A 6-month Study to Evaluate the Efficacy and Safety of Fluticasone Furoate (FF)/GW642444 Inhalation Powder in Subjects With Chronic Obstructive Pulmonary Disease (COPD)

Pulmonary Disease, Chronic Obstructive Clinical Trial

Official title:

A 24-Week Study to Evaluate the Efficacy and Safety of Fluticasone Furoate (FF)/GW642444 Inhalation Powder and the Individual Components Delivered Once Daily (AM) Via a Novel Dry Powder Inhaler Compared With Placebo in Subjects With Chronic Obstructive Pulmonary Disease (COPD)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01053988
• Other study ID #: 112206
• Status: Completed
• Phase: Phase 3
• Start date: October 5, 2009
• Est. completion date: April 14, 2011

Study information

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

Clinical Trial Summary

The Purpose of this study is to assess the efficacy and safety of two strengths of the FF/GW642444 Inhalation Powder in subjects with chronic obstructive pulmonary disease (COPD)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1031
• Est. completion date: April 14, 2011
• Est. primary completion date: February 1, 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

Inclusion Criteria:

• Type of subject: outpatient

• Informed consent: Subjects must give their signed and dated written informed consent to participate.

• Gender: Male or female subjects A female is eligible to enter and participate in the study if she is of:

• Non-child bearing potential OR

• Child bearing potential, has a negative pregnancy test at screening, and agrees to one of the acceptable contraceptive methods defined in the protocol

• Age: =40 years of age at Screening (Visit 1)

• COPD diagnosis: Subjects with a clinical history of COPD in accordance with the definition by the American Thoracic Society/European Respiratory Society [Celli, 2004]

• Tobacco use: Subjects with a current or prior history of =10 pack-years of cigarette smoking at Screening (Visit 1).

• Severity of Disease: Subjects with a Screening (Visit 1) measured post-albuterol/salbutamol:

• FEV1/FVC ratio of =0.70 and

• FEV1 =70% of predicted normal values

• Dyspnea: Achieved a score of =2 on the Modified Medical Research Council Dyspnea Scale (mMRC) at Screening (Visit 1).

Exclusion Criteria:

Subjects meeting any of the following criteria must not be enrolled in the study:

• Pregnancy: Women who are pregnant or lactating or are planning on becoming pregnant during the study.

• Asthma: Subjects with a current diagnosis of asthma

• a1-antitrypsin deficiency: Subjects with a1-antitrypsin deficiency as the underlying cause of COPD

• Other respiratory disorders: Subjects with active tuberculosis, lung cancer, bronchiectasis, sarcoidosis, lung fibrosis, pulmonary hypertension, interstitial lung diseases, or other active pulmonary diseases

• Lung resection: Subjects with lung volume reduction surgery within the 12 months prior to Screening (Visit 1)

• Chest X-ray (or CT scan): Subjects with a chest X-ray (or CT scan) that reveals evidence of clinically significant abnormalities not believed to be due to the presence of COPD.

• Hospitalization: Subjects who are hospitalized due to poorly controlled COPD within 12 weeks of Visit 1.

• Poorly controlled COPD: Subjects with poorly controlled COPD, defined as the occurrence of the following in the 6 weeks prior to Visit 1: Acute worsening of COPD that is managed by subject with corticosteroids or antibiotics or that requires treatment prescribed by a physician.

• Lower respiratory tract infection: Subjects with lower respiratory tract infection that required the use of antibiotics within 6 weeks prior to Visit 1.

• Other diseases/abnormalities: Subjects with historical or current evidence of clinically significant cardiovascular (i.e., pacemaker), neurological, psychiatric, renal, hepatic, immunological, endocrine (including uncontrolled diabetes or thyroid disease) or haematological abnormalities that are uncontrolled.

• Peptic Ulcer disease: Subjects with clinically significant peptic ulcer disease that is uncontrolled.

• Hypertension: Subjects with clinically significant hypertension that is uncontrolled.

