Asthma
Conditions
Keywords
asthma, fluticasone propionate, children, fluticasone propionate/salmeterol
Brief summary
This study is to assess the safety of an investigational drug in children 4 to 11 years of age who have asthma. The subjects will attend 7 clinic visits, of which up to 3 will be in the morning, and have lung function tests performed.
Interventions
DRUGfluticasone propionate
fluticasone propionate 100mcg HFA
fluticasone propionate/salmeterol 100/50mcg HFA
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
4 Years to 11 Years
Healthy volunteers
No
Inclusion criteria
* Must have asthma. * Must be currently taking an inhaled corticosteroid. * Must be able to attend 7 clinic visits, of which up to 3 will be in the morning, and have lung function tests that are at least 60% of normal (AM FEV1 or PEF). * Have a historical or current FEV1 or PEF reversibility of \>=12%.
Exclusion criteria
* Has ever had life-threatening asthma (for example respiratory arrest, mechanical ventilation). * Has a current ear or respiratory tract infection. * Has ever had any other major illnesses (such as cystic fibrosis, heart problems, tuberculosis).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Possible Drug-Related Adverse Events | Treatment period (weeks 1-12) and Post Treatment (≥1 day after last time study drug) | 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. |
| Geometric Mean Values of 24-hour Urinary Cortisol Excretion at Baseline and Week 12 | Baseline and Week 12 | 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. |
| Geometric Mean Ratio for Week12:Baseline for 24-hour Urinary Cortisol Excretion | Baseline and Week 12 | 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). |
| Investigator Evaluations of Electrocardiogram (ECG) Results | Baseline and Week 12 | 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. |
| Clinically Significant Unfavorable ECGs at Week 12 | Baseline, Week 12 | 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. |
| ECG Measures - Heart Rate | Baseline and Week 12 | The range of heart rates for this study was between 49-144 beats per minute |
| ECG Measures - QT Interval | Baseline and Week 12 | 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. |
| Cardiovascular Adverse Events Reported During Treatment Period | 12-Week Treatment Period | 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. |
| Cardiovascular Adverse Events Reported During the Post-Treatment Period | 5 Days after Week 12 | 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. |
| Asthma Exacerbations: Worsening of Asthma Requiring Emergency Intervention, Hospitalization, or Treatment With Asthma Medications Prohibited by the Protocols | Treatment period (weeks 1-12) | 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. |
| Number of Participants With the Indicated Levels of 24-hour Urinary Cortisol Excretion | Baseline and week 12 | 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. |
| Number of Participants With the Indicated Levels of 24 Hour Urinary Cortisol Excretion by Spacer Use | Baseline and Week 12 | 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. |
| Geometric Mean Values of 24 Hour Urinary Cortisol Excretion by Spacer Use at Baseline and Week 12 | Baseline and Week 12 | 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. |
| Geometric Mean Ratio for Week12: Baseline for 24 Hour Urinary Cortisol Excretion by Spacer Use | Baseline and Week 12 | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Albuterol-free Days | Baseline and 12-Week Treatment Period | Percentage of days when Albuterol use was unnecessary based on daily record and symptom free days. |
| Clinic Morning (AM) Forced Expiratory Volume in Participants 6-11 Years | Baseline and week 12 | 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. |
| AM Peak Expiratory Flow | Baseline and 12-Week Treatment Period | 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. |
| Asthma Symptom Scores | Baseline and 12-Week Treatment Period | 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. |
| Percentage of Symptom Free Days | Baseline and 12-Week Treatment Period | 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 . |
| Albuterol Use | Baseline and 12-Week Treatment Period | 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. |
Countries
Australia, Canada, Chile, Costa Rica, Germany, Latvia, Lithuania, Mexico, Peru, Poland, Russia, Spain, United States
Participant flow
Recruitment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Fluticasone Propionate/Salmeterol 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. | 173 |
| Fluticasone Propionate HFA Participants who were randomly assigned to Fluticasone Propionate 100 µg HFA (2 inhalations of 50 µg), twice daily for 12 weeks. | 177 |
| Total | 350 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 1 |
| Overall Study | Exacerbation of asthma | 1 | 2 |
| Overall Study | Other | 3 | 3 |
| Overall Study | Protocol Violation | 4 | 6 |
| Overall Study | Withdrawal by Subject | 1 | 2 |
Baseline characteristics
| Characteristic | Fluticasone Propionate/Salmeterol HFA | Total | Fluticasone Propionate HFA |
|---|---|---|---|
| Age, Customized 4-5 years | 36 participants | 77 participants | 41 participants |
| Age, Customized 6-11 years | 137 participants | 273 participants | 136 participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 70 Participants | 143 Participants | 73 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 103 Participants | 207 Participants | 104 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Gender Female | 66 Participants | 137 Participants | 71 Participants |
| Gender Male | 107 Participants | 213 Participants | 106 Participants |
| Race/Ethnicity, Customized African American/African Heritage | 7 participants | 15 participants | 8 participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 24 participants | 51 participants | 27 participants |
| Race/Ethnicity, Customized Arabic/North African Heritage | 2 participants | 4 participants | 2 participants |
| Race/Ethnicity, Customized Central/South Asian Heritage | 8 participants | 16 participants | 8 participants |
| Race/Ethnicity, Customized Japanese Heritage | 3 participants | 3 participants | 0 participants |
| Race/Ethnicity, Customized Mixed Race | 13 participants | 32 participants | 19 participants |
| Race/Ethnicity, Customized South East Asian Heritage | 2 participants | 2 participants | 0 participants |
| Race/Ethnicity, Customized White/Caucasian/European Heritage | 114 participants | 227 participants | 113 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 61 / 173 | 68 / 177 |
| serious Total, serious adverse events | 1 / 173 | 0 / 177 |
Outcome results
Primary
Asthma Exacerbations: Worsening of Asthma Requiring Emergency Intervention, Hospitalization, or Treatment With Asthma Medications Prohibited by the Protocols
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.
