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Clinical Trial Results:
A RANDOMISED, DOUBLE-BLIND, PLACEBO CONTROLLED, MULTI-CENTER STUDY TO INVESTIGATE THE USE OF MEPOLIZUMAB (SB-240563) IN REDUCING THE NEED FOR SURGERY IN SUBJECTS WITH SEVERE BILATERAL NASAL POLYPOSIS

Summary
EudraCT number	2008-003772-21
Trial protocol	NL GB BE
Global end of trial date	05 Dec 2014

Results information
Results version number	v1
This version publication date	22 Apr 2016
First version publication date	16 Aug 2015
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

MPP111782

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

09 Jun 2015

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

05 Dec 2014

Was the trial ended prematurely?

Main objective of the trial

• To define the effect of mepolizumab in reducing the need for surgery, defined as reduced endoscopic polyp score and symptom score after six months of dosing.

Protection of trial subjects

Not applicable

Background therapy

Evidence for comparator

Actual start date of recruitment

12 May 2009

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

United Kingdom: 38

Country: Number of subjects enrolled

Belgium: 36

Country: Number of subjects enrolled

Netherlands: 33

Worldwide total number of subjects

107

EEA total number of subjects

107

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)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

At the end of a 10- to 14-day Run-in Period, participants were assessed for entry into the Treatment Period, comprised of 8 outpatient visits. For 6 of these visits, participants received a dose of either 750 milligrams (mg) mepolizumab or placebo. Dosing occured in 4-week intervals.

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

Mepolizumab 750 mg

Arm description

Participants received a total of six doses (one every 4 weeks) of mepolizumab 750 milligrams (mg) by intravenous infusion.

Arm type

Experimental

Investigational medicinal product name

Mepolizumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

750 milligrams (mg) mepolizumab by intravenous (IV) infusion over 30 minutes

Placebo

Arm description

Participants received a total of six doses (one every 4 weeks) of matching placebo by intravenous infusion.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Placebo by IV infusion over 30 minutes

Number of subjects in period 1 ^[1]	Mepolizumab 750 mg	Placebo
Started	54	51
Completed	22	19
Not completed	32	32
Did Not Meet Continuation Criteria	17	11
Consent withdrawn by subject	2	1
Adverse event, non-fatal	3	5
Protocol-defined Stopping Criteria	-	1
Lost to follow-up	-	2
Lack of efficacy	5	11
Protocol deviation	5	1

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: Baseline data are reported for those enrolled participants comprising the Intent-to-Treat Population, defined as randomized participants who received at least one dose of study treatment.

Baseline characteristics

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Reporting group title

Mepolizumab 750 mg

Reporting group description

Participants received a total of six doses (one every 4 weeks) of mepolizumab 750 milligrams (mg) by intravenous infusion.

Reporting group title

Placebo

Reporting group description

Participants received a total of six doses (one every 4 weeks) of matching placebo by intravenous infusion.

Reporting group values	Mepolizumab 750 mg	Placebo	Total
Number of subjects	54	51	105
Age categorical
Units: Subjects
Age continuous
Units: years
arithmetic mean (standard deviation)	50.6 ± 10.73	49.7 ± 10.38	-
Gender categorical
Units: Subjects
Female	13	17	30
Male	41	34	75
Race, Customized
Units: Subjects
Central/South Asian Heritage (Htg)	2	0	2
Japanese/East Asian Heritage/ South East Asian Htg	0	1	1
White	52	50	102

End points

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Reporting group title

Mepolizumab 750 mg

Reporting group description

Participants received a total of six doses (one every 4 weeks) of mepolizumab 750 milligrams (mg) by intravenous infusion.

Reporting group title

Placebo

Reporting group description

Participants received a total of six doses (one every 4 weeks) of matching placebo by intravenous infusion.

Primary: Number of participants with a reduced need for surgery at the end of the study (Week 25)

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End point title

Number of participants with a reduced need for surgery at the end of the study (Week 25)

End point description

Assessment of the nasal polyposis condition was performed after six months of dosing to determine the situation indicative of a reduction in the need for surgery. The components used to determine the need for surgery were endoscopic polyp scores and a severity of condition as measured by a visual analogue scale (VAS). Surgery was still deemed required for a participant with an ENP score of >=3, or an ENP score of 2 and a VAS symptom score of >7. The number of participants with reduced need for polyp surgery are presented as missing data set to non-responders (NR) and missing data last observation carry forward (LOCF). LOCF is defined as missing responses at Week 25 imputed with the last non-missing post-dose observation for that participant. The Per Protocol (PP) Population is comprised of all randomized participants who received at least one dose of study treatment and who complied with the protocol.

End point type

Primary

End point timeframe

Week 25

End point values	Mepolizumab 750 mg	Placebo
Number of subjects analysed	49 ^[1]	51 ^[2]
Units: participants
NR, Responders	16	5
NR, Non-Responders	33	46
LOCF, Responders	17	8
LOCF, Non- Responders	32	43

Notes
[1] - PP Population
[2] - PP Population

Statistical Analysis of NR

Comparison groups

Mepolizumab 750 mg v Placebo

Number of subjects included in analysis

100

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.003

Method

Fisher exact

Confidence interval

Statistical Analysis of LOCF

Comparison groups

Mepolizumab 750 mg v Placebo

Number of subjects included in analysis

100

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.016

Method

Fisher exact

Confidence interval

Secondary: Number of participants with endoscopic nasal polyp (ENP) score dynamics at Screening and Weeks 1, 2, 5, 9, 13, 17, 21, and 25

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End point title

Number of participants with endoscopic nasal polyp (ENP) score dynamics at Screening and Weeks 1, 2, 5, 9, 13, 17, 21, and 25

End point description

Each nostril was assessed for polyps and graded at Screening and at Weeks 1, 2, 5, 9, 13, 17, 21, and 25. The ENP score ranges from 0 (no polyps) to 4, with a higher score indicating a larger polyp. The ENP score was recorded for both the right and the left nostril. The higher of the two scores was derived and used for the analysis. Only those participants available at the specified time points (represented by n=X, X) were analyzed.

End point type

Secondary

End point timeframe

Screening; Weeks 1, 2, 5, 9, 13, 17, 21, and 25

End point values	Mepolizumab 750 mg	Placebo
Number of subjects analysed	49 ^[3]	51 ^[4]
Units: participants
Week 1, ENP score 0, n=49, 51	0	0
Week 1, ENP score 1, n=49, 51	0	0
Week 1, ENP score 2, n=49, 51	0	0
Week 1, ENP score >=3, n=49, 51	49	51
Week 2, ENP score 0, n=48, 51	0	0
Week 2, ENP score 1, n=48, 51	0	0
Week 2, ENP score 2, n=48, 51	1	0
Week 2, ENP score >=3, n=48, 51	47	51
Week 5, ENP score 0, n=49, 48	0	0
Week 5, ENP score 1, n=49, 48	0	0
Week 5, ENP score 2, n=49, 48	8	6
Week 5, ENP score >=3, n=49, 48	41	42
Week 9, ENP score 0, n=49, 45	0	0
Week 9, ENP score 1, n=49, 45	5	0
Week 9, ENP score 2, n=49, 45	8	5
Week 9, ENP score >=3, n=49, 45	36	40
Week 13, ENP score 0, n=44, 37	3	0
Week 13, ENP score 1, n=44, 37	5	0
Week 13, ENP score 2, n=44, 37	5	2
Week 13, ENP score >=3, n=44, 37	31	35
Week 17, ENP score 0, n=43, 34	3	1
Week 17, ENP score 1, n=43, 34	4	1
Week 17, ENP score 2, n=43, 34	7	6
Week 17, ENP score >=3, n=43, 34	29	26
Week 21, ENP score 0, n=42, 34	4	1
Week 21, ENP score 1, n=42, 34	6	2
Week 21, ENP score 2, n=42, 34	5	4
Week 21, ENP score >=3, n=42, 34	27	27
Week 25, ENP score 0, n=41, 31	3	1
Week 25, ENP score 1, n=41, 31	7	2
Week 25, ENP score 2, n=41, 31	7	4
Week 25, ENP score >=3, n=41, 31	24	24

Notes
[3] - PP Population
[4] - PP Population

Week 1

Comparison groups

Mepolizumab 750 mg v Placebo

Number of subjects included in analysis

100

Analysis specification

Pre-specified

Analysis type

other ^[5]

P-value

= 0.708

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

0.74

Confidence interval

level

95%

sides

2-sided

lower limit

0.15

upper limit

3.63

Notes
[5] - ordinal logistic model with random subject effects

Week 2

Comparison groups

Mepolizumab 750 mg v Placebo

Number of subjects included in analysis

100

Analysis specification

Pre-specified

Analysis type

other ^[6]

P-value

= 0.675

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.4

Confidence interval

level

95%

sides

2-sided

lower limit

0.29

upper limit

6.85

Notes
[6] - ordinal logistic model with random subject effects

Week 5

Comparison groups

Mepolizumab 750 mg v Placebo

Number of subjects included in analysis

100

Analysis specification

Pre-specified

Analysis type

other ^[7]

P-value

= 0.943

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

0.95

Confidence interval

level

95%

sides

2-sided

lower limit

0.2

upper limit

4.49

Notes
[7] - ordinal logistic model with random subject effects

Week 9

Comparison groups

Mepolizumab 750 mg v Placebo

Number of subjects included in analysis

100

Analysis specification

Pre-specified

Analysis type

other ^[8]

P-value

= 0.091

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

3.9

Confidence interval

level

95%

sides

2-sided

lower limit

0.8

upper limit

18.94

Notes
[8] - ordinal logistic model with random subject effects

Week 13

Comparison groups

Mepolizumab 750 mg v Placebo

Number of subjects included in analysis

100

Analysis specification

Pre-specified

Analysis type

other ^[9]

P-value

= 0.004

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

11.65

Confidence interval

level

95%

sides

2-sided

lower limit

2.18

upper limit

62.19

Notes
[9] - ordinal logistic model with random subject effects

Week 17

Comparison groups

Mepolizumab 750 mg v Placebo

Number of subjects included in analysis

100

Analysis specification

Pre-specified

Analysis type

other ^[10]

P-value

= 0.223

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.74

Confidence interval

level

95%

sides

2-sided

lower limit

0.54

upper limit

13.9

Notes
[10] - ordinal logistic model with random subject effects

Week 21

Comparison groups

Mepolizumab 750 mg v Placebo

Number of subjects included in analysis

100

Analysis specification

Pre-specified

Analysis type

other ^[11]

P-value

= 0.037

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

5.85

Confidence interval

level

95%

sides

2-sided

lower limit

1.12

upper limit

30.66

Notes
[11] - ordinal logistic model with random subject effects

Week 25

Comparison groups

Mepolizumab 750 mg v Placebo

Number of subjects included in analysis

100

Analysis specification

Pre-specified

Analysis type

other ^[12]

P-value

= 0.047

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

1.03

upper limit

28.42

Notes
[12] - ordinal logistic model with random subject effects

Secondary: Number of participants who required polyp surgery at Weeks 1, 2, 5, 9, 13, 17, 21, and 25

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End point title

Number of participants who required polyp surgery at Weeks 1, 2, 5, 9, 13, 17, 21, and 25

End point description

Assessment of the nasal polyposis condition was performed after 6 months of dosing to determine the situation indicative of a reduction in the need for surgery. The components used to determine the need for surgery were endoscopic polyp scores and a severity of condition as measured by a VAS. Surgery was required for participants with ENP scores of >=3, or ENP scores of 2 and a VAS symptom score of >7.

End point type

Secondary

End point timeframe

Weeks 1, 2, 5, 9, 13, 17, 21, and 25

End point values	Mepolizumab 750 mg	Placebo
Number of subjects analysed	49 ^[13]	51 ^[14]
Units: participants
Week 1	49	51
Week 2	48	51
Week 5	44	49
Week 9	39	48
Week 13	38	50
Week 17	37	46
Week 21	35	46
Week 25	33	46

Notes
[13] - PP Population
[14] - PP Population

No statistical analyses for this end point

Secondary: Mean change from Baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP) at Weeks 2, 5, 9, 13, 21, and 25

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End point title

Mean change from Baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP) at Weeks 2, 5, 9, 13, 21, and 25

End point description

SBP and DBP were measured at Baseline (Week 1) and at Weeks 2, 5, 9, 13, 17, 21, and 25. Baseline is defined as the Week 1 pre-dose assessment. Change from Baseline is defined as the difference between the post-dose post-Baseline visit value and the Baseline value. The Safety Population is comprised of all participants who received at least one dose of study treatment. Only those participants available at the specified time points (represented by n=X, X) were analyzed.