• Cancer: Subjects with carcinoma that has not been in complete remission for at least 5 years. Carcinoma in situ of the cervix, squamous cell carcinoma and basal cell carcinoma of the skin would not be excluded if the subject has been considered cured within 5 years since diagnosis.

• Drug/food allergy: Subjects with a history of hypersensitivity to any of the study medication or components of the inhalation powder

• Drug/alcohol abuse: Subjects with a known or suspected history of alcohol or drug abuse within the last 2 years

• Medication prior to spirometry: Subjects who are medically unable to withhold their albuterol/salbutamol and/or their ipratropium 4 hours prior to spirometry testing at each study visit

• Additional medication: Use of certain medications such as bronchodilators and corticosteroids for the protocol-specified times prior to Visit 1 (the Investigator will discuss the specific medications)

• Oxygen therapy: Subjects receiving treatment with long-term oxygen therapy (LTOT) or nocturnal oxygen therapy required for greater than 12 hours a day. Oxygen prn use (i.e., =12 hours per day) is not exclusionary.

• Sleep apnea: Subjects with clinically significant sleep apnea who require use of continuous positive airway pressure (CPAP) device or non-invasive positive pressure ventilation (NIPPV) device.

• Pulmonary rehabilitation: Subjects who have participated in the acute phase of a Pulmonary Rehabilitation Program within 4 weeks prior to Screening (Visit 1) or who will enter the acute phase of a Pulmonary Rehabilitation Program during the study.

• Non-compliance: Subjects at risk of non-compliance, or unable to comply with the study procedures. Any infirmity, disability, or geographic location that would limit compliance for scheduled visits.

• Questionable validity of consent: Subjects with a history of psychiatric disease, intellectual deficiency, poor motivation or other conditions that will limit the validity of informed consent to participate in the study.

• Prior use of study medication/other investigational drugs

• Affiliation with investigator site: Study investigators, sub-investigators, study coordinators, employees of a participating investigator or immediate family members of the aforementioned are excluded from participating in this study.

Related Conditions & MeSH terms

• Chronic Disease
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• FF/GW642444 Inhalation Powder
Inhaled Corticosteroid (ICS)/ Long Acting Beta Agonist(LABA) for COPD
• FF Inhalation Powder
Inhaled Corticosteroid (ICS)
• GW642444 Inhalation Powder
Long Acting Beta Agonist(LABA)
• Placebo
Placebo

