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Clinical Trial Results:
Study 117113: Mepolizumab vs. Placebo as add-on treatment for frequently exacerbating COPD patients characterized by eosinophil level

Summary
EudraCT number	2013-004297-98
Trial protocol	NL SK DE GB DK RO
Global end of trial date	16 Jan 2017

Results information
Results version number	v1
This version publication date	28 Jan 2018
First version publication date	28 Jan 2018
Other versions	v2

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

117113

ISRCTN number

US NCT number

WHO universal trial number (UTN)

Sponsor organisation name

GlaxoSmithKline

Sponsor organisation address

980 Great West Road, Brentford, Middlesex, United Kingdom,

Public contact

GSK Response Center, GlaxoSmithKline, 1 866-435-7343,

Scientific contact

GSK Response Center, GlaxoSmithKline, 1 866-435-7343,

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

24 May 2017

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

16 Jan 2017

Was the trial ended prematurely?

Main objective of the trial

To evaluate the efficacy and safety of mepolizumab 100 milligrams (mg) and 300 mg subcutaneous (SC) given every 4 weeks compared to placebo on the frequency of moderate and severe exacerbations in chronic obstructive pulmonary disease (COPD) participants at high risk of exacerbations despite the use of optimized standard of care background therapy.

Protection of trial subjects

Not Applicable

Background therapy

Evidence for comparator

Actual start date of recruitment

24 Apr 2014

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Denmark: 23

Country: Number of subjects enrolled

Germany: 93

Country: Number of subjects enrolled

Netherlands: 52

Country: Number of subjects enrolled

United Kingdom: 22

Country: Number of subjects enrolled

Romania: 76

Country: Number of subjects enrolled

Slovakia: 30

Country: Number of subjects enrolled

Ukraine: 32

Country: Number of subjects enrolled

Japan: 40

Country: Number of subjects enrolled

Korea, Republic of: 70

Country: Number of subjects enrolled

Taiwan: 12

Country: Number of subjects enrolled

United States: 79

Country: Number of subjects enrolled

Argentina: 84

Country: Number of subjects enrolled

Chile: 34

Country: Number of subjects enrolled

Australia: 11

Country: Number of subjects enrolled

Canada: 17

Worldwide total number of subjects

675

EEA total number of subjects

296

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

316

From 65 to 84 years

356

85 years and over

Subject disposition

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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 study. Participants were randomized to receive mepolizumab (100 or 300 milligrams [mg]) or placebo by subcutaneous (SC) injection every 4 weeks for 52 week

Screening details

A total of 1071 participants were enrolled of which 59 were pre-screen failures; 337 were screen failures. 674 were randomized and received at least one dose of study treatment and included in the modified intent to treat (mITT) population. One participant randomized to mepolizumab 300 mg was withdrawn without receiving study treatment.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Data analyst, Carer, Assessor

Are arms mutually exclusive

Yes

Placebo

Arm 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.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Placebo was 0.9 percent sodium chloride solution, which was administered as three SC injections every 4 weeks up to 52 weeks along with standard of care therapy.

Mepolizumab 100 mg SC

Arm description

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.

Arm type

Experimental

Investigational medicinal product name

Mepolizumab 100 mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Mepolizumab was available as lyophilized cake which was reconstituted with Sterile water for injection prior to use. Mepolizumab 100 mg was administered as three SC injections given every 4 weeks for up to 52 weeks along with standard of care therapy.

Mepolizumab 300 mg SC

Arm description

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.

Arm type

Experimental

Investigational medicinal product name

Mepolizumab 300 mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Mepolizumab was available as lyophilized cake which was reconstituted with Sterile water for injection prior to use. Mepolizumab 300 mg was administered as three SC injections given every 4 weeks for up to 52 weeks along with standard of care therapy.

Number of subjects in period 1 ^[1]	Placebo	Mepolizumab 100 mg SC	Mepolizumab 300 mg SC
Started	226	223	225
Completed Investigational Product (IP)	170 ^[2]	196 ^[3]	183 ^[4]
Not completed IP	56 ^[5]	27 ^[6]	42 ^[7]
Withdrew IP due to: Adverse event	27 ^[8]	9 ^[9]	25 ^[10]
Withdrew IP due to: stopping criteria	1 ^[11]	1 ^[12]	0 ^[13]
Withdrew IP due to: Lack of efficacy	6 ^[14]	2 ^[15]	2 ^[16]
Withdrew IP due to: Protocol deviation	2 ^[17]	0 ^[18]	1 ^[19]
Withdrew IP due to: Lost to Follow-up	1 ^[20]	1 ^[21]	1 ^[22]
Withdrew IP due to: Physician decision	2 ^[23]	3 ^[24]	1 ^[25]
Withdrew IP due to: Withdrawal by subj.	16 ^[26]	11 ^[27]	11 ^[28]
Withdrew IP due to: site closed	1 ^[29]	0 ^[30]	1 ^[31]
Completed	185	206	195
Not completed	41	17	30
Adverse event, serious fatal	7	4	8
Consent withdrawn by subject	15	7	11
Physician decision	3	3	2
Adverse event, non-fatal	11	3	5
Lost to follow-up	2	-	1
Lack of efficacy	3	-	3

