Clinical trial NCT02301975: An Efficacy and Safety Study of Fluticasone Furoate/Vilanterol 100/25 Microgram (mcg) Inhalation Powder, Fluticasone Propionate/Salmeterol 250/50 mcg Inhalation Powder, and Fluticasone Propionate 250 mcg Inhalation Powder in Adults and Adolescents With Persistent Asthma
Official title: A Randomized, Double-blind, Double-dummy, Parallel Group, Multicenter Study of Once Daily Fluticasone Furoate/Vilanterol 100/25 mcg Inhalation Powder, Twice Daily Fluticasone Propionate/Salmeterol 250/50 mcg Inhalation Powder, and Twice Daily Fluticasone Propionate 250 mcg Inhalation Powder in the Treatment of Persistent Asthma in Adults and Adolescents Already Adequately Controlled on Twice-daily Inhaled Corticosteroid and Long-acting beta2 Agonist
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Asthma
Keywords: Adult
asthma
Fluticasone Propionate
Adolescents
Salmeterol
Vilanterol
ELLIPTA
ACCUHALER/DISKUS
Non-inferior
Fluticasone Furoate
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2014-11-26
Enrollment: 1526
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is a randomized, double-blind, double-dummy, parallel group, multicenter, non-inferiority study. The study will enroll adult and adolescent asthmatic subjects who are currently receiving mid dose inhaled corticosteroids (ICS) plus long-acting beta2-agonist (LABA) (equivalent to fluticasone propionate \[FP\]/salmeterol 250/50 microgram \[mcg\]twice daily \[BD\]), either via a fixed dose combination product or through separate inhalers. The study consists of a LABA washout period of 5 days and a run-in period of 4 weeks, followed by a treatment period of 24 weeks, and a follow up contact period of one week. The total duration of the study is 30 weeks. Approximately 1461 subjects will be randomized to one of the following three treatments (487 per treatment): fluticasone furoate (FF)/vilanterol (VI) 100/25 mcg once daily (OD) in the evening (PM) via ELLIPTA™ inhaler plus placebo BD via ACCUHALER™/DISKUS™; FP/salmeterol 250/50 mcg BD via ACCUHALER/DISKUS inhaler plus placebo OD (PM) via ELLIPTA inhaler; FP 250 mcg BD via ACCUHALER/DISKUS inhaler plus placebo OD (PM) via ELLIPTA inhaler. In addition, all subjects will be supplied with albuterol/salbutamol inhalation aerosol to use as needed to treat acute asthma symptoms. This study will determine if FF/VI 100/25 mcg OD via ELLIPTA inhaler is non-inferior to FP/salmeterol 250/50 mcg BD via ACCUHALER/DISKUS inhaler in adult and adolescent asthmatic subjects already adequately controlled on a twice-daily ICS/LABA.

SERETIDE, ELLIPTA, ACCUHALER, RELVAR, and DISKUS are trademarks of the GlaxoSmithKline Group of Companies.


Eligibility criteria: Inclusion Criteria

* Subjects must give their signed and dated written informed consent to participate prior to commencing any study related activities.
* Subjects must be outpatients \>=12 years of age at Visit 1 who have had a diagnosis of asthma, as defined by the National Institutes of Health, for at least 12 weeks prior to Visit 1 (Note: Countries with local restrictions prohibiting enrollment of adolescents will enroll subjects \>=18 years of age only).
* Subjects may be male or an eligible female. An eligible female is defined as having non-childbearing potential or having childbearing potential and a negative urine pregnancy test at Screening and agrees to use an acceptable method of birth control consistently and correctly.
* Subjects must have a FEV1 of \>=80% of the predicted normal value.
* Subjects are eligible if they have received mid dose ICS plus LABA (equivalent to FP/salmeterol 250/50 twice daily or an equivalent combination via separate inhalers) for at least the 12 weeks immediately preceding Visit 1.
* 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. Subjects must be able to withhold albuterol/salbutamol for at least 6 hours prior to study visits.
* If in the opinion of the investigator the subject's asthma is well controlled. Exclusion Criteria
* History of Life-Threatening Asthma, defined for this protocol as an asthma episode that required intubation and/or associated with hypercapnea, respiratory arrest or hypoxic seizures within the last 5 years.
* 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.
* Any asthma exacerbation requiring oral corticosteroids within 12 weeks of Visit 1 or resulting in an overnight hospitalization requiring additional treatment for asthma within 6 months prior to Visit 1.
* A subject must not have current evidence of Atlectasis, Bronchopulmonary dysplasia, Chronic bronchitis, Chronic obstructive pulmonary disease, Pneumonia, Pneumothorax, Interstitial lung disease, or any evidence of concurrent respiratory disease other than asthma
* A subject must not have any clinically significant, uncontrolled condition or disease state that, in the opinion of the investigator, would put the safety of the subject at risk through study participation or would confound the interpretation of the results if the condition/disease exacerbated during the study.