Locations

Country	Name	City	State
Chile	GSK Investigational Site	Puente Alto - 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
Estonia	GSK Investigational Site	Parnu
Estonia	GSK Investigational Site	Tallinn
Estonia	GSK Investigational Site	Tallinn
Estonia	GSK Investigational Site	Tartu
Germany	GSK Investigational Site	Aschaffenburg	Bayern
Germany	GSK Investigational Site	Deggingen	Baden-Wuerttemberg
Germany	GSK Investigational Site	Dortmund	Nordrhein-Westfalen
Germany	GSK Investigational Site	Erlangen	Bayern
Germany	GSK Investigational Site	Eschwege	Hessen
Germany	GSK Investigational Site	Gelsenkirchen	Nordrhein-Westfalen
Germany	GSK Investigational Site	Goerlitz	Sachsen
Germany	GSK Investigational Site	Hamburg
Germany	GSK Investigational Site	Hamburg
Germany	GSK Investigational Site	Hannover	Niedersachsen
Germany	GSK Investigational Site	Hannover	Niedersachsen
Germany	GSK Investigational Site	Kassel	Hessen
Germany	GSK Investigational Site	Leipzig	Sachsen
Germany	GSK Investigational Site	Luebeck	Schleswig-Holstein
Germany	GSK Investigational Site	Magdeburg	Sachsen-Anhalt
Germany	GSK Investigational Site	Mainz	Rheinland-Pfalz
Germany	GSK Investigational Site	Muenchen	Bayern
Germany	GSK Investigational Site	Muenchen	Bayern
Germany	GSK Investigational Site	Ruedersdorf	Brandenburg
Germany	GSK Investigational Site	Ruesselsheim	Hessen
Germany	GSK Investigational Site	Schmoelln	Thueringen
Germany	GSK Investigational Site	Schwetzingen	Baden-Wuerttemberg
Japan	GSK Investigational Site	Fukuoka
Japan	GSK Investigational Site	Fukuoka
Japan	GSK Investigational Site	Ibaraki
Japan	GSK Investigational Site	Kagawa
Japan	GSK Investigational Site	Kanagawa
Japan	GSK Investigational Site	Nagano
Japan	GSK Investigational Site	Osaka
Japan	GSK Investigational Site	Shizuoka
Japan	GSK Investigational Site	Tokyo
Japan	GSK Investigational Site	Tokyo
Korea, Republic of	GSK Investigational Site	Bucheon-si,
Korea, Republic of	GSK Investigational Site	Daegu
Korea, Republic of	GSK Investigational Site	Gyeonggi-do
Korea, Republic of	GSK Investigational Site	Incheon
Korea, Republic of	GSK Investigational Site	Kangwon-do
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	Seoul
Korea, Republic of	GSK Investigational Site	Uijeongbu-si, Kyonggi-do
Mexico	GSK Investigational Site	Guadalajara	Jalisco
Mexico	GSK Investigational Site	Mexico City
Mexico	GSK Investigational Site	Monterrey	Nuevo León
Mexico	GSK Investigational Site	Monterrey	Nuevo León
Mexico	GSK Investigational Site	Monterrey NL	Nuevo León
Philippines	GSK Investigational Site	Iloilo City
Philippines	GSK Investigational Site	Lipa City
Philippines	GSK Investigational Site	Pasig City
Philippines	GSK Investigational Site	Quezon City
Philippines	GSK Investigational Site	Quezon City
Poland	GSK Investigational Site	Bialystok
Poland	GSK Investigational Site	Bialystok
Poland	GSK Investigational Site	Gdansk
Poland	GSK Investigational Site	Grudziadz
Poland	GSK Investigational Site	Krakow
Poland	GSK Investigational Site	Lodz
Poland	GSK Investigational Site	Lodz
Poland	GSK Investigational Site	Lublin
Poland	GSK Investigational Site	Ostrow Wielkopolski
Poland	GSK Investigational Site	Poznan
Poland	GSK Investigational Site	Wilkowice
Poland	GSK Investigational Site	Wodzislaw Slaski
Poland	GSK Investigational Site	Zabrze
