A Study to Compare the Pharmacokinetics of Mepolizumab as... | NCT03014674

ID	Type	Description	Link
2016-002405-19	EudraCT Number

Status Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Liquid mepolizumab in safety syringe	Experimental	Subjects will receive a single dose of 100 mg liquid mepolizumab administered subcutaneously using a prefilled syringe within a safety syringe according to randomization.	Biological: Liquid mepolizumab Device: Prefilled Safety Syringe
Liquid mepolizumab in an autoinjector	Experimental	Subjects will receive a single dose of 100 mg liquid mepolizumab administered subcutaneously using a prefilled autoinjector, according to randomization.	Biological: Liquid mepolizumab Device: Prefilled autoinjector
Lyophilised mepolizumab from vial	Active Comparator	Subjects will receive a single dose of 100 mg reconstituted lyophilized mepolizumab manually administered subcutaneously according to randomization	Biological: Lyophilized mepolizumab

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Lyophilized mepolizumab	Biological	Mepolizumab will be provided as white, uniform, lyophilized cake in vials with unit dose strength of 100 mg/vial for reconstitution in 1.2 mL sterile water for injection (SWFI). Following reconstitution it forms a clear to opalescent, colorless to pale yellow solution for SC injection.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Maximum Observed Plasma Concentration (Cmax) of Mepolizumab	Blood samples were collected at indicated time points. Cmax following a single dose administration of liquid mepolizumab using a safety syringe and an autoinjector were compared with reconstituted lyophilized drug product from the vial. Pharmacokinetic (PK) Population comprised of all participants receiving study drug for whom a pharmacokinetic sample was obtained and analyzed.	Day 1 (pre-dose, 2 hours, and 8 hours post-dose), Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 22, 29, 43, 57 and 85 post-dose
Area Under the Plasma Concentration Time Curve (AUC) From Time Zero to the Time of Last Quantifiable Concentration (AUC[0-t]), AUC From Time Zero Extrapolated to Infinite Time (AUC[0-inf]) of Mepolizumab	Blood samples were collected at indicated time points. AUC(0-t) and AUC(0-inf) following a single dose administration of liquid mepolizumab using a safety syringe and an autoinjector were compared with lyophilized drug product. Fixed effects analysis of covariance model was used for analysis. Only those participants with data available at the specified data points were analyzed (represented by n=X in category titles).	Day 1 (pre-dose, 2 hours, and 8 hours post-dose), Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 22, 29, 43, 57 and 85 post-dose

Secondary Outcomes

Measure	Description	Time Frame
Time to Cmax (Tmax) and Last Time Point Where the Concentration is Above the Limit of Quantification (Tlast) of Mepolizumab	Blood samples were collected at indicated time points. Tmax and tlast following a single dose administration of liquid mepolizumab using a safety syringe and an autoinjector were compared with lyophilized drug product.	Day 1 (pre-dose, 2 hours, and 8 hours post-dose), Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 22, 29, 43, 57 and 85 post-dose

Eligibility Module

Eligibility Criteria

Inclusion Criteria

18 years of age and over at the time of signing the informed consent.
Healthy as determined by the investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, vital signs, laboratory tests, and cardiac monitoring. A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria, outside the reference range for the population being studied may be included only if the investigator agrees and documents that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures or ability to interpret study results.
Body weight >=50 kg and body mass index (BMI) within the range 19.0-30 kg/square meter(m^2) (inclusive)
Male or Female: A female subject is eligible to participate if she is not pregnant (as confirmed by a negative human chorionic gonadotrophin (hCG) test), not lactating, and at least one of the following conditions applies: Non-reproductive potential defined as: pre-menopausal females with documented tubal ligation; documented hysteroscopic tubal occlusion procedure with follow-up; confirmation of bilateral tubal occlusion; hysterectomy; documented bilateral oophorectomy; post- menopausal females. Subject is of reproductive potential and agrees to follow one of the options listed in the Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential (FRP) from 30 days prior to the first dose of study medication and until 16 weeks after the administration of the single dose of study medication.
Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the consent form and in the protocol. The subject must be able to understand and communicate in the native language of the site, e.g. German in German sites.

