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Study to Evaluate Efficacy and Safety of Mepolizumab for Frequently Exacerbating Chronic Obstructive Pulmonary Disease (COPD) Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02105948
Recruitment Status : Completed
First Posted : April 7, 2014
Results First Posted : April 6, 2018
Last Update Posted : August 31, 2018
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Pulmonary Disease, Chronic Obstructive
Interventions Drug: Mepolizumab
Drug: Placebo
Enrollment 837
Recruitment Details Participants with chronic obstructive pulmonary disease (COPD) with frequent exacerbations and on high dose inhaled corticosteroid (ICS)-based triple inhaled maintenance therapy were included in this study. Participants were randomized to receive mepolizumab 100 milligrams (mg) or placebo by subcutaneous (SC) injection every 4 weeks for 52 weeks.
Pre-assignment Details A total of 836 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 One participant randomized to the placebo group was withdrawn without receiving study treatment.
Arm/Group Title Placebo - High Stratum Mepolizumab 100 mg - High Stratum Placebo - Low Stratum Mepolizumab 100 mg - Low Stratum
Hide Arm/Group Description Participants with blood eosinophil counts >=150 cells per microliter (cells/µL) at Screening or >=300 cells/µL in the 12 months prior were assigned to the high stratum group. These 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. Participants with blood eosinophil counts >=150 cells/µL at Screening or >=300 cells/ µL in the 12 months prior were assigned to the high stratum group. These 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. Participants with blood eosinophil counts <150 cells/µL at Screening and no evidence of blood eosinophil counts >=300 cells/µL in the 12 months prior were assigned to the low stratum group. These 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. Participants with blood eosinophil counts <150 cells/µL at Screening and no evidence of blood eosinophil counts >=300 cells/µL in the 12 months prior were assigned to the low stratum group. These 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.
Period Title: Overall Study
Started 229 233 190 184
Completed Investigational Product (IP) 185 203 148 149
Not Completed IP 44 30 42 35
Withdrew IP Due to: Adverse Event 20 16 15 13
Withdrew IP Due to: Lack of Efficacy 5 2 8 2
Withdrew IP Due to: Protocol Deviation 1 3 3 0
Withdrew IP Due to: Lost to Follow-up 0 0 1 2
Withdrew IP Due to: Withdrawal by Subj. 16 8 11 15
Withdrew IP Due to: Physician Decision 2 1 4 2
Withdrew IP Due to: Stopping Criteria 0 0 0 1
Completed 202 213 162 157
Not Completed 27 20 28 27
Reason Not Completed
Adverse Event             10             7             11             11
Lack of Efficacy             0             1             3             2
Lost to Follow-up             0             0             2             1
Physician Decision             2             2             2             2
Withdrawal by Subject             15             10             10             11
Arm/Group Title Placebo - High Stratum Mepolizumab 100 mg - High Stratum Placebo - Low Stratum Mepolizumab 100 mg - Low Stratum Total
Hide Arm/Group Description Participants with blood eosinophil counts >=150 cells/µL at Screening or >=300 cells/µL in the 12 months prior were assigned to the high stratum group. These 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. Participants with blood eosinophil counts >=150 cells/µL at Screening or >=300 cells/ µL in the 12 months prior were assigned to the high stratum group. These 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. Participants with blood eosinophil counts <150 cells/µL at Screening and no evidence of blood eosinophil counts >=300 cells/µL in the 12 months prior were assigned to the low stratum group. These 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. Participants with blood eosinophil counts <150 cells/µL at Screening and no evidence of blood eosinophil counts >=300 cells/µL in the 12 months prior were assigned to the low stratum group. These 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. Total of all reporting groups
Overall Number of Baseline Participants 229 233 190 184 836
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 229 participants 233 participants 190 participants 184 participants 836 participants
65.3  (8.53) 65.2  (8.36) 65.2  (8.62) 66.1  (9.14) 65.4  (8.64)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 229 participants 233 participants 190 participants 184 participants 836 participants
Female
79
  34.5%
84
  36.1%
77
  40.5%
76
  41.3%
316
  37.8%
Male
150
  65.5%
149
  63.9%
113
  59.5%
108
  58.7%
520
  62.2%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Race customized Number Analyzed 229 participants 233 participants 190 participants 184 participants 836 participants
American Indian/ Alaska native Heritage
14
   6.1%
19
   8.2%
22
  11.6%
14
   7.6%
69
   8.3%
Asian- East Asian Heritage
0
   0.0%
2
   0.9%
0
   0.0%
0
   0.0%
2
   0.2%
Asian- Japanese Heritage
3
   1.3%
0
   0.0%
1
   0.5%
1
   0.5%
5
   0.6%
Black/ African American Heritage
4
   1.7%
2
   0.9%
3
   1.6%
2
   1.1%
11
   1.3%
White- Arabic/ North African Heritage
2
   0.9%
1
   0.4%
0
   0.0%
1
   0.5%
4
   0.5%
White- White/ Caucasian/ European Heritage
190
  83.0%
198
  85.0%
145
  76.3%
143
  77.7%
676
  80.9%
Multiple - American Indian/Alaska Native and White
16
   7.0%
11
   4.7%
19
  10.0%
23
  12.5%
69
   8.3%
1.Primary Outcome
Title Rate of Moderate or Severe Exacerbations in Participants in the High Stratum
Hide 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 investigational product by subjects who remained in the study, were included in the analysis. The analysis was performed on the mITT high stratum (mITT-H) Population which comprised of participants in the mITT Population (all randomized participants who received at least one dose of study treatment) with blood eosinophil counts >=150 cells/µL at Screening or >=300 cells/ µL in the 12 months prior.
Time Frame From randomization to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
mITT-H Population
Arm/Group Title Placebo - High Stratum Mepolizumab 100 mg - High Stratum
Hide Arm/Group Description:
Participants with blood eosinophil counts >=150 cells/µL at Screening or >=300 cells/µL in the 12 months prior were assigned to the high stratum group. These 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.
Participants with blood eosinophil counts >=150 cells/µL at Screening or >=300 cells/ µL in the 12 months prior were assigned to the high stratum group. These 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.
Overall Number of Participants Analyzed 229 233
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Moderate/severe exacerbations per year
1.71
(1.51 to 1.94)
1.40
(1.23 to 1.60)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo - High Stratum, Mepolizumab 100 mg - High Stratum
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.036
Comments Adjusted p-value to account for two treatment comparisons
Method Negative binomial model
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate ratio (mepolizumab/placebo)
Estimated Value 0.82
Confidence Interval (2-Sided) 95%
0.68 to 0.98
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 for FEV1,smoking status and offset of log (time in on-and off-treatment period)
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo - High Stratum, Mepolizumab 100 mg - High Stratum
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.029
Comments Unadjusted p-value.
