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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

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ClinicalTrials.gov Identifier: NCT00441441
Recruitment Status : Completed
First Posted : March 1, 2007
Results First Posted : September 23, 2010
Last Update Posted : December 16, 2016
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Asthma
Interventions Drug: fluticasone propionate
Drug: fluticasone propionate/salmeterol
Enrollment 351
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.
Pre-assignment Details  
Arm/Group Title Fluticasone Propionate/Salmeterol Hydrofluoroalkane (HFA) Fluticasone Propionate HFA
Hide Arm/Group Description 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. Participants who were randomly assigned to Fluticasone Propionate 100 µg HFA (2 inhalations of 50 µg), twice daily for 12 weeks.
Period Title: Overall Study
Started 173 177
Completed 162 163
Not Completed 11 14
Reason Not Completed
Adverse Event             2             1
Protocol Violation             4             6
Exacerbation of asthma             1             2
Withdrawal by Subject             1             2
Not specified             3             3
Arm/Group Title Fluticasone Propionate/Salmeterol HFA Fluticasone Propionate HFA Total
Hide Arm/Group Description 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. Participants who were randomly assigned to Fluticasone Propionate 100 µg HFA (2 inhalations of 50 µg), twice daily for 12 weeks. Total of all reporting groups
Overall Number of Baseline Participants 173 177 350
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 173 participants 177 participants 350 participants
4-5 years 36 41 77
6-11 years 137 136 273
Gender  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 173 participants 177 participants 350 participants
Female
66
  38.2%
71
  40.1%
137
  39.1%
Male
107
  61.8%
106
  59.9%
213
  60.9%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 173 participants 177 participants 350 participants
Hispanic or Latino
70
  40.5%
73
  41.2%
143
  40.9%
Not Hispanic or Latino
103
  59.5%
104
  58.8%
207
  59.1%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 173 participants 177 participants 350 participants
White/Caucasian/European Heritage 114 113 227
American Indian or Alaska Native 24 27 51
Central/South Asian Heritage 8 8 16
African American/African Heritage 7 8 15
Japanese Heritage 3 0 3
Arabic/North African Heritage 2 2 4
South East Asian Heritage 2 0 2
Mixed Race 13 19 32
1.Primary Outcome
Title Possible Drug-Related Adverse Events
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (IITT) Population - All participants who were randomized and received at least one dose of double-blind study treatment.
Arm/Group Title Fluticasone Propionate/Salmeterol HFA Fluticasone Propionate HFA
Hide Arm/Group Description:
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.
Participants who were randomly assigned to Fluticasone Propionate 100 µg HFA (2 inhalations of 50 µg), twice daily for 12 weeks.
Overall Number of Participants Analyzed 173 177
Measure Type: Number
Unit of Measure: participants
Participants with any drug-related event 13 16
Investigations - ECG QTc interval prolonged 9 4
Investigations - QT interval prolonged 0 2
Investigations - ECG QT borderline prolonged 1 0
Investigations - ECG QT interval abnormal 1 0
Cardiac - Defect conduction intraventricular 2 7
Cardiac - Conduction disorder 1 1
Cardiac - Sinus tachycardia 1 0
Cardiac - Supraventricular ectopics 0 1
Infections/Infestations - Oral candidiasis 0 1
Infections/Infest - Oropharyngeal candidiasis 0 1
Respiratory/thoracic/mediastinal - Dysphonia 2 0
2.Primary Outcome
Title Investigator Evaluations of Electrocardiogram (ECG) Results
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Fluticasone Propionate/Salmeterol HFA Fluticasone Propionate HFA
Hide Arm/Group Description:
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.
Participants who were randomly assigned to Fluticasone Propionate 100 µg HFA (2 inhalations of 50 µg), twice daily for 12 weeks.
Overall Number of Participants Analyzed 173 177
Measure Type: Number
Unit of Measure: participants
Baseline - Normal 145 155
Baseline - Abnormal: Not Clinically Significant 27 21
Baseline - Abnormal: Clinically Significant 1 0
Week 12-No Change or insignificant Change 136 142
Week 12-Clinically Significant Change-Favorable 2 0
Week 12-Clinically Significant Change-Unfavorable 24 18
PD-No Change or insignificant Change 7 9
PD-Clinically Significant Change-Favorable 0 1
PD-Clinically Significant Change-Unfavorable 0 1
3.Primary Outcome
Title Clinically Significant Unfavorable ECGs at Week 12
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Fluticasone Propionate/Salmeterol HFA Fluticasone Propionate HFA
Hide Arm/Group Description:
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.
