Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Safety and Efficacy Study of Fluticasone Furoate/Vilanterol (FF/VI) Fixed Dose Combination (FDC) Compared to FF Alone in Subjects With Asthma

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: NCT03248128
Recruitment Status : Recruiting
First Posted : August 14, 2017
Last Update Posted : March 3, 2020
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Brief Summary:
The goal of asthma treatment is to achieve and maintain asthma control and to reduce the future risk of exacerbations. Inhaled corticosteroids (ICS) are considered as the most effective anti- inflammatory treatment for all severities of persistent asthma. For children >=5 years of age and adolescents whose asthma is uncontrolled, low-dose ICS plus adjunctive therapy with long-acting beta agonist (LABA) is considered as effective. Thus, this study is designed to evaluate the efficacy and safety of FF (ICS component)/VI (LABA component) compared to FF alone for the treatment of asthma, in subjects aged 5 to 17 years old currently uncontrolled on ICS. The study will be conducted over a total duration of approximately 29 weeks: 4 week run-in period, 24-week double-blind treatment period and 1-week follow-up period. Subjects will be randomized to receive FDC of FF/VI or FF administered via ELLIPTA® dry powder inhaler (DPI). The dose of both FF/VI and FF alone will be selected based on the age of subjects. Subjects will receive a short acting beta 2 agonist (SABA) (albuterol /salbutamol) as a rescue medication throughout the study. A total of 870 subjects will be randomized in the study. Of this, 652 subjects will be aged 5 to 11 years (cohort A), and 218 will be aged 12 to 17 years inclusive (cohort B). ELLIPTA is a registered trademark of GlaxoSmithKline (GSK) group of companies.

Condition or disease Intervention/treatment Phase
Asthma Drug: FF/VI via ELLIPTA DPI Drug: FF via ELLIPTA DPI Phase 3

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 870 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Subjects will be randomized to receive FDC of FF/VI inhalation powder compared to FF inhalation powder, once daily in cohort A and cohort B.
Masking: Double (Participant, Investigator)
Masking Description: This will be a double blind study. Subjects and investigator will be masked.
Primary Purpose: Treatment
Official Title: A Randomised, Double-blind, Parallel Group, Multicentre, Stratified, Study Evaluating the Efficacy and Safety of Once Daily Fluticasone Furoate/Vilanterol Inhalation Powder Compared to Once Daily Fluticasone Furoate Inhalation Powder in the Treatment of Asthma in Participants Aged 5 to 17 Years Old (Inclusive) Currently Uncontrolled on Inhaled Corticosteroids
Actual Study Start Date : October 20, 2017
Estimated Primary Completion Date : August 26, 2022
Estimated Study Completion Date : August 26, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Asthma

Arm Intervention/treatment
Experimental: Subjects receiving FF/VI in cohort A
Subjects will be randomized in 1:1 ratio to receive a FDC of FF/VI with a dose of 50/25 mcg administered once daily in the morning via ELLIPTA DPI.
Drug: FF/VI via ELLIPTA DPI
ELLIPTA DPI inhaler will contain two individual blister strips; the first strip will contain FF(50 or 100 mcg) and second strip will contain VI (25 mcg).

Active Comparator: Subjects receiving FF in cohort A
Subjects will be randomized in 1:1 ratio to receive FF with a dose of 50 mcg administered once daily in the morning via ELLIPTA DPI.
Drug: FF via ELLIPTA DPI
ELLIPTA DPI inhaler will contain a single blister strip of FF (50 or 100 mcg).

Experimental: Subjects receiving FF/VI in cohort B
Subjects will be randomized in 1:1 ratio to receive a FDC of FF/VI with a dose of 100/25 mcg administered once daily in the morning via ELLIPTA DPI.
Drug: FF/VI via ELLIPTA DPI
ELLIPTA DPI inhaler will contain two individual blister strips; the first strip will contain FF(50 or 100 mcg) and second strip will contain VI (25 mcg).

Active Comparator: Subjects receiving FF in cohort B
Subjects will be randomized in 1:1 ratio to receive FF with a dose of 100 mcg administered once daily in the morning via ELLIPTA DPI.
Drug: FF via ELLIPTA DPI
ELLIPTA DPI inhaler will contain a single blister strip of FF (50 or 100 mcg).




Primary Outcome Measures :
  1. Cohort A: Change from Baseline, in pre-dose (i.e. trough) morning peak expiratory flow (PEF) averaged over weeks 1-12 of the treatment period [ Time Frame: Baseline and up to Week 12 ]
    PEF is defined as the maximum speed of expiration of a person. PEF will be measured using a hand-held electronic peak flow meter each morning prior to the dose of study medication and any rescue albuterol/salbutamol inhalation aerosol use. The best of three measurements will be recorded in the daily diary.