End point type

Secondary

End point timeframe

Baseline and Weeks 2, 5, 9, 13, 17, 21, and 25

End point values	Mepolizumab 750 mg	Placebo
Number of subjects analysed	53 ^[15]	51 ^[16]
Units: millimeters of mercury (mmHg)
arithmetic mean (standard deviation)
SBP, Week 2, n=53, 52	-2 ± 14.14	4.6 ± 13.33
SBP, Week 5, n=53, 49	-1.2 ± 11.74	0.5 ± 10.5
SBP, Week 9, n=51, 46	-0.9 ± 15.01	1 ± 12.84
SBP, Week 13, n=45, 40	-2.9 ± 12.17	0.9 ± 11.97
SBP, Week 17, n=45, 36	-1.9 ± 13.15	0.3 ± 11.72
SBP, Week 21, n=42, 34	-2 ± 14.55	-1.7 ± 12.14
SBP, Week 25, n=42, 32	-2.4 ± 15.47	-1.8 ± 15.39
DBP, Week 2, n=53, 52	-1.3 ± 7.97	-0.9 ± 10.44
DBP, Week 5, n=53, 49	0 ± 8.56	-0.1 ± 7.98
DBP, Week 9, n=51, 46	-1.8 ± 12.05	0 ± 7.29
DBP, Week 13, n=45, 40	-0.6 ± 9.99	-0.5 ± 9.56
DBP, Week 17, n=45, 36	-2.2 ± 8.9	-0.4 ± 9.43
DBP, Week 21, n=42, 34	-0.3 ± 7.95	-1.5 ± 9.32
DBP, Week 25, n=42, 32	-1.5 ± 10.27	-2.2 ± 9.58

Notes
[15] - Safety Population
[16] - Safety Population. Due to a system limitation, n=51 (ITT Pop.) is shown for this arm; however, n=52.

No statistical analyses for this end point

Secondary: Mean change from Baseline in pulse rate at Weeks 2, 5, 9, 13, 17, 21, and 25

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End point title

Mean change from Baseline in pulse rate at Weeks 2, 5, 9, 13, 17, 21, and 25

End point description

Pulse rate was measured at Baseline (Week 1) and at Weeks 2, 5, 9, 13, 17, 21, and 25. Baseline is defined as the Week 1 pre-dose assessment. Change from Baseline is defined as the difference between the post-dose post-Baseline visit value and the Baseline value. Only those participants available at the specified time points (represented by n=X, X) were analyzed.

End point type

Secondary

End point timeframe

Baseline and Weeks 2, 5, 9, 13, 17, 21, and 25

End point values	Mepolizumab 750 mg	Placebo
Number of subjects analysed	53 ^[17]	51 ^[18]
Units: beats per minute
arithmetic mean (standard deviation)
Week 2, n=53, 52	0.2 ± 8.88	0 ± 7.86
Week 5, n=53, 50	-1.1 ± 9.09	-1 ± 7.91
Week 9, n=51, 46	-1.7 ± 8.4	-0.8 ± 7.5
Week 13, n=45, 40	-0.4 ± 11.05	-2.4 ± 9.42
Week 17, n=45, 36	-0.4 ± 9.71	-0.6 ± 9.35
Week 21, n=41, 34	-2 ± 9.56	-1.2 ± 8.7
Week 25, n=41, 32	-0.4 ± 9.29	0 ± 8.29

Notes
[17] - Safety Population
[18] - Safety Population. Due to a system limitation, n=51 (ITT Pop.) is shown for this arm; however, n=52.

No statistical analyses for this end point

Secondary: Number of participants with the indicated electrocardiogram (ECG) findings at Weeks 1, 2, 5, 9, 13, 17, 21, and 25

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End point title

Number of participants with the indicated electrocardiogram (ECG) findings at Weeks 1, 2, 5, 9, 13, 17, 21, and 25

End point description

A single safety 12-lead ECG was performed using a standard 12-lead ECG machine at Weeks 1, 2, 5, 9, 13, 17, 21, and 25. Any abnormal clinically significant (CS) and not clinically significant (NCS) findings were identified. ECG abnormaility with respect to CS and NCS findings were judged by the investigator or appropriately qualified designee. Only those participants available at the specified time points (represented by n=X, X) were analyzed.

End point type

Secondary

End point timeframe

Weeks 1, 2, 5, 9, 13, 17, 21, and 25

End point values	Mepolizumab 750 mg	Placebo
Number of subjects analysed	53 ^[19]	51 ^[20]
Units: participants
Week 1, NCS, n=53, 52	8	8
Week 1, CS, n=53, 52	0	0
Week 2, NCS, n=52, 52	7	9
Week 2, CS, n=52, 52	0	0
Week 5, NCS, n=53, 50	8	8
Week 5, CS, n=53, 50	0	0
Week 9, NCS, n=52, 46	5	3
Week 9, CS, n=52, 46	0	0
Week 13, NCS, n=45, 40	6	4
Week 13, CS, n=45, 40	0	0
Week 17, NCS, n=45, 36	9	4
Week 17, CS, n=45, 36	0	0
Week 21, NCS, n=42, 34	3	1
Week 21, CS, n=42, 34	0	0
Week 25, NCS, n=41, 31	2	3
Week 25, CS, n=41, 31	0	0

Notes
[19] - Safety Population
[20] - Safety Population. Due to a system limitation, n=51 (ITT Pop.) is shown for this arm; however, n=52.

No statistical analyses for this end point

Secondary: Absolute values of clinical chemistry parameters including blood urea nitrogen (BUN), glucose fasting, chloride, sodium, potassium, carbon dioxide, and calcium at Weeks 1, 2, 5, 9, 13, 17, 21, and 25

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End point title

Absolute values of clinical chemistry parameters including blood urea nitrogen (BUN), glucose fasting, chloride, sodium, potassium, carbon dioxide, and calcium at Weeks 1, 2, 5, 9, 13, 17, 21, and 25

End point description

BUN, glucose fasting, chloride, sodium, potassium, carbon dioxide (CO2), and calcium were assessed at Weeks 1, 2, 5, 9, 13, 17, 21, and 25. Only those participants available at the specified time points (represented by n=X, X) were analyzed.

End point type

Secondary

End point timeframe

Weeks 1, 2, 5, 9, 13, 17, 21, and 25

End point values	Mepolizumab 750 mg	Placebo
Number of subjects analysed	53 ^[21]	51 ^[22]
Units: Millimoles per liter (mmol/L)
arithmetic mean (standard deviation)
Calcium, Week 1, pre-dose, n=46, 46	2.33529 ± 0.0792	2.31724 ± 0.08132
Calcium, Week 2, n=53, 52	2.34262 ± 0.07908	2.35237 ± 0.09561
Calcium, Week 5, pre-dose, n=52, 49	2.31874 ± 0.09841	2.34182 ± 0.09948
Calcium, Week 9, pre-dose, n=52, 46	2.31885 ± 0.07624	2.36803 ± 0.18232
Calcium, Week 13, pre-dose, n=44, 40	2.32566 ± 0.07731	2.34848 ± 0.08552
Calcium, Week 17, pre-dose, n=45, 35	2.31207 ± 0.09495	2.3561 ± 0.10049
Calcium, Week 21, pre-dose, n=42, 34	2.30473 ± 0.08874	2.32699 ± 0.10993
Calcium, Week 25, 4 weeks post last dose, n=41, 32	2.31374 ± 0.13942	2.36884 ± 0.08507
Chloride, Week 1, pre-dose, n=50, 51	103.7 ± 2.57	103.8 ± 2.52
Chloride, Week 2, n=50, 51	103.8 ± 2.23	103.5 ± 2.39
Chloride, Week 5, pre-dose, n=51, 49	103.5 ± 3.24	103.6 ± 2.34
Chloride, Week 9, pre-dose, n=51, 44	103.7 ± 2.85	103.6 ± 2.33
Chloride, Week 13, pre-dose, n=45, 40	103.4 ± 2.36	103.2 ± 2.55
Chloride, Week 17, pre-dose, n=45, 34	103.6 ± 2.72	103.4 ± 2.32
Chloride, Week 21, pre-dose, n=42, 34	103.6 ± 2.55	103.4 ± 2.53
Chloride, Week 25, 4 weeks post last dose, n=40,32	103 ± 2.36	103.2 ± 2.73
CO2, Week 1, pre-dose, n=47, 51	27.3 ± 2.38	26.4 ± 2.31
CO2, Week 2, n=50, 50	26.5 ± 2.71	26.4 ± 2.36
CO2, Week 5, pre-dose, n=50, 50	26.4 ± 2.76	26.1 ± 2.66
CO2, Week 9, pre-dose, n=51, 45	27.2 ± 2.63	26.1 ± 2.81
CO2, Week 13, pre-dose, n=45, 38	27.4 ± 2.32	26.4 ± 2.11
CO2, Week 17, pre-dose, n=45, 34	26.4 ± 2.98	26.3 ± 2.31
CO2, Week 21, pre-dose, n=40, 34	27.2 ± 2.05	26.4 ± 2.39
CO2, Week 25, 4 weeks post last dose, n=41, 32	27.2 ± 2.73	27 ± 2.21
Glucose, Week 1, pre-dose, n=49, 51	5.02333 ± 1.06419	4.90943 ± 0.55713
Glucose, Week 2, n=49, 45	5.07525 ± 0.94855	4.85985 ± 0.69818
Glucose, Week 5, pre-dose, n=52, 49	4.97329 ± 0.75574	4.97545 ± 0.68857
Glucose, Week 9, pre-dose, n=50, 44	5.07978 ± 0.82661	5.01449 ± 0.70049
Glucose, Week 13, pre-dose, n=45, 40	5.09957 ± 0.90555	4.95848 ± 0.63337
Glucose, Week 17, pre-dose, n=44, 34	5.19291 ± 1.20604	4.99349 ± 0.65387
Glucose, Week 21, pre-dose, n=40, 33	5.12557 ± 1.14974	5.01559 ± 0.55765
Glucose, Week 25, 4 weeks post last dose, n=40, 31	5.31222 ± 1.55173	5.08589 ± 0.57875
Potassium, Week 1, pre-dose, n=52, 52	4.11 ± 0.352	4.17 ± 0.353
Potassium, Week 2, n=53, 51	4.26 ± 0.345	4.23 ± 0.312
Potassium, Week 5, pre-dose, n=51, 49	4.1 ± 0.42	4.15 ± 0.357
Potassium, Week 9, pre-dose, n=52, 45	4.13 ± 0.364	4.19 ± 0.432
Potassium, Week 13, pre-dose, n=45, 40	4.09 ± 0.325	4.19 ± 0.378
Potassium, Week 17, pre-dose, n=44, 35	4.15 ± 0.389	4.28 ± 0.438
Potassium, Week 21, pre-dose, n=40, 34	4.19 ± 0.428	4.27 ± 0.415
Potassium, Week 25,4 weeks post last dose, n=41,32	4.19 ± 0.404	4.29 ± 0.376
Sodium, Week 1, pre-dose, n=52, 52	141.9 ± 2.15	141.7 ± 2.15
Sodium, Week 2, n=53, 51	142.1 ± 1.95	141.5 ± 2.25
Sodium, Week 5, pre-dose, n=52, 49	141.7 ± 2.16	141.7 ± 1.91
Sodium, Week 9, pre-dose, n=52, 46	142 ± 2.27	141.5 ± 2.3
Sodium, Week 13, pre-dose, n=45, 40	141.8 ± 1.93	141.4 ± 2.47
Sodium, Week 17, pre-dose, n=45, 35	141.6 ± 2.34	141.5 ± 2.15
Sodium, Week 21, pre-dose, n=42, 34	141.5 ± 2.04	141.6 ± 2.48
Sodium, Week 25, 4 weeks post last dose, n=41, 32	141.4 ± 2.11	141.7 ± 2.36
Urea, Week 1, pre-dose, n=51, 51	7.6929 ± 3.6977	7.1568 ± 3.35084
Urea, Week 2, n=52, 52	7.8847 ± 3.86054	7.187 ± 3.81593
Urea, Week 5, pre-dose, n=52, 49	7.9122 ± 3.86267	7.2488 ± 4.02159
Urea, Week 9, pre-dose, n=51, 46	7.5806 ± 3.77958	7.0658 ± 3.40683
Urea, Week 13, pre-dose, n=45, 40	7.4124 ± 3.50688	7.5311 ± 3.68104
Urea, Week 17, pre-dose, n=45, 35	7.3499 ± 3.6194	7.9377 ± 3.595
Urea, Week 21, pre-dose, n=42, 34	7.7361 ± 3.58351	7.2357 ± 3.21507
Urea, Week 25, 4 weeks post last dose, n=41, 32	7.877 ± 3.86299	6.9864 ± 3.01889

Notes
[21] - Safety Population
[22] - Safety Population. Due to a system limitation, n=51 (ITT Pop.) is shown for this arm; however, n=52.

No statistical analyses for this end point

Secondary: Absolute values of the clinical chemistry parameters of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and gamma glutamyltransferase (GGT) at Weeks 1, 2, 5, 9, 13, 17, 21, and 25

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End point title

Absolute values of the clinical chemistry parameters of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and gamma glutamyltransferase (GGT) at Weeks 1, 2, 5, 9, 13, 17, 21, and 25

End point description

ALT, AST, ALP, and GGT were assessed at Weeks 1, 2, 5, 9, 13, 17, 21, and 25. Only those participants available at the specified time points (represented by n=X, X) were analyzed. “99999” indicates that data are not available because either (1) no participants were analyzed for a parameter at a particular time point, or that (2) a standard deviation cannot be calculated because only one participant was analyzed for a parameter at a particular time point.