Participants who were randomly assigned to Fluticasone Propionate 100 µg HFA (2 inhalations of 50 µg), twice daily for 12 weeks.
Overall Number of Participants Analyzed 173 177
Measure Type: Number
Unit of Measure: participants
Clinically significant unfavorable change 24 18
AEs Reported for ECG findings 22 18
Clinically significant unfavorable ECGs repeated 11 11
Repeated ECGs w/ no change or insignificant change 6 5
4.Primary Outcome
Title ECG Measures – Heart Rate
Hide Description The range of heart rates for this study was between 49-144 beats per minute
Time Frame Baseline and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population - All subjects who were randomized and received at least one dose of double-blind study treatment.
Arm/Group Title Fluticasone Propionate/Salmeterol HFA Fluticasone Propionate HFA
Hide Arm/Group Description:
Participants who were randomly assigned to Fluticasone propionate/salmeterol 100/50 micrograms (µg) HFA (2 inhalations of 50/25µg), twice daily for 12 weeks.
Participants who were randomly assigned to Fluticasone Propionate 100 µg HFA (2 inhalations of 50 µg), twice daily for 12 weeks.
Overall Number of Participants Analyzed 173 177
Mean (Full Range)
Unit of Measure: beats per minute
Mean Heart Rate - Baseline
84
(53 to 144)
82.6
(51 to 136)
Mean Heart Rate - Week 12
85.5
(59 to 138)
81.9
(52 to 121)
Mean Heart Rate - Premature Discontinuation
73.1
(53 to 90)
92.4
(49 to 130)
5.Primary Outcome
Title ECG Measures - QT Interval
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population - All participants who were randomized and received at least one dose of double-blind study treatment.
Arm/Group Title Fluticasone Propionate/Salmeterol HFA Fluticasone Propionate HFA
Hide Arm/Group Description:
Participants who were randomly assigned to Fluticasone propionate/salmeterol 100/50 micrograms (µg) HFA (2 inhalations of 50/25µg), twice daily for 12 weeks.
Participants who were randomly assigned to Fluticasone propionate 100 µg HFA (2inhalations of 50 µg), twice daily for 12 weeks.
Overall Number of Participants Analyzed 173 177
Mean (Full Range)
Unit of Measure: milliseconds
Mean QTc Interval (Fridericia)- Baseline
394.5
(340 to 449)
390.8
(338 to 429)
Mean QTc Interval (Fridericia) - Week 12
397.5
(355 to 439)
393.6
(329 to 449)
Premature Discontinuation (Fridericia)
392
(359 to 417)
394.8
(376 to 408)
Mean QTc Interval (Bazett) - Baseline
416.3
(356 to 464)
411.4
(346 to 471)
Mean QTc Interval (Bazett) - Week 12
420.8
(368 to 466)
413.7
(351 to 477)
Premature Discontinuation (Bazett)
403.3
(376 to 446)
422.7
(378 to 454)
6.Primary Outcome
Title Cardiovascular Adverse Events Reported During Treatment Period
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population - All participants who were randomized and received at least one dose of double-blind study treatment.
Arm/Group Title Fluticasone Propionate/Salmeterol HFA Fluticasone Propionate HFA
Hide Arm/Group Description:
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.
Participants who were randomly assigned to Fluticasone Propionate 100 µg HFA (2 inhalations of 50 µg), twice daily for 12 weeks.
Overall Number of Participants Analyzed 173 177
Measure Type: Number
Unit of Measure: participants
Participants with Any Event 98 103
Electrocardiogram (ECG) Change 3 2
ECG QTc Interval Prolonged 2 1
ECG Abnormal 1 1
ECG QT Borderline Prolonged 1 0
Defect Conduction Intraventricular 4 3
Cardiac Arrhythmia 1 0
Premature Atrial Contraction 1 0
7.Primary Outcome
Title Cardiovascular Adverse Events Reported During the Post-Treatment Period
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population - All participants who were randomized and received at least one dose of double-blind study treatment.
Arm/Group Title Fluticasone Propionate/Salmeterol HFA Fluticasone Propionate HFA
Hide Arm/Group Description:
Participants who were randomly assigned to Fluticasone Propionate/salmeterol 100/50 µg HFA (2 inhalations of 50/25 µg), twice daily for 12 weeks.
Participants who were randomly assigned to Fluticasone Propionate 100 µg HFA (2 inhalations of 50 µg), twice daily for 12 weeks.
