Drug-Related Side Effects and Adverse Reactions
Conditions
Keywords
89Zirconium, Open label, Pharmacokinetics, Radioactive, Clearance, Biodistribution
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.
Interventions
DRUG89Zr-GSK3128349 1 mg
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.
Sponsors
PRA Health Sciences for clinical study conduct.
GlaxoSmithKline
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
50 Years to 65 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Standardized Uptake Values (SUVs) Derived From Positron Emission Tomography-Computer Tomography (PET-CT) Data | Up to Day 7 | SUV is a mathematically derived ratio of tissue radioactivity concentration and the injected dose of radioactivity per kilogram of the participant's body weight at a given point in time. SUV was analyzed 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 were conducted in each participant. Mean SUV derived from PET-CT has been presented. |
| Mean Volume of ROI for Each Organ at All Time Points | Up to Day 7 | Volume of ROI is the volume specified in organs as measured in PET or CT images. Mean volume of ROI for each organ has been presented. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) of 89Zr-GSK3128349 | Pre-dose, 1 h, 3 h, 6 h, 8h, 24 h post-dose, Day 4, Day 6, Day 14, Day 22, Day 33 and Day 45 | PK parameters included Cmax. Cmax for 89Zr-GSK3128349 was calculated from the whole blood and plasma concentration-time data, measured by scintillation counting. |
| Cmax of GSK3128349 | Pre-dose, 1 h, 3 h, 6 h, 8h, 24 h post-dose, Day 4, Day 6, Day 14, Day 22, Day 33 and Day 45 | PK parameters included Cmax. Cmax for GSK3128349 was calculated from the whole blood and plasma concentration-time data, measured by mass spectrometry. |
| Apparent Terminal Phase Half-life (t1/2) and Mean Residence Time (MRT) of 89Zr-GSK3128349 and GSK3128349 | Pre-dose, 1 h, 3 h, 6 h, 8h, 24 h post-dose, Day 4, Day 6, Day 14, Day 22, Day 33 and Day 45 | PK parameters included t1/2 and MRT. t1/2 and MRT for 89Zr-GSK3128349 was calculated from the whole blood and plasma concentration-time data, measured by scintillation counting. t1/2 and MRT for GSK3128349 was calculated from the whole blood and plasma concentration-time data, measured by mass spectrometry. |
| Elimination Rate Constant (Lambda-z) of 89Zr-GSK3128349 | Pre-dose, 1 h, 3 h, 6 h, 8h, 24 h post-dose, Day 4, Day 6, Day 14, Day 22, Day 33 and Day 45 | PK parameters included lambda-z. Cmax for 89Zr-GSK3128349 was calculated from the whole blood and plasma concentration-time data, measured by scintillation counting. |
| Volume of Distribution at a Steady State (Vss) and Volume of Distribution in the Terminal Phase (Vz) of 89Zr-GSK3128349 and GSK3128349 | Pre-dose, 1 h, 3 h, 6 h, 8h, 24 h post-dose, Day 4, Day 6, Day 14, Day 22, Day 33 and Day 45 | PK parameters included Vss and Vz. Vss and Vz for 89Zr-GSK3128349 was calculated from the whole blood and plasma concentration-time data, measured by scintillation counting. Vss and Vz for GSK3128349 was calculated from the whole blood and plasma concentration-time data, measured by mass spectrometry. |
| 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 | Pre-dose, 1 h, 3 h, 6 h, 8h, 24 h post-dose, Day 4, Day 6, Day 14, Day 22, Day 33 and Day 45 | PK parameters included AUMC (0-inf) and AUMC (0-t). AUMC (0-inf) and AUMC (0-t) for 89Zr-GSK3128349 was calculated from the whole blood and plasma concentration-time data, measured by scintillation counting. |
| AUMC (0-inf) and AUMC (0-t) of GSK3128349 | Pre-dose, 1 h, 3 h, 6 h, 8h, 24 h post-dose, Day 4, Day 6, Day 14, Day 22, Day 33 and Day 45 | PK parameters included AUMC (0-inf) and AUMC (0-t). AUMC (0-inf) and AUMC (0-t) for GSK3128349 was calculated from the whole blood and plasma concentration-time data, measured by mass spectrometry. |