Exclusion Criteria

Alanine transaminase >1.5x upper limit of normal (ULN)
Bilirubin >1.5xULN (isolated bilirubin >1.5x ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
QTc corrected by Fridericia's (QTcF) formula>450 milliseconds (msec)
Any clinically relevant abnormality identified at the screening medical assessment (physical examination/medical history), clinical laboratory tests, or 12-lead electrocardiogram.
Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half lives (whichever is longer) before the first dose of study medication and until study completion, unless in the opinion of the investigator and GlaxoSmithKline Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
History of regular alcohol consumption within 6 months of the study defined as: an average weekly intake of >14 units for females and >21 units for males. One unit is equivalent to 8 grams of alcohol: a half-pint (~240 milliliter [mL]) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
Urinary nicotine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening. Limit of >500 nanogram/mL.
Involved in any activities likely to result in any significant decrease or increase in body weight during the study period (e.g. 'crash' dieting, bodybuilding).
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 Medical Monitor, contraindicates their participation.
Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study treatment.
A positive test for human immunodeficiency virus antibody.
Subjects with known, pre-existing helminthes infestation within 6 months prior to Day 1.
Where participation in the study would result in donation of blood or blood products in excess of 500 mL within 3 months.
The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
A positive pre-study drug/alcohol screen.
A vulnerable subject. Defined as individuals whose willingness to volunteer in a clinical trial may be unduly influenced by the expectation, whether justified or not, of benefits associated with participation, or of a retaliatory response from senior members of a hierarchy in case of refusal to participate.
Subjects who work for the Sponsor, contract research organization, or one of the study centers.

Name	Affiliation	Role
GSK Clinical Trials	GlaxoSmithKline	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
GSK Investigational Site		Baltimore	Maryland	21225	United States
GSK Investigational Site

PubMed Identifier	Type	Citation	Retractions
31317668	Background	Shabbir S, Pouliquen IJ, Bentley JH, Bradford ES, C Kaisermann M, Albayaty M. The Pharmacokinetics and Relative Bioavailability of Mepolizumab 100 mg Liquid Formulation Administered Subcutaneously to Healthy Participants: A Randomized Trial. Clin Pharmacol Drug Dev. 2020 Apr;9(3):375-385. doi: 10.1002/cpdd.726. Epub 2019 Jul 17.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Lyophilized Vial	Participants were administered 100 milligram per milliliter (mg/mL) subcutaneous (SC) dose of mepolizumab as lyophilized powder reconstituted with sterile water for injection from vial. Participants were administered a single SC dose in upper arm, abdomen or thigh.
FG001

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jul 10, 2017	Mar 6, 2018

ID	Title	Description
BG000	Lyophilized Vial	Participants were administered 100 milligram per milliliter (mg/mL) subcutaneous (SC) dose of mepolizumab as lyophilized powder reconstituted with sterile water for injection from vial. Participants were administered a single SC dose in upper arm, abdomen or thigh.
BG001	Liquid Autoinjector	Participants were administered 100 mg/mL SC dose of mepolizumab liquid formulation via disposable pre-filled autoinjector. Participants were administered a single SC dose in upper arm, abdomen or thigh.
BG002	Liquid Safety Syringe	Participants were administered 100 mg/mL SC dose of mepolizumab liquid formulation via disposable pre-filled safety syringe. Participants were administered a single SC dose in upper arm, abdomen or thigh.
BG003	Total	Total of all reporting groups

Units	Counts
Participants	BG00085 BG00179 BG00280 BG003244

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Maximum Observed Plasma Concentration (Cmax) of Mepolizumab

Blood samples were collected at indicated time points. Cmax following a single dose administration of liquid mepolizumab using a safety syringe and an autoinjector were compared with reconstituted lyophilized drug product from the vial. Pharmacokinetic (PK) Population comprised of all participants receiving study drug for whom a pharmacokinetic sample was obtained and analyzed.