Russian Federation	GSK Investigational Site	Barnaul
Russian Federation	GSK Investigational Site	Ekaterinburg
Russian Federation	GSK Investigational Site	Irkutsk
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Pyatigorsk
Russian Federation	GSK Investigational Site	Samara
Russian Federation	GSK Investigational Site	Shakhty, Rostov Region
Russian Federation	GSK Investigational Site	Tomsk
Russian Federation	GSK Investigational Site	Tumen
Russian Federation	GSK Investigational Site	Ufa
Russian Federation	GSK Investigational Site	Yaroslavl
United States	GSK Investigational Site	Atlanta	Georgia
United States	GSK Investigational Site	Austell	Georgia
United States	GSK Investigational Site	Baltimore	Maryland
United States	GSK Investigational Site	Charleston	South Carolina
United States	GSK Investigational Site	Charlotte	North Carolina
United States	GSK Investigational Site	Clearwater	Florida
United States	GSK Investigational Site	Coeur d'Alene	Idaho
United States	GSK Investigational Site	Columbus	Ohio
United States	GSK Investigational Site	DeLand	Florida
United States	GSK Investigational Site	Edina	Minnesota
United States	GSK Investigational Site	Encinitas	California
United States	GSK Investigational Site	Evansville	Indiana
United States	GSK Investigational Site	Fall River	Massachusetts
United States	GSK Investigational Site	Gaffney	South Carolina
United States	GSK Investigational Site	Greenville	South Carolina
United States	GSK Investigational Site	Hazard	Kentucky
United States	GSK Investigational Site	Livonia	Michigan
United States	GSK Investigational Site	Madisonville	Kentucky
United States	GSK Investigational Site	Maitland	Florida
United States	GSK Investigational Site	Marietta	Georgia
United States	GSK Investigational Site	Medford	Oregon
United States	GSK Investigational Site	Miami	Florida
United States	GSK Investigational Site	Minneapolis	Minnesota
United States	GSK Investigational Site	Mobile	Alabama
United States	GSK Investigational Site	Montgomery	Alabama
United States	GSK Investigational Site	New Orleans	Louisiana
United States	GSK Investigational Site	Orlando	Florida
United States	GSK Investigational Site	Panama City	Florida
United States	GSK Investigational Site	Pelzer	South Carolina
United States	GSK Investigational Site	Phoenix	Arizona
United States	GSK Investigational Site	Rancho Mirage	California
United States	GSK Investigational Site	Riverside	California
United States	GSK Investigational Site	Saint Louis	Missouri
United States	GSK Investigational Site	Saint Louis	Missouri
United States	GSK Investigational Site	San Antonio	Texas
United States	GSK Investigational Site	San Diego	California
United States	GSK Investigational Site	Scottsdale	Arizona
United States	GSK Investigational Site	Sepulveda	California
United States	GSK Investigational Site	Spartanburg	South Carolina
United States	GSK Investigational Site	Stockbridge	Georgia
United States	GSK Investigational Site	Sunset	Louisiana
United States	GSK Investigational Site	Tamarac	Florida
United States	GSK Investigational Site	Wichita	Kansas
United States	GSK Investigational Site	Wichita	Kansas
United States	GSK Investigational Site	Wichita Falls	Texas
United States	GSK Investigational Site	Wilmington	North Carolina
United States	GSK Investigational Site	Winter Park	Florida