| Clearance of 89Zr-GSK3128349 and GSK3128349 | Pre-dose, 1 h, 3 h, 6 h, 8h, 24 h post-dose, Day 4, Day 6, Day 14, Day 22, Day 33 and Day 45 | PK parameters included clearance. Clearance for 89Zr-GSK3128349 was calculated from the whole blood and plasma concentration-time data, measured by scintillation counting. Clearance for GSK3128349 was calculated from the whole blood and plasma concentration-time data, measured by mass spectrometry. |
| 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 | Pre-dose, 1 hour (h), 3 h, 6 h, 8h, 24 h post-dose, Day 4, Day 6, Day 14, Day 22, Day 33 and Day 45 | PK parameters included AUC (0-t) and AUC (0-inf). AUC (0-t) and AUC (0-inf) for 89Zr-GSK3128349 was calculated from the whole blood and plasma concentration-time data, measured by scintillation counting. AUC (0-t) and AUC (0-inf) for GSK3128349 was calculated from the whole blood and plasma concentration-time data, measured by mass spectrometry. |
| Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) | Up to 45 days | AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For marketed medicinal products, this also includes failure to produce expected benefits (i.e., lack of efficacy), abuse or misuse. SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant or is associated with liver injury or impaired liver function. |
| Number of Participants With Clinical Chemistry Data of Potential Clinical Concern | Up to 45 days | The potential clinical concern range for clinical chemistry parameters were: glucose (low: \< 3 millimole \[mmol\]/L and high: \> 9 mmol/L), creatinine (high: Change from Baseline or Day 1 should be positive and \> 44.2 mmol/L), phosphorous (low: \< 0.8 mmol/L and high: \> 1.6 mmol/L), magnesium (low: \< 0.5 mmol/L and high: \> 1.23 mmol/L), calcium (low: \<2 mmoL/L and high: \> 2.75 mmol/L), carbon dioxide content (low: \< 18 mmol/L and high: \> 32 mmol/L), albumin (low: \< 30 mmol/L), potassium (low: \< 3.0 mmol/L and high: \> 5.5 mmol/L) and sodium (low: \< 130 mmol/L and high: \> 130 mmol/L). Number of participants with clinical chemistry abnormalities of potential clinical importance are presented |
| Number of Participants With Hematology Data of Potential Clinical Concern | Up to 45 days | The potential clinical concern range for hematology parameters were: Hemoglobin (low: \> 25 gram per Liter change from Baseline/Day 1 and high: \> 180 gram per Liter), lymphocytes (low: \< 0.8 gigacells/L), hematocrit (low: \> 0.075 ratio change from Baseline and high: \> 0.54 ratio), neutrophil count (low: \< 1.5\*10\^9/Liter), platelet count (low: \< 100 gigacells/L and high: \> 550 gigacells/L), white blood cell (WBC) count (low: \< 3 gigacells/L and high: \> 20 gigacells/L). Number of participants with hematology abnormalities of potential clinical importance are presented. |
| Number of Participants With Electrocardiogram (ECG) Values of Potential Clinical Concern | Pre-dose on Day 1, 1 h and 24 h post-dose on Day 1 and Day 45 | ECG measurements were made with the participant in a supine position having rested in this position for at least 5 minutes before each reading. Triplicate 12-lead ECGS were obtained pre dose at Day 1 and single 12-lead ECGs will be obtained at other time points during the study. The potential clinical concern range for ECG parameters was as follows: Absolute corrected QT (QTc) interval (lower: \>450 milliseconds \[msec\], \>450 msec, \>=480 msec and \>=500 msec) and (higher: \<=479 msec and \<=499 msec); absolute PR interval (lower: \<110 and higher \>220 msec) and absolute QRS interval (lower: \<75 msec and \>110 msec). Number of participants with ECG values of potential clinical concern are presented. |
| Number of Participants With Vital Signs of Potential Clinical Concern | Up to 45 days | Vital signs included pulse rate, systolic and diastolic blood pressure and body temperature. All vital sign measurements were made with the participant in a supine position and rested in this position for at least 5 minutes before each reading. The potential clinical concern range for systolic blood pressure: \<85 and \>160 millimeters of mercury (mmHg), for diastolic: \<45 and \>100 mmHg and heart rate: \<40 and \>110 beats per minute. Number of participants with vital signs of potential clinical concern are presented. |