End point type

Secondary

End point timeframe

Weeks 1, 2, 5, 9, 13, 17, 21, and 25

End point values	Mepolizumab 750 mg	Placebo
Number of subjects analysed	53 ^[23]	51 ^[24]
Units: International units per liter (IU/L)
arithmetic mean (standard deviation)
ALP, Week 1, pre-dose, n=52, 52	76 ± 17.09	67.8 ± 20
ALP, Week 2, n=53, 52	75.3 ± 15.92	69 ± 20.91
ALP, Week 5, pre-dose, n=51, 50	75.1 ± 17.31	68.5 ± 21.84
ALP, Week 9, pre-dose, n=51, 45	75.9 ± 17.63	69.8 ± 20.88
ALP, Week 13, pre-dose, n=45, 40	75.1 ± 16.92	69.7 ± 21.27
ALP, Week 17, pre-dose, n=45, 35	72.5 ± 16.3	69.5 ± 19.58
ALP, Week 21, pre-dose, n=41, 34	72.4 ± 14.75	70.4 ± 21.81
ALP, Week 25, 4 weeks post last dose, n=41, 32	73.9 ± 14.56	72.4 ± 22.05
ALT, Week 1, pre-dose, n=52, 52	27.5 ± 13.33	26.1 ± 14.85
ALT, Week 2, n=53, 51	26.3 ± 11.6	26.9 ± 15.89
ALT, Week 5, pre-dose, n=51, 50	26.5 ± 15.11	25 ± 13.36
ALT, Week 9, pre-dose, n=52, 45	26.4 ± 10.78	24.7 ± 12.41
ALT, Week 13, pre-dose, n=45, 40	29.1 ± 18.21	25.2 ± 11.18
ALT, Week 17, pre-dose, n=45, 35	25.7 ± 11.98	27.1 ± 15.11
ALT, Week 21, pre-dose, n=42, 34	26.2 ± 14.32	27.6 ± 14.02
ALT, Week 25, 4 weeks post last dose, n=41, 32	28.4 ± 15.43	26.4 ± 13.18
AST, Week 1, pre-dose, n=52, 52	24.6 ± 7.73	25.5 ± 9.13
AST, Week 2, n=51, 51	24.2 ± 5.54	24.3 ± 7.51
AST, Week 5, pre-dose, n=51, 50	24.3 ± 6.51	23.6 ± 6.61
AST, Week 9, pre-dose, n=51, 45	24.6 ± 6.06	23.6 ± 5.94
AST, Week 13, pre-dose, n=45, 40	25.4 ± 6.86	23.9 ± 6.04
AST, Week 17, pre-dose, n=44, 34	24 ± 8.34	23.9 ± 6.42
AST, Week 21, pre-dose, n=40, 34	24.5 ± 6.2	23.8 ± 5.18
AST, Week 25, 4 weeks post last dose, n=41, 32	25.1 ± 5.63	24 ± 7.77
GGT, Week 1, pre-dose, n=50, 51	34.4 ± 49.18	26.6 ± 20.37
GGT, Week 2, n=53, 52	32.6 ± 4.31	28.3 ± 24.67
GGT, Week 5, pre-dose, n=50, 50	33.9 ± 59.91	28 ± 25.08
GGT, Week 9, pre-dose, n=50, 44	33.7 ± 41.07	29.5 ± 24.86
GGT, Week 13, pre-dose, n=45, 40	37.2 ± 69.6	29.2 ± 21.56
GGT, Week 17, pre-dose, n=44,34	34.8 ± 57.83	34.6 ± 32.72
GGT, Week 21, pre-dose, n=41, 34	38.6 ± 78.78	32.9 ± 27.27
GGT, Week 25, 4 weeks post last dose, n=41, 32	37 ± 54.09	28.4 ± 17.24

Notes
[23] - Safety Population
[24] - Safety Population. Due to a system limitation, n=51 (ITT Pop.) is shown for this arm; however, n=52.

No statistical analyses for this end point

Secondary: Absolute values of the clinical chemistry parameters of albumin and protein at Weeks 1, 2, 5, 9, 13, 17, 21, and 25

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End point title

Absolute values of the clinical chemistry parameters of albumin and protein at Weeks 1, 2, 5, 9, 13, 17, 21, and 25

End point description

Albumin and protein were assessed at Weeks 1, 2, 5, 9, 13, 17, 21, and 25. Only those participants available at the specified time points (represented by n=X, X) were analyzed.

End point type

Secondary

End point timeframe

Weeks 1, 2, 5, 9, 13, 17, 21, and 25

End point values	Mepolizumab 750 mg	Placebo
Number of subjects analysed	53 ^[25]	51 ^[26]
Units: Grams per liter (g/L)
arithmetic mean (standard deviation)
Albumin, Week 1, pre-dose, n=52, 52	46 ± 3	46.1 ± 2.4
Albumin, Week 2, n=53, 52	45.2 ± 2.74	46.3 ± 3.17
Albumin, Week 5, pre-dose, n=52, 50	45.2 ± 2.46	45.8 ± 2.4
Albumin, Week 9, pre-dose, n=52, 46	45.3 ± 2.71	45.2 ± 2.51
Albumin, Week 13, pre-dose, n=45, 40	45.1 ± 2.26	45.8 ± 2.97
Albumin, Week 17, pre-dose, n=44, 35	44.8 ± 2.45	45.6 ± 2.13
Albumin, Week 21, pre-dose, n=42, 34	45 ± 2.69	45.1 ± 2.81
Albumin, Week 25, 4 weeks post last dose, n=41, 32	45.7 ± 2.55	45.3 ± 2.5
Protein, Week 1, pre-dose, n=50, 48	73.1 ± 5.09	73.7 ± 4.54
Protein, Week 2, n=52, 49	72.4 ± 5.27	73.7 ± 5.3
Protein, Week 5, pre-dose, n=50, 49	72.8 ± 5.33	72.6 ± 4.75
Protein, Week 9, pre-dose, n=51, 46	73 ± 5.39	72.6 ± 4.5
Protein, Week 13, pre-dose, n=44, 40	73.1 ± 4.76	72.8 ± 5.11
Protein, Week 17, pre-dose, n=45, 35	71.3 ± 4.08	72.1 ± 4.26
Protein, Week 21, pre-dose, n=42, 34	71.3 ± 4.3	71.4 ± 3.88
Protein, Week 25, 4 weeks post last dose, n=41, 32	72.1 ± 4.41	71.7 ± 4.53

Notes
[25] - Safety Population
[26] - Safety Population. Due to a system limitation, n=51 (ITT Pop.) is shown for this arm; however, n=52.

No statistical analyses for this end point

Secondary: Absolute values of the clinical chemistry parameters of total and direct bilirubin, creatinine (CRT), and uric acid (UA) at Weeks 1, 2, 5, 9, 13, 17, 21, and 25

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End point title

Absolute values of the clinical chemistry parameters of total and direct bilirubin, creatinine (CRT), and uric acid (UA) at Weeks 1, 2, 5, 9, 13, 17, 21, and 25

End point description

Total and direct bilirubin, creatinine, and uric acid were assessed at Weeks 1, 2, 5, 9, 13, 17, 21, and 25. Only those participants available at the specified time points (represented by n=X, X) were analyzed. “99999” indicates that data are not available because either (1) no participants were analyzed for a parameter at a particular time point, or that (2) a standard deviation cannot be calculated because only one participant was analyzed for a parameter at a particular time point.

End point type

Secondary

End point timeframe

Weeks 1, 2, 5, 9, 13, 17, 21, and 25

End point values	Mepolizumab 750 mg	Placebo
Number of subjects analysed	53 ^[27]	51 ^[28]
Units: Micromoles per liter
arithmetic mean (standard deviation)
UA, Week 1, pre-dose, n=48, 50	6280.75 ± 40503.47	9943.59 ± 47675.43
UA, Week 2, n=49, 49	7734.39 ± 50942.24	10906.56 ± 51211.16
UA, Week 5, pre-dose, n=50, 49	12991.02 ± 65048.95	13352.52 ± 64149.31
UA, Week 9, pre-dose, n=49, 44	13147.62 ± 62976.19	24031.3 ± 90312.49
UA, Week 13, pre-dose, n=45, 40	14802.92 ± 69028.68	25208.07 ± 90067.04
UA, Week 17, pre-dose, n=45, 35	15378.37 ± 70783.69	21723.77 ± 89724.11
UA, Week 21, pre-dose, n=40, 34	10414.21 ± 63827.1	22994.49 ± 94463.05
UA, Week 25, 4 weeks post last dose, n=40, 32	9602.1 ± 58607.26	24506.63 ± 96050.66
CRT, Week 1, pre-dose, n=52, 52	80.2445 ± 15.7113	77.5162 ± 14.87768
CRT, Week 2, n=53, 51	80.545 ± 14.66619	78.362 ± 13.55791
CRT, Week 5, pre-dose, n=52, 49	79.0978 ± 14.80378	77.7282 ± 13.97357
CRT, Week 9, pre-dose, n=52, 46	81.0171 ± 15.27077	75.9868 ± 13.78284
CRT, Week 13, pre-dose, n=45, 40	81.5454 ± 17.47683	77.5522 ± 13.18623
CRT, Week 17, pre-dose, n=45, 35	81.5074 ± 17.96973	76.7809 ± 12.15771
CRT, Week 21, pre-dose, n=42, 34	80.8093 ± 17.58041	75.1511 ± 11.77313
CRT, Week 25,4 weeks post last dose,n=41, 32	81.9687 ± 17.48642	77.7839 ± 12.25219
TB, Week 1, pre-dose, n=52, 52	9.878 ± 3.2705	10.595 ± 6.2074
TB, Week 2, n=53, 52	10.016 ± 4.5747	10.52 ± 4.1684
TB, Week 5, pre-dose, n=51, 50	10.189 ± 4.0635	10.878 ± 4.4865
TB, Week 9, pre-dose, n=51, 45	10.145 ± 3.5212	10.484 ± 4.2254
TB, Week 13, pre-dose, n=45, 40	9.918 ± 3.6143	10.012 ± 5.0501
TB, Week 17, pre-dose, n=44, 35	10.624 ± 4.0522	9.877 ± 4.6822
TB, Week 17, 4-6 months, n=2, 2	7 ± 2.8284	7.775 ± 1.096
TB, Week 21, pre-dose, n=40, 34	10.266 ± 3.6078	10.622 ± 6.0172
TB, Week 25, 4 weeks post last dose, n=41, 32	9.82 ± 3.0792	10.162 ± 6.3294
DB, Week 1, pre-dose, n=50, 50	2.6685 ± 0.91566	2.8818 ± 1.54541
DB, Week 2, n=53, 51	2.916 ± 1.0256	3.069 ± 1.25759
DB, Week 5, pre-dose, n=49, 49	2.7981 ± 0.90148	2.9939 ± 1.12944
DB, Week 9, pre-dose, n=51, 43	2.9203 ± 1.10282	2.9693 ± 1.03703
DB, Week 13, pre-dose, n=43, 40	2.7958 ± 0.82254	3.0299 ± 1.55388
DB, Week 17, pre-dose, n=43, 35	2.9931 ± 0.85581	2.8714 ± 1.18421
DB, Week 17, 4-6 months, n=2, 2	1.9995 ± 0.00071	2.197 ± 0.2786
DB, Week 21, pre-dose, n=39, 34	2.9267 ± 0.98861	3.0561 ± 1.33234
DB, Week 25, 4 weeks post last dose, n=41, 32	3.0011 ± 0.95645	2.9864 ± 1.42919

Notes
[27] - Safety Population
[28] - Safety Population. Due to a system limitation, n=51 (ITT Pop.) is shown for this arm; however, n=52.

No statistical analyses for this end point

Secondary: Absolute values of the hematology parameters of platelet count and white blood cell (WBC) count, basophils, eosinophils, lymphocytes, monocytes, and neutrophils at Weeks 1, 2, 5, 9, 13, 17, 21, and 25

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End point title

Absolute values of the hematology parameters of platelet count and white blood cell (WBC) count, basophils, eosinophils, lymphocytes, monocytes, and neutrophils at Weeks 1, 2, 5, 9, 13, 17, 21, and 25

End point description

Platelet count, WBC count, basophils, eosinophils, lymphocytes, monocytes, and neutrophils were assessed at Weeks 1, 2, 5, 9, 13, 17, 21, and 25.

