A 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:

HZC102871: A 52-week Efficacy and Safety Study to Compare the Effect of Three Dosage Strengths of Fluticasone Furoate/GW642444 Inhalation Powder With GW642444 on the Annual Rate of Exacerbations in Subjects With Chronic Obstructive Pulmonary Disease (COPD)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01009463
• Other study ID #: 102871
• Status: Completed
• Phase: Phase 3
• First received: November 5, 2009
• Last updated: October 9, 2017
• Start date: September 25, 2009
• Est. completion date: October 31, 2011

Study information

• Verified date: October 2017
• 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 three strengths of the FF/GW642444 Inhalation Powder in subject with Chronic Obstructive Pulmonary Disease (COPD)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1626
• Est. completion date: October 31, 2011
• Est. primary completion date: October 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 (i.e., physiologically incapable of becoming pregnant, including any female who is post-menopausal or surgically sterile). Surgically sterile females are defined as those with a documented hysterectomy and/or bilateral oophorectomy or tubal ligation. Post-menopausal females are defined as being amenorrhoeic for greater than 1 year with an appropriate clinical profile, e.g., age appropriate, history of vasomotor symptoms. However in questionable cases, a blood sample with FSH > 40MIU/ml and estradiol <40pg/ml (<140 pmol/L) is confirmatory. OR

Child bearing potential, has a negative pregnancy test at screening, and agrees to one of the following acceptable contraceptive methods used consistently and correctly (i.e., in accordance with the approved product label and the instructions of the physician for the duration of the study - screening to follow-up contact):

• Complete abstinence from intercourse from screening until the Follow-Up Phone Contact; or

• Male partner is sterile (vasectomy with documentation of azoospermia) prior to female subject entry into the study, and this male partner is the sole partner for that subject; or

• Implants of levonorgestral inserted for at least 1 month prior to the study medication administration but not beyond the third successive year following insertion; or

• Injectable progestogen administered for at least 1 month prior to study medication administration and administered until the Follow-Up Phone Contact; or

• Oral contraceptive (combined or progestogen only) administered for at least one monthly cycle prior to study medication administration; or

• Double barrier method: condom or occlusive cap (diaphragm or cervical/vault caps) plus spermicidal agent (foam/gel/film/cream/suppository); or

• An intrauterine device (IUD), inserted by a qualified physician, with published data showing that the highest expected failure rate is less than 1% per year; or

• Estrogenic vaginal ring; or

• Percutaneous contraceptive patches

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

• COPD diagnosis: Subjects with a clinical history of COPD in accordance with the following definition by the American Thoracic Society/European Respiratory Society [Celli, 2004]: COPD is a preventable and treatable disease characterized by airflow limitation that is not fully reversible. The airflow limitation is usually progressive and is associated with an abnormal inflammatory response of the lungs to noxious particles or gases, primarily caused by cigarette smoking. Although COPD affects the lungs, it also produces significant systemic consequences.

• Tobacco use: Subjects with a current or prior history of =10 pack-years of cigarette smoking at Screening (Visit 1). Former smokers are defined as those who have stopped smoking for at least 6 months prior to Visit 1. Note: Pipe and/or cigar use cannot be used to calculate pack-year history. Number of pack years = (number of cigarettes per day/20) x number of years smoked

• Severity of Disease:

• Subject with a measured post-albuterol/salbutamol FEV1/FVC ratio of =0.70 at Screening (Visit 1)

• Subjects with a measured post-albuterol/salbutamol FEV1 <70% of predicted normal values calculated (via centralized vendor equipment) using NHANES III reference equations [Hankinson, 1999] at Screening (Visit 1). Post-bronchodilator spirometry will be performed approximately 10-15 minutes after the subject has self-administered 4 inhalations (i.e., total 400mcg) of albuterol/salbutamol via an MDI with a valved-holding chamber. The study provided central spirometry equipment will calculate the FEV1/FVC ratio and FEV1 percent predicted values.

• History of Exacerbations: A documented history (e.g., medical record verification) of at least one COPD exacerbation in the 12 months prior to Visit 1 that required either oral corticosteroids, antibiotics and/or hospitalization. Prior use of antibiotics alone does not qualify as an exacerbation history unless the use was associated with treatment of worsening symptoms of COPD, such as increased dyspnea, sputum volume, or sputum purulence (color). Subject verbal reports are not acceptable.

