Study HZA106829: Efficacy/Safety Study of Fluticasone Furoate/Vilanterol (GW642444) in Adult and Adolescent Asthmatics

Asthma Clinical Trial

Official title:

HZA106829: A Randomised, Double-blind, Parallel Group, Multicentre Study of Fluticasone Furoate/GW642444 Inhalation Powder, Fluticasone Furoate Inhalation Powder Alone, and Fluticasone Propionate Alone in the Treatment of Persistent Asthma in Adults and Adolescents

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01134042
• Other study ID #: 106829
• Status: Completed
• Phase: Phase 3
• First received: May 27, 2010
• Last updated: July 31, 2014
• Start date: June 2010
• Est. completion date: October 2011

Study information

• Verified date: July 2014
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Health authority: Poland: Centralna Ewidencja Badan Klinicznych Urzad Rejestracji Produktów Leczniczych, Wyrobów Medycznych i Produktów BiobójczychJapan: Pharmaceutical and Medical Device AgencyRussia: Federal Service of Surveillance in Healthcare and Social development of Russian federationRomania: National Medicines AgencyGermany: Federal Institute for Drugs and Medical DevicesUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of the study is to compare the efficacy and safety of fluticasone furoate/vilanterol (GW642444) inhalation powder administered once daily each evening with fluticasone furoate inhalation powder administered alone once daily each evening in adolescent and adult subjects 12 years of age and older with persistent bronchial asthma over a 24-week period.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 587
• Est. completion date: October 2011
• Est. primary completion date: October 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 12 Years and older

Eligibility

Inclusion Criteria:

• Outpatient at least 12 years of age

• Both genders; females of childbearing potential must be willing to use birth control method

• Pre-bronchodilator FEV1 of 40-90% predicted

• Reversibility FEV1 of at least 12% and 200mls

• Current asthma therapy that includes an inhaled corticosteroid for at least 12 weeks prior to first visit

Exclusion Criteria:

• History of life-threatening asthma

• Respiratory infection or oral candidiasis

• Asthma exacerbation within 12 weeks

• Concurrent respiratory disease or other disease that would confound study participation or affect subject safety

• Allergies to study drugs, study drugs' excipients, medications related to study drugs

• Taking another investigational medication or medication prohibited for use during this study

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Asthma

Intervention

Drug:
• Fluticasone Furoate/Vilanterol Inhalation Powder
Fluticasone furoate/Vilanterol inhalation powder inhaled orally once daily for 24 weeks
• Fluticasone Furoate Inhalation Powder
Fluticasone furoate inhalation powder inhaled orally once daily for 24 weeks
• Fluticasone Propionate Inhalation Powder
Fluticasone propionate inhalation powder inhaled orally twice daily for 24 weeks

Other:
• Placebo Inhalation Powder 1
Placebo in novel dry powder inhaler once daily
• Placebo Inhalation Powder 2
Placebo in Diskus inhaler twice daily