Method Negative binomial mode
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate ratio (mepolizumab/placebo)
Estimated Value 0.82
Confidence Interval (2-Sided) 95%
0.68 to 0.98
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.Primary Outcome
Title Rate of Moderate or Severe Exacerbations in the mITT Population
Hide Description Moderate and severe exacerbations 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. The analysis was performed on the mITT Population which comprised of all randomized participants who received at least one dose of trial medication. The strata were combined as pre-specified in the protocol and reporting and analysis plan (RAP).
Time Frame From randomization to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
mITT Population
Arm/Group Title Placebo Mepolizumab 100 mg
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 419 417
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Moderate/severe exacerbations per year
1.52
(1.38 to 1.68)
1.49
(1.35 to 1.64)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Mepolizumab 100 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.999
Comments Adjusted p-value to account for two treatment comparisons
Method Negative Binomial Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate ratio (mepolizumab/placebo)
Estimated Value 0.98
Confidence Interval (2-Sided) 95%
0.85 to 1.12
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)
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Mepolizumab 100 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.731
Comments Unadjusted p-value.
Method Negative binomial mode
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate ratio (mepolizumab/placebo)
Estimated Value 0.98
Confidence Interval (2-Sided) 95%
0.85 to 1.12
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)
3.Secondary Outcome
Title Time to First Moderate/Severe Exacerbation in Participants in the High Stratum
Hide 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 was performed on the mITT-H 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
Hide Outcome Measure Data
Hide Analysis Population Description
mITT-H Population
Arm/Group Title Placebo - High Stratum Mepolizumab 100 mg - High Stratum
Hide Arm/Group Description:
Participants with blood eosinophil counts >=150 cells/µL at Screening or >=300 cells/µL in the 12 months prior were assigned to the high stratum group. These 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.
Participants with blood eosinophil counts >=150 cells/µL at Screening or >=300 cells/ µL in the 12 months prior were assigned to the high stratum group. These 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.
Overall Number of Participants Analyzed 229 233
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
Week 8
28.1
(22.7 to 34.4)
20.2
(15.6 to 26.0)
Week 16
45.5
(39.3 to 52.3)
34.9
(29.2 to 41.5)
Week 24
53.4
(47.0 to 60.1)
45.8
(39.6 to 52.4)
Week 32
60.9
(54.5 to 67.4)
55.3
(49.0 to 61.8)
Week 40
68.5
(62.2 to 74.5)
59.3
(53.0 to 65.7)
Week 48
71.8
(65.7 to 77.6)
62.0
(55.8 to 68.3)
Week 52
75.2
(69.3 to 80.8)
64.6
(58.3 to 70.8)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo - High Stratum, Mepolizumab 100 mg - High Stratum
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.036
Comments Adjusted p-value
Method Cox Proportional Hazards Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard ratio (Mepolizumab/placebo)
Estimated Value 0.75
Confidence Interval (2-Sided) 95%
0.60 to 0.94
Estimation Comments Analysis performed using a Cox Proportional Hazards Model with covariates of treatment, geographic region, no. moderate/severe exacerbations in previous year, Baseline percent predicted FEV1 and smoking status
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo - High Stratum, Mepolizumab 100 mg - High Stratum
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.012
Comments Unadjusted p-value
Method Cox Proportional Hazards Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard ratio (Mepolizumab/placebo)
Estimated Value 0.75
Confidence Interval (2-Sided) 95%
0.60 to 0.94
Estimation Comments Analysis performed using a Cox Proportional Hazards Model with covariates of treatment, geographic region, no. moderate/severe exacerbations in previous year, Baseline percent predicted FEV1 and smoking status
4.Secondary Outcome
Title Rate of COPD Exacerbations Requiring an Emergency Department (ED) Visit and/or Hospitalization (Hosp.) in Participants in the High Stratum
Hide 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. The analysis was performed on mITT-H Population.
Time Frame From randomization to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
mITT-H Population
Arm/Group Title Placebo - High Stratum Mepolizumab 100 mg - High Stratum
Hide Arm/Group Description:
Participants with blood eosinophil counts >=150 cells/µL at Screening or >=300 cells/µL in the 12 months prior were assigned to the high stratum group. These 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.
Participants with blood eosinophil counts >=150 cells/µL at Screening or >=300 cells/ µL in the 12 months prior were assigned to the high stratum group. These 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.
Overall Number of Participants Analyzed 229 233
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Exacerbations requiring ED/hosp per year
0.26
(0.19 to 0.36)
0.30
(0.22 to 0.40)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo - High Stratum, Mepolizumab 100 mg - High Stratum
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.598
Comments Adjusted p-value
Method Negative binomial model
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate ratio (mepolizumab/placebo)
Estimated Value 1.16
Confidence Interval (2-Sided) 95%
0.77 to 1.75
Estimation Comments Analysis using a negative binomial model with covariates of treatment, geographic region, no. moderate/severe exacerbations in previous year, Baseline percent predicted FEV1, smoking status and offset of log (time in on- and off-treatment period).
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo - High Stratum, Mepolizumab 100 mg - High Stratum
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.479
Comments Unadjusted p-value
Method Negative binomial model
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate ratio (mepolizumab/placebo)
Estimated Value 1.16
Confidence Interval (2-Sided) 95%
0.77 to 1.75
Estimation Comments Analysis using a negative binomial model with covariates of treatment, geographic region, no. moderate/severe exacerbations in previous year, Baseline percent predicted FEV1, smoking status and offset of log (time in on- and off-treatment period).
5.Secondary Outcome
Title Change From Baseline in Mean Total St. George's Respiratory Questionnaire (SGRQ) Score in Participants in the High Stratum
Hide 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 ranges 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
Hide Outcome Measure Data
Hide Analysis Population Description
mITT-H Population. Participants analyzed represents those with a Baseline and at least one post-Baseline assessment, and with no missing covariates.
Arm/Group Title Placebo - High Stratum Mepolizumab 100 mg - High Stratum
Hide Arm/Group Description:
Participants with blood eosinophil counts >=150 cells/µL at Screening or >=300 cells/µL in the 12 months prior were assigned to the high stratum group. These 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.
Participants with blood eosinophil counts >=150 cells/µL at Screening or >=300 cells/ µL in the 12 months prior were assigned to the high stratum group. These 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.
Overall Number of Participants Analyzed 214 226
Least Squares Mean (Standard Error)
Unit of Measure: Score on SGRQ scale
-3.0  (1.11) -2.8  (1.06)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo - High Stratum, Mepolizumab 100 mg - High Stratum
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.999
Comments Adjusted p-value
Method Mixed Model Repeated Measure Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Mepolizumab - Placebo)
Estimated Value 0.2
Confidence Interval (2-Sided) 95%
-2.8 to 3.2
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.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo - High Stratum, Mepolizumab 100 mg - High Stratum
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.901
Comments Unadjusted p-value
Method Mixed Model Repeated Measure Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Mepolizumab - Placebo)
Estimated Value 0.2
Confidence Interval (2-Sided) 95%
-2.8 to 3.2
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.
