Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02889809
Recruitment Status : Recruiting
First Posted : September 7, 2016
Last Update Posted : June 20, 2019
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

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.

Condition or disease Intervention/treatment Phase
Asthma Drug: Fluticasone furoate Drug: Placebo Drug: Montelukast Drug: Short Acting Beta 2 Agonist Phase 4

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 450 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Study HZA114971, A Multicentre Randomised, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Effects of a One-Year Regimen of Orally Inhaled Fluticasone Furoate 50 mcg Once Daily on Growth Velocity in Prepubertal, Paediatric Subjects With Asthma
Actual Study Start Date : October 20, 2016
Estimated Primary Completion Date : February 13, 2021
Estimated Study Completion Date : February 13, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 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.
Drug: Fluticasone furoate
Fluticasone furoate will be supplied as 50 mcg per blister dry white powder for inhalation using ELLIPTA inhaler.

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

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)

Drug: Short Acting Beta 2 Agonist
Albuterol/salbutamol will be supplied as inhalation aerosol or nebulizer.

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

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)

Drug: Short Acting Beta 2 Agonist
Albuterol/salbutamol will be supplied as inhalation aerosol or nebulizer.




Primary Outcome Measures :
  1. Growth Velocity (centimetre/year cm/yr]) over the double-blind treatment period, as determined by stadiometry [ Time Frame: 52 weeks ]
    Growth velocity (cm/yr) will be calculated for each subject based on stadiometry data by fitting a regression line to all height measurements recorded for that subject during the period and determined by the slope of the fitted regression line. Height assessments will be conducted at the time of clinic visits at Week 4, 8, 12, 16, 28, 40 and 52.


Secondary Outcome Measures :
  1. Proportion of subjects below the 3rd percentile of growth velocity [ Time Frame: 52 weeks ]
    Growth velocity (cm/yr) will be calculated for each subject based on stadiometry data by fitting a regression line to all height measurements recorded for that subject during the period and determined by the slope of the fitted regression line. Height assessments will be conducted at the time of clinic visits at Week 4, 8, 12, 16, 28, 40 and 52.

  2. Change in growth velocity quartiles from baseline to endpoint [ Time Frame: Baseline and up to Week 52 ]
    Growth velocity (cm/yr) will be calculated for each subject based on stadiometry data by fitting a regression line to all height measurements recorded for that subject during the period and determined by the slope of the fitted regression line. Height assessments will be conducted at the time of clinic visits at Week 4, 8, 12, 16, 28, 40 and 52.

  3. Growth velocity over the first 12 weeks of double-blind treatment period [ Time Frame: 12 weeks ]
    Growth velocity (cm/yr) will be calculated for each subject based on stadiometry data by fitting a regression line to all height measurements recorded for that subject during the period and determined by the slope of the fitted regression line.

  4. Height standard deviation scores (SDS) at each visit [ Time Frame: Up to 60 weeks ]
    Height assessments will be conducted at the time of clinic visits at Week 4, 8, 12, 16, 28, 40, 52, 56, and 60.

  5. Number of subjects with incidence of adverse events [ Time Frame: Approximately 76 weeks ]
  6. Number of subjects with incidence of asthma exacerbations [ Time Frame: Approximately 76 weeks ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   5 Years to 9 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02889809


Contacts
Layout table for location contacts
Contact: US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com
Contact: EU GSK Clinical Trials Call Center +44 (0) 20 89904466 GSKClinicalSupportHD@gsk.com

  Show 63 Study Locations
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Layout table for investigator information
Study Director: GSK Clinical Trials GlaxoSmithKline

Layout table for additonal information
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT02889809     History of Changes
Other Study ID Numbers: 114971
First Posted: September 7, 2016    Key Record Dates
Last Update Posted: June 20, 2019
Last Verified: June 2019
Keywords provided by GlaxoSmithKline:
Growth Velocity
Prepubertal
Asthma
Paediatric
Additional relevant MeSH terms:
Layout table for MeSH terms
Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Fluticasone
Albuterol
Montelukast
Anti-Inflammatory Agents
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Dermatologic Agents
Anti-Allergic Agents
Leukotriene Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Cytochrome P-450 CYP1A2 Inducers
Cytochrome P-450 Enzyme Inducers
Molecular Mechanisms of Pharmacological Action
Tocolytic Agents
Reproductive Control Agents
Adrenergic beta-2 Receptor Agonists