Time frame: Treatment period (weeks 1-12)
Population: ITT Population - All participants who were randomized and received at least one dose of double-blind study treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Fluticasone Propionate/Salmeterol HFA | 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 |
| Fluticasone Propionate/Salmeterol HFA | Asthma Exacerbations: Worsening of Asthma Requiring Emergency Intervention, Hospitalization, or Treatment With Asthma Medications Prohibited by the Protocols | Severity - Mild | 1 participants |
| Fluticasone Propionate/Salmeterol HFA | Asthma Exacerbations: Worsening of Asthma Requiring Emergency Intervention, Hospitalization, or Treatment With Asthma Medications Prohibited by the Protocols | Severity - Moderate/Severe | 0 participants |
| Fluticasone Propionate/Salmeterol HFA | 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 |
| Fluticasone Propionate HFA | Asthma Exacerbations: Worsening of Asthma Requiring Emergency Intervention, Hospitalization, or Treatment With Asthma Medications Prohibited by the Protocols | Withdrawal due to Asthma Exacerbation | 2 participants |
| Fluticasone Propionate HFA | Asthma Exacerbations: Worsening of Asthma Requiring Emergency Intervention, Hospitalization, or Treatment With Asthma Medications Prohibited by the Protocols | Participants with any asthma exacerbation | 3 participants |
| Fluticasone Propionate HFA | Asthma Exacerbations: Worsening of Asthma Requiring Emergency Intervention, Hospitalization, or Treatment With Asthma Medications Prohibited by the Protocols | Severity - Moderate/Severe | 1 participants |
| Fluticasone Propionate HFA | Asthma Exacerbations: Worsening of Asthma Requiring Emergency Intervention, Hospitalization, or Treatment With Asthma Medications Prohibited by the Protocols | Severity - Mild | 2 participants |
Primary
Cardiovascular Adverse Events Reported During the Post-Treatment Period
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.
Time frame: 5 Days after Week 12
Population: ITT Population - All participants who were randomized and received at least one dose of double-blind study treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Fluticasone Propionate/Salmeterol HFA | Cardiovascular Adverse Events Reported During the Post-Treatment Period | Conduction disorder | 1 participants |
| Fluticasone Propionate/Salmeterol HFA | Cardiovascular Adverse Events Reported During the Post-Treatment Period | Defect Conduction Intraventricular | 2 participants |
| Fluticasone Propionate/Salmeterol HFA | Cardiovascular Adverse Events Reported During the Post-Treatment Period | QT interval prolonged | 1 participants |
| Fluticasone Propionate/Salmeterol HFA | Cardiovascular Adverse Events Reported During the Post-Treatment Period | ECG QTc interval prolonged | 11 participants |
| Fluticasone Propionate/Salmeterol HFA | Cardiovascular Adverse Events Reported During the Post-Treatment Period | Sinus Tachycardia | 1 participants |
| Fluticasone Propionate/Salmeterol HFA | Cardiovascular Adverse Events Reported During the Post-Treatment Period | ECG QT interval Abnormal | 1 participants |
| Fluticasone Propionate/Salmeterol HFA | Cardiovascular Adverse Events Reported During the Post-Treatment Period | Supraventricular Ectopics | 0 participants |
| Fluticasone Propionate/Salmeterol HFA | Cardiovascular Adverse Events Reported During the Post-Treatment Period | Participants with Any Event | 19 participants |
| Fluticasone Propionate HFA | Cardiovascular Adverse Events Reported During the Post-Treatment Period | Supraventricular Ectopics | 1 participants |
| Fluticasone Propionate HFA | Cardiovascular Adverse Events Reported During the Post-Treatment Period | Participants with Any Event | 19 participants |
| Fluticasone Propionate HFA | Cardiovascular Adverse Events Reported During the Post-Treatment Period | ECG QTc interval prolonged | 5 participants |
| Fluticasone Propionate HFA | Cardiovascular Adverse Events Reported During the Post-Treatment Period | QT interval prolonged | 2 participants |
| Fluticasone Propionate HFA | Cardiovascular Adverse Events Reported During the Post-Treatment Period | ECG QT interval Abnormal | 0 participants |
| Fluticasone Propionate HFA | Cardiovascular Adverse Events Reported During the Post-Treatment Period | Defect Conduction Intraventricular | 7 participants |
| Fluticasone Propionate HFA | Cardiovascular Adverse Events Reported During the Post-Treatment Period | Conduction disorder | 1 participants |
| Fluticasone Propionate HFA | Cardiovascular Adverse Events Reported During the Post-Treatment Period | Sinus Tachycardia | 0 participants |
Primary
Cardiovascular Adverse Events Reported During Treatment Period
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.