6.Secondary Outcome
Title Change From Baseline in Mean COPD Assessment Test (CAT) Score in Participants in the High Stratum
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
mITT-H Population. Participants analyzed represents those with a Baseline and at least one post-Baseline assessment, and with no missing covariates.
Arm/Group Title Placebo - High Stratum Mepolizumab 100 mg - High Stratum
Hide Arm/Group Description:
Participants with blood eosinophil counts >=150 cells/µL at Screening or >=300 cells/µL in the 12 months prior were assigned to the high stratum group. These 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.
Participants with blood eosinophil counts >=150 cells/µL at Screening or >=300 cells/ µL in the 12 months prior were assigned to the high stratum group. These 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.
Overall Number of Participants Analyzed 212 224
Least Squares Mean (Standard Error)
Unit of Measure: Score on CAT scale
0.0  (0.47) -0.8  (0.45)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo - High Stratum, Mepolizumab 100 mg - High Stratum
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.999
Comments Adjusted p-value
Method Mixed Model Repeated Measures Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Mepolizumab - Placebo)
Estimated Value -0.8
Confidence Interval (2-Sided) 95%
-2.0 to 0.5
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.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo - High Stratum, Mepolizumab 100 mg - High Stratum
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.244
Comments Unadjusted p-value
Method Mixed Model Repeated Measures Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Mepolizumab - Placebo)
Estimated Value -0.8
Confidence Interval (2-Sided) 95%
-2.0 to 0.5
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.
7.Secondary Outcome
Title Time to First Moderate/Severe Exacerbation in the mITT Population
Hide Description Kaplan Meier estimates of the probability of a moderate/severe exacerbation are expressed as the percentage of participants with an exacerbation over time (by Week 8, 16, 24, 32, 40, 48, 52). The analysis 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. The strata were combined as pre-specified in the protocol and reporting and analysis plan (RAP).
Time Frame From randomization to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
mITT Population
Arm/Group Title Placebo Mepolizumab 100 mg
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 419 417
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
Week 8
25.1
(21.3 to 29.6)
23.6
(19.8 to 28.0)
Week 16
39.8
(35.2 to 44.6)
37.4
(32.9 to 42.3)
Week 24
49.2
(44.5 to 54.1)
46.3
(41.6 to 51.3)
Week 32
57.3
(52.6 to 62.2)
54.1
(49.3 to 59.0)
Week 40
63.8
(59.1 to 68.5)
59.7
(54.9 to 64.5)
Week 48
67.3
(62.7 to 71.9)
62.5
(57.8 to 67.2)
Week 52
71.2
(66.6 to 75.6)
65.5
(60.7 to 70.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Mepolizumab 100 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.999
Comments Adjusted p-value
Method Cox Proportional Hazards Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard ratio (Mepolizumab/Placebo)
Estimated Value 0.89
Confidence Interval (2-Sided) 95%
0.75 to 1.05
Estimation Comments Analysis performed using a Cox Proportional Hazards Model with covariates of treatment, geographic region, no. moderate/severe exacerbations in previous year, Baseline percent predicted FEV1 and smoking status
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Mepolizumab 100 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.160
Comments Unadjusted p-value
Method Cox Proportional Hazards Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard ratio (Mepolizumab/Placebo)
Estimated Value 0.89
Confidence Interval (2-Sided) 95%
0.75 to 1.05
Estimation Comments Analysis performed using a Cox Proportional Hazards Model with covariates of treatment, geographic region, no. moderate/severe exacerbations in previous year, Baseline percent predicted FEV1 and smoking status
8.Secondary Outcome
Title Rate of COPD Exacerbations Requiring ED Visit and/or Hosp in the mITT Population
Hide Description COPD exacerbations requiring 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. The analysis was performed on mITT Population. The strata were combined as pre-specified in the protocol and reporting and analysis plan (RAP).
Time Frame From randomization to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
mITT Population
Arm/Group Title Placebo Mepolizumab 100 mg
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 419 417
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Exacerbations requiring ED/hosp per year
0.26
(0.21 to 0.33)
0.29
(0.23 to 0.36)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Mepolizumab 100 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.999
Comments Adjusted p-value
Method Negative binomial model
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate ratio (mepolizumab/placebo)
Estimated Value 1.10
Confidence Interval (2-Sided) 95%
0.81 to 1.49
Estimation Comments Analysis using a negative binomial model with covariates of treatment, geographic region, no. moderate/severe exacerbations in previous year, Baseline percent predicted FEV1, smoking status and offset of log (time in on- and off-treatment period).
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Mepolizumab 100 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.556
Comments Unadjusted p-value
Method Negative binomial model
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate ratio (mepolizumab/placebo)
Estimated Value 1.10
Confidence Interval (2-Sided) 95%
0.81 to 1.49
Estimation Comments Analysis using a negative binomial model with covariates of treatment, geographic region, no. moderate/severe exacerbations in previous year, Baseline percent predicted FEV1, smoking status and offset of log (time in on- and off-treatment period).
9.Secondary Outcome
Title Change From Baseline in Mean Total SGRQ Score in the mITT Population
Hide 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 ranges 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. The strata were combined as pre-specified in the protocol and reporting and analysis plan (RAP).
Time Frame Baseline and Week 52
Hide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 396 397
Least Squares Mean (Standard Error)
Unit of Measure: Score on SGRQ scale
-4.0  (0.81) -3.2  (0.80)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Mepolizumab 100 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.999
Comments Adjusted p-value
Method Mixed Model Repeated Measures Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean difference (Mepolizumab - Placebo)
Estimated Value 0.7
Confidence Interval (2-Sided) 95%
-1.5 to 2.9
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.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Mepolizumab 100 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.532
Comments Unadjusted p-value
Method Mixed Model Repeated Measures Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean difference (Mepolizumab - Placebo)
Estimated Value 0.7
Confidence Interval (2-Sided) 95%
-1.5 to 2.9
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.
10.Secondary Outcome
Title Change From Baseline in Mean CAT Score in the mITT Population
Hide 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. Participants with a Baseline and at least one post-Baseline assessment were included in the analysis. Mean change from Baseline in CAT score at Week 52 has been presented. The strata were combined as pre-specified in the protocol and reporting and analysis plan (RAP).
Time Frame Baseline and Week 52
Hide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 392 401
Least Squares Mean (Standard Error)
Unit of Measure: Score on CAT scale
-0.4  (0.35) -1.0  (0.34)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Mepolizumab 100 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.999
Comments Adjusted p-value
Method Mixed Model Repeated Measures Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean difference (Mepolizumab - Placebo)
Estimated Value -0.6
Confidence Interval (2-Sided) 95%
-1.5 to 0.4
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.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Mepolizumab 100 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.252
Comments Unadjusted p-value
Method Mixed Model Repeated Measures Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean difference (Mepolizumab - Placebo)
Estimated Value -0.6
Confidence Interval (2-Sided) 95%
-1.5 to 0.4
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.
