Clinical trial NCT01686633: An Efficacy and Safety Study of Fluticasone Furoate/Vilanterol (FF/VI) 200/25 Microgram (mcg) , FF/VI 100/25 mcg, and FF 100 mcg in Adults and Adolescents With Persistent Asthma.
Official title: A Randomized, Double-Blind, Parallel Group, Multicenter Study of Fluticasone Furoate/Vilanterol 200/25 mcg Inhalation Powder, Fluticasone Furoate/Vilanterol 100/25 mcg Inhalation Powder, and Fluticasone Furoate 100 mcg Inhalation Powder in the Treatment of Persistent Asthma in Adults and Adolescents
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Asthma
Keywords: asthma
pharmacogenetics
adult
vilanterol
adolescents
fluticasone furoate
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2012-09-18
Enrollment: 1040
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a Phase III, multicenter, randomized, double-blind, stratified, parallel-group study with three active comparators in subjects with moderate to severe persistent asthma. The study consists of a run-in period of 4 weeks, followed by a treatment period of 12 weeks, and a follow up contact period of one week. The total duration of the study is 17 weeks. 990 subjects will be randomized to one of three treatments (FF/VI Inhalation Powder 200/25 mcg once daily in the evening; FF/VI Inhalation Powder 100/25 mcg once daily in the evening; FF 100 Inhalation Powder once daily in the evening) for 12 weeks. In addition, all subjects will be supplied albuterol/salbutamol inhalation aerosol at Visit 1 to use as needed for acute asthma symptoms throughout the entire study. Subjects will attend four on-treatment visits at Weeks 2, 4, 8, and 12 (Visits 4 through 7).


Eligibility criteria: Inclusion Criteria:

* Subjects must give their signed and dated (written) informed consent to participate. Written informed consent must be obtained if a subject's current medication is changed as a result of study participation
* Outpatient \>=12 years of age at Visit 1 who have had a diagnosis of asthma, as defined by the National Institutes of Health. Countries with local restrictions prohibiting enrolment of adolescents will only enroll subjects \>=18 years of age
* Male or an eligible female. Eligible female is defined as having non-childbearing potential or having childbearing potential and using an acceptable method of birth control consistently and correctly.
* Best pre-bronchodilator FEV1 of 40% to 80% of their predicted normal value.
* Demonstrate \>=12% and \>=200 mL reversibility of FEV1 within 10 to 40 minutes following 4 inhalations of albuterol/salbutamol inhalation aerosol (or an equivalent nebulized treatment with albuterol/salbutamol solution) or have documented reversibility testing within the 6 months prior to Visit 1 meeting this measure of reversibility. A spacer device may be used for testing, if required.
* If subject have received ICS for at least 12 weeks prior to Visit 1 and their treatment during the 4 weeks immediately prior to Visit 1 consisted of either of the two regimens (a or b).a.) A stable mid-dose or high-dose of ICS alone (e.g., \>=FP 250 mcg twice daily) or b.) A stable dose of a mid-dose ICS/LABA combination (e.g., FP/Salmeterol \[SALM\] 250/50 mcg twice daily) or an equivalent combination via separate inhalers.
* Use of ICS/LABA are not permitted with LABA on the day of Visit 1.
* Must be able to replace current SABA treatment with albuterol/salbutamol aerosol inhaler at Visit 1 for use as needed, during the study. Subjects must be able to withhold albuterol/salbutamol for at least 6 hours prior to study visits

Exclusion Criteria:

* History of life-threatening asthma, defined as an asthma episode that required intubation and/or was associated with hypercapnia, respiratory arrest or hypoxic seizures within the last 5 years.
* 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 that required oral corticosteroids within the 12 weeks prior to Visit 1 or, resulted in an overnight hospitalization requiring additional treatment for asthma within 6 months prior to Visit 1.
* A subject must not have current evidence of atelectasis (segmental or larger), bronchopulmonary dysplasia, chronic obstructive pulmonary 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 efficacy results if the condition/disease exacerbated during the study
* Chronic stable hepatitis B or C are acceptable provided their screening alanine transaminase (ALT) is \<2x upper limit of normal (ULN) and the y otherwise meet the entry criteria. Chronic co-infection with both hepatitis B and hepatitis C are not eligible
* Clinical visual evidence of candidiasis at Visit 1
* Use of any investigational drug within 30 days prior to Visit 1 or within five half-lives (t½), whichever is longer of the two.
* Allergies to drug or milk protein: any adverse reaction, to any beta2-agonist, sympathomimetic drug, or any intranasal, inhaled, or systemic corticosteroid therapy or known or suspected sensitivity to the constituents of the NDPI, or history of severe milk protein allergy
* Administration of medication that would significantly affect the course of asthma, or interact with study drug
* Use of immunosuppressive medications during the study.
* Use of potent CYP3A4 inhibitor within 4 weeks of Visit 1.
* A subject or his/her parent or legal guardian has any infirmity, disability, disease, or resides in a 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 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 within the past 3 months (i.e., cigarettes, cigars, or pipe tobacco).
* If subject is an immediate family member of the participating investigator, sub-investigator, study coordinator, or employee of the participating investigator.
* Subject previously randomized to treatment with FF/VI or FF in another Phase III study
* Subjects working on night shift a week prior to Visit 1 or during the study period.
* Adolescents who are wards of the state or government