End point type

Secondary

End point timeframe

Weeks 1, 2, 5, 9, 13, 17, 21, and 25

End point values	Mepolizumab 750 mg	Placebo
Number of subjects analysed	53 ^[29]	51 ^[30]
Units: 10^9 cells per liter
arithmetic mean (standard deviation)
Platelets, Week 1, pre-dose, n=52, 52	246.1 ± 45.91	262.9 ± 53.61
Platelets, Week 2, n=53, 52	250.1 ± 47.25	264.6 ± 56.54
Platelets, Week 5, pre-dose, n=53, 50	240.7 ± 46.67	266.4 ± 61.2
Platelets, Week 9, pre-dose, n=51, 46	239.1 ± 43.29	267 ± 57.64
Platelets, Week 13, pre-dose, n=45, 40	242.7 ± 53.68	273.2 ± 56.18
Platelets, Week 17, pre-dose, n=45, 35	236.4 ± 45.59	270.2 ± 52.58
Platelets, Week 21, pre-dose, n=42, 34	233 ± 44.39	271.2 ± 53.89
Platelet, Week 25, 4 weeks post last dose, n=41,32	242.1 ± 48.64	279.3 ± 60.44
WBC, Week 1, pre-dose, n=52, 52	7.16 ± 1.794	6.81 ± 1.634
WBC, Week 2, n=53, 52	6.2 ± 1.535	6.9 ± 2.014
WBC, Week 5, pre-dose, n=53, 50	6.17 ± 1.58	6.77 ± 1.574
WBC, Week 9, pre-dose, n=51, 46	5.9 ± 1.508	6.92 ± 1.553
WBC, Week 13, pre-dose, n=45, 40	5.93 ± 1.541	7.18 ± 2.095
WBC, Week 17, pre-dose, n=45, 35	6.03 ± 1.78	6.99 ± 1.916
WBC, Week 21, pre-dose, n=42, 34	5.86 ± 1.143	6.92 ± 1.576
WBC, Week 25, 4 weeks post last dose, n=41, 32	5.93 ± 1.357	7 ± 1.922
Basophils, Week 1, pre-dose, n=52, 52	0.05 ± 0.029	0.05 ± 0.026
Basophils, Week 2, n=53, 51	0.03 ± 0.021	0.05 ± 0.026
Basophils, Week 5, pre-dose, n=53, 50	0.02 ± 0.013	0.05 ± 0.032
Basophils, Week 9, pre-dose, n=51, 45	0.03 ± 0.017	0.05 ± 0.028
Basophils, Week 13, pre-dose, n=45, 40	0.03 ± 0.024	0.06 ± 0.082
Basophils, Week 17, pre-dose, n=45, 35	0.03 ± 0.021	0.05 ± 0.027
Basophils, Week 21, pre-dose, n=42, 34	0.03 ± 0.021	0.05 ± 0.041
Basophils, Week 25, 4 weeks post last dose,n=41,32	0.03 ± 0.021	0.05 ± 0.023
Eosinophils, Week 1, pre-dose, n=52, 52	0.063 ± 0.496	0.54 ± 0.305
Eosinophils, Week 2, n=53, 52	0.1 ± 0.079	0.55 ± 0.346
Eosinophils, Week 5, pre-dose, n=53, 50	0.05 ± 0.03	0.051 ± 0.276
Eosinophils, Week 9, pre-dose, n=51, 46	0.04 ± 0.027	0.55 ± 0.392
Eosinophils, Week 13, pre-dose, n=45, 40	0.07 ± 0.196	0.056 ± 0.476
Eosinophils, Week 17, pre-dose, n=45, 35	0.05 ± 0.125	0.45 ± 0.314
Eosinophils, Week 21, pre-dose, n=42, 34	0.04 ± 0.023	0.49 ± 0.411
Eosinophil, Week 25,4 weeks post last dose,n=41,32	0.04 ± 0.029	0.44 ± 0.256
Lymphocytes, Week 1, pre-dose, n=52, 52	1.94 ± 0.568	1.99 ± 0.615
Lymphocytes, Week 2, n=53, 52	1.84 ± 0.531	1.96 ± 0.516
Lymphocytes, Week 5, pre-dose, n=53, 50	1.83 ± 0.635	1.9 ± 0.466
Lymphocytes, Week 9, pre-dose, n=51, 46	1.83 ± 0.596	2.03 ± 0.616
Lymphocytes, Week 13, pre-dose, n=45, 40	1.8 ± 0.457	2.02 ± 0.555
Lymphocytes, Week 17, pre-dose, n=45, 35	1.77 ± 0.466	1.92 ± 0.453
Lymphocytes, Week 21, pre-dose, n=42, 34	1.83 ± 0.541	1.98 ± 0.514
Lymphocyte, Week 25,4 weeks post last dose,n=41, 3	1.88 ± 0.604	1.91 ± 0.523
Monocytes, Week 1, pre-dose, n=52, 51	0.56 ± 0.166	0.5 ± 0.131
Monocytes, Week 2, n=53, 52	0.56 ± 1.75	0.54 ± 0.19
Monocytes, Week 5, pre-dose, n=53, 50	0.53 ± 0.17	0.51 ± 0.138
Monocytes, Week 9, pre-dose, n=51, 46	0.5 ± 0.14	0.53 ± 0.163
Monocytes, Week 13, pre-dose, n=45, 40	0.5 ± 0.188	0.55 ± 0.159
Monocytes, Week 17, pre-dose, n=45, 35	0.51 ± 0.172	0.52 ± 0.142
Monocytes, Week 21, pre-dose, n=42, 34	0.5 ± 0.15	0.55 ± 0.158
Monocytes, Week 25,4 weeks post last dose,n=41, 32	0.51 ± 0.13	0.57 ± 0.201
Neutrophils, Week 1, pre-dose, n=52, 52	3.96481 ± 1.374461	3.72673 ± 1.085727
Neutrophils, Week 2, n=53, 52	3.65642 ± 1.295348	3.80635 ± 1.525888
Neutrophils, Week 5, pre-dose, n=53, 50	3.73509 ± 1.238233	3.7872 ± 1.237163
Neutrophils, Week 9, pre-dose, n=51, 45	3.49333 ± 1.160355	3.76333 ± 1.095441
Neutrophils, Week 13, pre-dose, n=45, 39	3.524 ± 1.287322	3.96169 ± 1.563461
Neutrophils, Week 17, pre-dose, n=45, 35	3.65711 ± 1.624295	4.06657 ± 1.550068
Neutrophils, Week 21, pre-dose, n=42, 34	3.45738 ± 0.907831	3.83824 ± 1.137039
Neutrophil, Week 25,4 weeks post last dose,n=41, 3	3.46854 ± 1.045869	4.03125 ± 1.452175

Notes
[29] - Safety Population
[30] - Safety Population. Due to a system limitation, n=51 (ITT Pop.) is shown for this arm; however, n=52.

No statistical analyses for this end point

Secondary: Absolute values of the hematology parameters of hemoglobin and mean corpuscular hemoglobin concentration (MCHC) at Weeks 1, 2, 5, 9, 13, 17, 21, and 25

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End point title

Absolute values of the hematology parameters of hemoglobin and mean corpuscular hemoglobin concentration (MCHC) at Weeks 1, 2, 5, 9, 13, 17, 21, and 25

End point description

Hemoglobin and MCHC were assessed at Weeks 1, 2, 5, 9, 13, 17, 21, and 25. Only those participants available at the specified time points (represented by n=X, X) were analyzed.

End point type

Secondary

End point timeframe

Weeks 1, 2, 5, 9, 13, 17, 21, and 25

End point values	Mepolizumab 750 mg	Placebo
Number of subjects analysed	53 ^[31]	51 ^[32]
Units: Grams per liter (g/L)
arithmetic mean (standard deviation)
Hemoglobin, Week 1, pre-dose, n=51, 52	148.445 ± 11.5174	145.566 ± 22.1192
Hemoglobin, Week 2, n=53, 52	148.013 ± 12.2563	147.625 ± 11.1436
Hemoglobin, Week 5, pre-dose, n=53, 50	147.955 ± 10.886	146.071 ± 12.7175
Hemoglobin, Week 9, pre-dose, n=51, 46	147.135 ± 11.0248	146.252 ± 12.0539
Hemoglobin, Week 13, pre-dose, n=45, 40	147.498 ± 10.951	147.427 ± 11.9305
Hemoglobin, Week 17, pre-dose, n=45, 35	145.988 ± 11.4327	148.045 ± 12.0595
Hemoglobin, Week 21, pre-dose, n=42, 34	146.597 ± 11.8831	146.953 ± 10.9213
Hemoglobin, Week 25,4 weeks post last dose,n=41, 3	148.927 ± 10.5835	147.94 ± 8.989
MCHC, Week 1, pre-dose, n=52, 51	338.3 ± 8.71	338.6 ± 16.71
MCHC, Week 2, n=52, 52	338.1 ± 10.34	335.2 ± 9.33
MCHC, Week 5, pre-dose, n=53, 50	338.1 ± 7.71	338.6 ± 15.85
MCHC, Week 9, pre-dose, n=51, 46	336.5 ± 10.4	337.7 ± 9.52
MCHC, Week 13, pre-dose, n=44, 40	338.7 ± 9.52	339.6 ± 17.77
MCHC, Week 17, pre-dose, n=45, 35	338.6 ± 9.56	337 ± 10.02
MCHC, Week 21, pre-dose, n=42, 34	338.9 ± 9.35	336.4 ± 9.84
MCHC, Week 25,4 weeks post last dose,n=40, 32	338.9 ± 9.23	339.3 ± 18.86

Notes
[31] - Safety Population
[32] - Safety Population. Due to a system limitation, n=51 (ITT Pop.) is shown for this arm; however, n=52.

No statistical analyses for this end point

Secondary: Absolute values of the hematology parameter of red blood cell (RBC) count and reticulocyte count (RC) at Weeks 1, 2, 5, 9, 13, 17, 21, and 25

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End point title

Absolute values of the hematology parameter of red blood cell (RBC) count and reticulocyte count (RC) at Weeks 1, 2, 5, 9, 13, 17, 21, and 25

End point description

RBC count and RC were assessed at Weeks 1, 2, 5, 9, 13, 17, 21, and 25. Only those participants available at the specified time points (represented by n=X, X) were analyzed.

End point type

Secondary

End point timeframe

Weeks 1, 2, 5, 9, 13, 17, 21, and 25

End point values	Mepolizumab 750 mg	Placebo
Number of subjects analysed	53 ^[33]	51 ^[34]
Units: 10^12 cells per liter
arithmetic mean (standard deviation)
RBC, Week 1, pre-dose, n=52, 52	4.889 ± 0.3758	4.93 ± 0.483
RBC, Week 2, n=53, 52	4.868 ± 0.4024	4.937 ± 0.434
RBC, Week 5, pre-dose, n=53, 50	4.876 ± 0.3494	4.867 ± 0.5115
RBC, Week 9, pre-dose, n=51, 46	4.875 ± 0.3792	4.879 ± 0.4758
RBC, Week 13, pre-dose, n=45, 40	4.889 ± 0.3511	4.923 ± 0.4828
RBC, Week 17, pre-dose, n=45, 35	4.824 ± 0.3735	4.938 ± 0.5058
RBC, Week 21, pre-dose, n=42, 34	4.84 ± 0.3743	4.91 ± 0.5165
RBC, Week 25,4 weeks post last dose,n=41, 32	4.902 ± 0.3551	4.901 ± 0.3343
RC, Week 1, pre-dose, n=28, 32	0.0537 ± 0.01651	0.0495 ± 0.01666
RC, Week 2, n=33, 35	0.0495 ± 0.01682	0.0506 ± 0.01879
RC, Week 5, pre-dose, n=33, 33	0.0461 ± 0.01416	0.0496 ± 0.0253
RC, Week 9, pre-dose, n=29, 29	0.0443 ± 0.01327	0.0513 ± 0.02581
RC, Week 13, pre-dose, n=28, 23	0.0473 ± 0.0153	0.0528 ± 0.0178
RC, Week 17, pre-dose, n=28, 20	0.0482 ± 0.01604	0.0493 ± 0.01847
RC, Week 21, pre-dose, n=26, 19	0.0459 ± 0.01592	0.0521 ± 0.01594
RC, Week 25,4 weeks post last dose,n=24, 20	0.0489 ± 0.0164	0.058 ± 0.02625

Notes
[33] - Safety Population
[34] - Safety Population. Due to a system limitation, n=51 (ITT Pop.) is shown for this arm; however, n=52.

No statistical analyses for this end point

Secondary: Absolute values of the hematology parameter of mean corpuscular hemoglobin (MCH) at Weeks 1, 2, 5, 9, 13, 17, 21, and 25

Top of page

End point title

Absolute values of the hematology parameter of mean corpuscular hemoglobin (MCH) at Weeks 1, 2, 5, 9, 13, 17, 21, and 25

End point description

MCH was assessed at Weeks 1, 2, 5, 9, 13, 17, 21, and 25. Only those participants available at the specified time points (represented by n=X, X) were analyzed.

End point type

Secondary

End point timeframe

Weeks 1, 2, 5, 9, 13, 17, 21, and 25

End point values	Mepolizumab 750 mg	Placebo
Number of subjects analysed	53 ^[35]	51 ^[36]
Units: Picograms (pg)
arithmetic mean (standard deviation)
Week 1, pre-dose, n=52, 51	30.44 ± 1.215	30.26 ± 1.804
Week 2, n=52, 52	30.46 ± 1.359	29.94 ± 1.631
Week 5, pre-dose, n=53, 50	30.37 ± 1.301	30.1 ± 1.686
Week 9, pre-dose, n=51, 46	30.23 ± 1.378	30.07 ± 1.793
Week 13, pre-dose, n=44, 40	30.22 ± 1.292	29.94 ± 2.187
Week 17, pre-dose, n=45, 35	30.29 ± 1.339	30.1 ± 1.951
Week 21, pre-dose, n=42, 34	30.33 ± 1.354	30 ± 2.035
Week 25,4 weeks post last dose,n=40, 32	30.41 ± 1.196	30.26 ± 1.243

Notes
[35] - Safety Population
[36] - Safety Population. Due to a system limitation, n=51 (ITT Pop.) is shown for this arm; however, n=52.

