Mepolizumab in Nasal Polyposis

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01362244
• Collaborator: (none)
• Enrollment: 109
• Locations: 6
• Arms: 3
• Actual Duration (Months): 66.8
• Patients Per Site: 18.2
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

A two-part, randomised, double-blind, placebo controlled, multi-centre study to investigate the use of mepolizumab (SB-240563) in reducing the need for surgery in subjects with severe bilateral nasal polyposis.

Condition or Disease	Intervention/Treatment	Phase
Nasal Polyps	Drug: Mepolizumab; Drug: Placebo; Drug: Run In Medication	Phase 2

Detailed Description

Nasal polyposis has long been known as chronic inflammatory disease of the nasal mucosa. This disease is characterized by the presence of polyps in the upper nasal cavity, originating from within the ostiomeatal complex. The presence of polyps can cause long-term symptoms such as prominent nasal obstruction, post-nasal drip, loss of smell, and discharge. These symptoms can impact greatly upon a patient's quality of life.The etiology of nasal polyposis is currently unknown.

The aim of this present study is to investigate the use of mepolizumab in reducing the potential need for surgery in subjects with severe bilateral nasal polyposis. The study is split into two parts: Part A is the treatment phase and focuses on the reduction of the need for surgery by exploring the efficacy of six doses of mepolizumab (one dose every four weeks) on nasal polyposis. This dosing regime will build upon the previous PoC study by exploring the potential for increased clinical efficacy as assessed by the potential need for surgery, and also and increased duration of action as assessed by time to relapse. Part B is the follow-up phase and will assess post-treatment nasal polyposis dynamics with a focus on time to relapse. All subjects participating in this study will undergo a run-in period on a low dose of intranasal steroids (INS) prior to first dosing. INS will be continued throughout the study up until study exit. This is to reflect the real life circumstances in which mepolizumab is intended to be used as a therapy. The overall aim of the study design is to further assess the impact in the potential need for surgery and explore an appropriate mepolizumab therapeutic regimen strategy for the treatment of nasal polyposis.

In this study, the assessment of nasal polyposis will be performed by means of combining endoscopic polyp score with subject reported symptoms. This approach reflects real-life clinical assessment of nasal polyposis. Also, this study incorporates condition specific and general medical questionnaires in order to obtain a better understanding of the impact of severe nasal polyposis of the subject's quality of life (QOL). This is in line with increasing focus in the medical field on the effects of medical conditions and treatments on the quality of life of patients (Fokkens et al 2007).

Study Design

• Study Type: Interventional
• Actual Enrollment: 109 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: May 12, 2009
• Actual Primary Completion Date: Dec 5, 2014
• Actual Study Completion Date: Dec 5, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment Periods 1-8 Part A comprises eight outpatient visits (Visits 1 - 8). For six of these visits, subjects will receive a dose of either 750 mg mepolizumab or placebo. Dosing occurs in four week intervals. Assessment for entry into Part B will take place at the last visit in Part A (Visit 8). Subjects not eligible for Part B will have study exit procedures performed and be discontinued.	Drug: Mepolizumab; 750 mg of mepolizumab by IV infusion; Drug: Placebo; Placebo by IV infusion
Other: Run In period 10-14 day run in period to assess the patients suitability for entry into Part A of the trial.	Drug: Run In Medication; subjects will undergo a run-in period of 10 - 14 days on a low dose of Intranasal Steroids (INS).
No Intervention: Treatment periods 9-13 Subjects eligible for Part B will attend the clinic for up to 5 more outpatient visits (Visits 9 - 13) for assessments. Visits occur every four weeks. There is no dosing in Part B. At the point when each subject meets Study Exit criteria, study exit procedures will be performed and the subject will exit the study.

Outcome Measures

Primary Outcome Measures

1. Number of Participants With a Reduced Need for Surgery at Week 25 [Week 25]

   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 (ENP) 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.

Secondary Outcome Measures

1. Number of Participants With Endoscopic Nasal Polyp (ENP) Score Dynamics at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 [Weeks 1, 2, 5, 9, 13, 17, 21, and 25]

   Each nostril was assessed for polyps and graded at Weeks 1, 2, 5, 9, 13, 17, 21, and 25. The right and left nostrils were scored from 0 to 4, where, 0 = No polyps; 1 = Small polyps in the middle meatus not reaching below the inferior border of the middle concha; 2 = Polyps reaching below the lower border of the middle turbinate; 3 = Large polyps reaching the lower border of the inferior turbinate or polyps medial to the middle concha; and 4 = Large polyps causing complete obstruction/congestion of the inferior meatus. 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. The ENP score ranges from 0 to 4, with a higher score indicating a larger polyp.

2. Number of Participants Who Required Polyp Surgery at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 [Weeks 1, 2, 5, 9, 13, 17, 21, and 25]

   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.

3. Mean Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Weeks 2, 5, 9, 13, 17, 21, and 25 [Baseline and Weeks 2, 5, 9, 13, 17, 21, and 25]

   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.

4. Mean Change From Baseline in Pulse Rate at Weeks 2, 5, 9, 13, 17, 21, and 25 [Baseline and Weeks 2, 5, 9, 13, 17, 21, and 25]

   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.

5. Number of Participants With the Indicated Electrocardiogram (ECG) Findings at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 [Weeks 1, 2, 5, 9, 13, 17, 21, and 25]

   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. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition.

6. 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 [Week 1 pre-dose, Week 2, Week 5 pre-dose, Week 9 pre-dose, Week 13 pre-dose, Week 17 pre-dose, Week 21 pre-dose, and Week 25 (4 Weeks post last dose)]

   BUN, glucose fasting, chloride, sodium, potassium, carbon dioxide (CO2), and calcium were assessed at Week 1 pre-dose, Week 2, Week 5 pre-dose, Week 9 pre-dose, Week 13 pre-dose, Week 17 pre-dose, Week 21 pre-dose, and Week 25 (4 Weeks post last dose).

7. 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 [Week 1 pre-dose, Week 2, Week 5 pre-dose, Week 9 pre-dose, Week 13 pre-dose, Week 17 pre-dose, Week 21 pre-dose, and Week 25 (4 Weeks post last dose)]

   ALT, AST, ALP, and GGT were assessed at Week 1 pre-dose, Week 2, Week 5 pre-dose, Week 9 pre-dose, Week 13 pre-dose, Week 17 pre-dose, Week 21 pre-dose, and Week 25 (4 Weeks post last dose).

8. Absolute Values of the Clinical Chemistry Parameters of Albumin and Protein at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 [Week 1 pre-dose, Week 2, Week 5 pre-dose, Week 9 pre-dose, Week 13 pre-dose, Week 17 pre-dose, Week 21 pre-dose, and Week 25 (4 Weeks post last dose)]

   Albumin and protein were assessed at Week 1 pre-dose, Week 2, Week 5 pre-dose, Week 9 pre-dose, Week 13 pre-dose, Week 17 pre-dose, Week 21 pre-dose, and Week 25 (4 Weeks post last dose).

9. 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 [Week 1 pre-dose, Week 2, Week 5 pre-dose, Week 9 pre-dose, Week 13 pre-dose, Week 17 pre-dose, Week 21 pre-dose, and Week 25 (4 Weeks post last dose)]

   Total bilirubin (TB) and direct bilirubin (DB), creatinine, and uric acid were assessed at Week 1 pre-dose, Week 2, Week 5 pre-dose, Week 9 pre-dose, Week 13 pre-dose, Week 17 pre-dose, Week 21 pre-dose, and Week 25 (4 Weeks post last dose).

10. 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 [Week 1 pre-dose, Week 2, Week 5 pre-dose, Week 9 pre-dose, Week 13 pre-dose, Week 17 pre-dose, Week 21 pre-dose, and Week 25 (4 Weeks post last dose)]

    Platelet count, WBC count, basophils, eosinophils, lymphocytes, monocytes, and neutrophils were assessed at Week 1 pre-dose, Week 2, Week 5 pre-dose, Week 9 pre-dose, Week 13 pre-dose, Week 17 pre-dose, Week 21 pre-dose, and Week 25 (4 Weeks post last dose).

11. 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 [Week 1 pre-dose, Week 2, Week 5 pre-dose, Week 9 pre-dose, Week 13 pre-dose, Week 17 pre-dose, Week 21 pre-dose, and Week 25 (4 Weeks post last dose)]

    Hemoglobin and MCHC were assessed at Week 1 pre-dose, Week 2, Week 5 pre-dose, Week 9 pre-dose, Week 13 pre-dose, Week 17 pre-dose, Week 21 pre-dose, and Week 25 (4 Weeks post last dose).

12. 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 [Week 1 pre-dose, Week 2, Week 5 pre-dose, Week 9 pre-dose, Week 13 pre-dose, Week 17 pre-dose, Week 21 pre-dose, and Week 25 (4 Weeks post last dose)]

    RBC count and RC were assessed at Week 1 pre-dose, Week 2, Week 5 pre-dose, Week 9 pre-dose, Week 13 pre-dose, Week 17 pre-dose, Week 21 pre-dose, and Week 25 (4 Weeks post last dose).

13. Absolute Values of the Hematology Parameter of Mean Corpuscular Hemoglobin (MCH) at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 [Week 1 pre-dose, Week 2, Week 5 pre-dose, Week 9 pre-dose, Week 13 pre-dose, Week 17 pre-dose, Week 21 pre-dose, and Week 25 (4 Weeks post last dose)]

    MCH was assessed at Week 1 pre-dose, Week 2, Week 5 pre-dose, Week 9 pre-dose, Week 13 pre-dose, Week 17 pre-dose, Week 21 pre-dose, and Week 25 (4 Weeks post last dose).

14. Absolute Values of the Hematology Parameter of Mean Corpuscular Volume (MCV) at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 [Week 1 pre-dose, Week 2, Week 5 pre-dose, Week 9 pre-dose, Week 13 pre-dose, Week 17 pre-dose, Week 21 pre-dose, and Week 25 (4 Weeks post last dose)]

    MCV was assessed at Week 1 pre-dose, Week 2, Week 5 pre-dose, Week 9 pre-dose, Week 13 pre-dose, Week 17 pre-dose, Week 21 pre-dose, and Week 25 (4 Weeks post last dose).

15. Absolute Value of the Hematology Parameter of Reticulocyte Count/Erythrocyte Uncorrected at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 [Week 1 pre-dose, Week 2, Week 5 pre-dose, Week 9 pre-dose, Week 13 pre-dose, Week 17 pre-dose, Week 21 pre-dose, and Week 25 (4 Weeks post last dose)]

    Reticulocyte count was assessed at Week 1 pre-dose, Week 2, Week 5 pre-dose, Week 9 pre-dose, Week 13 pre-dose, Week 17 pre-dose, Week 21 pre-dose, and Week 25 (4 Weeks post last dose).

16. Number of Participants With Positive Clinically Relevant Urinalysis Results at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 [Weeks 1, 2, 5, 9, 13, 17, 21, and 25]

    Specific gravity, power of hydrogen (pH), glucose, protein, blood, and ketones were assessed at Weeks (Wk) 1, 2, 5, 9, 13, 17, 21, and 25. Results for all urinalysis parameters were assessed for clinical relevance by physician. Clinically relevant positive results are presented. Clinically relevant positive results are defined as those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition.

17. Number of Participants With Any Treatment-emergent Adverse Event (AE) and Serious Adverse Event (SAE) [Up to 11 months]

    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.

18. Mean of the Forced Expiratory Volume in 1 Second (FEV1) at Weeks 2, 5, 9, 13, 17, 21, and 25 [Weeks 2, 5, 9, 13, 17, 21, and 25]

    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.