| Number of Participants With Positive Anti-GSK3128349 Antibody Assay | Pre-dose on Day 1 and Day 43 | Blood samples for testing antibodies against GSK3128349 will be collected on Day 1 (pre-dose) and on Day 43. The actual date and time of each blood sample collection was recorded. The first blood sample was taken pre-dose on Day 1 to determine the presence, if any, of pre-existing Anti Drug Antibodies (ADAs). The presence of such antibodies was assessed using an electrochemiluminescent (ECL) immuno assay. If sera contain anti-GSK3128349 antibodies, they were further analyzed for the antibody specificity and titres. Number of participants who were found to have anti-GSK3128349 antibodies are presented. |
| Serum Titers of Anti-GSK3128349 Antibodies | Pre-dose on Day 1 and Day 43 | Blood samples for testing antibodies against GSK3128349 will be collected on Day 1 (pre-dose) and on Day 43. The actual date and time of each blood sample collection was recorded. The first blood sample was taken pre-dose on Day 1 to determine the presence, if any, of pre-existing ADAs. The presence of such antibodies and serum titers of anti-GSK3128349 antibodies was assessed using an ECL immuno-assay. If sera contain anti-GSK3128349 antibodies, they were further analyzed for the antibody specificity and titers. |
| Mean Organ and Effective Dose | Up to Day 7 | Organ dose was defined as the amount of radiation delivered to a particular organ. Effective dose was defined as the tissue-weighted sum of the organ doses in all specified tissues and organs of the human body. The organ and effective dose is a fraction of milliSievert (mSv) and MegaBecquerel (MBq). The mean relative uptake of 89Zr-GSK3128349 in different organs for all participants across all PET scans is presented. |
| 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 | Pre-dose, 1 h, 3 h, 6 h, 8h, 24 h post-dose, Day 4, Day 6, Day 14, Day 22, Day 33 and Day 45 | PK parameters included AUCex and AUMCex. AUCex and AUMCex for 89Zr-GSK3128349 was calculated from the whole blood and plasma concentration-time data, measured by scintillation counting. AUCex and AUMCex for GSK3128349 was calculated from the whole blood and plasma concentration-time data, measured by mass spectrometry. |
Countries
Netherlands
Participant flow
Recruitment details
This study was conducted at a single center in Netherlands from 23-Aug-16 to 27-Jan-17. A total of 8 participants were randomized in the study who received 89Zr-GSK3128349 which was a mixture of unlabelled and zirconium-labelled GSK3128349, in the form of solution for intravenous (IV) administration.
Pre-assignment details
A total of 34 participants were screened, of which 26 were screen failures. The reasons for screen failure were: did not meet the inclusion/exclusion criteria (11 participants) and investigator discretion (15 participants).
Participants by arm
| Arm | Count |
|---|---|
| 89Zr-GSK3128349 Eligible participants received a single dose of 89Zr-GSK3128349 as an IV infusion over 20 minutes to deliver a dose of 1 mg. | 8 |
| Total | 8 |
Baseline characteristics
| Characteristic | 89Zr-GSK3128349 |
|---|---|
| Age, Continuous | 55.0 Years STANDARD_DEVIATION 2.33 |
| Race/Ethnicity, Customized American Indian or Alaskan Native | 1 Participants |
| Race/Ethnicity, Customized White- White/Caucasian/ European Heritage | 7 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 8 |
| other Total, other adverse events | 2 / 8 |
| serious Total, serious adverse events | 0 / 8 |
Outcome results
Primary
Mean Standardized Uptake Values (SUVs) Derived From Positron Emission Tomography-Computer Tomography (PET-CT) Data