Time frame: 12-Week Treatment Period
Population: ITT Population - All participants who were randomized and received at least one dose of double-blind study treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Fluticasone Propionate/Salmeterol HFA | Cardiovascular Adverse Events Reported During Treatment Period | Electrocardiogram (ECG) Change | 3 participants |
| Fluticasone Propionate/Salmeterol HFA | Cardiovascular Adverse Events Reported During Treatment Period | Defect Conduction Intraventricular | 4 participants |
| Fluticasone Propionate/Salmeterol HFA | Cardiovascular Adverse Events Reported During Treatment Period | ECG Abnormal | 1 participants |
| Fluticasone Propionate/Salmeterol HFA | Cardiovascular Adverse Events Reported During Treatment Period | Cardiac Arrhythmia | 1 participants |
| Fluticasone Propionate/Salmeterol HFA | Cardiovascular Adverse Events Reported During Treatment Period | ECG QTc Interval Prolonged | 2 participants |
| Fluticasone Propionate/Salmeterol HFA | Cardiovascular Adverse Events Reported During Treatment Period | Premature Atrial Contraction | 1 participants |
| Fluticasone Propionate/Salmeterol HFA | Cardiovascular Adverse Events Reported During Treatment Period | ECG QT Borderline Prolonged | 1 participants |
| Fluticasone Propionate/Salmeterol HFA | Cardiovascular Adverse Events Reported During Treatment Period | Participants with Any Event | 98 participants |
| Fluticasone Propionate HFA | Cardiovascular Adverse Events Reported During Treatment Period | ECG QT Borderline Prolonged | 0 participants |
| Fluticasone Propionate HFA | Cardiovascular Adverse Events Reported During Treatment Period | Electrocardiogram (ECG) Change | 2 participants |
| Fluticasone Propionate HFA | Cardiovascular Adverse Events Reported During Treatment Period | ECG QTc Interval Prolonged | 1 participants |
| Fluticasone Propionate HFA | Cardiovascular Adverse Events Reported During Treatment Period | ECG Abnormal | 1 participants |
| Fluticasone Propionate HFA | Cardiovascular Adverse Events Reported During Treatment Period | Participants with Any Event | 103 participants |
| Fluticasone Propionate HFA | Cardiovascular Adverse Events Reported During Treatment Period | Defect Conduction Intraventricular | 3 participants |
| Fluticasone Propionate HFA | Cardiovascular Adverse Events Reported During Treatment Period | Cardiac Arrhythmia | 0 participants |
| Fluticasone Propionate HFA | Cardiovascular Adverse Events Reported During Treatment Period | Premature Atrial Contraction | 0 participants |
Primary
Clinically Significant Unfavorable ECGs at Week 12
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.
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Fluticasone Propionate/Salmeterol HFA | Clinically Significant Unfavorable ECGs at Week 12 | Clinically significant unfavorable change | 24 participants |
| Fluticasone Propionate/Salmeterol HFA | Clinically Significant Unfavorable ECGs at Week 12 | AEs Reported for ECG findings | 22 participants |
| Fluticasone Propionate/Salmeterol HFA | Clinically Significant Unfavorable ECGs at Week 12 | Clinically significant unfavorable ECGs repeated | 11 participants |
| Fluticasone Propionate/Salmeterol HFA | Clinically Significant Unfavorable ECGs at Week 12 | Repeated ECGs w/ no change or insignificant change | 6 participants |
| Fluticasone Propionate HFA | Clinically Significant Unfavorable ECGs at Week 12 | Repeated ECGs w/ no change or insignificant change | 5 participants |
| Fluticasone Propionate HFA | Clinically Significant Unfavorable ECGs at Week 12 | Clinically significant unfavorable change | 18 participants |
| Fluticasone Propionate HFA | Clinically Significant Unfavorable ECGs at Week 12 | Clinically significant unfavorable ECGs repeated | 11 participants |
| Fluticasone Propionate HFA | Clinically Significant Unfavorable ECGs at Week 12 | AEs Reported for ECG findings | 18 participants |
Primary
ECG Measures - Heart Rate
The range of heart rates for this study was between 49-144 beats per minute
Time frame: Baseline and Week 12
Population: ITT Population - All subjects who were randomized and received at least one dose of double-blind study treatment.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Fluticasone Propionate/Salmeterol HFA | ECG Measures - Heart Rate | Mean Heart Rate - Baseline | 84 beats per minute |
| Fluticasone Propionate/Salmeterol HFA | ECG Measures - Heart Rate | Mean Heart Rate - Week 12 | 85.5 beats per minute |
| Fluticasone Propionate/Salmeterol HFA | ECG Measures - Heart Rate | Mean Heart Rate - Premature Discontinuation | 73.1 beats per minute |
| Fluticasone Propionate HFA | ECG Measures - Heart Rate | Mean Heart Rate - Baseline | 82.6 beats per minute |
| Fluticasone Propionate HFA | ECG Measures - Heart Rate | Mean Heart Rate - Week 12 | 81.9 beats per minute |
| Fluticasone Propionate HFA | ECG Measures - Heart Rate | Mean Heart Rate - Premature Discontinuation | 92.4 beats per minute |
Primary
ECG Measures - QT Interval
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.
Time frame: Baseline and Week 12
Population: ITT Population - All participants who were randomized and received at least one dose of double-blind study treatment.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Fluticasone Propionate/Salmeterol HFA | ECG Measures - QT Interval | Mean QTc Interval (Fridericia)- Baseline | 394.5 milliseconds |
| Fluticasone Propionate/Salmeterol HFA | ECG Measures - QT Interval | Mean QTc Interval (Fridericia) - Week 12 | 397.5 milliseconds |
| Fluticasone Propionate/Salmeterol HFA | ECG Measures - QT Interval | Premature Discontinuation (Fridericia) | 392 milliseconds |
| Fluticasone Propionate/Salmeterol HFA | ECG Measures - QT Interval | Mean QTc Interval (Bazett) - Baseline | 416.3 milliseconds |
| Fluticasone Propionate/Salmeterol HFA | ECG Measures - QT Interval | Mean QTc Interval (Bazett) - Week 12 | 420.8 milliseconds |
| Fluticasone Propionate/Salmeterol HFA | ECG Measures - QT Interval | Premature Discontinuation (Bazett) | 403.3 milliseconds |
| Fluticasone Propionate HFA | ECG Measures - QT Interval | Mean QTc Interval (Bazett) - Week 12 | 413.7 milliseconds |
| Fluticasone Propionate HFA | ECG Measures - QT Interval | Mean QTc Interval (Fridericia)- Baseline | 390.8 milliseconds |
| Fluticasone Propionate HFA | ECG Measures - QT Interval | Mean QTc Interval (Bazett) - Baseline | 411.4 milliseconds |
| Fluticasone Propionate HFA | ECG Measures - QT Interval | Mean QTc Interval (Fridericia) - Week 12 | 393.6 milliseconds |
| Fluticasone Propionate HFA | ECG Measures - QT Interval | Premature Discontinuation (Bazett) | 422.7 milliseconds |
| Fluticasone Propionate HFA | ECG Measures - QT Interval | Premature Discontinuation (Fridericia) | 394.8 milliseconds |
Primary
Geometric Mean Ratio for Week12:Baseline for 24-hour Urinary Cortisol Excretion
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).
