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

Sponsor
GlaxoSmithKline (Industry)
Overall Status
Completed
CT.gov ID
NCT02105961
Collaborator
(none)
674
Enrollment
170
Locations
3
Arms
32.8
Actual Duration (Months)
4
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
674 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
Study MEA117113: Mepolizumab vs. Placebo as Add-on Treatment for Frequently Exacerbating COPD Patients Characterized by Eosinophil Level
Actual Study Start Date :
Apr 24, 2014
Actual Primary Completion Date :
Jan 16, 2017
Actual Study Completion Date :
Jan 16, 2017

Arms and Interventions

Arm Intervention/Treatment
Experimental: Arm 1

Each subject will receive 100 mg mepolizumab SC injection every 4 weeks (13 administrations during 52 week treatment period) along with their baseline standard of care COPD medication

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.
Experimental: Arm 2

Each subject will receive 300 mg mepolizumab SC injection every 4 weeks (13 administrations during 52 week treatment period) along with their baseline standard of care COPD medication

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.
Experimental: Arm 3

Each subject will receive placebo (0.9percent sodium chloride) SC injection every 4 weeks (13 administrations during 52 week treatment period) their baseline standard of care COPD medication

Drug: Placebo
Sterile 0.9percent sodium chloride solution

Outcome Measures

Primary Outcome Measures

  1. Rate of Moderate or Severe Exacerbations [From randomization to Week 52]

    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).

Secondary Outcome Measures

  1. Time to First Moderate/Severe Exacerbation [From randomization to Week 52]

    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.

  2. Rate of COPD Exacerbations Requiring Emergency Department (ED) Visits and/or Hospitalizations (Hosp) [From randomization to Week 52]

    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.

  3. Change From Baseline in Mean Total St. George's Respiratory Questionnaire (SGRQ) Score [Baseline and Week 52]

    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.

  4. Change From Baseline in Mean COPD Assessment Test (CAT) Score [Baseline and Week 52]

    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.

Eligibility Criteria

Criteria

Ages Eligible for Study:
40 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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.