Notes
[1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
Justification: One participant randomized to mepolizumab 300 mg was withdrawn without receiving study treatment.
[2] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: One participant randomized to mepolizumab 300 mg was withdrawn without receiving study treatment.
[3] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: One participant randomized to mepolizumab 300 mg was withdrawn without receiving study treatment.
[4] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: One participant randomized to mepolizumab 300 mg was withdrawn without receiving study treatment.
[5] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: One participant randomized to mepolizumab 300 mg was withdrawn without receiving study treatment.
[6] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: One participant randomized to mepolizumab 300 mg was withdrawn without receiving study treatment.
[7] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: One participant randomized to mepolizumab 300 mg was withdrawn without receiving study treatment.
[8] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: One participant randomized to mepolizumab 300 mg was withdrawn without receiving study treatment.
[9] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: One participant randomized to mepolizumab 300 mg was withdrawn without receiving study treatment.
[10] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: One participant randomized to mepolizumab 300 mg was withdrawn without receiving study treatment.
[11] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: One participant randomized to mepolizumab 300 mg was withdrawn without receiving study treatment.
[12] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: One participant randomized to mepolizumab 300 mg was withdrawn without receiving study treatment.
[13] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: One participant randomized to mepolizumab 300 mg was withdrawn without receiving study treatment.
[14] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: One participant randomized to mepolizumab 300 mg was withdrawn without receiving study treatment.
[15] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: One participant randomized to mepolizumab 300 mg was withdrawn without receiving study treatment.
[16] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: One participant randomized to mepolizumab 300 mg was withdrawn without receiving study treatment.
[17] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: One participant randomized to mepolizumab 300 mg was withdrawn without receiving study treatment.
[18] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: One participant randomized to mepolizumab 300 mg was withdrawn without receiving study treatment.
[19] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: One participant randomized to mepolizumab 300 mg was withdrawn without receiving study treatment.
[20] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: One participant randomized to mepolizumab 300 mg was withdrawn without receiving study treatment.
[21] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: One participant randomized to mepolizumab 300 mg was withdrawn without receiving study treatment.
[22] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: One participant randomized to mepolizumab 300 mg was withdrawn without receiving study treatment.
[23] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: One participant randomized to mepolizumab 300 mg was withdrawn without receiving study treatment.
[24] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: One participant randomized to mepolizumab 300 mg was withdrawn without receiving study treatment.
[25] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: One participant randomized to mepolizumab 300 mg was withdrawn without receiving study treatment.
[26] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: One participant randomized to mepolizumab 300 mg was withdrawn without receiving study treatment.
[27] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: One participant randomized to mepolizumab 300 mg was withdrawn without receiving study treatment.
[28] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: One participant randomized to mepolizumab 300 mg was withdrawn without receiving study treatment.
[29] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: One participant randomized to mepolizumab 300 mg was withdrawn without receiving study treatment.
[30] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: One participant randomized to mepolizumab 300 mg was withdrawn without receiving study treatment.
[31] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: One participant randomized to mepolizumab 300 mg was withdrawn without receiving study treatment.

Baseline characteristics

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Reporting group title

Placebo

Reporting group description

Reporting group title

Mepolizumab 100 mg SC

Reporting group description

Reporting group title

Mepolizumab 300 mg SC

Reporting group description

Reporting group values	Placebo	Mepolizumab 100 mg SC	Mepolizumab 300 mg SC	Total
Number of subjects	226	223	225
Age categorical
Units: Subjects
Age continuous
Units: years
arithmetic mean (standard deviation)	65.8 ± 8.64	64.8 ± 9.06	64.8 ± 8.96	-
Gender categorical
Units: Subjects
Female	70	91	67	228
Male	156	132	158	446
Race/Ethnicity, Customized
Units: Subjects
Asian-Central/South Asian Heritage	0	0	1	1
Asian-East Asian Heritage	25	26	26	77
Asian-Japanese Heritage	14	13	13	40
Asian-South East Asian Heritage	3	2	1	6
Black or African American	2	4	2	8
White-White/Caucasian/European Heritage	182	178	182	542

End points

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Reporting group title

Placebo

Reporting group description

Reporting group title

Mepolizumab 100 mg SC

Reporting group description

Reporting group title

Mepolizumab 300 mg SC

Reporting group description

Primary: Rate of moderate or severe exacerbations

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End point title

Rate of moderate or severe exacerbations

End point 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).

End point type

Primary

End point timeframe

From randomization to Week 52

End point values	Placebo	Mepolizumab 100 mg SC	Mepolizumab 300 mg SC
Number of subjects analysed	226 ^[1]	223 ^[2]	225 ^[3]
Units: Rate per year
number (not applicable)
Rate per year	1.49	1.19	1.27

Notes
[1] - mITT Population
[2] - mITT Population
[3] - mITT Population

Statistical analysis 1

Statistical analysis description

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)

Comparison groups

Mepolizumab 100 mg SC v Placebo

Number of subjects included in analysis

449

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.068 ^[4]

Method

Negative binomial model

Parameter type

Rate ratio (Mepolizumab 100/Placebo)

Point estimate

0.8

Confidence interval

level

95%

sides

2-sided

lower limit

0.65

upper limit

0.98

Notes
[4] - Adjusted p-value; Family wise type I error controlled within each endpoint using a Hochberg testing procedure

Statistical analysis 2

Statistical analysis description

Comparison groups

Mepolizumab 100 mg SC v Placebo

Number of subjects included in analysis

449

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.034 ^[5]

Method

Negative binomial model

Parameter type

Rate ratio (Mepolizumab 100/Placebo)

Point estimate

0.8

Confidence interval

level

95%

sides

2-sided

lower limit

0.65

upper limit

0.98

Notes
[5] - Unadjusted p-value

Statistical analysis 3

Statistical analysis description

Comparison groups

Mepolizumab 300 mg SC v Placebo

Number of subjects included in analysis

451

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.14 ^[6]

Method

Negative binomial model

Parameter type

Rate ratio (Mepolizumab 300/Placebo)

Point estimate

0.86

Confidence interval

level

95%

sides

2-sided

lower limit

0.7

upper limit

1.05

Notes
[6] - Adjusted p-value; Family wise type I error controlled within each endpoint using a Hochberg testing procedure

Statistical analysis 4

Statistical analysis description

Comparison groups

Mepolizumab 300 mg SC v Placebo

Number of subjects included in analysis

451

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.14 ^[7]

Method

Negative binomial model

Parameter type

Rate ratio (Mepolizumab 300/Placebo)

Point estimate

0.86

Confidence interval

level

95%

sides

2-sided

lower limit

0.7

upper limit

1.05

Notes
[7] - Unadjusted p-value

Secondary: Time to first moderate/severe exacerbation

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End point title

Time to first moderate/severe exacerbation

End point 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.