PK Population

Posted

Geometric Mean

Geometric Coefficient of Variation

micrograms per milliliter (µg/mL)

Day 1 (pre-dose, 2 hours, and 8 hours post-dose), Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 22, 29, 43, 57 and 85 post-dose

ID	Title	Description
OG000	Lyophilized Vial	Participants were administered 100 milligram per milliliter (mg/mL) subcutaneous (SC) dose of mepolizumab as lyophilized powder reconstituted with sterile water for injection from vial. Participants were administered a single SC dose in upper arm, abdomen or thigh.
OG001	Liquid Autoinjector	Participants were administered 100 mg/mL SC dose of mepolizumab liquid formulation via disposable pre-filled autoinjector. Participants were administered a single SC dose in upper arm, abdomen or thigh.
OG002	Liquid Safety Syringe	Participants were administered 100 mg/mL SC dose of mepolizumab liquid formulation via disposable pre-filled safety syringe. Participants were administered a single SC dose in upper arm, abdomen or thigh.

Units	Counts
Participants	OG00085 OG00179 OG00280

Title

Denominators

Categories

Title	Measurements
	OG00011.57± 27.43 OG00111.98± 24.96 OG00212.07± 27.29

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001						Ratio	1.04			2-Sided	90	0.98	1.11			Ratio (autoinjector/lyophilized drug) for Cmax has been presented		Equivalence	Interpretation of the comparability of the autoinjector and safety syringe with the reconstituted lyophilized drug product was guided by a two-sided 90% confidence interval (CI) for the ratio of the geometric mean of test treatment to reference treatment in the range (0.80, 1.25) for Cmax.

Primary

Area Under the Plasma Concentration Time Curve (AUC) From Time Zero to the Time of Last Quantifiable Concentration (AUC[0-t]), AUC From Time Zero Extrapolated to Infinite Time (AUC[0-inf]) of Mepolizumab

Blood samples were collected at indicated time points. AUC(0-t) and AUC(0-inf) following a single dose administration of liquid mepolizumab using a safety syringe and an autoinjector were compared with lyophilized drug product. Fixed effects analysis of covariance model was used for analysis. Only those participants with data available at the specified data points were analyzed (represented by n=X in category titles).

PK Population

Posted

Geometric Mean

Geometric Coefficient of Variation

Days*µg/mL

Day 1 (pre-dose, 2 hours, and 8 hours post-dose), Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 22, 29, 43, 57 and 85 post-dose

ID	Title	Description
OG000	Lyophilized Vial	Participants were administered 100 milligram per milliliter (mg/mL) subcutaneous (SC) dose of mepolizumab as lyophilized powder reconstituted with sterile water for injection from vial. Participants were administered a single SC dose in upper arm, abdomen or thigh.
OG001	Liquid Autoinjector	Participants were administered 100 mg/mL SC dose of mepolizumab liquid formulation via disposable pre-filled autoinjector. Participants were administered a single SC dose in upper arm, abdomen or thigh.

Secondary

Time to Cmax (Tmax) and Last Time Point Where the Concentration is Above the Limit of Quantification (Tlast) of Mepolizumab

Blood samples were collected at indicated time points. Tmax and tlast following a single dose administration of liquid mepolizumab using a safety syringe and an autoinjector were compared with lyophilized drug product.

PK Population

Posted

Median

Full Range

Days

Day 1 (pre-dose, 2 hours, and 8 hours post-dose), Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 22, 29, 43, 57 and 85 post-dose

ID	Title	Description
OG000	Lyophilized Vial	Participants were administered 100 milligram per milliliter (mg/mL) subcutaneous (SC) dose of mepolizumab as lyophilized powder reconstituted with sterile water for injection from vial. Participants were administered a single SC dose in upper arm, abdomen or thigh.
OG001	Liquid Autoinjector	Participants were administered 100 mg/mL SC dose of mepolizumab liquid formulation via disposable pre-filled autoinjector. Participants were administered a single SC dose in upper arm, abdomen or thigh.
OG002	Liquid Safety Syringe	Participants were administered 100 mg/mL SC dose of mepolizumab liquid formulation via disposable pre-filled safety syringe. Participants were administered a single SC dose in upper arm, abdomen or thigh.