Contacts and Locations

Locations

Site City State Country Postal Code
1 GSK Investigational Site Birmingham Alabama United States 35294
2 GSK Investigational Site Mobile Alabama United States 36608
3 GSK Investigational Site Riverside California United States 92506
4 GSK Investigational Site Upland California United States 91786
5 GSK Investigational Site Broomfield Colorado United States 80023
6 GSK Investigational Site Stamford Connecticut United States 06902
7 GSK Investigational Site Boynton Beach Florida United States 33436
8 GSK Investigational Site DeLand Florida United States 32720
9 GSK Investigational Site Edgewater Florida United States 32132
10 GSK Investigational Site Gainesville Florida United States 32608
11 GSK Investigational Site Orlando Florida United States 32825
12 GSK Investigational Site Saint Petersburg Florida United States 33704
13 GSK Investigational Site Adairsville Georgia United States 30103
14 GSK Investigational Site Duluth Georgia United States 30096
15 GSK Investigational Site Woodstock Georgia United States 30189
16 GSK Investigational Site Coeur d'Alene Idaho United States 83814
17 GSK Investigational Site Bowling Green Kentucky United States 42101
18 GSK Investigational Site Albuquerque New Mexico United States 87108
19 GSK Investigational Site Charlotte North Carolina United States 28207
20 GSK Investigational Site Gastonia North Carolina United States 28054
21 GSK Investigational Site Huntersville North Carolina United States 28078
22 GSK Investigational Site Columbus Ohio United States 43213
23 GSK Investigational Site Portland Oregon United States 97220
24 GSK Investigational Site Hershey Pennsylvania United States 17033
25 GSK Investigational Site Oaks Pennsylvania United States 19456
26 GSK Investigational Site Philadelphia Pennsylvania United States 19140
27 GSK Investigational Site Charleston South Carolina United States 29406-7108
28 GSK Investigational Site Easley South Carolina United States 29640
29 GSK Investigational Site Greenville South Carolina United States 29615
30 GSK Investigational Site Mount Pleasant South Carolina United States 29464
31 GSK Investigational Site Rock Hill South Carolina United States 29732
32 GSK Investigational Site Fort Worth Texas United States 76104
33 GSK Investigational Site Richmond Virginia United States 23225
34 GSK Investigational Site Richmond Virginia United States 23249
35 GSK Investigational Site Morgantown West Virginia United States 26505
36 GSK Investigational Site Bahía Blanca Buenos Aires Argentina B8000AAK
37 GSK Investigational Site Ciudad Autonoma de Buenos Aires Buenos Aires Argentina C1414AIF
38 GSK Investigational Site La Plata Buenos Aires Argentina 1900
39 GSK Investigational Site Mar del Plata Buenos Aires Argentina 7600
40 GSK Investigational Site Berazategui Argentina 1886
41 GSK Investigational Site Buenos Aires Argentina C1425BEN
42 GSK Investigational Site Ciudad Autónoma de Buenos Aires Argentina C1121ABE
43 GSK Investigational Site Mendoza Argentina 5500
44 GSK Investigational Site Mendoza Argentina M5500CCG
45 GSK Investigational Site Coffs Harbour New South Wales Australia 2450
46 GSK Investigational Site Maroubra New South Wales Australia 2035
47 GSK Investigational Site Murdoch Western Australia Australia 6150
48 GSK Investigational Site Truro Nova Scotia Canada B2N 1L2
49 GSK Investigational Site Burlington Ontario Canada L7N 3V2
50 GSK Investigational Site Toronto Ontario Canada M5T 3A9
51 GSK Investigational Site Windsor Ontario Canada N8X 5A6
52 GSK Investigational Site St-Charles-Borromée Quebec Canada J6E 2B4
53 GSK Investigational Site Trois Rivieres Quebec Canada G8T 7A1
54 GSK Investigational Site Talca Región Del Maule Chile 3460001
55 GSK Investigational Site Santiago Región Metro De Santiago Chile 7500692
56 GSK Investigational Site Santiago Región Metro De Santiago Chile 7860406
57 GSK Investigational Site Santiago Región Metro De Santiago Chile 8242238
58 GSK Investigational Site Valparaiso Valparaíso Chile 2341131
59 GSK Investigational Site Santiago Chile 7500698
60 GSK Investigational Site Santiago Chile 8380453
61 GSK Investigational Site Aarhus C Denmark 8000
62 GSK Investigational Site Hvidovre Denmark 2650
63 GSK Investigational Site Kobenhavn NV Denmark 2400
64 GSK Investigational Site Odense C Denmark 5000
65 GSK Investigational Site Stuttgart Baden-Wuerttemberg Germany 70378
66 GSK Investigational Site Ruedersdorf Brandenburg Germany 15562
67 GSK Investigational Site Frankfurt Hessen Germany 60389
68 GSK Investigational Site Frankfurt Hessen Germany 60596
69 GSK Investigational Site Neu-Isenburg Hessen Germany 63263
70 GSK Investigational Site Hannover Niedersachsen Germany 30173
71 GSK Investigational Site Mainz Rheinland-Pfalz Germany 55131
72 GSK Investigational Site Magdeburg Sachsen-Anhalt Germany 39112
73 GSK Investigational Site Dresden Sachsen Germany 01307
74 GSK Investigational Site Leipzig Sachsen Germany 04357
75 GSK Investigational Site Luebeck Schleswig-Holstein Germany 23552
76 GSK Investigational Site Berlin Germany 10717
77 GSK Investigational Site Berlin Germany 12157
78 GSK Investigational Site Berlin Germany 12203
79 GSK Investigational Site Hamburg Germany 22299
80 GSK Investigational Site Ehime Japan 791-0281
81 GSK Investigational Site Fukui Japan 910-1193
82 GSK Investigational Site Fukuoka Japan 811-1394
83 GSK Investigational Site Fukushima Japan 960-1295
84 GSK Investigational Site Gifu Japan 509-6134
85 GSK Investigational Site Hiroshima Japan 722-8503
86 GSK Investigational Site Hiroshima Japan 734-8530
87 GSK Investigational Site Hokkaido Japan 053-8506
88 GSK Investigational Site Hyogo Japan 650-0047
89 GSK Investigational Site Kagawa Japan 762-8550
90 GSK Investigational Site Kanagawa Japan 227-8501
91 GSK Investigational Site Kumamoto Japan 861-1196
92 GSK Investigational Site Mie Japan 515-8544
93 GSK Investigational Site Miyagi Japan 980-8574
94 GSK Investigational Site Miyagi Japan 983-8520
95 GSK Investigational Site Miyagi Japan 986-8522
96 GSK Investigational Site Oita Japan 876-0813
97 GSK Investigational Site Okayama Japan 702-8055
98 GSK Investigational Site Okayama Japan 711-0921
99 GSK Investigational Site Okinawa Japan 901-2121
100 GSK Investigational Site Osaka Japan 573-0153
101 GSK Investigational Site Osaka Japan 589-8511
102 GSK Investigational Site Osaka Japan 591-8555
103 GSK Investigational Site Shimane Japan 693-8501
104 GSK Investigational Site Shizuoka Japan 436-0022
105 GSK Investigational Site Shizuoka Japan 438-8550
106 GSK Investigational Site Tokyo Japan 103-0027
107 GSK Investigational Site Tokyo Japan 104-8560
108 GSK Investigational Site Tokyo Japan 136-0075
109 GSK Investigational Site Tokyo Japan 142-8666
110 GSK Investigational Site Tokyo Japan 152-0021
111 GSK Investigational Site Tokyo Japan 204-8585
112 GSK Investigational Site Anyang-Si Gyeonggi-do Korea, Republic of 431-070
113 GSK Investigational Site Bucheon city, Gyenggi-do Korea, Republic of 420-767
114 GSK Investigational Site Busan Korea, Republic of 602-715
115 GSK Investigational Site Cheongju, Chungcheongbuk-do Korea, Republic of 361-711
116 GSK Investigational Site Daegu Korea, Republic of 705-703
117 GSK Investigational Site Incheon Korea, Republic of 403-720
118 GSK Investigational Site Jeonju-si Korea, Republic of 561-712
119 GSK Investigational Site Seoul, Korea, Republic of 120-752
120 GSK Investigational Site Seoul Korea, Republic of 130-709
121 GSK Investigational Site Seoul Korea, Republic of 130-872
122 GSK Investigational Site Seoul Korea, Republic of 138-736
123 GSK Investigational Site Seoul Korea, Republic of 140-743
124 GSK Investigational Site Seoul Korea, Republic of
125 GSK Investigational Site Wonju-si, Kanwon-do Korea, Republic of 220-701
126 GSK Investigational Site Almelo Netherlands 7609 PP
127 GSK Investigational Site Breda Netherlands 4818 CK
128 GSK Investigational Site Den Bosch Netherlands 5223 GZ
129 GSK Investigational Site Groningen Netherlands 9713 GZ
130 GSK Investigational Site Hoofddorp Netherlands 2134 TM
131 GSK Investigational Site Horn Netherlands 6085 NM
132 GSK Investigational Site Leiden Netherlands 2333 ZA
133 GSK Investigational Site Sittard-geleen Netherlands 6162 BG
134 GSK Investigational Site Utrecht Netherlands 3584 CX
135 GSK Investigational Site Zutphen Netherlands 7207 AE
136 GSK Investigational Site Bucharest Romania 020125
137 GSK Investigational Site Bucharest Romania 050159
138 GSK Investigational Site Cluj Napoca Romania 400371
139 GSK Investigational Site Cluj-Napoca Romania 400371
140 GSK Investigational Site Codlea Romania 505100
141 GSK Investigational Site Craiova Romania 200642
142 GSK Investigational Site Focsani Romania 620043
143 GSK Investigational Site Iasi Romania 700115
144 GSK Investigational Site Pitesti Romania 110084
145 GSK Investigational Site Ploiesti Romania 100024
146 GSK Investigational Site Timisoara Romania 300310
147 GSK Investigational Site Humenne Slovakia 066 01
148 GSK Investigational Site Poprad Slovakia 058 01
149 GSK Investigational Site Sala Slovakia 927 01
150 GSK Investigational Site Spisska Nova Ves Slovakia 052 01
151 GSK Investigational Site Vrable Slovakia 952 01
152 GSK Investigational Site Kaohsiung Taiwan 824
153 GSK Investigational Site Taichung Taiwan 404
154 GSK Investigational Site Taipei Taiwan 220
155 GSK Investigational Site Taipei Taiwan
156 GSK Investigational Site Tau-Yuan County Taiwan 333
157 GSK Investigational Site Dnipropetrovsk Ukraine 49051
158 GSK Investigational Site Kharkiv Ukraine 61035
159 GSK Investigational Site Kharkiv Ukraine 61124
160 GSK Investigational Site Kiev Ukraine 03680
161 GSK Investigational Site Kyiv Ukraine 03038
162 GSK Investigational Site Kyiv Ukraine 03680
163 GSK Investigational Site Mykolayiv Ukraine 54003
164 GSK Investigational Site Vinnytsia Ukraine 21018
165 GSK Investigational Site Bradford United Kingdom BD9 6RJ
166 GSK Investigational Site Cambridge United Kingdom CB2 0QQ
167 GSK Investigational Site Oxford United Kingdom OX3 7LE
168 GSK Investigational Site Plymouth United Kingdom PL6 8DH
169 GSK Investigational Site Sheffield United Kingdom S5 7AU
170 GSK Investigational Site Stevenage United Kingdom SG1 4AB

Sponsors and Collaborators

  • GlaxoSmithKline

Investigators

  • Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Publications

None provided.
Responsible Party:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT02105961
Other Study ID Numbers:
  • 117113
First Posted:
Apr 7, 2014
Last Update Posted:
Aug 16, 2018
Last Verified:
Jul 1, 2018
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Keywords provided by GlaxoSmithKline
Chronic Obstructive Pulmonary Disease
exacerbations
SB240563
mepolizumab
eosinophils
Additional relevant MeSH terms:
Lung Diseases
Pulmonary Disease, Chronic Obstructive