Locations

Country	Name	City	State
Germany	GSK Investigational Site	Cottbus	Brandenburg
Germany	GSK Investigational Site	Frankfurt	Hessen
Germany	GSK Investigational Site	Geesthacht	Schleswig-Holstein
Germany	GSK Investigational Site	Gelnhausen	Hessen
Germany	GSK Investigational Site	Hamburg
Germany	GSK Investigational Site	Hannover	Niedersachsen
Germany	GSK Investigational Site	Kassel	Hessen
Germany	GSK Investigational Site	Luebeck	Schleswig-Holstein
Germany	GSK Investigational Site	Ruesselsheim	Hessen
Germany	GSK Investigational Site	Schwedt	Brandenburg
Japan	GSK Investigational Site	Fukuoka
Japan	GSK Investigational Site	Hiroshima
Japan	GSK Investigational Site	Hyogo
Japan	GSK Investigational Site	Ishikawa
Japan	GSK Investigational Site	Kagawa
Japan	GSK Investigational Site	Kyoto
Japan	GSK Investigational Site	Okayama
Japan	GSK Investigational Site	Okinawa
Japan	GSK Investigational Site	Shizuoka
Japan	GSK Investigational Site	Shizuoka
Japan	GSK Investigational Site	Tokyo
Japan	GSK Investigational Site	Tokyo
Poland	GSK Investigational Site	Bialystok
Poland	GSK Investigational Site	Dzialdowo
Poland	GSK Investigational Site	Gdansk
Poland	GSK Investigational Site	Gdansk
Poland	GSK Investigational Site	Gliwice
Poland	GSK Investigational Site	Krakow
Poland	GSK Investigational Site	Piekary Slaskie
Poland	GSK Investigational Site	Sopot
Romania	GSK Investigational Site	Bucharest
Romania	GSK Investigational Site	Bucharest
Romania	GSK Investigational Site	Iasi
Romania	GSK Investigational Site	Oradea
Romania	GSK Investigational Site	Ploiesti
Romania	GSK Investigational Site	Suceava
Romania	GSK Investigational Site	Timisoara
Russian Federation	GSK Investigational Site	Ekaterinburg
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	Moscow
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Ryazan,
Russian Federation	GSK Investigational Site	Smolensk
Russian Federation	GSK Investigational Site	St. Petersburg
Russian Federation	GSK Investigational Site	Yaroslavl
United States	GSK Investigational Site	Asheville	North Carolina
United States	GSK Investigational Site	Atlanta	Georgia
United States	GSK Investigational Site	Austin	Texas
United States	GSK Investigational Site	Bell Gardens	California
United States	GSK Investigational Site	Cincinnati	Ohio
United States	GSK Investigational Site	Clearwater	Florida
United States	GSK Investigational Site	El Paso	Texas
United States	GSK Investigational Site	Huntington Beach	California
United States	GSK Investigational Site	Lake Oswego	Oregon
United States	GSK Investigational Site	Long Beach	California
United States	GSK Investigational Site	Los Angeles	California
United States	GSK Investigational Site	Medford	Oregon
United States	GSK Investigational Site	Miami	Florida
United States	GSK Investigational Site	Normal	Illinois
United States	GSK Investigational Site	Oklahoma City	Oklahoma
United States	GSK Investigational Site	Oklahoma City	Oklahoma
United States	GSK Investigational Site	Orangeburg	South Carolina
United States	GSK Investigational Site	Panama City	Florida
United States	GSK Investigational Site	River Forest	Illinois
United States	GSK Investigational Site	Riverside	California
United States	GSK Investigational Site	Roseville	California
United States	GSK Investigational Site	San Diego	California
United States	GSK Investigational Site	Sugar Land	Texas

