Trial Outcomes & Findings for Effect of Fluticasone Furoate Inhalation Powder on the Hypothalamic-pituitary-adrenocortical Axis of Children Aged 5-11 Years With Asthma (NCT NCT02483975)

Last Updated: 2020-04-27

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

111 participants

Primary outcome timeframe

Baseline, D 0 (Pre-dose, 2hr, 4hr, 8hr, 12hr, 16hr and 24hr) and Day 42 (0hr, 2hr, 4hr, 8hr, 16hr and 24hr)

Results posted on

2020-04-27

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure	Fluticasone Furoate 50 mcg 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.	Placebo 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 Study STARTED	56	55
Overall Study COMPLETED	54	53
Overall Study NOT COMPLETED	2	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Fluticasone Furoate 50 mcg 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.	Placebo 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 Study Adverse Event	0	1
Overall Study Lost to Follow-up	0	1
Overall Study Physician Decision	2	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Fluticasone Furoate 50 mcg n=56 Participants 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.	Placebo n=55 Participants 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 n=111 Participants Total of all reporting groups
Age, Continuous Overall study	8.4 Years STANDARD_DEVIATION 1.97 • n=5 Participants	8.4 Years STANDARD_DEVIATION 2.00 • n=7 Participants	8.4 Years STANDARD_DEVIATION 1.97 • n=5 Participants
Sex: Female, Male Female	20 Participants n=5 Participants	30 Participants n=7 Participants	50 Participants n=5 Participants
Sex: Female, Male Male	36 Participants n=5 Participants	25 Participants n=7 Participants	61 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	15 Participants n=5 Participants	17 Participants n=7 Participants	32 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	41 Participants n=5 Participants	38 Participants n=7 Participants	79 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	32 Participants n=5 Participants	29 Participants n=7 Participants	61 Participants n=5 Participants
Race/Ethnicity, Customized White- White/Caucasian/European Heritage	21 Participants n=5 Participants	21 Participants n=7 Participants	42 Participants n=5 Participants
Race/Ethnicity, Customized Multiple-American Indian or Alaskan native & white	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Multiple-East Asian Heritage & African American	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Multiple- Asian-Japanese Heritage and White	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Multiple- Black or African American and White	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, D 0 (Pre-dose, 2hr, 4hr, 8hr, 12hr, 16hr and 24hr) and Day 42 (0hr, 2hr, 4hr, 8hr, 16hr and 24hr)

Population: 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.

Outcome measures

Outcome measures
Measure	Fluticasone Furoate 50 mcg n=53 Participants 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.	Placebo n=51 Participants 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.
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	1.02 Ratio Geometric Coefficient of Variation 46.71	1.01 Ratio Geometric Coefficient of Variation 44.79

PRIMARY outcome

Timeframe: Baseline, Day 0 (Predose, 2hr, 4hr, 8hr, 12hr, 16hr and 24hr) and Day 42 (0hr, 2hr, 4hr, 8hr, 16hr and 24hr)

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Fluticasone Furoate 50 mcg n=53 Participants 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.	Placebo n=51 Participants 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.
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	1.02 Ratio Geometric Coefficient of Variation 47.16	1.00 Ratio Geometric Coefficient of Variation 44.77

SECONDARY outcome

Timeframe: Baseline and Week Baseline, Day 0 (Predose, 2hr, 4hr, 8hr, 12hr, 16hr and 24hr) and Day 42 (0hr, 2hr, 4hr, 8hr, 16hr and 24hr)

Population: The SC population

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

Outcome measures

Outcome measures
Measure	Fluticasone Furoate 50 mcg n=52 Participants 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.	Placebo n=50 Participants 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.
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).	1.02 Ratio Geometric Coefficient of Variation 47.11	1.00 Ratio Geometric Coefficient of Variation 44.73

SECONDARY outcome

Timeframe: Baseline (Day 0) Day 42

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Fluticasone Furoate 50 mcg n=51 Participants 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.	Placebo n=50 Participants 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.
Change From Baseline (Expressed as a Ratio) in 24-hour Urinary Cortisol Excretion at the End of the Six Week Treatment Period (Day 42)	0.69 Ratio Geometric Coefficient of Variation 90.20	1.05 Ratio Geometric Coefficient of Variation 123.86

SECONDARY outcome

Timeframe: Baseline (Day 0) Day 42

Population: The UC Population.

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.

Outcome measures

Outcome measures
Measure	Fluticasone Furoate 50 mcg n=50 Participants 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.	Placebo n=49 Participants 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.
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).	0.78 Ratio Geometric Coefficient of Variation 67.43	0.90 Ratio Geometric Coefficient of Variation 65.54

Adverse Events

Fluticasone Furoate 50 mcg

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Fluticasone Furoate 50 mcg n=56 participants at risk 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.	Placebo n=55 participants at risk 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.
Respiratory, thoracic and mediastinal disorders Upper respiratory tract infection	5.4% 3/56 • Adverse events (AEs) and serious adverse events (SAEs) were collected from participants up to 9 weeks. 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.	5.5% 3/55 • Adverse events (AEs) and serious adverse events (SAEs) were collected from participants up to 9 weeks. 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.
Nervous system disorders Headache	1.8% 1/56 • Adverse events (AEs) and serious adverse events (SAEs) were collected from participants up to 9 weeks. 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.	5.5% 3/55 • Adverse events (AEs) and serious adverse events (SAEs) were collected from participants up to 9 weeks. 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.

Additional Information

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Phone: 866-435-7343

Results disclosure agreements

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