Overall Number of Participants Analyzed 173 177
Measure Type: Number
Unit of Measure: participants
Participants with Any Event 19 19
ECG QTc interval prolonged 11 5
QT interval prolonged 1 2
ECG QT interval Abnormal 1 0
Defect Conduction Intraventricular 2 7
Conduction disorder 1 1
Sinus Tachycardia 1 0
Supraventricular Ectopics 0 1
8.Primary Outcome
Title Asthma Exacerbations: Worsening of Asthma Requiring Emergency Intervention, Hospitalization, or Treatment With Asthma Medications Prohibited by the Protocols
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population - All participants who were randomized and received at least one dose of double-blind study treatment.
Arm/Group Title Fluticasone Propionate/Salmeterol HFA Fluticasone Propionate HFA
Hide Arm/Group Description:
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.
Participants who were randomly assigned to Fluticasone Propionate 100 µg HFA (2 inhalations of 50 µg), twice daily for 12 weeks.
Overall Number of Participants Analyzed 173 177
Measure Type: Number
Unit of Measure: participants
Participants with any asthma exacerbation 1 3
Severity - Mild 1 2
Severity - Moderate/Severe 0 1
Withdrawal due to Asthma Exacerbation 1 2
9.Primary Outcome
Title Number of Participants With the Indicated Levels of 24-hour Urinary Cortisol Excretion
Hide Description "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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Fluticasone Propionate/Salmeterol HFA Fluticasone Propionate HFA
Hide Arm/Group Description:
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.
Participants who were randomly assigned to Fluticasone Propionate 100 µg HFA (2 inhalations of 50 µg), twice daily for 12 weeks.
Overall Number of Participants Analyzed 147 144
Measure Type: Number
Unit of Measure: participants
Baseline - Abnormal high cortisol excretion, n 13 17
Baseline - Abnormal low cortisol excretion, n 1 0
Week 12 - Abnormal high cortisol excretion, n 13 8
Week 12 - Abnormal low cortisol excretion, n 2 0
10.Primary Outcome
Title Geometric Mean Values of 24-hour Urinary Cortisol Excretion at Baseline and Week 12
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Cortisol Population
Arm/Group Title Fluticasone Propionate/Salmeterol HFA Fluticasone Propionate HFA
Hide Arm/Group Description:
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.
Participants who were randomly assigned to Fluticasone Propionate 100 µg HFA (2 inhalations of 50 µg), twice daily for 12 weeks.
Overall Number of Participants Analyzed 147 144
Geometric Mean (Full Range)
Unit of Measure: Nanomoles per 24 hours (nmol/24 hrs)
Baseline - Geometric Mean
32.71
(2.7 to 156.2)
30.88
(4.2 to 891.6)
Week 12 - Geometric Mean
25.03
(1.7 to 152.6)
23.17
(5.3 to 145.8)
11.Primary Outcome
Title Geometric Mean Ratio for Week12:Baseline for 24-hour Urinary Cortisol Excretion
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Cortisol Population
Arm/Group Title Fluticasone Propionate/Salmeterol HFA Fluticasone Propionate HFA
Hide Arm/Group Description:
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.
Participants who were randomly assigned to Fluticasone Propionate 100 µg HFA (2 inhalations of 50 µg), twice daily for 12 weeks.
