Efficacy and Safety of Mepolizumab as an Add-on Treatment in Chronic Obstructive Pulmonary Disease (COPD)

Pulmonary Disease, Chronic Obstructive Clinical Trial

Official title:

Study MEA117113: Mepolizumab vs. Placebo as Add-on Treatment for Frequently Exacerbating COPD Patients Characterized by Eosinophil Level

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02105961
• Other study ID #: 117113
• Status: Completed
• Phase: Phase 3
• Start date: April 24, 2014
• Est. completion date: January 16, 2017

Study information

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

Clinical Trial Summary

This is a multi-centered, randomized, placebo-controlled, double-blind, parallel group, trial evaluating 2 doses of mepolizumab against placebo given every 4 weeks through subcutaneous (SC) injection. In severe COPD subjects, sputum eosinophils levels are elevated to similar levels as those seen in severe asthmatics. It is hypothesized that the reduction of eosinophils with mepolizumab in COPD subjects would translate into a reduction of COPD exacerbations. The study will evaluate the efficacy and safety of mepolizumab, in subjects who are at or above the baseline blood eosinophil count of at least 150 cells/microliters who exacerbate despite regular use of maximal tolerated therapy, appropriate for severe COPD subjects, in the 12 months prior to study start. In total, 660 subjects will be randomized in 1:1:1 ratio to receive mepolizumab 300 mg, mepolizumab 100mg, or placebo administered SC. The total duration of subject participation will be approximately 62 weeks, consisting of a 1 to 2 week screening period, 52-week treatment period and 8-week follow-up period.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 674
• Est. completion date: January 16, 2017
• Est. primary completion date: January 16, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

Inclusion Criteria:

• COPD diagnosis: Subjects with a clinically documented history of COPD for at least 1 year in accordance with the following definition by the American Thoracic Society/European Respiratory Society

• Severity of COPD: Subjects must present with the following: a measured pre and post-salbutamol Forced expiratory volume in one second/ Forced vital capacity (FEV1/FVC) ratio of <0.70 at Visit 1 to confirm the diagnosis of COPD; a measured post-salbutamol FEV1> 20 percent and <=80 percent of predicted normal values calculated using National Health and Nutrition Examination Survey (NHANES) III reference equations at Visit 1

• History of exacerbations: A well documented history (e.g., medical record verification) in the 12 months prior to Visit 1 of ; at least two moderate COPD exacerbations. Moderate is defined as the use of systemic corticosteroids (intramuscular (IM), intravenous, or oral) and/or treatment with antibiotics or; at least one severe COPD exacerbation. Severe is defined as having required hospitalization. Note: At least one exacerbation must have occurred while the subject was taking Inhaled corticosteroid (ICS) plus long acting beta2-agonist (LABA) plus long acting muscarinic antagonist (LAMA). Prior use of antibiotics alone does not qualify as a moderate exacerbation unless the use was specifically for the treatment of worsening symptoms of COPD.

• Concomitant COPD therapy: A well documented requirement for optimized standard of care background therapy that includes Inhaled corticosteroid (ICS) plus 2 additional COPD medications (i.e., triple therapy) for the 12 months prior to Visit 1 and meets the following criteria: Immediately prior to Visit 1, minimum of 3 months of use of an; Inhaled corticosteroid at a dose >= 500 micrograms (mcg)/day fluticasone propionate dose equivalent plus; LABA and LAMA.

For subjects who are not continually maintained on ICS plus LABA plus LAMA for the entire 12 months prior to Visit 1 use of following is allowed (but not in the 3 months immediately prior to Visit 1); inhaled corticosteroid at a dose >=500 mcg/day fluticasone propionate dose equivalent plus; a LABA or a LAMA and; use of at least one other class of COPD medication (i.e., phosphodiesterase-4-inhibitors, methylxanthines, or a combination of short acting beta2-agonist and short acting muscarinic antagonist).

• Informed Consent: Able to give written informed consent prior to participation in the study, which will include the ability to comply with the requirements and restrictions listed in the consent form. Subjects must be able to read, comprehend, and write at a level sufficient to complete study related materials.

• Gender: Male or Eligible Female; To be eligible for entry into the study females of child bearing potential must commit to consistent and correct use of an acceptable method of birth control from the time of consent, for the duration of the trial, and for 4 months after last study drug administration.