19. Mean of Forced Vital Capacity (FVC) at Weeks 2, 5, 9, 13, 17, 21, and 25 [Weeks 2, 5, 9, 13, 17, 21, and 25]

    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.

20. Mean Peak Expiratory Flow Rate (PEFR) at Indicated Weeks 2, 5, 9, 13, 17, 21, and 25 [Weeks 2, 5, 9, 13, 17, 21, and 25]

    PEFR is defined as the maximum airflowrate 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.

21. Individual Symptoms Visual Analogue Scale (VAS) Scores at Weeks 1, 2, 5, 9, 13, 17, 21, and 25 [Weeks 1, 2, 5, 9, 13, 17, 21, and 25]

    Participants were asked to indicate on a VAS (0 to 10 centimeters) the severity of nasal polyposis and its four 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." Hence the score ranges between 0 to 10, with higher scores indicating greater severity.

22. Mean Peak Nasal Inspiratory Flow (PNIF) at Weeks 2, 5, 9, 13, 17, 21, and 25 [Weeks 2, 5, 9, 13, 17, 21, and 25]

    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.

23. Olfaction Testing: Worst Nostril Score (WNS) and Mean Nostril Score (MNS) at Weeks 2, 5, 9, 13, 17, 21, and 25 [Weeks 2, 5, 9, 13, 17, 21, and 25]

    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.

24. Sino-Nasal Outcome Test (SNOT)-22 Questionnaire Total Score at Week 25 (Adjusted for Week 1 Baseline) [Week 1 (Baseline) and Week 25]

    SNOT-22 questionnaire is a modification of the SNOT-20 and contains the questions (ques) related to smell and nasal obstruction. Each ques is graded with a numerical score for each response (resp); scores range from 0 for "no symptoms" to 5 for "as bad as things could be." Scores for each of the ques is summed to derive the total score for that par. at that visit. If the par. did not complete any ques 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 par. had some missing scores (but no more than 50% missing at that visit), then scores for the missing resp were imputed as the mean of the non-missing resp for that par. 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 at Week 25, adjusting for Week 1 Baseline scores.

25. Index Score of the EuroQoL Quality of Life-5D (EQ-5D) Questionnaire at Week 25 (Adjusting for Week 1 Baseline Scores) [Week 1 (Baseline) and Week 25]

    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 by taking sum of weights. Index score ranges from -0.718 to 1, with lower scores indicating poor health. ANCOVA model with treatment, Baseline (Week 1 scores) and country as factors was used to calculate treatment difference and confidence intervals at Week 25.

26. VAS Score of the EQ-5D Questionnaire at Week 25 (Adjusting for Week 1 Baseline Scores) [Week 1 (Baseline) and Week 25]

    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). ANCOVA model with treatment, Baseline (Week 1 scores) and country as factors was used to calculate treatment difference and confidence intervals at Week 25.

27. Systemic Clearance of Mepolizumab 750 mg [Weeks 1, 2, 5, 9, 13, and 25]

    Blood samples were collected for the assessment of systemic clearance at Weeks 1, 2, 5, 9, 13, and 25. Systemic Clearance (CL) is estimated using a population-Pharmacokinetic model incorporating all available data points from all participants. Individual values were estimated from the model as post-hoc values after incorporating between-participant variability.

28. Volume of Distribution of Mepolizumab 750 mg [Weeks 1, 2, 5, 9, 13, and 25]

    Volume of distribution at steady-state was derived from pharmacokinetic parameter estimates of a population pharmacokinetic model. Blood samples were collected for analysis of volume of distribution at Weeks 1, 2, 5, 9, 13, and 25. All available concentrations at all available datapoints from all participants were incorporated into the model. Individual values were estimated from the model as post-hoc values after incorporating between-participant variability.

29. Bodyweight-adjusted Clearance [Weeks 1, 2, 5, 9, 13, and 25]

    Clearance is the volume of plasma that would contain the amount of drug excreted per day. Blood samples were collected for the assessment of bodyweight-adjusted clearance at Weeks 1, 2, 5, 9, 13, and 25. Clearance was estimated using a population-pharmacokinetic model incorporating all available data points from all participants. Individual values were estimated from the model as post-hoc values after incorporating between-participant variability.

30. Steady-State Volume of Distribution [Weeks 1, 2, 5, 9, 13, and 25]

    Steady-state volume of distribution is the blood and tissue volume into which a drug is distributed and the relative binding of drug to protein in these spaces. Blood samples were collected for the assessment of steady-state volume of distribution at Weeks 1, 2, 5, 9, 13, and 25. Steady-state volume of distribution was estimated using a population-pharmacokinetic model incorporating all available data points from all participants. Individual values were estimated from the model as post-hoc values after incorporating between-participant variability.

31. Maximum Observed Plasma Drug Concentration (Cmax), Average Concentration (Cav[0-inf]), and Steady State Maximum Observed Plasma Drug Concentration (Cmax SS) [Weeks 1, 2, 5, 9, 13, and 25]

    Blood samples were collected for the assessment of Cmax, Cav(0-inf), and Cmax SS at Weeks 1, 2, 5, 9, 13, and 25. These parameters were estimated using a population-pharmacokinetic model incorporating all available data points from all participants. Individual values were estimated from the model as post-hoc values after incorporating between-participant variability.

32. Area Under the Plasma Drug Concentration Versus Time Curve From Time 0 Extrapolated to Infinite Time (AUC[0-inf]) [Weeks 1, 2, 5, 9, 13, and 25]

    Blood samples were scheduled to be collected for the assessment of AUC(0-inf) at Weeks 1, 2, 5, 9, 13, and 25 AUC[0-inf] is derived from individual systemic clearance estimates using the expression AUC[0-inf] = Dose/CL. Hence all data are incorporated into the estimation of CL and by implication AUC[0-inf].

33. Half-life (Alpha) and Half-life (Beta) [Weeks 1, 2, 5, 9, 13, and 25]

    Half-life (Alpha) is the rate of decline in plasma concentrations due to the process of drug redistribution from the central to the peripheral compartment and half-life (Beta ) is the rate of decline due to the process of drug elimination due to metabolism. Blood samples were collected for the assessment of half-life (Alpha) and half-life (Beta) at Weeks 1, 2, 5, 9, 13, and 25. Half-life was estimated using a population-pharmacokinetic model incorporating all available data points from all participants. Individual values were estimated from the model as post-hoc values after incorporating between-participant variability.

34. Pharmacokinetic/Pharmacodynamic (PK/PD) Model Derived Baseline [Weeks 1, 2, 5, 9, 13, 17, 21 and 25]

    Blood samples were collected for the assessment of PK/PD model derived Baseline at Weeks 1, 2, 5, 9, 13, 17, 21 and 25. An exploratory Emax direct response model was fitted to serial blood eosinophil count data (including placebo) using model-predicted mepolizumab concentrations (with zero imputed for placebo treated participants). All available blood eosinophil count data were incorporated into the model. Individual values were estimated from the model as post-hoc values after incorporating between-participant variability.

35. PK/PD Model Derived Coefficient of Variation of Baseline (CV[Baseline]), Variation of Maximal Effect of Drug (CV[Emax]), and Residual [Weeks 1, 2, 5, 9, 13, 17, 21 and 25]

    A residual is the difference between the observed and predicted values. Blood samples were collected for the assessment of PK/PD model derived CV(Baseline), CV(Emax), and residual at Weeks 1, 2, 5, 9, 13, 17, 21 and 25. An exploratory Emax direct response model was fitted to serial blood eosinophil count data (including placebo) using model-predicted mepolizumab concentrations (with zero imputed for placebo treated subjects). All available datapoints were incorporated into the model. Individual values are estimated from the model as post-hoc values after incorporating between-participant variability.

36. PK/PD Model Derived Half Maximal Effective Drug Concentration (EC50) [Weeks 1, 2, 5, 9, 13, 17, 21 and 25]

    Blood samples were collected for the assessment of PK/PD model derived EC50 at Weeks 1, 2, 5, 9, 13, 17, 21 and 25. An exploratory Emax direct response model was fitted to serial blood eosinophil count data (including placebo) using model-predicted mepolizumab concentrations (with zero imputed for placebo treated participants). All available datapoints were incorporated into the model. Individual values are estimated from the model as post-hoc values after incorporating between-partcipant variability.

37. PK/PD Model Derived Maximum Inhibition [Weeks 1, 2, 5, 9, 13, 17, 21 and 25]

    Blood samples were collected for the assessment of Maximum Inhibition at Weeks 1, 2, 5, 9, 13, 17, 21 and 25. An exploratory Emax direct response model was fitted to serial blood eosinophil count data (including placebo) using model-predicted mepolizumab concentrations (with zero imputed for placebo treated participants). All available datapoints were incorporated into the model. Individual values are estimated from the model as post-hoc values after incorporating between-participant variability.

38. Number of Participants With Positive Immunogenicity (Anti-mepolizumab Antibody Testing) [Week 1 pre-dose, Week 5 pre-dose, Week 13 pre-dose and Week 25 (4 weeks post last dose)]

    Blood samples were collected at Week 1 pre-dose, Week 5 pre-dose, Week 13 pre-dose and Week 25 (4 weeks post last dose) for anti-mepolizumab antibody testing using a validated electrochemiluminescent (ECL) immunoassay. The assay involved screening, confirmation and titration steps. If serum samples tested positive in the screening assay, they were considered 'potentially positive' and were further analyzed for the specificity using the confirmation assay. Samples that confirmed positive in the confirmation assay were reported as 'positive'.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion:

A subject will be eligible for inclusion in this study only if all of the following criteria apply:

1. Subjects have a diagnosis of severe bilateral nasal polyposis at the screening visit and Visit 1 (i.e. at end of run-in period) which meets the definition of the situation indicative of the need for surgery as described in Decision Table 1 in Appendix 3.

2. Subjects must have had at least one previous surgery for the removal of nasal polyps.

3. Subjects must have an history of refractory response to steroid therapy as shown by being deemed potentially eligible for surgery despite having been on a regular/continuous course of nasal corticosteroids for the treatment of nasal polyposis for at least 3 months and/or have received a short course of oral steroids in the past for nasal polyp treatment.

4. Male or female between 18 and 70 years of age, inclusive at time of signing informed consent.

5. BMI within the range 19.0 to 31.0 kg/m2 (inclusive).

6. Subjects must be free of any clinically significant disease that would interfere with the study schedule or procedures or compromise his/her safety.

7. Subjects with concurrent asthma must be maintained on no more than 10mg/day of Prednisolone or the equivalent.

8. Female subjects of childbearing potential must agree to use one of the contraception methods listed in Section 8.1. This criterion must be followed from 1 month prior to first dose of study medication until four months after last dose of study medication.

Females of non -childbearing potential are defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods in Section 8.1 if they wish to continue their HRT during the study (from 1 month prior to first dose of study medication until four months after last dose of study medication). Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment. For most forms of HRT, at least 2- 4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method.

1. Male subjects must agree to use one of the contraception methods listed in Section 8.1. This criterion must be followed from the time of the first dose of study medication until four months after last dose of study medication.

2. Subjects are capable of giving written informed consent, which includes agreeing to be compliant with the study requirements and restrictions listed in the consent form.

3. Subjects are willing and available to complete the study and all measurements.

4. Subjects are capable of reading, comprehending, and writing the local language at a sufficient level to complete study related materials.

Exclusion:

A subject will not be eligible for inclusion in this study if any of the following criteria apply:

1. As a result of medical interview, physical examination, or screening investigation the physician responsible considers the subject unfit for the study.

