AsthmaPhase 3NCT03014674
A Study to Compare the Pharmacokinetics of Mepolizumab as a Liquid Drug in a Safety Syringe or an Autoinjector Versus Lyophilised Drug
A Phase 3 study testing Lyophilized mepolizumab, Liquid mepolizumab and Prefilled autoinjector in people with Asthma, run by GlaxoSmithKline at 3 sites in 3 countries.
Trial summary
Mepolizumab (SB-240563) is a humanized monoclonal antibody (Immunoglobulin G1, kappa, mAb) that blocks human interleukin-5 (hIL-5) from binding to the interleukin (IL)-5 receptor complex expressed on the eosinophil cell surface and thus inhibits signaling. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Asthma
- What is being tested?
- Lyophilized mepolizumab, Liquid mepolizumab and Prefilled autoinjector
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 246 participants
- Where
- 3 sitesin 3 countries
- Study dates
- 6 Jan 2017to 11 Aug 2017
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 19Show fewer
- 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.
Trial locations and contacts
3 sites in 3 countries.
3 sites in 3 countries
United Kingdom1 site
GSK Investigational Site
Harrow, Middlesex, HA1 3UJ
About this study
Official title: An Open Label, Randomised, Three Arm, Single Dose, Multicentre, Parallel Group Study in Healthy Subjects to Compare the Pharmacokinetics of Subcutaneous Mepolizumab When Delivered as a Liquid Drug Product in a Safety Syringe or an Auto Injector With a Reconstituted Lyophilised Drug Product From a Vial
Mepolizumab (SB-240563) is a humanized monoclonal antibody (Immunoglobulin G1, kappa, mAb) that blocks human interleukin-5 (hIL-5) from binding to the interleukin (IL)-5 receptor complex expressed on the eosinophil cell surface and thus inhibits signaling. This study will compare the pharmacokinetics and safety of mepolizumab administered as a liquid drug product in two different devices with the reconstituted lyophilized drug product in healthy subjects. Subjects will receive a single administration of 100 milligram (mg) mepolizumab as a single injection. The randomization will be stratified by body weight (<70 kilogram (kg), 70 <80 kg and >=80 kg) and the site of injection will be randomized 1:1:1 to the upper arm, abdomen or thigh. Approximately 243 healthy subjects will be randomized so that at least 9 subjects are randomized to each mepolizumab treatment within each weight strata and 3 subjects within each mepolizumab treatment, weight strata and injection site. Each subject will participate in the study for up to approximately 16 weeks (up to 85 days after drug administration), and will have a screening visit, a single dose treatment period, and a follow-up visit.
- Conditions
- Asthma
- Being tested
- Lyophilized mepolizumab, Liquid mepolizumab, Prefilled autoinjector, Prefilled Safety Syringe
- Keywords
- SB-240563, subcutaneous, lyophilized drug product, Mepolizumab, liquid drug product, safety syringe, auto injector
- Medical subject headings
- Asthma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lyophilized mepolizumabBiological
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.
Liquid mepolizumabBiological
Mepolizumab will be provided as a clear to opalescent, colorless to pale yellow sterile solution for SC injection, supplied in a single-use, prefilled autoinjector or safety syringe containing 100 mg/mL mepolizumab with sodium phosphate, citric acid, sucrose ethylenediaminetetraacetic acid and polysorbate 80.
Prefilled autoinjectorDevice
Single use, disposable autoinjector will be assembled with the prefilled syringe containing the drug product. It will enable automatic delivery of the drug product under the power of a spring mechanism following activation of the device. Start and end of injection clicks will inform the user of correct use. A plastic needle will cover shield the needle before and after injection to minimize the potential for needle stick injuries.
Prefilled Safety SyringeDevice
Single use, disposable safety syringe with a retracting needle guard and locking system.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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 Receives: Biological: Lyophilized mepolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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).
Measured: 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 (17)
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: Up to 28 days post-dose
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.
Measured: Up to 28 days post-dose
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.
Measured: Up to Day 85
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.
Measured: Up to Day 85
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.
Measured: Baseline and up to Day 85
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.
Measured: Baseline and up to Day 85
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.
Measured: Baseline and up to Day 85
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.
Measured: Baseline and up to Day 85
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.
Measured: Baseline and Day 85
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.
Measured: Up to Day 85
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.
Measured: Up to Day 85
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jan 2017 (estimated)
- Study start6 Jan 2017
- Primary completion11 Aug 2017
- Study completion11 Aug 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for AsthmaStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 246 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03014674
- Sponsor's protocol ID
- 204958
- Other IDs
- 2016-002405-19, 2016
- Status last verified
- Nov 2019
- First submitted
- 15 Dec 2016
- Last updated
- 3 Dec 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: IPD for this study will be made available via the Clinical Study Data Request site.
- Expanded access
- Available
Publications
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.
