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Effect of Fluticasone Furoate Inhalation Powder on the Hypothalamic-pituitary-adrenocortical Axis of Children Aged 5-11 Years With Asthma

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ClinicalTrials.gov Identifier: NCT02483975
Recruitment Status : Completed
First Posted : June 29, 2015
Results First Posted : March 8, 2017
Last Update Posted : June 14, 2017
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Asthma
Interventions Drug: FF
Drug: Placebo
Drug: Montelukast
Drug: Albuterol/Salbutamol
Enrollment 111
Recruitment Details Eligible participants (par.) aged between 5 to 11 years with asthma were enrolled to either receive fluticasone furoate (FF) or placebo by inhalation through ELLIPTA for 6 weeks (wks) (42 days (D)). A total of 156 par. were screened, of which 111 par. were randomized in the study.
Pre-assignment Details Par. receiving non-corticosteroid controller and/or short-acting beta 2-agonist (SABA) therapy were screened for the study. Par. went through a Run-in Period of 7 to 14 D before the 6 Wk Treatment Period.
Arm/Group Title Fluticasone Furoate 50 mcg Placebo
Hide Arm/Group Description Par. received one inhalation, once daily of FF 50 microgram (mcg) in the morning via ELLIPTA inhaler for 6 wks. Par. also received open label montelukast throughout the treatment period and were supplied with albuterol/salbutamol inhalation aerosol to use as needed to treat acute asthma symptoms. Par. received one inhalation, once daily of placebo in the morning via ELLIPTA inhaler for 6 wks. Par. also received open label montelukast throughout the treatment period and were supplied with albuterol/salbutamol inhalation aerosol to use as needed to treat acute asthma symptoms.
Period Title: Overall Study
Started 56 55
Completed 54 53 [1]
Not Completed 2 2
Reason Not Completed
Adverse Event             0             1
Lost to Follow-up             0             1
Physician Decision             2             0
[1]
Subject reported as not completed due to AE was discontinued due to exacerbation, was not an AE/SAE
Arm/Group Title Fluticasone Furoate 50 mcg Placebo Total
Hide Arm/Group Description Par. received one inhalation, once daily of FF 50 mcg in the morning via ELLIPTA inhaler for 6 wks. Par. also received open label montelukast throughout the treatment period and were supplied with albuterol/salbutamol inhalation aerosol to use as needed to treat acute asthma symptoms. Par. received one inhalation, once daily of placebo in the morning via ELLIPTA inhaler for 6 wks. Participants also received open label montelukast throughout the treatment period and were supplied with albuterol/salbutamol inhalation aerosol to use as needed to treat acute asthma symptoms. Total of all reporting groups
Overall Number of Baseline Participants 56 55 111
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Overall study Number Analyzed 56 participants 55 participants 111 participants
8.4  (1.97) 8.4  (2.00) 8.4  (1.97)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 56 participants 55 participants 111 participants
Female
20
  35.7%
30
  54.5%
50
  45.0%
Male
36
  64.3%
25
  45.5%
61
  55.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 56 participants 55 participants 111 participants
Hispanic or Latino
15
  26.8%
17
  30.9%
32
  28.8%
Not Hispanic or Latino
41
  73.2%
38
  69.1%
79
  71.2%
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 56 participants 55 participants 111 participants
Black or African American 32 29 61
White- White/Caucasian/European Heritage 21 21 42
Multiple-American Indian or Alaskan native & white 0 1 1
Multiple-East Asian Heritage & African American 0 2 2
Multiple- Asian-Japanese Heritage and White 1 1 2
Multiple- Black or African American and White 2 1 3
1.Primary Outcome
Title Change From Baseline (Expressed as a Ratio) in 0-24 Hour Weighted Mean Serum Cortisol at the End of the Six Week Treatment Period (D 42) in Intention-to-treat (ITT) Population
Hide Description The blood samples for statistical analysis of serum cortisol (SC) endpoints were collected on D 0 and D 42 at the indicated time points. The weighted mean was calculated by dividing the area under the curve (AUC) over the 24-hour (hr) time period by the time period. Change from Baseline in 0-24 hr weighted mean SC was calculated as a ratio from Baseline defined as the SC weighted mean (0-24 hours) at Week 6 divided by the Baseline SC weighted mean (0-24 hours).The ratio from Baseline was loge transformed prior to analysis. The loge transformed ratios were compared between treatment groups as treatment ratios, using an analysis of covariance (ANCOVA) model, allowing for the effects of Baseline (loge transformed), age, sex and region. Treatment ratios for comparison was calculated by back-transforming the difference between the Least square (LS) means. Using the pooled estimate of variance, 95% Confidence Intervals (CIs) was calculated for the difference.
