A Phase 3 interventional study of FF and Placebo in Asthma, sponsored by GlaxoSmithKline. Completed at 17 sites in 2 countries. Open to participants aged 5 Years to 11 Years. Per ClinicalTrials.gov, last updated 2020-04-27.
Sponsored by GlaxoSmithKline · Phase 3, Interventional, and Treatment
Inhaled corticosteroids (ICS) have a number of known class effects including hypothalamic-pituitary-adrenocortical (HPA) axis suppression. Although the safety of inhaled Fluticasone Furoate (FF) on the HPA axis of adults and adolescent asthmatic patients has been established, it is important to assess the risk of suppression in children so as to establish whether this medicine can be safely used in this young population. This study aims to evaluate the effect of inhaled FF on the HPA axis of children 5-11 years of age (inclusive) with persistent asthma compared with placebo. Approximately 143 subjects will be enrolled. Subjects will enter a 7 to 14 day run-in period on oral montelukast 4 milligrams (mg) (5 year old subjects) or 5 mg (6-11 year old subjects) once daily. Eligible subjects will be randomized to receive once-daily FF inhalation powder 50 micrograms (mcg) or once-daily placebo inhalation powder in the morning via the ELLIPTA™ inhaler for 42 days. Subjects will continue to receive open label montelukast during the treatment period. All subjects will be provided albuterol/salbutamol inhalation aerosol, to use as needed to treat acute asthma symptoms throughout the study.
ELLIPTA is a registered trademark of the GlaxoSmithKline group of companies.
4,010 studies on the registry are indexed under Asthma; 514 are open to participants now.
This study's enrollment of 111 is above the median of 83 across 2,814 interventional studies indexed under Asthma.
Browse Asthma studies →GlaxoSmithKline is the lead sponsor of 3,647 studies on the registry; 118 are open to participants now.
Of its 264 completed or terminated interventional studies of FDA-regulated products, 239 (91%) have results posted.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
If applicable, subject must be able and willing to give assent to take part in the study according to the local requirement. The study investigator is accountable for determining a child's capacity to assent to participation in a research study, taking into consideration any standards set by the responsible Independent Ethics Committee (IEC)/Institutional Review Board (IRB).
Subject and their legal guardian understands that they must comply with study medication and study assessments.
Exclusion Criteria:
Drug Allergy/Intolerance: Any adverse reaction including immediate or delayed hypersensitivity to any Leukotriene receptor antagonist (LTRA), or intranasal, inhaled, or systemic corticosteroid therapy. Known or suspected sensitivity/intolerance to the constituents of the powder inhaler (i.e. lactose) or montelukast (e.g. phenylalanine).
Milk Protein Allergy: History of severe milk protein allergy.
Administration of systemic, oral, or depot corticosteroids within 12 weeks of Visit 1 is prohibited and during the study.
Use of an ICS is prohibited during the 8 weeks prior to Visit 1 and during the study.
Use of intranasal corticosteroids is prohibited during the 4 weeks prior to Visit 1 and during the study.
Use of dermatological/topical corticosteroids during the 8 weeks prior to Visit 1 and during the study.
Subjects will receive by oral inhalation FF 50 mcg once daily in the morning via ELLIPTA for 42 days. Subjects will continue to receive oral montelukast once daily in the evening and may use albuterol/salbutamol inhalation aerosol as needed.
Drug: FF · Drug: Montelukast · Drug: Albuterol/Salbutamol
Subjects will receive by oral inhalation placebo once daily in the morning via ELLIPTA for 42 days. Subjects will continue to receive oral montelukast once daily in the evening and may use albuterol/salbutamol inhalation aerosol as needed.
Drug: Placebo · Drug: Montelukast · Drug: Albuterol/Salbutamol
FF will be provided as a dry powder inhaler with 30 doses per device, each containing 50 mcg of FF as a dry white powder per blister, to be inhaled orally via ELLIPTA.
Placebo will be provided as dry powder inhaler with 30 doses per device, each containing placebo as a dry white powder per blister, to be inhaled orally via ELLIPTA.
