Effects of a Orally Inhaled Fluticasone Furoate on Growth Velocity in Prepubertal, Paediatric Subjects With Asthma Over a Year

NCT ID: NCT02889809

Last Updated: 2024-01-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 477 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-07-10
• Study Completion Date: 2021-06-04

Brief Summary

There is a regulatory requirement to evaluate the extent of reduction (if any) of growth velocity associated with inhaled corticosteroid (ICS) containing products that are to be administered to children, and to this end there is Food and Drug Administration (FDA) regulatory guidance. This is a randomised, single-blind (run-in period)/double-blind (treatment period), parallel group, placebo controlled, multicentre study to assess the effect of once daily (OD) inhaled fluticasone furoate (FF) 50 microgram (mcg) on growth velocity in prepubertal asthmatic children on a background therapy of open-label montelukast. This study will be conducted over a total duration of approximately 76 weeks: 16-week run-in period (single-blind placebo inhaler), 52-week double-blind treatment period (inhaled FF 50 mcg /placebo administered OD in the morning for 52 weeks) and 8-week follow-up period. The purpose of the study is to evaluate the magnitude of effect (with a level of precision) on growth velocity of prepubertal asthmatic paediatric subjects (aged 5 to <9 years) following administration of OD inhaled FF 50 mcg for one year. This study fulfills European Union (EU) and United States (US) regulatory requirements for the evaluation of potential growth suppression in children.

Conditions

Asthma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Fluticasone furoate 50 mcg

During run-in period, subjects will receive inhaled placebo for 16 weeks using ELLIPTA inhaler. Followed by treatment period where subjects will receive inhaled FF 50 mcg administered once daily in the morning for 52 weeks using ELLIPTA inhaler. Subjects will also receive open-label montelukast (4 milligrams \[mg\] for subjects who are 5 years old and 5 mg for subjects who are \>= 6 years old) to be administered as one tablet of montelukast each evening for the duration of the study. Each subject will receive a SABA (albuterol/salbutamol \[inhalation aerosol or nebuliser\]) to be used as needed throughout the entire study period as rescue medication for symptomatic relief of asthma symptoms.

Group Type: EXPERIMENTAL

Fluticasone furoate

Intervention Type: DRUG

Fluticasone furoate will be supplied as 50 mcg per blister dry white powder for inhalation using ELLIPTA inhaler.

Placebo

Intervention Type: DRUG

Placebo will be supplied as dry white powder Lactose for inhalation using ELLIPTA inhaler.

Montelukast

Intervention Type: DRUG

Montelukast will be supplied as 4 mg chewable tablet (5 year old subjects) and as 5 mg chewable tablet (\>=6 year old subjects)

Short Acting Beta 2 Agonist

Intervention Type: DRUG

Albuterol/salbutamol will be supplied as inhalation aerosol or nebulizer.

Placebo

During run-in period, subjects will receive inhaled placebo for 16 weeks using ELLIPTA inhaler. Followed by treatment period where subjects will receive inhaled placebo administered once daily in the morning for 52 weeks using ELLIPTA inhaler. Subjects will also receive open-label montelukast (4 milligrams \[mg\] for subjects who are 5 years old and 5 mg for subjects who are \>=6 years old) to be administered as one tablet of montelukast each evening for the duration of the study. Each subject will receive a SABA (albuterol/salbutamol \[inhalation aerosol or nebuliser\]) to be used as needed throughout the entire study period as rescue medication for symptomatic relief of asthma symptoms.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo will be supplied as dry white powder Lactose for inhalation using ELLIPTA inhaler.

Montelukast

Intervention Type: DRUG

Montelukast will be supplied as 4 mg chewable tablet (5 year old subjects) and as 5 mg chewable tablet (\>=6 year old subjects)

Short Acting Beta 2 Agonist

Intervention Type: DRUG

Albuterol/salbutamol will be supplied as inhalation aerosol or nebulizer.

Interventions

Fluticasone furoate

Fluticasone furoate will be supplied as 50 mcg per blister dry white powder for inhalation using ELLIPTA inhaler.

