Efficacy and Safety Study of Fluticasone Furoate (FF)/GW642444 Inhalation Powder and the Individual Components 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: NCT01054885
• Other study ID #: 112207
• Status: Completed
• Phase: Phase 3
• First received: January 14, 2010
• Last updated: January 18, 2018
• Start date: October 19, 2009
• Est. completion date: February 8, 2011

Study information

• Verified date: January 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 subject with Chronic Obstructive Pulmonary Disease (COPD)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1226
• Est. completion date: February 8, 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 Inhalation Powder
Inhaled Corticosteroid (ICS)
• FF/GW642444 Inhalation Powder
Inhaled Corticosteroid (ICS)/ Long Acting Beta Agonist(LABA) for COPD
• GW642444 Inhalation Powder
Long Acting Beta Agonist(LABA)
• Placebo
Placebo

Locations

Country	Name	City	State
Argentina	GSK Investigational Site	Buenos Aires
Argentina	GSK Investigational Site	Cipolletti	Río Negro
Argentina	GSK Investigational Site	Ciudad Autónoma de Buenos Aires
Argentina	GSK Investigational Site	San Miguel de Tucumán
Czechia	GSK Investigational Site	Brno
Czechia	GSK Investigational Site	Jindrichuv Hradec
Czechia	GSK Investigational Site	Kralupy nad Vltavou
Czechia	GSK Investigational Site	Liberec
Czechia	GSK Investigational Site	Ostrava - Poruba
Czechia	GSK Investigational Site	Plzen
Czechia	GSK Investigational Site	Plzen
Czechia	GSK Investigational Site	Praha 8
Czechia	GSK Investigational Site	Praha 8
Czechia	GSK Investigational Site	Rokycany
Czechia	GSK Investigational Site	Tabor
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	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Darmstadt	Hessen
Germany	GSK Investigational Site	Dresden	Sachsen
Germany	GSK Investigational Site	Frankfurt	Hessen
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	Hamburg
Germany	GSK Investigational Site	Hamburg
Germany	GSK Investigational Site	Koeln	Nordrhein-Westfalen
Germany	GSK Investigational Site	Leipzg	Sachsen
Germany	GSK Investigational Site	Muenchen	Bayern
Germany	GSK Investigational Site	Radebeul	Sachsen
Germany	GSK Investigational Site	Rhaunen	Rheinland-Pfalz
Germany	GSK Investigational Site	Schwerin	Mecklenburg-Vorpommern
Japan	GSK Investigational Site	Chiba
Japan	GSK Investigational Site	Ehime
Japan	GSK Investigational Site	Fukuoka
Japan	GSK Investigational Site	Ibaraki
Japan	GSK Investigational Site	Kyoto
Japan	GSK Investigational Site	Kyoto
Japan	GSK Investigational Site	Mie
Japan	GSK Investigational Site	Okinawa
Japan	GSK Investigational Site	Okinawa
Japan	GSK Investigational Site	Osaka
Japan	GSK Investigational Site	Osaka
Japan	GSK Investigational Site	Shizuoka
Japan	GSK Investigational Site	Tokyo
Poland	GSK Investigational Site	Czestochowa
Poland	GSK Investigational Site	Gdansk
Poland	GSK Investigational Site	Gidle
Poland	GSK Investigational Site	Gizycko
Poland	GSK Investigational Site	Lomza
Poland	GSK Investigational Site	Piekary Slaskie
Poland	GSK Investigational Site	Szczecin
Poland	GSK Investigational Site	Warszawa
Poland	GSK Investigational Site	Warszawa
Romania	GSK Investigational Site	Brasov
Romania	GSK Investigational Site	Bucharest
Romania	GSK Investigational Site	Bucharest
Romania	GSK Investigational Site	Bucharest
Romania	GSK Investigational Site	Bucharest
Romania	GSK Investigational Site	Bucharest
Romania	GSK Investigational Site	Bucharest
Romania	GSK Investigational Site	Bucuresti
Romania	GSK Investigational Site	Bucuresti
Romania	GSK Investigational Site	Cluj-Napoca
Romania	GSK Investigational Site	Cluj-Napoca
Romania	GSK Investigational Site	Constanta
Romania	GSK Investigational Site	Deva
Romania	GSK Investigational Site	Iasi
Romania	GSK Investigational Site	Popesti Leordeni
Romania	GSK Investigational Site	Suceava
Romania	GSK Investigational Site	Timisoara
Russian Federation	GSK Investigational Site	Chelyabinsk
Russian Federation	GSK Investigational Site	Ivanovo
Russian Federation	GSK Investigational Site	Kazan
Russian Federation	GSK Investigational Site	Kemerovo
Russian Federation	GSK Investigational Site	Krasnoyarsk