No statistical analyses for this end point

Secondary: Absolute values of the hematology parameter of mean corpuscular volume (MCV) at Weeks 1, 2, 5, 9, 13, 17, 21, and 25

Top of page

End point title

Absolute values of the hematology parameter of mean corpuscular volume (MCV) at Weeks 1, 2, 5, 9, 13, 17, 21, and 25

End point description

MCV was assessed at Weeks 1, 2, 5, 9, 13, 17, 21, and 25. Only those participants available at the specified time points (represented by n=X, X) were analyzed.

End point type

Secondary

End point timeframe

Weeks 1, 2, 5, 9, 13, 17, 21, and 25

End point values	Mepolizumab 750 mg	Placebo
Number of subjects analysed	53 ^[37]	51 ^[38]
Units: Femtoliters
arithmetic mean (standard deviation)
Week 1, pre-dose, n=52, 52	90.04 ± 3.85	89.43 ± 5.051
Week 2, n=53, 52	90.06 ± 3.997	89.41 ± 4.765
Week 5, pre-dose, n=53, 50	89.85 ± 3.911	89.38 ± 4.876
Week 9, pre-dose, n=51, 46	89.81 ± 3.897	89.07 ± 5.019
Week 13, pre-dose, n=45, 40	89.19 ± 3.934	89.12 ± 5.358
Week 17, pre-dose, n=45, 35	89.5 ± 3.714	89.33 ± 5.469
Week 21, pre-dose, n=42, 34	89.46 ± 3.673	89.23 ± 5.542
Week 25,4 weeks post last dose, n=41, 32	89.68 ± 3.364	89.91 ± 3.831

Notes
[37] - Safety Population
[38] - Safety Population. Due to a system limitation, n=51 (ITT Pop.) is shown for this arm; however, n=52.

No statistical analyses for this end point

Secondary: Absolute value of the hematology parameter of reticulocyte count/erythrocyte uncorrected at Weeks 1, 2, 5, 9, 13, 17, 21, and 25

Top of page

End point title

Absolute value of the hematology parameter of reticulocyte count/erythrocyte uncorrected at Weeks 1, 2, 5, 9, 13, 17, 21, and 25

End point description

Reticulocyte count was assessed at Weeks 1, 2, 5, 9, 13, 17, 21, and 25. Only those participants available at the specified time points (represented by n=X, X) were analyzed.

End point type

Secondary

End point timeframe

Weeks 1, 2, 5, 9, 13, 17, 21, and 25

End point values	Mepolizumab 750 mg	Placebo
Number of subjects analysed	19 ^[39]	16 ^[40]
Units: Fraction of 1
arithmetic mean (standard deviation)
Week 1, pre-dose, n=19, 16	0.1723 ± 0.16091	0.1053 ± 0.0575
Week 2, n=19, 16	0.171 ± 0.15032	0.1271 ± 0.09305
Week 5, pre-dose, n=19, 16	0.1731 ± 0.16016	0.1464 ± 0.13471
Week 9, pre-dose, n=18, 16	0.1556 ± 0.12224	0.1299 ± 0.10015
Week 13, pre-dose, n=15, 16	0.1483 ± 0.12563	0.1324 ± 0.10103
Week 17, pre-dose, n=15, 14	0.1645 ± 0.17438	0.1423 ± 0.13603
Week 21, pre-dose, n=15, 13	0.1446 ± 0.1135	0.1395 ± 0.11754
Week 25,4 weeks post last dose, n=15, 12	0.1465 ± 0.12045	0.1402 ± 0.0966

Notes
[39] - Safety Population
[40] - Safety Population

No statistical analyses for this end point

Secondary: Number of participants with positive urinalysis results at Weeks 1, 2, 5, 9, 13, 17, 21, and 25

Top of page

End point title

Number of participants with positive urinalysis results at Weeks 1, 2, 5, 9, 13, 17, 21, and 25

End point description

Specific gravity, power of hydrogen (pH), glucose, protein, blood, and ketones were assessed at Weeks 1, 2, 5, 9, 13, 17, 21, and 25. Data was not summarized for this outcome measure.

End point type

Secondary

End point timeframe

Weeks 1, 2, 5, 9, 13, 17, 21, and 25

End point values	Mepolizumab 750 mg	Placebo
Number of subjects analysed	0 ^[41]	0 ^[42]
Units: participants

Notes
[41] - Safety Population
[42] - Safety Population

No statistical analyses for this end point

Secondary: Number of participants with any treatment-emergent adverse event (AE) and serious adverse event (SAE)

Top of page

End point title

Number of participants with any treatment-emergent adverse event (AE) and serious adverse event (SAE)

End point description

An AE is defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, is an important medical event that jeopardizes the participants or may require medical or surgical intervention to prevent one of the other outcomes listed in the above definition, or is associated with liver injury and impaired liver function.

End point type

Secondary

End point timeframe

Up to Week 25

End point values	Mepolizumab 750 mg	Placebo
Number of subjects analysed	53 ^[43]	51 ^[44]
Units: participants
Any AE	41	42
Any SAE	0	0

Notes
[43] - Safety Population
[44] - Safety Population. Due to a system limitation, n=51 (ITT Pop.) is shown for this arm; however, n=52.

No statistical analyses for this end point

Secondary: Mean of the forced expiratory volume in 1 second (FEV1) at Weeks 2, 5, 9, 13, 17, 21, and 25

Top of page

End point title

Mean of the forced expiratory volume in 1 second (FEV1) at Weeks 2, 5, 9, 13, 17, 21, and 25

End point description

FEV1 is defined as the volume of air forcefully expelled from the lungs in one second. FEV1 measurements were taken by spirometry at each clinic visit. FEV1 was calculated as the maximum of three readings taken at each time point for each participant. Spirometry data is plotted and analyzed using a repeated measures model to calculate treatment difference, confidence intervals and p-values. Only those participants available at the specified time points (represented by n=X, X) were analyzed.

End point type

Secondary

End point timeframe

Weeks 2, 5, 9, 13, 17, 21, and 25

End point values	Mepolizumab 750 mg	Placebo
Number of subjects analysed	54 ^[45]	51 ^[46]
Units: Liters (L)
least squares mean (confidence interval 95%)
Week 2, n=54, 51	3.24 (3.14 to 3.35)	3.2 (3.1 to 3.31)
Week 5, n=54, 49	3.33 (3.23 to 3.44)	3.28 (3.17 to 3.39)
Week 9, n=47, 44	3.32 (3.19 to 3.45)	3.23 (3.09 to 3.37)
Week 13, n=44, 37	3.35 (3.23 to 3.47)	3.18 (3.06 to 3.31)
Week 17, n=43, 34	3.33 (3.18 to 3.48)	3.12 (2.96 to 3.28)
Week 21, n=42, 32	3.41 (3.27 to 3.54)	3.18 (3.04 to 3.33)
Week 25, n=42, 32	3.35 (3.23 to 3.47)	3.18 (3.05 to 3.32)

Notes
[45] - ITT Population: all randomized participants who received at least one dose of study treatment
[46] - ITT Population: all randomized participants who received at least one dose of study treatment

Week 2

Comparison groups

Placebo v Mepolizumab 750 mg

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

other ^[47]

P-value

= 0.567

Method

repeated measures model

Parameter type

Mean difference (final values)

Point estimate

0.04

Confidence interval

level

95%

sides

2-sided

lower limit

-0.1

upper limit

0.19

Notes
[47] - repeated measures model

Week 5

Comparison groups

Mepolizumab 750 mg v Placebo

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

other ^[48]

P-value

= 0.495

Method

repeated measures model

Parameter type

Mean difference (final values)

Point estimate

0.05

Confidence interval

level

95%

sides

2-sided

lower limit

-0.1

upper limit

0.21

Notes
[48] - repeated measures model

Week 9

Comparison groups

Mepolizumab 750 mg v Placebo

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

other ^[49]

P-value

= 0.365

Method

repeated measures model

Parameter type

Mean difference (final values)

Point estimate

0.09

Confidence interval

level

95%

sides

2-sided

lower limit

-0.1

upper limit

0.28

Notes
[49] - repeated measures model

Week 13

Comparison groups

Mepolizumab 750 mg v Placebo

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

other ^[50]

P-value

= 0.058

Method

repeated measures model

Parameter type

Mean difference (final values)

Point estimate

0.17

Confidence interval

level

95%

sides

2-sided

lower limit

-0.01

upper limit

0.34

Notes
[50] - repeated measures model

Week 17

Comparison groups

Mepolizumab 750 mg v Placebo

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

other ^[51]

P-value

= 0.056

Method

repeated measures model

Parameter type

Mean difference (final values)

Point estimate

0.21

Confidence interval

level

95%

sides

2-sided

lower limit

-0.01

upper limit

0.43

Notes
[51] - repeated measures model

Week 21

Comparison groups

Mepolizumab 750 mg v Placebo

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

other ^[52]

P-value

= 0.028

Method

repeated measures model

Parameter type

Mean difference (final values)

Point estimate

0.23

Confidence interval

level

95%

sides

2-sided

lower limit

0.03

upper limit

0.42

Notes
[52] - repeated measures model

Week 25

Comparison groups

Mepolizumab 750 mg v Placebo

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

other ^[53]

P-value

= 0.077

Method

repeated measures model

Parameter type

Mean difference (final values)

Point estimate

0.16

Confidence interval

level

95%

sides

2-sided

lower limit

-0.02

upper limit

0.34

Notes
[53] - repeated measures model

Secondary: Mean of forced vital capacity (FVC) at Weeks 1, 2, 5, 9, 13, 17, 21, and 25

Top of page

End point title

Mean of forced vital capacity (FVC) at Weeks 1, 2, 5, 9, 13, 17, 21, and 25

End point description

FVC is defined as the maximum amount of air that can forcibly be blown out after a maximum inspiration. FVC was calculated as the maximum of three readings taken at each time point for each participant. Spirometry data are plotted and analyzed using a repeated measures model to calculate treatment difference, confidence intervals and p-values. Only those participants available at the specified time points (represented by n=X, X) were analyzed.

End point type

Secondary

End point timeframe

Weeks 1, 2, 5, 9, 13, 17, 21, and 25

End point values	Mepolizumab 750 mg	Placebo
Number of subjects analysed	54 ^[54]	51 ^[55]
Units: Liters
least squares mean (confidence interval 95%)
Week 2, n=54, 51	4.51 (4.39 to 4.62)	4.45 (4.34 to 4.56)
Week 5, n=54, 49	4.55 (4.45 to 4.66)	4.49 (4.38 to 4.6)
Week 9, n=47, 44	4.52 (4.38 to 4.66)	4.46 (4.32 to 4.6)
Week 13, n=44, 37	4.62 (4.49 to 4.75)	4.43 (4.28 to 4.57)
Week 17, n=43, 34	4.59 (4.43 to 4.74)	4.37 (4.19 to 4.54)
Week 21, n=42, 32	4.66 (4.51 to 4.81)	4.38 (4.22 to 4.55)
Week 25, n=42, 32	4.59 (4.45 to 4.74)	4.41 (4.25 to 4.57)

Notes
[54] - ITT Population
[55] - ITT Population

Week 2

Comparison groups

Mepolizumab 750 mg v Placebo

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

other ^[56]

P-value

= 0.486

Method

repeated measures model

Parameter type

Mean difference (final values)

Point estimate

0.06

Confidence interval

level

95%

sides

2-sided

lower limit

-0.1

upper limit

0.22

Notes
[56] - repeated measures model

Week 5

Comparison groups

Mepolizumab 750 mg v Placebo

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

other ^[57]

P-value

= 0.384

Method

repeated measures model

Parameter type

Mean difference (final values)

Point estimate

0.07

Confidence interval

level

95%

sides

2-sided

lower limit

-0.08

upper limit

0.22

Notes
[57] - repeated measures model

Week 9

Comparison groups

Mepolizumab 750 mg v Placebo

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

other ^[58]

P-value

= 0.546

Method

repeated measures model

Parameter type

Mean difference (final values)

Point estimate

0.06

Confidence interval

level

95%

sides

2-sided

lower limit

-0.14

upper limit

0.26

Notes
[58] - repeated measures model

Week 13

Comparison groups

Mepolizumab 750 mg v Placebo

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

other ^[59]

P-value

= 0.05

Method

repeated measures model

Parameter type

Mean difference (final values)

Point estimate

0.2

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

0.39

Notes
[59] - repeated measures model

Week 17

Comparison groups

Mepolizumab 750 mg v Placebo

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

other ^[60]

P-value

= 0.061

Method

repeated measures model

Parameter type

Mean difference (final values)

Point estimate

0.22

Confidence interval

level

95%

sides

2-sided

lower limit

-0.01

upper limit

0.45

Notes
[60] - repeated measures model

Week 21

Comparison groups

Mepolizumab 750 mg v Placebo

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

other ^[61]

P-value

= 0.016

Method

repeated measures model

Parameter type

Mean difference (final values)

Point estimate

0.28

Confidence interval

level

95%

sides

2-sided

lower limit

0.05

upper limit

0.51

Notes
[61] - repeated measures model

Week 25

Comparison groups

Mepolizumab 750 mg v Placebo

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

other ^[62]

P-value

= 0.094

Method

repeated measures model

Parameter type

Mean difference (final values)

Point estimate

0.18

Confidence interval

level

95%

sides

2-sided

lower limit

-0.03

upper limit

0.4

Notes
[62] - repeated measures model

Secondary: Mean peak expiratory flow rate (PEFR) at indicated Weeks 1, 2, 5, 9, 13, 17, 21, and 25

Top of page

End point title

Mean peak expiratory flow rate (PEFR) at indicated Weeks 1, 2, 5, 9, 13, 17, 21, and 25

End point description

PEFR is defined as the maximum airflow generated during a forced expiration beginning with the lungs fully inflated. PEFR was calculated as the maximum of three readings taken at each time point for each participant. Spirometry data is plotted and analyzed using a repeated measures model to calculate treatment difference, confidence intervals and p-values. Only those participants available at the specified time points (represented by n=X, X) were analyzed.