SUV is a mathematically derived ratio of tissue radioactivity concentration and the injected dose of radioactivity per kilogram of the participant's body weight at a given point in time. SUV was analyzed 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 were conducted in each participant. Mean SUV derived from PET-CT has been presented.
Time frame: Up to Day 7
Population: Pharmacokinetic (PK) Population comprised of participants in the Safety Population for whom a PK sample was obtained and analyzed, and/or for which a PET scan was completed. Only those participants available at the specified time points were analyzed represented by n=X in the category titles.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 89Zr-GSK3128349 | Mean Standardized Uptake Values (SUVs) Derived From Positron Emission Tomography-Computer Tomography (PET-CT) Data | Thigh muscle: PET scan 4; n=7 | 0.623 Ratio | Standard Deviation 0.1509 |
| 89Zr-GSK3128349 | Mean Standardized Uptake Values (SUVs) Derived From Positron Emission Tomography-Computer Tomography (PET-CT) Data | Pancreas: PET scan 3; n=6 | 1.887 Ratio | Standard Deviation 0.4131 |
| 89Zr-GSK3128349 | Mean Standardized Uptake Values (SUVs) Derived From Positron Emission Tomography-Computer Tomography (PET-CT) Data | Pancreas: PET scan 4; n=6 | 1.917 Ratio | Standard Deviation 1.0314 |
| 89Zr-GSK3128349 | Mean Standardized Uptake Values (SUVs) Derived From Positron Emission Tomography-Computer Tomography (PET-CT) Data | Bladder: PET scan 1; n=8 | 2.750 Ratio | Standard Deviation 1.0483 |
| 89Zr-GSK3128349 | Mean Standardized Uptake Values (SUVs) Derived From Positron Emission Tomography-Computer Tomography (PET-CT) Data | Bladder: PET scan 4; n=7 | 1.609 Ratio | Standard Deviation 0.4176 |
| 89Zr-GSK3128349 | Mean Standardized Uptake Values (SUVs) Derived From Positron Emission Tomography-Computer Tomography (PET-CT) Data | Kidney: PET scan 1; n=8 | 7.845 Ratio | Standard Deviation 1.1487 |
| 89Zr-GSK3128349 | Mean Standardized Uptake Values (SUVs) Derived From Positron Emission Tomography-Computer Tomography (PET-CT) Data | Kidney: PET scan 2; n=8 | 9.516 Ratio | Standard Deviation 1.0005 |
| 89Zr-GSK3128349 | Mean Standardized Uptake Values (SUVs) Derived From Positron Emission Tomography-Computer Tomography (PET-CT) Data | Lung: PET scan 2; n=8 | 1.345 Ratio | Standard Deviation 0.4381 |
| 89Zr-GSK3128349 | Mean Standardized Uptake Values (SUVs) Derived From Positron Emission Tomography-Computer Tomography (PET-CT) Data | Aorta: PET scan 1; n=8 | 10.835 Ratio | Standard Deviation 2.0289 |
| 89Zr-GSK3128349 | Mean Standardized Uptake Values (SUVs) Derived From Positron Emission Tomography-Computer Tomography (PET-CT) Data | Aorta: PET scan 2; n=8 | 6.573 Ratio | Standard Deviation 1.5621 |
| 89Zr-GSK3128349 | Mean Standardized Uptake Values (SUVs) Derived From Positron Emission Tomography-Computer Tomography (PET-CT) Data | Aorta: PET scan 3; n=7 | 5.516 Ratio | Standard Deviation 1.4879 |
| 89Zr-GSK3128349 | Mean Standardized Uptake Values (SUVs) Derived From Positron Emission Tomography-Computer Tomography (PET-CT) Data | Heart: PET scan 3; n=7 | 4.829 Ratio | Standard Deviation 1.3661 |
| 89Zr-GSK3128349 | Mean Standardized Uptake Values (SUVs) Derived From Positron Emission Tomography-Computer Tomography (PET-CT) Data | Kidney, medulla: PET scan 4; n=7 | 6.691 Ratio | Standard Deviation 1.1767 |
| 89Zr-GSK3128349 | Mean Standardized Uptake Values (SUVs) Derived From Positron Emission Tomography-Computer Tomography (PET-CT) Data | Body: PET scan 1; n=8 | 0.739 Ratio | Standard Deviation 0.1647 |
| 89Zr-GSK3128349 | Mean Standardized Uptake Values (SUVs) Derived From Positron Emission Tomography-Computer Tomography (PET-CT) Data | Body: PET scan 4; n=7 | 0.631 Ratio | Standard Deviation 0.168 |
| 89Zr-GSK3128349 | Mean Standardized Uptake Values (SUVs) Derived From Positron Emission Tomography-Computer Tomography (PET-CT) Data | Thigh muscle: PET scan 1; n=8 | 0.515 Ratio | Standard Deviation 0.1387 |
| 89Zr-GSK3128349 | Mean Standardized Uptake Values (SUVs) Derived From Positron Emission Tomography-Computer Tomography (PET-CT) Data | Thigh muscle: PET scan 2; n=8 | 0.566 Ratio | Standard Deviation 0.1315 |
