A Study to Compare the Pharmacokinetics of Mepolizumab as a Liquid Drug in a Safety Syringe or an Autoinjector Versus Lyophilised Drug
Condition: Asthma
Intervention: Lyophilized mepolizumab; Liquid mepolizumab; Prefilled autoinjector; Prefilled Safety Syringe
Intervention description: 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.; 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.; 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.; Single use, disposable safety syringe with a retracting needle guard and locking system.
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 246.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: SB-240563; subcutaneous; lyophilized drug product; Mepolizumab; liquid drug product; safety syringe; auto injector

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. 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.
    

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.