* A subject must not have used any investigational drug within 30 days prior to Visit 1 or within five half-lives (t½) of the prior investigational study, whichever is longer of the two.
* Any adverse reaction including immediate or delayed hypersensitivity to any beta2-agonist, sympathomimetic drug, or any intranasal, inhaled, or systemic corticosteroid therapy. Known or suspected sensitivity to the constituents of RELVAR™ ELLIPTA inhaler, SERETIDE™ ACCUHALER/DISKUS inhaler or FP 250.
* History of severe milk protein allergy.
* Administration of prescription or non-prescription medication that would significantly affect the course of asthma, or interact with study drug.
* A subject must not be using or require the use of immunosuppressive medications during the study.
* A subject will not be eligible if he/she or his/her parent or legal guardian has any infirmity, disability, disease, or geographical location which seems likely (in the opinion of the Investigator) to impair compliance with any aspect of this study protocol, including visit schedule and completion of the daily diaries.
* Current tobacco smoker or has a smoking history of 10 pack-years (20 cigarettes/day for 10 years). A subject may not have used inhaled tobacco products or inhaled marijuana within the past 3 months (e.g., cigarettes, cigars, electronic cigarettes, or pipe tobacco).
* 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.

Primary outcomes:
measure: Change From Baseline in Evening (Post Meridiem [PM]) Forced Expiratory Volume in One Second (FEV1) Using Intent-to-Treat (ITT) Population
timeFrame: Baseline and Week 24
measure: Change From Baseline in PM FEV1 Using Per Protocol (PP) Population
timeFrame: Baseline and Week 24
Secondary outcomes:
measure: Change From Baseline in the Percentage of Rescue-free 24-hour Periods
timeFrame: Baseline and Weeks 1-24
measure: Change From Baseline in the Percentage of Symptom-free 24-hour Periods
timeFrame: Baseline and Weeks 1-24
measure: Change From Baseline in Morning (Ante Meridiem [AM]) Peak Expiratory Flow (PEF)
timeFrame: Baseline and Weeks 1-24
measure: Percentage of Participants With Asthma Control Test (ACT) Score Greater Than or Equal to 20
timeFrame: Week 24
measure: Change From Baseline in PM PEF
timeFrame: Baseline and Weeks 1-24
Other outcomes:
Locations:
city: Huntington Beach
country: United States
facility: GSK Investigational Site
state: California
city: Riverside
country: United States
facility: GSK Investigational Site
state: California
city: Rolling Hills Estates
country: United States
facility: GSK Investigational Site
state: California
city: San Diego
country: United States
facility: GSK Investigational Site
state: California
city: Upland
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facility: GSK Investigational Site
state: California
city: Denver
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facility: GSK Investigational Site
state: Colorado
city: Miami
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state: Florida
city: Miami
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city: Albany
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state: Georgia
city: Baltimore
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state: Maryland
city: Columbia
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state: Maryland
city: Minneapolis
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state: Minnesota
city: Plymouth
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facility: GSK Investigational Site
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state: Missouri
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facility: GSK Investigational Site
state: Nebraska
city: Charlotte
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city: Hendersonville
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facility: GSK Investigational Site
state: North Carolina
city: Huntersville
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facility: GSK Investigational Site
state: North Carolina
city: Canton
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facility: GSK Investigational Site
state: Ohio
city: Cincinnati
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facility: GSK Investigational Site
state: Ohio
city: Middleburg Heights
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facility: GSK Investigational Site
state: Ohio
city: Medford
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facility: GSK Investigational Site
state: Oregon
city: Bethlehem
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facility: GSK Investigational Site
state: Pennsylvania
city: Greenville
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facility: GSK Investigational Site
state: South Carolina
city: Orangeburg
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Rock Hill
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facility: GSK Investigational Site
state: South Carolina
city: Spartanburg
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Austin
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state: Texas
city: Lewisville
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state: Texas
city: Richmond
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state: Virginia