• Age: At least 40 years of age at Visit 1

• Smoking status: Subject with confirmed COPD are eligible to participate independent of their smoking status and smoking history, i.e. current smokers, never smokers or ex-smokers can be enrolled into the study. Current smokers are defined as those with a history of cigarette smoking of >=10 pack-years [number of pack years = (number of cigarettes per day / 20) x number of years smoked (e.g., 20 cigarettes per day for 10 years, or 10 cigarettes per day for 20 years)]. Former smokers are defined as those who meet the definition of a current smoker but have stopped smoking for at least 6 months prior to Visit 1. Never smokers are those that do not meet the definition of a current or former smoker.

• French subjects: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.

Exclusion Criteria:

• Subjects with Asthma: Current and Former Smokers: Subjects with a current diagnosis of asthma (those with a prior history are eligible if they meet inclusion criteria for a current diagnosis of COPD); Never-Smokers: Subjects with any history of asthma.

• Other respiratory disorders: The investigator must judge that COPD is the primary diagnosis accounting for the clinical manifestations of the lung disease. Subjects with alpha1-antitrypsin deficiency as the underlying cause of COPD are excluded. Also, excluded are subjects with active tuberculosis, lung cancer, bronchiectasis, sarcoidosis, lung fibrosis, primary pulmonary hypertension, interstitial lung diseases or other active pulmonary diseases. Subjects are also excluded if maintenance use of bi-level positive airway pressure is required for the treatment of respiratory disorder.

• COPD stability: Subjects with pneumonia, exacerbation, lower respiratory infection within the 4 weeks prior to Visit 1.

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

• Pulmonary rehabilitation program: Participation in the acute phase of a pulmonary rehabilitation program within 4 weeks prior to Visit 1. Subjects who are in the maintenance phase of a pulmonary rehabilitation program are not excluded.

• Oxygen: Subjects receiving treatment with oxygen more than 4.0 liters/minute (L/min). While breathing supplemental oxygen, subjects should demonstrate an oxyhemoglobin saturation greater than or equal to 89 percent.

• 12-lead Electrocardiography (ECG) finding: An abnormal and significant ECG finding from the 12-lead ECG conducted at Visit 1, if considered to be clinically significant by the Investigator. 12-lead ECGs will be over-read by a centralized independent cardiologist to assist in consistent evaluation of subject eligibility. Results from the 12-lead ECG over-read must be received prior to assessing eligibility at Visit 2.

• Unstable or life threatening cardiac disease: Subjects with any of the following would be excluded: Myocardial infarction or unstable angina in the last 6 months ; Unstable or life threatening cardiac arrhythmia requiring intervention in the last 3 months ; New York Heart Association (NYHA) Class IV Heart failure

• Other diseases/abnormalities: Subjects with (historical or) current evidence of clinically significant, 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.

• Eosinophilic disease: Subjects with other conditions that could lead to elevated eosinophils such as Hypereosinophilic syndromes including Eosinophilic Granulomatosis with Polyangiitis (EGPA, also known as Churg-Strauss Syndrome), or Eosinophilic Esophagitis.

• Parasitic infection: Subjects with a pre-existing helminthes infestation within 6 months prior to Visit 1 are also excluded.

• Malignancy: A current malignancy or previous history of cancer in remission for less than 12 months prior to Visit 1 (Subjects that had localized carcinoma of the skin or cervix which was resected for cure will not be excluded). South Korea subjects with a diagnosis of malignancy within 5 years of Visit 1 are excluded.

• Immunodeficiency: A known immunodeficiency (e.g. human immunodeficiency virus HIV), other than that explained by the use of corticosteroids taken for COPD.

• Liver disease: Unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, esophageal or gastric varices, or persistent jaundice), cirrhosis, and known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones). Chronic stable hepatitis B and C are acceptable if subject otherwise meets entry criteria (e.g., presence of hepatitis B surface antigen or positive hepatitis C test result within 3 months of screening)

• Monoclonal antibodies: Subjects who have received any monoclonal antibody within 5 half-lives of Visit 1.

• Investigational medications: Subjects who have received an investigational drug within 30 days of Visit 1, or within 5 drug half-lives of the investigational drug, whichever is longer (this also includes investigational formulations of a marketed product).

• Hypersensitivity: Subjects with a known allergy or intolerance to another monoclonal antibody or biologic including history of anaphylaxis to another biologic

• Inability to read: In the opinion of the investigator, any subject who is unable to read and/or would not be able to complete study related materials.

• 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.

• Drug or alcohol abuse: A known or suspected history of alcohol or drug abuse within 2 years prior to Visit 1.

• Previous participation: Subjects who have previously participated in any study of mepolizumab.

• Affiliation with Investigator Site: Is an investigator, sub-investigator, study coordinator, employee of a participating investigator or study site, or immediate family member of the aforementioned that is involved in this study.