End point type

Secondary

End point timeframe

From randomization to Week 52

End point values	Placebo	Mepolizumab 100 mg SC	Mepolizumab 300 mg SC
Number of subjects analysed	226 ^[8]	223 ^[9]	225 ^[10]
Units: Percentage of participants
number (confidence interval 95%)
Week 8	22.6 (17.7 to 28.6)	22.9 (17.9 to 29.0)	18.3 (13.8 to 24.0)
Week 16	40.7 (34.6 to 47.5)	36.0 (30.0 to 42.6)	29.0 (23.5 to 35.4)
Week 24	51.1 (44.6 to 57.8)	42.4 (36.2 to 49.2)	36.7 (30.8 to 43.4)
Week 32	58.3 (51.8 to 64.9)	46.1 (39.8 to 52.9)	44.9 (38.7 to 51.7)
Week 40	62.3 (55.8 to 68.7)	50.8 (44.4 to 57.6)	51.8 (45.4 to 58.6)
Week 48	64.2 (57.8 to 70.6)	55.5 (49.1 to 62.2)	58.3 (51.9 to 64.9)
Week 52	66.7 (60.2 to 73.1)	57.9 (51.5 to 64.5)	58.8 (52.4 to 65.3)

Notes
[8] - mITT Population
[9] - mITT Population
[10] - mITT Population

Statistical analysis 1

Statistical analysis description

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

Comparison groups

Mepolizumab 100 mg SC v Placebo

Number of subjects included in analysis

449

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.14 ^[11]

Method

Cox Proportional Hazards Model

Parameter type

Hazard Ratio (Mepolizumab 100/Placebo)

Point estimate

0.82

Confidence interval

level

95%

sides

2-sided

lower limit

0.64

upper limit

1.04

Notes
[11] - Adjusted p-value; Family wise type I error controlled within each endpoint using a Hochberg testing procedure

Statistical analysis 2

Statistical analysis description

Comparison groups

Mepolizumab 100 mg SC v Placebo

Number of subjects included in analysis

449

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.103 ^[12]

Method

Cox Proportional Hazards Model

Parameter type

Hazard Ratio (Mepolizumab 100/Placebo)

Point estimate

0.82

Confidence interval

level

95%

sides

2-sided

lower limit

0.64

upper limit

1.04

Notes
[12] - Unadjusted p-value

Statistical analysis 3

Statistical analysis description

Comparison groups

Mepolizumab 300 mg SC v Placebo

Number of subjects included in analysis

451

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.14 ^[13]

Method

Cox Proportional Hazards Model

Parameter type

Hazard Ratio (Mepolizumab 300/Placebo)

Point estimate

0.77

Confidence interval

level

95%

sides

2-sided

lower limit

0.6

upper limit

0.97

Notes
[13] - Adjusted p-value; Family wise type I error controlled within each endpoint using a Hochberg testing procedure

Statistical analysis 4

Statistical analysis description

Comparison groups

Mepolizumab 300 mg SC v Placebo

Number of subjects included in analysis

451

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.03 ^[14]

Method

Cox Proportional Hazards Model

Parameter type

Hazard Ratio (Mepolizumab 300/Placebo)

Point estimate

0.77

Confidence interval

level

95%

sides

2-sided

lower limit

0.6

upper limit

0.97

Notes
[14] - Unadjusted p-value

Secondary: Rate of COPD exacerbations requiring emergency department (ED) visits and/or hospitalizations

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End point title

Rate of COPD exacerbations requiring emergency department (ED) visits and/or hospitalizations

End point description

COPD exacerbations requiring an ED visit and/or hospitalization 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.

End point type

Secondary

End point timeframe

From randomization to Week 52

End point values	Placebo	Mepolizumab 100 mg SC	Mepolizumab 300 mg SC
Number of subjects analysed	226 ^[15]	223 ^[16]	225 ^[17]
Units: Rate per year
number (not applicable)
Rate per year	0.28	0.17	0.23

Notes
[15] - mITT Population
[16] - mITT Population
[17] - mITT Population

Statistical analysis 1

Statistical analysis description

Comparison groups

Placebo v Mepolizumab 100 mg SC

Number of subjects included in analysis

449

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.14 ^[18]

Method

Negative binomial model

Parameter type

Rate ratio (Mepolizumab 100/Placebo)

Point estimate

0.59

Confidence interval

level

95%

sides

2-sided

lower limit

0.35

upper limit

0.98

Notes
[18] - Adjusted p-value; Family wise type I error controlled within each endpoint using a Hochberg testing procedure

Statistical analysis 2

Statistical analysis description

Comparison groups

Placebo v Mepolizumab 100 mg SC

Number of subjects included in analysis

449

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.042 ^[19]

Method

Negative binomial model

Parameter type

Rate ratio (Mepolizumab 100/Placebo)

Point estimate

0.59

Confidence interval

level

95%

sides

2-sided

lower limit

0.35

upper limit

0.98

Notes
[19] - Unadjusted p-value

Statistical analysis 3

Statistical analysis description

Comparison groups

Placebo v Mepolizumab 300 mg SC

Number of subjects included in analysis

451

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.447 ^[20]

Method

Negative binomial model

Parameter type

Rate ratio (Mepolizumab 300/Placebo)

Point estimate

0.83

Confidence interval

level

95%

sides

2-sided

lower limit

0.51

upper limit

1.34

Notes
[20] - Adjusted p-value; Family wise type I error controlled within each endpoint using a Hochberg testing procedure

Statistical analysis 4

Statistical analysis description

Comparison groups

Placebo v Mepolizumab 300 mg SC

Number of subjects included in analysis

451

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.447 ^[21]

Method

Negative binomial model

Parameter type

Rate ratio (Mepolizumab 300/Placebo)

Point estimate

0.83

Confidence interval

level

95%

sides

2-sided

lower limit

0.51

upper limit

1.34

Notes
[21] - Unadjusted p-value

Secondary: Change from Baseline in mean total St. George’s Respiratory Questionnaire (SGRQ) score

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End point title

Change from Baseline in mean total St. George’s Respiratory Questionnaire (SGRQ) score

End point 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. Participants with a Baseline and at least one post-Baseline assessment were included in the analysis. Mean change from Baseline in SGRQ score at Week 52 has been presented.