city: Greenfield
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city: Florida
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state: Buenos Aires
city: La Plata
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facility: GSK Investigational Site
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city: Mar del Plata
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facility: GSK Investigational Site
state: Buenos Aires
city: Quilmes
country: Argentina
facility: GSK Investigational Site
state: Buenos Aires
city: Rosario
country: Argentina
facility: GSK Investigational Site
state: Santa Fe
city: Rosario
country: Argentina
facility: GSK Investigational Site
state: Santa Fe
city: Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: Ciudad Autónoma de Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: Ciudad Autónoma de Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: Mar del Plata
country: Argentina
facility: GSK Investigational Site
city: Mendoza
country: Argentina
facility: GSK Investigational Site
city: Mendoza
country: Argentina
facility: GSK Investigational Site
city: San Miguel de Tucumán
country: Argentina
facility: GSK Investigational Site
city: Salvador
country: Brazil
facility: GSK Investigational Site
state: Bahía
city: Goiânia
country: Brazil
facility: GSK Investigational Site
state: Goiás
city: Porto Alegre
country: Brazil
facility: GSK Investigational Site
state: Rio Grande Do Sul
city: São Paulo
country: Brazil
facility: GSK Investigational Site
city: São Paulo
country: Brazil
facility: GSK Investigational Site
city: Concepción
country: Chile
facility: GSK Investigational Site
state: Región Del Biobio
city: Santiago
country: Chile
facility: GSK Investigational Site
state: Región Metro De Santiago
city: Santiago
country: Chile
facility: GSK Investigational Site
state: Región Metro De Santiago
city: Santiago
country: Chile
facility: GSK Investigational Site
state: Región Metro De Santiago
city: Valparaiso
country: Chile
facility: GSK Investigational Site
state: Valparaíso
city: Santiago
country: Chile
facility: GSK Investigational Site
city: Viña del Mar
country: Chile
facility: GSK Investigational Site
city: Ceska Lipa
country: Czechia
facility: GSK Investigational Site
city: Hlucin
country: Czechia
facility: GSK Investigational Site
city: Hradec Kralove
country: Czechia
facility: GSK Investigational Site
city: Kutna Hora
country: Czechia
facility: GSK Investigational Site
city: Lovosice
country: Czechia
facility: GSK Investigational Site
city: Olomouc
country: Czechia
facility: GSK Investigational Site
city: Ostrava - Poruba
country: Czechia
facility: GSK Investigational Site
city: Rokycany
country: Czechia
facility: GSK Investigational Site
city: Tabor
country: Czechia
facility: GSK Investigational Site
city: Teplice
country: Czechia
facility: GSK Investigational Site
city: Varnsdorf
country: Czechia
facility: GSK Investigational Site
city: Stuttgart
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Bamberg
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Muenchen
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Muenchen
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Potsdam
country: Germany
facility: GSK Investigational Site
state: Brandenburg
city: Frankfurt
country: Germany
facility: GSK Investigational Site
state: Hessen
city: Frankfurt
country: Germany
facility: GSK Investigational Site
state: Hessen
city: Marburg
country: Germany
facility: GSK Investigational Site
state: Hessen
city: Neu isenburg
country: Germany
facility: GSK Investigational Site
state: Hessen
city: Hannover
country: Germany
facility: GSK Investigational Site
state: Niedersachsen
city: Peine
country: Germany
facility: GSK Investigational Site
state: Niedersachsen
city: Essen
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Essen
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Warendorf
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Witten
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Koblenz
country: Germany
facility: GSK Investigational Site
state: Rheinland-Pfalz
city: Teuchern
country: Germany
facility: GSK Investigational Site
state: Sachsen-Anhalt
city: Delitzsch
country: Germany
facility: GSK Investigational Site
state: Sachsen
city: Leipzg
country: Germany
facility: GSK Investigational Site
state: Sachsen
city: Leipzig
country: Germany
facility: GSK Investigational Site
state: Sachsen
city: Leipzig
country: Germany
facility: GSK Investigational Site
state: Sachsen
city: Leipzig
country: Germany
facility: GSK Investigational Site
state: Sachsen
city: Geesthacht
country: Germany
facility: GSK Investigational Site
state: Schleswig-Holstein
city: Luebeck
country: Germany
facility: GSK Investigational Site
state: Schleswig-Holstein
city: Schleswig
country: Germany
facility: GSK Investigational Site
state: Schleswig-Holstein
city: Schmoelln
country: Germany
facility: GSK Investigational Site
state: Thueringen
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Hamburg
country: Germany
facility: GSK Investigational Site
city: Cheongju-si, Chungcheongbuk-do
country: Korea, Republic of
facility: GSK Investigational Site
city: Incheon