Randomization Criteria

In order to be randomized to study drug the subject must meet the following randomization criteria at Visit 2:

• Blood eosinophils: Documented elevated peripheral blood eosinophil count of >=300 cells/microliter within the past 12 months prior to Visit 1; OR A peripheral baseline blood eosinophil count of >=150 cells/microliter from haematology conducted at Visit 1

• Electronic Diary Compliance: Compliance with completion of the eDiary defined as completion of all questions on 5 or more days out of the 7 days immediately preceding Visit 2.

• 12-lead ECG: No evidence of an abnormal and significant ECG finding from the 12-lead ECG conducted at Visit 1 as indicated on the over-read provided by the centralized independent cardiologist. Subjects with a QT interval corrected with Fridericia's formulas (QTcF)>=450 msec are not eligible. For subjects with a QRS interval >=120msec, those with QTcF>=480 msec are not eligible. Specific ECG findings that preclude subject eligibility are listed in the protocol.

• Abnormal chest X-ray (or Computerized Tomography [CT] scan): No chest X-ray (or CT scan) that reveals evidence of clinically significant abnormalities not believed to be due to the presence of COPD. If a chest X-ray or CT scan is not available within 6 months prior to Visit 1, then a chest X-ray must be taken at Visit 1 and the results reviewed prior to randomization. For sites in Germany: If a chest X-ray (or CT scan) within 6 months prior to Screening (Visit 1) is not available, the subject will not be eligible for the study.

• Laboratory abnormality: No evidence of clinically significant abnormality in the haematological, biochemical, or urinalysis screen at Visit 1, as judged by the investigator.

• Hepatitis B: Subjects who are HBsAg positive or HBcAb positive must not have a HBV DNA level >=2000 International Units (IU)/millilitre (mL).

• Liver function test: Subjects must meet the following based on results from sample taken at Visit 1: Alanine aminotransferase (ALT) <2x ULN (upper limit of normal); Alkaline Phosphatase (Alk Phos) <=2x ULN; Bilirubin <=1.5x ULN (isolated bilirubin>1.5x ULN is acceptable if bilirubin is fractionated and direct bilirubin <35 percent)

• Pregnancy: No subjects who are pregnant or breastfeeding. Subjects should not be enrolled if they plan to become pregnant during the time of study participation.

Related Conditions & MeSH terms

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

Intervention

Drug:
• Mepolizumab
Humanised IgG antibody (IgG1, kappa) with human heavy and light chain frameworks, provided as a lyophilised cake in sterile vial. Vial to be reconstituted with Sterile Water for Injection, just prior to use.
• Placebo
Sterile 0.9percent sodium chloride solution