2. Subjects requiring oral corticosteroids at a dose greater than 10mg Prednisolone or equivalent during the study will be terminated from the study.

3. Subjects who have had an asthma exacerbation requiring admission to hospital within 4 weeks of Screening.

4. Subjects who have received immunotherapy within the previous 12 months.

5. Subjects with a positive pre-study drug/alcohol screen. A minimum list of drugs that will be screened for include amphetamines, barbiturates, cocaine, opiates, cannabinoids and benzodiazepines.

6. Subjects with a known medical history of Hepatitis B, Hepatitis C, or HIV infection.

7. Subjects with a history or suspicion of drug abuse or alcohol abuse within the last 6 months.

8. Subjects who are currently receiving, or have received within 3 months prior to first mepolizumab dose, chemotherapy, radiotherapy or investigational medications/therapies.

9. Subjects with one or more of the following abnormal laboratory values:

• Serum creatinine ≥ 3 times institutional ULN

• AST or/ALT ≥ 5 times institutional ULN

• Platelet count < 50,000/μL

1. Subjects with a history of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation. Aspirin-sensitive subjects are acceptable.

2. Subjects with a history of allergic reaction to anti-IL-5 or other antibody therapy.

3. Pregnant females as determined by positive serum pregnancy test at screening or positive urine pregnancy test prior to each dosing occasion.

4. Breastfeeding/Lactating females.

5. Subjects who currently smoke or have smoked in the last 6 months.

6. Subjects who are unwilling or unable to follow the procedures outlined in the protocol.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Gent		Belgium	9000
2	GSK Investigational Site	Amsterdam		Netherlands	1105 AZ
3	GSK Investigational Site	Cambridge		United Kingdom
4	GSK Investigational Site	London		United Kingdom	EC1M 6BQ
5	GSK Investigational Site	London		United Kingdom	SW3 6NP
6	GSK Investigational Site	London		United Kingdom	WC1X 8DA

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Publications

• Bachert C, Sousa AR, Lund VJ, Scadding GK, Gevaert P, Nasser S, Durham SR, Cornet ME, Kariyawasam HH, Gilbert J, Austin D, Maxwell AC, Marshall RP, Fokkens WJ. Reduced need for surgery in severe nasal polyposis with mepolizumab: Randomized trial. J Allergy Clin Immunol. 2017 Oct;140(4):1024-1031.e14. doi: 10.1016/j.jaci.2017.05.044. Epub 2017 Jul 4.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT01362244
• Other Study ID Numbers: 111782; 2008-003772-21
• First Posted: May 30, 2011
• Last Update Posted: Apr 12, 2021
• Last Verified: Mar 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by GlaxoSmithKline: Quality of Life; Intranasal Steroids; Severe Nasal Polyposis; Polyp Relapse; Endoscopic Polyp Score; Surgery
• Additional relevant MeSH terms: Nasal Polyps

Study Results

Participant Flow

Pre-assignment Detail	At the end of a 10- to 14-day Run-in Period, participants (par.) were assessed for entry into the Treatment Period, comprised of 8 outpatient visits. For 6 of these visits, participants received a 4-weekly dose of either 750 milligrams (mg) mepolizumab or placebo. Four of the par. withdrew prior to 1st dose and are not included in the par. flow.

Arm/Group Title	Mepolizumab 750 mg	Placebo
Arm/Group Description	Participants received up to a total of six doses (one every 4 weeks) of mepolizumab 750 milligrams (mg) by intravenous infusion.	Participants received up to a total of six doses (one every 4 weeks) of matching placebo by intravenous infusion.
Period Title: Overall Study
STARTED	54	51
COMPLETED	22	19
NOT COMPLETED	32	32

Baseline Characteristics

Arm/Group Title	Mepolizumab 750 mg	Placebo	Total
Arm/Group Description	Participants received up to a total of six doses (one every 4 weeks) of mepolizumab 750 milligrams (mg) by intravenous infusion	Participants received up to a total of six doses (one every 4 weeks) of matching placebo by intravenous infusion.	Total of all reporting groups
Overall Participants	54	51	105
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	50.6 (10.73)	49.7 (10.38)	50.2 (10.52)
Sex: Female, Male (Count of Participants)
Female	13 24.1%	17 33.3%	30 28.6%
Male	41 75.9%	34 66.7%	75 71.4%
Race/Ethnicity, Customized (Count of Participants)
Central/South Asian Heritage (Htg)	2 3.7%	0 0%	2 1.9%
Japanese/East Asian Heritage/ South East Asian Htg	0 0%	1 2%	1 1%
White	52 96.3%	50 98%	102 97.1%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With a Reduced Need for Surgery at Week 25
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 (ENP) 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.
Time Frame	Week 25

Outcome Measure Data

Analysis Population Description

Per Protocol Population: all randomized participants who received at least one dose of study treatment and who complied with the protocol.

Arm/Group Title	Mepolizumab 750 mg	Placebo
Arm/Group Description	Participants received up to a total of six doses (one every 4 weeks) of mepolizumab 750 milligrams (mg) by intravenous infusion.	Participants received up to a total of six doses (one every 4 weeks) of matching placebo by intravenous infusion.
Measure Participants	49	51
NR, Responders	16 29.6%	5 9.8%
NR, Non-Responders	33 61.1%	46 90.2%
LOCF, Responders	17 31.5%	8 15.7%
LOCF, Non- Responders	32 59.3%	43 84.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 750 mg, Placebo
	Comments	Statistical data is presented for NR
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.003
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 750 mg, Placebo
	Comments	Statistical data is presented for LOCF
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.016
	Comments
	Method	Fisher Exact
	Comments

2. Secondary Outcome

Title	Number of Participants With Endoscopic Nasal Polyp (ENP) Score Dynamics at Weeks 1, 2, 5, 9, 13, 17, 21, and 25
Description	Each nostril was assessed for polyps and graded at Weeks 1, 2, 5, 9, 13, 17, 21, and 25. The right and left nostrils were scored from 0 to 4, where, 0 = No polyps; 1 = Small polyps in the middle meatus not reaching below the inferior border of the middle concha; 2 = Polyps reaching below the lower border of the middle turbinate; 3 = Large polyps reaching the lower border of the inferior turbinate or polyps medial to the middle concha; and 4 = Large polyps causing complete obstruction/congestion of the inferior meatus. 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. The ENP score ranges from 0 to 4, with a higher score indicating a larger polyp.
Time Frame	Weeks 1, 2, 5, 9, 13, 17, 21, and 25

Outcome Measure Data

Analysis Population Description

PP Population. Only those participants available at the specified time points (represented by n=X, X) were analyzed.

Arm/Group Title	Mepolizumab 750 mg	Placebo
Arm/Group Description	Participants received up to a total of six doses (one every 4 weeks) of mepolizumab 750 milligrams (mg) by intravenous infusion.	Participants received up to a total of six doses (one every 4 weeks) of matching placebo by intravenous infusion.
Measure Participants	49	51
Week 1, ENP score 0, n=49, 51	0 0%	0 0%
Week 1, ENP score 1, n=49, 51	0 0%	0 0%
Week 1, ENP score 2, n=49, 51	0 0%	0 0%
Week 1, ENP score >=3, n=49, 51	49 90.7%	51 100%
Week 2, ENP score 0, n=48, 51	0 0%	0 0%
Week 2, ENP score 1, n=48, 51	0 0%	0 0%
Week 2, ENP score 2, n=48, 51	1 1.9%	0 0%
Week 2, ENP score >=3, n=48, 51	47 87%	51 100%
Week 5, ENP score 0, n=49, 48	0 0%	0 0%
Week 5, ENP score 1, n=49, 48	0 0%	0 0%
Week 5, ENP score 2, n=49, 48	8 14.8%	6 11.8%
Week 5, ENP score >=3, n=49, 48	41 75.9%	42 82.4%
Week 9, ENP score 0, n=49, 45	0 0%	0 0%
Week 9, ENP score 1, n=49, 45	5 9.3%	0 0%
Week 9, ENP score 2, n=49, 45	8 14.8%	5 9.8%
Week 9, ENP score >=3, n=49, 45	36 66.7%	40 78.4%
Week 13, ENP score 0, n=44, 37	3 5.6%	0 0%
Week 13, ENP score 1, n=44, 37	5 9.3%	0 0%
Week 13, ENP score 2, n=44, 37	5 9.3%	2 3.9%
Week 13, ENP score >=3, n=44, 37	31 57.4%	35 68.6%
Week 17, ENP score 0, n=43, 34	3 5.6%	1 2%
Week 17, ENP score 1, n=43, 34	4 7.4%	1 2%
Week 17, ENP score 2, n=43, 34	7 13%	6 11.8%
Week 17, ENP score >=3, n=43, 34	29 53.7%	26 51%
Week 21, ENP score 0, n=42, 34	4 7.4%	1 2%
Week 21, ENP score 1, n=42, 34	6 11.1%	2 3.9%
Week 21, ENP score 2, n=42, 34	5 9.3%	4 7.8%
Week 21, ENP score >=3, n=42, 34	27 50%	27 52.9%
Week 25, ENP score 0, n=42, 31	3 5.6%	1 2%
Week 25, ENP score 1, n=42, 31	7 13%	2 3.9%
Week 25, ENP score 2, n=42, 31	7 13%	4 7.8%
Week 25, ENP score >=3, n=42, 31	25 46.3%	24 47.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 750 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.710
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.74
	Confidence Interval	(2-Sided) 95%; 0.15 to 3.64
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 1

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 750 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.674
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.40
	Confidence Interval	(2-Sided) 95%; 0.29 to 6.87
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 2

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 750 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.942
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.94
	Confidence Interval	(2-Sided) 95%; 0.20 to 4.49
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 5

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 750 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.091
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	3.90
	Confidence Interval	(2-Sided) 95%; 0.80 to 18.96
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 9

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 750 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.004
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	11.66
	Confidence Interval	(2-Sided) 95%; 2.18 to 62.33
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 13

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 750 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.224
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.74
	Confidence Interval	(2-Sided) 95%; 0.54 to 13.90
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 17

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 750 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.037
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	5.85
	Confidence Interval	(2-Sided) 95%; 1.11 to 30.69
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 21

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 750 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.051
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	5.22
	Confidence Interval	(2-Sided) 95%; 0.99 to 27.44
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 25

3. Secondary Outcome

Title	Number of Participants Who Required Polyp Surgery at Weeks 1, 2, 5, 9, 13, 17, 21, and 25
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.
Time Frame	Weeks 1, 2, 5, 9, 13, 17, 21, and 25

Outcome Measure Data

Analysis Population Description

PP Population

Arm/Group Title	Mepolizumab 750 mg	Placebo
Arm/Group Description	Participants received up to a total of six doses (one every 4 weeks) of mepolizumab 750 milligrams (mg) by intravenous infusion.	Participants received up to a total of six doses (one every 4 weeks) of matching placebo by intravenous infusion.
Measure Participants	49	51
Week 1	49 90.7%	51 100%
Week 2	48 88.9%	51 100%
Week 5	44 81.5%	49 96.1%
Week 9	39 72.2%	48 94.1%
Week 13	38 70.4%	50 98%
Week 17	37 68.5%	46 90.2%
Week 21	35 64.8%	46 90.2%
Week 25	33 61.1%	46 90.2%

4. Secondary Outcome

Title	Mean Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Weeks 2, 5, 9, 13, 17, 21, and 25
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.
Time Frame	Baseline and Weeks 2, 5, 9, 13, 17, 21, and 25

Outcome Measure Data

Analysis Population Description

Safety Population: participants who received >=1 dose of study treatment (based on actual treatment received). One participant randomized to mepolizumab took placebo in error. Thus, "N" for the placebo arm of the SP is greater than for the ITT Population. Participants available at the specified time points (represented by n=X, X) were analyzed.