Overall Number of Participants Analyzed 147 144
Measure Type: Number
Unit of Measure: ratio
0.77 0.75
12.Primary Outcome
Title Number of Participants With the Indicated Levels of 24 Hour Urinary Cortisol Excretion by Spacer Use
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Cortisol Population
Arm/Group Title Fluticasone Propionate/Salmeterol HFA - Spacer Fluticasone Propionate/Salmeterol HFA - No Spacer Fluticasone Propionate HFA - Spacer Fluticasone Propionate HFA - No Spacer
Hide Arm/Group Description:
Fluticasone propionate/salmeterol 100/50 micrograms (µg) HFA (2 inhalations of 50/25µg) twice daily in participants 4-11 years of age for 12 weeks - Participants who also used Spacers
Fluticasone propionate/salmeterol 100/50 µg HFA (2 inhalations of 50/25 µg) twice daily in participants 4-11 years of age for 12 weeks
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 100 µg HFA (2 inhalation of 50 µg) twice daily in participants 4-11 years of age for 12 weeks
Overall Number of Participants Analyzed 115 32 113 31
Measure Type: Number
Unit of Measure: participants
Baseline - Abnormal high cortisol excretion 12 1 14 3
Baseline - Abnormal low cortisol excretion 0 1 0 0
Week 12 - Abnormal high cortisol excretion 10 3 7 1
Week 12 - Abnormal low cortisol excretion 2 0 0 0
13.Primary Outcome
Title Geometric Mean Values of 24 Hour Urinary Cortisol Excretion by Spacer Use at Baseline and Week 12
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Cortisol Population
Arm/Group Title Fluticasone Propionate/Salmeterol HFA - Spacer Fluticasone Propionate/Salmeterol HFA - No Spacer Fluticasone Propionate HFA - Spacer Fluticasone Propionate HFA - No Spacer
Hide Arm/Group Description:
Fluticasone propionate/salmeterol 100/50 micrograms (µg) HFA (2 inhalations of 50/25 µg) twice daily in participants 4-11 years of age for 12 weeks - Participants who also used Spacers
Fluticasone propionate/salmeterol 100/50 µg HFA (2 inhalations of 50/25 µg) twice daily in participants 4-11 years of age for 12 weeks
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 100 µg HFA (2 inhalation of 50 µg) twice daily in participants 4-11 years of age for 12 weeks
Overall Number of Participants Analyzed 115 32 113 31
Geometric Mean (Full Range)
Unit of Measure: Nanomoles per 24 hours (nmol/24 hrs)
Baseline - Geometric Mean
31.89
(3.6 to 156.2)
35.84
(2.7 to 143.3)
30.61
(4.2 to 891.6)
31.89
(7.9 to 335.0)
Week 12 - Geometric Mean
23.37
(1.7 to 143.3)
32.05
(4.6 to 152.6)
23.20
(5.3 to 103.2)
23.06
(5.4 to 145.8)
14.Primary Outcome
Title Geometric Mean Ratio for Week12: Baseline for 24 Hour Urinary Cortisol Excretion by Spacer Use
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Cortisol Population
Arm/Group Title Fluticasone Propionate/Salmeterol HFA - Spacer Fluticasone Propionate/Salmeterol HFA - No Spacer Fluticasone Propionate HFA - Spacer Fluticasone Propionate HFA - No Spacer
Hide Arm/Group Description:
Fluticasone propionate/salmeterol 100/50 micrograms (µg) HFA (2 inhalations of 50/25 µg) twice daily in participants 4-11 years of age for 12 weeks - Participants who also used Spacers
Fluticasone propionate/salmeterol 100/50 µg HFA (2 inhalations of 50/25 µg) twice daily in participants 4-11 years of age for 12 weeks
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 100 µg HFA (2 inhalation of 50 µg) twice daily in participants 4-11 years of age for 12 weeks
Overall Number of Participants Analyzed 115 32 113 31
Measure Type: Number
Unit of Measure: ratio
0.73 0.89 0.76 0.72
15.Secondary Outcome
Title Clinic Morning (AM) Forced Expiratory Volume in Participants 6-11 Years
Hide Description 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
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Hide Analysis Population Description
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/Group Title Fluticasone Propionate/Salmeterol HFA Fluticasone Propionate HFA
Hide Arm/Group Description:
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.
Participants who were randomly assigned to Fluticasone Propionate 100 µg HFA (2 inhalations of 50 µg), twice daily for 12 weeks.
Overall Number of Participants Analyzed 137 136
Mean (Standard Error)
Unit of Measure: Liters per second (L/sec)
Baseline - Mean FEV1 1.67  (0.035) 1.64  (0.035)
Week 12 - Mean FEV1 1.91  (0.038) 1.82  (0.036)
Week 12 - Mean Change from baseline 0.24  (0.023) 0.18  (0.023)
Premature discontinuation - Mean FEV1 1.81  (0.14) 1.70  (0.212)
Premature discontin. - Mean Change from baseline 0.03  (0.09) -0.07  (0.120)
16.Secondary Outcome
Title AM Peak Expiratory Flow
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Fluticasone Propionate/Salmeterol HFA Fluticasone Propionate HFA
Hide Arm/Group Description:
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.
Participants who were randomly assigned to Fluticasone Propionate 100 µg HFA (2 inhalations of 50 µg), twice daily for 12 weeks.