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. (Subjects with a prior history of asthma are eligible if they have a current diagnosis of COPD)

• 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. A chest X-ray must be taken at Screening (Visit 1) if a chest X-ray or CT scan is not available within 6 months prior to Visit 1. For sites in Germany, if a chest X-ray (or CT scan) is not available in the 6 months preceding Screening (Visit 1), the subject will not be eligible for the study.

• Risk Factors for Pneumonia: immune suppression (HIV, Lupus, etc) or other risk for pneumonia (e.g. neurological disorders affecting control of the upper airway, such as Parkinson's, Myasthenia Gravis, etc).

• A moderate and severe COPD exacerbation that has not resolved at least 14 days prior to Visit 1 and at least 30 days following the last dose of oral corticosteroids (if applicable).

• Pneumonia and/or moderate and severe COPD exacerbation at Visit 1 Note: Subjects who experience a pneumonia and/or exacerbation at Screening (Visit 1) must be not continue in the study, but may be re-screened at a later time provided the pneumonia and/or COPD exacerbation has resolved prior to the re-screening visit. At the Re-screening Visit, the chest x-ray should confirm resolution of pneumonia. The Re-screening Visit must be conducted at least = 14 days following the resolution date of the exacerbation and/or pneumonia and at least 30 days following the last dose of oral corticosteroids (if applicable).

• 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. Significant is defined as any disease that, in the opinion of the investigator, would put the safety of the subject at risk through participation, or which would affect the efficacy or safety analysis if the disease/condition exacerbated during the study.

• 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 medications (e.g., beta-agonists, corticosteroid) or components of the inhalation powder (e.g., lactose, magnesium stearate). In addition, subjects with a history of severe milk protein allergy that, in the opinion of the study physician, contraindicates the subject's participation will also be excluded.

• 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 for the 4-hour period required prior to spirometry testing at each study visit.

• Additional medication: Unable to stop using 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. Subjects who are in the maintenance phase of a Pulmonary Rehabilitation Program are not excluded.

• 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: Subjects who have previously been randomized to treatment with GW642444 Inhalation Powder in the B2C111045 study, randomized to treatment in the HZC111348 study or have participated in the HZC112207, HZC102871, HZC102970, or HZC110946 studies. Subjects who have received an investigational drug within 30 days of entry into this study (Screening), or within 5 drug half-lives of the investigational drug, whichever is longer.

• 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) delivered within one dry powder inhaler (DPI) device for COPD
• GW642444 Inhalation Powder
Long Acting Beta Agonist(LABA) Inhalation Powder via DPI