Arm/Group Title	Mepolizumab 750 mg	Placebo
Arm/Group Description	Participants received up to a total of six doses (one every 4 weeks) of mepolizumab 750 milligrams (mg) by intravenous infusion.	Participants received up to a total of six doses (one every 4 weeks) of matching placebo by intravenous infusion.
Measure Participants	53	52
SBP, Week 2, n=53, 52	-2.0 (14.14)	4.6 (13.33)
SBP, Week 5, n=53, 49	-1.2 (11.74)	0.5 (10.50)
SBP, Week 9, n=51, 46	-0.9 (15.01)	1.0 (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	-2.0 (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	0.0 (8.56)	-0.1 (7.98)
DBP, Week 9, n=51, 46	-1.8 (12.05)	0.0 (7.29)
DBP, Week 13, n=45, 40	-0.6 (9.99)	-0.5 (9.56)
DBP, Week 17, n=45, 36	-2.2 (8.90)	-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)

5. Secondary Outcome

Title	Mean Change From Baseline in Pulse Rate at Weeks 2, 5, 9, 13, 17, 21, and 25
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.
Time Frame	Baseline and Weeks 2, 5, 9, 13, 17, 21, and 25

Outcome Measure Data

Analysis Population Description

Safety Population. One participant randomized to mepolizumab took placebo in error. Thus, "N" for the placebo arm of the SP is greater than for the ITT Population. Only those participants available at the specified time points (represented by n=X, X) were analyzed.

Arm/Group Title	Mepolizumab 750 mg	Placebo
Arm/Group Description	Participants received up to a total of six doses (one every 4 weeks) of mepolizumab 750 milligrams (mg) by intravenous infusion.	Participants received up to a total of six doses (one every 4 weeks) of matching placebo by intravenous infusion.
Measure Participants	53	52
Week 2, n=53, 52	0.2 (8.88)	0.0 (7.86)
Week 5, n=53, 50	-1.1 (9.09)	-1.0 (7.91)
Week 9, n=51, 46	-1.7 (8.40)	-0.8 (7.50)
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	-2.0 (9.56)	-1.2 (8.70)
Week 25, n=41, 32	-0.4 (9.29)	0.0 (8.29)

6. Secondary Outcome

Title	Number of Participants With the Indicated Electrocardiogram (ECG) Findings at Weeks 1, 2, 5, 9, 13, 17, 21, and 25
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. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition.
Time Frame	Weeks 1, 2, 5, 9, 13, 17, 21, and 25

Outcome Measure Data

Analysis Population Description

Safety Population. One participant randomized to mepolizumab took placebo in error. Thus, "N" for the placebo arm of the SP is greater than for the ITT Population. Only those participants available at the specified time points (represented by n=X, X) were analyzed.

Arm/Group Title	Mepolizumab 750 mg	Placebo
Arm/Group Description	Participants received up to a total of six doses (one every 4 weeks) of mepolizumab 750 milligrams (mg) by intravenous infusion.	Participants received up to a total of six doses (one every 4 weeks) of matching placebo by intravenous infusion.
Measure Participants	53	52
Week 1, NCS, n=53, 52	8 14.8%	8 15.7%
Week 1, CS, n=53, 52	0 0%	0 0%
Week 2, NCS, n=52, 52	7 13%	9 17.6%
Week 2, CS, n=52, 52	0 0%	0 0%
Week 5, NCS, n=53, 50	8 14.8%	8 15.7%
Week 5, CS, n=53, 50	0 0%	0 0%
Week 9, NCS, n=52, 46	5 9.3%	3 5.9%
Week 9, CS, n=52, 46	0 0%	0 0%
Week 13, NCS, n=45, 40	6 11.1%	4 7.8%
Week 13, CS, n=45, 40	0 0%	0 0%
Week 17, NCS, n=45, 36	9 16.7%	4 7.8%
Week 17, CS, n=45, 36	0 0%	0 0%
Week 21, NCS, n=42, 34	3 5.6%	1 2%
Week 21, CS, n=42, 34	0 0%	0 0%
Week 25, NCS, n=41, 31	2 3.7%	3 5.9%
Week 25, CS, n=41, 31	0 0%	0 0%

7. Secondary Outcome

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
Description	BUN, glucose fasting, chloride, sodium, potassium, carbon dioxide (CO2), and calcium were assessed at Week 1 pre-dose, Week 2, Week 5 pre-dose, Week 9 pre-dose, Week 13 pre-dose, Week 17 pre-dose, Week 21 pre-dose, and Week 25 (4 Weeks post last dose).
Time Frame	Week 1 pre-dose, Week 2, Week 5 pre-dose, Week 9 pre-dose, Week 13 pre-dose, Week 17 pre-dose, Week 21 pre-dose, and Week 25 (4 Weeks post last dose)

Outcome Measure Data

Analysis Population Description

Safety Population. One participant randomized to mepolizumab took placebo in error. Thus, "N" for the placebo arm of the SP is greater than for the ITT Population. Only those participants available at the specified time points (represented by n=X, X) were analyzed.

Arm/Group Title	Mepolizumab 750 mg	Placebo
Arm/Group Description	Participants received up to a total of six doses (one every 4 weeks) of mepolizumab 750 milligrams (mg) by intravenous infusion.	Participants received up to a total of six doses (one every 4 weeks) of matching placebo by intravenous infusion.
Measure Participants	53	52
Calcium, Week 1, pre-dose, n=46, 46	2.33529 (0.07920)	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)	2.35610 (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	103.0 (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)	27.0 (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	4.10 (0.420)	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	142.0 (2.27)	141.5 (2.30)
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 (3.69770)	7.1568 (3.35084)
Urea, Week 2, n=52, 52	7.8847 (3.86054)	7.1870 (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 (3.61940)	7.9377 (3.59500)
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	7.8770 (3.86299)	6.9864 (3.01889)

8. Secondary Outcome

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
Description	ALT, AST, ALP, and GGT were assessed at Week 1 pre-dose, Week 2, Week 5 pre-dose, Week 9 pre-dose, Week 13 pre-dose, Week 17 pre-dose, Week 21 pre-dose, and Week 25 (4 Weeks post last dose).
Time Frame	Week 1 pre-dose, Week 2, Week 5 pre-dose, Week 9 pre-dose, Week 13 pre-dose, Week 17 pre-dose, Week 21 pre-dose, and Week 25 (4 Weeks post last dose)

Outcome Measure Data

Analysis Population Description

Safety Population. One participant randomized to mepolizumab took placebo in error. Thus, "N" for the placebo arm of the SP is greater than for the ITT Population. Only those participants available at the specified time points (represented by n=X, X) were analyzed.

Arm/Group Title	Mepolizumab 750 mg	Placebo
Arm/Group Description	Participants received up to a total of six doses (one every 4 weeks) of mepolizumab 750 milligrams (mg) by intravenous infusion.	Participants received up to a total of six doses (one every 4 weeks) of matching placebo by intravenous infusion.
Measure Participants	53	52
ALP, Week 1, pre-dose, n=52, 52	76.0 (17.09)	67.8 (20.00)
ALP, Week 2, n=53, 52	75.3 (15.92)	69.0 (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 (16.30)	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 (11.60)	26.9 (15.89)
ALT, Week 5, pre-dose, n=51, 50	26.5 (15.11)	25.0 (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	24.0 (8.34)	23.9 (6.42)
AST, Week 21, pre-dose, n=40, 34	24.5 (6.20)	23.8 (5.18)
AST, Week 25, 4 weeks post last dose, n=41, 32	25.1 (5.63)	24.0 (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 (46.31)	28.3 (24.67)
GGT, Week 5, pre-dose, n=50, 50	33.9 (59.91)	28.0 (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 (69.60)	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	37.0 (54.09)	28.4 (17.24)

9. Secondary Outcome

Title	Absolute Values of the Clinical Chemistry Parameters of Albumin and Protein at Weeks 1, 2, 5, 9, 13, 17, 21, and 25
Description	Albumin and protein were assessed at Week 1 pre-dose, Week 2, Week 5 pre-dose, Week 9 pre-dose, Week 13 pre-dose, Week 17 pre-dose, Week 21 pre-dose, and Week 25 (4 Weeks post last dose).
Time Frame	Week 1 pre-dose, Week 2, Week 5 pre-dose, Week 9 pre-dose, Week 13 pre-dose, Week 17 pre-dose, Week 21 pre-dose, and Week 25 (4 Weeks post last dose)

Outcome Measure Data

Analysis Population Description

Safety Population. One participant randomized to mepolizumab took placebo in error. Thus, "N" for the placebo arm of the SP is greater than for the ITT Population. Only those participants available at the specified time points (represented by n=X, X) were analyzed.

Arm/Group Title	Mepolizumab 750 mg	Placebo
Arm/Group Description	Participants received up to a total of six doses (one every 4 weeks) of mepolizumab 750 milligrams (mg) by intravenous infusion.	Participants received up to a total of six doses (one every 4 weeks) of matching placebo by intravenous infusion.
Measure Participants	53	52
Albumin, Week 1, pre-dose, n=52, 52	46.0 (3.00)	46.1 (2.40)
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 (2.40)
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	45.0 (2.69)	45.1 (2.81)
Albumin, Week 25, 4 weeks post last dose, n=41, 32	45.7 (2.55)	45.3 (2.50)
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 (5.30)
Protein, Week 5, pre-dose, n=50, 49	72.8 (5.33)	72.6 (4.75)
Protein, Week 9, pre-dose, n=51, 46	73.0 (5.39)	72.6 (4.50)
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 (4.30)	71.4 (3.88)
Protein, Week 25, 4 weeks post last dose, n=41, 32	72.1 (4.41)	71.7 (4.53)

10. Secondary Outcome

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
Description	Total bilirubin (TB) and direct bilirubin (DB), creatinine, and uric acid were assessed at Week 1 pre-dose, Week 2, Week 5 pre-dose, Week 9 pre-dose, Week 13 pre-dose, Week 17 pre-dose, Week 21 pre-dose, and Week 25 (4 Weeks post last dose).
Time Frame	Week 1 pre-dose, Week 2, Week 5 pre-dose, Week 9 pre-dose, Week 13 pre-dose, Week 17 pre-dose, Week 21 pre-dose, and Week 25 (4 Weeks post last dose)

Outcome Measure Data

Analysis Population Description

Safety Population. One participant randomized to mepolizumab took placebo in error. Thus, "N" for the placebo arm of the SP is greater than for the ITT Population. Only those participants available at the specified time points (represented by n=X, X) were analyzed.