Time frame: Baseline and Week 12
Population: Cortisol Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fluticasone Propionate/Salmeterol HFA | Geometric Mean Ratio for Week12:Baseline for 24-hour Urinary Cortisol Excretion | 0.77 ratio |
| Fluticasone Propionate HFA | Geometric Mean Ratio for Week12:Baseline for 24-hour Urinary Cortisol Excretion | 0.75 ratio |
Primary
Geometric Mean Ratio for Week12: Baseline for 24 Hour Urinary Cortisol Excretion by Spacer Use
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).
Time frame: Baseline and Week 12
Population: Cortisol Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fluticasone Propionate/Salmeterol HFA | Geometric Mean Ratio for Week12: Baseline for 24 Hour Urinary Cortisol Excretion by Spacer Use | 0.73 ratio |
| Fluticasone Propionate HFA | Geometric Mean Ratio for Week12: Baseline for 24 Hour Urinary Cortisol Excretion by Spacer Use | 0.89 ratio |
| Fluticasone Propionate HFA - Spacer | Geometric Mean Ratio for Week12: Baseline for 24 Hour Urinary Cortisol Excretion by Spacer Use | 0.76 ratio |
| Fluticasone Propionate HFA - No Spacer | Geometric Mean Ratio for Week12: Baseline for 24 Hour Urinary Cortisol Excretion by Spacer Use | 0.72 ratio |
Primary
Geometric Mean Values of 24-hour Urinary Cortisol Excretion at Baseline and Week 12
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.
Time frame: Baseline and Week 12
Population: Cortisol Population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Fluticasone Propionate/Salmeterol HFA | 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) |
| Fluticasone Propionate/Salmeterol HFA | 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) |
| Fluticasone Propionate HFA | Geometric Mean Values of 24-hour Urinary Cortisol Excretion at Baseline and Week 12 | Week 12 - Geometric Mean | 23.17 Nanomoles per 24 hours (nmol/24 hrs) |
| Fluticasone Propionate HFA | Geometric Mean Values of 24-hour Urinary Cortisol Excretion at Baseline and Week 12 | Baseline - Geometric Mean | 30.88 Nanomoles per 24 hours (nmol/24 hrs) |
Primary
Geometric Mean Values of 24 Hour Urinary Cortisol Excretion by Spacer Use at Baseline and Week 12
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.
Time frame: Baseline and Week 12
Population: Cortisol Population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Fluticasone Propionate/Salmeterol HFA | 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) |
| Fluticasone Propionate/Salmeterol HFA | 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) |
| Fluticasone Propionate HFA | Geometric Mean Values of 24 Hour Urinary Cortisol Excretion by Spacer Use at Baseline and Week 12 | Week 12 - Geometric Mean | 32.05 Nanomoles per 24 hours (nmol/24 hrs) |
| Fluticasone Propionate HFA | Geometric Mean Values of 24 Hour Urinary Cortisol Excretion by Spacer Use at Baseline and Week 12 | Baseline - Geometric Mean | 35.84 Nanomoles per 24 hours (nmol/24 hrs) |
| Fluticasone Propionate HFA - Spacer | Geometric Mean Values of 24 Hour Urinary Cortisol Excretion by Spacer Use at Baseline and Week 12 | Baseline - Geometric Mean | 30.61 Nanomoles per 24 hours (nmol/24 hrs) |
| Fluticasone Propionate HFA - Spacer | Geometric Mean Values of 24 Hour Urinary Cortisol Excretion by Spacer Use at Baseline and Week 12 | Week 12 - Geometric Mean | 23.20 Nanomoles per 24 hours (nmol/24 hrs) |
| Fluticasone Propionate HFA - No Spacer | 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) |
| Fluticasone Propionate HFA - No Spacer | Geometric Mean Values of 24 Hour Urinary Cortisol Excretion by Spacer Use at Baseline and Week 12 | Week 12 - Geometric Mean | 23.06 Nanomoles per 24 hours (nmol/24 hrs) |
Primary
Investigator Evaluations of Electrocardiogram (ECG) Results
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.
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Fluticasone Propionate/Salmeterol HFA | Investigator Evaluations of Electrocardiogram (ECG) Results | Baseline - Abnormal: Not Clinically Significant | 27 participants |
| Fluticasone Propionate/Salmeterol HFA | Investigator Evaluations of Electrocardiogram (ECG) Results | Week 12-Clinically Significant Change-Unfavorable | 24 participants |
| Fluticasone Propionate/Salmeterol HFA | Investigator Evaluations of Electrocardiogram (ECG) Results | Week 12-No Change or insignificant Change | 136 participants |
| Fluticasone Propionate/Salmeterol HFA | Investigator Evaluations of Electrocardiogram (ECG) Results | PD-No Change or insignificant Change | 7 participants |
| Fluticasone Propionate/Salmeterol HFA | Investigator Evaluations of Electrocardiogram (ECG) Results | Baseline - Abnormal: Clinically Significant | 1 participants |
| Fluticasone Propionate/Salmeterol HFA | Investigator Evaluations of Electrocardiogram (ECG) Results | PD-Clinically Significant Change-Favorable | 0 participants |
| Fluticasone Propionate/Salmeterol HFA | Investigator Evaluations of Electrocardiogram (ECG) Results | Week 12-Clinically Significant Change-Favorable | 2 participants |
| Fluticasone Propionate/Salmeterol HFA | Investigator Evaluations of Electrocardiogram (ECG) Results | PD-Clinically Significant Change-Unfavorable | 0 participants |
| Fluticasone Propionate/Salmeterol HFA | Investigator Evaluations of Electrocardiogram (ECG) Results | Baseline - Normal | 145 participants |
| Fluticasone Propionate HFA | Investigator Evaluations of Electrocardiogram (ECG) Results | PD-Clinically Significant Change-Unfavorable | 1 participants |
| Fluticasone Propionate HFA | Investigator Evaluations of Electrocardiogram (ECG) Results | Baseline - Normal | 155 participants |
| Fluticasone Propionate HFA | Investigator Evaluations of Electrocardiogram (ECG) Results | Baseline - Abnormal: Not Clinically Significant | 21 participants |
| Fluticasone Propionate HFA | Investigator Evaluations of Electrocardiogram (ECG) Results | Baseline - Abnormal: Clinically Significant | 0 participants |
| Fluticasone Propionate HFA | Investigator Evaluations of Electrocardiogram (ECG) Results | Week 12-No Change or insignificant Change | 142 participants |
| Fluticasone Propionate HFA | Investigator Evaluations of Electrocardiogram (ECG) Results | Week 12-Clinically Significant Change-Favorable | 0 participants |
| Fluticasone Propionate HFA | Investigator Evaluations of Electrocardiogram (ECG) Results | Week 12-Clinically Significant Change-Unfavorable | 18 participants |
| Fluticasone Propionate HFA | Investigator Evaluations of Electrocardiogram (ECG) Results | PD-No Change or insignificant Change | 9 participants |
| Fluticasone Propionate HFA | Investigator Evaluations of Electrocardiogram (ECG) Results | PD-Clinically Significant Change-Favorable | 1 participants |
Primary
Number of Participants With the Indicated Levels of 24-hour Urinary Cortisol Excretion
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.