| 89Zr-GSK3128349 | Mean Standardized Uptake Values (SUVs) Derived From Positron Emission Tomography-Computer Tomography (PET-CT) Data | Thigh muscle: PET scan 3; n=7 | 0.607 Ratio | Standard Deviation 0.0767 |
| 89Zr-GSK3128349 | Mean Standardized Uptake Values (SUVs) Derived From Positron Emission Tomography-Computer Tomography (PET-CT) Data | Liver: PET scan 1; n=8 | 4.929 Ratio | Standard Deviation 0.7219 |
| 89Zr-GSK3128349 | Mean Standardized Uptake Values (SUVs) Derived From Positron Emission Tomography-Computer Tomography (PET-CT) Data | Liver: PET scan 2; n=8 | 3.231 Ratio | Standard Deviation 0.4981 |
| 89Zr-GSK3128349 | Mean Standardized Uptake Values (SUVs) Derived From Positron Emission Tomography-Computer Tomography (PET-CT) Data | Liver: PET scan 3; n=7 | 2.994 Ratio | Standard Deviation 0.7314 |
| 89Zr-GSK3128349 | Mean Standardized Uptake Values (SUVs) Derived From Positron Emission Tomography-Computer Tomography (PET-CT) Data | Liver: PET scan 4; n=7 | 2.280 Ratio | Standard Deviation 0.3151 |
| 89Zr-GSK3128349 | Mean Standardized Uptake Values (SUVs) Derived From Positron Emission Tomography-Computer Tomography (PET-CT) Data | Pancreas: PET scan 1; n=7 | 2.177 Ratio | Standard Deviation 0.4573 |
| 89Zr-GSK3128349 | Mean Standardized Uptake Values (SUVs) Derived From Positron Emission Tomography-Computer Tomography (PET-CT) Data | Pancreas: PET scan 2; n=7 | 2.029 Ratio | Standard Deviation 0.6621 |
| 89Zr-GSK3128349 | Mean Standardized Uptake Values (SUVs) Derived From Positron Emission Tomography-Computer Tomography (PET-CT) Data | Thyroid gland: PET scan 1; n=8 | 2.338 Ratio | Standard Deviation 0.8821 |
| 89Zr-GSK3128349 | Mean Standardized Uptake Values (SUVs) Derived From Positron Emission Tomography-Computer Tomography (PET-CT) Data | Thyroid gland: PET scan 2; n=8 | 2.171 Ratio | Standard Deviation 0.8408 |
| 89Zr-GSK3128349 | Mean Standardized Uptake Values (SUVs) Derived From Positron Emission Tomography-Computer Tomography (PET-CT) Data | Thyroid gland: PET scan 3; n=7 | 2.330 Ratio | Standard Deviation 1.051 |
| 89Zr-GSK3128349 | Mean Standardized Uptake Values (SUVs) Derived From Positron Emission Tomography-Computer Tomography (PET-CT) Data | Thyroid gland: PET scan 4; n=7 | 1.789 Ratio | Standard Deviation 0.4791 |
| 89Zr-GSK3128349 | Mean Standardized Uptake Values (SUVs) Derived From Positron Emission Tomography-Computer Tomography (PET-CT) Data | Testis: PET scan 1; n=8 | 3.336 Ratio | Standard Deviation 0.7479 |
| 89Zr-GSK3128349 | Mean Standardized Uptake Values (SUVs) Derived From Positron Emission Tomography-Computer Tomography (PET-CT) Data | Testis: PET scan 2; n=8 | 3.733 Ratio | Standard Deviation 0.7793 |
| 89Zr-GSK3128349 | Mean Standardized Uptake Values (SUVs) Derived From Positron Emission Tomography-Computer Tomography (PET-CT) Data | Testis: PET scan 3; n=7 | 3.259 Ratio | Standard Deviation 0.9988 |
| 89Zr-GSK3128349 | Mean Standardized Uptake Values (SUVs) Derived From Positron Emission Tomography-Computer Tomography (PET-CT) Data | Testis: PET scan 4; n=7 | 3.280 Ratio | Standard Deviation 0.4789 |
| 89Zr-GSK3128349 | Mean Standardized Uptake Values (SUVs) Derived From Positron Emission Tomography-Computer Tomography (PET-CT) Data | Bladder: PET scan 2; n=8 | 1.149 Ratio | Standard Deviation 0.4572 |
| 89Zr-GSK3128349 | Mean Standardized Uptake Values (SUVs) Derived From Positron Emission Tomography-Computer Tomography (PET-CT) Data | Bladder: PET scan 3; n=7 | 1.630 Ratio | Standard Deviation 0.4938 |
| 89Zr-GSK3128349 | Mean Standardized Uptake Values (SUVs) Derived From Positron Emission Tomography-Computer Tomography (PET-CT) Data | Kidney: PET scan 3; n=7 | 10.466 Ratio | Standard Deviation 2.2765 |
| 89Zr-GSK3128349 | Mean Standardized Uptake Values (SUVs) Derived From Positron Emission Tomography-Computer Tomography (PET-CT) Data | Kidney: PET scan 4; n=7 | 8.603 Ratio | Standard Deviation 1.6626 |
