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

Asthma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02301975
• Other study ID #: 201378
• Status: Completed
• Phase: Phase 3
• Start date: March 1, 2015
• Est. completion date: November 25, 2016

Study information

• Verified date: August 2018
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1526
• Est. completion date: November 25, 2016
• Est. primary completion date: November 1, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Asthma
• Respiratory Aspiration

Intervention

Drug:
• Fluticasone Furoate/Vilanterol 100/25 mcg via ELLIPTA inhaler
FF/Vilanterol 100/25 mcg inhalation powders administered once daily via ELLIPTA inhaler. 30 doses per device and 100/25 mcg per actuation.
• Placebo inhalation powders via ELLIPTA inhaler
Placebo inhalation powders administered once daily via ELLIPTA inhaler. 30 doses per device.
• Fluticasone Propionate/Salmeterol 250/50 mcg via ACCUHALER/DISKUS inhaler
FP/Salmeterol 250/50 mcg inhalation powder administered twice daily via ACCUHALER/DISKUS inhaler. 60 doses per device and 250/50 mcg per actuation.
• Placebo inhalation powder via ACCUHALER/DISKUS inhaler
Placebo inhalation powder administered twice daily via ACCUHALER/DISKUS inhaler. 60 doses per device.
• Fluticasone Propionate 250 mcg via ACCUHALER/DISKUS inhaler
FP 250 mcg inhalation powder administered twice daily via ACCUHALER/DISKUS inhaler. 60 doses per device and 250 mcg per actuation.