Overall Number of Participants Analyzed 173 177
Mean (Standard Error)
Unit of Measure: Liters/minute (L/min)
Baseline - Mean AM PEF 213  (4.83) 203  (4.37)
Weeks 1-12 - Mean AM PEF 233  (5.07) 220  (4.43)
Weeks 1-12 - Mean Change from Baseline 20.2  (2.04) 17.4  (1.86)
Last 7 Days on Treatment - Mean AM PEF 238  (5.39) 226  (4.73)
Last 7 Days on Treatment-Mean Change from Baseline 25.3  (2.58) 23.3  (2.47)
17.Secondary Outcome
Title Asthma Symptom Scores
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Fluticasone Propionate/Salmeterol HFA Fluticasone Propionate HFA
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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.
Participants who were randomly assigned to Fluticasone Propionate 100 µg HFA (2 inhalations of 50 µg), twice daily for 12 weeks.
Overall Number of Participants Analyzed 177 173
Mean (Standard Error)
Unit of Measure: Score in scale
Baseline - Mean Score 1.3  (0.06) 1.4  (0.06)
Weeks 1-12 - Mean Score 0.9  (0.06) 0.8  (0.05)
Weeks 1-12 – Mean change from baseline -0.4  (0.06) -0.6  (0.06)
Last 7 Days on Treatment - Mean Score 0.8  (0.07) 0.8  (0.07)
Last 7 Days on Treat. - Mean change from baseline -0.5  (0.07) -0.6  (0.08)
18.Secondary Outcome
Title Percentage of Symptom Free Days
Hide Description 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
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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/Group Title Fluticasone Propionate/Salmeterol HFA Fluticasone Propionate HFA
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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.
Participants who were randomly assigned to Fluticasone Propionate 100 µg HFA (2 inhalations of 50 µg), twice daily for 12 weeks.
Overall Number of Participants Analyzed 173 177
Mean (Standard Error)
Unit of Measure: Percentage of days
Baseline - Mean Percent 20.0  (2.02) 18.4  (2.00)
Weeks 1-12 - Mean Percent 46.7  (2.77) 48.7  (2.80)
Weeks 1-12 – Mean change from baseline 26.8  (2.47) 30.5  (2.62)
Last 7 Days on Treatment - Mean Percent 51.9  (3.51) 53.4  (3.44)
Last 7 Days on Treat. - Mean change from baseline 32.1  (3.32) 34.9  (3.43)
19.Secondary Outcome
Title Albuterol Use
Hide Description 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
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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/Group Title Fluticasone Propionate/Salmeterol HFA Fluticasone Propionate HFA
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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.
Participants who were randomly assigned to Fluticasone Propionate 100 µg HFA (2 inhalations of 50 µg), twice daily for 12 weeks.
Overall Number of Participants Analyzed 173 177
Mean (Standard Error)
Unit of Measure: Number of puffs per 24 hours
Baseline - Mean number of puffs 1.5  (0.12) 1.8  (0.19)
Weeks 1-12 - Mean number of puffs 1.0  (0.09) 0.9  (0.09)
Weeks 1-12 – Mean change from baseline -0.6  (0.12) -1.0  (0.16)
Last 7 Days on Treatment - Mean number of puffs 0.7  (0.11) 0.7  (0.11)
Last 7 Days on Treat. - Mean change from baseline 0.15  (0.8) -1.2  (0.19)
20.Secondary Outcome
Title Percent of Albuterol-free Days
Hide Description Percentage of days when Albuterol use was unnecessary based on daily record and symptom free days.
Time Frame Baseline and 12-Week Treatment Period
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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/Group Title Fluticasone Propionate/Salmeterol HFA Fluticasone Propionate HFA
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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.
Participants who were randomly assigned to Fluticasone Propionate 100 µg HFA (2 inhalations of 50 µg), twice daily for 12 weeks.
Overall Number of Participants Analyzed 173 177
Mean (Standard Error)
Unit of Measure: Percentage of days
Baseline - Mean percent rescue free 43.7  (2.85) 42.5  (3.04)
Weeks 1-12 - Mean percent rescue free 67.1  (2.46) 70.0  (2.40)
Weeks 1-12 – Mean change from baseline 23.6  (2.79) 28.3  (2.93)
Last 7 Days on Treat. - Mean percent rescue free 75.4  (2.96) 75.8  (2.98)
Last 7 Days on Treat. - Mean change from baseline 30.4  (3.50) 32.8  (3.58)
21.Post-Hoc Outcome
Title Geometric Mean Values of 24-hour Urinary Cortisol Excretion at Baseline and Week 12
Hide Description 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
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Cortisol Population
Arm/Group Title Fluticasone Propionate/Salmeterol HFA Fluticasone Propionate HFA
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Samples provided by 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.