| 89Zr-GSK3128349 | Mean Standardized Uptake Values (SUVs) Derived From Positron Emission Tomography-Computer Tomography (PET-CT) Data | Parotid gland: PET scan 1; n=8 | 1.514 Ratio | Standard Deviation 0.3005 |
| 89Zr-GSK3128349 | Mean Standardized Uptake Values (SUVs) Derived From Positron Emission Tomography-Computer Tomography (PET-CT) Data | Parotid gland: PET scan 2; n=8 | 1.430 Ratio | Standard Deviation 0.3091 |
| 89Zr-GSK3128349 | Mean Standardized Uptake Values (SUVs) Derived From Positron Emission Tomography-Computer Tomography (PET-CT) Data | Parotid gland: PET scan 3; n=7 | 1.541 Ratio | Standard Deviation 0.2084 |
| 89Zr-GSK3128349 | Mean Standardized Uptake Values (SUVs) Derived From Positron Emission Tomography-Computer Tomography (PET-CT) Data | Parotid gland: PET scan 4; n=7 | 1.531 Ratio | Standard Deviation 0.1643 |
| 89Zr-GSK3128349 | Mean Standardized Uptake Values (SUVs) Derived From Positron Emission Tomography-Computer Tomography (PET-CT) Data | Bone marrow: PET scan 1; n=8 | 1.746 Ratio | Standard Deviation 0.2575 |
| 89Zr-GSK3128349 | Mean Standardized Uptake Values (SUVs) Derived From Positron Emission Tomography-Computer Tomography (PET-CT) Data | Bone marrow: PET scan 2; n=8 | 1.378 Ratio | Standard Deviation 0.2066 |
| 89Zr-GSK3128349 | Mean Standardized Uptake Values (SUVs) Derived From Positron Emission Tomography-Computer Tomography (PET-CT) Data | Bone marrow: PET scan 3; n=7 | 1.289 Ratio | Standard Deviation 0.2998 |
| 89Zr-GSK3128349 | Mean Standardized Uptake Values (SUVs) Derived From Positron Emission Tomography-Computer Tomography (PET-CT) Data | Bone marrow: PET scan 4; n=7 | 1.350 Ratio | Standard Deviation 0.2802 |
| 89Zr-GSK3128349 | Mean Standardized Uptake Values (SUVs) Derived From Positron Emission Tomography-Computer Tomography (PET-CT) Data | Spleen: PET scan 1; n=8 | 5.220 Ratio | Standard Deviation 0.6398 |
| 89Zr-GSK3128349 | Mean Standardized Uptake Values (SUVs) Derived From Positron Emission Tomography-Computer Tomography (PET-CT) Data | Spleen: PET scan 2; n=8 | 3.691 Ratio | Standard Deviation 0.4638 |
| 89Zr-GSK3128349 | Mean Standardized Uptake Values (SUVs) Derived From Positron Emission Tomography-Computer Tomography (PET-CT) Data | Spleen: PET scan 3; n=7 | 3.296 Ratio | Standard Deviation 0.8611 |
| 89Zr-GSK3128349 | Mean Standardized Uptake Values (SUVs) Derived From Positron Emission Tomography-Computer Tomography (PET-CT) Data | Spleen: PET scan 4; n=7 | 3.097 Ratio | Standard Deviation 0.4946 |
| 89Zr-GSK3128349 | Mean Standardized Uptake Values (SUVs) Derived From Positron Emission Tomography-Computer Tomography (PET-CT) Data | Brain: PET scan 1; n=8 | 0.461 Ratio | Standard Deviation 0.0762 |
| 89Zr-GSK3128349 | Mean Standardized Uptake Values (SUVs) Derived From Positron Emission Tomography-Computer Tomography (PET-CT) Data | Brain: PET scan 2; n=8 | 0.295 Ratio | Standard Deviation 0.0901 |
| 89Zr-GSK3128349 | Mean Standardized Uptake Values (SUVs) Derived From Positron Emission Tomography-Computer Tomography (PET-CT) Data | Brain: PET scan 3; n=7 | 0.231 Ratio | Standard Deviation 0.0689 |
| 89Zr-GSK3128349 | Mean Standardized Uptake Values (SUVs) Derived From Positron Emission Tomography-Computer Tomography (PET-CT) Data | Brain: PET scan 4; n=7 | 0.201 Ratio | Standard Deviation 0.0348 |
| 89Zr-GSK3128349 | Mean Standardized Uptake Values (SUVs) Derived From Positron Emission Tomography-Computer Tomography (PET-CT) Data | Lung: PET scan 1; n=8 | 1.884 Ratio | Standard Deviation 0.5968 |
| 89Zr-GSK3128349 | Mean Standardized Uptake Values (SUVs) Derived From Positron Emission Tomography-Computer Tomography (PET-CT) Data | Lung: PET scan 3; n=7 | 1.186 Ratio | Standard Deviation 0.472 |
| 89Zr-GSK3128349 | Mean Standardized Uptake Values (SUVs) Derived From Positron Emission Tomography-Computer Tomography (PET-CT) Data | Lung: PET scan 4; n=7 | 0.893 Ratio | Standard Deviation 0.2583 |