End point type

Secondary

End point timeframe

Baseline and Week 52

End point values	Placebo	Mepolizumab 100 mg SC	Mepolizumab 300 mg SC
Number of subjects analysed	218 ^[22]	218 ^[23]	219 ^[24]
Units: Total score on SGRQ scale
least squares mean (standard error)
Total score on SGRQ scale	-3.1 ± 0.98	-5.0 ± 0.95	-3.3 ± 0.96

Notes
[22] - mITT Population
[23] - mITT Population
[24] - mITT Population

Statistical analysis 1

Statistical analysis description

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.

Comparison groups

Placebo v Mepolizumab 100 mg SC

Number of subjects included in analysis

436

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.447 ^[25]

Method

Mixed Model Repeated Measures Analysis

Parameter type

Mean difference(Mepolizumab 100-Placebo)

Point estimate

-1.8

Confidence interval

level

95%

sides

2-sided

lower limit

-4.5

upper limit

0.8

Notes
[25] - Adjusted p-value; Family wise type I error controlled within each endpoint using a Hochberg testing procedure

Statistical analysis 2

Statistical analysis description

Comparison groups

Placebo v Mepolizumab 100 mg SC

Number of subjects included in analysis

436

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.18 ^[26]

Method

Mixed Model Repeated Measures Analysis

Parameter type

Mean difference(Mepolizumab 100-Placebo)

Point estimate

-1.8

Confidence interval

level

95%

sides

2-sided

lower limit

-4.5

upper limit

0.8

Notes
[26] - Unadjusted p-value

Statistical analysis 3

Statistical analysis description

Comparison groups

Placebo v Mepolizumab 300 mg SC

Number of subjects included in analysis

437

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.926 ^[27]

Method

Mixed Model Repeated Measures Analysis

Parameter type

Mean difference(Mepolizumab 300-Placebo)

Point estimate

-0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-2.8

upper limit

2.6

Notes
[27] - Adjusted p-value; Family wise type I error controlled within each endpoint using a Hochberg testing procedure

Statistical analysis 4

Statistical analysis description

Comparison groups

Placebo v Mepolizumab 300 mg SC

Number of subjects included in analysis

437

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.926 ^[28]

Method

Mixed Model Repeated Measures Analysis

Parameter type

Mean difference(Mepolizumab 300-Placebo)

Point estimate

-0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-2.8

upper limit

2.6

Notes
[28] - Unadjusted p-value

Secondary: Change from Baseline in Mean COPD assessment test (CAT) score

Top of page

End point title

Change from Baseline in Mean COPD assessment test (CAT) score

End point 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.

End point type

Secondary

End point timeframe

Baseline and Week 52

End point values	Placebo	Mepolizumab 100 mg SC	Mepolizumab 300 mg SC
Number of subjects analysed	222 ^[29]	216 ^[30]	219 ^[31]
Units: Score on CAT scale
least squares mean (standard error)
Score on CAT scale	-0.4 ± 0.42	-1.6 ± 0.42	-0.8 ± 0.42

Notes
[29] - mITT Population
[30] - mITT Population
[31] - mITT Population

Statistical analysis 1

Statistical analysis description

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.

Comparison groups

Mepolizumab 100 mg SC v Placebo

Number of subjects included in analysis

438

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.926 ^[32]

Method

Mixed Model Repeated Measures Analysis

Parameter type

Mean difference(Mepolizumab 100-Placebo)

Point estimate

-1.1

Confidence interval

level

95%

sides

2-sided

lower limit

-2.3

upper limit

Notes
[32] - Adjusted p-value; Family wise type I error controlled within each endpoint using a Hochberg testing procedure

Statistical analysis 2

Statistical analysis description

Comparison groups

Mepolizumab 100 mg SC v Placebo

Number of subjects included in analysis

438

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.055 ^[33]

Method

Mixed Model Repeated Measures Analysis

Parameter type

Mean difference(Mepolizumab 100-Placebo)

Point estimate

-1.1

Confidence interval

level

95%

sides

2-sided

lower limit

-2.3

upper limit

Notes
[33] - Unadjusted p-value

Statistical analysis 3

Statistical analysis description

Comparison groups

Mepolizumab 300 mg SC v Placebo

Number of subjects included in analysis

441

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.926 ^[34]

Method

Mixed Model Repeated Measures Analysis

Parameter type

Mean difference(Mepolizumab 300-Placebo)

Point estimate

-0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.5

upper limit

0.8

Notes
[34] - Adjusted p-value; Family wise type I error controlled within each endpoint using a Hochberg testing procedure

Statistical analysis 4

Statistical analysis description

Comparison groups

Mepolizumab 300 mg SC v Placebo

Number of subjects included in analysis

441

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.547 ^[35]

Method

Mixed Model Repeated Measures Analysis

Parameter type

Mean difference(Mepolizumab 300-Placebo)

Point estimate

-0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.5

upper limit

0.8

Notes
[35] - Unadjusted p-value

Adverse events

Top of page

Timeframe for reporting adverse events

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 additional description

AEs and SAEs were collected in Safety Population which comprised of all randomized participants who received at least one dose of study treatment.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

19.1

Reporting group title

Placebo

Reporting 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.

