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.

Asthma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01686633
• Other study ID #: 116863
• Status: Completed
• Phase: Phase 3
• First received: September 13, 2012
• Last updated: January 18, 2018
• Start date: September 20, 2012
• Est. completion date: October 15, 2013

Study information

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

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1040
• Est. completion date: October 15, 2013
• Est. primary completion date: October 1, 2013
• 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. 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

Related Conditions & MeSH terms

• Asthma

Intervention

Drug:
• Fluticasone Furoate/ Vilanterol 200/25 mcg
Fluticasone furoate/ vilanterol will be available as 200/25 mcg Novel dry powder inhaler (NDPI) with 30 doses per device and 200/25 mcg per actuation
• Fluticasone Furoate/ Vilanterol 100/25 mcg
Fluticasone furoate/ vilanterol will be available as 100/25 mcg NDPI with 30 doses per device and 100/25 mcg per actuation
• Fluticasone Furoate 100 mcg
Fluticasone furoate will be available as 100 mcg NDPI with 30 doses per device and 100/25 mcg per actuation

Locations

Country	Name	City	State
Argentina	GSK Investigational Site	Berazategui
Argentina	GSK Investigational Site	Buenos Aires
Argentina	GSK Investigational Site	Buenos Aires
Argentina	GSK Investigational Site	Buenos Aires
Argentina	GSK Investigational Site	Ciudad Autonoma de Buenos Aires	Buenos Aires
Argentina	GSK Investigational Site	Ciudad Autónoma de Buenos Aires
Argentina	GSK Investigational Site	Mendoza
Argentina	GSK Investigational Site	Mendoza
Argentina	GSK Investigational Site	Nueve de Julio	Buenos Aires
Argentina	GSK Investigational Site	Rosario	Santa Fe
Argentina	GSK Investigational Site	San Miguel de Tucumán
Argentina	GSK Investigational Site	San Rafael	Mendoza
Argentina	GSK Investigational Site	Tucuman
Chile	GSK Investigational Site	Puente Alto - Santiago	Región Metro De Santiago
Chile	GSK Investigational Site	Quillota	Valparaíso
Chile	GSK Investigational Site	Rancagua	Reg Del Libert Bern Ohiggins
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	Valparaíso
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	Frankfurt	Hessen
Germany	GSK Investigational Site	Frankfurt	Hessen
Germany	GSK Investigational Site	Grosshansdorf	Schleswig-Holstein
Germany	GSK Investigational Site	Koblenz	Rheinland-Pfalz
Germany	GSK Investigational Site	Leipzg	Sachsen
Germany	GSK Investigational Site	Magdeburg	Sachsen-Anhalt
Germany	GSK Investigational Site	Potsdam	Brandenburg
Mexico	GSK Investigational Site	Monterrey	Nuevo León
Mexico	GSK Investigational Site	Morelia	Michoacán
Mexico	GSK Investigational Site	Villahermosa	Tabasco
Mexico	GSK Investigational Site	Zapopan	Jalisco
Netherlands	GSK Investigational Site	Almelo
Netherlands	GSK Investigational Site	Breda
Netherlands	GSK Investigational Site	Eindhoven
Netherlands	GSK Investigational Site	Enschede
Netherlands	GSK Investigational Site	Hoorn
Netherlands	GSK Investigational Site	Veldhoven
Netherlands	GSK Investigational Site	Zutphen
Poland	GSK Investigational Site	Bialystok
Poland	GSK Investigational Site	Krakow
Poland	GSK Investigational Site	Krakow
Poland	GSK Investigational Site	Krakow
Poland	GSK Investigational Site	Lodz
Poland	GSK Investigational Site	Tarnow
Poland	GSK Investigational Site	Warszawa
Poland	GSK Investigational Site	Wroclaw
Romania	GSK Investigational Site	Bacau
Romania	GSK Investigational Site	Brasov
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	Craiova
Romania	GSK Investigational Site	Deva
Romania	GSK Investigational Site	Iasi
Romania	GSK Investigational Site	Pitesti