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Fluticasone Propionate/Salmeterol HFA | Number of Participants With the Indicated Levels of 24-hour Urinary Cortisol Excretion | Baseline - Abnormal high cortisol excretion, n | 13 participants |
| Fluticasone Propionate/Salmeterol HFA | Number of Participants With the Indicated Levels of 24-hour Urinary Cortisol Excretion | Baseline - Abnormal low cortisol excretion, n | 1 participants |
| Fluticasone Propionate/Salmeterol HFA | Number of Participants With the Indicated Levels of 24-hour Urinary Cortisol Excretion | Week 12 - Abnormal high cortisol excretion, n | 13 participants |
| Fluticasone Propionate/Salmeterol HFA | Number of Participants With the Indicated Levels of 24-hour Urinary Cortisol Excretion | Week 12 - Abnormal low cortisol excretion, n | 2 participants |
| Fluticasone Propionate HFA | Number of Participants With the Indicated Levels of 24-hour Urinary Cortisol Excretion | Week 12 - Abnormal low cortisol excretion, n | 0 participants |
| Fluticasone Propionate HFA | Number of Participants With the Indicated Levels of 24-hour Urinary Cortisol Excretion | Baseline - Abnormal high cortisol excretion, n | 17 participants |
| Fluticasone Propionate HFA | Number of Participants With the Indicated Levels of 24-hour Urinary Cortisol Excretion | Week 12 - Abnormal high cortisol excretion, n | 8 participants |
| Fluticasone Propionate HFA | Number of Participants With the Indicated Levels of 24-hour Urinary Cortisol Excretion | Baseline - Abnormal low cortisol excretion, n | 0 participants |
Primary
Number of Participants With the Indicated Levels of 24 Hour Urinary Cortisol Excretion by Spacer Use
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.
Time frame: Baseline and Week 12
Population: Cortisol Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Fluticasone Propionate/Salmeterol HFA | Number of Participants With the Indicated Levels of 24 Hour Urinary Cortisol Excretion by Spacer Use | Baseline - Abnormal high cortisol excretion | 12 participants |
| Fluticasone Propionate/Salmeterol HFA | Number of Participants With the Indicated Levels of 24 Hour Urinary Cortisol Excretion by Spacer Use | Baseline - Abnormal low cortisol excretion | 0 participants |
| Fluticasone Propionate/Salmeterol HFA | Number of Participants With the Indicated Levels of 24 Hour Urinary Cortisol Excretion by Spacer Use | Week 12 - Abnormal high cortisol excretion | 10 participants |
| Fluticasone Propionate/Salmeterol HFA | Number of Participants With the Indicated Levels of 24 Hour Urinary Cortisol Excretion by Spacer Use | Week 12 - Abnormal low cortisol excretion | 2 participants |
| Fluticasone Propionate HFA | Number of Participants With the Indicated Levels of 24 Hour Urinary Cortisol Excretion by Spacer Use | Baseline - Abnormal low cortisol excretion | 1 participants |
| Fluticasone Propionate HFA | Number of Participants With the Indicated Levels of 24 Hour Urinary Cortisol Excretion by Spacer Use | Week 12 - Abnormal high cortisol excretion | 3 participants |
| Fluticasone Propionate HFA | Number of Participants With the Indicated Levels of 24 Hour Urinary Cortisol Excretion by Spacer Use | Week 12 - Abnormal low cortisol excretion | 0 participants |
| Fluticasone Propionate HFA | Number of Participants With the Indicated Levels of 24 Hour Urinary Cortisol Excretion by Spacer Use | Baseline - Abnormal high cortisol excretion | 1 participants |
| Fluticasone Propionate HFA - Spacer | Number of Participants With the Indicated Levels of 24 Hour Urinary Cortisol Excretion by Spacer Use | Week 12 - Abnormal high cortisol excretion | 7 participants |
| Fluticasone Propionate HFA - Spacer | Number of Participants With the Indicated Levels of 24 Hour Urinary Cortisol Excretion by Spacer Use | Baseline - Abnormal low cortisol excretion | 0 participants |
| Fluticasone Propionate HFA - Spacer | Number of Participants With the Indicated Levels of 24 Hour Urinary Cortisol Excretion by Spacer Use | Week 12 - Abnormal low cortisol excretion | 0 participants |
| Fluticasone Propionate HFA - Spacer | Number of Participants With the Indicated Levels of 24 Hour Urinary Cortisol Excretion by Spacer Use | Baseline - Abnormal high cortisol excretion | 14 participants |
| Fluticasone Propionate HFA - No Spacer | Number of Participants With the Indicated Levels of 24 Hour Urinary Cortisol Excretion by Spacer Use | Week 12 - Abnormal low cortisol excretion | 0 participants |
| Fluticasone Propionate HFA - No Spacer | Number of Participants With the Indicated Levels of 24 Hour Urinary Cortisol Excretion by Spacer Use | Baseline - Abnormal low cortisol excretion | 0 participants |
| Fluticasone Propionate HFA - No Spacer | Number of Participants With the Indicated Levels of 24 Hour Urinary Cortisol Excretion by Spacer Use | Baseline - Abnormal high cortisol excretion | 3 participants |
| Fluticasone Propionate HFA - No Spacer | Number of Participants With the Indicated Levels of 24 Hour Urinary Cortisol Excretion by Spacer Use | Week 12 - Abnormal high cortisol excretion | 1 participants |
Primary
Possible Drug-Related Adverse Events
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.