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 were reported from start of study treatment until 4 weeks after last dose, up to Week 52.
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 - High Stratum Mepolizumab 100 mg - High Stratum Placebo - Low Stratum Mepolizumab 100 mg - Low Stratum
Hide Arm/Group Description Participants with blood eosinophil counts >=150 cells/µL at Screening or >=300 cells/µL in the 12 months prior were assigned to the high stratum group. These 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. Participants with blood eosinophil counts >=150 cells/µL at Screening or >=300 cells/ µL in the 12 months prior were assigned to the high stratum group. These 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. Participants with blood eosinophil counts <150 cells/µL at Screening and no evidence of blood eosinophil counts >=300 cells/µL in the 12 months prior were assigned to the low stratum group. These 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. Participants with blood eosinophil counts <150 cells/µL at Screening and no evidence of blood eosinophil counts >=300 cells/µL in the 12 months prior were assigned to the low stratum group. These 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.
All-Cause Mortality
Placebo - High Stratum Mepolizumab 100 mg - High Stratum Placebo - Low Stratum Mepolizumab 100 mg - Low Stratum
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   8/229 (3.49%)      6/233 (2.58%)      9/190 (4.74%)      10/184 (5.43%)    
Hide Serious Adverse Events
Placebo - High Stratum Mepolizumab 100 mg - High Stratum Placebo - Low Stratum Mepolizumab 100 mg - Low Stratum
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   80/229 (34.93%)      65/233 (27.90%)      51/190 (26.84%)      50/184 (27.17%)    
Blood and lymphatic system disorders         
Anaemia   2/229 (0.87%)  2 0/233 (0.00%)  0 0/190 (0.00%)  0 0/184 (0.00%)  0
Cardiac disorders         
Atrial fibrillation   2/229 (0.87%)  2 4/233 (1.72%)  5 1/190 (0.53%)  1 0/184 (0.00%)  0
Cardiac failure congestive   3/229 (1.31%)  3 1/233 (0.43%)  1 0/190 (0.00%)  0 3/184 (1.63%)  6
Acute myocardial infarction   1/229 (0.44%)  1 1/233 (0.43%)  1 2/190 (1.05%)  2 1/184 (0.54%)  1
Cardiac failure   1/229 (0.44%)  2 1/233 (0.43%)  1 0/190 (0.00%)  0 1/184 (0.54%)  1
Cardiac arrest   1/229 (0.44%)  1 0/233 (0.00%)  0 0/190 (0.00%)  0 1/184 (0.54%)  1
Cardiac failure chronic   1/229 (0.44%)  1 1/233 (0.43%)  1 0/190 (0.00%)  0 0/184 (0.00%)  0
Myocardial infarction   1/229 (0.44%)  1 1/233 (0.43%)  1 0/190 (0.00%)  0 0/184 (0.00%)  0
Myocardial ischaemia   1/229 (0.44%)  1 1/233 (0.43%)  1 0/190 (0.00%)  0 0/184 (0.00%)  0
Ventricular tachycardia   0/229 (0.00%)  0 0/233 (0.00%)  0 1/190 (0.53%)  1 1/184 (0.54%)  1
Acute coronary syndrome   0/229 (0.00%)  0 1/233 (0.43%)  1 0/190 (0.00%)  0 0/184 (0.00%)  0
Angina pectoris   1/229 (0.44%)  1 0/233 (0.00%)  0 0/190 (0.00%)  0 0/184 (0.00%)  0
Atrial flutter   0/229 (0.00%)  0 0/233 (0.00%)  0 0/190 (0.00%)  0 1/184 (0.54%)  1
Atrioventricular block second degree   0/229 (0.00%)  0 1/233 (0.43%)  1 0/190 (0.00%)  0 0/184 (0.00%)  0
Bundle branch block left   1/229 (0.44%)  1 0/233 (0.00%)  0 0/190 (0.00%)  0 0/184 (0.00%)  0
Cardiac failure acute   0/229 (0.00%)  0 0/233 (0.00%)  0 0/190 (0.00%)  0 1/184 (0.54%)  1
Cardiomyopathy   0/229 (0.00%)  0 0/233 (0.00%)  0 0/190 (0.00%)  0 1/184 (0.54%)  1
Cardiopulmonary failure   0/229 (0.00%)  0 1/233 (0.43%)  1 0/190 (0.00%)  0 0/184 (0.00%)  0
Congestive cardiomyopathy   0/229 (0.00%)  0 0/233 (0.00%)  0 0/190 (0.00%)  0 1/184 (0.54%)  1
Cor pulmonale   0/229 (0.00%)  0 0/233 (0.00%)  0 1/190 (0.53%)  1 0/184 (0.00%)  0
Palpitations   0/229 (0.00%)  0 1/233 (0.43%)  1 0/190 (0.00%)  0 0/184 (0.00%)  0
Pericarditis   0/229 (0.00%)  0 0/233 (0.00%)  0 1/190 (0.53%)  1 0/184 (0.00%)  0
Sinus tachycardia   0/229 (0.00%)  0 1/233 (0.43%)  1 0/190 (0.00%)  0 0/184 (0.00%)  0
Ventricular extrasystoles   0/229 (0.00%)  0 0/233 (0.00%)  0 1/190 (0.53%)  1 0/184 (0.00%)  0
Gastrointestinal disorders         
Gastrointestinal haemorrhage   1/229 (0.44%)  1 0/233 (0.00%)  0 0/190 (0.00%)  0 1/184 (0.54%)  1
Abdominal hernia   0/229 (0.00%)  0 0/233 (0.00%)  0 1/190 (0.53%)  1 0/184 (0.00%)  0
Abdominal pain   0/229 (0.00%)  0 0/233 (0.00%)  0 0/190 (0.00%)  0 1/184 (0.54%)  1