Locations

Country	Name	City	State
Argentina	GSK Investigational Site	Bahía Blanca	Buenos Aires
Argentina	GSK Investigational Site	Berazategui
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	La Plata	Buenos Aires
Argentina	GSK Investigational Site	Mar del Plata	Buenos Aires
Argentina	GSK Investigational Site	Mendoza
Argentina	GSK Investigational Site	Mendoza
Australia	GSK Investigational Site	Coffs Harbour	New South Wales
Australia	GSK Investigational Site	Maroubra	New South Wales
Australia	GSK Investigational Site	Murdoch	Western Australia
Canada	GSK Investigational Site	Burlington	Ontario
Canada	GSK Investigational Site	St-Charles-Borromée	Quebec
Canada	GSK Investigational Site	Toronto	Ontario
Canada	GSK Investigational Site	Trois Rivieres	Quebec
Canada	GSK Investigational Site	Truro	Nova Scotia
Canada	GSK Investigational Site	Windsor	Ontario
Chile	GSK Investigational Site	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	Santiago
Chile	GSK Investigational Site	Talca	Región Del Maule
Chile	GSK Investigational Site	Valparaiso	Valparaíso
Denmark	GSK Investigational Site	Aarhus C
Denmark	GSK Investigational Site	Hvidovre
Denmark	GSK Investigational Site	Kobenhavn NV
Denmark	GSK Investigational Site	Odense C
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Dresden	Sachsen
Germany	GSK Investigational Site	Frankfurt	Hessen
Germany	GSK Investigational Site	Frankfurt	Hessen
Germany	GSK Investigational Site	Hamburg
Germany	GSK Investigational Site	Hannover	Niedersachsen
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	Neu-Isenburg	Hessen
Germany	GSK Investigational Site	Ruedersdorf	Brandenburg
Germany	GSK Investigational Site	Stuttgart	Baden-Wuerttemberg
Japan	GSK Investigational Site	Ehime
Japan	GSK Investigational Site	Fukui
Japan	GSK Investigational Site	Fukuoka
Japan	GSK Investigational Site	Fukushima
Japan	GSK Investigational Site	Gifu
Japan	GSK Investigational Site	Hiroshima
Japan	GSK Investigational Site	Hiroshima
Japan	GSK Investigational Site	Hokkaido
Japan	GSK Investigational Site	Hyogo
Japan	GSK Investigational Site	Kagawa
Japan	GSK Investigational Site	Kanagawa
Japan	GSK Investigational Site	Kumamoto
Japan	GSK Investigational Site	Mie
Japan	GSK Investigational Site	Miyagi
Japan	GSK Investigational Site	Miyagi
Japan	GSK Investigational Site	Miyagi
Japan	GSK Investigational Site	Oita
Japan	GSK Investigational Site	Okayama
Japan	GSK Investigational Site	Okayama
Japan	GSK Investigational Site	Okinawa
Japan	GSK Investigational Site	Osaka
Japan	GSK Investigational Site	Osaka
Japan	GSK Investigational Site	Osaka
Japan	GSK Investigational Site	Shimane
Japan	GSK Investigational Site	Shizuoka
Japan	GSK Investigational Site	Shizuoka
Japan	GSK Investigational Site	Tokyo
Japan	GSK Investigational Site	Tokyo
Japan	GSK Investigational Site	Tokyo
Japan	GSK Investigational Site	Tokyo
Japan	GSK Investigational Site	Tokyo
Japan	GSK Investigational Site	Tokyo
Korea, Republic of	GSK Investigational Site	Anyang-Si Gyeonggi-do
Korea, Republic of	GSK Investigational Site	Bucheon city, Gyenggi-do
Korea, Republic of	GSK Investigational Site	Busan
Korea, Republic of	GSK Investigational Site	Cheongju, Chungcheongbuk-do
Korea, Republic of	GSK Investigational Site	Daegu
Korea, Republic of	GSK Investigational Site	Incheon
Korea, Republic of	GSK Investigational Site	Jeonju-si
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	Seoul
Korea, Republic of	GSK Investigational Site	Seoul,
Korea, Republic of	GSK Investigational Site	Wonju-si, Kanwon-do
Netherlands	GSK Investigational Site	Almelo
Netherlands	GSK Investigational Site	Breda
Netherlands	GSK Investigational Site	Den Bosch
Netherlands	GSK Investigational Site	Groningen
Netherlands	GSK Investigational Site	Hoofddorp
Netherlands	GSK Investigational Site	Horn
Netherlands	GSK Investigational Site	Leiden
Netherlands	GSK Investigational Site	Sittard-geleen
Netherlands	GSK Investigational Site	Utrecht
Netherlands	GSK Investigational Site	Zutphen
Romania	GSK Investigational Site	Bucharest
Romania	GSK Investigational Site	Bucharest
Romania	GSK Investigational Site	Cluj Napoca
Romania	GSK Investigational Site	Cluj-Napoca
Romania	GSK Investigational Site	Codlea
Romania	GSK Investigational Site	Craiova
Romania	GSK Investigational Site	Focsani
Romania	GSK Investigational Site	Iasi
Romania	GSK Investigational Site	Pitesti
Romania	GSK Investigational Site	Ploiesti
Romania	GSK Investigational Site	Timisoara
Slovakia	GSK Investigational Site	Humenne
Slovakia	GSK Investigational Site	Poprad
Slovakia	GSK Investigational Site	Sala
Slovakia	GSK Investigational Site	Spisska Nova Ves
Slovakia	GSK Investigational Site	Vrable
Taiwan	GSK Investigational Site	Kaohsiung
Taiwan	GSK Investigational Site	Taichung
Taiwan	GSK Investigational Site	Taipei
Taiwan	GSK Investigational Site	Taipei
Taiwan	GSK Investigational Site	Tau-Yuan County
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	Mykolayiv
Ukraine	GSK Investigational Site	Vinnytsia
United Kingdom	GSK Investigational Site	Bradford
United Kingdom	GSK Investigational Site	Cambridge
United Kingdom	GSK Investigational Site	Oxford
United Kingdom	GSK Investigational Site	Plymouth
United Kingdom	GSK Investigational Site	Sheffield
United Kingdom	GSK Investigational Site	Stevenage
United States	GSK Investigational Site	Adairsville	Georgia
United States	GSK Investigational Site	Albuquerque	New Mexico
United States	GSK Investigational Site	Birmingham	Alabama
United States	GSK Investigational Site	Bowling Green	Kentucky
United States	GSK Investigational Site	Boynton Beach	Florida
United States	GSK Investigational Site	Broomfield	Colorado
United States	GSK Investigational Site	Charleston	South Carolina
United States	GSK Investigational Site	Charlotte	North Carolina
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	Duluth	Georgia
United States	GSK Investigational Site	Easley	South Carolina
United States	GSK Investigational Site	Edgewater	Florida
United States	GSK Investigational Site	Fort Worth	Texas
United States	GSK Investigational Site	Gainesville	Florida
United States	GSK Investigational Site	Gastonia	North Carolina
United States	GSK Investigational Site	Greenville	South Carolina
United States	GSK Investigational Site	Hershey	Pennsylvania
United States	GSK Investigational Site	Huntersville	North Carolina
United States	GSK Investigational Site	Mobile	Alabama
United States	GSK Investigational Site	Morgantown	West Virginia
United States	GSK Investigational Site	Mount Pleasant	South Carolina
United States	GSK Investigational Site	Oaks	Pennsylvania
United States	GSK Investigational Site	Orlando	Florida
United States	GSK Investigational Site	Philadelphia	Pennsylvania
United States	GSK Investigational Site	Portland	Oregon
United States	GSK Investigational Site	Richmond	Virginia
United States	GSK Investigational Site	Richmond	Virginia
United States	GSK Investigational Site	Riverside	California
United States	GSK Investigational Site	Rock Hill	South Carolina
United States	GSK Investigational Site	Saint Petersburg	Florida
United States	GSK Investigational Site	Stamford	Connecticut
United States	GSK Investigational Site	Upland	California
United States	GSK Investigational Site	Woodstock	Georgia