Time Frame Baseline, D 0 (Pre-dose, 2hr, 4hr, 8hr, 12hr, 16hr and 24hr) and Day 42 (0hr, 2hr, 4hr, 8hr, 16hr and 24hr)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population (pop) comprised of all randomized par. who received at least one dose of study medication. Randomized par. were assumed to have received study medication unless definitive evidence to the contrary exists. Par. with SC weighted mean (0-24 hr) calculated at Baseline and Week 6 were analyzed.
Arm/Group Title Fluticasone Furoate 50 mcg Placebo
Hide Arm/Group Description:
Par. received one inhalation, once daily of FF 50 mcg in the morning via ELLIPTA inhaler for 6 wks. Par. also received open label montelukast throughout the treatment period and were supplied with albuterol/salbutamol inhalation aerosol to use as needed to treat acute asthma symptoms.
Par. received one inhalation, once daily of placebo in the morning via ELLIPTA inhaler for 6 wks. Par. also received open label montelukast throughout the treatment period and were supplied with albuterol/salbutamol inhalation aerosol to use as needed to treat acute asthma symptoms.
Overall Number of Participants Analyzed 53 51
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Ratio
1.02
(46.71%)
1.01
(44.79%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Fluticasone Furoate 50 mcg, Placebo
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments Non inferiority was demonstrated if the lower limit of the two-sided 95% CI for the geometric mean ratio of each dose of fluticasone furoate 50 µg versus placebo was greater than 0.8.
Method of Estimation Estimation Parameter Least square Geometric Mean ratio
Estimated Value 0.92
Confidence Interval (2-Sided) 95%
0.8040 to 1.0505
Estimation Comments [Not Specified]
2.Primary Outcome
Title Change From Baseline (Expressed as a Ratio) in 0-24 Hour Weighted Mean Serum Cortisol at the End of the Six Week Treatment Period (Day 42) in SC Population
Hide Description The blood samples for statistical analysis of serum cortisol (SC) endpoints were collected on D0 and D42 at indicated time points. The weighted mean was calculated by dividing the area under curve (AUC) over the 24-hr time period by time period. Change from Baseline in 0-24 hr weighted mean SC was calculated as a ratio from baseline defined as SC weighted mean (0-24 hrs) at Wk 6 divided by the baseline SC weighted mean (0-24 hrs). The ratio as treatment ratios, using an analysis of covariance (ANCOVA) model, allowing for the effects of baseline (loge transformed from baseline was loge transformed prior to analysis. The loge transformed ratios were compared between treatment groups), age, sex and region. Treatment ratios for comparison was calculated by back-transforming the difference between Least square (LS) means. Using the pooled estimate of variance, 95% CIs) was calculated for the difference.
Time Frame Baseline, Day 0 (Predose, 2hr, 4hr, 8hr, 12hr, 16hr and 24hr) and Day 42 (0hr, 2hr, 4hr, 8hr, 16hr and 24hr)
Hide Outcome Measure Data
Hide Analysis Population Description
SC Population consisted of all par. in the ITT pop who did not have protocol violations that considered to affect the SC endpoint and whose serum samples were not considered to have confounding factors that would affect the interpretation of results. Par. with SC weighted mean (0-24 hr) calculated at baseline and Wk 6 were analyzed.
Arm/Group Title Fluticasone Furoate 50 mcg Placebo
Hide Arm/Group Description:
Par. received one inhalation, once daily of FF 50 mcg in the morning via ELLIPTA inhaler for 6 wks. Par. also received open label montelukast throughout the treatment period and were supplied with albuterol/salbutamol inhalation aerosol to use as needed to treat acute asthma symptoms.
Par. received one inhalation, once daily of placebo in the morning via ELLIPTA inhaler for 6 wks. Par. also received open label montelukast throughout the treatment period and were supplied with albuterol/salbutamol inhalation aerosol to use as needed to treat acute asthma symptoms.
Overall Number of Participants Analyzed 53 51
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Ratio
1.02
(47.16%)
1.00
(44.77%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Fluticasone Furoate 50 mcg, Placebo
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments Non inferiority was demonstrated if the lower limit of the two-sided 95% CI for the geometric mean ratio of each dose of fluticasone furoate 50 µg versus placebo was greater than 0.8.