Study Results

Participant Flow

Recruitment Details Participants with chronic obstructive pulmonary disease (COPD) with frequent exacerbations, on high dose inhaled corticosteroid (ICS)-based triple inhaled maintenance therapy were included. Participants were randomized to receive mepolizumab (100 or 300 milligrams [mg]) or placebo by subcutaneous (SC) injection every 4 weeks for up to 52 weeks.
Pre-assignment Detail A total of 674 participants were randomized and received at least one dose of study treatment and were included in the modified intent to treat (mITT) population. One participant randomized to the mepolizumab 300 mg group was withdrawn without receiving study treatment.
Arm/Group Title Placebo Mepolizumab 100 mg SC Mepolizumab 300 mg SC
Arm/Group Description Eligible participants were randomized to and received placebo by SC injection every 4 weeks for up to 52 weeks in addition to their standard of care (SoC) therapy. Salbutamol metered dose inhaler (MDI) was issued for use as rescue medication throughout the study. Eligible participants were randomized to and received mepolizumab 100 mg by SC injection every 4 weeks for up to 52 weeks in addition to their SoC therapy. Salbutamol MDI was issued for use as rescue medication throughout the study. Eligible participants were randomized to and received mepolizumab 300 mg by SC injection every 4 weeks for up to 52 weeks in addition to their SoC therapy. Salbutamol MDI was issued for use as rescue medication throughout the study.
Period Title: Overall Study
STARTED 226 223 225
Completed Investigational Product (IP) 170 196 183
Not Completed IP 56 27 42
Withdrew IP Due to: Adverse Event 27 9 25
Withdrew IP Due to: Stopping Criteria 1 1 0
Withdrew IP Due to: Lack of Efficacy 6 2 2
Withdrew IP Due to: Protocol Deviation 2 0 1
Withdrew IP Due to: Lost to Follow-up 1 1 1
Withdrew IP Due to: Physician Decision 2 3 1
Withdrew IP Due to: Withdrawal by Subj. 16 11 11
Withdrew IP Due to: Site Closed 1 0 1
COMPLETED 185 206 195
NOT COMPLETED 41 17 30

Baseline Characteristics

Arm/Group Title Placebo Mepolizumab 100 mg SC Mepolizumab 300 mg SC Total
Arm/Group Description Eligible participants were randomized to and received placebo by SC injection every 4 weeks for up to 52 weeks in addition to their SoC therapy. Salbutamol MDI was issued for use as rescue medication throughout the study. Eligible participants were randomized to and received mepolizumab 100 mg by SC injection every 4 weeks for up to 52 weeks in addition to their SoC therapy. Salbutamol MDI was issued for use as rescue medication throughout the study. Eligible participants were randomized to and received mepolizumab 300 mg by SC injection every 4 weeks for up to 52 weeks in addition to their SoC therapy. Salbutamol MDI was issued for use as rescue medication throughout the study. Total of all reporting groups
Overall Participants 226 223 225 674
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]
65.8
(8.64)
64.8
(9.06)
64.8
(8.96)
65.1
(8.89)
Sex: Female, Male (Count of Participants)
Female
70
31%
91
40.8%
67
29.8%
228
33.8%
Male
156
69%
132
59.2%
158
70.2%
446
66.2%
Race/Ethnicity, Customized (Count of Participants)
Asian-Central/South Asian Heritage
0
0%
0
0%
1
0.4%
1
0.1%
Asian-East Asian Heritage
25
11.1%
26
11.7%
26
11.6%
77
11.4%
Asian-Japanese Heritage
14
6.2%
13
5.8%
13
5.8%
40
5.9%
Asian-South East Asian Heritage
3
1.3%
2
0.9%
1
0.4%
6
0.9%
Black or African American
2
0.9%
4
1.8%
2
0.9%
8
1.2%
White-White/Caucasian/European Heritage
182
80.5%
178
79.8%
182
80.9%
542
80.4%

Outcome Measures

1. Primary Outcome
Title Rate of Moderate or Severe Exacerbations
Description 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).
Time Frame From randomization to Week 52

Outcome Measure Data

Analysis Population Description
mITT Population
Arm/Group Title Placebo Mepolizumab 100 mg SC Mepolizumab 300 mg SC
Arm/Group Description Eligible participants were randomized to and received placebo by SC injection every 4 weeks for up to 52 weeks in addition to their SoC therapy. Salbutamol MDI was issued for use as rescue medication throughout the study. Eligible participants were randomized to and received mepolizumab 100 mg by SC injection every 4 weeks for up to 52 weeks in addition to their SoC therapy. Salbutamol MDI was issued for use as rescue medication throughout the study. Eligible participants were randomized to and received mepolizumab 100 mg by SC injection every 4 weeks for up to 52 weeks in addition to their SoC therapy. Salbutamol MDI was issued for use as rescue medication throughout the study.
Measure Participants 226 223 225
Least Squares Mean (95% Confidence Interval) [Moderate/severe exacerbations per year]
1.49
1.19
1.27
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Mepolizumab 100 mg SC
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.068
Comments Adjusted p-value; Family wise type I error controlled within each endpoint using a Hochberg testing procedure
Method Negative binomial model
Comments
Method of Estimation Estimation Parameter Rate ratio (Mepolizumab 100/Placebo)
Estimated Value 0.80
Confidence Interval (2-Sided) 95%
0.65 to 0.98
Parameter Dispersion Type:
Value:
Estimation Comments Analysis using a negative binomial model with covariates of treatment, geographic region, no. of moderate/severe exacerbations in previous year, Baseline percent predicted FEV1, smoking status and offset of log (time in on- and off- treatment period)
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Mepolizumab 100 mg SC
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.034
Comments Unadjusted p-value
Method Negative binomial model
Comments
Method of Estimation Estimation Parameter Rate ratio (Mepolizumab 100/Placebo)
Estimated Value 0.80
Confidence Interval (2-Sided) 95%
0.65 to 0.98
Parameter Dispersion Type:
Value:
Estimation Comments Analysis using a negative binomial model with covariates of treatment, geographic region, no. of moderate/severe exacerbations in previous year, Baseline percent predicted FEV1, smoking status and offset of log (time in on- and off- treatment period)
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Mepolizumab 300 mg SC
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.140
Comments Adjusted p-value; Family wise type I error controlled within each endpoint using a Hochberg testing procedure
Method Negative binomial model
Comments
Method of Estimation Estimation Parameter Rate ratio (Mepolizumab 300/Placebo)
Estimated Value 0.86
Confidence Interval (2-Sided) 95%
0.70 to 1.05
Parameter Dispersion Type:
Value:
Estimation Comments Analysis using a negative binomial model with covariates of treatment, geographic region, no. of moderate/severe exacerbations in previous year, Baseline percent predicted FEV1, smoking status and offset of log (time in on- and off- treatment period
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Mepolizumab 300 mg SC
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.140
Comments Unadjusted p-value
Method Negative binomial model
Comments
Method of Estimation Estimation Parameter Rate ratio (Mepolizumab 300/Placebo)
Estimated Value 0.86
Confidence Interval (2-Sided) 95%
0.70 to 1.05
Parameter Dispersion Type:
Value:
Estimation Comments Analysis using a negative binomial model with covariates of treatment, geographic region, no. of moderate/severe exacerbations in previous year, Baseline percent predicted FEV1, smoking status and offset of log (time in on- and off- treatment period)
2. Secondary Outcome
Title Time to First Moderate/Severe Exacerbation
Description 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.
Time Frame From randomization to Week 52