Secondary

Apparent Clearance (CL/F) of Mepolizumab

Blood samples were collected at indicated time points . CL/F following a single dose administration of liquid mepolizumab using a safety syringe and an autoinjector were compared with lyophilized drug product. Only those participants with data available were analyzed.

PK Population

Posted

Geometric Mean

Geometric Coefficient of Variation

Liters per hour (L/h)

Day 1 (pre-dose, 2 hours, and 8 hours post-dose), Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 22, 29, 43, 57 and 85 post-dose

ID	Title	Description
OG000	Lyophilized Vial	Participants were administered 100 milligram per milliliter (mg/mL) subcutaneous (SC) dose of mepolizumab as lyophilized powder reconstituted with sterile water for injection from vial. Participants were administered a single SC dose in upper arm, abdomen or thigh.
OG001	Liquid Autoinjector	Participants were administered 100 mg/mL SC dose of mepolizumab liquid formulation via disposable pre-filled autoinjector. Participants were administered a single SC dose in upper arm, abdomen or thigh.
OG002	Liquid Safety Syringe	Participants were administered 100 mg/mL SC dose of mepolizumab liquid formulation via disposable pre-filled safety syringe. Participants were administered a single SC dose in upper arm, abdomen or thigh.

Secondary

Apparent Volume of Distribution (Vd/F) of Mepolizumab

Blood samples were collected at indicated time points. Vd/F following a single dose administration of liquid mepolizumab using a safety syringe and an autoinjector were compared with lyophilized drug product. Only those participants with data available were analyzed.

PK Population

Posted

Geometric Mean

Geometric Coefficient of Variation

Liters (L)

Day 1 (pre-dose, 2 hours, and 8 hours post-dose), Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 22, 29, 43, 57 and 85 post-dose

ID	Title	Description
OG000	Lyophilized Vial	Participants were administered 100 milligram per milliliter (mg/mL) subcutaneous (SC) dose of mepolizumab as lyophilized powder reconstituted with sterile water for injection from vial. Participants were administered a single SC dose in upper arm, abdomen or thigh.
OG001	Liquid Autoinjector	Participants were administered 100 mg/mL SC dose of mepolizumab liquid formulation via disposable pre-filled autoinjector. Participants were administered a single SC dose in upper arm, abdomen or thigh.
OG002	Liquid Safety Syringe	Participants were administered 100 mg/mL SC dose of mepolizumab liquid formulation via disposable pre-filled safety syringe. Participants were administered a single SC dose in upper arm, abdomen or thigh.

Secondary

Terminal Phase Elimination Rate Constant (Lambda z) of Mepolizumab

Blood samples were collected at indicated time points. Lambda z following a single dose administration of liquid mepolizumab using a safety syringe and an autoinjector were compared with lyophilized drug product. Only those participants with data available were analyzed.

PK Population

Posted

Geometric Mean

Geometric Coefficient of Variation

Per hours

Day 1 (pre-dose, 2 hours, and 8 hours post-dose), Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 22, 29, 43, 57 and 85 post-dose

ID	Title	Description
OG000	Lyophilized Vial	Participants were administered 100 milligram per milliliter (mg/mL) subcutaneous (SC) dose of mepolizumab as lyophilized powder reconstituted with sterile water for injection from vial. Participants were administered a single SC dose in upper arm, abdomen or thigh.
OG001	Liquid Autoinjector	Participants were administered 100 mg/mL SC dose of mepolizumab liquid formulation via disposable pre-filled autoinjector. Participants were administered a single SC dose in upper arm, abdomen or thigh.
OG002	Liquid Safety Syringe	Participants were administered 100 mg/mL SC dose of mepolizumab liquid formulation via disposable pre-filled safety syringe. Participants were administered a single SC dose in upper arm, abdomen or thigh.

Secondary

Terminal Phase Half-life (t½) of Mepolizumab

Blood samples were collected at indicated time points for calculating t½. t½ following a single dose administration of liquid mepolizumab using a safety syringe and an autoinjector were compared with lyophilized drug product. Only those participants with data available were analyzed.