Reporting group title

Mepolizumab 100 mg SC

Reporting group description

Reporting group title

Mepolizumab 300 mg SC

Reporting group description

Serious adverse events	Placebo	Mepolizumab 100 mg SC	Mepolizumab 300 mg SC
Total subjects affected by serious adverse events
subjects affected / exposed	68 / 226 (30.09%)	57 / 223 (25.56%)	60 / 225 (26.67%)
number of deaths (all causes)	9	4	8
number of deaths resulting from adverse events
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer
subjects affected / exposed	1 / 226 (0.44%)	0 / 223 (0.00%)	2 / 225 (0.89%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Breast cancer
subjects affected / exposed	1 / 226 (0.44%)	1 / 223 (0.45%)	0 / 225 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Non-small cell lung cancer
subjects affected / exposed	1 / 226 (0.44%)	0 / 223 (0.00%)	1 / 225 (0.44%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Adenocarcinoma of colon
subjects affected / exposed	1 / 226 (0.44%)	0 / 223 (0.00%)	0 / 225 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Benign lung neoplasm
subjects affected / exposed	0 / 226 (0.00%)	0 / 223 (0.00%)	1 / 225 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Bowen's disease
subjects affected / exposed	0 / 226 (0.00%)	1 / 223 (0.45%)	0 / 225 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastric cancer
subjects affected / exposed	0 / 226 (0.00%)	1 / 223 (0.45%)	0 / 225 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0
Lung adenocarcinoma
subjects affected / exposed	0 / 226 (0.00%)	0 / 223 (0.00%)	1 / 225 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Lung neoplasm malignant
subjects affected / exposed	0 / 226 (0.00%)	1 / 223 (0.45%)	0 / 225 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0
Malignant melanoma
subjects affected / exposed	1 / 226 (0.44%)	0 / 223 (0.00%)	0 / 225 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Oropharyngeal cancer
subjects affected / exposed	1 / 226 (0.44%)	0 / 223 (0.00%)	0 / 225 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Rectal adenocarcinoma
subjects affected / exposed	0 / 226 (0.00%)	1 / 223 (0.45%)	0 / 225 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Vascular disorders
Aortic aneurysm
subjects affected / exposed	0 / 226 (0.00%)	1 / 223 (0.45%)	0 / 225 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Aortic stenosis
subjects affected / exposed	0 / 226 (0.00%)	1 / 223 (0.45%)	0 / 225 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Essential hypertension
subjects affected / exposed	0 / 226 (0.00%)	1 / 223 (0.45%)	0 / 225 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hypertension
subjects affected / exposed	0 / 226 (0.00%)	1 / 223 (0.45%)	0 / 225 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hypertensive crisis
subjects affected / exposed	1 / 226 (0.44%)	0 / 223 (0.00%)	0 / 225 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hypotension
subjects affected / exposed	0 / 226 (0.00%)	1 / 223 (0.45%)	0 / 225 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Orthostatic hypotension
subjects affected / exposed	0 / 226 (0.00%)	1 / 223 (0.45%)	0 / 225 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Non-cardiac chest pain
subjects affected / exposed	1 / 226 (0.44%)	1 / 223 (0.45%)	0 / 225 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pyrexia
subjects affected / exposed	1 / 226 (0.44%)	0 / 223 (0.00%)	1 / 225 (0.44%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Death
subjects affected / exposed	0 / 226 (0.00%)	0 / 223 (0.00%)	1 / 225 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1
General physical health deterioration
subjects affected / exposed	0 / 226 (0.00%)	0 / 223 (0.00%)	1 / 225 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Vascular stent thrombosis
subjects affected / exposed	0 / 226 (0.00%)	1 / 223 (0.45%)	0 / 225 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Reproductive system and breast disorders
Benign prostatic hyperplasia
subjects affected / exposed	1 / 226 (0.44%)	1 / 223 (0.45%)	0 / 225 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Prostatic obstruction
subjects affected / exposed	1 / 226 (0.44%)	0 / 223 (0.00%)	0 / 225 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
subjects affected / exposed	37 / 226 (16.37%)	25 / 223 (11.21%)	32 / 225 (14.22%)
occurrences causally related to treatment / all	0 / 52	0 / 34	0 / 54
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 2
Acute respiratory failure
subjects affected / exposed	2 / 226 (0.88%)	3 / 223 (1.35%)	0 / 225 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 4	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
Respiratory failure
subjects affected / exposed	1 / 226 (0.44%)	1 / 223 (0.45%)	2 / 225 (0.89%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 2
Pulmonary embolism
subjects affected / exposed	1 / 226 (0.44%)	0 / 223 (0.00%)	2 / 225 (0.89%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pneumothorax
subjects affected / exposed	0 / 226 (0.00%)	0 / 223 (0.00%)	2 / 225 (0.89%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Atelectasis
subjects affected / exposed	1 / 226 (0.44%)	0 / 223 (0.00%)	0 / 225 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Chronic respiratory failure
subjects affected / exposed	1 / 226 (0.44%)	0 / 223 (0.00%)	0 / 225 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hypercapnia
subjects affected / exposed	0 / 226 (0.00%)	1 / 223 (0.45%)	0 / 225 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hypoxia
subjects affected / exposed	0 / 226 (0.00%)	0 / 223 (0.00%)	1 / 225 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Interstitial lung disease
subjects affected / exposed	1 / 226 (0.44%)	0 / 223 (0.00%)	0 / 225 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pleurisy
subjects affected / exposed	0 / 226 (0.00%)	1 / 223 (0.45%)	0 / 225 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pneumonia aspiration
subjects affected / exposed	0 / 226 (0.00%)	1 / 223 (0.45%)	0 / 225 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pneumothorax spontaneous
subjects affected / exposed	1 / 226 (0.44%)	0 / 223 (0.00%)	0 / 225 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
Psychiatric disorders
Confusional state
subjects affected / exposed	0 / 226 (0.00%)	1 / 223 (0.45%)	0 / 225 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Delirium
subjects affected / exposed	0 / 226 (0.00%)	1 / 223 (0.45%)	0 / 225 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Investigations
Haematocrit increased
subjects affected / exposed	1 / 226 (0.44%)	0 / 223 (0.00%)	0 / 225 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Rib fracture
subjects affected / exposed	0 / 226 (0.00%)	1 / 223 (0.45%)	1 / 225 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Clavicle fracture
subjects affected / exposed	0 / 226 (0.00%)	1 / 223 (0.45%)	0 / 225 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Femoral neck fracture
subjects affected / exposed	0 / 226 (0.00%)	1 / 223 (0.45%)	0 / 225 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Foot fracture
subjects affected / exposed	0 / 226 (0.00%)	1 / 223 (0.45%)	0 / 225 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Humerus fracture
subjects affected / exposed	1 / 226 (0.44%)	0 / 223 (0.00%)	0 / 225 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Injection related reaction
subjects affected / exposed	1 / 226 (0.44%)	0 / 223 (0.00%)	0 / 225 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Meniscus injury
subjects affected / exposed	0 / 226 (0.00%)	1 / 223 (0.45%)	0 / 225 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Post procedural haemorrhage
subjects affected / exposed	1 / 226 (0.44%)	0 / 223 (0.00%)	0 / 225 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Spinal compression fracture
subjects affected / exposed	1 / 226 (0.44%)	0 / 223 (0.00%)	0 / 225 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cardiac disorders
Acute myocardial infarction
subjects affected / exposed	3 / 226 (1.33%)	1 / 223 (0.45%)	2 / 225 (0.89%)
occurrences causally related to treatment / all	0 / 3	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 1
Atrial fibrillation
subjects affected / exposed	3 / 226 (1.33%)	3 / 223 (1.35%)	0 / 225 (0.00%)
occurrences causally related to treatment / all	0 / 6	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cardio-respiratory arrest
subjects affected / exposed	0 / 226 (0.00%)	1 / 223 (0.45%)	1 / 225 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 1
Coronary artery disease
subjects affected / exposed	1 / 226 (0.44%)	0 / 223 (0.00%)	1 / 225 (0.44%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Stress cardiomyopathy
subjects affected / exposed	1 / 226 (0.44%)	0 / 223 (0.00%)	1 / 225 (0.44%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Supraventricular tachycardia
subjects affected / exposed	0 / 226 (0.00%)	0 / 223 (0.00%)	2 / 225 (0.89%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Acute coronary syndrome
subjects affected / exposed	0 / 226 (0.00%)	0 / 223 (0.00%)	1 / 225 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Angina pectoris
subjects affected / exposed	0 / 226 (0.00%)	1 / 223 (0.45%)	0 / 225 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Angina unstable
subjects affected / exposed	0 / 226 (0.00%)	1 / 223 (0.45%)	0 / 225 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Arrhythmia
subjects affected / exposed	1 / 226 (0.44%)	0 / 223 (0.00%)	0 / 225 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cardiac arrest