Outcome Measure Data

Analysis Population Description
mITT Population
Arm/Group Title Placebo Mepolizumab 100 mg SC Mepolizumab 300 mg SC
Arm/Group Description Eligible participants were randomized to and received placebo by SC injection every 4 weeks for up to 52 weeks in addition to their SoC therapy. Salbutamol MDI was issued for use as rescue medication throughout the study. Eligible participants were randomized to and received mepolizumab 100 mg by SC injection every 4 weeks for up to 52 weeks in addition to their SoC therapy. Salbutamol MDI was issued for use as rescue medication throughout the study. Eligible participants were randomized to and received mepolizumab 300 mg by SC injection every 4 weeks for up to 52 weeks in addition to their SoC therapy. Salbutamol MDI was issued for use as rescue medication throughout the study.
Measure Participants 226 223 225
Week 8
22.6
10%
22.9
10.3%
18.3
8.1%
Week 16
40.7
18%
36.0
16.1%
29.0
12.9%
Week 24
51.1
22.6%
42.4
19%
36.7
16.3%
Week 32
58.3
25.8%
46.1
20.7%
44.9
20%
Week 40
62.3
27.6%
50.8
22.8%
51.8
23%
Week 48
64.2
28.4%
55.5
24.9%
58.3
25.9%
Week 52
66.7
29.5%
57.9
26%
58.8
26.1%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Mepolizumab 100 mg SC
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.140
Comments Adjusted p-value; Family wise type I error controlled within each endpoint using a Hochberg testing procedure
Method Cox Proportional Hazards Model
Comments
Method of Estimation Estimation Parameter Hazard Ratio(Mepolizumab 100/Placebo)
Estimated Value 0.82
Confidence Interval (2-Sided) 95%
0.64 to 1.04
Parameter Dispersion Type:
Value:
Estimation Comments Analysis performed using a Cox Proportional Hazards Model with covariates of treatment, geographic region, number of moderate/severe exacerbations in previous year, Baseline percent predicted FEV1 and smoking status
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Mepolizumab 100 mg SC
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.103
Comments Unadjusted p-value
Method Cox Proportional Hazards Model
Comments
Method of Estimation Estimation Parameter Hazard Ratio (Mepolizumab/Placebo)
Estimated Value 0.82
Confidence Interval (2-Sided) 95%
0.64 to 1.04
Parameter Dispersion Type:
Value:
Estimation Comments Analysis performed using a Cox Proportional Hazards Model with covariates of treatment, geographic region, number of moderate/severe exacerbations in previous year, Baseline percent predicted FEV1 and smoking status
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Mepolizumab 300 mg SC
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.140
Comments Adjusted p-value; Family wise type I error controlled within each endpoint using a Hochberg testing procedure
Method Cox Proportional Hazards Model
Comments
Method of Estimation Estimation Parameter Hazard Ratio (Mepolizumab 300/Placebo)
Estimated Value 0.77
Confidence Interval (2-Sided) 95%
0.60 to 0.97
Parameter Dispersion Type:
Value:
Estimation Comments Analysis performed using a Cox Proportional Hazards Model with covariates of treatment, geographic region, number of moderate/severe exacerbations in previous year, Baseline percent predicted FEV1 and smoking status
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Mepolizumab 300 mg SC
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.030
Comments Unadjusted p-value
Method Cox Proportional Hazards Model
Comments
Method of Estimation Estimation Parameter Hazard Ratio (Mepolizumab 300/Placebo)
Estimated Value 0.77
Confidence Interval (2-Sided) 95%
0.60 to 0.97
Parameter Dispersion Type:
Value:
Estimation Comments Analysis performed using a Cox Proportional Hazards Model with covariates of treatment, geographic region, number of moderate/severe exacerbations in previous year, Baseline percent predicted FEV1 and smoking status
3. Secondary Outcome
Title Rate of COPD Exacerbations Requiring Emergency Department (ED) Visits and/or Hospitalizations (Hosp)
Description 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.
Time Frame From randomization to Week 52

Outcome Measure Data

Analysis Population Description
mITT Population
Arm/Group Title Placebo Mepolizumab 100 mg SC Mepolizumab 300 mg SC
Arm/Group Description Eligible participants were randomized to and received placebo by SC injection every 4 weeks for up to 52 weeks in addition to their SoC therapy. Salbutamol MDI was issued for use as rescue medication throughout the study. Eligible participants were randomized to and received mepolizumab 100 mg by SC injection every 4 weeks for up to 52 weeks in addition to their SoC therapy. Salbutamol MDI was issued for use as rescue medication throughout the study. Eligible participants were randomized to and received mepolizumab 300 mg by SC injection every 4 weeks for up to 52 weeks in addition to their SoC therapy. Salbutamol MDI was issued for use as rescue medication throughout the study.
Measure Participants 226 223 225
Least Squares Mean (95% Confidence Interval) [Exacerbations requiring ED/hosp per year]
0.28
0.17
0.23
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Mepolizumab 100 mg SC
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.140
Comments Adjusted p-value; Family wise type I error controlled within each endpoint using a Hochberg testing procedure
Method Negative binomial model
Comments
Method of Estimation Estimation Parameter Rate ratio (Mepolizumab 100/Placebo)
Estimated Value 0.59
Confidence Interval (2-Sided) 95%
0.35 to 0.98
Parameter Dispersion Type:
Value:
Estimation Comments Analysis using a negative binomial model with covariates of treatment, geographic region, no. of moderate/severe exacerbations in previous year, Baseline percent predicted FEV1, smoking status and offset of log (time in on- and off- treatment period)
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Mepolizumab 100 mg SC
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.042
Comments Unadjusted p-value
Method Negative binomial model
Comments
Method of Estimation Estimation Parameter Rate ratio (Mepolizumab 100/Placebo)
Estimated Value 0.59
Confidence Interval (2-Sided) 95%
0.35 to 0.98
Parameter Dispersion Type:
Value:
Estimation Comments Analysis using a negative binomial model with covariates of treatment, geographic region, no. of moderate/severe exacerbations in previous year, Baseline percent predicted FEV1, smoking status and offset of log (time in on- and off- treatment period)
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Mepolizumab 300 mg SC
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.447
Comments Adjusted p-value; Family wise type I error controlled within each endpoint using a Hochberg testing procedure
Method Negative binomial model
Comments
Method of Estimation Estimation Parameter Rate ratio (Mepolizumab 300/Placebo)
Estimated Value 0.83
Confidence Interval (2-Sided) 95%
0.51 to 1.34
Parameter Dispersion Type:
Value:
Estimation Comments Analysis using a negative binomial model with covariates of treatment, geographic region, no. of moderate/severe exacerbations in previous year, Baseline percent predicted FEV1, smoking status and offset of log (time in on- and off- treatment period)
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Mepolizumab 300 mg SC
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.447
Comments Unadjusted p-value
Method Negative binomial model
Comments
Method of Estimation Estimation Parameter Rate ratio (Mepolizumab 300/Placebo)
Estimated Value 0.83
Confidence Interval (2-Sided) 95%
0.51 to 1.34
Parameter Dispersion Type:
Value:
Estimation Comments Analysis using a negative binomial model with covariates of treatment, geographic region, no. of moderate/severe exacerbations in previous year, Baseline percent predicted FEV1, smoking status and offset of log (time in on- and off- treatment period)
4. Secondary Outcome
Title Change From Baseline in Mean Total St. George's Respiratory Questionnaire (SGRQ) Score
Description 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.
Time Frame Baseline and Week 52