End point type

Secondary

End point timeframe

Weeks 1, 2, 5, 9, 13, 17, 21, and 25

End point values	Mepolizumab 750 mg	Placebo
Number of subjects analysed	54 ^[63]	51 ^[64]
Units: Liters/minute (L/min)
least squares mean (confidence interval 95%)
Week 2, n=54, 51	481.05 (462.19 to 511.95)	467.7 (449.78 to 485.63)
Week 5, n=54, 49	472.81 (455.37 to 490.25)	474.53 (453.61 to 495.45)
Week 9, n=47, 45	489.08 (469.08 to 509.07)	478.16 (452.57 to 503.75)
Week 13, n=44, 37	487.07 (470.85 to 517.23)	470.81 (445.97 to 495.65)
Week 17, n=43, 34	494.04 (467.67 to 519.69)	455.52 (427.15 to 483.89)
Week 21, n=42, 32	493.68 (476.83 to 526.93)	463.17 (435.53 to 490.81)
Week 25, n=42, 32	501.88 (454.31 to 507.79)	466.93 (437.33 to 496.52)

Notes
[63] - ITT Population
[64] - ITT Population

Week 2

Comparison groups

Mepolizumab 750 mg v Placebo

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

other ^[65]

P-value

= 0.686

Method

repeated measures model

Parameter type

Mean difference (final values)

Point estimate

5.11

Confidence interval

level

95%

sides

2-sided

lower limit

-19.91

upper limit

30.12

Notes
[65] - repeated measures model

Week 5

Comparison groups

Mepolizumab 750 mg v Placebo

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

other ^[66]

P-value

= 0.321

Method

repeated measures model

Parameter type

Mean difference (final values)

Point estimate

14.55

Confidence interval

level

95%

sides

2-sided

lower limit

-14.4

upper limit

43.5

Notes
[66] - repeated measures model

Week 9

Comparison groups

Mepolizumab 750 mg v Placebo

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

other ^[67]

P-value

= 0.622

Method

repeated measures model

Parameter type

Mean difference (final values)

Point estimate

8.91

Confidence interval

level

95%

sides

2-sided

lower limit

-26.79

upper limit

44.6

Notes
[67] - repeated measures model

Week 13

Comparison groups

Placebo v Mepolizumab 750 mg

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

other ^[68]

P-value

= 0.178

Method

repeated measures model

Parameter type

Mean difference (final values)

Point estimate

23.24

Confidence interval

level

95%

sides

2-sided

lower limit

-10.75

upper limit

57.22

Notes
[68] - repeated measures model

Week 17

Comparison groups

Mepolizumab 750 mg v Placebo

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

other ^[69]

P-value

= 0.052

Method

repeated measures model

Parameter type

Mean difference (final values)

Point estimate

38.16

Confidence interval

level

95%

sides

2-sided

lower limit

-0.33

upper limit

76.66

Notes
[69] - repeated measures model

Week 21

Comparison groups

Mepolizumab 750 mg v Placebo

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

other ^[70]

P-value

= 0.042

Method

repeated measures model

Parameter type

Mean difference (final values)

Point estimate

38.72

Confidence interval

level

95%

sides

2-sided

lower limit

1.41

upper limit

76.02

Notes
[70] - repeated measures model

Week 25

Comparison groups

Mepolizumab 750 mg v Placebo

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

other ^[71]

P-value

= 0.484

Method

repeated measures model

Parameter type

Mean difference (final values)

Point estimate

14.13

Confidence interval

level

95%

sides

2-sided

lower limit

-25.76

upper limit

54.02

Notes
[71] - repeated measures model

Secondary: Individual symptoms visual analogue scale (VAS) scores at Weeks 1, 2, 5, 9, 13, 17, 21, and 25

Top of page

End point title

Individual symptoms visual analogue scale (VAS) scores at Weeks 1, 2, 5, 9, 13, 17, 21, and 25

End point description

Participants were asked to indicate on a VAS (0 to 10 centimeters) the severity of four nasal polyposis symptoms (one VAS for each symptom): rhinorrhea; mucus in the throat; nasal blockage; loss of smell. The left-hand side of the scale (0) represents “not troublesome,” and the right hand side of the scale (10) represents “worst possible troublesome." Only those participants available at the specified time points (represented by n=X, X) were analyzed.

End point type

Secondary

End point timeframe

Weeks 1, 2, 5, 9, 13, 17, 21, and 25

End point values	Mepolizumab 750 mg	Placebo
Number of subjects analysed	49 ^[72]	51 ^[73]
Units: Scores on a scale
arithmetic mean (standard deviation)
Nasal Polyposis, Week 1, n=49, 51	8.51 ± 0.928	8.64 ± 1.101
Nasal Polyposis, Week 2, n=49, 51	7.91 ± 1.766	8.47 ± 1.326
Nasal Polyposis, Week 5, n=49, 49	7.1 ± 2.31	7.75 ± 2.083
Nasal Polyposis, Week 9, n=47, 46	6.14 ± 3.022	7.74 ± 2.112
Nasal Polyposis, Week 13, n=45, 39	5.79 ± 3.524	7.21 ± 2.563
Nasal Polyposis, Week 17, n=44, 34	5 ± 3.518	6.44 ± 3.164
Nasal Polyposis, Week 21, n=42, 33	4.7 ± 3.513	6.47 ± 3.098
Nasal Polyposis, Week 25, n=41, 31	4.18 ± 3.624	6.21 ± 3.357
Rhinorrhea, Week 1, n=49, 51	6.6 ± 2.694	6.17 ± 3.086
Rhinorrhea, Week 2, n=49, 51	5.59 ± 2.863	6.28 ± 2.992
Rhinorrhea, Week 5, n=49, 49	4.98 ± 3.365	5.98 ± 2.926
Rhinorrhea, Week 9, n=48, 46	4.65 ± 3.309	6.28 ± 3.129
Rhinorrhea, Week 13, n=45, 39	4.18 ± 3.34	5.19 ± 3.106
Rhinorrhea, Week 17, n=44, 34	3.33 ± 3.338	4.82 ± 3.399
Rhinorrhea, Week 21, n=42, 34	3.5 ± 3.408	4.7 ± 3.512
Rhinorrhea, Week 25, n=41, 31	3.09 ± 3.452	4.71 ± 3.812
Mucus in Throat, Week 1, n=49, 51	5.92 ± 2.878	6.53 ± 2.732
Mucus in Throat, Week 2, n=49, 51	5.27 ± 2.807	6.15 ± 2.764
Mucus in Throat, Week 5, n=49, 49	4.92 ± 3.012	5.92 ± 2.64
Mucus in Throat, Week 9, n=48, 46	3.93 ± 3.232	6.37 ± 2.942
Mucus in Throat, Week 13, n=45, 39	4.11 ± 3.079	5.49 ± 3.28
Mucus in Throat, Week 17, n=44, 34	3.28 ± 3.19	5.16 ± 3.482
Mucus in Throat, Week 21, n=42, 34	3.3 ± 3.356	4.84 ± 3.457
Mucus in Throat, Week 25, n=41, 31	3.27 ± 3.298	5.23 ± 3.405
Nasal Blockage, Week 1, n=49, 51	7.76 ± 2.459	8.36 ± 1.783
Nasal Blockage, Week 2, n=49, 51	6.41 ± 3.02	7.84 ± 2.466
Nasal Blockage, Week 5, n=49, 49	5.66 ± 3.169	7.33 ± 2.489
Nasal Blockage, Week 9, n=48, 46	5.03 ± 3.387	7.22 ± 2.959
Nasal Blockage, Week 13, n=45, 39	4.66 ± 3.729	6.27 ± 3.268
Nasal Blockage, Week 17, n=44, 34	4.18 ± 3.556	5.71 ± 3.597
Nasal Blockage, Week 21, n=42, 34	4.04 ± 3.563	5.77 ± 3.397
Nasal Blockage, Week 25, n=41, 31	3.69 ± 3.476	5.81 ± 3.494
Loss of Smell, Week 1, n=49, 51	9.03 ± 1.739	9.22 ± 1.912
Loss of Smell, Week 2, n=49, 51	8.79 ± 1.823	9.02 ± 1.942
Loss of Smell, Week 5, n=49, 49	8.28 ± 2.243	8.69 ± 2.511
Loss of Smell, Week 9, n=48, 46	7.43 ± 3.192	8.67 ± 2.647
Loss of Smell, Week 13, n=45, 39	7.42 ± 3.296	8.59 ± 2.318
Loss of Smell, Week 17, n=44, 34	6.85 ± 3.648	8.18 ± 2.682
Loss of Smell, Week 21, n=42, 34	6.74 ± 3.562	8.2 ± 2.835
Loss of Smell, Week 25, n=41, 31	6.09 ± 4.089	7.9 ± 3.378

Notes
[72] - PP Population
[73] - PP Population

No statistical analyses for this end point

Secondary: Mean peak nasal inspiratory flow (PNIF) at Weeks 1, 2, 5, 9, 13, 17, 21, and 25

Top of page

End point title

Mean peak nasal inspiratory flow (PNIF) at Weeks 1, 2, 5, 9, 13, 17, 21, and 25

End point description

Participants used a portable hand-held inspiratory flow meter to measure and record PNIF in the morning prior to taking the study medication. Three measurements were taken, and the largest measurement was recorded in the electronic diary. PNIF data is plotted and analyzed using a repeated measures model to calculate treatment difference, confidence intervals and p-values. Only those participants available at the specified time points (represented by n=X, X) were analyzed.

End point type

Secondary

End point timeframe

Weeks 1, 2, 5, 9, 13, 17, 21, and 25

End point values	Mepolizumab 750 mg	Placebo
Number of subjects analysed	54 ^[74]	51 ^[75]
Units: L/min
least squares mean (confidence interval 95%)
Week 2, n=54, 51	120.82 (110.59 to 131.04)	99.66 (89.14 to 110.18)
Week 5, n=54, 49	127.21 (116.76 to 137.66)	110.32 (99.39 to 121.24)
Week 9, n=47, 46	123.91 (110.4 to 137.77)	116.71 (102.52 to 130.9)
Week 13, n=45, 37	137.5 (123.49 to 151.51)	109.79 (94.8 to 124.78)
Week 17, n=44, 34	132.41 (119.4 to 145.43)	117.02 (102.91 to 131.12)
Week 21, n=42, 33	143.03 (127.13 to 158.93)	113.52 (96.28 to 130.76)
Week 25, n=42, 32	137.02 (121.17 to 152.87)	110.37 (92.94 to 127.8)

Notes
[74] - ITT Population
[75] - ITT Population

Week 2

Comparison groups

Mepolizumab 750 mg v Placebo

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

other ^[76]

P-value

= 0.005

Method

repeated measures model

Parameter type

Mean difference (final values)

Point estimate

21.16

Confidence interval

level

95%

sides

2-sided

lower limit

6.49

upper limit

35.83

Notes
[76] - repeated measures model

Week 5

Comparison groups

Mepolizumab 750 mg v Placebo

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

other ^[77]

P-value

= 0.029

Method

repeated measures model

Parameter type

Mean difference (final values)

Point estimate

16.89

Confidence interval

level

95%

sides

2-sided

lower limit

1.77

upper limit

32.01

Notes
[77] - repeated measures model

Week 9

Comparison groups

Mepolizumab 750 mg v Placebo

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

other ^[78]

P-value

= 0.472

Method

repeated measures model

Parameter type

Mean difference (final values)

Point estimate

7.2

Confidence interval

level

95%

sides

2-sided

lower limit

-12.64

upper limit

27.03

Notes
[78] - repeated measures model

Week 13

Comparison groups

Mepolizumab 750 mg v Placebo

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

other ^[79]

P-value

= 0.009

Method

repeated measures model

Parameter type

Mean difference (final values)

Point estimate

27.71

Confidence interval

level

95%

sides

2-sided

lower limit

7.19

upper limit

48.23

Notes
[79] - repeated measures model

Week 17

Comparison groups

Mepolizumab 750 mg v Placebo

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

other ^[80]

P-value

= 0.114

Method

repeated measures model

Parameter type

Mean difference (final values)

Point estimate

15.4

Confidence interval

level

95%

sides

2-sided

lower limit

-3.8

upper limit

34.59

Notes
[80] - repeated measures model

Week 21

Comparison groups

Mepolizumab 750 mg v Placebo

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

other ^[81]

P-value

= 0.014

Method

repeated measures model

Parameter type

Mean difference (final values)

Point estimate

29.51

Confidence interval

level

95%

sides

2-sided

lower limit

6.06

upper limit

52.96

Notes
[81] - repeated measures model

Week 25

Comparison groups

Mepolizumab 750 mg v Placebo

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

other ^[82]

P-value

= 0.027

Method

repeated measures model

Parameter type

Mean difference (final values)

Point estimate

26.65

Confidence interval

level

95%

sides

2-sided

lower limit

3.1

upper limit

50.21

Notes
[82] - repeated measures model

Secondary: Olfaction testing: worst nostril score (WNS) and mean nostril score (MNS) at Weeks 1, 2, 5, 9, 13, 17, 21, and 25

Top of page

End point title

Olfaction testing: worst nostril score (WNS) and mean nostril score (MNS) at Weeks 1, 2, 5, 9, 13, 17, 21, and 25

End point description

Sniffin’Sticks were used to assess each participant’s sense of smell (olfaction). Olfaction testing results were recorded for both the right and left nostrils The worst nostril score (number of correct answers for the worst nostril) and the mean nostril score (mean number of correct answers across both nostrils) were recorded. Scores range from 0 to 12 (high score indicating normal olfactory sensation). Olfaction data are plotted and analyzed using a repeated measures model to calculate treatment difference, confidence intervals and p-values. Only those participants available at the specified time points (represented by n=X, X) were analyzed.