subjects affected / exposed	1 / 226 (0.44%)	0 / 223 (0.00%)	0 / 225 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
Cardiac failure congestive
subjects affected / exposed	0 / 226 (0.00%)	1 / 223 (0.45%)	0 / 225 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cor pulmonale
subjects affected / exposed	0 / 226 (0.00%)	1 / 223 (0.45%)	0 / 225 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Myocardial infarction
subjects affected / exposed	0 / 226 (0.00%)	0 / 223 (0.00%)	1 / 225 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1
Nervous system disorders
Cerebral ischaemia
subjects affected / exposed	0 / 226 (0.00%)	0 / 223 (0.00%)	1 / 225 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cerebrovascular accident
subjects affected / exposed	0 / 226 (0.00%)	1 / 223 (0.45%)	0 / 225 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Haemorrhagic stroke
subjects affected / exposed	1 / 226 (0.44%)	0 / 223 (0.00%)	0 / 225 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
Peroneal nerve palsy
subjects affected / exposed	0 / 226 (0.00%)	1 / 223 (0.45%)	0 / 225 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Post herpetic neuralgia
subjects affected / exposed	0 / 226 (0.00%)	0 / 223 (0.00%)	1 / 225 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Syncope
subjects affected / exposed	0 / 226 (0.00%)	0 / 223 (0.00%)	1 / 225 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Transient ischaemic attack
subjects affected / exposed	1 / 226 (0.44%)	0 / 223 (0.00%)	0 / 225 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Eye disorders
Cataract
subjects affected / exposed	1 / 226 (0.44%)	0 / 223 (0.00%)	1 / 225 (0.44%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Macular fibrosis
subjects affected / exposed	0 / 226 (0.00%)	0 / 223 (0.00%)	1 / 225 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	0 / 226 (0.00%)	3 / 223 (1.35%)	1 / 225 (0.44%)
occurrences causally related to treatment / all	0 / 0	1 / 3	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Abdominal pain
subjects affected / exposed	0 / 226 (0.00%)	1 / 223 (0.45%)	0 / 225 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Diverticulum intestinal
subjects affected / exposed	0 / 226 (0.00%)	1 / 223 (0.45%)	0 / 225 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Duodenal ulcer
subjects affected / exposed	0 / 226 (0.00%)	1 / 223 (0.45%)	0 / 225 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastric haemorrhage
subjects affected / exposed	0 / 226 (0.00%)	0 / 223 (0.00%)	1 / 225 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastritis
subjects affected / exposed	0 / 226 (0.00%)	1 / 223 (0.45%)	0 / 225 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastrointestinal haemorrhage
subjects affected / exposed	1 / 226 (0.44%)	0 / 223 (0.00%)	0 / 225 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
Ileus
subjects affected / exposed	0 / 226 (0.00%)	0 / 223 (0.00%)	1 / 225 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Inguinal hernia
subjects affected / exposed	0 / 226 (0.00%)	0 / 223 (0.00%)	1 / 225 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Large intestine perforation
subjects affected / exposed	0 / 226 (0.00%)	1 / 223 (0.45%)	0 / 225 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Vomiting
subjects affected / exposed	0 / 226 (0.00%)	0 / 223 (0.00%)	1 / 225 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Hepatocellular injury
subjects affected / exposed	1 / 226 (0.44%)	0 / 223 (0.00%)	0 / 225 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Acute kidney injury
subjects affected / exposed	1 / 226 (0.44%)	0 / 223 (0.00%)	0 / 225 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Calculus urinary
subjects affected / exposed	0 / 226 (0.00%)	1 / 223 (0.45%)	0 / 225 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Haematuria
subjects affected / exposed	0 / 226 (0.00%)	1 / 223 (0.45%)	0 / 225 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Renal colic
subjects affected / exposed	0 / 226 (0.00%)	1 / 223 (0.45%)	0 / 225 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Renal tubular necrosis
subjects affected / exposed	0 / 226 (0.00%)	1 / 223 (0.45%)	0 / 225 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Urinary retention
subjects affected / exposed	0 / 226 (0.00%)	1 / 223 (0.45%)	0 / 225 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Endocrine disorders
Inappropriate antidiuretic hormone secretion
subjects affected / exposed	0 / 226 (0.00%)	1 / 223 (0.45%)	0 / 225 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Back pain
subjects affected / exposed	1 / 226 (0.44%)	0 / 223 (0.00%)	0 / 225 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Rhabdomyolysis
subjects affected / exposed	1 / 226 (0.44%)	0 / 223 (0.00%)	0 / 225 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Spinal osteoarthritis
subjects affected / exposed	0 / 226 (0.00%)	1 / 223 (0.45%)	0 / 225 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Spondyloarthropathy
subjects affected / exposed	0 / 226 (0.00%)	1 / 223 (0.45%)	0 / 225 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Infections and infestations
Pneumonia
subjects affected / exposed	18 / 226 (7.96%)	16 / 223 (7.17%)	15 / 225 (6.67%)
occurrences causally related to treatment / all	0 / 19	0 / 21	0 / 16
deaths causally related to treatment / all	0 / 2	0 / 0	0 / 1
Infective exacerbation of chronic obstructive airways disease
subjects affected / exposed	5 / 226 (2.21%)	1 / 223 (0.45%)	3 / 225 (1.33%)
occurrences causally related to treatment / all	0 / 6	0 / 1	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Sepsis
subjects affected / exposed	1 / 226 (0.44%)	3 / 223 (1.35%)	0 / 225 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0
Urinary tract infection
subjects affected / exposed	0 / 226 (0.00%)	3 / 223 (1.35%)	1 / 225 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 3	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Lower respiratory tract infection
subjects affected / exposed	1 / 226 (0.44%)	1 / 223 (0.45%)	1 / 225 (0.44%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Bronchitis
subjects affected / exposed	1 / 226 (0.44%)	0 / 223 (0.00%)	1 / 225 (0.44%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Influenza
subjects affected / exposed	1 / 226 (0.44%)	0 / 223 (0.00%)	1 / 225 (0.44%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pneumonia pseudomonal
subjects affected / exposed	0 / 226 (0.00%)	0 / 223 (0.00%)	2 / 225 (0.89%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Upper respiratory tract infection
subjects affected / exposed	1 / 226 (0.44%)	0 / 223 (0.00%)	1 / 225 (0.44%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Abdominal wall abscess
subjects affected / exposed	0 / 226 (0.00%)	1 / 223 (0.45%)	0 / 225 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Appendicitis
subjects affected / exposed	0 / 226 (0.00%)	1 / 223 (0.45%)	0 / 225 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Atypical mycobacterial infection
subjects affected / exposed	0 / 226 (0.00%)	1 / 223 (0.45%)	0 / 225 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Clostridium difficile colitis
subjects affected / exposed	1 / 226 (0.44%)	0 / 223 (0.00%)	0 / 225 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Colonic abscess
subjects affected / exposed	0 / 226 (0.00%)	1 / 223 (0.45%)	0 / 225 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cystitis
subjects affected / exposed	0 / 226 (0.00%)	1 / 223 (0.45%)	0 / 225 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastrointestinal infection
subjects affected / exposed	1 / 226 (0.44%)	0 / 223 (0.00%)	0 / 225 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Lung abscess
subjects affected / exposed	1 / 226 (0.44%)	0 / 223 (0.00%)	0 / 225 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Orchitis
subjects affected / exposed	0 / 226 (0.00%)	1 / 223 (0.45%)	0 / 225 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Osteomyelitis
subjects affected / exposed	1 / 226 (0.44%)	0 / 223 (0.00%)	0 / 225 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pneumonia bacterial
subjects affected / exposed	0 / 226 (0.00%)	1 / 223 (0.45%)	0 / 225 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pneumonia haemophilus
subjects affected / exposed	1 / 226 (0.44%)	0 / 223 (0.00%)	0 / 225 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pneumonia necrotising
subjects affected / exposed	1 / 226 (0.44%)	0 / 223 (0.00%)	0 / 225 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pneumonia pneumococcal
subjects affected / exposed	0 / 226 (0.00%)	1 / 223 (0.45%)	0 / 225 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pulmonary tuberculosis
subjects affected / exposed	0 / 226 (0.00%)	0 / 223 (0.00%)	1 / 225 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Respiratory tract infection
subjects affected / exposed	0 / 226 (0.00%)	0 / 223 (0.00%)	1 / 225 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Viral infection
subjects affected / exposed	0 / 226 (0.00%)	1 / 223 (0.45%)	0 / 225 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Vulvovaginal mycotic infection
subjects affected / exposed	0 / 226 (0.00%)	1 / 223 (0.45%)	0 / 225 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Diabetes mellitus inadequate control
subjects affected / exposed	0 / 226 (0.00%)	1 / 223 (0.45%)	0 / 225 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 3%