Locations

Country	Name	City	State
Argentina	GSK Investigational Site	Buenos Aires
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	Ciudad Autónoma de Buenos Aires
Argentina	GSK Investigational Site	Mendoza
Australia	GSK Investigational Site	Cairns	Queensland
Australia	GSK Investigational Site	Daw Park	South Australia
Australia	GSK Investigational Site	Frankston	Victoria
Australia	GSK Investigational Site	Garran	Australian Capital Territory
Australia	GSK Investigational Site	Geelong	Victoria
Australia	GSK Investigational Site	Heidelberg	Victoria
Australia	GSK Investigational Site	Kippa Ring	Queensland
Australia	GSK Investigational Site	Nedlands	Western Australia
Canada	GSK Investigational Site	Burlington	Ontario
Canada	GSK Investigational Site	Corunna	Ontario
Canada	GSK Investigational Site	Montreal	Quebec
Canada	GSK Investigational Site	Quebec
Canada	GSK Investigational Site	St. John's	Newfoundland and Labrador
Canada	GSK Investigational Site	Sudbury	Ontario
Canada	GSK Investigational Site	Toronto	Ontario
Canada	GSK Investigational Site	Toronto	Ontario
Canada	GSK Investigational Site	Toronto	Ontario
Canada	GSK Investigational Site	Vancouver	British Columbia
Chile	GSK Investigational Site	Santiago
Chile	GSK Investigational Site	Temuco	Región De La Araucania
Chile	GSK Investigational Site	Valparaiso	Valparaíso
Estonia	GSK Investigational Site	Rakvere
Estonia	GSK Investigational Site	Tallinn
Estonia	GSK Investigational Site	Tallinn
Estonia	GSK Investigational Site	Tartu
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Geesthacht	Schleswig-Holstein
Italy	GSK Investigational Site	Cassano Murge (BA)	Puglia
Italy	GSK Investigational Site	Eboli (SA)	Campania
Italy	GSK Investigational Site	Ferrara	Emilia-Romagna
Italy	GSK Investigational Site	Genova	Liguria
Italy	GSK Investigational Site	Milano	Lombardia
Italy	GSK Investigational Site	Roma	Lazio
Italy	GSK Investigational Site	Roma	Lazio
Italy	GSK Investigational Site	Telese Terme (BN)	Campania
Italy	GSK Investigational Site	Torrette (AN)	Marche
Italy	GSK Investigational Site	Tradate (VA)	Lombardia
Mexico	GSK Investigational Site	Guadalajara	Jalisco
Mexico	GSK Investigational Site	Monterrey	Nuevo León
Mexico	GSK Investigational Site	Tijuana	Baja California Norte
Mexico	GSK Investigational Site	Zapopan	Jalisco
Netherlands	GSK Investigational Site	Bunnik
Netherlands	GSK Investigational Site	Enschede
Netherlands	GSK Investigational Site	Etten-leur
Netherlands	GSK Investigational Site	Harderwijk
Netherlands	GSK Investigational Site	Heerlen
Netherlands	GSK Investigational Site	Helmond
Netherlands	GSK Investigational Site	Nijverdal
Netherlands	GSK Investigational Site	Rotterdam
Netherlands	GSK Investigational Site	Sneek
Netherlands	GSK Investigational Site	Spijkenisse
Netherlands	GSK Investigational Site	Veldhoven
Netherlands	GSK Investigational Site	Voerendaal
Peru	GSK Investigational Site	Jesus Maria	Lima
Peru	GSK Investigational Site	Lima
Peru	GSK Investigational Site	Lima
Peru	GSK Investigational Site	San Martin de Porres	Lima
Philippines	GSK Investigational Site	Dagupan City
Philippines	GSK Investigational Site	Quezon City
Philippines	GSK Investigational Site	Quezon City
Philippines	GSK Investigational Site	Quezon City
South Africa	GSK Investigational Site	Boksburg North
South Africa	GSK Investigational Site	Cape Town
South Africa	GSK Investigational Site	Cape Town	Gauteng
South Africa	GSK Investigational Site	Durban
South Africa	GSK Investigational Site	Durban
South Africa	GSK Investigational Site	Groenkloof
South Africa	GSK Investigational Site	Lynnwood Manor
South Africa	GSK Investigational Site	Lyttleton
South Africa	GSK Investigational Site	Mueckelneck	Gauteng
South Africa	GSK Investigational Site	Paarl
South Africa	GSK Investigational Site	Panorama
South Africa	GSK Investigational Site	Reiger Park
South Africa	GSK Investigational Site	Somerset West
South Africa	GSK Investigational Site	Witbank
Sweden	GSK Investigational Site	Göteborg
Sweden	GSK Investigational Site	Göteborg
Sweden	GSK Investigational Site	Höllviken
Sweden	GSK Investigational Site	KIL
Sweden	GSK Investigational Site	Örebro
United Kingdom	GSK Investigational Site	Doncaster
United Kingdom	GSK Investigational Site	High Heaton, Newcastle upon Tyne	Tyne & Wear
United Kingdom	GSK Investigational Site	Liverpool
United Kingdom	GSK Investigational Site	London
United Kingdom	GSK Investigational Site	London
United Kingdom	GSK Investigational Site	London
United States	GSK Investigational Site	Abingdon	Virginia
United States	GSK Investigational Site	Anderson	South Carolina
United States	GSK Investigational Site	Austell	Georgia
United States	GSK Investigational Site	Austin	Texas
United States	GSK Investigational Site	Avon	Indiana
United States	GSK Investigational Site	Bay Pines	Florida
United States	GSK Investigational Site	Belleville	Illinois
United States	GSK Investigational Site	Billings	Montana