End point type

Secondary

End point timeframe

Weeks 1, 2, 5, 9, 13, 17, 21, and 25

End point values	Mepolizumab 750 mg	Placebo
Number of subjects analysed	54 ^[83]	51 ^[84]
Units: Scores on a scale
least squares mean (confidence interval 95%)
MNS, Week 2, n=54, 51	3.78 (3.29 to 4.26)	3.68 (3.18 to 4.18)
MNS, Week 5, n=54, 49	4.2 (3.63 to 4.78)	3.07 (2.46 to 3.67)
MNS, Week 9, n=47, 45	4.48 (3.89 to 5.07)	3.69 (3.08 to 4.29)
MNS, Week 13, n=45, 37	4.39 (3.75 to 5.03)	3.66 (2.97 to 4.35)
MNS, Week 17, n=43, 34	4.64 (3.93 to 5.36)	4.26 (3.45 to 5.07)
MNS, Week 21, n=42, 33	4.77 (3.93 to 5.61)	4.12 (3.19 to 5.05)
MNS, Week 25, n=41, 32	4.4 (3.61 to 5.18)	3.69 (2.81 to 4.56)
WNS, Week 2, n=54, 51	3.18 (2.67 to 3.69)	2.89 (2.37 to 3.42)
WNS, Week 5, n=54, 49	3.72 (3.16 to 4.27)	2.41 (1.82 to 2.99)
WNS, Week 9, n=47, 45	3.85 (3.21 to 4.49)	3.17 (2.51 to 3.82)
WNS, Week 13, n=45, 37	3.76 (3.06 to 4.46)	3.14 (2.38 to 3.9)
WNS, Week 17, n=43, 34	3.93 (3.15 to 4.7)	3.74 (2.87 to 4.61)
WNS, Week 21, n=42, 33	4.16 (3.3 to 5.02)	3.52 (2.58 to 4.47)
WNS, Week 25, n=41, 32	3.75 (2.93 to 4.56)	3.3 (2.4 to 4.2)

Notes
[83] - ITT Population
[84] - ITT Population

MNS, Week 2

Comparison groups

Mepolizumab 750 mg v Placebo

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

other ^[85]

P-value

= 0.79

Method

repeated measures model

Parameter type

Mean difference (final values)

Point estimate

0.09

Confidence interval

level

95%

sides

2-sided

lower limit

-0.61

upper limit

0.79

Notes
[85] - repeated measures model

MNS, Week 5

Comparison groups

Mepolizumab 750 mg v Placebo

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

other ^[86]

P-value

= 0.008

Method

repeated measures model

Parameter type

Mean difference (final values)

Point estimate

1.14

Confidence interval

level

95%

sides

2-sided

lower limit

0.3

upper limit

1.97

Notes
[86] - repeated measures model

MNS, Week 9

Comparison groups

Mepolizumab 750 mg v Placebo

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

other ^[87]

P-value

= 0.066

Method

repeated measures model

Parameter type

Mean difference (final values)

Point estimate

0.79

Confidence interval

level

95%

sides

2-sided

lower limit

-0.05

upper limit

1.64

Notes
[87] - repeated measures model

MNS, Week 13

Comparison groups

Mepolizumab 750 mg v Placebo

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

other ^[88]

P-value

= 0.127

Method

repeated measures model

Parameter type

repeated measures model

Point estimate

0.73

Confidence interval

level

95%

sides

2-sided

lower limit

-0.21

upper limit

1.67

Notes
[88] - repeated measures model

MNS, Week 17

Comparison groups

Mepolizumab 750 mg v Placebo

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

other ^[89]

P-value

= 0.481

Method

repeated measures model

Parameter type

Mean difference (final values)

Point estimate

0.38

Confidence interval

level

95%

sides

2-sided

lower limit

-0.69

upper limit

1.46

Notes
[89] - repeated measures model

MNS, Week 21

Comparison groups

Placebo v Mepolizumab 750 mg

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

other ^[90]

P-value

= 0.308

Method

repeated measures model

Parameter type

Mean difference (final values)

Point estimate

0.65

Confidence interval

level

95%

sides

2-sided

lower limit

-0.61

upper limit

1.9

Notes
[90] - repeated measures model

MNS, Week 25

Comparison groups

Mepolizumab 750 mg v Placebo

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

other ^[91]

P-value

= 0.233

Method

repeated measures model

Parameter type

Mean difference (final values)

Point estimate

0.71

Confidence interval

level

95%

sides

2-sided

lower limit

-0.46

upper limit

1.88

Notes
[91] - repeated measures model

WNS, Week 2

Comparison groups

Mepolizumab 750 mg v Placebo

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

other ^[92]

P-value

= 0.444

Method

repeated measures model

Parameter type

Mean difference (final values)

Point estimate

0.28

Confidence interval

level

95%

sides

2-sided

lower limit

-0.45

upper limit

1.02

Notes
[92] - repeated measures model

WNS, Week 5

Comparison groups

Mepolizumab 750 mg v Placebo

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

other ^[93]

P-value

= 0.002

Method

repeated measures model

Parameter type

Mean difference (final values)

Point estimate

1.31

Confidence interval

level

95%

sides

2-sided

lower limit

0.5

upper limit

2.12

Notes
[93] - repeated measures model

WNS, Week 9

Comparison groups

Mepolizumab 750 mg v Placebo

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

other ^[94]

P-value

= 0.143

Method

repeated measures model

Parameter type

Mean difference (final values)

Point estimate

0.68

Confidence interval

level

95%

sides

2-sided

lower limit

-0.24

upper limit

1.6

Notes
[94] - repeated measures model

WNS, Week 13

Comparison groups

Mepolizumab 750 mg v Placebo

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

other ^[95]

P-value

= 0.24

Method

repeated measures model

Parameter type

Mean difference (final values)

Point estimate

0.62

Confidence interval

level

95%

sides

2-sided

lower limit

-0.42

upper limit

1.65

Notes
[95] - repeated measures model

WNS, Week 17

Comparison groups

Mepolizumab 750 mg v Placebo

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

other ^[96]

P-value

= 0.75

Method

repeated measures model

Parameter type

Mean difference (final values)

Point estimate

0.19

Confidence interval

level

95%

sides

2-sided

lower limit

-0.98

upper limit

1.35

Notes
[96] - repeated measures model

WNS, Week 21

Comparison groups

Mepolizumab 750 mg v Placebo

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

other ^[97]

P-value

= 0.324

Method

repeated measures model

Parameter type

Mean difference (final values)

Point estimate

0.64

Confidence interval

level

95%

sides

2-sided

lower limit

-0.64

upper limit

1.91

Notes
[97] - repeated measures model

WNS, Week 25

Comparison groups

Mepolizumab 750 mg v Placebo

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

other ^[98]

P-value

= 0.468

Method

repeated measures model

Parameter type

Mean difference (final values)

Point estimate

0.44

Confidence interval

level

95%

sides

2-sided

lower limit

-0.77

upper limit

1.66

Notes
[98] - repeated measures model

Secondary: Sino-Nasal Outcome Test (SNOT)-22 questionnaire total score at Week 1 and Week 25

Top of page

End point title

Sino-Nasal Outcome Test (SNOT)-22 questionnaire total score at Week 1 and Week 25

End point description

The SNOT-22 questionnaire is a modification of the SNOT-20 and contains the questions related to smell and nasal obstruction. Each question is graded with a numerical score for each response; scores range from 0 for "no symptoms" to 5 for "as bad as things could be." The scores for each of the questions is summed to derive the total score for that participant at that visit. If the participant did not complete any questions at a visit, then he/she were not to have any missing values imputed, and his/her total score for that visit was set to missing. If a participant had some missing scores (but no more than 50% missing at that visit), then scores for the missing responses were imputed as the mean of the non-missing responses for that participant at that visit. The SNOT-22 total score ranges from 0 to 110, with higher scores representing a worse quality of life. Questionnaire data analysis was done using an ANCOVA to obtain the LS-means, treatment difference and confidence interval.

End point type

Secondary

End point timeframe

Week 1 and Week 25

End point values	Mepolizumab 750 mg	Placebo
Number of subjects analysed	54 ^[99]	51 ^[100]
Units: Scores on a scale
least squares mean (standard error)	27.13 ± 2.96	40.36 ± 3.39

Notes
[99] - ITT Population
[100] - ITT Population

Statistical Analysis 1

Comparison groups

Mepolizumab 750 mg v Placebo

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

other ^[101]

P-value

= 0.005

Method

ANCOVA

Parameter type

Mixed effects model

Point estimate

-13.2

Confidence interval

level

95%

sides

2-sided

lower limit

-22.2

upper limit

-4.22

Notes
[101] - ANCOVA model

Secondary: Index score of the EuroQoL Quality of Life-5D (EQ-5D) questionnaire at Week 1 and Week 25

Top of page

End point title

Index score of the EuroQoL Quality of Life-5D (EQ-5D) questionnaire at Week 1 and Week 25

End point description

The EQ-5D is a standardized, 2-part questionnaire used to measure health outcomes. The first part contains descriptions of the following five components: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Responses to each of the five domains are measured on a 3-point scale (1-no problems, 2-some problems, and 3-severe problems). An index for the descriptive scores was derived using the general European weights, obtained for each of the countries in this study. Index scores were derived for each participant at each time point. ANCOVA model with treatment, Baseline and country as factors was used to calculate treatment difference and confidence intervals.

End point type

Secondary

End point timeframe

Week 1 and Week 25

End point values	Mepolizumab 750 mg	Placebo
Number of subjects analysed	54 ^[102]	51 ^[103]
Units: Scores on a scale
least squares mean (standard error)	0.91 ± 0.02	0.91 ± 0.02

Notes
[102] - ITT Population
[103] - ITT Population

Statistical Analysis 1

Comparison groups

Mepolizumab 750 mg v Placebo

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

other ^[104]

Method

Parameter type

Mean difference (final values)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.06

upper limit

0.07

Notes
[104] - ANCOVA model

Secondary: VAS score of the EQ-5D questionnaire at Week 1 and Week 25

Top of page

End point title

VAS score of the EQ-5D questionnaire at Week 1 and Week 25

End point description

The EQ-5D is a standardized, 2-part questionnaire used to measure health outcomes. The second part of the questionnaire is a VAS question, requiring the participant to self rate his/her health score on a scale of 0 (worst imaginable health state) to 100 (best imaginable health state).

End point type

Secondary

End point timeframe

Week 1 and Week 25

End point values	Mepolizumab 750 mg	Placebo
Number of subjects analysed	54 ^[105]	51 ^[106]
Units: Scores on a scale
least squares mean (standard error)	81.13 ± 2.3	75.45 ± 2.64

Notes
[105] - ITT Population
[106] - ITT Population

Statistical Analysis 1

Comparison groups

Mepolizumab 750 mg v Placebo

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

other ^[107]

Method

Parameter type

Mean difference (final values)

Point estimate

5.68

Confidence interval

level

95%

sides

2-sided

lower limit

-1.33

upper limit

12.68

Notes
[107] - ANCOVA model

Secondary: Number of participants with positive immunogenicity (anti-mepolizumab antibody testing)

Top of page

End point title

Number of participants with positive immunogenicity (anti-mepolizumab antibody testing)

End point description

Blood samples were collected at Weeks 1, 5, 13, and 25 for anti-mepolizumab antibody testing. Only those participants available at the specified time points (represented by n=X, X) were analyzed.

End point type

Secondary

End point timeframe

Weeks 1, 5, 13, and 25

End point values	Mepolizumab 750 mg	Placebo
Number of subjects analysed	53 ^[108]	51 ^[109]
Units: participants
Week 1, pre-dose, n=53, 52	0	2
Week 5, pre-dose, n=53, 50	0	2
Week 13, pre-dose, n=45, 40	0	2
Week 13, 4-6 months, n=1, 4	0	1
Week 25, 4-6 months, n=25, 24	0	1
Week 25, study exit, n=2, 2	0	1

Notes
[108] - ITT Population
[109] - ITT Population; n=52

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of flixonase administration (at the start of the Run-in Period) up to the end of the study (up to 11 months).

Adverse event reporting additional description

SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all enrolled participants who received at least one dose of study medication.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

17.1

Reporting group title

Mepolizumab 750 mg

Reporting group description

Participants received a total of six doses (one every 4 weeks) of mepolizumab 750 milligrams (mg) by intravenous infusion.