Non-serious adverse events	Placebo	Mepolizumab 100 mg SC	Mepolizumab 300 mg SC
Total subjects affected by non serious adverse events
subjects affected / exposed	137 / 226 (60.62%)	147 / 223 (65.92%)	137 / 225 (60.89%)
Injury, poisoning and procedural complications
Contusion
subjects affected / exposed	2 / 226 (0.88%)	7 / 223 (3.14%)	3 / 225 (1.33%)
occurrences all number	2	7	3
Vascular disorders
Hypertension
subjects affected / exposed	3 / 226 (1.33%)	8 / 223 (3.59%)	7 / 225 (3.11%)
occurrences all number	3	9	7
Nervous system disorders
Headache
subjects affected / exposed	20 / 226 (8.85%)	34 / 223 (15.25%)	22 / 225 (9.78%)
occurrences all number	29	62	39
General disorders and administration site conditions
Injection site reaction
subjects affected / exposed	10 / 226 (4.42%)	6 / 223 (2.69%)	11 / 225 (4.89%)
occurrences all number	17	6	27
Pyrexia
subjects affected / exposed	9 / 226 (3.98%)	6 / 223 (2.69%)	12 / 225 (5.33%)
occurrences all number	9	7	17
Non-cardiac chest pain
subjects affected / exposed	7 / 226 (3.10%)	5 / 223 (2.24%)	7 / 225 (3.11%)
occurrences all number	7	8	8
Fatigue
subjects affected / exposed	4 / 226 (1.77%)	6 / 223 (2.69%)	8 / 225 (3.56%)
occurrences all number	4	6	8
Oedema peripheral
subjects affected / exposed	3 / 226 (1.33%)	7 / 223 (3.14%)	4 / 225 (1.78%)
occurrences all number	3	7	6
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	14 / 226 (6.19%)	13 / 223 (5.83%)	8 / 225 (3.56%)
occurrences all number	14	16	12
Constipation
subjects affected / exposed	10 / 226 (4.42%)	7 / 223 (3.14%)	5 / 225 (2.22%)
occurrences all number	10	8	6
Nausea
subjects affected / exposed	3 / 226 (1.33%)	9 / 223 (4.04%)	9 / 225 (4.00%)
occurrences all number	3	10	13
Abdominal pain upper
subjects affected / exposed	1 / 226 (0.44%)	9 / 223 (4.04%)	5 / 225 (2.22%)
occurrences all number	1	9	5
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	12 / 226 (5.31%)	14 / 223 (6.28%)	16 / 225 (7.11%)
occurrences all number	16	14	22
Dyspnoea
subjects affected / exposed	18 / 226 (7.96%)	12 / 223 (5.38%)	10 / 225 (4.44%)
occurrences all number	19	14	17
Oropharyngeal pain
subjects affected / exposed	4 / 226 (1.77%)	15 / 223 (6.73%)	11 / 225 (4.89%)
occurrences all number	4	15	13
Chronic obstructive pulmonary disease
subjects affected / exposed	5 / 226 (2.21%)	8 / 223 (3.59%)	10 / 225 (4.44%)
occurrences all number	9	12	24
Musculoskeletal and connective tissue disorders
Back pain
subjects affected / exposed	11 / 226 (4.87%)	15 / 223 (6.73%)	17 / 225 (7.56%)
occurrences all number	11	18	21
Arthralgia
subjects affected / exposed	6 / 226 (2.65%)	10 / 223 (4.48%)	6 / 225 (2.67%)
occurrences all number	7	10	6
Pain in extremity
subjects affected / exposed	5 / 226 (2.21%)	7 / 223 (3.14%)	6 / 225 (2.67%)
occurrences all number	6	7	10
Musculoskeletal pain
subjects affected / exposed	2 / 226 (0.88%)	4 / 223 (1.79%)	7 / 225 (3.11%)
occurrences all number	2	4	8
Infections and infestations
Nasopharyngitis
subjects affected / exposed	48 / 226 (21.24%)	39 / 223 (17.49%)	40 / 225 (17.78%)
occurrences all number	65	57	52
Upper respiratory tract infection
subjects affected / exposed	20 / 226 (8.85%)	16 / 223 (7.17%)	12 / 225 (5.33%)
occurrences all number	27	19	15
Pneumonia
subjects affected / exposed	8 / 226 (3.54%)	10 / 223 (4.48%)	10 / 225 (4.44%)
occurrences all number	9	13	11
Bronchitis
subjects affected / exposed	8 / 226 (3.54%)	8 / 223 (3.59%)	11 / 225 (4.89%)
occurrences all number	8	12	15
Sinusitis
subjects affected / exposed	7 / 226 (3.10%)	8 / 223 (3.59%)	7 / 225 (3.11%)
occurrences all number	11	11	9
Influenza
subjects affected / exposed	11 / 226 (4.87%)	6 / 223 (2.69%)	3 / 225 (1.33%)
occurrences all number	11	7	3
Oral candidiasis
subjects affected / exposed	5 / 226 (2.21%)	3 / 223 (1.35%)	8 / 225 (3.56%)
occurrences all number	7	3	9
Rhinitis
subjects affected / exposed	5 / 226 (2.21%)	7 / 223 (3.14%)	4 / 225 (1.78%)
occurrences all number	6	9	4
Urinary tract infection
subjects affected / exposed	7 / 226 (3.10%)	7 / 223 (3.14%)	1 / 225 (0.44%)
occurrences all number	8	8	1