Method of Estimation Estimation Parameter Least square Geometric Mean ratio
Estimated Value 0.93
Confidence Interval (2-Sided) 95%
0.8096 to 1.0620
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Change From Baseline (Expressed as a Ratio) in Area Under the Curve (AUC) 0-24 Hour Serum Cortisol at the End of the Six Week Treatment Period (Day 42).
Hide Description The blood samples for statistical analysis of area under the curve over the 24 hours (AUC 0-24 hours) endpoints were collected on Day 0 and Day 42 at the indicated time points. The AUC 0-24 hours was calculated using trapezoidal rule. Change from baseline in AUC 0-24 hour was calculated as a ratio from baseline defined as the AUC (0-24 hours) at Week 6 divided by the baseline AUC (0-24 hours) The ratio from baseline was loge transformed prior to analysis. The loge transformed ratios were compared between treatment groups as treatment ratios using an analysis of covariance (ANCOVA) model, allowing for the effects of baseline (loge transformed), age, sex and region. Treatment ratios for comparison was calculated by back-transforming the difference between the Least square (LS) means. Using the pooled estimate of variance, 95% Confidence Intervals (CIs) was calculated for the difference. Par. with SC weighted mean (0-24hr) calculated at baseline and Week 6 were analyzed
Time Frame Baseline and Week Baseline, Day 0 (Predose, 2hr, 4hr, 8hr, 12hr, 16hr and 24hr) and Day 42 (0hr, 2hr, 4hr, 8hr, 16hr and 24hr)
Hide Outcome Measure Data
Hide Analysis Population Description
The SC population
Arm/Group Title Fluticasone Furoate 50 mcg Placebo
Hide Arm/Group Description:
Par. received one inhalation, once daily of FF 50 mcg in the morning via ELLIPTA inhaler for 6 wks. Par. also received open label montelukast throughout the treatment period and were supplied with albuterol/salbutamol inhalation aerosol to use as needed to treat acute asthma symptoms.
Par. received one inhalation, once daily of placebo in the morning via ELLIPTA inhaler for 6 wks. Par. also received open label montelukast throughout the treatment period and were supplied with albuterol/salbutamol inhalation aerosol to use as needed to treat acute asthma symptoms.
Overall Number of Participants Analyzed 52 50
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Ratio
1.02
(47.11%)
1.00
(44.73%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Fluticasone Furoate 50 mcg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least square Geometric Mean ratio
Estimated Value 0.93
Confidence Interval (2-Sided) 95%
0.81 to 1.06
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Change From Baseline (Expressed as a Ratio) in 24-hour Urinary Cortisol Excretion at the End of the Six Week Treatment Period (Day 42)
Hide Description The 24 hr urinary cortisol excretion was collected over a 24 hour period on Day 0 and Day 42. Change from baseline in 24- hr urinary cortisol excretion was calculated as a ratio from baseline defined as 24-hr urinary cortisol excretion at Week 6 divided by the baseline 24-hr urinary cortisol excretion. The ratio from baseline was loge transformed prior to analysis. The loge transformed ratio was compared between treatment groups using an analysis of covariance (ANCOVA) model, allowing for the effects of baseline (loge transformed), age, sex and region. Treatment ratios for comparison was calculated by back-transforming the difference between the Least square (LS) means. Using the pooled estimate of variance, 95% Confidence Intervals (CIs) was calculated for the difference. Participants with 24-hr urinary cortisol excretion at baseline and Week 6 were analyzed.
Time Frame Baseline (Day 0) Day 42
Hide Outcome Measure Data
Hide Analysis Population Description
The Urinary Cortisol (UC) Population used consisted of all participants who did not have protocol violations that were considered to affect the urine cortisol endpoint and whose urine samples were not considered to have confounding factors that affect the interpretation of the results.
Arm/Group Title Fluticasone Furoate 50 mcg Placebo
Hide Arm/Group Description:
Par. received one inhalation, once daily of FF 50 mcg in the morning via ELLIPTA inhaler for 6 wks. Par. also received open label montelukast throughout the treatment period and were supplied with albuterol/salbutamol inhalation aerosol to use as needed to treat acute asthma symptoms.
Par. received one inhalation, once daily of placebo in the morning via ELLIPTA inhaler for 6 wks. Par also received open label montelukast throughout the treatment period and were supplied with albuterol/salbutamol inhalation aerosol to use as needed to treat acute asthma symptoms.