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Suwon-si, Gyeonggi-do
country: Korea, Republic of
facility: GSK Investigational Site
city: Zapopan
country: Mexico
facility: GSK Investigational Site
state: Jalisco
city: Zapopan
country: Mexico
facility: GSK Investigational Site
state: Jalisco
city: Morelia
country: Mexico
facility: GSK Investigational Site
state: Michoacán
city: Monterrey NL
country: Mexico
facility: GSK Investigational Site
state: Nuevo León
city: Villahermosa
country: Mexico
facility: GSK Investigational Site
state: Tabasco
city: Mexico DF
country: Mexico
facility: GSK Investigational Site
city: Almelo
country: Netherlands
facility: GSK Investigational Site
city: Almere
country: Netherlands
facility: GSK Investigational Site
city: Almere
country: Netherlands
facility: GSK Investigational Site
city: Breda
country: Netherlands
facility: GSK Investigational Site
city: Breda
country: Netherlands
facility: GSK Investigational Site
city: Eindhoven
country: Netherlands
facility: GSK Investigational Site
city: Harderwijk
country: Netherlands
facility: GSK Investigational Site
city: Hoorn
country: Netherlands
facility: GSK Investigational Site
city: Kloosterhaar
country: Netherlands
facility: GSK Investigational Site
city: Nijverdal
country: Netherlands
facility: GSK Investigational Site
city: Zutphen
country: Netherlands
facility: GSK Investigational Site
city: Bacau
country: Romania
facility: GSK Investigational Site
city: Bacau
country: Romania
facility: GSK Investigational Site
city: Brasov
country: Romania
facility: GSK Investigational Site
city: Bucharest
country: Romania
facility: GSK Investigational Site
city: Bucharest
country: Romania
facility: GSK Investigational Site
city: Bucharest
country: Romania
facility: GSK Investigational Site
city: Bucuresti
country: Romania
facility: GSK Investigational Site
city: Cluj Napoca
country: Romania
facility: GSK Investigational Site
city: Codlea
country: Romania
facility: GSK Investigational Site
city: Craiova
country: Romania
facility: GSK Investigational Site
city: Deva
country: Romania
facility: GSK Investigational Site
city: Pitesti
country: Romania
facility: GSK Investigational Site
city: Suceava
country: Romania
facility: GSK Investigational Site
city: Timisoara
country: Romania
facility: GSK Investigational Site
city: Barnaul
country: Russian Federation
facility: GSK Investigational Site
city: Blagoveshchensk
country: Russian Federation
facility: GSK Investigational Site
city: Irkutsk
country: Russian Federation
facility: GSK Investigational Site
city: Kemerovo
country: Russian Federation
facility: GSK Investigational Site
city: Kemerovo
country: Russian Federation
facility: GSK Investigational Site
city: Krasnodar
country: Russian Federation
facility: GSK Investigational Site
city: Moscow
country: Russian Federation
facility: GSK Investigational Site
city: Moscow
country: Russian Federation
facility: GSK Investigational Site
city: Moscow
country: Russian Federation
facility: GSK Investigational Site
city: Moscow
country: Russian Federation
facility: GSK Investigational Site
city: Omsk
country: Russian Federation
facility: GSK Investigational Site
city: Pyatigorsk
country: Russian Federation
facility: GSK Investigational Site
city: Saint Petesburg
country: Russian Federation
facility: GSK Investigational Site
city: Saint-Petersburg
country: Russian Federation
facility: GSK Investigational Site
city: Saint-Petersburg
country: Russian Federation
facility: GSK Investigational Site
city: Saratov
country: Russian Federation
facility: GSK Investigational Site
city: St'Petersburg
country: Russian Federation
facility: GSK Investigational Site
city: St. Petersburg
country: Russian Federation
facility: GSK Investigational Site
city: Stavropol
country: Russian Federation
facility: GSK Investigational Site
city: Tomsk
country: Russian Federation
facility: GSK Investigational Site
city: Tomsk
country: Russian Federation
facility: GSK Investigational Site
city: Ufa
country: Russian Federation
facility: GSK Investigational Site
city: Ulyanovsk
country: Russian Federation
facility: GSK Investigational Site
city: Vladimir
country: Russian Federation
facility: GSK Investigational Site
city: Volgodonsk
country: Russian Federation
facility: GSK Investigational Site
city: Voronezh
country: Russian Federation
facility: GSK Investigational Site
city: Alicante
country: Spain
facility: GSK Investigational Site
city: Alzira/Valencia
country: Spain
facility: GSK Investigational Site
city: Badalona
country: Spain
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Centelles (Barcelona)
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Pozuelo De Alarcón/Madrid
country: Spain
facility: GSK Investigational Site
city: Santander
country: Spain
facility: GSK Investigational Site
city: Santiago de Compostela
country: Spain
facility: GSK Investigational Site
city: Valencia
country: Spain
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Bernstein D, Andersen L, Forth R, Jacques L, Yates L. Once-daily fluticasone furoate/vilanterol versus twice-daily fluticasone propionate/salmeterol in patients with asthma well controlled on ICS/LABA. J Asthma. 2018 Sep;55(9):984-993. doi: 10.1080/02770903.2017.1386214. Epub 2018 Apr 13.