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Were there any global substantial amendments to the protocol? Yes

05 Mar 2014

Amendment No. 1 - Removal of 36-Item Short Form Survey (SF-36) health outcomes endpoint - Removal of electrocardiogram (ECG) at Visit 2 - Update of ECG exclusion and discontinuation criteria - Addition of adverse event causality assessment guidance language - Update of chest x-ray randomization criterion for Germany - Wording edited for consistency and clarification of statements in multiple sections

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical Trial Results:
Study 117113: Mepolizumab vs. Placebo as add-on treatment for frequently exacerbating COPD patients characterized by eosinophil level

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Primary: Rate of moderate or severe exacerbations

Primary: Rate of moderate or severe exacerbations

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Secondary: Time to first moderate/severe exacerbation

Secondary: Rate of COPD exacerbations requiring emergency department (ED) visits and/or hospitalizations

Secondary: Rate of COPD exacerbations requiring emergency department (ED) visits and/or hospitalizations

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Clinical trials

Clinical Trial Results: Study 117113: Mepolizumab vs. Placebo as add-on treatment for frequently exacerbating COPD patients characterized by eosinophil level

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Rate of moderate or severe exacerbations

Primary: Rate of moderate or severe exacerbations

Secondary: Time to first moderate/severe exacerbation

Secondary: Time to first moderate/severe exacerbation

Secondary: Rate of COPD exacerbations requiring emergency department (ED) visits and/or hospitalizations

Secondary: Rate of COPD exacerbations requiring emergency department (ED) visits and/or hospitalizations

Secondary: Change from Baseline in mean total St. George’s Respiratory Questionnaire (SGRQ) score

Secondary: Change from Baseline in mean total St. George’s Respiratory Questionnaire (SGRQ) score

Secondary: Change from Baseline in Mean COPD assessment test (CAT) score

Secondary: Change from Baseline in Mean COPD assessment test (CAT) score

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Substantial protocol amendments (globally)

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Clinical Trial Results:
Study 117113: Mepolizumab vs. Placebo as add-on treatment for frequently exacerbating COPD patients characterized by eosinophil level