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Fluticasone Propionate/Salmeterol HFA | Possible Drug-Related Adverse Events | Participants with any drug-related event | 13 participants |
| Fluticasone Propionate/Salmeterol HFA | Possible Drug-Related Adverse Events | Investigations - ECG QTc interval prolonged | 9 participants |
| Fluticasone Propionate/Salmeterol HFA | Possible Drug-Related Adverse Events | Investigations - QT interval prolonged | 0 participants |
| Fluticasone Propionate/Salmeterol HFA | Possible Drug-Related Adverse Events | Investigations - ECG QT borderline prolonged | 1 participants |
| Fluticasone Propionate/Salmeterol HFA | Possible Drug-Related Adverse Events | Investigations - ECG QT interval abnormal | 1 participants |
| Fluticasone Propionate/Salmeterol HFA | Possible Drug-Related Adverse Events | Cardiac - Defect conduction intraventricular | 2 participants |
| Fluticasone Propionate/Salmeterol HFA | Possible Drug-Related Adverse Events | Cardiac - Conduction disorder | 1 participants |
| Fluticasone Propionate/Salmeterol HFA | Possible Drug-Related Adverse Events | Cardiac - Sinus tachycardia | 1 participants |
| Fluticasone Propionate/Salmeterol HFA | Possible Drug-Related Adverse Events | Cardiac - Supraventricular ectopics | 0 participants |
| Fluticasone Propionate/Salmeterol HFA | Possible Drug-Related Adverse Events | Infections/Infestations - Oral candidiasis | 0 participants |
| Fluticasone Propionate/Salmeterol HFA | Possible Drug-Related Adverse Events | Infections/Infest - Oropharyngeal candidiasis | 0 participants |
| Fluticasone Propionate/Salmeterol HFA | Possible Drug-Related Adverse Events | Respiratory/thoracic/mediastinal - Dysphonia | 2 participants |
| Fluticasone Propionate HFA | Possible Drug-Related Adverse Events | Infections/Infest - Oropharyngeal candidiasis | 1 participants |
| Fluticasone Propionate HFA | Possible Drug-Related Adverse Events | Participants with any drug-related event | 16 participants |
| Fluticasone Propionate HFA | Possible Drug-Related Adverse Events | Cardiac - Conduction disorder | 1 participants |
| Fluticasone Propionate HFA | Possible Drug-Related Adverse Events | Investigations - ECG QTc interval prolonged | 4 participants |
| Fluticasone Propionate HFA | Possible Drug-Related Adverse Events | Infections/Infestations - Oral candidiasis | 1 participants |
| Fluticasone Propionate HFA | Possible Drug-Related Adverse Events | Investigations - QT interval prolonged | 2 participants |
| Fluticasone Propionate HFA | Possible Drug-Related Adverse Events | Cardiac - Sinus tachycardia | 0 participants |
| Fluticasone Propionate HFA | Possible Drug-Related Adverse Events | Investigations - ECG QT borderline prolonged | 0 participants |
| Fluticasone Propionate HFA | Possible Drug-Related Adverse Events | Respiratory/thoracic/mediastinal - Dysphonia | 0 participants |
| Fluticasone Propionate HFA | Possible Drug-Related Adverse Events | Investigations - ECG QT interval abnormal | 0 participants |
| Fluticasone Propionate HFA | Possible Drug-Related Adverse Events | Cardiac - Supraventricular ectopics | 1 participants |
| Fluticasone Propionate HFA | Possible Drug-Related Adverse Events | Cardiac - Defect conduction intraventricular | 7 participants |
Secondary
Albuterol Use
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Fluticasone Propionate/Salmeterol HFA | Albuterol Use | Weeks 1-12 - Mean number of puffs | 1.0 Number of puffs per 24 hours | Standard Error 0.09 |
| Fluticasone Propionate/Salmeterol HFA | Albuterol Use | Last 7 Days on Treatment - Mean number of puffs | 0.7 Number of puffs per 24 hours | Standard Error 0.11 |
| Fluticasone Propionate/Salmeterol HFA | Albuterol Use | Weeks 1-12 - Mean change from baseline | -0.6 Number of puffs per 24 hours | Standard Error 0.12 |
| Fluticasone Propionate/Salmeterol HFA | Albuterol Use | Last 7 Days on Treat. - Mean change from baseline | 0.15 Number of puffs per 24 hours | Standard Error 0.8 |
| Fluticasone Propionate/Salmeterol HFA | Albuterol Use | Baseline - Mean number of puffs | 1.5 Number of puffs per 24 hours | Standard Error 0.12 |
| Fluticasone Propionate HFA | Albuterol Use | Last 7 Days on Treat. - Mean change from baseline | -1.2 Number of puffs per 24 hours | Standard Error 0.19 |
| Fluticasone Propionate HFA | Albuterol Use | Baseline - Mean number of puffs | 1.8 Number of puffs per 24 hours | Standard Error 0.19 |
| Fluticasone Propionate HFA | Albuterol Use | Weeks 1-12 - Mean number of puffs | 0.9 Number of puffs per 24 hours | Standard Error 0.09 |
| Fluticasone Propionate HFA | Albuterol Use | Weeks 1-12 - Mean change from baseline | -1.0 Number of puffs per 24 hours | Standard Error 0.16 |
| Fluticasone Propionate HFA | Albuterol Use | Last 7 Days on Treatment - Mean number of puffs | 0.7 Number of puffs per 24 hours | Standard Error 0.11 |
