Phase 1
Completed N=8
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
Drug-Related Side Effects and Adverse Reactions
Source: ClinicalTrials.gov NCT02829307 ↗
Enrolled (actual)
8
Serious AEs
0.0%
Results posted
Sep 2018
Primary outcomePrimary: Mean Standardized Uptake Values (SUVs) Derived From Positron Emission Tomography-Computer Tomography (PET-CT) Data — 0.515; 0.566; 0.607; 0.623 Ratio
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Mean Standardized Uptake Values (SUVs) Derived From Positron Emission Tomography-Computer Tomography (PET-CT) Data |
0.515; 0.566; 0.607; 0.623; 4.929; 3.231 | — |
| PRIMARY Mean Volume of ROI for Each Organ at All Time Points |
45.001; 40.975; 40.094; 38.874; 574.546; 532.373 | — |
| SECONDARY Area Under Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC [0-t]) and Area Under the Concentration-time Curve From Time Zero Extrapolated to Infinite Time (AUC [0-inf]) of 89Zr-GSK3128349 and GSK3128349 |
461526.5722; 930260.1961; 82177.6360; 104257.7700 | — |
| SECONDARY Percent Area Under the Curve Obtained by Extrapolation (AUCex) and Percent Area Under the First Moment Curve Obtained by Extrapolation (AUMCex) of 89Zr-GSK3128349 and GSK3128349 |
48.5838; 84.0346; 20.7353; 55.9698 | — |
| SECONDARY Maximum Observed Plasma Concentration (Cmax) of 89Zr-GSK3128349 |
3872.7027 | — |
| SECONDARY Cmax of GSK3128349 |
374.3868 | — |
| SECONDARY Apparent Terminal Phase Half-life (t1/2) and Mean Residence Time (MRT) of 89Zr-GSK3128349 and GSK3128349 |
279.3697; 404.8882; 420.6105; 562.3356 | — |
| SECONDARY Elimination Rate Constant (Lambda-z) of 89Zr-GSK3128349 |
0.0025 | — |
| SECONDARY Volume of Distribution at a Steady State (Vss) and Volume of Distribution in the Terminal Phase (Vz) of 89Zr-GSK3128349 and GSK3128349 |
5440.5241; 5415.7602; 5393.6763; 5820.3069 | — |
| SECONDARY Area Under the First Moment Curve From Pre-dose Extrapolated to Infinite Time (AUMC [0-inf]) and Area Under the First Moment Curve From Pre-dose Extrapolated to Last Time of Quantifiable Concentration (AUMC [0-t]) of 89Zr-GSK3128349 |
376651413.6839; 53242134.4377 | — |
| SECONDARY AUMC (0-inf) and AUMC (0-t) of GSK3128349 |
58627561.8533; 25366300.3864 | — |
| SECONDARY Clearance of 89Zr-GSK3128349 and GSK3128349 |
13.4371; 9.5918 | — |
| SECONDARY Mean Organ and Effective Dose |
0.7909; 0.5701; 0.4004; 0.4827; 0.2889; 1.3871 | — |
| SECONDARY Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) |
2; 0 | — |
| SECONDARY Number of Participants With Clinical Chemistry Data of Potential Clinical Concern |
— | — |
| SECONDARY Number of Participants With Hematology Data of Potential Clinical Concern |
— | — |
| SECONDARY Number of Participants With Electrocardiogram (ECG) Values of Potential Clinical Concern |
1; 0; 0; 0; 0; 0 | — |
| SECONDARY Number of Participants With Vital Signs of Potential Clinical Concern |
— | — |
| SECONDARY Number of Participants With Positive Anti-GSK3128349 Antibody Assay |
1 | — |
| SECONDARY Serum Titers of Anti-GSK3128349 Antibodies |
80; 40 | — |
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 1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin 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) 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.
Data sourced from ClinicalTrials.gov (NCT02829307). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.