Montelukast will be provided as 4 mg and 5 mg chewable tablets.
Drug page: Albuterol
Albuterol/Salbutamol will be provided as inhalation aerosol.
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
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)
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
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)
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).
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)
Change From Baseline (Expressed as a Ratio) in 24-hour Urinary Cortisol Excretion at the End of the Six Week Treatment Period (Day 42)
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
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).
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
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.
| Milestone | Fluticasone Furoate 50 mcg | Placebo |
|---|---|---|
| Started | 56 | 55 |
| Completed | 54 | 53 |
| Not completed | 2 | 2 |
| Withdrew: Adverse event | 0 | 1 |
| Withdrew: Lost to follow-up | 0 | 1 |
| Withdrew: Physician decision | 2 | 0 |
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.
| Ratio | Fluticasone Furoate 50 mcg | Placebo |
|---|---|---|
| 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 ± 46.71 | 1.01 ± 44.79 |
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.
| Ratio | Fluticasone Furoate 50 mcg | Placebo |
|---|---|---|
| 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 ± 47.16 | 1.00 ± 44.77 |
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
| Ratio | Fluticasone Furoate 50 mcg | Placebo |
|---|---|---|
| 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 ± 47.11 | 1.00 ± 44.73 |
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.
| Ratio | Fluticasone Furoate 50 mcg | Placebo |
|---|---|---|
| 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 ± 90.20 | 1.05 ± 123.86 |
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.
| Ratio | Fluticasone Furoate 50 mcg | Placebo |
|---|---|---|
| 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 ± 67.43 | 0.90 ± 65.54 |
Collected over Adverse events (AEs) and serious adverse events (SAEs) were collected from participants up to 9 weeks.. Non-serious events are listed at a 3% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Fluticasone Furoate 50 mcg | — | 0/56 (0%) | 4/56 (7.1%) |
| Placebo | — | 0/55 (0%) | 6/55 (10.9%) |
| Event | Fluticasone Furoate 50 mcg | Placebo |
|---|---|---|
| Upper respiratory tract infectionRespiratory, thoracic and mediastinal disorders | 3/56 | 3/55 |
| HeadacheNervous system disorders | 1/56 | 3/55 |
| Age, Continuous(Years) | Fluticasone Furoate 50 mcg | Placebo | Total |
|---|---|---|---|
| Overall study | 8.4 ± 1.97 | 8.4 ± 2.00 | 8.4 ± 1.97 |
| Sex: Female, Male(Participants) | Fluticasone Furoate 50 mcg | Placebo | Total |
|---|---|---|---|
| Female | 20 | 30 | 50 |
| Male | 36 | 25 | 61 |
| Ethnicity (NIH/OMB)(Participants) | Fluticasone Furoate 50 mcg | Placebo | Total |
|---|---|---|---|
| Hispanic or Latino | 15 | 17 | 32 |
| Not Hispanic or Latino | 41 | 38 | 79 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Race/Ethnicity, Customized(Participants) | Fluticasone Furoate 50 mcg | Placebo | Total |
|---|---|---|---|
| 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 |
Plan to share: Yes — IPD for this study will be made available via the Clinical Study Data Request site.
Supporting information: Study protocol, Statistical analysis plan, Informed consent form, Clinical study report
Time frame: IPD is available via the Clinical Study Data Request site (click on the link provided below)
Access criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
Data sharing details ↗ · clinicalstudydatarequest.com
Ran from Oct 2015 to primary completion in Jun 2016, 8 months.
Results were first posted in Mar 2017, 8 months after primary completion.
Of 167 industry-sponsored phase 3 interventional studies under Asthma, half reached primary completion within 26 months of starting (the median), counting those still running; a quarter within 13 and three quarters within 42. This study's 8 months is below that.
Counting every sponsor, half of 194 studies reached it within 27 months; a quarter within 14 and three quarters within 42.
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This study is completed, as verified in Apr 2020. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Fluticasone furoate