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