Intervention Type: DRUG

Placebo

Placebo will be supplied as dry white powder Lactose for inhalation using ELLIPTA inhaler.

Intervention Type: DRUG

Montelukast

Montelukast will be supplied as 4 mg chewable tablet (5 year old subjects) and as 5 mg chewable tablet (\>=6 year old subjects)

Intervention Type: DRUG

Short Acting Beta 2 Agonist

Albuterol/salbutamol will be supplied as inhalation aerosol or nebulizer.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Male or female subjects.
• Age: Males between 5 and <9 years old; Females between 5 and <8 years old.
• Subjects must be pre-pubertal (Tanner Stage 1).
• Height centile between 3% and 97% based on local growth charts.
• Subjects with body weight and body mass index that is between 3rd and 97th centile based on the United State (US) Centres for Disease Control and Prevention (CDC) standard statistics or any local standards outside the US.
• A documented history of symptoms consistent with a diagnosis of asthma for at least 6 months prior to Visit 1.
• A pre-bronchodilatory forced expiratory flow in 1 second (FEV1) at Visit 1 (Screening) of between >=60% to <=95% predicted. There should be no short acting beta 2 agonist (SABA) use within 4 hours of this measurement.
• Able to replace their current SABA treatment with study supplied rescue albuterol/salbutamol provided at Visit 1 for use as needed for the duration of the study.
• A childhood asthma control test (cACT) score of >19.
• Subjects should have required at least one course of corticosteroid for their asthma (inhaled or oral) in the past year.
• There must be no ICS use within 6 weeks of Visit 1 (Screening).
• There must be no oral corticosteroids use within 12 weeks of Visit 1 (Screening).
• Using one or more of the following asthma therapies prior to entry into the study:

Short acting beta-agonist (SABA) inhaler alone (example given [e.g.] salbutamol) on an as needed basis and/or regular non-ICS controller medications for asthma (e.g. cromones or leukotriene receptor antagonists).

• 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. If applicable, subject must be able and willing to give assent to take part in the study according to local requirement. The study investigator is accountable for determining a child's capacity to assent for participation in a research study, taking into consideration any standards set by the responsible Independent Ethics Committee (IEC). Subject and their legal guardian(s) understand that they must comply with study medication administration regimens and study assessments including recording of symptom scores and rescue albuterol/salbutamol use, attending all study visits, and being accessible by telephone.

Exclusion Criteria

• Growth Criteria: Any previous or current condition that affects growth, including sleep disorders, endocrine disorders, skeletal dysplasia, Turner and Noonan syndromes, Marfan, Beckwith-Wiedeman and Sotos syndromes, Klinefelter's syndrome, coeliac disease, inflammatory bowel diseases and renal failure or any significant abnormality or medical condition that is identified at the screening medical assessment (including serious psychological disorder) that is likely to interfere with the conduct of the study.
• Subjects with premature adrenarche.
• A child who is unable to stand, or who finds standing difficult due to illness or physical disabilities should be excluded.
• Disease Criteria: Subjects with a history of asthma exacerbation requiring the use of systemic corticosteroids (tablets, suspension, or injection) for at least 3 days or use of a depot corticosteroid injection within 3 months or those requiring hospitalisation for asthma (within 6 months) prior to screening.
• 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.
• Clinical visual evidence of candidiasis at Visit 1 (Screening).
• Any significant abnormality or medical condition identified at the screening medical assessment 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.
• General: Prior use of any medication or treatment that might affect growth including, but not limited to: amphetamines, anticonvulsants, biphosphonates, calcitonin, calcitriol, erythropoietin, growth hormone, methylphenidate, phosphate binders, antithyroid drugs (e.g., Methimazole) or thyroid hormone.
• Use of any of the prohibited medications listed in the study protocol.
• Hypersensitivity: Known hypersensitivity to corticosteroids, leukotrienes, or any excipients in the ELLIPTA (ELLIPTA is a Glaxosmithkline owned trademark for dry powder inhaler) inhaler and study tablets.
• 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.
• Children who are 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 known or suspected 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.

