Clinical trial NCT02502734: Effect of Inhaled Fluticasone Furoate on Short-term Growth in Paediatric Subjects With Asthma
Official title: A Randomised, Double-blind, Two-way Crossover Study to Investigate the Effect of Inhaled Fluticasone Furoate on Short-term Growth in Paediatric Subjects With Asthma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Asthma
Keywords: inhaled corticosteroids
pediatric subjects
asthma
fluticasone furoate
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2015-07-20
Enrollment: 60
Sex: ALL
Minimum age (years): 5
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: This study will be conducted to evaluate the effect of once daily treatment with fluticasone furoate (FF) on lower leg growth in pediatric subjects with persistent asthma by using knemometry. Approximately 65 paediatric asthmatic subjects, aged 5 to 11 years (inclusive), will be screened to achieve 60 randomised and 50 evaluable subjects. Subjects meeting the eligibility criteria will enter the 2 week run-in period. After completing run-in period, each subject will be randomly allocated to one of two treatment sequences: inhaled fluticasone furoate followed by placebo or placebo followed by inhaled fluticasone furoate. Each treatment will be administered via the ELLIPTA™ dry powder inhaler. The two treatment periods will be separated by a two-week wash-out period. Subjects completing two treatment period will enter into 7 days follow-up period. ARNUITY™ ELLIPTA (FF) is approved in the US for adults and adolescents aged 12 and above.

ARNUITY and ELLIPTA are a registered trademarks of the GlaxoSmithKline group of companies.


Eligibility criteria: Inclusion Criteria:

* Aged 5 years to less than 12 years at Visit 1. At least 15 (25%) children of the total study population must be aged 5 to less than 8 years.
* Male or pre-menarchial female subjects.
* Subjects must be pre-adolescent without any signs of puberty (Tanner Stage 1).
* Normal range for their height and weight. Weight and height measurements should fall within the percentile range 3-97% of normal values for age according to Danish growth charts.
* Have a documented diagnosis of persistent asthma, as defined by the National Institutes of Health for at least 3 months prior to the Screening Visit.
* A pre-bronchodilatory forced expiratory flow in 1 second (FEV1) at Visit 1 (Screening) \>=80% predicted. There should be no Short acting beta-agonist (SABA) use within 4 hours of this measurement.
* Using one of the following asthma therapies prior to entry into the study: SABA inhaler alone (e.g. salbutamol) on an as required basis and/or Regular non-inhaled corticosteroid (ICS) controller medications for asthma (e.g. cromones or leukotriene receptor antagonists) and/or Previously treated with ICS (equipotent to inhaled budesonide \<=400 micrograms (mcg) total daily dose). There must be no ICS use within 2 weeks of Visit 1 (Screening).
* Able to replace their current SABA treatment with study supplied rescue SABA provided at Visit 1 for use as needed for the duration of the study.
* Written informed consent from at least one parent/care giver (legal guardian) and accompanying informed assent from the subject (where the subject is able to provide assent) prior to admission to the study: (1) 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). (2) Subject and their legal guardian(s) understand that the study requires them to be treated on an outpatient basis. (3) Subject and their legal guardian(s) understand that they must comply with study medication and study assessments including recording of peak expiratory flow and rescue SABA use, attending scheduled study visits, and being accessible by a telephone call.

Exclusion Criteria:

* 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).
* 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 or emergency room attendance (within 3 months) or requiring hospitalization for asthma (within 6 months) prior to screening.
* Significant, non-reversible active pulmonary disease (e.g. cystic fibrosis, bronchiectasis, tuberculosis).
* 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, is expected to affect the subject's asthma status or the subject's ability to participate in the study.
* Any fracture in the leg to be measured within 6 months prior to the screening visit.
* Any metabolic disorders or other diseases that may impact on normal growth patterns.
* No major surgery requiring general anaesthesia for at least 3 months prior to the screening visit.
* No febrile illnesses with temperature \>39 degree celsius for more than five consecutive days within the week preceding the Screening Visit.
* Any significant abnormality or medical condition identified at the screening medical assessment (including serious psychological disorder) that in the Investigator's opinion, preclude entry into the study due to risk to the subject or that may interfere with the outcome of the study.
* Clinical visual evidence of candidiasis at Visit 1 (Screening).
* Use of any of the prohibited medications listed in protocol.
* Strenuous physical exercise within 3 hours of Visit 1 (Screening)
* Drug allergies: Any adverse reaction including immediate or delayed hypersensitivity to any intranasal, inhaled, or systemic corticosteroid therapy. Known or suspected sensitivity to the constituents of the ELLIPTA Inhaler (i.e., lactose, FF).
* Milk Protein Allergy: History of severe milk protein allergy.
* The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
* Exposure to more than 4 investigational medicinal products within 12 months prior to the first dosing day.
* Unable to use the ELLIPTA inhaler and peak flow meter correctly.
* An affiliation with the Investigator site: the parents/guardians or child is an immediate family member of the participating Investigator, sub-Investigator, study coordinator, or employee of the participating Investigator.
* The Parent or Guardian has 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); 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.

Primary outcomes:
measure: Mean Growth Rate in Lower-leg Growth, as Determined by Knemometry.
timeFrame: Over a two week (14 day) treatment period for FF 50mcg OD and Placebo respectively.
Secondary outcomes:
measure: Number of Participants With Any Adverse Events (AE) and Any Serious Adverse Event (SAE).
timeFrame: From the start of study treatment until follow-up (assessed up to 54 days)
Other outcomes:
Locations:
city: Randers
country: Denmark
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Wolthers OD, Stone S, Bareille P, Tomkins S, Khindri S. Knemometry Assessment of Short-term Growth in Children With Asthma Receiving Fluticasone Furoate for 2 Weeks: A Randomized, Placebo-controlled, Crossover Trial. Clin Ther. 2017 Jun;39(6):1191-1199. doi: 10.1016/j.clinthera.2017.04.011. Epub 2017 May 22.