Outcome Measure Data

Analysis Population Description
mITT Population. Participants analyzed represents those with a Baseline and at least one post-Baseline assessment, and with no missing covariates.
Arm/Group Title Placebo Mepolizumab 100 mg SC Mepolizumab 300 mg SC
Arm/Group Description Eligible participants were randomized to and received placebo by SC injection every 4 weeks for up to 52 weeks in addition to their SoC therapy. Salbutamol MDI was issued for use as rescue medication throughout the study. Eligible participants were randomized to and received mepolizumab 100 mg by SC injection every 4 weeks for up to 52 weeks in addition to their SoC therapy. Salbutamol MDI was issued for use as rescue medication throughout the study. Eligible participants were randomized to and received mepolizumab 300 mg by SC injection every 4 weeks for up to 52 weeks in addition to their SoC therapy. Salbutamol MDI was issued for use as rescue medication throughout the study.
Measure Participants 218 218 219
Least Squares Mean (Standard Error) [Score on SGRQ scale]
-3.1
(0.98)
-5.0
(0.95)
-3.3
(0.96)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Mepolizumab 100 mg SC
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.447
Comments Adjusted p-value; Family wise type I error controlled within each endpoint using a Hochberg testing procedure
Method Mixed Model Repeated Measures Analysis
Comments
Method of Estimation Estimation Parameter Mean difference(Mepolizumab 100-Placebo)
Estimated Value -1.8
Confidence Interval (2-Sided) 95%
-4.5 to 0.8
Parameter Dispersion Type:
Value:
Estimation Comments Analysis performed using mixed model repeated measures with covariates of Baseline SGRQ total score, geographic region, smoking status, treatment and visit, plus interaction terms for visit by Baseline and visit by treatment group.
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Mepolizumab 100 mg SC
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.180
Comments Unadjusted p-value
Method Mixed Model Repeated Measures Analysis
Comments
Method of Estimation Estimation Parameter Mean difference(Mepolizumab 100-Placebo)
Estimated Value -1.8
Confidence Interval (2-Sided) 95%
-4.5 to 0.8
Parameter Dispersion Type:
Value:
Estimation Comments Analysis performed using mixed model repeated measures with covariates of Baseline SGRQ total score, geographic region, smoking status, treatment and visit, plus interaction terms for visit by Baseline and visit by treatment group.
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Mepolizumab 300 mg SC
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.926
Comments Adjusted p-value; Family wise type I error controlled within each endpoint using a Hochberg testing procedure
Method Mixed Model Repeated Measures Analysis
Comments
Method of Estimation Estimation Parameter Mean difference(Mepolizumab 300-Placebo)
Estimated Value -0.1
Confidence Interval (2-Sided) 95%
-2.8 to 2.6
Parameter Dispersion Type:
Value:
Estimation Comments Analysis performed using mixed model repeated measures with covariates of Baseline SGRQ total score, geographic region, smoking status, treatment and visit, plus interaction terms for visit by Baseline and visit by treatment group.
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Mepolizumab 300 mg SC
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.926
Comments Unadjusted p-value
Method Mixed Model Repeated Measures Analysis
Comments
Method of Estimation Estimation Parameter Mean difference(Mepolizumab 300-Placebo)
Estimated Value -0.1
Confidence Interval (2-Sided) 95%
-2.8 to 2.6
Parameter Dispersion Type:
Value:
Estimation Comments Analysis performed using mixed model repeated measures with covariates of Baseline SGRQ total score, geographic region, smoking status, treatment and visit, plus interaction terms for visit by Baseline and visit by treatment group.
5. Secondary Outcome
Title Change From Baseline in Mean COPD Assessment Test (CAT) Score
Description 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.
Time Frame Baseline and Week 52

Outcome Measure Data

Analysis Population Description
mITT Population. Participants analyzed represents those with a Baseline and at least one post-Baseline assessment, and with no missing covariates.
Arm/Group Title Placebo Mepolizumab 100 mg SC Mepolizumab 300 mg SC
Arm/Group Description Eligible participants were randomized to and received placebo by SC injection every 4 weeks for up to 52 weeks in addition to their SoC therapy. Salbutamol MDI was issued for use as rescue medication throughout the study. Eligible participants were randomized to and received mepolizumab 100 mg by SC injection every 4 weeks for up to 52 weeks in addition to their SoC therapy. Salbutamol MDI was issued for use as rescue medication throughout the study. Eligible participants were randomized to and received mepolizumab 300 mg by SC injection every 4 weeks for up to 52 weeks in addition to their SoC therapy. Salbutamol MDI was issued for use as rescue medication throughout the study.
Measure Participants 222 216 219
Least Squares Mean (Standard Error) [Score on CAT scale]
-0.4
(0.42)
-1.6
(0.42)
-0.8
(0.42)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Mepolizumab 100 mg SC
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.926
Comments Adjusted p-value; Family wise type I error controlled within each endpoint using a Hochberg testing procedure
Method Mixed Model Repeated Measures Analysis
Comments
Method of Estimation Estimation Parameter Mean difference(Mepolizumab 100-Placebo)
Estimated Value -1.1
Confidence Interval (2-Sided) 95%
-2.3 to 0.0
Parameter Dispersion Type:
Value:
Estimation Comments Analysis performed using mixed model repeated measures with covariates of Baseline CAT score, geographic region, smoking status, treatment and visit, plus interaction terms for visit by Baseline and visit by treatment group.
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Mepolizumab 100 mg SC
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.055
Comments Unadjusted p-value
Method Mixed Model Repeated Measures Analysis
Comments
Method of Estimation Estimation Parameter Mean difference(Mepolizumab 100-Placebo)
Estimated Value -1.1
Confidence Interval (2-Sided) 95%
-2.3 to 0.0
Parameter Dispersion Type:
Value:
Estimation Comments Analysis performed using mixed model repeated measures with covariates of Baseline CAT score, geographic region, smoking status, treatment and visit, plus interaction terms for visit by Baseline and visit by treatment group.
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Mepolizumab 300 mg SC
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.926
Comments Adjusted p-value; Family wise type I error controlled within each endpoint using a Hochberg testing procedure
Method Mixed Model Repeated Measures Analysis
Comments
Method of Estimation Estimation Parameter Mean difference(Mepolizumab 300-Placebo)
Estimated Value -0.4
Confidence Interval (2-Sided) 95%
-1.5 to 0.8
Parameter Dispersion Type:
Value:
Estimation Comments Analysis performed using mixed model repeated measures with covariates of Baseline CAT score, geographic region, smoking status, treatment and visit, plus interaction terms for visit by Baseline and visit by treatment group.
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Mepolizumab 300 mg SC
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.547
Comments Unadjusted p-value
Method Mixed Model Repeated Measures Analysis
Comments
Method of Estimation Estimation Parameter Mean difference(Mepolizumab 300-Placebo)
Estimated Value -0.4
Confidence Interval (2-Sided) 95%
-1.5 to 0.8
Parameter Dispersion Type:
Value:
Estimation Comments Analysis performed using mixed model repeated measures with covariates of Baseline CAT score, geographic region, smoking status, treatment and visit, plus interaction terms for visit by Baseline and visit by treatment group.