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Saint-Petersburg
Russian Federation	GSK Investigational Site	Saint-Petersburg
Russian Federation	GSK Investigational Site	Yaroslavl
Ukraine	GSK Investigational Site	Dnipropetrovsk
Ukraine	GSK Investigational Site	Kharkiv
Ukraine	GSK Investigational Site	Kiev
Ukraine	GSK Investigational Site	Kyiv
Ukraine	GSK Investigational Site	Kyiv
Ukraine	GSK Investigational Site	Kyiv
Ukraine	GSK Investigational Site	Kyiv
Ukraine	GSK Investigational Site	Odesa
Ukraine	GSK Investigational Site	Simferopol
Ukraine	GSK Investigational Site	Vinnytsia
United States	GSK Investigational Site	Bay Pines	Florida
United States	GSK Investigational Site	Birmingham	Alabama
United States	GSK Investigational Site	Boerne	Texas
United States	GSK Investigational Site	Brandon	Florida
United States	GSK Investigational Site	Brooklyn	New York
United States	GSK Investigational Site	Cherry Hill	New Jersey
United States	GSK Investigational Site	Cincinnati	Ohio
United States	GSK Investigational Site	Clearwater	Florida
United States	GSK Investigational Site	Cocoa	Florida
United States	GSK Investigational Site	Columbia	South Carolina
United States	GSK Investigational Site	Corsicana	Texas
United States	GSK Investigational Site	Dayton	Ohio
United States	GSK Investigational Site	Decatur	Georgia
United States	GSK Investigational Site	Easley	South Carolina
United States	GSK Investigational Site	Elizabeth City	North Carolina
United States	GSK Investigational Site	Fort Lauderdale	Florida
United States	GSK Investigational Site	Fredericksburg	Virginia
United States	GSK Investigational Site	Gaffney	South Carolina
United States	GSK Investigational Site	Gainesville	Georgia
United States	GSK Investigational Site	Jasper	Alabama
United States	GSK Investigational Site	Johnson City	Tennessee
United States	GSK Investigational Site	Kingwood	Texas
United States	GSK Investigational Site	Lakewood	California
United States	GSK Investigational Site	Lenexa	Kansas
United States	GSK Investigational Site	Long Beach	California
United States	GSK Investigational Site	Los Angeles	California
United States	GSK Investigational Site	Martinez	Georgia
United States	GSK Investigational Site	Medford	Oregon
United States	GSK Investigational Site	Monterey Park	California
United States	GSK Investigational Site	Morgantown	West Virginia
United States	GSK Investigational Site	National City	California
United States	GSK Investigational Site	New Tazewell	Tennessee
United States	GSK Investigational Site	Ocean City	New Jersey
United States	GSK Investigational Site	Oklahoma City	Oklahoma
United States	GSK Investigational Site	Orangeburg	South Carolina
United States	GSK Investigational Site	Oxnard	California
United States	GSK Investigational Site	Pensacola	Florida
United States	GSK Investigational Site	Portland	Oregon
United States	GSK Investigational Site	Saint Charles	Missouri
United States	GSK Investigational Site	San Diego	California
United States	GSK Investigational Site	Santa Monica	California
United States	GSK Investigational Site	Seneca	South Carolina
United States	GSK Investigational Site	Spartanburg	South Carolina
United States	GSK Investigational Site	Statesville	North Carolina
United States	GSK Investigational Site	Temple	Texas
United States	GSK Investigational Site	Tulsa	Oklahoma
United States	GSK Investigational Site	Union	South Carolina
United States	GSK Investigational Site	Wheaton	Maryland
United States	GSK Investigational Site	Wilmington	Delaware

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

United States,  Argentina,  Czechia,  Germany,  Japan,  Poland,  Romania,  Russian Federation,  Ukraine, 

References & Publications (1)

Martinez FJ, Boscia J, Feldman G, Scott-Wilson C, Kilbride S, Fabbri L, Crim C, Calverley PM. Fluticasone furoate/vilanterol (100/25; 200/25 µg) improves lung function in COPD: a randomised trial. Respir Med. 2013 Apr;107(4):550-9. doi: 10.1016/j.rmed.2012.12.016. Epub 2013 Jan 16. Erratum in: Respir Med. 2013 Dec;107(12):2092-3. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Weighted Mean FEV1 Over 0-4 Hours (h) 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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