| 89Zr-GSK3128349 | Mean Standardized Uptake Values (SUVs) Derived From Positron Emission Tomography-Computer Tomography (PET-CT) Data | Aorta: PET scan 4; n=7 | 4.299 Ratio | Standard Deviation 0.8195 |
| 89Zr-GSK3128349 | Mean Standardized Uptake Values (SUVs) Derived From Positron Emission Tomography-Computer Tomography (PET-CT) Data | Heart: PET scan 1; n=8 | 8.601 Ratio | Standard Deviation 1.8566 |
| 89Zr-GSK3128349 | Mean Standardized Uptake Values (SUVs) Derived From Positron Emission Tomography-Computer Tomography (PET-CT) Data | Heart: PET scan 2; n=8 | 5.851 Ratio | Standard Deviation 1.5742 |
| 89Zr-GSK3128349 | Mean Standardized Uptake Values (SUVs) Derived From Positron Emission Tomography-Computer Tomography (PET-CT) Data | Heart: PET scan 4; n=7 | 3.701 Ratio | Standard Deviation 0.677 |
| 89Zr-GSK3128349 | Mean Standardized Uptake Values (SUVs) Derived From Positron Emission Tomography-Computer Tomography (PET-CT) Data | Kidney, cortex: PET scan 1; n=8 | 8.805 Ratio | Standard Deviation 1.4835 |
| 89Zr-GSK3128349 | Mean Standardized Uptake Values (SUVs) Derived From Positron Emission Tomography-Computer Tomography (PET-CT) Data | Kidney, cortex: PET scan 2; n=8 | 12.145 Ratio | Standard Deviation 1.7704 |
| 89Zr-GSK3128349 | Mean Standardized Uptake Values (SUVs) Derived From Positron Emission Tomography-Computer Tomography (PET-CT) Data | Kidney, cortex: PET scan 3; n=7 | 11.966 Ratio | Standard Deviation 1.5492 |
| 89Zr-GSK3128349 | Mean Standardized Uptake Values (SUVs) Derived From Positron Emission Tomography-Computer Tomography (PET-CT) Data | Kidney, cortex: PET scan 4; n=7 | 10.479 Ratio | Standard Deviation 1.6047 |
| 89Zr-GSK3128349 | Mean Standardized Uptake Values (SUVs) Derived From Positron Emission Tomography-Computer Tomography (PET-CT) Data | Kidney, medulla: PET scan 1; n=8 | 6.996 Ratio | Standard Deviation 1.5577 |
| 89Zr-GSK3128349 | Mean Standardized Uptake Values (SUVs) Derived From Positron Emission Tomography-Computer Tomography (PET-CT) Data | Kidney, medulla: PET scan 2; n=8 | 7.416 Ratio | Standard Deviation 1.2101 |
| 89Zr-GSK3128349 | Mean Standardized Uptake Values (SUVs) Derived From Positron Emission Tomography-Computer Tomography (PET-CT) Data | Kidney, medulla: PET scan 3; n=7 | 8.247 Ratio | Standard Deviation 2.3436 |
| 89Zr-GSK3128349 | Mean Standardized Uptake Values (SUVs) Derived From Positron Emission Tomography-Computer Tomography (PET-CT) Data | Body: PET scan 2; n=8 | 0.654 Ratio | Standard Deviation 0.1632 |
| 89Zr-GSK3128349 | Mean Standardized Uptake Values (SUVs) Derived From Positron Emission Tomography-Computer Tomography (PET-CT) Data | Body: PET scan 3; n=7 | 0.701 Ratio | Standard Deviation 0.1728 |
Primary
Mean Volume of ROI for Each Organ at All Time Points
Volume of ROI is the volume specified in organs as measured in PET or CT images. Mean volume of ROI for each organ has been presented.
Time frame: Up to Day 7
Population: PK Population. Only those participants available at the specified time points were analyzed represented by n=X in the category titles.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 89Zr-GSK3128349 | Mean Volume of ROI for Each Organ at All Time Points | Pancreas: PET scan 4; n=6 | 6.877 Milliliter (mL) | Standard Deviation 4.7283 |
| 89Zr-GSK3128349 | Mean Volume of ROI for Each Organ at All Time Points | Thyroid gland: PET scan 1; n=8 | 2.750 Milliliter (mL) | Standard Deviation 1.5549 |
| 89Zr-GSK3128349 | Mean Volume of ROI for Each Organ at All Time Points | Thyroid gland: PET scan 2; n=8 | 3.004 Milliliter (mL) | Standard Deviation 0.9845 |
| 89Zr-GSK3128349 | Mean Volume of ROI for Each Organ at All Time Points | Testis: PET scan 3; n=7 | 11.583 Milliliter (mL) | Standard Deviation 4.5054 |
| 89Zr-GSK3128349 | Mean Volume of ROI for Each Organ at All Time Points | Testis: PET scan 4; n=7 | 13.871 Milliliter (mL) | Standard Deviation 7.6413 |
| 89Zr-GSK3128349 | Mean Volume of ROI for Each Organ at All Time Points | Kidney: PET scan 3; n=7 | 152.031 Milliliter (mL) | Standard Deviation 36.5278 |