PubMed 31317668
Study at a glance
From the registry record, last updated by the sponsor on 3 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Label, Randomised, Three Arm, Single Dose, Multicentre, Parallel Group Study in Healthy Subjects to Compare the Pharmacokinetics of Subcutaneous Mepolizumab When Delivered as a Liquid Drug Product in a Safety Syringe or an Auto Injector With a Reconstituted Lyophilised Drug Product From a Vial
- ClinicalTrials.gov ID
- NCT03014674
- Acronym / sponsor ID
- 204958
- Conditions
- Asthma
- Keywords
- SB-240563, subcutaneous, lyophilized drug product, Mepolizumab, liquid drug product, safety syringe, auto injector
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 246 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 6 Jan 2017 (actual)
- Primary completion
- 11 Aug 2017 (actual)
- Study completion
- 11 Aug 2017 (actual)
- First posted
- 9 Jan 2017 (estimated)
- Results
- Posted 14 Aug 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Mepolizumab (SB-240563) is a humanized monoclonal antibody (Immunoglobulin G1, kappa, mAb) that blocks human interleukin-5 (hIL-5) from binding to the interleukin (IL)-5 receptor complex expressed on the eosinophil cell surface and thus inhibits signaling. This study will compare the pharmacokinetics and safety of mepolizumab administered as a liquid drug product in two different devices with the reconstituted lyophilized drug product in healthy subjects. Subjects will receive a single administration of 100 milligram (mg) mepolizumab as a single injection. The randomization will be stratified by body weight (<70 kilogram (kg), 70 <80 kg and >=80 kg) and the site of injection will be randomized 1:1:1 to the upper arm, abdomen or thigh. Approximately 243 healthy subjects will be randomized so that at least 9 subjects are randomized to each mepolizumab treatment within each weight strata and 3 subjects within each mepolizumab treatment, weight strata and injection site. Each subject will participate in the study for up to approximately 16 weeks (up to 85 days after drug administration), and will have a screening visit, a single dose treatment period, and a follow-up visit.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Liquid mepolizumab in safety syringe | Experimental | Biological: Liquid mepolizumab, Device: Prefilled Safety SyringeSubjects will receive a single dose of 100 mg liquid mepolizumab administered subcutaneously using a prefilled syringe within a safety syringe according to randomization. |
| Liquid mepolizumab in an autoinjector | Experimental | Biological: Liquid mepolizumab, Device: Prefilled autoinjectorSubjects will receive a single dose of 100 mg liquid mepolizumab administered subcutaneously using a prefilled autoinjector, according to randomization. |
| Lyophilised mepolizumab from vial | Active comparator | Biological: Lyophilized mepolizumabSubjects will receive a single dose of 100 mg reconstituted lyophilized mepolizumab manually administered subcutaneously according to randomization |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (19 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Lyophilized mepolizumabMepolizumab 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. | Biological | Lyophilised mepolizumab from vial |
| Liquid mepolizumabMepolizumab will be provided as a clear to opalescent, colorless to pale yellow sterile solution for SC injection, supplied in a single-use, prefilled autoinjector or safety syringe containing 100 mg/mL mepolizumab with sodium phosphate, citric acid, sucrose ethylenediaminetetraacetic acid and polysorbate 80. | Biological | Liquid mepolizumab in an autoinjector, Liquid mepolizumab in safety syringe |
| Prefilled autoinjectorSingle use, disposable autoinjector will be assembled with the prefilled syringe containing the drug product. It will enable automatic delivery of the drug product under the power of a spring mechanism following activation of the device. Start and end of injection clicks will inform the user of correct use. A plastic needle will cover shield the needle before and after injection to minimize the potential for needle stick injuries. | Device | Liquid mepolizumab in an autoinjector |
| Prefilled Safety SyringeSingle use, disposable safety syringe with a retracting needle guard and locking system. | Device | Liquid mepolizumab in safety syringe |
Primary outcome
Maximum Observed Plasma Concentration (Cmax) of Mepolizumab
Time frame: 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
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.
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
Time frame: 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
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).
17 secondary outcomes
Time to Cmax (Tmax) and Last Time Point Where the Concentration is Above the Limit of Quantification (Tlast) of Mepolizumab
Time frame: 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
Apparent Clearance (CL/F) of Mepolizumab
Time frame: 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
Apparent Volume of Distribution (Vd/F) of Mepolizumab
Time frame: 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
Terminal Phase Elimination Rate Constant (Lambda z) of Mepolizumab
Time frame: 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
Terminal Phase Half-life (t½) of Mepolizumab
Time frame: 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
Percentage of AUC(0-inf) Obtained by Extrapolation (% AUCex) of Mepolizumab
Time frame: 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
Number of Participants With On-treatment Non-serious Adverse Events (AEs) and Serious AEs (SAEs)
Time frame: Up to 28 days post-dose
Number of Participants With On-treatment Systemic Reactions and Injection Site Reactions
Time frame: Up to 28 days post-dose
Number of Participants With Hematology Parameters Shifts From Baseline Relative to Normal Range
Time frame: Up to Day 85
Number of Participants With Clinical Chemistry Parameters Shifts From Baseline Relative to Normal Range
Time frame: Up to Day 85
Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
Time frame: Baseline and up to Day 85
Change From Baseline in Pulse Rate
Time frame: Baseline and up to Day 85
Change From Baseline in Temperature
Time frame: Baseline and up to Day 85
Change From Baseline in Respiratory Rate
Time frame: Baseline and up to Day 85
Number of Participants With Change From Baseline in Electrocardiogram (ECG) Findings
Time frame: Baseline and Day 85
Number of Participants With Positive Anti-mepolizumab Binding Antibodies
Time frame: Up to Day 85
Number of Participants With Positive Neutralizing Antibodies
Time frame: Up to Day 85
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Dec 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 31317668Shabbir 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.
- Individual participant dataSharing planned: Yes. IPD for this study will be made available via the Clinical Study Data Request site.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
3 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Lyophilized mepolizumab, Liquid mepolizumab and Prefilled autoinjector in people with Asthma, run by GlaxoSmithKline at 3 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States, Germany, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Aug 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Observed Plasma Concentration (Cmax) of Mepolizumab (time frame: 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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03014674, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Dec 2019.