PK Population

Posted

Geometric Mean

Geometric Coefficient of Variation

Days

Day 1 (pre-dose, 2 hours, and 8 hours post-dose), Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 22, 29, 43, 57 and 85 post-dose

ID	Title	Description
OG000	Lyophilized Vial	Participants were administered 100 milligram per milliliter (mg/mL) subcutaneous (SC) dose of mepolizumab as lyophilized powder reconstituted with sterile water for injection from vial. Participants were administered a single SC dose in upper arm, abdomen or thigh.
OG001	Liquid Autoinjector	Participants were administered 100 mg/mL SC dose of mepolizumab liquid formulation via disposable pre-filled autoinjector. Participants were administered a single SC dose in upper arm, abdomen or thigh.
OG002	Liquid Safety Syringe	Participants were administered 100 mg/mL SC dose of mepolizumab liquid formulation via disposable pre-filled safety syringe. Participants were administered a single SC dose in upper arm, abdomen or thigh.

Secondary

Percentage of AUC(0-inf) Obtained by Extrapolation (% AUCex) of Mepolizumab

Blood samples were collected at indicated time points. Percentage AUCex following a single dose administration of liquid mepolizumab using a safety syringe and an autoinjector were compared with lyophilized drug product. Only those participants with data available were analyzed.

PK Population

Posted

Geometric Mean

Geometric Coefficient of Variation

Percentage

Day 1 (pre-dose, 2 hours, and 8 hours post-dose), Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 22, 29, 43, 57 and 85 post-dose

ID	Title	Description
OG000	Lyophilized Vial	Participants were administered 100 milligram per milliliter (mg/mL) subcutaneous (SC) dose of mepolizumab as lyophilized powder reconstituted with sterile water for injection from vial. Participants were administered a single SC dose in upper arm, abdomen or thigh.
OG001	Liquid Autoinjector	Participants were administered 100 mg/mL SC dose of mepolizumab liquid formulation via disposable pre-filled autoinjector. Participants were administered a single SC dose in upper arm, abdomen or thigh.
OG002	Liquid Safety Syringe	Participants were administered 100 mg/mL SC dose of mepolizumab liquid formulation via disposable pre-filled safety syringe. Participants were administered a single SC dose in upper arm, abdomen or thigh.

Secondary

Number of Participants With On-treatment Non-serious Adverse Events (AEs) and Serious AEs (SAEs)

An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment or events associated with liver injury and impaired liver function were categorized as SAE. All Treated Subjects (Safety) comprised of all participants who received mepolizumab. Participants with non-serious AEs (3 percentage threshold) and SAEs has been reported.

All Treated Subjects (Safety) Population

Posted

Number

Participants

Up to 28 days post-dose

ID	Title	Description
OG000	Lyophilized Vial	Participants were administered 100 milligram per milliliter (mg/mL) subcutaneous (SC) dose of mepolizumab as lyophilized powder reconstituted with sterile water for injection from vial. Participants were administered a single SC dose in upper arm, abdomen or thigh.
OG001	Liquid Autoinjector	Participants were administered 100 mg/mL SC dose of mepolizumab liquid formulation via disposable pre-filled autoinjector. Participants were administered a single SC dose in upper arm, abdomen or thigh.

Secondary

Number of Participants With On-treatment Systemic Reactions and Injection Site Reactions

Adverse events of special interest like local injection site reactions and systemic reactions like allergic Type I hypersensitivity were reported along with AEs and SAEs. Participants with local injection site reaction and Allergic Type I hypersensitivity systemic reactions are reported here.

All Treated Subjects (Safety) Population

Posted

Number

Participants

Up to 28 days post-dose

ID	Title	Description
OG000	Lyophilized Vial	Participants were administered 100 milligram per milliliter (mg/mL) subcutaneous (SC) dose of mepolizumab as lyophilized powder reconstituted with sterile water for injection from vial. Participants were administered a single SC dose in upper arm, abdomen or thigh.
OG001	Liquid Autoinjector	Participants were administered 100 mg/mL SC dose of mepolizumab liquid formulation via disposable pre-filled autoinjector. Participants were administered a single SC dose in upper arm, abdomen or thigh.
OG002	Liquid Safety Syringe	Participants were administered 100 mg/mL SC dose of mepolizumab liquid formulation via disposable pre-filled safety syringe. Participants were administered a single SC dose in upper arm, abdomen or thigh.

