A Positron Emission Tomography (PET) Imaging Study to Investigate the Biodistribution and Clearance of an Albumin Binding Domain Antibody (AlbudAb) GSK3128349 in Healthy Male Subjects
Condition: Drug-Related Side Effects and Adverse Reactions
MeSH terms: Drug-Related Side Effects and Adverse Reactions
Intervention: 89Zr-GSK3128349 1 mg
Intervention description: 89Zr-GSK3128349 is a mixture of unlabelled and zirconium-labelled GSK3128349, in the form of solution for IV administration, and is associated with about 15 MBq of radioactivity.
Phase: Phase 1
Study type: Interventional
Primary purpose: Basic Science
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 8.0
Sex: Male
Minimum age: 50 Years
Maximum age: 65 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: 89Zirconium; Open label; Pharmacokinetics; Radioactive; Clearance; Biodistribution

Summary:

      GSK3128349 is a small protein molecule (biopharmaceutical) that binds to albumin in the body,
      and by itself, has no pharmacological action. A pharmacologically active drug can be attached
      to GSK3128349 with the goal of changing the distribution and/or duration of action of the
      attached drug. This study will determine the distribution and pharmacokinetics (duration) of
      GSK3128349 itself after a single intravenous infusion. GSK3128349 has been labeled with and
      the radioisotope 89Zirconium allowing it to be visualized in the organs of the body using a
      PET scanner at multiple time points after GSK3128349 dosing. The data from this study will
      help predict the distribution of future drugs attached to GSK3128349. The total duration of a
      subject's participation is about approximately 10 weeks, including the screening period.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Healthy as determined by a responsible and experienced physician, based on a medical
             evaluation including medical history, physical examination, laboratory tests and
             cardiac monitoring. - Aspartate aminotransferase (AST), alanine aminotransferase
             (ALT), alkaline phosphatase and bilirubin <=1.5x Upper Limit Normal (ULN) (isolated
             bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35
             percent).

          -  Body Mass Index (BMI) within the range 19.0 - 31.0 kilogram (kg)/meter (m^2)
             (inclusive).

          -  Subjects must agree to use one of the contraception methods listed in the protocol.

          -  Capable of giving written informed consent, which includes compliance with the study
             requirements and restrictions.

          -  Average Corrected QT interval (QTc) <=450 milliseconds (msec)

        Exclusion Criteria:

          -  Current evidence or history of an influenza-like illness.

          -  Current or chronic history of liver disease, or known hepatic or biliary abnormalities
             (with the exception of Gilbert's syndrome or asymptomatic gallstones).

          -  History of, or current, acute renal failure, known renal disease, or a renal disorder
             or abnormality that may compromise renal function. This includes having one kidney.

          -  Previous inclusion in a research and/or medical protocol involving nuclear medicine,
             PET or radiological investigations or occupational exposure that, together with the
             proposed study, will result in a total radiation exposure greater than 10 mSv over a 3
             year period. Clinical exposure from which the subject receives a direct benefit
             (example, diagnostic test) is not included in these calculations.

          -  History of regular alcohol consumption within 6 months of the study defined as:

        An average weekly intake of >21 units. One unit is equivalent to 8 g of alcohol: a
        half-pint (~240 milliliter [mL]) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of
        spirits.

          -  Unable to refrain from the use of prescription drugs within 7 days or 5 half-lives
             (whichever is longer) prior to the first dose of study treatment, unless in the
             opinion of the Investigator and GSK Medical Monitor the medication will not interfere
             with the study procedures or compromise subject safety.

          -  Subject is a smoker >=5 cigarettes/day or with a smoking history of >5 pack years

          -  History of sensitivity to any of the study treatment 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.

          -  Subject suffers from claustrophobia that limits the ability to remain still in the
             PET/CT scanner for the required amount of time.

          -  Subject has metal present in their body that will interfere with the PET/CT scanning.

          -  Estimate glomerular filtration rate (eGFR) <60 mL/min/1.73 m^2 (utilizing the Chronic
             Kidney Disease Epidemiology Collaboration (CKI-EPI) equation).

          -  Urine mg protein/mg creatinine Urine Protein Creatinine Ratio (UPCR) >0.3.

          -  Evidence of hematuria by urinalysis (1plus or greater dipstick test).

          -  A positive pre-study Hepatitis B surface antigen or positive Hepatitis C (Hep C)
             antibody result within 3 months of screening.

          -  A positive test for Human Immunodeficiency Virus (HIV) antibody.

          -  A positive pre-study drug/alcohol screen.

          -  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.

          -  Where participation in the study would result in donation of blood or blood products
             in excess of 500 mL within a 56 day period.