Arm/Group Title	Mepolizumab 750 mg	Placebo
Arm/Group Description	Participants received up to a total of six doses (one every 4 weeks) of mepolizumab 750 milligrams (mg) by intravenous infusion.	Participants received up to a total of six doses (one every 4 weeks) of matching placebo by intravenous infusion.
Measure Participants	53	52
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)	24031.30 (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 (63827.10)	22994.49 (94463.05)
UA, Week 25, 4 weeks post last dose, n=40, 32	9602.10 (58607.26)	24506.63 (96050.66)
CRT, Week 1, pre-dose, n=52, 52	80.2445 (15.71113)	77.5162 (14.87768)
CRT, Week 2, n=53, 51	80.5450 (14.66619)	78.3620 (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)	10.520 (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 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	9.820 (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	2.9160 (1.02560)	3.0690 (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 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)

11. Secondary Outcome

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
Description	Platelet count, WBC count, basophils, eosinophils, lymphocytes, monocytes, and neutrophils were assessed at Week 1 pre-dose, Week 2, Week 5 pre-dose, Week 9 pre-dose, Week 13 pre-dose, Week 17 pre-dose, Week 21 pre-dose, and Week 25 (4 Weeks post last dose).
Time Frame	Week 1 pre-dose, Week 2, Week 5 pre-dose, Week 9 pre-dose, Week 13 pre-dose, Week 17 pre-dose, Week 21 pre-dose, and Week 25 (4 Weeks post last dose)

Outcome Measure Data

Analysis Population Description

Safety Population. One participant randomized to mepolizumab took placebo in error. Thus, "N" for the placebo arm of the SP is greater than for the ITT Population. Only those participants available at the specified time points (represented by n=X, X) were analyzed.

Arm/Group Title	Mepolizumab 750 mg	Placebo
Arm/Group Description	Participants received up to a total of six doses (one every 4 weeks) of mepolizumab 750 milligrams (mg) by intravenous infusion.	Participants received up to a total of six doses (one every 4 weeks) of matching placebo by intravenous infusion.
Measure Participants	53	52
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 (61.20)
Platelets, Week 9, pre-dose, n=51, 46	239.1 (43.29)	267.0 (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	233.0 (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	6.20 (1.535)	6.90 (2.014)
WBC, Week 5, pre-dose, n=53, 50	6.17 (1.580)	6.77 (1.574)
WBC, Week 9, pre-dose, n=51, 46	5.90 (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 (1.780)	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)	7.00 (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)
Basophil, 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	0.63 (0.496)	0.54 (0.305)
Eosinophils, Week 2, n=53, 52	0.10 (0.079)	0.55 (0.346)
Eosinophils, Week 5, pre-dose, n=53, 50	0.05 (0.030)	0.51 (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)	0.56 (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)	1.90 (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	1.80 (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, 32	1.88 (0.604)	1.91 (0.523)
Monocytes, Week 1, pre-dose, n=52, 51	0.56 (0.166)	0.50 (0.131)
Monocytes, Week 2, n=53, 52	0.56 (0.175)	0.54 (0.190)
Monocytes, Week 5, pre-dose, n=53, 50	0.53 (0.170)	0.51 (0.138)
Monocytes, Week 9, pre-dose, n=51, 46	0.50 (0.140)	0.53 (0.163)
Monocytes, Week 13, pre-dose, n=45, 40	0.50 (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	0.50 (0.150)	0.55 (0.158)
Monocytes, Week 25,4 weeks post last dose,n=41, 32	0.51 (0.130)	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)	3.78720 (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	3.52400 (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, 32	3.46854 (1.045869)	4.03125 (1.452175)

12. Secondary Outcome

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
Description	Hemoglobin and MCHC were assessed at Week 1 pre-dose, Week 2, Week 5 pre-dose, Week 9 pre-dose, Week 13 pre-dose, Week 17 pre-dose, Week 21 pre-dose, and Week 25 (4 Weeks post last dose).
Time Frame	Week 1 pre-dose, Week 2, Week 5 pre-dose, Week 9 pre-dose, Week 13 pre-dose, Week 17 pre-dose, Week 21 pre-dose, and Week 25 (4 Weeks post last dose)

Outcome Measure Data

Analysis Population Description

Safety Population. One participant randomized to mepolizumab took placebo in error. Thus, "N" for the placebo arm of the SP is greater than for the ITT Population. Only those participants available at the specified time points (represented by n=X, X) were analyzed.

Arm/Group Title	Mepolizumab 750 mg	Placebo
Arm/Group Description	Participants received up to a total of six doses (one every 4 weeks) of mepolizumab 750 milligrams (mg) by intravenous infusion.	Participants received up to a total of six doses (one every 4 weeks) of matching placebo by intravenous infusion.
Measure Participants	53	52
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 (10.8860)	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 (10.9510)	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, 32	148.927 (10.5835)	147.940 (8.9890)
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 (10.40)	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)	337.0 (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)

13. Secondary Outcome

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
Description	RBC count and RC were assessed at Week 1 pre-dose, Week 2, Week 5 pre-dose, Week 9 pre-dose, Week 13 pre-dose, Week 17 pre-dose, Week 21 pre-dose, and Week 25 (4 Weeks post last dose).
Time Frame	Week 1 pre-dose, Week 2, Week 5 pre-dose, Week 9 pre-dose, Week 13 pre-dose, Week 17 pre-dose, Week 21 pre-dose, and Week 25 (4 Weeks post last dose)

Outcome Measure Data

Analysis Population Description

Safety Population. One participant randomized to mepolizumab took placebo in error. Thus, "N" for the placebo arm of the SP is greater than for the ITT Population. Only those participants available at the specified time points (represented by n=X, X) were analyzed.

Arm/Group Title	Mepolizumab 750 mg	Placebo
Arm/Group Description	Participants received up to a total of six doses (one every 4 weeks) of mepolizumab 750 milligrams (mg) by intravenous infusion.	Participants received up to a total of six doses (one every 4 weeks) of matching placebo by intravenous infusion.
Measure Participants	53	52
RBC, Week 1, pre-dose, n=52, 52	4.889 (0.3758)	4.930 (0.4830)
RBC, Week 2, n=53, 52	4.868 (0.4024)	4.937 (0.4340)
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	4.840 (0.3743)	4.910 (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 (0.02530)
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 (0.01530)	0.0528 (0.01780)
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 (0.01640)	0.0580 (0.02625)

14. Secondary Outcome

Title	Absolute Values of the Hematology Parameter of Mean Corpuscular Hemoglobin (MCH) at Weeks 1, 2, 5, 9, 13, 17, 21, and 25
Description	MCH was assessed at Week 1 pre-dose, Week 2, Week 5 pre-dose, Week 9 pre-dose, Week 13 pre-dose, Week 17 pre-dose, Week 21 pre-dose, and Week 25 (4 Weeks post last dose).
Time Frame	Week 1 pre-dose, Week 2, Week 5 pre-dose, Week 9 pre-dose, Week 13 pre-dose, Week 17 pre-dose, Week 21 pre-dose, and Week 25 (4 Weeks post last dose)

Outcome Measure Data

Analysis Population Description

Safety Population. One participant randomized to mepolizumab took placebo in error. Thus, "N" for the placebo arm of the SP is greater than for the ITT Population. Only those participants available at the specified time points (represented by n=X, X) were analyzed.

Arm/Group Title	Mepolizumab 750 mg	Placebo
Arm/Group Description	Participants received up to a total of six doses (one every 4 weeks) of mepolizumab 750 milligrams (mg) by intravenous infusion.	Participants received up to a total of six doses (one every 4 weeks) of matching placebo by intravenous infusion.
Measure Participants	53	52
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)	30.10 (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)	30.10 (1.951)
Week 21, pre-dose, n=42, 34	30.33 (1.354)	30.00 (2.035)
Week 25,4 weeks post last dose,n=40, 32	30.41 (1.196)	30.26 (1.243)

15. Secondary Outcome

Title	Absolute Values of the Hematology Parameter of Mean Corpuscular Volume (MCV) at Weeks 1, 2, 5, 9, 13, 17, 21, and 25
Description	MCV was assessed at Week 1 pre-dose, Week 2, Week 5 pre-dose, Week 9 pre-dose, Week 13 pre-dose, Week 17 pre-dose, Week 21 pre-dose, and Week 25 (4 Weeks post last dose).
Time Frame	Week 1 pre-dose, Week 2, Week 5 pre-dose, Week 9 pre-dose, Week 13 pre-dose, Week 17 pre-dose, Week 21 pre-dose, and Week 25 (4 Weeks post last dose)

Outcome Measure Data

Analysis Population Description

Safety Population. One participant randomized to mepolizumab took placebo in error. Thus, "N" for the placebo arm of the SP is greater than for the ITT Population. Only those participants available at the specified time points (represented by n=X, X) were analyzed.

Arm/Group Title	Mepolizumab 750 mg	Placebo
Arm/Group Description	Participants received up to a total of six doses (one every 4 weeks) of mepolizumab 750 milligrams (mg) by intravenous infusion.	Participants received up to a total of six doses (one every 4 weeks) of matching placebo by intravenous infusion.
Measure Participants	53	52
Week 1, pre-dose, n=52, 52	90.04 (3.850)	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	89.50 (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)

16. Secondary Outcome

Title	Absolute Value of the Hematology Parameter of Reticulocyte Count/Erythrocyte Uncorrected at Weeks 1, 2, 5, 9, 13, 17, 21, and 25
Description	Reticulocyte count was assessed at Week 1 pre-dose, Week 2, Week 5 pre-dose, Week 9 pre-dose, Week 13 pre-dose, Week 17 pre-dose, Week 21 pre-dose, and Week 25 (4 Weeks post last dose).
Time Frame	Week 1 pre-dose, Week 2, Week 5 pre-dose, Week 9 pre-dose, Week 13 pre-dose, Week 17 pre-dose, Week 21 pre-dose, and Week 25 (4 Weeks post last dose)

Outcome Measure Data

Analysis Population Description

Safety Population. One participant randomized to mepolizumab took placebo in error. Thus, "N" for the placebo arm of the SP is greater than for the ITT Population. Only those participants available at the specified time points (represented by n=X, X) were analyzed.

Arm/Group Title	Mepolizumab 750 mg	Placebo
Arm/Group Description	Participants received up to a total of six doses (one every 4 weeks) of mepolizumab 750 milligrams (mg) by intravenous infusion.	Participants received up to a total of six doses (one every 4 weeks) of matching placebo by intravenous infusion.
Measure Participants	19	16
Week 1, pre-dose, n=19, 16	0.1723 (0.16091)	0.1053 (0.05750)
Week 2, n=19, 16	0.1710 (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 (0.11350)	0.1395 (0.11754)
Week 25,4 weeks post last dose, n=15, 12	0.1465 (0.12045)	0.1402 (0.09660)

17. Secondary Outcome

Title	Number of Participants With Positive Clinically Relevant Urinalysis Results at Weeks 1, 2, 5, 9, 13, 17, 21, and 25
Description	Specific gravity, power of hydrogen (pH), glucose, protein, blood, and ketones were assessed at Weeks (Wk) 1, 2, 5, 9, 13, 17, 21, and 25. Results for all urinalysis parameters were assessed for clinical relevance by physician. Clinically relevant positive results are presented. Clinically relevant positive results are defined as those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition.
Time Frame	Weeks 1, 2, 5, 9, 13, 17, 21, and 25

Outcome Measure Data

Analysis Population Description

Safety Population. One participant randomized to mepolizumab took placebo in error. Thus, "N" for the placebo arm of the SP is greater than for the ITT Population. Only those participants available at the specified time points (represented by n=X, X) were analyzed.