Adverse Events

Time Frame Serious adverse events (SAEs) collected from the start of study participation until the end of follow up (up to Week 60). On-treatment non-serious adverse events (AEs) reported from start of study treatment until 4 weeks after last dose.
Adverse Event Reporting Description AEs and SAEs were collected in Safety Population which comprised of all randomized participants who received at least one dose of study treatment
Arm/Group Title Placebo Mepolizumab 100 mg SC Mepolizumab 300 mg SC
Arm/Group Description Eligible participants were randomized to and received placebo by SC injection every 4 weeks for up to 52 weeks in addition to their SoC therapy. Salbutamol MDI was issued for use as rescue medication throughout the study. Eligible participants were randomized to and received mepolizumab 100 mg by SC injection every 4 weeks for up to 52 weeks in addition to their SoC therapy. Salbutamol MDI was issued for use as rescue medication throughout the study. Eligible participants were randomized to and received mepolizumab 300 mg by SC injection every 4 weeks for up to 52 weeks in addition to their SoC therapy. Salbutamol MDI was issued for use as rescue medication throughout the study.
All Cause Mortality
Placebo Mepolizumab 100 mg SC Mepolizumab 300 mg SC
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 9/226 (4%) 4/223 (1.8%) 8/225 (3.6%)
Serious Adverse Events
Placebo Mepolizumab 100 mg SC Mepolizumab 300 mg SC
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 68/226 (30.1%) 57/223 (25.6%) 60/225 (26.7%)
Cardiac disorders
Acute myocardial infarction 3/226 (1.3%) 3 1/223 (0.4%) 1 2/225 (0.9%) 2
Atrial fibrillation 3/226 (1.3%) 6 3/223 (1.3%) 3 0/225 (0%) 0
Cardio-respiratory arrest 0/226 (0%) 0 1/223 (0.4%) 1 1/225 (0.4%) 1
Coronary artery disease 1/226 (0.4%) 1 0/223 (0%) 0 1/225 (0.4%) 1
Stress cardiomyopathy 1/226 (0.4%) 1 0/223 (0%) 0 1/225 (0.4%) 1
Supraventricular tachycardia 0/226 (0%) 0 0/223 (0%) 0 2/225 (0.9%) 2
Acute coronary syndrome 0/226 (0%) 0 0/223 (0%) 0 1/225 (0.4%) 1
Angina pectoris 0/226 (0%) 0 1/223 (0.4%) 1 0/225 (0%) 0
Angina unstable 0/226 (0%) 0 1/223 (0.4%) 1 0/225 (0%) 0
Arrhythmia 1/226 (0.4%) 1 0/223 (0%) 0 0/225 (0%) 0
Cardiac arrest 1/226 (0.4%) 1 0/223 (0%) 0 0/225 (0%) 0
Cardiac failure congestive 0/226 (0%) 0 1/223 (0.4%) 1 0/225 (0%) 0
Cor pulmonale 0/226 (0%) 0 1/223 (0.4%) 1 0/225 (0%) 0
Myocardial infarction 0/226 (0%) 0 0/223 (0%) 0 1/225 (0.4%) 1
Endocrine disorders
Inappropriate antidiuretic hormone secretion 0/226 (0%) 0 1/223 (0.4%) 1 0/225 (0%) 0
Eye disorders
Cataract 1/226 (0.4%) 1 0/223 (0%) 0 1/225 (0.4%) 1
Macular fibrosis 0/226 (0%) 0 0/223 (0%) 0 1/225 (0.4%) 1
Gastrointestinal disorders
Diarrhoea 0/226 (0%) 0 3/223 (1.3%) 3 1/225 (0.4%) 1
Abdominal pain 0/226 (0%) 0 1/223 (0.4%) 1 0/225 (0%) 0
Diverticulum intestinal 0/226 (0%) 0 1/223 (0.4%) 1 0/225 (0%) 0
Duodenal ulcer 0/226 (0%) 0 1/223 (0.4%) 1 0/225 (0%) 0
Gastric haemorrhage 0/226 (0%) 0 0/223 (0%) 0 1/225 (0.4%) 1
Gastritis 0/226 (0%) 0 1/223 (0.4%) 1 0/225 (0%) 0
Gastrointestinal haemorrhage 1/226 (0.4%) 1 0/223 (0%) 0 0/225 (0%) 0
Ileus 0/226 (0%) 0 0/223 (0%) 0 1/225 (0.4%) 1
Inguinal hernia 0/226 (0%) 0 0/223 (0%) 0 1/225 (0.4%) 1
Large intestine perforation 0/226 (0%) 0 1/223 (0.4%) 1 0/225 (0%) 0
Vomiting 0/226 (0%) 0 0/223 (0%) 0 1/225 (0.4%) 1
General disorders
Non-cardiac chest pain 1/226 (0.4%) 1 1/223 (0.4%) 1 0/225 (0%) 0
Pyrexia 1/226 (0.4%) 1 0/223 (0%) 0 1/225 (0.4%) 1
Death 0/226 (0%) 0 0/223 (0%) 0 1/225 (0.4%) 1
General physical health deterioration 0/226 (0%) 0 0/223 (0%) 0 1/225 (0.4%) 1
Vascular stent thrombosis 0/226 (0%) 0 1/223 (0.4%) 1 0/225 (0%) 0
Hepatobiliary disorders
Hepatocellular injury 1/226 (0.4%) 1 0/223 (0%) 0 0/225 (0%) 0
Infections and infestations
Pneumonia 18/226 (8%) 19 16/223 (7.2%) 21 15/225 (6.7%) 16
Infective exacerbation of chronic obstructive airways disease 5/226 (2.2%) 6 1/223 (0.4%) 1 3/225 (1.3%) 4
Sepsis 1/226 (0.4%) 1 3/223 (1.3%) 3 0/225 (0%) 0
Urinary tract infection 0/226 (0%) 0 3/223 (1.3%) 3 1/225 (0.4%) 1
Lower respiratory tract infection 1/226 (0.4%) 1 1/223 (0.4%) 1 1/225 (0.4%) 1