Secondary
AM Peak Expiratory Flow
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Fluticasone Propionate/Salmeterol HFA | AM Peak Expiratory Flow | Weeks 1-12 - Mean AM PEF | 233 Liters/minute (L/min) | Standard Error 5.07 |
| Fluticasone Propionate/Salmeterol HFA | AM Peak Expiratory Flow | Last 7 Days on Treatment - Mean AM PEF | 238 Liters/minute (L/min) | Standard Error 5.39 |
| Fluticasone Propionate/Salmeterol HFA | AM Peak Expiratory Flow | Weeks 1-12 - Mean Change from Baseline | 20.2 Liters/minute (L/min) | Standard Error 2.04 |
| Fluticasone Propionate/Salmeterol HFA | AM Peak Expiratory Flow | Last 7 Days on Treatment-Mean Change from Baseline | 25.3 Liters/minute (L/min) | Standard Error 2.58 |
| Fluticasone Propionate/Salmeterol HFA | AM Peak Expiratory Flow | Baseline - Mean AM PEF | 213 Liters/minute (L/min) | Standard Error 4.83 |
| Fluticasone Propionate HFA | AM Peak Expiratory Flow | Last 7 Days on Treatment-Mean Change from Baseline | 23.3 Liters/minute (L/min) | Standard Error 2.47 |
| Fluticasone Propionate HFA | AM Peak Expiratory Flow | Baseline - Mean AM PEF | 203 Liters/minute (L/min) | Standard Error 4.37 |
| Fluticasone Propionate HFA | AM Peak Expiratory Flow | Weeks 1-12 - Mean AM PEF | 220 Liters/minute (L/min) | Standard Error 4.43 |
| Fluticasone Propionate HFA | AM Peak Expiratory Flow | Weeks 1-12 - Mean Change from Baseline | 17.4 Liters/minute (L/min) | Standard Error 1.86 |
| Fluticasone Propionate HFA | AM Peak Expiratory Flow | Last 7 Days on Treatment - Mean AM PEF | 226 Liters/minute (L/min) | Standard Error 4.73 |
Secondary
Asthma Symptom Scores
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Fluticasone Propionate/Salmeterol HFA | Asthma Symptom Scores | Weeks 1-12 - Mean Score | 0.9 Score in scale | Standard Error 0.06 |
| Fluticasone Propionate/Salmeterol HFA | Asthma Symptom Scores | Last 7 Days on Treatment - Mean Score | 0.8 Score in scale | Standard Error 0.07 |
| Fluticasone Propionate/Salmeterol HFA | Asthma Symptom Scores | Weeks 1-12 - Mean change from baseline | -0.4 Score in scale | Standard Error 0.06 |
| Fluticasone Propionate/Salmeterol HFA | Asthma Symptom Scores | Last 7 Days on Treat. - Mean change from baseline | -0.5 Score in scale | Standard Error 0.07 |
| Fluticasone Propionate/Salmeterol HFA | Asthma Symptom Scores | Baseline - Mean Score | 1.3 Score in scale | Standard Error 0.06 |
| Fluticasone Propionate HFA | Asthma Symptom Scores | Last 7 Days on Treat. - Mean change from baseline | -0.6 Score in scale | Standard Error 0.08 |
| Fluticasone Propionate HFA | Asthma Symptom Scores | Baseline - Mean Score | 1.4 Score in scale | Standard Error 0.06 |
| Fluticasone Propionate HFA | Asthma Symptom Scores | Weeks 1-12 - Mean Score | 0.8 Score in scale | Standard Error 0.05 |
| Fluticasone Propionate HFA | Asthma Symptom Scores | Weeks 1-12 - Mean change from baseline | -0.6 Score in scale | Standard Error 0.06 |
| Fluticasone Propionate HFA | Asthma Symptom Scores | Last 7 Days on Treatment - Mean Score | 0.8 Score in scale | Standard Error 0.07 |
Secondary
Clinic Morning (AM) Forced Expiratory Volume in Participants 6-11 Years
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Fluticasone Propionate/Salmeterol HFA | 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 |
| Fluticasone Propionate/Salmeterol HFA | 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 |
| Fluticasone Propionate/Salmeterol HFA | 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 |
| Fluticasone Propionate/Salmeterol HFA | 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 |
| Fluticasone Propionate/Salmeterol HFA | 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 |
| Fluticasone Propionate HFA | Clinic Morning (AM) Forced Expiratory Volume in Participants 6-11 Years | Premature discontin. - Mean Change from baseline | -0.07 Liters per second (L/sec) | Standard Error 0.12 |
| Fluticasone Propionate HFA | Clinic Morning (AM) Forced Expiratory Volume in Participants 6-11 Years | Baseline - Mean FEV1 | 1.64 Liters per second (L/sec) | Standard Error 0.035 |
| Fluticasone Propionate HFA | Clinic Morning (AM) Forced Expiratory Volume in Participants 6-11 Years | Week 12 - Mean FEV1 | 1.82 Liters per second (L/sec) | Standard Error 0.036 |
| Fluticasone Propionate HFA | Clinic Morning (AM) Forced Expiratory Volume in Participants 6-11 Years | Week 12 - Mean Change from baseline | 0.18 Liters per second (L/sec) | Standard Error 0.023 |
| Fluticasone Propionate HFA | Clinic Morning (AM) Forced Expiratory Volume in Participants 6-11 Years | Premature discontinuation - Mean FEV1 | 1.70 Liters per second (L/sec) | Standard Error 0.212 |
Secondary
Percentage of Symptom Free Days
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 .