• Minimum Eligible Age: 5 Years
• Maximum Eligible Age: 9 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Little Rock, Arkansas, United States

GSK Investigational Site

Huntington Beach, California, United States

GSK Investigational Site

Homestead, Florida, United States

GSK Investigational Site

Loxahatchee Groves, Florida, United States

GSK Investigational Site

Miami, Florida, United States

GSK Investigational Site

Miami, Florida, United States

GSK Investigational Site

Miami, Florida, United States

GSK Investigational Site

Miami, Florida, United States

GSK Investigational Site

St. Petersburg, Florida, United States

GSK Investigational Site

Gainesville, Georgia, United States

GSK Investigational Site

Ypsilanti, Michigan, United States

GSK Investigational Site

Bellevue, Nebraska, United States

GSK Investigational Site

Raleigh, North Carolina, United States

GSK Investigational Site

Medford, Oregon, United States

GSK Investigational Site

Pittsburgh, Pennsylvania, United States

GSK Investigational Site

Orangeburg, South Carolina, United States

GSK Investigational Site

San Antonio, Texas, United States

GSK Investigational Site

Waco, Texas, United States

GSK Investigational Site

Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina

GSK Investigational Site

Lanús, Buenos Aires, Argentina

GSK Investigational Site

Buenos Aires, , Argentina

GSK Investigational Site

Buenos Aires, , Argentina

GSK Investigational Site

Mendoza, , Argentina

GSK Investigational Site

Bialystok, , Poland

GSK Investigational Site

Bialystok, , Poland

GSK Investigational Site

Bydgoszcz, , Poland

GSK Investigational Site

Gdansk-Wrzeszcz, , Poland

GSK Investigational Site

Krakow, , Poland

GSK Investigational Site

Lublin, , Poland

GSK Investigational Site

Skarżysko-Kamienna, , Poland

GSK Investigational Site

Szczecin, , Poland

GSK Investigational Site

Tarnów, , Poland

GSK Investigational Site

Brasov, , Romania

GSK Investigational Site

Brasov, , Romania

GSK Investigational Site

Bucharest, , Romania

GSK Investigational Site

ClujNapoca, , Romania

GSK Investigational Site

Sangiorgiu de Mures, , Romania

GSK Investigational Site

Moscow, , Russia

GSK Investigational Site

Moscow, , Russia

GSK Investigational Site

Novosibirsk, , Russia

GSK Investigational Site

Saint Petersburg, , Russia

GSK Investigational Site

Saint Petersburg, , Russia

GSK Investigational Site

Saint Petersburg, , Russia

GSK Investigational Site

Saint Petersburg, , Russia

GSK Investigational Site

Saint Petersburg, , Russia

GSK Investigational Site

Saint Petersburg, , Russia

GSK Investigational Site

Tomsk, , Russia

GSK Investigational Site

Voronezh, , Russia

GSK Investigational Site

Yaroslavl, , Russia

GSK Investigational Site

Middelburg, Mpumalanga, South Africa

GSK Investigational Site

Bellville, , South Africa

GSK Investigational Site

Cape Town, , South Africa

GSK Investigational Site

Cape Town, , South Africa

GSK Investigational Site

Cape Town, , South Africa

Countries

United States; Argentina; Poland; Romania; Russia; South Africa

References

Bareille P, Imber V, Crawford J, Majorek-Olechowska B, Karam-Absi Z, Stone S, Birk R. A multicenter randomized, double-blind, placebo-controlled, parallel-group study to evaluate the effects of a 1-year regimen of orally inhaled fluticasone furoate 50 microg once daily on growth velocity in prepubertal, pediatric participants with well-controlled asthma. Pediatr Pulmonol. 2023 Dec;58(12):3487-3497. doi: 10.1002/ppul.26679. Epub 2023 Sep 20.

Reference Type: BACKGROUND

PMID: 37728224 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

114971

Identifier Type: -

Identifier Source: org_study_id