Bronchitis 1/226 (0.4%) 1 0/223 (0%) 0 1/225 (0.4%) 1
Influenza 1/226 (0.4%) 1 0/223 (0%) 0 1/225 (0.4%) 1
Pneumonia pseudomonal 0/226 (0%) 0 0/223 (0%) 0 2/225 (0.9%) 3
Upper respiratory tract infection 1/226 (0.4%) 2 0/223 (0%) 0 1/225 (0.4%) 1
Abdominal wall abscess 0/226 (0%) 0 1/223 (0.4%) 1 0/225 (0%) 0
Appendicitis 0/226 (0%) 0 1/223 (0.4%) 1 0/225 (0%) 0
Atypical mycobacterial infection 0/226 (0%) 0 1/223 (0.4%) 1 0/225 (0%) 0
Clostridium difficile colitis 1/226 (0.4%) 1 0/223 (0%) 0 0/225 (0%) 0
Colonic abscess 0/226 (0%) 0 1/223 (0.4%) 1 0/225 (0%) 0
Cystitis 0/226 (0%) 0 1/223 (0.4%) 1 0/225 (0%) 0
Gastrointestinal infection 1/226 (0.4%) 1 0/223 (0%) 0 0/225 (0%) 0
Lung abscess 1/226 (0.4%) 1 0/223 (0%) 0 0/225 (0%) 0
Orchitis 0/226 (0%) 0 1/223 (0.4%) 1 0/225 (0%) 0
Osteomyelitis 1/226 (0.4%) 1 0/223 (0%) 0 0/225 (0%) 0
Pneumonia bacterial 0/226 (0%) 0 1/223 (0.4%) 1 0/225 (0%) 0
Pneumonia haemophilus 1/226 (0.4%) 1 0/223 (0%) 0 0/225 (0%) 0
Pneumonia necrotising 1/226 (0.4%) 1 0/223 (0%) 0 0/225 (0%) 0
Pneumonia pneumococcal 0/226 (0%) 0 1/223 (0.4%) 1 0/225 (0%) 0
Pulmonary tuberculosis 0/226 (0%) 0 0/223 (0%) 0 1/225 (0.4%) 1
Respiratory tract infection 0/226 (0%) 0 0/223 (0%) 0 1/225 (0.4%) 1
Viral infection 0/226 (0%) 0 1/223 (0.4%) 1 0/225 (0%) 0
Vulvovaginal mycotic infection 0/226 (0%) 0 1/223 (0.4%) 1 0/225 (0%) 0
Injury, poisoning and procedural complications
Rib fracture 0/226 (0%) 0 1/223 (0.4%) 1 1/225 (0.4%) 1
Clavicle fracture 0/226 (0%) 0 1/223 (0.4%) 1 0/225 (0%) 0
Femoral neck fracture 0/226 (0%) 0 1/223 (0.4%) 1 0/225 (0%) 0
Foot fracture 0/226 (0%) 0 1/223 (0.4%) 1 0/225 (0%) 0
Humerus fracture 1/226 (0.4%) 1 0/223 (0%) 0 0/225 (0%) 0
Injection related reaction 1/226 (0.4%) 1 0/223 (0%) 0 0/225 (0%) 0
Meniscus injury 0/226 (0%) 0 1/223 (0.4%) 1 0/225 (0%) 0
Post procedural haemorrhage 1/226 (0.4%) 2 0/223 (0%) 0 0/225 (0%) 0
Spinal compression fracture 1/226 (0.4%) 1 0/223 (0%) 0 0/225 (0%) 0
Investigations
Haematocrit increased 1/226 (0.4%) 1 0/223 (0%) 0 0/225 (0%) 0
Metabolism and nutrition disorders
Diabetes mellitus inadequate control 0/226 (0%) 0 1/223 (0.4%) 1 0/225 (0%) 0
Musculoskeletal and connective tissue disorders
Back pain 1/226 (0.4%) 1 0/223 (0%) 0 0/225 (0%) 0
Rhabdomyolysis 1/226 (0.4%) 1 0/223 (0%) 0 0/225 (0%) 0
Spinal osteoarthritis 0/226 (0%) 0 1/223 (0.4%) 2 0/225 (0%) 0
Spondyloarthropathy 0/226 (0%) 0 1/223 (0.4%) 1 0/225 (0%) 0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer 1/226 (0.4%) 1 0/223 (0%) 0 2/225 (0.9%) 2
Breast cancer 1/226 (0.4%) 1 1/223 (0.4%) 1 0/225 (0%) 0
Non-small cell lung cancer 1/226 (0.4%) 1 0/223 (0%) 0 1/225 (0.4%) 1
Adenocarcinoma of colon 1/226 (0.4%) 1 0/223 (0%) 0 0/225 (0%) 0
Benign lung neoplasm 0/226 (0%) 0 0/223 (0%) 0 1/225 (0.4%) 1
Bowen's disease 0/226 (0%) 0 1/223 (0.4%) 1 0/225 (0%) 0
Gastric cancer 0/226 (0%) 0 1/223 (0.4%) 1 0/225 (0%) 0
Lung adenocarcinoma 0/226 (0%) 0 0/223 (0%) 0 1/225 (0.4%) 1
Lung neoplasm malignant 0/226 (0%) 0 1/223 (0.4%) 1 0/225 (0%) 0
Malignant melanoma 1/226 (0.4%) 1 0/223 (0%) 0 0/225 (0%) 0
Oropharyngeal cancer 1/226 (0.4%) 1 0/223 (0%) 0 0/225 (0%) 0
Rectal adenocarcinoma 0/226 (0%) 0 1/223 (0.4%) 1 0/225 (0%) 0
Nervous system disorders
Cerebral ischaemia 0/226 (0%) 0 0/223 (0%) 0 1/225 (0.4%) 1
Cerebrovascular accident 0/226 (0%) 0 1/223 (0.4%) 1 0/225 (0%) 0
Haemorrhagic stroke 1/226 (0.4%) 1 0/223 (0%) 0 0/225 (0%) 0
Peroneal nerve palsy 0/226 (0%) 0 1/223 (0.4%) 1 0/225 (0%) 0
Post herpetic neuralgia 0/226 (0%) 0 0/223 (0%) 0 1/225 (0.4%) 1
Syncope 0/226 (0%) 0 0/223 (0%) 0 1/225 (0.4%) 1
Transient ischaemic attack 1/226 (0.4%) 1 0/223 (0%) 0 0/225 (0%) 0
Psychiatric disorders
Confusional state 0/226 (0%) 0 1/223 (0.4%) 1 0/225 (0%) 0
Delirium 0/226 (0%) 0 1/223 (0.4%) 1 0/225 (0%) 0
Renal and urinary disorders
Acute kidney injury 1/226 (0.4%) 1 0/223 (0%) 0 0/225 (0%) 0
Calculus urinary 0/226 (0%) 0 1/223 (0.4%) 1 0/225 (0%) 0
Haematuria 0/226 (0%) 0 1/223 (0.4%) 1 0/225 (0%) 0
Renal colic 0/226 (0%) 0 1/223 (0.4%) 1 0/225 (0%) 0
Renal tubular necrosis 0/226 (0%) 0 1/223 (0.4%) 1 0/225 (0%) 0
