Clinical Trial: 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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: An Open Label Positron Emission Tomography (PET) Imaging Study Using 89Zirconium Labeled GSK3128349 to Investigate the Biodistribution and Clearance of an Albumin Binding Domain Antibody (AlbudAb) GSK

Brief 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.

Detailed Summary:
Sponsor: GlaxoSmithKline

Current Primary Outcome:

  • Standardised Uptake Values (SUVs) derived from Positron Emission Tomography - Computer Tomography (PET-CT) data [ Time Frame: Upto 12 days ]
    SUV is a mathematically derived ratio of tissue radioactivity concentration and the injected dose of radioactivity per kilogram of the subject's body weight at a given point in time. It can be assessed for each region of interest (ROI) such as liver, kidney, muscle, spleen, heart, lung, bladder, thymus, and if feasible blood and bone. A maximum of 4 PET scans will be conducted in each subject.
  • Volume of ROI derived from PET-CT data [ Time Frame: Upto 12 days ]
    Volume of ROI is the volume specified in organs as measured in PET or CT images.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Maximum observed concentration (Cmax) of 89Zr-GSK3128349 [ Time Frame: Blood samples will be collected at Pre-dose, 1 hour (hr), 3 hr, 6 hr, 8 hr, 24 hr, Day 4, Day 6 and Day 13 ]
    Cmax, if data permit, will be calculated from the whole blood and plasma concentration-time data, measured by scintillation counting.
  • Time to achieve Cmax (Tmax) of 89Zr-GSK3128349 [ Time Frame: Blood samples will be collected at Pre-dose, 1 hr, 3 hr, 6 hr, 8 hr, 24 hr, Day 4, Day 6 and Day 13 ]
    Tmax, if data permit, will be calculated from the whole blood and plasma concentration-time data, measured by scintillation counting.
  • Apparent terminal phase half-life(t1/2) of 89Zr-GSK3128349 [ Time Frame: Blood samples will be collected at Pre-dose, 1 hr, 3 hr, 6 hr, 8 hr, 24 hr, Day 4, Day 6 and Day 13. ]
    T1/2, if data permit, will be calculated from the whole blood and plasma concentration-time data, measured by scintillation counting.
  • Area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration within a subject (AUC[0-t]) for 89Zr-GSK3128349 [ Time Frame: Blood samples will be collected at Pre-dose, 1 hr, 3 hr, 6 hr, 8 hr, 24 hr, Day 4, Day 6 and Day 13 ]
    AUC[0-t]), if data permit, will be calculated from the whole blood and plasma concentration-time data, measured by scintillation counting.
  • Clearance of 89Zr-GSK3128349 [ Time Frame: Blood samples will be collected at Pre-dose, 1 hr, 3 hr, 6 hr, 8 hr, 24 hr, Day 4, Day 6 and Day 13 ]
    Clearance, if data permit, will be calculated from the whole blood and plasma concentration-time data, measured by scintillation counting.
  • Volume of distribution (VOD) 89Zr-GSK3128349 [ Time Frame: Blood samples will be collected at Pre-dose 1 hr, 3 hr, 6 hr, 8 hr, 24 hr, Day 4, Day 6 and Day 13 ]
    VOD, if data permit, will be calculated from the whole blood and plasma concentration-time data, measured by scintillation counting.
  • Urine concentration of 89Zr-GSK3128349. [ Time Frame: Upto 24 hours ]
    Total 89Zr-GSK3128349 eliminated in the urine
  • Cmax of GSK3128349 [ Time Frame: Blood samples will be collected at Pre-dose, 1 hr, 3 hr, 6 hr, 8 hr, 24 hr, Day 4, Day 6, Day 13, Day 20, Day 31, and Day 43. ]
    Cmax, if data permit, will be calculated from the whole blood and plasma concentration-time data, measured by scintillation counting.
  • Tmax of GSK3128349 [ Time Frame: Blood samples will be collected at Pre-dose, 1 hr, 3 hr, 6 hr, 8 hr, 24 hr, Day 4, Day 6, Day 13, Day 20, Day 31, and Day 43. ]
    Tmax, if data permit, will be calculated from the whole blood and plasma concentration-time data, measured by mass spectrometry.
  • t1/2 of GSK3128349 [ Time Frame: Blood samples will be collected at Pre-dose, 1 hr, 3 hr, 6 hr, 8 hr, 24 hr, Day 4, Day 6, Day 13, Day 20, Day 31, and Day 43. ]
    t1/2, if data permit, will be calculated from the whole blood and plasma concentration-time data, measured by mass spectrometry.
  • AUC (0-t) for GSK3128349 [ Time Frame: Blood samples will be collected at Pre-dose, 1 hr, 3 hr, 6 hr, 8 hr, 24 hr, Day 4, Day 6, Day 13, Day 20, Day 31, and Day 43. ]
    AUC (0-t), if data permit, will be calculated from the whole blood and plasma concentration-time data, measured by mass spectrometry.
  • Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC[0-infinity]) for GSK3128349 [ Time Frame: Blood samples will be collected at Pre-dose, 1 hr, 3 hr, 6 hr, 8 hr, 24 hr, Day 4, Day 6, Day 13, Day 20, Day 31, and Day 43. ]
    (AUC[0-infinity]), if data permit, will be calculated from the whole blood and plasma concentration-time data, measured by mass spectrometry.
  • Clearance of GSK3128349 [ Time Frame: Blood samples will be collected at Pre-dose, 1 hr, 3 hr, 6 hr, 8 hr, 24 hr, Day 4, Day 6, Day 13, Day 20, Day 31, and Day 43. ]
    Clearance, if data permit, will be calculated from the whole blood and plasma concentration-time data, measured by mass spectrometry.
  • VOD of GSK3128349 [ Time Frame: Blood samples will be collected at Pre-dose, 1 hr, 3 hr, 6 hr, 8 hr, 24 hr, Day 4, Day 6, Day 13, Day 20, Day 31, and Day 43. ]
    VOD, if data permit, will be calculated from the whole blood and plasma concentration-time data, measured by mass spectrometry.
  • Comparison of plasma exposure assessments via different GSK3128349 mass spectroscopy methods [ Time Frame: Upto Day 43 ]
  • Organ radiation dose of 89Zr-GSK3128349 [ Time Frame: 13 days ]

    Original Secondary Outcome: Same as current

    Information By: GlaxoSmithKline

    Dates:
    Date Received: July 8, 2016
    Date Started: August 2016
    Date Completion:
    Last Updated: February 2, 2017
    Last Verified: February 2017