Reporting group title

Placebo

Reporting group description

Participants received a total of six doses (one every 4 weeks) of matching placebo by intravenous infusion.

Serious adverse events	Mepolizumab 750 mg	Placebo
Total subjects affected by serious adverse events
subjects affected / exposed	0 / 53 (0.00%)	0 / 52 (0.00%)
number of deaths (all causes)	0	0
number of deaths resulting from adverse events

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Mepolizumab 750 mg	Placebo
Total subjects affected by non serious adverse events
subjects affected / exposed	35 / 53 (66.04%)	39 / 52 (75.00%)
Nervous system disorders
Headache
subjects affected / exposed	13 / 53 (24.53%)	22 / 52 (42.31%)
occurrences all number	55	35
Sinus headache
subjects affected / exposed	0 / 53 (0.00%)	3 / 52 (5.77%)
occurrences all number	0	5
General disorders and administration site conditions
Fatigue
subjects affected / exposed	1 / 53 (1.89%)	5 / 52 (9.62%)
occurrences all number	1	9
Pyrexia
subjects affected / exposed	3 / 53 (5.66%)	1 / 52 (1.92%)
occurrences all number	3	1
Ear and labyrinth disorders
Ear pain
subjects affected / exposed	1 / 53 (1.89%)	6 / 52 (11.54%)
occurrences all number	2	8
Otorrhoea
subjects affected / exposed	3 / 53 (5.66%)	0 / 52 (0.00%)
occurrences all number	3	0
Gastrointestinal disorders
Nausea
subjects affected / exposed	2 / 53 (3.77%)	4 / 52 (7.69%)
occurrences all number	8	6
Respiratory, thoracic and mediastinal disorders
Asthma
subjects affected / exposed	2 / 53 (3.77%)	3 / 52 (5.77%)
occurrences all number	3	3
Cough
subjects affected / exposed	2 / 53 (3.77%)	3 / 52 (5.77%)
occurrences all number	2	3
Dyspnoea
subjects affected / exposed	2 / 53 (3.77%)	4 / 52 (7.69%)
occurrences all number	2	5
Epistaxis
subjects affected / exposed	1 / 53 (1.89%)	4 / 52 (7.69%)
occurrences all number	6	6
Rhinorrhoea
subjects affected / exposed	0 / 53 (0.00%)	3 / 52 (5.77%)
occurrences all number	0	3
Paranasal sinus discomfort
subjects affected / exposed	0 / 53 (0.00%)	3 / 52 (5.77%)
occurrences all number	0	7
Oropharyngeal pain
subjects affected / exposed	6 / 53 (11.32%)	4 / 52 (7.69%)
occurrences all number	6	4
Skin and subcutaneous tissue disorders
Rash
subjects affected / exposed	4 / 53 (7.55%)	0 / 52 (0.00%)
occurrences all number	8	0
Psychiatric disorders
Insomnia
subjects affected / exposed	0 / 53 (0.00%)	3 / 52 (5.77%)
occurrences all number	0	5
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	5 / 53 (9.43%)	3 / 52 (5.77%)
occurrences all number	5	4
Back pain
subjects affected / exposed	5 / 53 (9.43%)	0 / 52 (0.00%)
occurrences all number	6	0
Infections and infestations
Influenza
subjects affected / exposed	4 / 53 (7.55%)	2 / 52 (3.85%)
occurrences all number	4	2
Nasopharyngitis
subjects affected / exposed	10 / 53 (18.87%)	14 / 52 (26.92%)
occurrences all number	12	17

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

20 Apr 2009

Amendment made to include more details surrounding dose administration and make minor protocol corrections. Changes and rationale described in Appendix 6.

11 Nov 2009

Amendment made to include revisions to the eligibility criteria relating to inhaled and oral steroid use, and to clarify the Serious Adverse Event definition. Changes and rationale described in Appendix 7.

13 Jul 2011

Amendment made to include revisions to the prohibited medications relating to leukotriene modifiers including montelukast and to make clarifications to the Time and Events table. Changes and rationale are described in Appendix 8.

09 Nov 2011

Amendment made to correct the inconsistency for the timing of the final immunogenicity sampling and the final laboratory and pregnancy testing. Changes and rationale are described in Appendix 9.

23 Jan 2012

Amendment made to remove Part B of the study.

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.

Safety Population (SP): actual treatment; Intent-to-Treat Population (ITTP): intended treatment. A placebo-randomized participant took mepolizumab; placebo SP “N” is greater than ITTP “N.” Due to system limitations, SP n=51 is shown (should be n=52).

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Clinical trials

Clinical Trial Results: A RANDOMISED, DOUBLE-BLIND, PLACEBO CONTROLLED, MULTI-CENTER STUDY TO INVESTIGATE THE USE OF MEPOLIZUMAB (SB-240563) IN REDUCING THE NEED FOR SURGERY IN SUBJECTS WITH SEVERE BILATERAL NASAL POLYPOSIS

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Number of participants with a reduced need for surgery at the end of the study (Week 25)

Primary: Number of participants with a reduced need for surgery at the end of the study (Week 25)

Secondary: Number of participants with endoscopic nasal polyp (ENP) score dynamics at Screening and Weeks 1, 2, 5, 9, 13, 17, 21, and 25

Secondary: Number of participants with endoscopic nasal polyp (ENP) score dynamics at Screening and Weeks 1, 2, 5, 9, 13, 17, 21, and 25

Secondary: Number of participants who required polyp surgery at Weeks 1, 2, 5, 9, 13, 17, 21, and 25

Secondary: Number of participants who required polyp surgery at Weeks 1, 2, 5, 9, 13, 17, 21, and 25

Secondary: Mean change from Baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP) at Weeks 2, 5, 9, 13, 21, and 25

Secondary: Mean change from Baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP) at Weeks 2, 5, 9, 13, 21, and 25

Secondary: Mean change from Baseline in pulse rate at Weeks 2, 5, 9, 13, 17, 21, and 25

Secondary: Mean change from Baseline in pulse rate at Weeks 2, 5, 9, 13, 17, 21, and 25

Secondary: Number of participants with the indicated electrocardiogram (ECG) findings at Weeks 1, 2, 5, 9, 13, 17, 21, and 25

Secondary: Number of participants with the indicated electrocardiogram (ECG) findings at Weeks 1, 2, 5, 9, 13, 17, 21, and 25

Secondary: Absolute values of clinical chemistry parameters including blood urea nitrogen (BUN), glucose fasting, chloride, sodium, potassium, carbon dioxide, and calcium at Weeks 1, 2, 5, 9, 13, 17, 21, and 25

Secondary: Absolute values of clinical chemistry parameters including blood urea nitrogen (BUN), glucose fasting, chloride, sodium, potassium, carbon dioxide, and calcium at Weeks 1, 2, 5, 9, 13, 17, 21, and 25

Secondary: Absolute values of the clinical chemistry parameters of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and gamma glutamyltransferase (GGT) at Weeks 1, 2, 5, 9, 13, 17, 21, and 25

Secondary: Absolute values of the clinical chemistry parameters of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and gamma glutamyltransferase (GGT) at Weeks 1, 2, 5, 9, 13, 17, 21, and 25

Secondary: Absolute values of the clinical chemistry parameters of albumin and protein at Weeks 1, 2, 5, 9, 13, 17, 21, and 25

Secondary: Absolute values of the clinical chemistry parameters of albumin and protein at Weeks 1, 2, 5, 9, 13, 17, 21, and 25

Secondary: Absolute values of the clinical chemistry parameters of total and direct bilirubin, creatinine (CRT), and uric acid (UA) at Weeks 1, 2, 5, 9, 13, 17, 21, and 25

Secondary: Absolute values of the clinical chemistry parameters of total and direct bilirubin, creatinine (CRT), and uric acid (UA) at Weeks 1, 2, 5, 9, 13, 17, 21, and 25

Secondary: Absolute values of the hematology parameters of platelet count and white blood cell (WBC) count, basophils, eosinophils, lymphocytes, monocytes, and neutrophils at Weeks 1, 2, 5, 9, 13, 17, 21, and 25

Secondary: Absolute values of the hematology parameters of platelet count and white blood cell (WBC) count, basophils, eosinophils, lymphocytes, monocytes, and neutrophils at Weeks 1, 2, 5, 9, 13, 17, 21, and 25

Secondary: Absolute values of the hematology parameters of hemoglobin and mean corpuscular hemoglobin concentration (MCHC) at Weeks 1, 2, 5, 9, 13, 17, 21, and 25

Secondary: Absolute values of the hematology parameters of hemoglobin and mean corpuscular hemoglobin concentration (MCHC) at Weeks 1, 2, 5, 9, 13, 17, 21, and 25

Secondary: Absolute values of the hematology parameter of red blood cell (RBC) count and reticulocyte count (RC) at Weeks 1, 2, 5, 9, 13, 17, 21, and 25

Secondary: Absolute values of the hematology parameter of red blood cell (RBC) count and reticulocyte count (RC) at Weeks 1, 2, 5, 9, 13, 17, 21, and 25

Secondary: Absolute values of the hematology parameter of mean corpuscular hemoglobin (MCH) at Weeks 1, 2, 5, 9, 13, 17, 21, and 25

Secondary: Absolute values of the hematology parameter of mean corpuscular hemoglobin (MCH) at Weeks 1, 2, 5, 9, 13, 17, 21, and 25

Secondary: Absolute values of the hematology parameter of mean corpuscular volume (MCV) at Weeks 1, 2, 5, 9, 13, 17, 21, and 25

Secondary: Absolute values of the hematology parameter of mean corpuscular volume (MCV) at Weeks 1, 2, 5, 9, 13, 17, 21, and 25

Secondary: Absolute value of the hematology parameter of reticulocyte count/erythrocyte uncorrected at Weeks 1, 2, 5, 9, 13, 17, 21, and 25

Secondary: Absolute value of the hematology parameter of reticulocyte count/erythrocyte uncorrected at Weeks 1, 2, 5, 9, 13, 17, 21, and 25

Secondary: Number of participants with positive urinalysis results at Weeks 1, 2, 5, 9, 13, 17, 21, and 25

Secondary: Number of participants with positive urinalysis results at Weeks 1, 2, 5, 9, 13, 17, 21, and 25

Secondary: Number of participants with any treatment-emergent adverse event (AE) and serious adverse event (SAE)

Secondary: Number of participants with any treatment-emergent adverse event (AE) and serious adverse event (SAE)

Secondary: Mean of the forced expiratory volume in 1 second (FEV1) at Weeks 2, 5, 9, 13, 17, 21, and 25

Secondary: Mean of the forced expiratory volume in 1 second (FEV1) at Weeks 2, 5, 9, 13, 17, 21, and 25

Secondary: Mean of forced vital capacity (FVC) at Weeks 1, 2, 5, 9, 13, 17, 21, and 25

Secondary: Mean of forced vital capacity (FVC) at Weeks 1, 2, 5, 9, 13, 17, 21, and 25

Secondary: Mean peak expiratory flow rate (PEFR) at indicated Weeks 1, 2, 5, 9, 13, 17, 21, and 25

Secondary: Mean peak expiratory flow rate (PEFR) at indicated Weeks 1, 2, 5, 9, 13, 17, 21, and 25

Secondary: Individual symptoms visual analogue scale (VAS) scores at Weeks 1, 2, 5, 9, 13, 17, 21, and 25

Secondary: Individual symptoms visual analogue scale (VAS) scores at Weeks 1, 2, 5, 9, 13, 17, 21, and 25

Secondary: Mean peak nasal inspiratory flow (PNIF) at Weeks 1, 2, 5, 9, 13, 17, 21, and 25

Secondary: Mean peak nasal inspiratory flow (PNIF) at Weeks 1, 2, 5, 9, 13, 17, 21, and 25

Secondary: Olfaction testing: worst nostril score (WNS) and mean nostril score (MNS) at Weeks 1, 2, 5, 9, 13, 17, 21, and 25

Secondary: Olfaction testing: worst nostril score (WNS) and mean nostril score (MNS) at Weeks 1, 2, 5, 9, 13, 17, 21, and 25

Secondary: Sino-Nasal Outcome Test (SNOT)-22 questionnaire total score at Week 1 and Week 25

Secondary: Sino-Nasal Outcome Test (SNOT)-22 questionnaire total score at Week 1 and Week 25

Secondary: Index score of the EuroQoL Quality of Life-5D (EQ-5D) questionnaire at Week 1 and Week 25

Secondary: Index score of the EuroQoL Quality of Life-5D (EQ-5D) questionnaire at Week 1 and Week 25

Secondary: VAS score of the EQ-5D questionnaire at Week 1 and Week 25

Secondary: VAS score of the EQ-5D questionnaire at Week 1 and Week 25

Secondary: Number of participants with positive immunogenicity (anti-mepolizumab antibody testing)

Secondary: Number of participants with positive immunogenicity (anti-mepolizumab antibody testing)

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A RANDOMISED, DOUBLE-BLIND, PLACEBO CONTROLLED, MULTI-CENTER STUDY TO INVESTIGATE THE USE OF MEPOLIZUMAB (SB-240563) IN REDUCING THE NEED FOR SURGERY IN SUBJECTS WITH SEVERE BILATERAL NASAL POLYPOSIS