Arm/Group Title	Mepolizumab 750 mg	Placebo
Arm/Group Description	Participants received up to a total of six doses (one every 4 weeks) of mepolizumab 750 milligrams (mg) by intravenous infusion.	Participants received up to a total of six doses (one every 4 weeks) of matching placebo by intravenous infusion.
Measure Participants	53	52
Clinically relevant positive results Wk 1, n=53,52	0 0%	0 0%
Clinically relevant positive results Wk 2, n=46,49	0 0%	0 0%
Clinically relevant positive results Wk 5, n=53,50	0 0%	0 0%
Clinically relevant positive results Wk 9, n=51,46	0 0%	0 0%
Clinically relevant positive results Wk 13,n=45,40	0 0%	0 0%
Clinically relevant positive results Wk 17,n=45,36	0 0%	0 0%
Clinically relevant positive results Wk 21,n=42,34	0 0%	0 0%
Clinically relevant positive results Wk 25,n=39,31	0 0%	0 0%

18. Secondary Outcome

Title	Number of Participants With Any Treatment-emergent Adverse Event (AE) and Serious Adverse Event (SAE)
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.
Time Frame	Up to 11 months

Outcome Measure Data

Analysis Population Description

Safety Population. One participant randomized to mepolizumab took placebo in error. Thus, "N" for the placebo arm of the SP is greater than for the ITT Population.

Arm/Group Title	Mepolizumab 750 mg	Placebo
Arm/Group Description	Participants received up to a total of six doses (one every 4 weeks) of mepolizumab 750 milligrams (mg) by intravenous infusion.	Participants received up to a total of six doses (one every 4 weeks) of matching placebo by intravenous infusion.
Measure Participants	53	52
Any AE	40 74.1%	42 82.4%
Any SAE	0 0%	0 0%

19. Secondary Outcome

Title	Mean of the Forced Expiratory Volume in 1 Second (FEV1) at Weeks 2, 5, 9, 13, 17, 21, and 25
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.
Time Frame	Weeks 2, 5, 9, 13, 17, 21, and 25

Outcome Measure Data

Analysis Population Description

ITT Population: all randomized 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.

Arm/Group Title	Mepolizumab 750 mg	Placebo
Arm/Group Description	Participants received up to a total of six doses (one every 4 weeks) of mepolizumab 750 milligrams (mg) by intravenous infusion.	Participants received up to a total of six doses (one every 4 weeks) of matching placebo by intravenous infusion.
Measure Participants	54	51
Week 2, n=54, 51	3.24	3.20
Week 5, n=54, 49	3.33	3.28
Week 9, n=47, 44	3.32	3.23
Week 13, n=44, 37	3.35	3.18
Week 17, n=43, 34	3.33	3.12
Week 21, n=42, 32	3.41	3.18
Week 25, n=42, 32	3.35	3.18

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 750 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.567
	Comments
	Method	repeated measures model
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.04
	Confidence Interval	(2-Sided) 95%; -0.10 to 0.19
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 2

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 750 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.495
	Comments
	Method	repeated measures model
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.05
	Confidence Interval	(2-Sided) 95%; -0.10 to 0.21
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 5

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 750 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.365
	Comments
	Method	repeated measures model
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.09
	Confidence Interval	(2-Sided) 95%; -0.10 to 0.28
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 9

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 750 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.058
	Comments
	Method	repeated measures model
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.17
	Confidence Interval	(2-Sided) 95%; -0.01 to 0.34
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 13

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 750 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.056
	Comments
	Method	repeated measures model
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.21
	Confidence Interval	(2-Sided) 95%; -0.01 to 0.43
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 17

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 750 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.028
	Comments
	Method	repeated measures model
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.23
	Confidence Interval	(2-Sided) 95%; 0.03 to 0.42
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 21

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 750 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.077
	Comments
	Method	repeated measures model
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.16
	Confidence Interval	(2-Sided) 95%; -0.02 to 0.34
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 25

20. Secondary Outcome

Title	Mean of Forced Vital Capacity (FVC) at Weeks 2, 5, 9, 13, 17, 21, and 25
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.
Time Frame	Weeks 2, 5, 9, 13, 17, 21, and 25

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants available at the specified time points (represented by n=X, X) were analyzed.

Arm/Group Title	Mepolizumab 750 mg	Placebo
Arm/Group Description	Participants received up to a total of six doses (one every 4 weeks) of mepolizumab 750 milligrams (mg) by intravenous infusion.	Participants received up to a total of six doses (one every 4 weeks) of matching placebo by intravenous infusion.
Measure Participants	54	51
Week 2, n=54, 51	4.51	4.45
Week 5, n=54, 49	4.55	4.49
Week 9, n=47, 44	4.52	4.46
Week 13, n=44, 37	4.62	4.43
Week 17, n=43, 34	4.59	4.37
Week 21, n=42, 32	4.66	4.38
Week 25, n=42, 32	4.59	4.41

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 750 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.486
	Comments
	Method	repeated measures model
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.06
	Confidence Interval	(2-Sided) 95%; -0.10 to 0.22
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 2

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 750 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.384
	Comments
	Method	repeated measures model
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.07
	Confidence Interval	(2-Sided) 95%; -0.08 to 0.22
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 5

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 750 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.546
	Comments
	Method	repeated measures model
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.06
	Confidence Interval	(2-Sided) 95%; -0.14 to 0.26
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 9

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 750 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.050
	Comments
	Method	repeated measures model
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.20
	Confidence Interval	(2-Sided) 95%; 0.00 to 0.39
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 13

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 750 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.061
	Comments
	Method	repeated measures model
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.22
	Confidence Interval	(2-Sided) 95%; -0.01 to 0.45
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 17

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 750 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.016
	Comments
	Method	repeated measures model
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.28
	Confidence Interval	(2-Sided) 95%; 0.05 to 0.51
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 21

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 750 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.094
	Comments
	Method	repeated measures model
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.18
	Confidence Interval	(2-Sided) 95%; -0.03 to 0.40
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 25

21. Secondary Outcome

Title	Mean Peak Expiratory Flow Rate (PEFR) at Indicated Weeks 2, 5, 9, 13, 17, 21, and 25
Description	PEFR is defined as the maximum airflowrate 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.
Time Frame	Weeks 2, 5, 9, 13, 17, 21, and 25

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants available at the specified time points (represented by n=X, X) were analyzed.

Arm/Group Title	Mepolizumab 750 mg	Placebo
Arm/Group Description	Participants received up to a total of six doses (one every 4 weeks) of mepolizumab 750 milligrams (mg) by intravenous infusion.	Participants received up to a total of six doses (one every 4 weeks) of matching placebo by intravenous infusion.
Measure Participants	54	51
Week 2, n=54, 51	472.81	467.70
Week 5, n=54, 49	489.08	474.53
Week 9, n=47, 45	487.07	478.16
Week 13, n=44, 37	494.04	470.81
Week 17, n=43, 34	493.68	455.52
Week 21, n=42, 32	501.88	463.17
Week 25, n=42, 32	481.05	466.93

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 750 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.686
	Comments
	Method	repeated measures model
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	5.11
	Confidence Interval	(2-Sided) 95%; -19.91 to 30.12
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 2

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 750 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.321
	Comments
	Method	repeated measures model
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	14.55
	Confidence Interval	(2-Sided) 95%; -14.40 to 43.50
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 5

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 750 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.622
	Comments
	Method	repeated measures model
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	8.91
	Confidence Interval	(2-Sided) 95%; -26.79 to 44.60
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 9

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 750 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.178
	Comments
	Method	repeated measures model
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	23.24
	Confidence Interval	(2-Sided) 95%; -10.75 to 57.22
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 13

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 750 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.052
	Comments
	Method	repeated measures model
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	38.16
	Confidence Interval	(2-Sided) 95%; -0.33 to 76.66
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 17

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 750 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.042
	Comments
	Method	repeated measures model
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	38.72
	Confidence Interval	(2-Sided) 95%; 1.41 to 76.02
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 21

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 750 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.484
	Comments
	Method	repeated measures model
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	14.13
	Confidence Interval	(2-Sided) 95%; -25.76 to 54.02
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 25

22. Secondary Outcome

Title	Individual Symptoms Visual Analogue Scale (VAS) Scores at Weeks 1, 2, 5, 9, 13, 17, 21, and 25
Description	Participants were asked to indicate on a VAS (0 to 10 centimeters) the severity of nasal polyposis and its four 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." Hence the score ranges between 0 to 10, with higher scores indicating greater severity.
Time Frame	Weeks 1, 2, 5, 9, 13, 17, 21, and 25

Outcome Measure Data

Analysis Population Description

PP Population. Only those participants available at the specified time points (represented by n=X, X) were analyzed.

Arm/Group Title	Mepolizumab 750 mg	Placebo
Arm/Group Description	Participants received up to a total of six doses (one every 4 weeks) of mepolizumab 750 milligrams (mg) by intravenous infusion.	Participants received up to a total of six doses (one every 4 weeks) of matching placebo by intravenous infusion.
Measure Participants	49	51
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	7.10 (2.310)	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	5.00 (3.518)	6.44 (3.164)
Nasal Polyposis, Week 21, n=42, 33	4.70 (3.513)	6.47 (3.098)
Nasal Polyposis, Week 25, n=42, 31	4.16 (3.582)	6.21 (3.357)
Rhinorrhea, Week 1, n=49, 51	6.60 (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 (3.340)	5.19 (3.106)
Rhinorrhea, Week 17, n=44, 34	3.33 (3.338)	4.82 (3.399)
Rhinorrhea, Week 21, n=42, 34	3.50 (3.408)	4.70 (3.512)
Rhinorrhea, Week 25, n=42, 31	3.03 (3.428)	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 (2.640)
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 (3.280)
Mucus in Throat, Week 17, n=44, 34	3.28 (3.190)	5.16 (3.482)
Mucus in Throat, Week 21, n=42, 34	3.30 (3.356)	4.84 (3.457)
Mucus in Throat, Week 25, n=42, 31	3.24 (3.263)	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 (3.020)	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=42, 31	3.61 (3.464)	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)	8.20 (2.835)
Loss of Smell, Week 25, n=42, 31	6.02 (4.069)	7.90 (3.378)

23. Secondary Outcome

Title	Mean Peak Nasal Inspiratory Flow (PNIF) at Weeks 2, 5, 9, 13, 17, 21, and 25
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.
Time Frame	Weeks 2, 5, 9, 13, 17, 21, and 25

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants available at the specified time points (represented by n=X, X) were analyzed.

Arm/Group Title	Mepolizumab 750 mg	Placebo
Arm/Group Description	Participants received up to a total of six doses (one every 4 weeks) of mepolizumab 750 milligrams (mg) by intravenous infusion.	Participants received up to a total of six doses (one every 4 weeks) of matching placebo by intravenous infusion.
Measure Participants	54	51
Week 2, n=54, 51	120.82	99.66
Week 5, n=54, 49	127.21	110.32
Week 9, n=47, 46	123.91	116.71
Week 13, n=45, 37	137.50	109.79
Week 17, n=44, 34	132.41	117.02
Week 21, n=42, 33	143.03	113.52
Week 25, n=42, 32	137.02	110.37

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 750 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.005
	Comments
	Method	repeated measures model
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	21.16
	Confidence Interval	(2-Sided) 95%; 6.49 to 35.83
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 2

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 750 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.029
	Comments
	Method	repeated measures model
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	16.89
	Confidence Interval	(2-Sided) 95%; 1.77 to 32.01
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 5

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 750 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.472
	Comments
	Method	repeated measures model
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	7.20
	Confidence Interval	(2-Sided) 95%; -12.64 to 27.03
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 9

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 750 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.009
	Comments
	Method	repeated measures model
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	27.71
	Confidence Interval	(2-Sided) 95%; 7.19 to 48.23
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 13

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 750 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.114
	Comments
	Method	repeated measures model
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	15.40
	Confidence Interval	(2-Sided) 95%; -3.80 to 34.59
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 17

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 750 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.014
	Comments
	Method	repeated measures model
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	29.51
	Confidence Interval	(2-Sided) 95%; 6.06 to 52.96
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 21

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 750 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.027
	Comments
	Method	repeated measures model
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	26.65
	Confidence Interval	(2-Sided) 95%; 3.10 to 50.21
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 25

24. Secondary Outcome

Title	Olfaction Testing: Worst Nostril Score (WNS) and Mean Nostril Score (MNS) at Weeks 2, 5, 9, 13, 17, 21, and 25
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.
Time Frame	Weeks 2, 5, 9, 13, 17, 21, and 25

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants available at the specified time points (represented by n=X, X) were analyzed.