Colitis   1/229 (0.44%)  1 0/233 (0.00%)  0 0/190 (0.00%)  0 0/184 (0.00%)  0
Constipation   0/229 (0.00%)  0 0/233 (0.00%)  0 0/190 (0.00%)  0 1/184 (0.54%)  1
Diverticulum   1/229 (0.44%)  1 0/233 (0.00%)  0 0/190 (0.00%)  0 0/184 (0.00%)  0
Haemorrhoidal haemorrhage   0/229 (0.00%)  0 0/233 (0.00%)  0 0/190 (0.00%)  0 1/184 (0.54%)  1
Haemorrhoids   1/229 (0.44%)  1 0/233 (0.00%)  0 0/190 (0.00%)  0 0/184 (0.00%)  0
Intestinal fistula   0/229 (0.00%)  0 0/233 (0.00%)  0 1/190 (0.53%)  1 0/184 (0.00%)  0
Intestinal haemorrhage   0/229 (0.00%)  0 1/233 (0.43%)  1 0/190 (0.00%)  0 0/184 (0.00%)  0
Intestinal obstruction   0/229 (0.00%)  0 0/233 (0.00%)  0 0/190 (0.00%)  0 1/184 (0.54%)  1
Mallory-Weiss syndrome   0/229 (0.00%)  0 0/233 (0.00%)  0 0/190 (0.00%)  0 1/184 (0.54%)  1
Pancreatitis   0/229 (0.00%)  0 0/233 (0.00%)  0 0/190 (0.00%)  0 1/184 (0.54%)  1
Pancreatitis acute   0/229 (0.00%)  0 1/233 (0.43%)  1 0/190 (0.00%)  0 0/184 (0.00%)  0
Pneumoperitoneum   1/229 (0.44%)  1 0/233 (0.00%)  0 0/190 (0.00%)  0 0/184 (0.00%)  0
Rectal polyp   0/229 (0.00%)  0 1/233 (0.43%)  1 0/190 (0.00%)  0 0/184 (0.00%)  0
Small intestinal obstruction   1/229 (0.44%)  1 0/233 (0.00%)  0 0/190 (0.00%)  0 0/184 (0.00%)  0
General disorders         
Death   1/229 (0.44%)  1 0/233 (0.00%)  0 0/190 (0.00%)  0 0/184 (0.00%)  0
Generalised oedema   0/229 (0.00%)  0 1/233 (0.43%)  1 0/190 (0.00%)  0 0/184 (0.00%)  0
Multiple organ dysfunction syndrome   0/229 (0.00%)  0 0/233 (0.00%)  0 0/190 (0.00%)  0 1/184 (0.54%)  1
Non-cardiac chest pain   1/229 (0.44%)  1 0/233 (0.00%)  0 0/190 (0.00%)  0 0/184 (0.00%)  0
Infections and infestations         
Pneumonia   16/229 (6.99%)  19 12/233 (5.15%)  15 13/190 (6.84%)  15 11/184 (5.98%)  13
Infective exacerbation of chronic obstructive airways disease   1/229 (0.44%)  1 2/233 (0.86%)  2 0/190 (0.00%)  0 1/184 (0.54%)  1
Sepsis   0/229 (0.00%)  0 1/233 (0.43%)  1 1/190 (0.53%)  1 1/184 (0.54%)  1
Urinary tract infection   2/229 (0.87%)  2 0/233 (0.00%)  0 1/190 (0.53%)  1 0/184 (0.00%)  0
Bronchitis   2/229 (0.87%)  2 0/233 (0.00%)  0 0/190 (0.00%)  0 0/184 (0.00%)  0
Cellulitis   1/229 (0.44%)  2 1/233 (0.43%)  1 0/190 (0.00%)  0 0/184 (0.00%)  0
Diverticulitis   0/229 (0.00%)  0 1/233 (0.43%)  1 0/190 (0.00%)  0 1/184 (0.54%)  1
Gastroenteritis   1/229 (0.44%)  1 1/233 (0.43%)  1 0/190 (0.00%)  0 0/184 (0.00%)  0
Lower respiratory tract infection   1/229 (0.44%)  1 0/233 (0.00%)  0 0/190 (0.00%)  0 1/184 (0.54%)  1
Abscess limb   1/229 (0.44%)  1 0/233 (0.00%)  0 0/190 (0.00%)  0 0/184 (0.00%)  0
Appendicitis   0/229 (0.00%)  0 0/233 (0.00%)  0 1/190 (0.53%)  1 0/184 (0.00%)  0
Bronchiolitis   0/229 (0.00%)  0 1/233 (0.43%)  1 0/190 (0.00%)  0 0/184 (0.00%)  0
Clostridium difficile infection   1/229 (0.44%)  1 0/233 (0.00%)  0 0/190 (0.00%)  0 0/184 (0.00%)  0
Cystitis   0/229 (0.00%)  0 1/233 (0.43%)  1 0/190 (0.00%)  0 0/184 (0.00%)  0
Escherichia urinary tract infection   0/229 (0.00%)  0 1/233 (0.43%)  1 0/190 (0.00%)  0 0/184 (0.00%)  0
Influenza   1/229 (0.44%)  1 0/233 (0.00%)  0 0/190 (0.00%)  0 0/184 (0.00%)  0
Klebsiella infection   1/229 (0.44%)  1 0/233 (0.00%)  0 0/190 (0.00%)  0 0/184 (0.00%)  0
Lung infection   0/229 (0.00%)  0 1/233 (0.43%)  1 0/190 (0.00%)  0 0/184 (0.00%)  0
Peritonitis   0/229 (0.00%)  0 1/233 (0.43%)  1 0/190 (0.00%)  0 0/184 (0.00%)  0
Pneumococcal infection   1/229 (0.44%)  1 0/233 (0.00%)  0 0/190 (0.00%)  0 0/184 (0.00%)  0
Pneumonia klebsiella   0/229 (0.00%)  0 1/233 (0.43%)  1 0/190 (0.00%)  0 0/184 (0.00%)  0
Pyelonephritis   1/229 (0.44%)  1 0/233 (0.00%)  0 0/190 (0.00%)  0 0/184 (0.00%)  0
Respiratory tract infection   1/229 (0.44%)  1 0/233 (0.00%)  0 0/190 (0.00%)  0 0/184 (0.00%)  0
Respiratory syncytial virus infection   0/229 (0.00%)  0 1/233 (0.43%)  1 0/190 (0.00%)  0 0/184 (0.00%)  0
Rhinovirus infection   0/229 (0.00%)  0 0/233 (0.00%)  0 0/190 (0.00%)  0 1/184 (0.54%)  1
Salmonellosis   0/229 (0.00%)  0 0/233 (0.00%)  0 1/190 (0.53%)  1 0/184 (0.00%)  0
Staphylococcal sepsis   0/229 (0.00%)  0 0/233 (0.00%)  0 1/190 (0.53%)  1 0/184 (0.00%)  0
Injury, poisoning and procedural complications         
Femur fracture   1/229 (0.44%)  1 0/233 (0.00%)  0 1/190 (0.53%)  1 0/184 (0.00%)  0
Foot fracture   0/229 (0.00%)  0 1/233 (0.43%)  1 1/190 (0.53%)  1 0/184 (0.00%)  0