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

United States,  Chile,  Estonia,  Germany,  Japan,  Korea, Republic of,  Mexico,  Philippines,  Poland,  Russian Federation, 

References & Publications (1)

Kerwin EM, Scott-Wilson C, Sanford L, Rennard S, Agusti A, Barnes N, Crim C. A randomised trial of fluticasone furoate/vilanterol (50/25 µg; 100/25 µg) on lung function in COPD. Respir Med. 2013 Apr;107(4):560-9. doi: 10.1016/j.rmed.2012.12.014. Epub 2013 Jan 23. Erratum in: Respir Med. 2013 Dec;107(12):2094. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Weighted Mean FEV1 Over 0-4 Hours Post-dose at Day 168	Co-Primary Endpoint: Pulmonary function was measured by forced expiratory volume in one second (FEV1), defined as the maximal amount of air that can be forcefully exhaled from the lungs in one second. Serial FEV1 measurements were taken electronically by spirometry at BL, weeks 2, 8, 12, and 84 (Day 168). Weighted mean (WM) was calculated using the 0 - 4 h post-dose FEV1 measurements that included the pre-dose (Day 1: 30 minutes [min] and 5 min prior to dosing; other serial visits:23 and 24 h after previous morning dose) and post-dose (5, 15, and 30 min and 1, 2, and 4 h) assessments. BL FEV1 is the mean of the two assessments made 30 and 5 min pre-dose at Day 1. WM change from BL was the WM at the visit minus the BL value. Analysis was performed using a repeated measures model with covariates of treatment, smoking status at screening (stratum), BL- mean of the two assessments made 30 and 5 min pre-dose on Day 1, centre grouping, Day, Day by BL and Day by treatment interactions.	Baseline (BL) to Day 168
Primary	Change From Baseline in Clinic Visit Trough (Pre-bronchodilator and Pre-dose) FEV1 at Day 169	Co-Primary Endpoint: Pulmonary function was measured by forced expiratory volume in one second (FEV1), defined as the maximal amount of air that can be forcefully exhaled from the lungs in one second. Trough FEV1 measurements were taken electronically by spirometry on Days 2, 7, 14, 28, 56, 84, 112, 140, 168, and 169. BL was defined as the mean of the assessments made 30 minutes pre-dose and 5 minutes pre-dose on Treatment Day 1.Trough FEV1 was defined as the mean of the FEV1 values obtained 23 and 24 hours after previous morning's dosing. Change from BL was calculated as the average at each visit minus the BL value. Analysis was performed using a repeated measures model with covariates of treatment, smoking status at screening (stratum), BL - mean of the two assessments made 30 minutes pre-dose and immediately pre-dose on Day 1, centre grouping, Day, Day by BL and Day by treatment interactions.	Baseline to Day 169
Secondary	Change From Baseline in Chronic Respiratory Disease Questionnaire Self-administered Standardized (CRQ-SAS) Dyspnea Score at Day 168	Considered an 'Other' endpoint by FDA. CRQ-SAS measures 4 domains (mastery, fatigue, emotional function, and dyspnea) of functioning of participants with COPD: mastery (amount of control the participant feels he/she has over COPD symptoms); fatigue (how tired the participant feels); emotional function (how anxious/depressed the participant feels); and dyspnea (how short of breath the participant feels during physical activities). Each domain is measured on a scale of 1-7 (1=maximum impairment; 7=no impairment). Each domain score is calculated separately. Current assessment was done only for dyspnea domain. BL scores are the derived scores for each domain and total at Day 1 pre-dose. Change from BL was calculated as the average at each visit minus the BL value. Analysis performed used a repeated measures model with covariates of treatment, smoking status at screening (stratum), BL (derived scores at Day 1 pre-dose), centre grouping, Day, Day by BL and Day by treatment interactions.	Baseline to Day 168
Secondary	Change From Baseline in Peak Post-dose FEV1 (0-4 Hour) on Day 1	Pulmonary function was measured by forced expiratory volume in one second (FEV1), defined as the maximal amount of air that can be forcefully exhaled from the lungs in one second. BL FEV1 is defined as the mean of the assessments made 30 minutes pre-dose and immediately pre-dose on Day 1. If one of these two assessments was missing then BL was defined as the single pre-dose FEV1 value on Day 1. Peak post-dose FEV1 (0-4 hours) is the maximum post-dose FEV1 recorded over the nominal timepoints of 5, 15 and 30 min, 1, 2 and 4 hours post the Day 1 dose. Change from BL is calculated as the peak post-dose FEV1 (0-4 hour) on Day 1 minus BL FEV1. Analysis performed used an Analysis of Covariance (ANCOVA) model with covariates of treatment, smoking status at screening (stratum), BL - mean of the two assessments made 30 minutes pre-dose and immediately pre-dose on Day 1, and centre grouping.	Baseline and Day 1
Secondary	Time to Onset (Increase of 100 Milliliter [mL] From Baseline in 0-4 Hours Post-dose FEV1) on Treatment Day 1	Pulmonary function was measured by forced expiratory volume in one second (FEV1), defined as the maximal amount of air that can be forcefully exhaled from the lungs in one second. Baseline FEV1 is defined as the mean of the two assessments made 30 minutes pre-dose and immediately pre-dose on Day 1. Time to onset on Treatment Day 1 is defined as a 100 mL increase from Baseline in FEV1. Time to increase of 100 mL from Baseline was calculated over the 5, 15, 30 minutes, and 1, 2, and 4 hours time points. A participant who had at least one post-dose FEV1 on Day 1, but did not achieve a 100 mL or more increase from Baseline at any scheduled time-point at which FEV1 was assessed up to and including 4 hours was censored.	Baseline and Day 1

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