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Canada,  Chile,  Denmark,  Germany,  Japan,  Korea, Republic of,  Netherlands,  Romania,  Slovakia,  Taiwan,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of Moderate or Severe Exacerbations	Moderate exacerbations are defined as clinically significant exacerbations that require treatment with oral/systemic corticosteroids and/or antibiotics. Severe exacerbations are defined as clinically significant exacerbations that require in-patient hospitalization (>=24 hours) or result in death. Moderate and severe exacerbations occurring from the start of investigational product (IP) up to the Week 52 visit, including exacerbations reported after early discontinuation from IP by participants who remained in the study, were included in the analysis. The analysis was performed on the modified intent-to-treat (mITT) Population (all randomized participants who received at least one dose of study treatment).	From randomization to Week 52
Secondary	Time to First Moderate/Severe Exacerbation	Kaplan Meier estimates of the probability of a moderate or severe exacerbation are expressed as the percentage of participants with an exacerbation over time (by Week 8, 16, 24, 32, 40, 48, 52). Analysis of time to first moderate/severe exacerbation was performed on the mITT population and included exacerbations reported on-treatment and those reported after early discontinuation from IP by participants who remained in the study.	From randomization to Week 52
Secondary	Rate of COPD Exacerbations Requiring Emergency Department (ED) Visits and/or Hospitalizations (Hosp)	COPD exacerbations requiring an ED visit and/or hosp occurring from the start of IP up to the Week 52 visit, including exacerbations reported after early discontinuation from IP by participants who remained in the study, were included in the analysis. This analysis was performed on the mITT population.	From randomization to Week 52
Secondary	Change From Baseline in Mean Total St. George's Respiratory Questionnaire (SGRQ) Score	The SGRQ for COPD is a 40-item questionnaire derived from the original SGRQ , designed to measure health impairment by addressing the frequency of respiratory symptoms and current state of the participant. SGRQ Total Scores range from 0 to 100 with higher scores indicating worse health-related quality of life and reductions indicating improvement. The Baseline value will be the last measurement collected prior to the first dose of investigational product.Change from Baseline is calculated as the post-dose visit value minus the Baseline value. Mean change from Baseline in SGRQ score at Week 52 has been presented.	Baseline and Week 52
Secondary	Change From Baseline in Mean COPD Assessment Test (CAT) Score	The CAT is an 8-item questionnaire developed for use in routine clinical practice to measure the health status of participants with COPD. Each question is assessed on a 6-point scale ranging from 0 (no impairment) to 5 (maximum impairment) with the CAT score ranging from 0-40. Higher scores indicate greater disease impact with reductions indicating improvement. The Baseline value will be the last measurement collected prior to the first dose of investigational product. Change from Baseline is calculated as the post-dose visit value minus the Baseline value. Mean change from Baseline in CAT score at Week 52 has been presented.	Baseline and Week 52

External Links

•   IPD for this study will be made available via the Clinical Study Data Request site.