United States	GSK Investigational Site	Birmingham	Alabama
United States	GSK Investigational Site	Birmingham	Alabama
United States	GSK Investigational Site	Boerne	Texas
United States	GSK Investigational Site	Charleston	South Carolina
United States	GSK Investigational Site	Charlottesville	Virginia
United States	GSK Investigational Site	Chattanooga	Tennessee
United States	GSK Investigational Site	Chester	South Carolina
United States	GSK Investigational Site	Chula Vista	California
United States	GSK Investigational Site	Clearwater	Florida
United States	GSK Investigational Site	Clearwater	Florida
United States	GSK Investigational Site	Columbia	Maryland
United States	GSK Investigational Site	Dayton	Ohio
United States	GSK Investigational Site	Decatur	Georgia
United States	GSK Investigational Site	Elizabeth City	North Carolina
United States	GSK Investigational Site	Fort Myers	Florida
United States	GSK Investigational Site	Fort Worth	Texas
United States	GSK Investigational Site	Fredericksburg	Virginia
United States	GSK Investigational Site	Gaffney	South Carolina
United States	GSK Investigational Site	Gainesville	Florida
United States	GSK Investigational Site	Greenwood	South Carolina
United States	GSK Investigational Site	Greer	South Carolina
United States	GSK Investigational Site	Iowa City	Iowa
United States	GSK Investigational Site	Jasper	Alabama
United States	GSK Investigational Site	Johnston	Rhode Island
United States	GSK Investigational Site	Kingwood	Texas
United States	GSK Investigational Site	Lafayette	Indiana
United States	GSK Investigational Site	Lake Jackson	Texas
United States	GSK Investigational Site	Lakewood	Washington
United States	GSK Investigational Site	Lawrenceville	Georgia
United States	GSK Investigational Site	Lebanon	New Hampshire
United States	GSK Investigational Site	Lenexa	Kansas
United States	GSK Investigational Site	Lincoln	California
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	Minneapolis	Minnesota
United States	GSK Investigational Site	Minneapolis	Minnesota
United States	GSK Investigational Site	Mission Viejo	California
United States	GSK Investigational Site	Muncie	Indiana
United States	GSK Investigational Site	Munfordville	Kentucky
United States	GSK Investigational Site	New Orleans	Louisiana
United States	GSK Investigational Site	New Tazewell	Tennessee
United States	GSK Investigational Site	New York	New York
United States	GSK Investigational Site	New York	New York
United States	GSK Investigational Site	Newburgh	Indiana
United States	GSK Investigational Site	Ocean City	New Jersey
United States	GSK Investigational Site	Oklahoma City	Oklahoma
United States	GSK Investigational Site	Oklahoma City	Oklahoma
United States	GSK Investigational Site	Orlando	Florida
United States	GSK Investigational Site	Ormond Beach	Florida
United States	GSK Investigational Site	Owensboro	Kentucky
United States	GSK Investigational Site	Palo Alto	California
United States	GSK Investigational Site	Peoria	Arizona
United States	GSK Investigational Site	Phoenix	Arizona
United States	GSK Investigational Site	Phoenix	Arizona
United States	GSK Investigational Site	Plymouth	Minnesota
United States	GSK Investigational Site	Poway	California
United States	GSK Investigational Site	Rancho Mirage	California
United States	GSK Investigational Site	Richmond	Virginia
United States	GSK Investigational Site	River Forest	Illinois
United States	GSK Investigational Site	Riverside	California
United States	GSK Investigational Site	Rolling Hills Estates	California
United States	GSK Investigational Site	Saint Charles	Missouri
United States	GSK Investigational Site	Saint Joseph	Michigan
United States	GSK Investigational Site	Salisbury	North Carolina
United States	GSK Investigational Site	San Antonio	Texas
United States	GSK Investigational Site	Santa Monica	California
United States	GSK Investigational Site	Scottsdale	Arizona
United States	GSK Investigational Site	Sellersville	Pennsylvania
United States	GSK Investigational Site	Seneca	South Carolina
United States	GSK Investigational Site	Sepulveda	California
United States	GSK Investigational Site	South Burlington	Vermont
United States	GSK Investigational Site	Southfield	Michigan
United States	GSK Investigational Site	Spokane	Washington
United States	GSK Investigational Site	Stamford	Connecticut
United States	GSK Investigational Site	Sunset	Louisiana
United States	GSK Investigational Site	Tacoma	Washington
United States	GSK Investigational Site	Tamarac	Florida
United States	GSK Investigational Site	Temple	Texas
United States	GSK Investigational Site	Torrance	California
United States	GSK Investigational Site	Tulsa	Oklahoma
United States	GSK Investigational Site	Virginia Beach	Virginia
United States	GSK Investigational Site	Wenatchee	Washington
United States	GSK Investigational Site	Wichita	Kansas
United States	GSK Investigational Site	Winter Park	Florida