Locations

Country	Name	City	State
Argentina	GSK Investigational Site	Buenos Aires
Argentina	GSK Investigational Site	Ciudad Autonoma de Buenos Aires
Argentina	GSK Investigational Site	Ciudad Autónoma de Buenos Aires
Argentina	GSK Investigational Site	Ciudad Autónoma de Buenos Aires
Argentina	GSK Investigational Site	Florida	Buenos Aires
Argentina	GSK Investigational Site	La Plata	Buenos Aires
Argentina	GSK Investigational Site	Mar del Plata	Buenos Aires
Argentina	GSK Investigational Site	Mar del Plata
Argentina	GSK Investigational Site	Mendoza
Argentina	GSK Investigational Site	Mendoza
Argentina	GSK Investigational Site	Quilmes	Buenos Aires
Argentina	GSK Investigational Site	Rosario	Santa Fe
Argentina	GSK Investigational Site	Rosario	Santa Fe
Argentina	GSK Investigational Site	San Miguel de Tucumán
Brazil	GSK Investigational Site	Goiânia	Goiás
Brazil	GSK Investigational Site	Porto Alegre	Rio Grande Do Sul
Brazil	GSK Investigational Site	Salvador	Bahía
Brazil	GSK Investigational Site	São Paulo
Brazil	GSK Investigational Site	São Paulo
Chile	GSK Investigational Site	Concepción	Región Del Biobio
Chile	GSK Investigational Site	Santiago	Región Metro De Santiago
Chile	GSK Investigational Site	Santiago	Región Metro De Santiago
Chile	GSK Investigational Site	Santiago	Región Metro De Santiago
Chile	GSK Investigational Site	Santiago
Chile	GSK Investigational Site	Valparaiso	Valparaíso
Chile	GSK Investigational Site	Viña del Mar
Czechia	GSK Investigational Site	Ceska Lipa
Czechia	GSK Investigational Site	Hlucin
Czechia	GSK Investigational Site	Hradec Kralove
Czechia	GSK Investigational Site	Kutna Hora
Czechia	GSK Investigational Site	Lovosice
Czechia	GSK Investigational Site	Olomouc
Czechia	GSK Investigational Site	Ostrava - Poruba
Czechia	GSK Investigational Site	Rokycany
Czechia	GSK Investigational Site	Tabor
Czechia	GSK Investigational Site	Teplice
Czechia	GSK Investigational Site	Varnsdorf
Germany	GSK Investigational Site	Bamberg	Bayern
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Delitzsch	Sachsen
Germany	GSK Investigational Site	Essen	Nordrhein-Westfalen
Germany	GSK Investigational Site	Essen	Nordrhein-Westfalen
Germany	GSK Investigational Site	Frankfurt	Hessen
Germany	GSK Investigational Site	Frankfurt	Hessen
Germany	GSK Investigational Site	Geesthacht	Schleswig-Holstein
Germany	GSK Investigational Site	Hamburg
Germany	GSK Investigational Site	Hannover	Niedersachsen
Germany	GSK Investigational Site	Koblenz	Rheinland-Pfalz
Germany	GSK Investigational Site	Leipzg	Sachsen
Germany	GSK Investigational Site	Leipzig	Sachsen
Germany	GSK Investigational Site	Leipzig	Sachsen
Germany	GSK Investigational Site	Leipzig	Sachsen
Germany	GSK Investigational Site	Luebeck	Schleswig-Holstein
Germany	GSK Investigational Site	Marburg	Hessen
Germany	GSK Investigational Site	Muenchen	Bayern
Germany	GSK Investigational Site	Muenchen	Bayern
Germany	GSK Investigational Site	Neu isenburg	Hessen
Germany	GSK Investigational Site	Peine	Niedersachsen
Germany	GSK Investigational Site	Potsdam	Brandenburg
Germany	GSK Investigational Site	Schleswig	Schleswig-Holstein
Germany	GSK Investigational Site	Schmoelln	Thueringen
Germany	GSK Investigational Site	Stuttgart	Baden-Wuerttemberg
Germany	GSK Investigational Site	Teuchern	Sachsen-Anhalt
Germany	GSK Investigational Site	Warendorf	Nordrhein-Westfalen
Germany	GSK Investigational Site	Witten	Nordrhein-Westfalen
Korea, Republic of	GSK Investigational Site	Cheongju-si, Chungcheongbuk-do
Korea, Republic of	GSK Investigational Site	Incheon
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Suwon-si, Gyeonggi-do
Mexico	GSK Investigational Site	Mexico DF
Mexico	GSK Investigational Site	Monterrey NL	Nuevo León
Mexico	GSK Investigational Site	Morelia	Michoacán
Mexico	GSK Investigational Site	Villahermosa	Tabasco
Mexico	GSK Investigational Site	Zapopan	Jalisco
Mexico	GSK Investigational Site	Zapopan	Jalisco
Netherlands	GSK Investigational Site	Almelo
Netherlands	GSK Investigational Site	Almere
Netherlands	GSK Investigational Site	Almere
Netherlands	GSK Investigational Site	Breda
Netherlands	GSK Investigational Site	Breda
Netherlands	GSK Investigational Site	Eindhoven
Netherlands	GSK Investigational Site	Harderwijk
Netherlands	GSK Investigational Site	Hoorn
Netherlands	GSK Investigational Site	Kloosterhaar