Romania	GSK Investigational Site	Ploiesti
Romania	GSK Investigational Site	Ploiesti
Romania	GSK Investigational Site	Timisoara
Russian Federation	GSK Investigational Site	Blagoveshchensk
Russian Federation	GSK Investigational Site	Chelyabinsk
Russian Federation	GSK Investigational Site	Chita
Russian Federation	GSK Investigational Site	Ekaterinburg
Russian Federation	GSK Investigational Site	Ivanovo
Russian Federation	GSK Investigational Site	Kazan
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Nizhniy Novgorod
Russian Federation	GSK Investigational Site	Pyatigorsk
Russian Federation	GSK Investigational Site	Ryazan
Russian Federation	GSK Investigational Site	St. Petersburg
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	Vladivostok
Russian Federation	GSK Investigational Site	Voronezh
Sweden	GSK Investigational Site	Göteborg
Sweden	GSK Investigational Site	Linköping
Sweden	GSK Investigational Site	Luleå
Sweden	GSK Investigational Site	Lund
Sweden	GSK Investigational Site	Uppsala
Ukraine	GSK Investigational Site	Dnipropetrovsk
Ukraine	GSK Investigational Site	Kharkiv
Ukraine	GSK Investigational Site	Kharkiv
Ukraine	GSK Investigational Site	Kiev
Ukraine	GSK Investigational Site	Kyiv
Ukraine	GSK Investigational Site	Kyiv
Ukraine	GSK Investigational Site	Poltava
Ukraine	GSK Investigational Site	Vinnytsia
Ukraine	GSK Investigational Site	Vinnytsia
Ukraine	GSK Investigational Site	Zaporizhia
Ukraine	GSK Investigational Site	Zaporizhia
Ukraine	GSK Investigational Site	Zaporizhia
United States	GSK Investigational Site	Bethesda	Maryland
United States	GSK Investigational Site	Charlotte	North Carolina
United States	GSK Investigational Site	Cincinnati	Ohio
United States	GSK Investigational Site	Cincinnati	Ohio
United States	GSK Investigational Site	Coeur d'Alene	Idaho
United States	GSK Investigational Site	Colorado Springs	Colorado
United States	GSK Investigational Site	Columbia	Maryland
United States	GSK Investigational Site	Denver	Colorado
United States	GSK Investigational Site	Easley	South Carolina
United States	GSK Investigational Site	El Paso	Texas
United States	GSK Investigational Site	Fort Mill	South Carolina
United States	GSK Investigational Site	Greenville	South Carolina
United States	GSK Investigational Site	Huntington Beach	California
United States	GSK Investigational Site	Little Rock	Arkansas
United States	GSK Investigational Site	Los Angeles	California
United States	GSK Investigational Site	Medford	Oregon
United States	GSK Investigational Site	Middleburg Heights	Ohio
United States	GSK Investigational Site	Minneapolis	Minnesota
United States	GSK Investigational Site	Newport Beach	California
United States	GSK Investigational Site	Normal	Illinois
United States	GSK Investigational Site	North Dartmouth	Massachusetts
United States	GSK Investigational Site	Orangeburg	South Carolina
United States	GSK Investigational Site	Raleigh	North Carolina
United States	GSK Investigational Site	Rancho Mirage	California
United States	GSK Investigational Site	Richmond	Virginia
United States	GSK Investigational Site	Rolla	Missouri
United States	GSK Investigational Site	Rolling Hills Estates	California
United States	GSK Investigational Site	Saint Louis	Missouri
United States	GSK Investigational Site	San Diego	California
United States	GSK Investigational Site	Seattle	Washington
United States	GSK Investigational Site	Shelby	North Carolina
United States	GSK Investigational Site	Skillman	New Jersey
United States	GSK Investigational Site	Spartanburg	South Carolina
United States	GSK Investigational Site	Tallahassee	Florida
United States	GSK Investigational Site	Vista	California
United States	GSK Investigational Site	Waco	Texas
United States	GSK Investigational Site	Wheat Ridge	Colorado