Primary outcomes:
measure: Change From Baseline in Weighted Mean Forced Expiratory Volume in One Second (FEV1) Over 0 to 24 Hours Post-dose at the End of the 12-week Treatment Period
timeFrame: Baseline and Week 12
Secondary outcomes:
measure: Change From Baseline in Clinic Visit Trough FEV1 at the End of the 12-week Treatment Period
timeFrame: Baseline and Week 12
measure: Change From Baseline in the Percentage of Rescue-free 24-hour (hr) Periods During the 12-week Treatment Period
timeFrame: Baseline and Weeks 1-12
measure: Change From Baseline in the Percentage of Symptom-free 24-hour (hr) Periods During the 12-week Treatment Period
timeFrame: Baseline and Weeks 1-12
measure: Change From Baseline in Daily Morning (AM) Peak Expiratory Flow (PEF) Averaged Over the 12-week Treatment Period
timeFrame: Baseline and Weeks 1-12
measure: Change From Baseline in Daily Evening (PM) PEF Averaged Over the 12-week Treatment Period
timeFrame: Baseline and Weeks 1-12
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: GSK Investigational Site
state: Arkansas
city: Huntington Beach
country: United States
facility: GSK Investigational Site
state: California
city: Los Angeles
country: United States
facility: GSK Investigational Site
state: California
city: Newport Beach
country: United States
facility: GSK Investigational Site
state: California
city: Rancho Mirage
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: Vista
country: United States
facility: GSK Investigational Site
state: California
city: Colorado Springs
country: United States
facility: GSK Investigational Site
state: Colorado
city: Denver
country: United States
facility: GSK Investigational Site
state: Colorado
city: Wheat Ridge
country: United States
facility: GSK Investigational Site
state: Colorado
city: Tallahassee
country: United States
facility: GSK Investigational Site
state: Florida
city: Coeur d'Alene
country: United States
facility: GSK Investigational Site
state: Idaho
city: Normal
country: United States
facility: GSK Investigational Site
state: Illinois
city: Bethesda
country: United States
facility: GSK Investigational Site
state: Maryland
city: Columbia
country: United States
facility: GSK Investigational Site
state: Maryland
city: North Dartmouth
country: United States
facility: GSK Investigational Site
state: Massachusetts
city: Minneapolis
country: United States
facility: GSK Investigational Site
state: Minnesota
city: Rolla
country: United States
facility: GSK Investigational Site
state: Missouri
city: Saint Louis
country: United States
facility: GSK Investigational Site
state: Missouri
city: Skillman
country: United States
facility: GSK Investigational Site
state: New Jersey
city: Charlotte
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Raleigh
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Shelby
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Cincinnati
country: United States
facility: GSK Investigational Site
state: Ohio
city: Cincinnati
country: United States
facility: GSK Investigational Site
state: Ohio
city: Middleburg Heights
country: United States
facility: GSK Investigational Site
state: Ohio
city: Medford
country: United States
facility: GSK Investigational Site
state: Oregon
city: Easley
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Fort Mill
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Greenville
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Orangeburg
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Spartanburg
country: United States
facility: GSK Investigational Site
state: South Carolina
city: El Paso
country: United States
facility: GSK Investigational Site
state: Texas
city: Waco
country: United States
facility: GSK Investigational Site
state: Texas
city: Richmond
country: United States
facility: GSK Investigational Site
state: Virginia
city: Seattle
country: United States
facility: GSK Investigational Site
state: Washington
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: GSK Investigational Site
state: Buenos Aires
city: Nueve de Julio
country: Argentina
facility: GSK Investigational Site
state: Buenos Aires
city: San Rafael
country: Argentina
facility: GSK Investigational Site
state: Mendoza
city: Rosario
country: Argentina
facility: GSK Investigational Site
state: Santa Fe
city: Berazategui
country: Argentina
facility: GSK Investigational Site
city: Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: Ciudad Autónoma de Buenos Aires
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: Tucuman
country: Argentina
facility: GSK Investigational Site
city: Rancagua
country: Chile
facility: GSK Investigational Site
state: Reg Del Libert Bern Ohiggins
city: Puente Alto - 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: Quillota
country: Chile
facility: GSK Investigational Site
state: Valparaíso
city: Valparaiso
country: Chile
facility: GSK Investigational Site