Contusion   0/229 (0.00%)  0 0/233 (0.00%)  0 1/190 (0.53%)  1 0/184 (0.00%)  0
Facial bones fracture   0/229 (0.00%)  0 0/233 (0.00%)  0 1/190 (0.53%)  2 0/184 (0.00%)  0
Fibula fracture   0/229 (0.00%)  0 0/233 (0.00%)  0 0/190 (0.00%)  0 1/184 (0.54%)  1
Head injury   1/229 (0.44%)  1 0/233 (0.00%)  0 0/190 (0.00%)  0 0/184 (0.00%)  0
Hip fracture   0/229 (0.00%)  0 0/233 (0.00%)  0 1/190 (0.53%)  1 0/184 (0.00%)  0
Injection related reaction   0/229 (0.00%)  0 0/233 (0.00%)  0 1/190 (0.53%)  1 0/184 (0.00%)  0
Jaw fracture   0/229 (0.00%)  0 0/233 (0.00%)  0 1/190 (0.53%)  1 0/184 (0.00%)  0
Laceration   0/229 (0.00%)  0 0/233 (0.00%)  0 1/190 (0.53%)  1 0/184 (0.00%)  0
Meniscus injury   1/229 (0.44%)  1 0/233 (0.00%)  0 0/190 (0.00%)  0 0/184 (0.00%)  0
Periorbital haematoma   0/229 (0.00%)  0 0/233 (0.00%)  0 1/190 (0.53%)  1 0/184 (0.00%)  0
Procedural haemorrhage   1/229 (0.44%)  1 0/233 (0.00%)  0 0/190 (0.00%)  0 0/184 (0.00%)  0
Respiratory fume inhalation disorder   1/229 (0.44%)  1 0/233 (0.00%)  0 0/190 (0.00%)  0 0/184 (0.00%)  0
Spinal fracture   0/229 (0.00%)  0 0/233 (0.00%)  0 1/190 (0.53%)  1 0/184 (0.00%)  0
Thermal burn   1/229 (0.44%)  1 0/233 (0.00%)  0 0/190 (0.00%)  0 0/184 (0.00%)  0
Tibia fracture   0/229 (0.00%)  0 0/233 (0.00%)  0 0/190 (0.00%)  0 1/184 (0.54%)  1
Wound haemorrhage   0/229 (0.00%)  0 0/233 (0.00%)  0 1/190 (0.53%)  1 0/184 (0.00%)  0
Investigations         
Influenza B virus test positive   0/229 (0.00%)  0 0/233 (0.00%)  0 0/190 (0.00%)  0 1/184 (0.54%)  1
Transaminases increased   1/229 (0.44%)  1 0/233 (0.00%)  0 0/190 (0.00%)  0 0/184 (0.00%)  0
Metabolism and nutrition disorders         
Dehydration   1/229 (0.44%)  1 0/233 (0.00%)  0 1/190 (0.53%)  1 0/184 (0.00%)  0
Fluid overload   0/229 (0.00%)  0 0/233 (0.00%)  0 2/190 (1.05%)  2 0/184 (0.00%)  0
Hyponatraemia   1/229 (0.44%)  1 0/233 (0.00%)  0 1/190 (0.53%)  1 0/184 (0.00%)  0
Malnutrition   1/229 (0.44%)  1 0/233 (0.00%)  0 0/190 (0.00%)  0 1/184 (0.54%)  1
Hypercalcaemia   0/229 (0.00%)  0 0/233 (0.00%)  0 1/190 (0.53%)  1 0/184 (0.00%)  0
Hypoglycaemia   1/229 (0.44%)  1 0/233 (0.00%)  0 0/190 (0.00%)  0 0/184 (0.00%)  0
Cholelithiasis   0/229 (0.00%)  0 2/233 (0.86%)  2 1/190 (0.53%)  1 0/184 (0.00%)  0
Cholecystitis acute   0/229 (0.00%)  0 1/233 (0.43%)  1 1/190 (0.53%)  1 0/184 (0.00%)  0
Acute hepatic failure   0/229 (0.00%)  0 0/233 (0.00%)  0 1/190 (0.53%)  1 0/184 (0.00%)  0
Musculoskeletal and connective tissue disorders         
Bursitis   1/229 (0.44%)  1 0/233 (0.00%)  0 1/190 (0.53%)  1 0/184 (0.00%)  0
Arthralgia   0/229 (0.00%)  0 1/233 (0.43%)  1 0/190 (0.00%)  0 0/184 (0.00%)  0
Arthritis   0/229 (0.00%)  0 1/233 (0.43%)  1 0/190 (0.00%)  0 0/184 (0.00%)  0
Lumbar spinal stenosis   0/229 (0.00%)  0 1/233 (0.43%)  1 0/190 (0.00%)  0 0/184 (0.00%)  0
Musculoskeletal chest pain   1/229 (0.44%)  1 0/233 (0.00%)  0 0/190 (0.00%)  0 0/184 (0.00%)  0
Osteonecrosis   0/229 (0.00%)  0 0/233 (0.00%)  0 1/190 (0.53%)  1 0/184 (0.00%)  0
Spinal osteoarthritis   0/229 (0.00%)  0 1/233 (0.43%)  1 0/190 (0.00%)  0 0/184 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Bladder cancer   2/229 (0.87%)  2 0/233 (0.00%)  0 0/190 (0.00%)  0 0/184 (0.00%)  0
Lung adenocarcinoma   1/229 (0.44%)  1 1/233 (0.43%)  1 0/190 (0.00%)  0 0/184 (0.00%)  0
Breast cancer   0/229 (0.00%)  0 1/233 (0.43%)  1 0/190 (0.00%)  0 0/184 (0.00%)  0
Colon cancer   0/229 (0.00%)  0 1/233 (0.43%)  1 0/190 (0.00%)  0 0/184 (0.00%)  0
Laryngeal cancer recurrent   0/229 (0.00%)  0 1/233 (0.43%)  1 0/190 (0.00%)  0 0/184 (0.00%)  0
Lung neoplasm malignant   0/229 (0.00%)  0 0/233 (0.00%)  0 0/190 (0.00%)  0 1/184 (0.54%)  1
Lung adenocarcinoma stage IV   1/229 (0.44%)  1 0/233 (0.00%)  0 0/190 (0.00%)  0 0/184 (0.00%)  0
Non-small cell lung cancer   0/229 (0.00%)  0 1/233 (0.43%)  1 0/190 (0.00%)  0 0/184 (0.00%)  0
Renal neoplasm   1/229 (0.44%)  1 0/233 (0.00%)  0 0/190 (0.00%)  0 0/184 (0.00%)  0
Retinal melanoma   0/229 (0.00%)  0 0/233 (0.00%)  0 0/190 (0.00%)  0 1/184 (0.54%)  1
Small cell lung cancer   0/229 (0.00%)  0 0/233 (0.00%)  0 1/190 (0.53%)  1 0/184 (0.00%)  0
Squamous cell carcinoma of lung   0/229 (0.00%)  0 0/233 (0.00%)  0 1/190 (0.53%)  1 0/184 (0.00%)  0
Squamous cell carcinoma of skin   0/229 (0.00%)  0 0/233 (0.00%)  0 1/190 (0.53%)  1 0/184 (0.00%)  0