  2. Cohort A and B: Weighted mean forced expiratory volume in 1 second (FEV1) (0-4 hours) at Week 12 [ Time Frame: Week 12 ]
    Pulmonary function will be measured by FEV1, defined as the maximal amount of air that can be forcefully exhaled in one second. FEV1 will be measured using a standardized calibrated spirometer prior to the dose of study medication and any rescue albuterol/salbutamol inhalation aerosol use.


Secondary Outcome Measures :
  1. Cohort A: Weighted mean of FEV1 (0-4 hours) at Week 12 [ Time Frame: Week 12 ]
    Pulmonary function will be measured by FEV1, defined as the maximal amount of air that can be forcefully exhaled in one second. FEV1 will be measured using a standardized calibrated spirometer prior to the dose of study medication and any rescue albuterol/salbutamol inhalation aerosol use.

  2. Cohort A and B: Change from Baseline, in pre-dose (i.e. trough) morning PEF averaged over weeks 1-12 of the treatment period [ Time Frame: Baseline and up to Week 12 ]
    PEF is defined as the maximum speed of expiration of a person. PEF will be measured using a hand-held electronic peak flow meter each morning prior to the dose of study medication and any rescue albuterol/salbutamol inhalation aerosol use. The best of three measurements will be recorded in the daily diary.

  3. Cohort A and B: Change from Baseline in the percentage of rescue-free 24-hour periods over weeks 1-12 of the treatment period [ Time Frame: Baseline and up to Week 12 ]
    The number of inhalations of rescue albuterol/salbutamol aerosol used during the day and night will be recorded in a daily electronic diary. A 24-hour period in which the response of subjects to both the morning and evening assessments indicated no use of rescue medication will be considered as 'rescue free'.

  4. Cohort A and B: Change from Baseline in the percentage of symptom-free 24-hour periods over weeks 1-12 of the treatment period [ Time Frame: Baseline and up to Week 12 ]
    The symptom-free days will be recorded in a daily electronic diary every day in the morning and evening before taking any rescue or study medication and before the PEF measurement. A 24-hour period in which the response of subjects to both the morning and evening assessments indicated no symptoms will be considered as 'symptom free'.

  5. Cohort A and B: Change from Baseline in morning (ante meridiem [AM]) FEV1 at Week 12 [ Time Frame: Baseline and at Week 12 ]
    Pulmonary function will be measured by FEV1, defined as the maximal amount of air that can be forcefully exhaled in one second. Morning FEV1 will be measured using a standardized calibrated spirometer prior to the dose of study medication and any rescue albuterol/salbutamol inhalation aerosol use.

  6. Cohort A and B: Change from Baseline in asthma control questionnaire (ACQ-5) at Week 24 [ Time Frame: Baseline and at Week 24 ]
    The ACQ-5 is a five-item questionnaire, which includes five questions (concerning nocturnal awakening, waking in the morning, activity limitation, shortness of breath and wheeze). The questions will enquire about the frequency and/or severity of symptoms over the previous week and will be self-completed by the subjects. The response options for all these questions will consist of a scale ranging from 0 (no impairment/limitation) to 6 (total impairment/ limitation). A score of <0.75 indicates well-controlled asthma and a score >=1.5 indicates poorly controlled asthma. A change of >=0.5 in score suggests a clinically important change in score.

  7. Cohort A and B: Number of subjects with incidence of exacerbations over the 24-Week treatment period [ Time Frame: Up to Week 24 ]
    An exacerbation is defined as deterioration of asthma requiring the use of systemic corticosteroids (tablets, suspension, or injection) for at least 3 days or a single depot corticosteroid injection or an in-patient hospitalization or emergency department visit due to asthma that required systemic corticosteroids. Information regarding asthma exacerbations will be collected and recorded over the specified period.

  8. Cohort A and B: Number of subjects with adverse events (AEs), serious adverse events (SAEs) [ Time Frame: Up to Week 25 ]
    An AE is any untoward medical occurrence in a subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment will be categorized as SAE.

  9. Cohort A and B: Number of subjects with abnormal electrocardiogram (ECG) findings [ Time Frame: Up to Week 24 ]
    A single 12-lead ECG will be obtained using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QT interval corrected (QTc).

  10. Cohort A and B:Number of subjects with abnormal fasting blood glucose levels [ Time Frame: Up to Week 24 ]
    Blood samples will be collected for evaluation of fasting blood glucose pre- and post-treatment.



