose Inhaler at Visit 1. AeroChamber Plus spacer delivers 22% more medication than the original AeroChamber and is available in three mask sizes and without a mask. The data provided are a direct calculation of the Week 12 geometric mean divided by the baseline value,nanomoles per 24 hours (nmol/24 hrs) .

Outcome measures

Measure	Fluticasone Propionate/Salmeterol HFA n=58 Participants Participants who were randomly assigned to Fluticasone Propionate/salmeterol 100/50 micrograms (µg) HFA (2 inhalations of 50/25 µg), twice daily for 12 weeks.	Fluticasone Propionate HFA n=202 Participants Participants who were randomly assigned to Fluticasone Propionate 100 µg HFA (2 inhalations of 50 µg), twice daily for 12 weeks.	Fluticasone Propionate HFA - Spacer Fluticasone Propionate 100 µg HFA (2 inhalation of 50 µg) twice daily in participants 4-11 years of age for 12 weeks. Participants who also used Spacers	Fluticasone Propionate HFA - No Spacer Fluticasone Propionate 100 µg HFA (2 inhalation of 50 µg) twice daily in participants 4-11 years of age for 12 weeks
Geometric Mean Ratio for Baseline: Week 12 24-hour Urinary Cortisol Excretion by Spacer Use Excluding Participants With Abnormal Urinary Cortisol Excretion Values at Baseline From the Cortisol Population	0.87 ratio	0.83 ratio	—	—

Adverse Events

Fluticasone Propionate/Salmeterol HFA

Serious events: 1 serious events

Other events: 61 other events

Deaths: 0 deaths

Fluticasone Propionate HFA

Serious events: 0 serious events

Other events: 68 other events

Deaths: 0 deaths

Serious adverse events

Measure	Fluticasone Propionate/Salmeterol HFA n=173 participants at risk Participants who were randomly assigned to Fluticasone Propionate/salmeterol 100/50 micrograms (µg) HFA (2 inhalations of 50/25 µg), twice daily for 12 weeks.	Fluticasone Propionate HFA n=177 participants at risk Participants who were randomly assigned to Fluticasone Propionate 100 µg HFA (2 inhalations of 50 µg), twice daily for 12 weeks.
Injury, poisoning and procedural complications Head Injury due to fall	0.58% 1/173	0.00% 0/177

Other adverse events

Measure	Fluticasone Propionate/Salmeterol HFA n=173 participants at risk Participants who were randomly assigned to Fluticasone Propionate/salmeterol 100/50 micrograms (µg) HFA (2 inhalations of 50/25 µg), twice daily for 12 weeks.	Fluticasone Propionate HFA n=177 participants at risk Participants who were randomly assigned to Fluticasone Propionate 100 µg HFA (2 inhalations of 50 µg), twice daily for 12 weeks.
Nervous system disorders Headache	15.0% 26/173	14.1% 25/177
Infections and infestations Upper Respiratory Tract Infection	6.4% 11/173	7.3% 13/177
Infections and infestations Nasopharyngitis	9.2% 16/173	11.9% 21/177
Infections and infestations Pharyngitis	2.3% 4/173	6.8% 12/177
Infections and infestations Rhinitis	4.6% 8/173	3.4% 6/177
Respiratory, thoracic and mediastinal disorders Cough	5.2% 9/173	4.0% 7/177
General disorders Pyrexia	4.6% 8/173	9.0% 16/177

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