T-cell lymphoma   0/229 (0.00%)  0 0/233 (0.00%)  0 1/190 (0.53%)  1 0/184 (0.00%)  0
Nervous system disorders         
Syncope   1/229 (0.44%)  1 1/233 (0.43%)  1 1/190 (0.53%)  1 1/184 (0.54%)  1
Transient ischaemic attack   0/229 (0.00%)  0 1/233 (0.43%)  1 0/190 (0.00%)  0 1/184 (0.54%)  1
Brain injury   0/229 (0.00%)  0 1/233 (0.43%)  1 0/190 (0.00%)  0 0/184 (0.00%)  0
Cerebral haematoma   0/229 (0.00%)  0 0/233 (0.00%)  0 0/190 (0.00%)  0 1/184 (0.54%)  1
Cerebral infarction   0/229 (0.00%)  0 1/233 (0.43%)  1 0/190 (0.00%)  0 0/184 (0.00%)  0
Dizziness   0/229 (0.00%)  0 0/233 (0.00%)  0 1/190 (0.53%)  1 0/184 (0.00%)  0
Generalised tonic-clonic seizure   0/229 (0.00%)  0 0/233 (0.00%)  0 1/190 (0.53%)  1 0/184 (0.00%)  0
Sensory loss   0/229 (0.00%)  0 0/233 (0.00%)  0 0/190 (0.00%)  0 1/184 (0.54%)  1
Product Issues         
Device dislocation   0/229 (0.00%)  0 0/233 (0.00%)  0 1/190 (0.53%)  1 0/184 (0.00%)  0
Psychiatric disorders         
Abnormal behaviour   1/229 (0.44%)  1 0/233 (0.00%)  0 0/190 (0.00%)  0 0/184 (0.00%)  0
Alcohol abuse   1/229 (0.44%)  1 0/233 (0.00%)  0 0/190 (0.00%)  0 0/184 (0.00%)  0
Confusional state   0/229 (0.00%)  0 1/233 (0.43%)  1 0/190 (0.00%)  0 0/184 (0.00%)  0
Personality change due to a general medical condition   1/229 (0.44%)  1 0/233 (0.00%)  0 0/190 (0.00%)  0 0/184 (0.00%)  0
Renal and urinary disorders         
Acute kidney injury   0/229 (0.00%)  0 2/233 (0.86%)  2 0/190 (0.00%)  0 0/184 (0.00%)  0
Renal colic   0/229 (0.00%)  0 1/233 (0.43%)  1 1/190 (0.53%)  1 0/184 (0.00%)  0
Urinary retention   1/229 (0.44%)  1 0/233 (0.00%)  0 0/190 (0.00%)  0 1/184 (0.54%)  1
Acute prerenal failure   0/229 (0.00%)  0/233 (0.00%)  0 0/190 (0.00%)  0 1/184 (0.54%)  1
Anuria   0/229 (0.00%)  0 0/233 (0.00%)  0 0/190 (0.00%)  0 1/184 (0.54%)  1
Bladder dilatation   0/229 (0.00%)  0 1/233 (0.43%)  1 0/190 (0.00%)  0 0/184 (0.00%)  0
Calculus urinary   0/229 (0.00%)  0 1/233 (0.43%)  1 0/190 (0.00%)  0 0/184 (0.00%)  0
Nephrolithiasis   1/229 (0.44%)  1 0/233 (0.00%)  0 0/190 (0.00%)  0 0/184 (0.00%)  0
Renal failure   1/229 (0.44%)  1 0/233 (0.00%)  0 0/190 (0.00%)  0 0/184 (0.00%)  0
Reproductive system and breast disorders         
Benign prostatic hyperplasia   1/229 (0.44%)  1 0/233 (0.00%)  0 0/190 (0.00%)  0 0/184 (0.00%)  0
Respiratory, thoracic and mediastinal disorders         
Chronic obstructive pulmonary disease   43/229 (18.78%)  61 33/233 (14.16%)  59 31/190 (16.32%)  44 31/184 (16.85%)  42
Respiratory failure   5/229 (2.18%)  5 5/233 (2.15%)  5 0/190 (0.00%)  0 1/184 (0.54%)  1
Acute respiratory failure   3/229 (1.31%)  4 2/233 (0.86%)  4 3/190 (1.58%)  3 0/184 (0.00%)  0
Pneumothorax   1/229 (0.44%)  1 1/233 (0.43%)  1 1/190 (0.53%)  1 0/184 (0.00%)  0
Pulmonary embolism   0/229 (0.00%)  0 2/233 (0.86%)  2 0/190 (0.00%)  0 0/184 (0.00%)  0
Alveolitis allergic   0/229 (0.00%)  0 1/233 (0.43%)  1 0/190 (0.00%)  0 0/184 (0.00%)  0
Bronchopneumopathy   1/229 (0.44%)  1 0/233 (0.00%)  0 0/190 (0.00%)  0 0/184 (0.00%)  0
Bronchospasm   0/229 (0.00%)  0 1/233 (0.43%)  1 0/190 (0.00%)  0 0/184 (0.00%)  0
Cough   0/229 (0.00%)  0 0/233 (0.00%)  0 0/190 (0.00%)  0 1/184 (0.54%)  1
Dyspnoea   1/229 (0.44%)  1 0/233 (0.00%)  0 0/190 (0.00%)  0 0/184 (0.00%)  0
Interstitial lung disease   0/229 (0.00%)  0 1/233 (0.43%)  1 0/190 (0.00%)  0 0/184 (0.00%)  0
Organising pneumonia   0/229 (0.00%)  0 0/233 (0.00%)  0 1/190 (0.53%)  1 0/184 (0.00%)  0
Respiratory arrest   0/229 (0.00%)  0 0/233 (0.00%)  0 1/190 (0.53%)  1 0/184 (0.00%)  0
Vascular disorders         
Deep vein thrombosis   1/229 (0.44%)  1 0/233 (0.00%)  0 0/190 (0.00%)  0 0/184 (0.00%)  0
Haematoma   0/229 (0.00%)  0 0/233 (0.00%)  0 1/190 (0.53%)  1 0/184 (0.00%)  0
Hypertension   1/229 (0.44%)  1 0/233 (0.00%)  0 0/190 (0.00%)  0 0/184 (0.00%)  0
Hypotension   0/229 (0.00%)  0 0/233 (0.00%)  0 1/190 (0.53%)  1 0/184 (0.00%)  0
Orthostatic hypotension   1/229 (0.44%)  1 0/233 (0.00%)  0 0/190 (0.00%)  0 0/184 (0.00%)  0
Peripheral ischaemia   0/229 (0.00%)  0 1/233 (0.43%)  1 0/190 (0.00%)  0 0/184 (0.00%)  0
Subclavian vein thrombosis   0/229 (0.00%)  0 1/233 (0.43%)  1 0/190 (0.00%)  0 0/184 (0.00%)  0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 3%
Placebo - High Stratum Mepolizumab 100 mg - High Stratum Placebo - Low Stratum Mepolizumab 100 mg - Low Stratum