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 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • For all subjects: Between 5 and 17 years of age inclusive, at the time of signing the informed consent.
  • A history of symptoms consistent with a diagnosis of asthma for at least 6 months.
  • Pre-bronchodilator FEV1 >50 percent to <=90 percent predicted normal. A minimum of 2 efforts that are considered acceptable (not necessarily repeatable) are required to be eligible.
  • Lung function reversibility defined as an increase of >=12 percent in FEV1 within 10 to 40 minutes following 2 to 4 inhalations of salbutamol inhalation aerosol (or 1 nebulized treatment with albuterol/salbutamol solution). Use of a spacer is permitted.
  • Uncontrolled asthma, with a childhood asthma control test (cACT)/ACT score <=19.
  • Receiving stable asthma therapy (SABA inhaler plus ICS [total daily dose <=FP 250 micrograms (mcg) or equivalent]) for at least 4 weeks prior to Visit 1 (i.e. screening).
  • Able to replace their current SABA treatment with salbutamol aerosol inhaler at Visit 1 for use as needed for the duration of the study. 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.
  • Male or female subjects will be included. Females of reproductive potential must agree to follow 1 of the options listed (which include abstinence) in the Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential (FRP) from 30 days prior to the first dose of study medication and until at least five terminal half-lives or until any continuing pharmacologic effect has ended, whichever is longer after the last dose of study medication and completion of the follow-up call. The investigator is responsible for ensuring that subjects understand how to properly use these methods of contraception.
  • Written informed consent from at least 1 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 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); subject and their legal guardian(s) understand that the study requires them to be treated on an outpatient basis; subject and their legal guardian(s) understand that they must comply with study medication and study assessments including recording of PEF and rescue SABA use, attending scheduled study visits, and being accessible by a telephone call.
  • For subjects eligible for randomization; asthma control: uncontrolled asthma, with a cACT/ACT score <=19.
  • A technically acceptable pre-bronchodilator FEV1 >50 percent to <=90 percent predicted normal at Visit 2. A minimum of 2 efforts that are considered acceptable and repeatable following the over read are required to be eligible.
  • Symptoms and rescue use: demonstrated and reported in a daily diary symptoms of asthma (a score of >=1 on the day-time or night-time asthma symptom scores) and/or daily albuterol/salbutamol on at least 3 of the last 7 consecutive days of the run-in period (not including the date of randomization).
  • Compliance with run-in medication: compliance is defined as use of run-in medication on at least 4 of the last 7 consecutive days of the run-in period (not including the date of randomization) recorded in the electronic subject diary.
  • Compliance with completion of the daily diary reporting: defined as completion of all questions on 4 out of the last 7 days during the run-in period (not including the date of randomization).

Exclusion Criteria:

  • For all subjects: History of life threatening asthma defined as an asthma episode that required intubation and/or was associated with hypercapnea, respiratory arrest or hypoxic seizures.
  • Any asthma exacerbation requiring the use of oral steroids within 6 weeks of Visit 1, systemic or depot corticosteroids within 12 weeks of Visit 1, or ER attendance within 3 months of Visit 1 or hospitalization within 6 months of Visit 1.
  • A culture documented or suspected bacterial or viral infection of the upper or lower respiratory tract, sinus or middle ear that has not resolved within 4 weeks of Visit 1 and which 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 oropharyngeal candidiasis.
  • Fasting blood glucose at screening >100 milligrams/deciliter (mg/dL) (5.6 moles per liter [mol/L]).
  • Obesity (Body Mass Index [BMI] above the 97th centile based on the centers for disease control and prevention [CDC] charts).
  • 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 conduct and/or outcome of the study.
  • QTc >450 milliseconds (msec) or QTc >480 msec in subjects with bundle branch block or any other clinically significant abnormality in the screening 12-lead ECG.
  • Use of any prohibited medications.
  • Present use of any tobacco products.
  • Drug allergies: any adverse reaction including immediate or delayed hypersensitivity to any beta 2-agonists, sympathomimetic drug or any intranasal, inhaled, or systemic corticosteroid therapy. Known or suspected sensitivity to the constituents of the ELLIPTA Inhaler (i.e. lactose or magnesium stearate).
  • Milk Protein Allergy: history of severe milk protein allergy.
  • 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, five half-lives or twice the duration of the biological effect of the study treatment (whichever is longer).
  • Exposure to more than 4 investigational medicinal products within 12 months prior to the first dosing day.
  • 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 (example, 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 (example, 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.
  • For subjects eligible for randomization; Changes in asthma medication that occur after screening.
  • Occurrence of a culture-documented or suspected bacterial or viral infection of the upper or lower respiratory tract, sinus or middle ear during the run-in period that 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.
  • Evidence of an exacerbation, defined as a: deterioration of asthma requiring the use of oral corticosteroids for at least 3 days, or a depot corticosteroid injection, or an in-patient hospitalization due to asthma that required systemic corticosteroids between screening and randomization.
  • Clinical visual evidence of oropharyngeal candidiasis at the randomization Visit.
  • Unable to use the ELLIPTA inhaler correctly.

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): NCT03248128


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

Locations
Show Show 142 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: NCT03248128    
Other Study ID Numbers: 107116
First Posted: August 14, 2017    Key Record Dates
Last Update Posted: March 3, 2020
Last Verified: March 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints of the study.
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.
URL: http://clinicalstudydatarequest.com

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by GlaxoSmithKline:
Fluticasone furoate
Efficacy
Vilanterol
Asthma
Safety
GW642444
GW685698
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