Samples provided by participants who were randomly assigned to Fluticasone Propionate 100 µg HFA (2 inhalations of 50 µg), twice daily for 12 weeks.
Overall Number of Participants Analyzed 147 140
Geometric Mean (Full Range)
Unit of Measure: Nanamoles per 24 hours (nmol/24 hrs)
Baseline - Geometric Mean
32.71
(2.7 to 156.2)
28.39
(4.2 to 146.9)
Week 12 - Geometric Mean
25.03
(1.7 to 152.6)
22.80
(5.3 to 145.8)
22.Post-Hoc Outcome
Title Geometric Mean Ratio for Baseline:Week12 24-hour Urinary Cortisol Excretion
Hide Description 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
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Cortisol Population
Arm/Group Title Fluticasone Propionate/Salmeterol HFA Fluticasone Propionate HFA
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Samples provided by 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.
Samples provided by participants who were randomly assigned to Fluticasone Propionate 100 µg HFA (2 inhalations of 50 µg), twice daily for 12 weeks.
Overall Number of Participants Analyzed 147 140
Measure Type: Number
Unit of Measure: ratio
0.77 0.80
23.Post-Hoc Outcome
Title 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
Hide Description 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
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Cortisol Population
Arm/Group Title No Spacer Spacer
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Participants who did not use spacer and were in either treatment group
Participants who required a spacer and were in either treatment group
Overall Number of Participants Analyzed 58 202
Geometric Mean (Full Range)
Unit of Measure: Nanomoles per 24 hr (nmoles/24 hr)
Baseline - Geometric Mean
31.88
(7.9 to 81.7)
27.08
(3.6 to 166.3)
Week 12 - Geometric Mean
27.85
(5.4 to 152.6)
22.38
(1.7 to 143.3)
24.Post-Hoc Outcome
Title 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
Hide Description 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
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Cortisol Population
Arm/Group Title Spacer No Spacer
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Participants who did not use spacer and were in either treatment group
Participants who required a spacer and were in either treatment group
Overall Number of Participants Analyzed 58 202
Measure Type: Number
Unit of Measure: ratio
0.87 0.83
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Fluticasone Propionate/Salmeterol HFA Fluticasone Propionate HFA
Hide Arm/Group Description 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. Participants who were randomly assigned to Fluticasone Propionate 100 µg HFA (2 inhalations of 50 µg), twice daily for 12 weeks.
All-Cause Mortality
Fluticasone Propionate/Salmeterol HFA Fluticasone Propionate HFA
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Fluticasone Propionate/Salmeterol HFA Fluticasone Propionate HFA
Affected / at Risk (%) Affected / at Risk (%)
Total   1/173 (0.58%)   0/177 (0.00%) 
Injury, poisoning and procedural complications     
Head Injury due to fall * 1  1/173 (0.58%)  0/177 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Fluticasone Propionate/Salmeterol HFA Fluticasone Propionate HFA
Affected / at Risk (%) Affected / at Risk (%)
Total   61/173 (35.26%)   68/177 (38.42%) 
General disorders     
Pyrexia  1  8/173 (4.62%)  16/177 (9.04%) 
Infections and infestations     
Upper Respiratory Tract Infection  1  11/173 (6.36%)  13/177 (7.34%) 
Nasopharyngitis  1  16/173 (9.25%)  21/177 (11.86%) 
Pharyngitis  1  4/173 (2.31%)  12/177 (6.78%) 
Rhinitis  1  8/173 (4.62%)  6/177 (3.39%) 
Nervous system disorders     
Headache  1  26/173 (15.03%)  25/177 (14.12%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  9/173 (5.20%)  7/177 (3.95%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
A post-hoc evaluation confirmed that no clinically relevant ECG abnormalities were present. Differences in the primary and post-hoc analyses were associated with variation in the method of ECG interpretation and are not fully interpretable.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
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Name/Title: GSK Response Center
Organization: GlaxoSmithKline
Phone: 866-435-7343
Publications:
Li JS, Qaqundah PY, Weinstein SF, LaForce CF, Ellsworth AV, Ortega HG, Ferro TJ. Fluticasone propionate/salmeterol combination in children with asthma: key cardiac and overall safety results. Clin Res Reg Affairs 2010;27(3):87-95.
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Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00441441     History of Changes
Other Study ID Numbers: SFA106484
First Submitted: February 28, 2007
First Posted: March 1, 2007
Results First Submitted: January 23, 2009
Results First Posted: September 23, 2010
Last Update Posted: December 16, 2016