Arm/Group Title	Mepolizumab 750 mg	Placebo
Arm/Group Description	Participants received up to a total of six doses (one every 4 weeks) of mepolizumab 750 milligrams (mg) by intravenous infusion.	Participants received up to a total of six doses (one every 4 weeks) of matching placebo by intravenous infusion.
Measure Participants	54	51
MNS, Week 2, n=54, 51	3.78	3.68
MNS, Week 5, n=54, 49	4.20	3.07
MNS, Week 9, n=47, 45	4.48	3.69
MNS, Week 13, n=45, 37	4.39	3.66
MNS, Week 17, n=43, 34	4.64	4.26
MNS, Week 21, n=42, 33	4.77	4.12
MNS, Week 25, n=41, 32	4.40	3.69
WNS, Week 2, n=54, 51	3.18	2.89
WNS, Week 5, n=54, 49	3.72	2.41
WNS, Week 9, n=47, 45	3.85	3.17
WNS, Week 13, n=45, 37	3.76	3.14
WNS, Week 17, n=43, 34	3.93	3.74
WNS, Week 21, n=42, 33	4.16	3.52
WNS, Week 25, n=41, 32	3.75	3.30

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 750 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.790
	Comments
	Method	repeated measures model
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.09
	Confidence Interval	(2-Sided) 95%; -0.61 to 0.79
	Parameter Dispersion	Type: Value:
	Estimation Comments	MNS, Week 2

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 750 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.008
	Comments
	Method	repeated measures model
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1.14
	Confidence Interval	(2-Sided) 95%; 0.30 to 1.97
	Parameter Dispersion	Type: Value:
	Estimation Comments	MNS, Week 5

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 750 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.066
	Comments
	Method	repeated measures model
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.79
	Confidence Interval	(2-Sided) 95%; -0.05 to 1.64
	Parameter Dispersion	Type: Value:
	Estimation Comments	MNS, Week 9

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 750 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.127
	Comments
	Method	repeated measures model
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.73
	Confidence Interval	(2-Sided) 95%; -0.21 to 1.67
	Parameter Dispersion	Type: Value:
	Estimation Comments	MNS, Week 13

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 750 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.481
	Comments
	Method	repeated measures model
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.38
	Confidence Interval	(2-Sided) 95%; -0.69 to 1.46
	Parameter Dispersion	Type: Value:
	Estimation Comments	MNS, Week 17

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 750 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.308
	Comments
	Method	repeated measures model
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.65
	Confidence Interval	(2-Sided) 95%; -0.61 to 1.90
	Parameter Dispersion	Type: Value:
	Estimation Comments	MNS, Week 21

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 750 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.233
	Comments
	Method	repeated measures model
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.71
	Confidence Interval	(2-Sided) 95%; -0.46 to 1.88
	Parameter Dispersion	Type: Value:
	Estimation Comments	MNS, Week 25

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 750 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.444
	Comments
	Method	repeated measures model
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.28
	Confidence Interval	(2-Sided) 95%; -0.45 to 1.02
	Parameter Dispersion	Type: Value:
	Estimation Comments	WNS, Week 2

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 750 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.002
	Comments
	Method	repeated measures model
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1.31
	Confidence Interval	(2-Sided) 95%; 0.50 to 2.12
	Parameter Dispersion	Type: Value:
	Estimation Comments	WNS, Week 5

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 750 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.143
	Comments
	Method	repeated measures model
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.68
	Confidence Interval	(2-Sided) 95%; -0.24 to 1.60
	Parameter Dispersion	Type: Value:
	Estimation Comments	WNS, Week 9

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 750 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.240
	Comments
	Method	repeated measures model
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.62
	Confidence Interval	(2-Sided) 95%; -0.42 to 1.65
	Parameter Dispersion	Type: Value:
	Estimation Comments	WNS, Week 13

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 750 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.750
	Comments
	Method	repeated measures model
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.19
	Confidence Interval	(2-Sided) 95%; -0.98 to 1.35
	Parameter Dispersion	Type: Value:
	Estimation Comments	WNS, Week 17

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 750 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.324
	Comments
	Method	repeated measures model
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.64
	Confidence Interval	(2-Sided) 95%; -0.64 to 1.91
	Parameter Dispersion	Type: Value:
	Estimation Comments	WNS, Week 21

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 750 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.468
	Comments
	Method	repeated measures model
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.44
	Confidence Interval	(2-Sided) 95%; -0.77 to 1.66
	Parameter Dispersion	Type: Value:
	Estimation Comments	WNS, Week 25

25. Secondary Outcome

Title	Sino-Nasal Outcome Test (SNOT)-22 Questionnaire Total Score at Week 25 (Adjusted for Week 1 Baseline)
Description	SNOT-22 questionnaire is a modification of the SNOT-20 and contains the questions (ques) related to smell and nasal obstruction. Each ques is graded with a numerical score for each response (resp); scores range from 0 for "no symptoms" to 5 for "as bad as things could be." Scores for each of the ques is summed to derive the total score for that par. at that visit. If the par. did not complete any ques 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 par. had some missing scores (but no more than 50% missing at that visit), then scores for the missing resp were imputed as the mean of the non-missing resp for that par. 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 at Week 25, adjusting for Week 1 Baseline scores.
Time Frame	Week 1 (Baseline) and Week 25

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Mepolizumab 750 mg	Placebo
Arm/Group Description	Participants received up to a total of six doses (one every 4 weeks) of mepolizumab 750 milligrams (mg) by intravenous infusion.	Participants received up to a total of six doses (one every 4 weeks) of matching placebo by intravenous infusion.
Measure Participants	54	51
Least Squares Mean (Standard Error) [Scores on a scale]	27.13 (2.96)	40.36 (3.39)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 750 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.005
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mixed effects model
	Estimated Value	-13.2
	Confidence Interval	(2-Sided) 95%; -22.2 to -4.22
	Parameter Dispersion	Type: Value:
	Estimation Comments

26. Secondary Outcome

Title	Index Score of the EuroQoL Quality of Life-5D (EQ-5D) Questionnaire at Week 25 (Adjusting for Week 1 Baseline Scores)
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 by taking sum of weights. Index score ranges from -0.718 to 1, with lower scores indicating poor health. ANCOVA model with treatment, Baseline (Week 1 scores) and country as factors was used to calculate treatment difference and confidence intervals at Week 25.
Time Frame	Week 1 (Baseline) and Week 25

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Mepolizumab 750 mg	Placebo
Arm/Group Description	Participants received up to a total of six doses (one every 4 weeks) of mepolizumab 750 milligrams (mg) by intravenous infusion.	Participants received up to a total of six doses (one every 4 weeks) of matching placebo by intravenous infusion.
Measure Participants	54	51
Least Squares Mean (Standard Error) [Scores on a scale]	0.91 (0.02)	0.91 (0.02)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 750 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.00
	Confidence Interval	(2-Sided) 95%; -0.06 to 0.07
	Parameter Dispersion	Type: Value:
	Estimation Comments

27. Secondary Outcome

Title	VAS Score of the EQ-5D Questionnaire at Week 25 (Adjusting for Week 1 Baseline Scores)
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). ANCOVA model with treatment, Baseline (Week 1 scores) and country as factors was used to calculate treatment difference and confidence intervals at Week 25.
Time Frame	Week 1 (Baseline) and Week 25

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Mepolizumab 750 mg	Placebo
Arm/Group Description	Participants received up to a total of six doses (one every 4 weeks) of mepolizumab 750 milligrams (mg) by intravenous infusion.	Participants received up to a total of six doses (one every 4 weeks) of matching placebo by intravenous infusion.
Measure Participants	54	51
Least Squares Mean (Standard Error) [Scores on a scale]	81.13 (2.30)	75.45 (2.64)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 750 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	5.68
	Confidence Interval	(2-Sided) 95%; -1.33 to 12.68
	Parameter Dispersion	Type: Value:
	Estimation Comments

28. Secondary Outcome

Title	Systemic Clearance of Mepolizumab 750 mg
Description	Blood samples were collected for the assessment of systemic clearance at Weeks 1, 2, 5, 9, 13, and 25. Systemic Clearance (CL) is estimated using a population-Pharmacokinetic model incorporating all available data points from all participants. Individual values were estimated from the model as post-hoc values after incorporating between-participant variability.
Time Frame	Weeks 1, 2, 5, 9, 13, and 25

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) Population: participants in the Safety Population for whom at least one PK sample was obtained and analyzed.

Arm/Group Title	Mepolizumab 750 mg
Arm/Group Description	Participants received up to a total of six doses (one every 4 weeks) of mepolizumab 750 milligrams (mg) by intravenous infusion.
Measure Participants	52
Mean (Standard Deviation) [Liters per day]	0.250 (0.0659)

29. Secondary Outcome

Title	Volume of Distribution of Mepolizumab 750 mg
Description	Volume of distribution at steady-state was derived from pharmacokinetic parameter estimates of a population pharmacokinetic model. Blood samples were collected for analysis of volume of distribution at Weeks 1, 2, 5, 9, 13, and 25. All available concentrations at all available datapoints from all participants were incorporated into the model. Individual values were estimated from the model as post-hoc values after incorporating between-participant variability.
Time Frame	Weeks 1, 2, 5, 9, 13, and 25

Outcome Measure Data

Analysis Population Description

PK Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	Mepolizumab 750 mg
Arm/Group Description	Participants received up to a total of six doses (one every 4 weeks) of mepolizumab 750 milligrams (mg) by intravenous infusion.
Measure Participants	52
Mean (Standard Deviation) [Liters]	8.387 (2.0062)

30. Secondary Outcome

Title	Bodyweight-adjusted Clearance
Description	Clearance is the volume of plasma that would contain the amount of drug excreted per day. Blood samples were collected for the assessment of bodyweight-adjusted clearance at Weeks 1, 2, 5, 9, 13, and 25. Clearance was estimated using a population-pharmacokinetic model incorporating all available data points from all participants. Individual values were estimated from the model as post-hoc values after incorporating between-participant variability.
Time Frame	Weeks 1, 2, 5, 9, 13, and 25

Outcome Measure Data

Analysis Population Description

PK Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	Mepolizumab 750 mg
Arm/Group Description	Participants received up to a total of six doses (one every 4 weeks) of mepolizumab 750 milligrams (mg) by intravenous infusion.
Measure Participants	52
Least Squares Mean (Standard Error) [Liters per day]	0.2170 (0.009547)

31. Secondary Outcome

Title	Steady-State Volume of Distribution
Description	Steady-state volume of distribution is the blood and tissue volume into which a drug is distributed and the relative binding of drug to protein in these spaces. Blood samples were collected for the assessment of steady-state volume of distribution at Weeks 1, 2, 5, 9, 13, and 25. Steady-state volume of distribution was estimated using a population-pharmacokinetic model incorporating all available data points from all participants. Individual values were estimated from the model as post-hoc values after incorporating between-participant variability.
Time Frame	Weeks 1, 2, 5, 9, 13, and 25