Overall Number of Participants Analyzed 51 50
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Ratio
0.69
(90.20%)
1.05
(123.86%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Fluticasone Furoate 50 mcg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least square Geometric Mean ratio
Estimated Value 0.79
Confidence Interval (2-Sided) 95%
0.61 to 1.03
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Change From Baseline (Expressed as a Ratio) in 24-hour 6-beta Hydroxycortisol Excretion at the End of the Six Week Treatment Period (Day 42).
Hide Description The 24 hr urinary 6-beta hydroxycortisol excretion was collected over a 24 hour period on Day 0 and Day 42. Change from baseline in 24- hr urinary 6-beta hydroxycortisol excretion was calculated as a ratio from baseline defined as 24-hr urinary 6-beta hydroxycortisol excretion at Week 6 divided by the baseline 24-hr urinary 6-beta hydroxycortisol excretion. The ratio from baseline was loge transformed prior to analysis. The loge transformed ratio was compared between treatment groups using an analysis of covariance (ANCOVA) model, allowing for the effects of baseline (loge transformed), age, sex and region. Treatment ratios for comparison was calculated by back-transforming the difference between the Least square (LS) means. Using the pooled estimate of variance, 95% Confidence Intervals (CIs) was calculated for the difference. Participants with 24-hr urinary cortisol excretion at baseline and Week 6 were analyzed.
Time Frame Baseline (Day 0) Day 42
Hide Outcome Measure Data
Hide Analysis Population Description
The UC Population.
Arm/Group Title Fluticasone Furoate 50 mcg Placebo
Hide Arm/Group Description:
Participants received one inhalation, once daily of FF 50 mcg in the morning via ELLIPTA inhaler for 6 wks. Participants also received open label montelukast throughout the treatment period and were supplied with albuterol/salbutamol inhalation aerosol to use as needed to treat acute asthma symptoms.
Participants received one inhalation, once daily of placebo in the morning via ELLIPTA inhaler for 6 wks. Participants also received open label montelukast throughout the treatment period and were supplied with albuterol/salbutamol inhalation aerosol to use as needed to treat acute asthma symptoms.
Overall Number of Participants Analyzed 50 49
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Ratio
0.78
(67.43%)
0.90
(65.54%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Fluticasone Furoate 50 mcg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least square Geometric Mean ratio
Estimated Value 0.88
Confidence Interval (2-Sided) 95%
0.72 to 1.07
Estimation Comments [Not Specified]
Time Frame Adverse events (AEs) and serious adverse events (SAEs) were collected from participants up to 9 weeks.
Adverse Event Reporting Description Safety analysis was based on Intent-to-Treat (ITT) population. Most frequent On-Treatment Non-serious AEs are reported. Most frequent is defined as >=3% (without rounding) in any treatment group. There were no fatal or non-fatal SAEs reported in the study.
 
Arm/Group Title Fluticasone Furoate 50 mcg Placebo
Hide Arm/Group Description Participants received one inhalation, once daily of FF 50 mcg in the morning via ELLIPTA inhaler for 6 wks. Participants also received open label montelukast throughout the treatment period and were supplied with albuterol/salbutamol inhalation aerosol to use as needed to treat acute asthma symptoms. Participants received one inhalation, once daily of placebo in the morning via ELLIPTA inhaler for 6 wks. Participants also received open label montelukast throughout the treatment period and were supplied with albuterol/salbutamol inhalation aerosol to use as needed to treat acute asthma symptoms.
All-Cause Mortality
Fluticasone Furoate 50 mcg Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Fluticasone Furoate 50 mcg Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   0/56 (0.00%)   0/55 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 3%
Fluticasone Furoate 50 mcg Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   4/56 (7.14%)   6/55 (10.91%) 
Nervous system disorders     
Headache  1  1/56 (1.79%)  3/55 (5.45%) 
Respiratory, thoracic and mediastinal disorders     
Upper respiratory tract infection  1  3/56 (5.36%)  3/55 (5.45%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 19.0
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
Layout table for Results Point of Contact information
Name/Title: GSK Response Center
Organization: GlaxoSmithKline
Phone: 866-435-7343
Layout table for additonal information
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT02483975     History of Changes
Other Study ID Numbers: 107118
First Submitted: June 25, 2015
First Posted: June 29, 2015
Results First Submitted: December 16, 2016
Results First Posted: March 8, 2017
Last Update Posted: June 14, 2017