Secondary

Number of Participants With Hematology Parameters Shifts From Baseline Relative to Normal Range

Hematology parameters included assessment of platelet count, erythrocytes, leukocytes, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), neutrophils, lymphocytes, monocytes, eosinophils, basophils, hemoglobin and hematocrit. Participants were counted in the worst case category that their value changes to Low, Normal or High. Participants whose value category was unchanged or whose value became normal, were recorded in the "To Normal or No Change" category. The worst case post-Baseline values has been reported. For basophils the "to low" category is not applicable (NA) as the lower limit of normal is zero for this parameter.

All Treated Subjects (Safety) Population

Posted

Number

Participants

Up to Day 85

ID	Title	Description
OG000	Lyophilized Vial	Participants were administered 100 milligram per milliliter (mg/mL) subcutaneous (SC) dose of mepolizumab as lyophilized powder reconstituted with sterile water for injection from vial. Participants were administered a single SC dose in upper arm, abdomen or thigh.
OG001	Liquid Autoinjector	Participants were administered 100 mg/mL SC dose of mepolizumab liquid formulation via disposable pre-filled autoinjector. Participants were administered a single SC dose in upper arm, abdomen or thigh.

Secondary

Number of Participants With Clinical Chemistry Parameters Shifts From Baseline Relative to Normal Range

Blood samples were collected to evaluate clinical chemistry parameters, which included assessment of creatinine, creatine kinase, glucose, protein, potassium, urea, sodium, calcium, alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), direct bilirubin (D.bili) and bilirubin, and albumin. Participants were counted in the worst case category that their value changes to Low, Normal or High. Participants whose value category was unchanged or whose value became normal, were recorded in the "To Normal or No Change" category. The worst case post-Baseline values has been reported. Only those participants with data available at the specified data points were analyzed. For the category "to low " NA indicates data was not available as the lower limit of normal is zero for this parameter.

All Treated Subjects (Safety) Population

Posted

Number

Participants

Up to Day 85

ID	Title	Description
OG000	Lyophilized Vial	Participants were administered 100 milligram per milliliter (mg/mL) subcutaneous (SC) dose of mepolizumab as lyophilized powder reconstituted with sterile water for injection from vial. Participants were administered a single SC dose in upper arm, abdomen or thigh.
OG001	Liquid Autoinjector	Participants were administered 100 mg/mL SC dose of mepolizumab liquid formulation via disposable pre-filled autoinjector. Participants were administered a single SC dose in upper arm, abdomen or thigh.

Secondary

Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)

SBP and DBP were measured in supine position after 5 minutes rest. Baseline values for each assessment was the latest available assessment prior to receiving the single dose of mepolizumab. Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value. Only those participants available at the specified time points (represented by n=X in the category titles) were analyzed.

All Treated Subjects (Safety) Population

Posted

Mean

Standard Deviation

Millimeter of mercury (mmHg)

Baseline and up to Day 85

ID	Title	Description
OG000	Lyophilized Vial	Participants were administered 100 milligram per milliliter (mg/mL) subcutaneous (SC) dose of mepolizumab as lyophilized powder reconstituted with sterile water for injection from vial. Participants were administered a single SC dose in upper arm, abdomen or thigh.
OG001	Liquid Autoinjector	Participants were administered 100 mg/mL SC dose of mepolizumab liquid formulation via disposable pre-filled autoinjector. Participants were administered a single SC dose in upper arm, abdomen or thigh.
OG002	Liquid Safety Syringe

Secondary

Change From Baseline in Pulse Rate

Pulse rate was measured in supine position after 5 minutes rest. Baseline values for each assessment was the latest available assessment prior to receiving the single dose of mepolizumab. Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value. Only those participants available at the specified time points (represented by n=X in the category titles) were analyzed.