Netherlands	GSK Investigational Site	Nijverdal
Netherlands	GSK Investigational Site	Zutphen
Romania	GSK Investigational Site	Bacau
Romania	GSK Investigational Site	Bacau
Romania	GSK Investigational Site	Brasov
Romania	GSK Investigational Site	Bucharest
Romania	GSK Investigational Site	Bucharest
Romania	GSK Investigational Site	Bucharest
Romania	GSK Investigational Site	Bucuresti
Romania	GSK Investigational Site	Cluj Napoca
Romania	GSK Investigational Site	Codlea
Romania	GSK Investigational Site	Craiova
Romania	GSK Investigational Site	Deva
Romania	GSK Investigational Site	Pitesti
Romania	GSK Investigational Site	Suceava
Romania	GSK Investigational Site	Timisoara
Russian Federation	GSK Investigational Site	Barnaul
Russian Federation	GSK Investigational Site	Blagoveshchensk
Russian Federation	GSK Investigational Site	Irkutsk
Russian Federation	GSK Investigational Site	Kemerovo
Russian Federation	GSK Investigational Site	Kemerovo
Russian Federation	GSK Investigational Site	Krasnodar
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Omsk
Russian Federation	GSK Investigational Site	Pyatigorsk
Russian Federation	GSK Investigational Site	Saint Petesburg
Russian Federation	GSK Investigational Site	Saint-Petersburg
Russian Federation	GSK Investigational Site	Saint-Petersburg
Russian Federation	GSK Investigational Site	Saratov
Russian Federation	GSK Investigational Site	St'Petersburg
Russian Federation	GSK Investigational Site	St. Petersburg
Russian Federation	GSK Investigational Site	Stavropol
Russian Federation	GSK Investigational Site	Tomsk
Russian Federation	GSK Investigational Site	Tomsk
Russian Federation	GSK Investigational Site	Ufa
Russian Federation	GSK Investigational Site	Ulyanovsk
Russian Federation	GSK Investigational Site	Vladimir
Russian Federation	GSK Investigational Site	Volgodonsk
Russian Federation	GSK Investigational Site	Voronezh
Spain	GSK Investigational Site	Alicante
Spain	GSK Investigational Site	Alzira/Valencia
Spain	GSK Investigational Site	Badalona
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Centelles (Barcelona)
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Pozuelo De Alarcón/Madrid
Spain	GSK Investigational Site	Santander
Spain	GSK Investigational Site	Santiago de Compostela
Spain	GSK Investigational Site	Valencia
United States	GSK Investigational Site	Albany	Georgia
United States	GSK Investigational Site	Austin	Texas
United States	GSK Investigational Site	Baltimore	Maryland
United States	GSK Investigational Site	Bellevue	Nebraska
United States	GSK Investigational Site	Bethlehem	Pennsylvania
United States	GSK Investigational Site	Canton	Ohio
United States	GSK Investigational Site	Charlotte	North Carolina
United States	GSK Investigational Site	Cincinnati	Ohio
United States	GSK Investigational Site	Columbia	Missouri
United States	GSK Investigational Site	Columbia	Maryland
United States	GSK Investigational Site	Denver	Colorado
United States	GSK Investigational Site	Gastonia	North Carolina
United States	GSK Investigational Site	Greenfield	Wisconsin
United States	GSK Investigational Site	Greenville	South Carolina
United States	GSK Investigational Site	Hendersonville	North Carolina
United States	GSK Investigational Site	Huntersville	North Carolina
United States	GSK Investigational Site	Huntington Beach	California
United States	GSK Investigational Site	Lewisville	Texas
United States	GSK Investigational Site	Medford	Oregon
United States	GSK Investigational Site	Miami	Florida
United States	GSK Investigational Site	Miami	Florida
United States	GSK Investigational Site	Middleburg Heights	Ohio
United States	GSK Investigational Site	Minneapolis	Minnesota
United States	GSK Investigational Site	Orangeburg	South Carolina
United States	GSK Investigational Site	Plymouth	Minnesota
United States	GSK Investigational Site	Richmond	Virginia
United States	GSK Investigational Site	Riverside	California
United States	GSK Investigational Site	Rock Hill	South Carolina
United States	GSK Investigational Site	Rolla	Missouri
United States	GSK Investigational Site	Rolling Hills Estates	California
United States	GSK Investigational Site	San Diego	California
United States	GSK Investigational Site	Spartanburg	South Carolina
United States	GSK Investigational Site	Upland	California
United States	GSK Investigational Site	Waco	Texas