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   146/229 (63.76%)      136/233 (58.37%)      116/190 (61.05%)      108/184 (58.70%)    
Gastrointestinal disorders         
Diarrhoea   6/229 (2.62%)  8 10/233 (4.29%)  11 9/190 (4.74%)  17 8/184 (4.35%)  11
Nausea   8/229 (3.49%)  18 6/233 (2.58%)  7 4/190 (2.11%)  6 4/184 (2.17%)  5
Abdominal pain   3/229 (1.31%)  4 4/233 (1.72%)  4 9/190 (4.74%)  9 4/184 (2.17%)  4
Constipation   5/229 (2.18%)  6 5/233 (2.15%)  6 1/190 (0.53%)  1 6/184 (3.26%)  7
General disorders         
Injection site reaction   7/229 (3.06%)  12 7/233 (3.00%)  9 5/190 (2.63%)  6 5/184 (2.72%)  13
Oedema peripheral   5/229 (2.18%)  5 8/233 (3.43%)  9 8/190 (4.21%)  8 1/184 (0.54%)  1
Pyrexia   9/229 (3.93%)  12 7/233 (3.00%)  9 4/190 (2.11%)  6 1/184 (0.54%)  2
Asthenia   8/229 (3.49%)  8 4/233 (1.72%)  4 0/190 (0.00%)  0 3/184 (1.63%)  3
Non-cardiac chest pain   2/229 (0.87%)  2 5/233 (2.15%)  6 6/190 (3.16%)  6 2/184 (1.09%)  2
Influenza like illness   7/229 (3.06%)  8 2/233 (0.86%)  2 2/190 (1.05%)  3 0/184 (0.00%)  0
Infections and infestations         
Nasopharyngitis   32/229 (13.97%)  49 38/233 (16.31%)  50 31/190 (16.32%)  39 26/184 (14.13%)  34
Upper respiratory tract infection   10/229 (4.37%)  10 10/233 (4.29%)  12 11/190 (5.79%)  16 11/184 (5.98%)  13
Influenza   10/229 (4.37%)  13 8/233 (3.43%)  9 13/190 (6.84%)  16 8/184 (4.35%)  12
Sinusitis   7/229 (3.06%)  8 14/233 (6.01%)  16 6/190 (3.16%)  6 5/184 (2.72%)  5
Pharyngitis   12/229 (5.24%)  13 7/233 (3.00%)  9 6/190 (3.16%)  6 5/184 (2.72%)  5
Urinary tract infection   9/229 (3.93%)  12 8/233 (3.43%)  9 4/190 (2.11%)  4 7/184 (3.80%)  8
Oral candidiasis   7/229 (3.06%)  9 8/233 (3.43%)  8 5/190 (2.63%)  6 6/184 (3.26%)  8
Pneumonia   10/229 (4.37%)  11 4/233 (1.72%)  4 2/190 (1.05%)  2 5/184 (2.72%)  5
Bronchitis   7/229 (3.06%)  10 5/233 (2.15%)  6 3/190 (1.58%)  6 4/184 (2.17%)  4
Gastroenteritis   1/229 (0.44%)  1 4/233 (1.72%)  4 5/190 (2.63%)  5 7/184 (3.80%)  7
Conjunctivitis   0/229 (0.00%)  0 3/233 (1.29%)  3 1/190 (0.53%)  1 6/184 (3.26%)  6
Injury, poisoning and procedural complications         
Contusion   3/229 (1.31%)  6 7/233 (3.00%)  7 5/190 (2.63%)  6 5/184 (2.72%)  5
Musculoskeletal and connective tissue disorders         
Back pain   16/229 (6.99%)  17 17/233 (7.30%)  20 15/190 (7.89%)  17 16/184 (8.70%)  19
Pain in extremity   6/229 (2.62%)  15 7/233 (3.00%)  7 10/190 (5.26%)  12 12/184 (6.52%)  12
Arthralgia   8/229 (3.49%)  16 9/233 (3.86%)  11 11/190 (5.79%)  11 4/184 (2.17%)  5
Myalgia   4/229 (1.75%)  8 4/233 (1.72%)  4 7/190 (3.68%)  8 4/184 (2.17%)  5
Musculoskeletal pain   9/229 (3.93%)  10 3/233 (1.29%)  5 3/190 (1.58%)  4 2/184 (1.09%)  2
Muscle spasms   3/229 (1.31%)  3 4/233 (1.72%)  4 7/190 (3.68%)  7 1/184 (0.54%)  1
Cough   9/229 (3.93%)  10 12/233 (5.15%)  17 6/190 (3.16%)  7 9/184 (4.89%)  11
Nervous system disorders         
Headache   31/229 (13.54%)  71 24/233 (10.30%)  36 25/190 (13.16%)  47 18/184 (9.78%)  36
Dizziness   6/229 (2.62%)  6 3/233 (1.29%)  4 11/190 (5.79%)  12 7/184 (3.80%)  9
Respiratory, thoracic and mediastinal disorders         
Oropharyngeal pain   6/229 (2.62%)  7 15/233 (6.44%)  15 12/190 (6.32%)  13 9/184 (4.89%)  12
Chronic obstructive pulmonary disease   7/229 (3.06%)  13 10/233 (4.29%)  15 8/190 (4.21%)  13 10/184 (5.43%)  22
Dyspnoea   8/229 (3.49%)  10 11/233 (4.72%)  15 4/190 (2.11%)  4 6/184 (3.26%)  9
Skin and subcutaneous tissue disorders         
Rash   3/229 (1.31%)  3 7/233 (3.00%)  7 1/190 (0.53%)  1 2/184 (1.09%)  2
Pruritus   1/229 (0.44%)  1 3/233 (1.29%)  3 7/190 (3.68%)  7 0/184 (0.00%)  0
Vascular disorders         
Hypertension   5/229 (2.18%)  5 8/233 (3.43%)  8 3/190 (1.58%)  3 4/184 (2.17%)  4
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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
Layout table for Results Point of Contact information
Name/Title: GSK Response Center
Organization: GlaxoSmithKline
Phone: 866-435-7343
Layout table for additonal information
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT02105948    
Other Study ID Numbers: 117106
First Submitted: April 3, 2014
First Posted: April 7, 2014
Results First Submitted: January 15, 2018
Results First Posted: April 6, 2018
Last Update Posted: August 31, 2018