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

United States,  Germany,  Japan,  Poland,  Romania,  Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Clinic Visit 12-hour Post-dose FEV1at Week 24	FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. 12-hour post-dose FEV1 measurements were taken electronically by spirometry at the Week 24 clinic visit. The highest of 3 technically acceptable measurements was recorded.	Week 24	No
Other	Change From Baseline in Weighted Mean Serial FEV1 Over 0 to 4 Hours Post-dose at Week 24	FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Serial FEV1 measurements were taken electronically by spirometry at Baseline. Weighted mean was calculated using the 4-hour serial FEV1 measurements that included the pre-dose assessment (within 5 minutes prior to dosing) and post-dose assessments after 5, 15, and 30 minutes and 1, 2, 3, and 4 hours. At each time point, the highest of 3 technically acceptable measurements was recorded. Baseline was the value obtained at Visit 3. Change from Baseline was calculated as the average Week 24 FEV1 value minus the Baseline value.	Baseline and Week 24	No
Other	Mean Change From Baseline in Daily Morning Trough (AM) and Evening (PM) Peak Expiratory Flow (PEF) Averaged Over the First 12 Weeks and 24 Weeks of the 24-week Treatment Period	PEF is a measure of lung function and 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 morning and evening prior to the dose of study medication and any rescue albuterol/salbutamol inhalation aerosol use. Trough PEF is the PEF measured approximately 24 hours after the last administration of study drug. Change from Baseline (defined as the last 7 days prior to randomization of the participants) was calculated as the value of the averaged daily trough AM/PM PEF over 12 weeks and 24 weeks of the 24-week Treatment Period (at Weeks 12 and 24) minus the Baseline value.	From Baseline up to Week 12 and Week 24	No
Other	The Number of Participants Who Withdrew Due to Lack of Efficacy During the 24-week Treatment Period	The number of participants whose primary reason for withdrawal was lack of efficacy was analyzed.	From the first dose of the study medication up to Week 24/Early Withdrawal	No
Other	Change From Baseline in the Asthma Control Test (ACT) Scores at Week 12 and Week 24	The ACT is a 5-item questionnaire developed as a measure of the participant's asthma control. Questions are designed to be self-completed by the participant and include the following: In the past 4 weeks, "How much of the time did your asthma keep you from getting as much done at work, school or at home?", "How often have you had shortness of breath?", "How often did your asthma symptoms wake you up at night or earlier than usual in the morning?", "How often have you used your rescue inhaler or nebulizer medication (such as albuterol)?" and "How would you rate your asthma control"? The ACT total score is defined as the sum of the scores from all 5 questions, provided all questions have been answered; thus, the total score ranges from 5 (poor control of asthma) to 25 (complete control of asthma). A score of 20 or higher indicates well-controlled asthma. Change from Baseline was calculated as the total score at Week 12 and Week 24/Early Withdrawal minus the total score at Baseline.	Baseline, Week 12, and Week 24/Early Withdrawal	No
Other	Number of Participants With the Indicated Global Assessment of Change Questionnaire Responses at Weeks 4, 12, and 24	At the end of Week 4, Week 8, and Week 24/Early Withdrawal, the Global Assessment of Change Questionnaire that assesses changes in asthma symptoms (AS) and rescue medication use (RMU) was completed by the participants. The number of participants who chose the following answers to the questionnaire were determined: much better, somewhat better, a little better, the same, a little worse, somewhat worse, much worse (to assess the changes in asthma symptoms); much less often, somewhat less often, a little less often, the same, a little more often, somewhat more often, much more often (to assess the changes in the frequency of rescue medication use).	Week 4, Week 12, and Week 24/Early Withdrawal	No
Other	Number of the Indicated Unscheduled Asthma-related Healthcare Visits During the Treatment Period	All unscheduled asthma-related visits to a physician's office, visits to urgent care, visits to the emergency department, and hospitalizations (ICU=intensive care unit; GW=general ward) associated with severe asthma exacerbations or other asthma-related healthcare issues were recorded.	From Baseline up to Week 24/Withdrawal Visit	No
Primary	Change From Baseline in Clinic Visit Trough (Pre-bronchodilator and Pre-dose) Forced Expiratory Volume in One Second (FEV1) at the End of the 24-week Treatment Period	FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Trough FEV1 is defined as the clinic visit (pre-bronchodilator and pre-dose) FEV1 measurement taken at the clinic visit while still on treatment. Pre-dose and pre-rescue albuterol/salbutamol trough FEV1 was measured electronically by spirometry in the evening at the Baseline (BL) through Week 24 clinic visits. The highest of 3 technically acceptable measurements was recorded. BL was the pre-dose value obtained at Visit 3. Change from BL was calculated as the Week 24 value minus the Baseline value. The analysis was performed using an Analysis of Covariance (ANCOVA) model with covariates of BL trough FEV1, country, sex, age, and treatment group.The last observation carried forward (LOCF) method was used to impute missing data, in which the last non-missing post-BL on-treatment measurement at scheduled clinic visits was used to impute the missing measurements.	Baseline and Week 24	No
Primary	Change From Baseline in Weighted Mean Serial FEV1 Over 0-24 Hours Post-dose at Week 24	FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Serial FEV1 measurements were taken electronically by spirometry at the Baseline and Week 24 clinic visits. Weighted mean was calculated using the 24-hour serial FEV1 measurements that included the pre-dose assessment (within 5 minutes prior to dosing) and the post-dose assessments after 5, 15, and 30 minutes and 1, 2, 3, 4, 5, 12, 16, 20, 23, and 24 hours. At each time point, the highest of 3 technically acceptable measurements was recorded. Baseline was the value obtained at Visit 3. Change from Baseline was calculated as the average Week 24 FEV1 value minus the Baseline value.	Baseline and Week 24	No
Secondary	Change From Baseline in the Percentage of Rescue-free and Symptom-free 24-hour Periods at the End of the 24-week Treatment Period	The number of inhalations of rescue bronchodilator, albuterol/salbutamol inhalation aerosol, used during the day and night was recorded by the participants in a daily electronic diary (eDiary). Similarly, 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 period in which a participant's responses to both the morning and evening assessments indicated no use of rescue medication/symptoms was considered to be rescue free/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.	Baseline and Week 24	No
Secondary	Change From Baseline in the Total Asthma Quality of Life Questionnaire (AQLQ) (+12) Score at Week 12 and Week 24/Early Withdrawal	The AQLQ is a disease-specific, self-administered quality of life questionnaire used to evaluate the impact of asthma treatments on the quality of life of asthma sufferers. The AQLQ for 12 years and older (AQLQ [+12]) is a modified version of the AQLQ for use in asthma patients between the age of 12 and 70. The AQLQ contains 32 items in 4 domains: activity limitation (11 items), symptoms (12 items), emotional function (5 items), and environmental stimuli (4 items). For the 32 items on the questionnaire, the response format consists of a seven-point scale, where a value of 1 indicates "total impairment" and a value of 7 indicates "no impairment." The AQLQ total score is defined as the average of the scores from all 32 questions; thus, the total score ranges from 1 (indicates "total impairment") to 7 (indicates "no impairment"). Baseline was the total score obtained at Visit 3. Change from Baseline was calculated as the total score at Weeks 12 and 24 minus the total score at Baseline.	Baseline, Week 12, and Week 24/Early Withdrawal	No