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  Chile,  Czechia,  Germany,  Korea, Republic of,  Mexico,  Netherlands,  Romania,  Russian Federation,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Evening (Post Meridiem [PM]) Forced Expiratory Volume in One Second (FEV1) Using Intent-to-Treat (ITT) Population	FEV1 was defined as the volume of air that can be forced out in one second after taking a deep breath. FEV1 (pre-bronchodilator and pre-dose) was measured at Baseline up to Week 24 at evening using spirometry. Repeated Measures analysis was adjusted for Baseline, region, sex, age, treatment, visit, visit by Baseline interaction and visit by treatment interaction. Visit 3 values were taken as Baseline value and change from Baseline was defined as the difference between the value of the endpoint at the time point of interest and the Baseline value. Statistical analysis was performed using the mixed model repeated measures (MMRM) model and least square mean and standard error were calculated. The analysis was performed on ITT Population which comprised of all participants randomized to treatment and who received at least one dose of study medication.	Baseline and Week 24
Primary	Change From Baseline in PM FEV1 Using Per Protocol (PP) Population	FEV1 was defined as the volume of air that can be forced out in one second after taking a deep breath. FEV1 (pre-bronchodilator and pre-dose) was measured at Baseline up to Week 24 at evening using spirometry. Repeated Measures analysis was adjusted for Baseline, region, sex, age, treatment, visit, visit by Baseline interaction and visit by treatment interaction. Visit 3 values were taken as Baseline value and change from Baseline was defined as the difference between the value of the endpoint at the time point of interest and the Baseline value. Statistical analysis was performed using the MMRM models and least square mean and standard error were calculated. The analysis was performed on PP Population which comprised of all participants in the ITT Population who did not had any full protocol deviations.	Baseline and Week 24
Secondary	Change From Baseline in the Percentage of Rescue-free 24-hour Periods	The number of inhalations of rescue medication used during the day and night were recorded by participants using an electronic diary (e-diary). A 24-hour (hr) period in which a participant's responses to both the morning and evening assessments indicated no use of rescue medication was considered to be rescue free. The Baseline value was derived from the last 7 days of the daily eDiary prior to the randomization of the participant. Change from Baseline was calculated as the averaged value during the 24-week treatment period minus the Baseline value. Statistical analysis was performed using an Analysis of Covariance (ANCOVA) model with covariates of Baseline, region, sex, age and treatment and least square mean and standard error were calculated.	Baseline and Weeks 1-24
Secondary	Change From Baseline in the Percentage of Symptom-free 24-hour Periods	Change from Baseline in the percentage of symptom-free 24 hour period was evaluated. A 24-hour (hr) period in which a participant's responses to both the morning and evening assessments indicated no symptoms was considered to be symptom free. The Baseline value was derived from the last 7 days of the daily eDiary prior to the randomization of the participant. Change from Baseline was calculated as the averaged value during the 24-week treatment period minus the Baseline value.Statistical analysis was performed using an ANCOVA model with covariates of Baseline, region, sex, age and treatment and least square mean and standard error were calculated.	Baseline and Weeks 1-24
Secondary	Change From Baseline in Morning (Ante Meridiem [AM]) Peak Expiratory Flow (PEF)	PEF was measured using an electric flow meter each morning. Change from Baseline (defined as the last 7 days prior to randomization of the participants) was calculated as the value of the averaged daily AM PEF over the 24-week treatment period minus the Baseline value. Statistical analysis was performed using an ANCOVA model with covariates of Baseline, region, sex, age and treatment and least square mean and standard error were calculated.	Baseline and Weeks 1-24
Secondary	Percentage of Participants With Asthma Control Test (ACT) Score Greater Than or Equal to 20	The ACT was a five-item questionnaire developed as a measure of participant's asthma control. The percentage of participants controlled, defined as having ACT score greater than or equal to 20 at the end of Week 24 were analyzed using logistic regression model with covariates of Baseline ACT score, region, sex, age and treatment group.	Week 24
Secondary	Change From Baseline in PM PEF	PEF was measured using an electric flow meter each evening. Change from Baseline (defined as the last 7 days prior to randomization of the participants) was calculated as the value of the averaged daily PM PEF over the 24-week treatment period minus the Baseline value. Statistical analysis was performed using an ANCOVA model with covariates of Baseline, region, sex, age and treatment and least square mean and standard error were calculated.	Baseline and Weeks 1-24