Clinical trial NCT02483975: Effect of Fluticasone Furoate Inhalation Powder on the Hypothalamic-pituitary-adrenocortical Axis of Children Aged 5-11 Years With Asthma
Official title: A Randomized, Double-blind, Placebo-controlled, Parallel Group Study of Once-daily Inhaled Fluticasone Furoate Inhalation Powder for Six Weeks on the Hypothalamic-pituitary-adrenocortical Axis of Children Aged 5-11 Years With Asthma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Asthma
Keywords: Fluticasone Furoate
Asthma
HPA axis
Children
Inhaled corticosteroid
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2015-06-29
Enrollment: 111
Sex: ALL
Minimum age (years): 5
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

* Informed consent: Written informed consent from at least one parent/care giver and the accompanying informed assent from the subject (where the subject is able to provide assent) prior to admission to the study.

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.

* Age: 5-11 years (inclusive) at Visit 1.
* Weight: Subjects must weigh at least 17 kilograms (kg).
* Gender: Male and pre-menarchial female. Pre-menarchial females are defined as any female who has yet to begin menses.
* Diagnosis of asthma: Subjects must have a diagnosis of asthma documented in their medical history at least 6 months prior to Visit 1.
* Childhood Asthma Control Test (C-ACT): Subjects must have a C-ACT score of \>19.
* Asthma Therapy Prior to Visit 1: Subjects are eligible if they have been using non-corticosteroid controller and/or short-acting beta2-agonist (SABA) bronchodilators alone for at least 4 weeks prior to Visit 1.
* Ability to use Dry Powder Inhalers: Subjects must demonstrate the ability to use the ELLIPTA inhaler under the supervision of their parents/caregiver.
* SABA: All subjects must be able to replace their current SABA treatment with albuterol/salbutamol aerosol inhaler at Visit 1 for use as needed for the duration of the study. Albuterol/salbutamol metered dose inhaler (MDI) will be administered with or without a spacer, to be used as determined by the investigator. The use or non-use of the spacer should be consistent for an individual subject throughout the study.
* Peak Flow Meter/Daily Diary Compliance: A subject must be able to use the study-provided peak flow meter and the subject/caregiver must be able to maintain the electronic diary record.

Exclusion Criteria:

* History of Life-Threatening Asthma: Subjects with a history of life-threatening asthma defined for this protocol as an asthma episode that required intubation, hypercapnea requiring non-invasive ventilatory support, respiratory arrest, hypoxic seizures or asthma-related syncopal episode(s).
* Asthma Exacerbation: Subjects with a history of asthma exacerbation requiring the use of systemic corticosteroids (tablets, suspension, or injection) for at least 3 days or a depot corticosteroid injection (within 3 months) or requiring hospitalization for asthma (within 6 months) prior to screening.
* Respiratory Infection: Culture-documented or suspected bacterial or viral infection of the upper or lower respiratory tract, sinus or middle ear that is not resolved within 4 weeks of Visit 1 and led to a change in asthma management or in the opinion of the Investigator, expected to affect the subject's asthma status or the subject's ability to participate in the study.
* Oropharyngeal Examination: A subject will not be eligible for the run-in if he/she has clinical visual evidence of candidiasis at Visit 1.
* Concurrent Disease: Any significant abnormality or medical condition identified at the screening medical assessment (including serious psychological disorder and congenital metabolic disorders) likely to interfere with the conduct of the study or affect the safety of the patient.
* Allergies/Intolerance:

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.

* Corticosteroid Use:

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.

* Concomitant Medication: Use of prescription or over-the-counter medications that would significantly affect the course of asthma or the HPA axis system of subjects. In addition, use of potent cytochrome P450 3A4 (CYP3A4) inhibitors within 4 weeks of Visit 1 and during the study (e.g., Clarithromycin, atazanavir, indinavir, itraconazole, ketoconazole, nefazadone, nelfinavir; ritonavir; saquinavir; telithromycin, troleandomycin, voriconazole, mibefradil, cyclosporine).
* Tobacco/Marijuana Use: Present use of any tobacco or marijuana products.
* Affiliation with Investigator's Site: A subject will not be eligible for this study if he/she is an immediate family member of the participating investigator, sub-investigator, study coordinator, or employee of the participating investigator.
* Parental/ Guardian Factors: Parent or Guardian with a history of psychiatric disease, intellectual deficiency, substance abuse or other condition (e.g. inability to read, comprehend or write) which may affect: validity of consent to participate in the study, adequate supervision of the subject during the study, compliance of subject with study medication and study procedures (e.g. completion of daily diary, attending scheduled clinic visits) and subject safety and well-being.
* Children in Care: Children who are wards of the government or state are not eligible for participation in this study.
* Clinically significant obesity: Defined as greater than 98th percentile.

Primary outcomes:
measure: 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
timeFrame: Baseline, D 0 (Pre-dose, 2hr, 4hr, 8hr, 12hr, 16hr and 24hr) and Day 42 (0hr, 2hr, 4hr, 8hr, 16hr and 24hr)
measure: 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
timeFrame: Baseline, Day 0 (Predose, 2hr, 4hr, 8hr, 12hr, 16hr and 24hr) and Day 42 (0hr, 2hr, 4hr, 8hr, 16hr and 24hr)
Secondary outcomes:
measure: 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).
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)
measure: Change From Baseline (Expressed as a Ratio) in 24-hour Urinary Cortisol Excretion at the End of the Six Week Treatment Period (Day 42)
timeFrame: Baseline (Day 0) Day 42
measure: 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).
timeFrame: Baseline (Day 0) Day 42
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: GSK Investigational Site
state: Arkansas
city: Alhambra
country: United States
facility: GSK Investigational Site
state: California
city: Costa Mesa
country: United States
facility: GSK Investigational Site
state: California
city: Huntington Beach
country: United States
facility: GSK Investigational Site
state: California
city: Newport Beach
country: United States
facility: GSK Investigational Site
state: California
city: Homestead
country: United States
facility: GSK Investigational Site
state: Florida
city: Miami
country: United States
facility: GSK Investigational Site
state: Florida
city: Miami
country: United States
facility: GSK Investigational Site
state: Florida
city: Miami
country: United States
facility: GSK Investigational Site
state: Florida
city: Raleigh
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Oklahoma City
country: United States
facility: GSK Investigational Site
state: Oklahoma
city: Oklahoma City
country: United States
facility: GSK Investigational Site
state: Oklahoma
city: Orangeburg
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Houston
country: United States
facility: GSK Investigational Site
state: Texas
city: Middelburg
country: South Africa
facility: GSK Investigational Site
state: Mpumalanga
city: Panorama
country: South Africa
facility: GSK Investigational Site
state: Western Province
city: Bellville
country: South Africa
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Bareille P, Tomkins S, Imber V, Tayob M, Dunn K, Mehta R, Khindri S. A randomized, double-blind, placebo-controlled, parallel-group study of once-daily inhaled fluticasone furoate on the hypothalamic-pituitary-adrenocortical axis of children with asthma. Allergy Asthma Clin Immunol. 2020 Feb 4;16:11. doi: 10.1186/s13223-020-0406-6. eCollection 2020.