Outcome Measure Data

Analysis Population Description

PK Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	Mepolizumab 750 mg
Arm/Group Description	Participants received up to a total of six doses (one every 4 weeks) of mepolizumab 750 milligrams (mg) by intravenous infusion.
Measure Participants	52
Least Squares Mean (Standard Error) [Liters]	7.0958 (0.3226)

32. Secondary Outcome

Title	Maximum Observed Plasma Drug Concentration (Cmax), Average Concentration (Cav[0-inf]), and Steady State Maximum Observed Plasma Drug Concentration (Cmax SS)
Description	Blood samples were collected for the assessment of Cmax, Cav(0-inf), and Cmax SS at Weeks 1, 2, 5, 9, 13, and 25. These parameters were estimated using a population-pharmacokinetic model incorporating all available data points from all participants. Individual values were estimated from the model as post-hoc values after incorporating between-participant variability.
Time Frame	Weeks 1, 2, 5, 9, 13, and 25

Outcome Measure Data

Analysis Population Description

PK Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	Mepolizumab 750 mg
Arm/Group Description	Participants received up to a total of six doses (one every 4 weeks) of mepolizumab 750 milligrams (mg) by intravenous infusion.
Measure Participants	52
Cmax	193.22 (7.8536)
Cav(0-inf)	123.45 (5.4324)
Cmax SS	268.40 (10.3703)

33. Secondary Outcome

Title	Area Under the Plasma Drug Concentration Versus Time Curve From Time 0 Extrapolated to Infinite Time (AUC[0-inf])
Description	Blood samples were scheduled to be collected for the assessment of AUC(0-inf) at Weeks 1, 2, 5, 9, 13, and 25 AUC[0-inf] is derived from individual systemic clearance estimates using the expression AUC[0-inf] = Dose/CL. Hence all data are incorporated into the estimation of CL and by implication AUC[0-inf].
Time Frame	Weeks 1, 2, 5, 9, 13, and 25

Outcome Measure Data

Analysis Population Description

PK Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	Mepolizumab 750 mg
Arm/Group Description	Participants received up to a total of six doses (one every 4 weeks) of mepolizumab 750 milligrams (mg) by intravenous infusion.
Measure Participants	52
Least Squares Mean (Standard Error) [Day*Microgram per milliliter]	3456.69 (152.11)

34. Secondary Outcome

Title	Half-life (Alpha) and Half-life (Beta)
Description	Half-life (Alpha) is the rate of decline in plasma concentrations due to the process of drug redistribution from the central to the peripheral compartment and half-life (Beta ) is the rate of decline due to the process of drug elimination due to metabolism. Blood samples were collected for the assessment of half-life (Alpha) and half-life (Beta) at Weeks 1, 2, 5, 9, 13, and 25. Half-life was estimated using a population-pharmacokinetic model incorporating all available data points from all participants. Individual values were estimated from the model as post-hoc values after incorporating between-participant variability.
Time Frame	Weeks 1, 2, 5, 9, 13, and 25

Outcome Measure Data

Analysis Population Description

PK Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	Mepolizumab 750 mg
Arm/Group Description	Participants received up to a total of six doses (one every 4 weeks) of mepolizumab 750 milligrams (mg) by intravenous infusion.
Measure Participants	52
Half-life (Alpha)	1.5456 (0.4108)
Half-life (Beta)	24.1258 (1.0250)

35. Secondary Outcome

Title	Pharmacokinetic/Pharmacodynamic (PK/PD) Model Derived Baseline
Description	Blood samples were collected for the assessment of PK/PD model derived Baseline at Weeks 1, 2, 5, 9, 13, 17, 21 and 25. An exploratory Emax direct response model was fitted to serial blood eosinophil count data (including placebo) using model-predicted mepolizumab concentrations (with zero imputed for placebo treated participants). All available blood eosinophil count data were incorporated into the model. Individual values were estimated from the model as post-hoc values after incorporating between-participant variability.
Time Frame	Weeks 1, 2, 5, 9, 13, 17, 21 and 25

Outcome Measure Data

Analysis Population Description

PK Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	Mepolizumab 750 mg
Arm/Group Description	Participants received up to a total of six doses (one every 4 weeks) of mepolizumab 750 milligrams (mg) by intravenous infusion.
Measure Participants	104
Least Squares Mean (Standard Error) [Giga units per liter]	0.4231 (0.02873)

36. Secondary Outcome

Title	PK/PD Model Derived Coefficient of Variation of Baseline (CV[Baseline]), Variation of Maximal Effect of Drug (CV[Emax]), and Residual
Description	A residual is the difference between the observed and predicted values. Blood samples were collected for the assessment of PK/PD model derived CV(Baseline), CV(Emax), and residual at Weeks 1, 2, 5, 9, 13, 17, 21 and 25. An exploratory Emax direct response model was fitted to serial blood eosinophil count data (including placebo) using model-predicted mepolizumab concentrations (with zero imputed for placebo treated subjects). All available datapoints were incorporated into the model. Individual values are estimated from the model as post-hoc values after incorporating between-participant variability.
Time Frame	Weeks 1, 2, 5, 9, 13, 17, 21 and 25

Outcome Measure Data

Analysis Population Description

PK Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	Mepolizumab 750 mg
Arm/Group Description	Participants received up to a total of six doses (one every 4 weeks) of mepolizumab 750 milligrams (mg) by intravenous infusion.
Measure Participants	104
CV(Baseline)	51.9951 (6.5318)
CV(Emax)	52.8910 (6.6193)
Residual	41.3787 (1.3763)

37. Secondary Outcome

Title	PK/PD Model Derived Half Maximal Effective Drug Concentration (EC50)
Description	Blood samples were collected for the assessment of PK/PD model derived EC50 at Weeks 1, 2, 5, 9, 13, 17, 21 and 25. An exploratory Emax direct response model was fitted to serial blood eosinophil count data (including placebo) using model-predicted mepolizumab concentrations (with zero imputed for placebo treated participants). All available datapoints were incorporated into the model. Individual values are estimated from the model as post-hoc values after incorporating between-partcipant variability.
Time Frame	Weeks 1, 2, 5, 9, 13, 17, 21 and 25

Outcome Measure Data

Analysis Population Description

PK Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	Mepolizumab 750 mg
Arm/Group Description	Participants received up to a total of six doses (one every 4 weeks) of mepolizumab 750 milligrams (mg) by intravenous infusion.
Measure Participants	104
Least Squares Mean (Standard Error) [Microgram per liter]	4.4303 (0.4404)

38. Secondary Outcome

Title	PK/PD Model Derived Maximum Inhibition
Description	Blood samples were collected for the assessment of Maximum Inhibition at Weeks 1, 2, 5, 9, 13, 17, 21 and 25. An exploratory Emax direct response model was fitted to serial blood eosinophil count data (including placebo) using model-predicted mepolizumab concentrations (with zero imputed for placebo treated participants). All available datapoints were incorporated into the model. Individual values are estimated from the model as post-hoc values after incorporating between-participant variability.
Time Frame	Weeks 1, 2, 5, 9, 13, 17, 21 and 25

Outcome Measure Data

Analysis Population Description

PK Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	Mepolizumab 750 mg
Arm/Group Description	Participants received up to a total of six doses (one every 4 weeks) of mepolizumab 750 milligrams (mg) by intravenous infusion.
Measure Participants	104
Least Squares Mean (Standard Error) [Percentage of inhibition]	90.0748 (1.0096)

39. Secondary Outcome

Title	Number of Participants With Positive Immunogenicity (Anti-mepolizumab Antibody Testing)
Description	Blood samples were collected at Week 1 pre-dose, Week 5 pre-dose, Week 13 pre-dose and Week 25 (4 weeks post last dose) for anti-mepolizumab antibody testing using a validated electrochemiluminescent (ECL) immunoassay. The assay involved screening, confirmation and titration steps. If serum samples tested positive in the screening assay, they were considered 'potentially positive' and were further analyzed for the specificity using the confirmation assay. Samples that confirmed positive in the confirmation assay were reported as 'positive'.
Time Frame	Week 1 pre-dose, Week 5 pre-dose, Week 13 pre-dose and Week 25 (4 weeks post last dose)

Outcome Measure Data

Analysis Population Description

Safety Population. One participant randomized to mepolizumab took placebo in error. Thus, "N" for the placebo arm of the SP is greater than for the ITT Population. Participants available at the specified time points (represented by n=X, X) were analyzed.

Arm/Group Title	Mepolizumab 750 mg	Placebo
Arm/Group Description	Participants received up to a total of six doses (one every 4 weeks) of mepolizumab 750 milligrams (mg) by intravenous infusion.	Participants received up to a total of six doses (one every 4 weeks) of matching placebo by intravenous infusion.
Measure Participants	53	52
Week 1, pre-dose, n=53, 52	0 0%	2 3.9%
Week 5, pre-dose, n=53, 50	0 0%	2 3.9%
Week 13, pre-dose, n=45, 40	0 0%	2 3.9%
Week 25, 4 weeks post last dose, n=40, 31	0 0%	0 0%

Adverse Events

Time Frame	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 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.One participant randomized to mepolizumab took placebo in error. Thus, "N" for the placebo arm of the SP is greater than for the ITT Population.
Arm/Group Title	Mepolizumab 750 mg		Placebo
Arm/Group Description	Participants received up to a total of six doses (one every 4 weeks) of mepolizumab 750 milligrams (mg) by intravenous infusion		Participants received up to a total of six doses (one every 4 weeks) of matching placebo by intravenous infusion.
All Cause Mortality
	Mepolizumab 750 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/53 (0%)		0/52 (0%)
Serious Adverse Events
	Mepolizumab 750 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/53 (0%)		0/52 (0%)
Other (Not Including Serious) Adverse Events
	Mepolizumab 750 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	32/53 (60.4%)		38/52 (73.1%)
Ear and labyrinth disorders
Ear pain	1/53 (1.9%)		6/52 (11.5%)
Gastrointestinal disorders
Nausea	2/53 (3.8%)		4/52 (7.7%)
General disorders
Fatigue	1/53 (1.9%)		5/52 (9.6%)
Pyrexia	3/53 (5.7%)		1/52 (1.9%)
Infections and infestations
Influenza	4/53 (7.5%)		2/52 (3.8%)
Nasopharyngitis	10/53 (18.9%)		14/52 (26.9%)
Musculoskeletal and connective tissue disorders
Arthralgia	5/53 (9.4%)		3/52 (5.8%)
Back pain	5/53 (9.4%)		0/52 (0%)
Nervous system disorders
Headache	13/53 (24.5%)		20/52 (38.5%)
Sinus headache	0/53 (0%)		3/52 (5.8%)
Psychiatric disorders
Insomnia	0/53 (0%)		3/52 (5.8%)
Respiratory, thoracic and mediastinal disorders
Asthma	2/53 (3.8%)		3/52 (5.8%)
Cough	2/53 (3.8%)		3/52 (5.8%)
Dyspnoea	2/53 (3.8%)		4/52 (7.7%)
Epistaxis	1/53 (1.9%)		3/52 (5.8%)
Rhinorrhoea	0/53 (0%)		3/52 (5.8%)
Paranasal sinus discomfort	0/53 (0%)		3/52 (5.8%)
Oropharyngeal pain	6/53 (11.3%)		4/52 (7.7%)
Skin and subcutaneous tissue disorders
Rash	3/53 (5.7%)		0/52 (0%)

Limitations/Caveats

Part B was removed due to the low numbers of participants enrolling into Part B. GSK determined it was no longer feasible to achieve a meaningful number of participants and therefore recruitment into this portion of the study was stopped.

More Information

Certain Agreements

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

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