All Treated Subjects (Safety) Population

Posted

Mean

Standard Deviation

Beats per minute

Baseline and up to Day 85

ID	Title	Description
OG000	Lyophilized Vial	Participants were administered 100 milligram per milliliter (mg/mL) subcutaneous (SC) dose of mepolizumab as lyophilized powder reconstituted with sterile water for injection from vial. Participants were administered a single SC dose in upper arm, abdomen or thigh.
OG001	Liquid Autoinjector	Participants were administered 100 mg/mL SC dose of mepolizumab liquid formulation via disposable pre-filled autoinjector. Participants were administered a single SC dose in upper arm, abdomen or thigh.
OG002	Liquid Safety Syringe	Participants were administered 100 mg/mL SC dose of mepolizumab liquid formulation via disposable pre-filled safety syringe. Participants were administered a single SC dose in upper arm, abdomen or thigh.

Secondary

Change From Baseline in Temperature

Temperature was measured in supine position after 5 minutes rest. Baseline values for each assessment was the latest available assessment prior to receiving the single dose of mepolizumab. Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value. Only those participants available at the specified time points (represented by n=X in the category titles) were analyzed.

All Treated Subjects (Safety) Population

Posted

Mean

Standard Deviation

degree Celsius

Baseline and up to Day 85

ID	Title	Description
OG000	Lyophilized Vial	Participants were administered 100 milligram per milliliter (mg/mL) subcutaneous (SC) dose of mepolizumab as lyophilized powder reconstituted with sterile water for injection from vial. Participants were administered a single SC dose in upper arm, abdomen or thigh.
OG001	Liquid Autoinjector	Participants were administered 100 mg/mL SC dose of mepolizumab liquid formulation via disposable pre-filled autoinjector. Participants were administered a single SC dose in upper arm, abdomen or thigh.
OG002	Liquid Safety Syringe	Participants were administered 100 mg/mL SC dose of mepolizumab liquid formulation via disposable pre-filled safety syringe. Participants were administered a single SC dose in upper arm, abdomen or thigh.

Secondary

Change From Baseline in Respiratory Rate

Respiratory rate was measured in supine position after 5 minutes rest. Baseline values for each assessment was the latest available assessment prior to receiving the single dose of mepolizumab. Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value. Only those participants available at the specified time points (represented by n=X in the category titles) were analyzed.

All Treated Subjects (Safety) Population

Posted

Mean

Standard Deviation

breaths per minute

Baseline and up to Day 85

ID	Title	Description
OG000	Lyophilized Vial	Participants were administered 100 milligram per milliliter (mg/mL) subcutaneous (SC) dose of mepolizumab as lyophilized powder reconstituted with sterile water for injection from vial. Participants were administered a single SC dose in upper arm, abdomen or thigh.
OG001	Liquid Autoinjector	Participants were administered 100 mg/mL SC dose of mepolizumab liquid formulation via disposable pre-filled autoinjector. Participants were administered a single SC dose in upper arm, abdomen or thigh.
OG002	Liquid Safety Syringe	Participants were administered 100 mg/mL SC dose of mepolizumab liquid formulation via disposable pre-filled safety syringe. Participants were administered a single SC dose in upper arm, abdomen or thigh.

Secondary

Number of Participants With Change From Baseline in Electrocardiogram (ECG) Findings

Single measurements of 12-lead ECGs were obtained after 5 minutes of rest in a supine position for the participant. ECG was performed on Day 1 and Day 85 using an automated ECG machine. Baseline values for each assessment was the latest available assessment prior to receiving the single dose of mepolizumab. Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value. Participants with abnormal ECG findings that are clinically not significant and clinically significant data has been presented here. The data of worst case post-Baseline is presented here. Only those participants available at the specified time points were analyzed.

All Treated Subjects (Safety) Population

Posted

Number

Participants

Baseline and Day 85

ID	Title	Description
OG000	Lyophilized Vial	Participants were administered 100 milligram per milliliter (mg/mL) subcutaneous (SC) dose of mepolizumab as lyophilized powder reconstituted with sterile water for injection from vial. Participants were administered a single SC dose in upper arm, abdomen or thigh.
OG001	Liquid Autoinjector	Participants were administered 100 mg/mL SC dose of mepolizumab liquid formulation via disposable pre-filled autoinjector. Participants were administered a single SC dose in upper arm, abdomen or thigh.