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Canada,  Chile,  Estonia,  Germany,  Italy,  Mexico,  Netherlands,  Peru,  Philippines,  South Africa,  Sweden,  United Kingdom, 

References & Publications (1)

Dransfield MT, Bourbeau J, Jones PW, Hanania NA, Mahler DA, Vestbo J, Wachtel A, Martinez FJ, Barnhart F, Sanford L, Lettis S, Crim C, Calverley PM. Once-daily inhaled fluticasone furoate and vilanterol versus vilanterol only for prevention of exacerbations of COPD: two replicate double-blind, parallel-group, randomised controlled trials. Lancet Respir Med. 2013 May;1(3):210-23. doi: 10.1016/S2213-2600(13)70040-7. Epub 2013 Apr 12. Erratum in: Lancet Respir Med. 2013 May;1(3):186. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Annual Rate of Moderate and Severe COPD Exacerbations Expressed as Least Square Mean	The annual rate of moderate and severe chronic obstructive pulmonary disease (COPD) exacerbations during the treatment (trt) period (per participant [par.] per year) was assessed. An exacerbation of COPD, is defined as the worsening of two or more major symptoms (dyspnea, sputum volume, sputum purulence [color]) for at least two consecutive days; or the worsening of any one major symptom together with any one of the minor symptoms (sore throat, cold, fever without other cause, increased cough, increased wheeze) for at least two consecutive days. The COPD exacerbation was categorized as mild, moderate and severe by the investigator. Mild: worsening symptoms of COPD that were self-managed by the par. without the use of oral corticosteroids or antibiotics; Moderate: worsening symptoms of COPD that required treatment with oral corticosteroids and/or antibiotics; Severe: worsening symptoms of COPD that required treatment with in-patient hospitalization.	From the start of the double blinded study medication until Visit 11 (Week 52)/Early Withdrawal
Secondary	Time to First Occurrence of Moderate or Severe COPD Exacerbation	Time to first occurrence analyzed by using a Cox proportional hazards model with covariates of treatment, smoking status at screening (stratum), baseline disease severity (pre-dose Day 1 % predicted FEV1) and centre grouping. An exacerbation of COPD is defined as the worsening of two or more major symptoms (dyspnea, sputum volume, sputum purulence [color]) for at least two consecutive days; or the worsening of any one major symptom together with any one of the minor symptoms (sore throat, cold, fever without other cause, increased cough, increased wheeze) for at least two consecutive days. A moderate exacerbation is defined as worsening symptoms of COPD that required treatment with oral corticosteroids and/or antibiotics. A severe exacerbation is defined as worsening symptoms of COPD that required treatment with in-patient hospitalization. The number of participants with a moderate or severe COPD exacerbation while on treatment are presented.	From the start of the double blind study medication until Visit 11 (Week 52)/Early Withdrawal
Secondary	Annual Rate of Exacerbations Requiring Systemic/Oral Corticosteroids Expressed as Least Square Mean	The annual rate of COPD exacerbations during the treatment period (per participant per year) that required systemic/oral corticosteroids was assessed. An exacerbation of COPD is defined as the worsening of two or more major symptoms (dyspnea, sputum volume, sputum purulence [color]) for at least two consecutive days; or the worsening of any one major symptom together with any one of the minor symptom (sore throat, cold, fever without other cause, increased cough, increased wheeze) for at least two consecutive days. The COPD exacerbation was categorized as mild, moderate, and severe by the investigator. Mild: worsening symptoms of COPD that were self-managed by the participant. Mild exacerbations were not associated with the use of oral corticosteroids or antibiotics. Moderate: worsening symptoms of COPD that required treatment with oral corticosteroids and/or antibiotics. Severe: worsening symptoms of COPD that required treatment with in-patient hospitalization.	From the start of the double blind study medication until Visit 11 (Week 52)/Early Withdrawal
Secondary	Change From Baseline in Trough FEV1 at Week 52 (Visit 11)	Pulmonary function was measured by forced expiratory volume in one second (FEV1). Trough FEV1 was defined as the 24-hour post-dose FEV1 assessment, which was obtained at each visit. Analysis performed using a repeated measures model with covariates of treatment, smoking status at Screening (stratum), baseline (pre-dose Day 1), centre grouping, Week, Week by Baseline, and Week by treatment interactions.	Baseline to Visit 11 (Week 52)/Early Withdrawal

External Links

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