state: Valparaíso
city: Viña del Mar
country: Chile
facility: GSK Investigational Site
state: Valparaíso
city: Santiago
country: Chile
facility: GSK Investigational Site
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: Koblenz
country: Germany
facility: GSK Investigational Site
state: Rheinland-Pfalz
city: Magdeburg
country: Germany
facility: GSK Investigational Site
state: Sachsen-Anhalt
city: Leipzg
country: Germany
facility: GSK Investigational Site
state: Sachsen
city: Grosshansdorf
country: Germany
facility: GSK Investigational Site
state: Schleswig-Holstein
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: Zapopan
country: Mexico
facility: GSK Investigational Site
state: Jalisco
city: Morelia
country: Mexico
facility: GSK Investigational Site
state: Michoacán
city: Monterrey
country: Mexico
facility: GSK Investigational Site
state: Nuevo León
city: Villahermosa
country: Mexico
facility: GSK Investigational Site
state: Tabasco
city: Almelo
country: Netherlands
facility: GSK Investigational Site
city: Breda
country: Netherlands
facility: GSK Investigational Site
city: Eindhoven
country: Netherlands
facility: GSK Investigational Site
city: Enschede
country: Netherlands
facility: GSK Investigational Site
city: Hoorn
country: Netherlands
facility: GSK Investigational Site
city: Veldhoven
country: Netherlands
facility: GSK Investigational Site
city: Zutphen
country: Netherlands
facility: GSK Investigational Site
city: Bialystok
country: Poland
facility: GSK Investigational Site
city: Krakow
country: Poland
facility: GSK Investigational Site
city: Krakow
country: Poland
facility: GSK Investigational Site
city: Krakow
country: Poland
facility: GSK Investigational Site
city: Lodz
country: Poland
facility: GSK Investigational Site
city: Tarnow
country: Poland
facility: GSK Investigational Site
city: Warszawa
country: Poland
facility: GSK Investigational Site
city: Wroclaw
country: Poland
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: Bucuresti
country: Romania
facility: GSK Investigational Site
city: Cluj Napoca
country: Romania
facility: GSK Investigational Site
city: Craiova
country: Romania
facility: GSK Investigational Site
city: Deva
country: Romania
facility: GSK Investigational Site
city: Iasi
country: Romania
facility: GSK Investigational Site
city: Pitesti
country: Romania
facility: GSK Investigational Site
city: Ploiesti
country: Romania
facility: GSK Investigational Site
city: Ploiesti
country: Romania
facility: GSK Investigational Site
city: Timisoara
country: Romania
facility: GSK Investigational Site
city: Blagoveshchensk
country: Russian Federation
facility: GSK Investigational Site
city: Chelyabinsk
country: Russian Federation
facility: GSK Investigational Site
city: Chita
country: Russian Federation
facility: GSK Investigational Site
city: Ekaterinburg
country: Russian Federation
facility: GSK Investigational Site
city: Ivanovo
country: Russian Federation
facility: GSK Investigational Site
city: Kazan
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: Nizhniy Novgorod
country: Russian Federation
facility: GSK Investigational Site
city: Pyatigorsk
country: Russian Federation
facility: GSK Investigational Site
city: Ryazan
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: 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: Vladivostok
country: Russian Federation
facility: GSK Investigational Site
city: Voronezh
country: Russian Federation
facility: GSK Investigational Site
city: Göteborg
country: Sweden
facility: GSK Investigational Site
city: Linköping
country: Sweden
facility: GSK Investigational Site
city: Luleå
country: Sweden
facility: GSK Investigational Site
city: Lund
country: Sweden
facility: GSK Investigational Site
city: Uppsala
country: Sweden
facility: GSK Investigational Site
city: Dnipropetrovsk
country: Ukraine
facility: GSK Investigational Site
city: Kharkiv
country: Ukraine
facility: GSK Investigational Site
city: Kharkiv
country: Ukraine
facility: GSK Investigational Site
city: Kiev
country: Ukraine
facility: GSK Investigational Site
city: Kyiv
country: Ukraine
facility: GSK Investigational Site
city: Kyiv
country: Ukraine
facility: GSK Investigational Site
city: Poltava
country: Ukraine
facility: GSK Investigational Site
city: Vinnytsia
country: Ukraine
facility: GSK Investigational Site
city: Vinnytsia
country: Ukraine
facility: GSK Investigational Site
city: Zaporizhia
country: Ukraine
facility: GSK Investigational Site
city: Zaporizhia
country: Ukraine
facility: GSK Investigational Site
city: Zaporizhia
country: Ukraine
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Bernstein DI, Bateman ED, Woodcock A, Toler WT, Forth R, Jacques L, Nunn C, O'Byrne PM. Fluticasone furoate (FF)/vilanterol (100/25 mcg or 200/25 mcg) or FF (100 mcg) in persistent asthma. J Asthma. 2015;52(10):1073-83. doi: 10.3109/02770903.2015.1056350. Epub 2015 Aug 18.