Urinary retention 0/226 (0%) 0 1/223 (0.4%) 1 0/225 (0%) 0
Reproductive system and breast disorders
Benign prostatic hyperplasia 1/226 (0.4%) 1 1/223 (0.4%) 1 0/225 (0%) 0
Prostatic obstruction 1/226 (0.4%) 1 0/223 (0%) 0 0/225 (0%) 0
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease 37/226 (16.4%) 52 25/223 (11.2%) 34 32/225 (14.2%) 54
Acute respiratory failure 2/226 (0.9%) 2 3/223 (1.3%) 4 0/225 (0%) 0
Respiratory failure 1/226 (0.4%) 1 1/223 (0.4%) 1 2/225 (0.9%) 2
Pulmonary embolism 1/226 (0.4%) 1 0/223 (0%) 0 2/225 (0.9%) 2
Pneumothorax 0/226 (0%) 0 0/223 (0%) 0 2/225 (0.9%) 2
Atelectasis 1/226 (0.4%) 1 0/223 (0%) 0 0/225 (0%) 0
Chronic respiratory failure 1/226 (0.4%) 1 0/223 (0%) 0 0/225 (0%) 0
Hypercapnia 0/226 (0%) 0 1/223 (0.4%) 1 0/225 (0%) 0
Hypoxia 0/226 (0%) 0 0/223 (0%) 0 1/225 (0.4%) 1
Interstitial lung disease 1/226 (0.4%) 1 0/223 (0%) 0 0/225 (0%) 0
Pleurisy 0/226 (0%) 0 1/223 (0.4%) 1 0/225 (0%) 0
Pneumonia aspiration 0/226 (0%) 0 1/223 (0.4%) 1 0/225 (0%) 0
Pneumothorax spontaneous 1/226 (0.4%) 2 0/223 (0%) 0 0/225 (0%) 0
Vascular disorders
Aortic aneurysm 0/226 (0%) 0 1/223 (0.4%) 1 0/225 (0%) 0
Aortic stenosis 0/226 (0%) 0 1/223 (0.4%) 1 0/225 (0%) 0
Essential hypertension 0/226 (0%) 0 1/223 (0.4%) 1 0/225 (0%) 0
Hypertension 0/226 (0%) 0 1/223 (0.4%) 1 0/225 (0%) 0
Hypertensive crisis 1/226 (0.4%) 1 0/223 (0%) 0 0/225 (0%) 0
Hypotension 0/226 (0%) 0 1/223 (0.4%) 1 0/225 (0%) 0
Orthostatic hypotension 0/226 (0%) 0 1/223 (0.4%) 1 0/225 (0%) 0
Other (Not Including Serious) Adverse Events
Placebo Mepolizumab 100 mg SC Mepolizumab 300 mg SC
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 137/226 (60.6%) 147/223 (65.9%) 137/225 (60.9%)
Gastrointestinal disorders
Diarrhoea 14/226 (6.2%) 14 13/223 (5.8%) 16 8/225 (3.6%) 12
Constipation 10/226 (4.4%) 10 7/223 (3.1%) 8 5/225 (2.2%) 6
Nausea 3/226 (1.3%) 3 9/223 (4%) 10 9/225 (4%) 13
Abdominal pain upper 1/226 (0.4%) 1 9/223 (4%) 9 5/225 (2.2%) 5
General disorders
Injection site reaction 10/226 (4.4%) 17 6/223 (2.7%) 6 11/225 (4.9%) 27
Pyrexia 9/226 (4%) 9 6/223 (2.7%) 7 12/225 (5.3%) 17
Non-cardiac chest pain 7/226 (3.1%) 7 5/223 (2.2%) 8 7/225 (3.1%) 8
Fatigue 4/226 (1.8%) 4 6/223 (2.7%) 6 8/225 (3.6%) 8
Oedema peripheral 3/226 (1.3%) 3 7/223 (3.1%) 7 4/225 (1.8%) 6
Infections and infestations
Nasopharyngitis 48/226 (21.2%) 65 39/223 (17.5%) 57 40/225 (17.8%) 52
Upper respiratory tract infection 20/226 (8.8%) 27 16/223 (7.2%) 19 12/225 (5.3%) 15
Pneumonia 8/226 (3.5%) 9 10/223 (4.5%) 13 10/225 (4.4%) 11
Bronchitis 8/226 (3.5%) 8 8/223 (3.6%) 12 11/225 (4.9%) 15
Sinusitis 7/226 (3.1%) 11 8/223 (3.6%) 11 7/225 (3.1%) 9
Influenza 11/226 (4.9%) 11 6/223 (2.7%) 7 3/225 (1.3%) 3
Oral candidiasis 5/226 (2.2%) 7 3/223 (1.3%) 3 8/225 (3.6%) 9
Rhinitis 5/226 (2.2%) 6 7/223 (3.1%) 9 4/225 (1.8%) 4
Urinary tract infection 7/226 (3.1%) 8 7/223 (3.1%) 8 1/225 (0.4%) 1
Injury, poisoning and procedural complications
Contusion 2/226 (0.9%) 2 7/223 (3.1%) 7 3/225 (1.3%) 3
Musculoskeletal and connective tissue disorders
Back pain 11/226 (4.9%) 11 15/223 (6.7%) 18 17/225 (7.6%) 21
Arthralgia 6/226 (2.7%) 7 10/223 (4.5%) 10 6/225 (2.7%) 6
Pain in extremity 5/226 (2.2%) 6 7/223 (3.1%) 7 6/225 (2.7%) 10
Musculoskeletal pain 2/226 (0.9%) 2 4/223 (1.8%) 4 7/225 (3.1%) 8
Nervous system disorders
Headache 20/226 (8.8%) 29 34/223 (15.2%) 62 22/225 (9.8%) 39
Respiratory, thoracic and mediastinal disorders
Cough 12/226 (5.3%) 16 14/223 (6.3%) 14 16/225 (7.1%) 22
Dyspnoea 18/226 (8%) 19 12/223 (5.4%) 14 10/225 (4.4%) 17
Oropharyngeal pain 4/226 (1.8%) 4 15/223 (6.7%) 15 11/225 (4.9%) 13
Chronic obstructive pulmonary disease 5/226 (2.2%) 9 8/223 (3.6%) 12 10/225 (4.4%) 24
Vascular disorders
Hypertension 3/226 (1.3%) 3 8/223 (3.6%) 9 7/225 (3.1%) 7

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.

Results Point of Contact

Name/Title GSK Response Center
Organization GlaxoSmithKline
Phone 866-435-7343
Email GSKClinicalSupportHD@gsk.com
Responsible Party:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT02105961
Other Study ID Numbers:
  • 117113
First Posted:
Apr 7, 2014
Last Update Posted:
Aug 16, 2018
Last Verified:
Jul 1, 2018