Secondary

Number of Participants With Positive Anti-mepolizumab Binding Antibodies

Blood samples were collected for the determination of anti-mepolizumab antibodies. A binding anti-drug antibody (ADA) assay was performed. There were three tiered analysis: screening, confirmation and titration. The results of binding ADA were categorized as negative, transient positive (defined as a single confirmatory positive immunogenic response that does not occur at the final study assessment) or persistent positive (defined as a confirmatory positive immunogenic response for at least 2 consecutive assessments excluding the Screening visit, or a single result at the final study assessment). A participant was considered positive if they had at least one positive post-Baseline ADA result. Number of participants with positive anti-mepolizumab antibodies at any time post-Baseline are presented here. Only those participants available at the specified time points were analyzed.

All Treated Subjects (Safety) Population

Posted

Number

Participants

Up to Day 85

ID	Title	Description
OG000	Lyophilized Vial	Participants were administered 100 milligram per milliliter (mg/mL) subcutaneous (SC) dose of mepolizumab as lyophilized powder reconstituted with sterile water for injection from vial. Participants were administered a single SC dose in upper arm, abdomen or thigh.
OG001	Liquid Autoinjector	Participants were administered 100 mg/mL SC dose of mepolizumab liquid formulation via disposable pre-filled autoinjector. Participants were administered a single SC dose in upper arm, abdomen or thigh.

Secondary

Number of Participants With Positive Neutralizing Antibodies

Blood samples were collected for the determination of positive neutralizing antibodies. A neutralizing antibody assay was performed. Neutralizing antibody test was only carried out for participants who have had a positive confirmatory binding antibody test result at visit. A participant was considered positive if they had at least one positive post-Baseline neutralizing antibody result. Number of participants with positive neutralizing antibodies at any time post-Baseline are presented here. Only those participants available at the specified time points were analyzed.

All Treated Subjects (Safety) Population

Posted

Number

Participants

Up to Day 85

ID	Title	Description
OG000	Lyophilized Vial	Participants were administered 100 milligram per milliliter (mg/mL) subcutaneous (SC) dose of mepolizumab as lyophilized powder reconstituted with sterile water for injection from vial. Participants were administered a single SC dose in upper arm, abdomen or thigh.
OG001	Liquid Autoinjector	Participants were administered 100 mg/mL SC dose of mepolizumab liquid formulation via disposable pre-filled autoinjector. Participants were administered a single SC dose in upper arm, abdomen or thigh.
OG002	Liquid Safety Syringe

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Headache	Nervous system disorders	MedDRA 20.0	Systematic Assessment	EG0006 events6 affected85 at risk EG0019 events9 affected79 at risk EG0029 events8 affected80 at risk
Viral upper respiratory tract infection	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0002 events2 affected85 at risk EG0013 events3 affected79 at risk EG0026 events6 affected80 at risk
Fatigue	General disorders	MedDRA 20.0	Systematic Assessment	EG0005 events5 affected85 at risk EG0012 events2 affected79 at risk EG0021 events1 affected80 at risk

ID	Term
D001982	Bronchial Diseases
D012140	Respiratory Tract Diseases
D008173	Lung Diseases, Obstructive
D008171	Lung Diseases
D012130	Respiratory Hypersensitivity
D006969	Hypersensitivity, Immediate
D006967	Hypersensitivity
D007154	Immune System Diseases

ID	Title	Description	Deaths (At Risk)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Lyophilized Vial	Participants were administered 100 milligram per milliliter (mg/mL) subcutaneous (SC) dose of mepolizumab as lyophilized powder reconstituted with sterile water for injection from vial. Participants were administered a single SC dose in upper arm, abdomen or thigh.	85	85	11	85
EG001	Liquid Autoinjector	Participants were administered 100 mg/mL SC dose of mepolizumab liquid formulation via disposable pre-filled autoinjector. Participants were administered a single SC dose in upper arm, abdomen or thigh.	79	79	13	79
EG002	Liquid Safety Syringe	Participants were administered 100 mg/mL SC dose of mepolizumab liquid formulation via disposable pre-filled safety syringe. Participants were administered a single SC dose in upper arm, abdomen or thigh.	80	80	14	80