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Fluticasone Propionate/Salmeterol HFA | Percentage of Symptom Free Days | Weeks 1-12 - Mean Percent | 46.7 Percentage of days | Standard Error 2.77 |
| Fluticasone Propionate/Salmeterol HFA | Percentage of Symptom Free Days | Last 7 Days on Treatment - Mean Percent | 51.9 Percentage of days | Standard Error 3.51 |
| Fluticasone Propionate/Salmeterol HFA | Percentage of Symptom Free Days | Weeks 1-12 - Mean change from baseline | 26.8 Percentage of days | Standard Error 2.47 |
| Fluticasone Propionate/Salmeterol HFA | Percentage of Symptom Free Days | Last 7 Days on Treat. - Mean change from baseline | 32.1 Percentage of days | Standard Error 3.32 |
| Fluticasone Propionate/Salmeterol HFA | Percentage of Symptom Free Days | Baseline - Mean Percent | 20.0 Percentage of days | Standard Error 2.02 |
| Fluticasone Propionate HFA | Percentage of Symptom Free Days | Last 7 Days on Treat. - Mean change from baseline | 34.9 Percentage of days | Standard Error 3.43 |
| Fluticasone Propionate HFA | Percentage of Symptom Free Days | Baseline - Mean Percent | 18.4 Percentage of days | Standard Error 2 |
| Fluticasone Propionate HFA | Percentage of Symptom Free Days | Weeks 1-12 - Mean Percent | 48.7 Percentage of days | Standard Error 2.8 |
| Fluticasone Propionate HFA | Percentage of Symptom Free Days | Weeks 1-12 - Mean change from baseline | 30.5 Percentage of days | Standard Error 2.62 |
| Fluticasone Propionate HFA | Percentage of Symptom Free Days | Last 7 Days on Treatment - Mean Percent | 53.4 Percentage of days | Standard Error 3.44 |
Secondary
Percent of Albuterol-free Days
Percentage of days when Albuterol use was unnecessary based on daily record and symptom free days.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Fluticasone Propionate/Salmeterol HFA | Percent of Albuterol-free Days | Weeks 1-12 - Mean percent rescue free | 67.1 Percentage of days | Standard Error 2.46 |
| Fluticasone Propionate/Salmeterol HFA | Percent of Albuterol-free Days | Last 7 Days on Treat. - Mean percent rescue free | 75.4 Percentage of days | Standard Error 2.96 |
| Fluticasone Propionate/Salmeterol HFA | Percent of Albuterol-free Days | Weeks 1-12 - Mean change from baseline | 23.6 Percentage of days | Standard Error 2.79 |
| Fluticasone Propionate/Salmeterol HFA | Percent of Albuterol-free Days | Last 7 Days on Treat. - Mean change from baseline | 30.4 Percentage of days | Standard Error 3.5 |
| Fluticasone Propionate/Salmeterol HFA | Percent of Albuterol-free Days | Baseline - Mean percent rescue free | 43.7 Percentage of days | Standard Error 2.85 |
| Fluticasone Propionate HFA | Percent of Albuterol-free Days | Last 7 Days on Treat. - Mean change from baseline | 32.8 Percentage of days | Standard Error 3.58 |
| Fluticasone Propionate HFA | Percent of Albuterol-free Days | Baseline - Mean percent rescue free | 42.5 Percentage of days | Standard Error 3.04 |
| Fluticasone Propionate HFA | Percent of Albuterol-free Days | Weeks 1-12 - Mean percent rescue free | 70.0 Percentage of days | Standard Error 2.4 |
| Fluticasone Propionate HFA | Percent of Albuterol-free Days | Weeks 1-12 - Mean change from baseline | 28.3 Percentage of days | Standard Error 2.93 |
| Fluticasone Propionate HFA | Percent of Albuterol-free Days | Last 7 Days on Treat. - Mean percent rescue free | 75.8 Percentage of days | Standard Error 2.98 |
Post Hoc
Geometric Mean Ratio for Baseline:Week12 24-hour Urinary Cortisol Excretion
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) .
Time frame: Baseline and Week 12
Population: Cortisol Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fluticasone Propionate/Salmeterol HFA | Geometric Mean Ratio for Baseline:Week12 24-hour Urinary Cortisol Excretion | 0.77 ratio |
| Fluticasone Propionate HFA | Geometric Mean Ratio for Baseline:Week12 24-hour Urinary Cortisol Excretion | 0.80 ratio |
Post Hoc
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
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) .
Time frame: Baseline and Week 12
Population: Cortisol Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fluticasone Propionate/Salmeterol HFA | 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 |
| Fluticasone Propionate HFA | 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 | 0.83 ratio |
Post Hoc
Geometric Mean Values of 24-hour Urinary Cortisol Excretion at Baseline and Week 12
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.
Time frame: Baseline and Week 12
Population: Cortisol Population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Fluticasone Propionate/Salmeterol HFA | 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) |
| Fluticasone Propionate/Salmeterol HFA | 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) |
| Fluticasone Propionate HFA | Geometric Mean Values of 24-hour Urinary Cortisol Excretion at Baseline and Week 12 | Baseline - Geometric Mean | 28.39 Nanamoles per 24 hours (nmol/24 hrs) |
| Fluticasone Propionate HFA | Geometric Mean Values of 24-hour Urinary Cortisol Excretion at Baseline and Week 12 | Week 12 - Geometric Mean | 22.80 Nanamoles per 24 hours (nmol/24 hrs) |
Post Hoc
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
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.
Time frame: Baseline and Week 12
Population: Cortisol Population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Fluticasone Propionate/Salmeterol HFA | 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) |
| Fluticasone Propionate/Salmeterol HFA | 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) |
| Fluticasone Propionate HFA | 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 | 27.08 Nanomoles per 24 hr (nmoles/24 hr) |
| Fluticasone Propionate HFA | 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 | 22.38 Nanomoles per 24 hr (nmoles/24 hr) |