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

United States,  Argentina,  Chile,  Germany,  Mexico,  Netherlands,  Poland,  Romania,  Russian Federation,  Sweden,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Pulmonary function was measured by FEV1, defined as the maximal amount of air that can be forcefully exhaled in one second. The weighted mean was calculated from the pre-dose FEV1 (within 30 minutes prior to dosing) and post-dose FEV1 measurements at 5, 15, and 30 minutes and at 1, 2, 3, 4, 5, 12, 16, 20, 23, and 24 hours on Day 84/Week 12. At each time point, the highest of three technically acceptable measurements was recorded. Change from Baseline was calculated as the weighted mean of the 24-hour serial FEV1 measures on Day 84/Week 12 minus the Baseline value. Baseline was the pre-dose FEV1 measurement value obtained at Visit 3. The analysis was performed using an Analysis of Covariance (ANCOVA) model with covariates of Baseline FEV1, region, sex, age, and treatment.	Baseline and Week 12
Secondary	Change From Baseline in Clinic Visit Trough FEV1 at the End of the 12-week Treatment Period	Pulmonary function was measured by FEV1, defined as the maximal amount of air that can be forcefully exhaled in one second. Trough FEV1 is defined as a pre-dose FEV1 measurement taken at a clinic visit while still on-treatment. Change from Baseline in trough FEV1 at the end of the 12-week treatment period was defined using the 24-hour post-dose serial FEV1 measurement taken at the Week 12 clinic visit. Change from Baseline was calculated as the Week 12 trough FEV1 value minus the Baseline value. The analysis was performed using an ANCOVA model with covariates of Baseline trough FEV1, region, sex, age, and treatment. The last observation carried forward (LOCF) method was used to impute missing data, in which the last non-missing post-Baseline on-treatment measurement at scheduled clinic visits was used to impute the missing measurements.	Baseline and Week 12
Secondary	Change From Baseline in the Percentage of Rescue-free 24-hour (hr) Periods During the 12-week Treatment Period	The number of inhalations of rescue albuterol/salbutamol inhalation aerosol used during the day and night was recorded by the participants in a daily electronic diary (eDiary). 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 12-week treatment period minus the Baseline value. The analysis was performed using an ANCOVA model with covariates of Baseline, region, sex, age, and treatment.	Baseline and Weeks 1-12
Secondary	Change From Baseline in the Percentage of Symptom-free 24-hour (hr) Periods During the 12-week Treatment Period	Asthma symptoms were recorded in a daily eDairy by the participants every day in the morning and evening before taking any rescue or study medication and before the peak expiratory flow measurement. 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 12-week treatment period minus the Baseline value. The analysis was performed using an ANCOVA model with covariates of Baseline, region, sex, age, and treatment.	Baseline and Weeks 1-12
Secondary	Change From Baseline in Daily Morning (AM) Peak Expiratory Flow (PEF) Averaged Over the 12-week Treatment Period	Peak Expiratory Flow (PEF) is defined as the maximum airflow during a forced expiration beginning with the lungs fully inflated. PEF was measured by the participants using a hand-held electronic peak flow meter each evening prior to the dose of study medication and any rescue albuterol/salbutamol inhalation aerosol use and each morning. The best of three measurements was recorded. 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 12-week treatment period minus the Baseline value. The analysis was performed using an ANCOVA model with covariates of Baseline, region, sex, age, and treatment.	Baseline and Weeks 1-12
Secondary	Change From Baseline in Daily Evening (PM) PEF Averaged Over the 12-week Treatment Period	PEF is defined as the maximum airflow during a forced expiration beginning with the lungs fully inflated. PEF was measured by the participants using a hand-held electronic peak flow meter each evening prior to the dose of study medication and any rescue albuterol/salbutamol inhalation aerosol use and each morning. The best of three measurements was recorded. 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 12-week treatment period minus the Baseline value. The analysis was performed using an ANCOVA model with covariates of Baseline, region, sex, age, and treatment.	Baseline and Weeks 1-12

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