| 89Zr-GSK3128349 | Mean Volume of ROI for Each Organ at All Time Points | Kidney: PET scan 4; n=7 | 177.840 Milliliter (mL) | Standard Deviation 30.9614 |
| 89Zr-GSK3128349 | Mean Volume of ROI for Each Organ at All Time Points | Parotid gland: PET scan 3; n=7 | 8.611 Milliliter (mL) | Standard Deviation 1.6606 |
| 89Zr-GSK3128349 | Mean Volume of ROI for Each Organ at All Time Points | Parotid gland: PET scan 4; n=7 | 9.896 Milliliter (mL) | Standard Deviation 2.6622 |
| 89Zr-GSK3128349 | Mean Volume of ROI for Each Organ at All Time Points | Bone marrow: PET scan 1; n=8 | 36.625 Milliliter (mL) | Standard Deviation 18.3824 |
| 89Zr-GSK3128349 | Mean Volume of ROI for Each Organ at All Time Points | Bone marrow: PET scan 2; n=8 | 37.495 Milliliter (mL) | Standard Deviation 15.1968 |
| 89Zr-GSK3128349 | Mean Volume of ROI for Each Organ at All Time Points | Bone marrow: PET scan 3; n=7 | 45.271 Milliliter (mL) | Standard Deviation 18.2245 |
| 89Zr-GSK3128349 | Mean Volume of ROI for Each Organ at All Time Points | Bone marrow: PET scan 4; n=7 | 42.871 Milliliter (mL) | Standard Deviation 14.4365 |
| 89Zr-GSK3128349 | Mean Volume of ROI for Each Organ at All Time Points | Spleen: PET scan 4; n=7 | 47.474 Milliliter (mL) | Standard Deviation 18.3678 |
| 89Zr-GSK3128349 | Mean Volume of ROI for Each Organ at All Time Points | Brain: PET scan 1; n=8 | 575.996 Milliliter (mL) | Standard Deviation 91.2147 |
| 89Zr-GSK3128349 | Mean Volume of ROI for Each Organ at All Time Points | Brain: PET scan 4; n=7 | 498.207 Milliliter (mL) | Standard Deviation 145.5429 |
| 89Zr-GSK3128349 | Mean Volume of ROI for Each Organ at All Time Points | Lung: PET scan 1; n=8 | 329.891 Milliliter (mL) | Standard Deviation 134.1686 |
| 89Zr-GSK3128349 | Mean Volume of ROI for Each Organ at All Time Points | Heart: PET scan 3; n=7 | 105.007 Milliliter (mL) | Standard Deviation 26.151 |
| 89Zr-GSK3128349 | Mean Volume of ROI for Each Organ at All Time Points | Heart: PET scan 4; n=7 | 103.971 Milliliter (mL) | Standard Deviation 40.0218 |
| 89Zr-GSK3128349 | Mean Volume of ROI for Each Organ at All Time Points | Thigh muscle: PET scan 1; n=8 | 45.001 Milliliter (mL) | Standard Deviation 16.6069 |
| 89Zr-GSK3128349 | Mean Volume of ROI for Each Organ at All Time Points | Thigh muscle: PET scan 2; n=8 | 40.975 Milliliter (mL) | Standard Deviation 12.4102 |
| 89Zr-GSK3128349 | Mean Volume of ROI for Each Organ at All Time Points | Thigh muscle: PET scan 3; n=7 | 40.094 Milliliter (mL) | Standard Deviation 6.7137 |
| 89Zr-GSK3128349 | Mean Volume of ROI for Each Organ at All Time Points | Thigh muscle: PET scan 4; n=7 | 38.874 Milliliter (mL) | Standard Deviation 10.7444 |
| 89Zr-GSK3128349 | Mean Volume of ROI for Each Organ at All Time Points | Liver: PET scan 1; n=8 | 574.546 Milliliter (mL) | Standard Deviation 301.458 |
| 89Zr-GSK3128349 | Mean Volume of ROI for Each Organ at All Time Points | Liver: PET scan 2; n=8 | 532.373 Milliliter (mL) | Standard Deviation 147.3186 |
| 89Zr-GSK3128349 | Mean Volume of ROI for Each Organ at All Time Points | Liver: PET scan 3; n=7 | 488.974 Milliliter (mL) | Standard Deviation 156.2512 |
| 89Zr-GSK3128349 | Mean Volume of ROI for Each Organ at All Time Points | Liver: PET scan 4; n=7 | 496.861 Milliliter (mL) | Standard Deviation 166.0174 |
| 89Zr-GSK3128349 | Mean Volume of ROI for Each Organ at All Time Points | Pancreas: PET scan 1; n=7 | 7.777 Milliliter (mL) | Standard Deviation 3.3295 |
| 89Zr-GSK3128349 | Mean Volume of ROI for Each Organ at All Time Points | Pancreas: PET scan 2; n=7 | 7.780 Milliliter (mL) | Standard Deviation 2.7156 |
| 89Zr-GSK3128349 | Mean Volume of ROI for Each Organ at All Time Points | Pancreas: PET scan 3; n=6 | 5.905 Milliliter (mL) | Standard Deviation 3.0366 |
| 89Zr-GSK3128349 | Mean Volume of ROI for Each Organ at All Time Points | Thyroid gland: PET scan 3; n=7 | 2.913 Milliliter (mL) | Standard Deviation 0.959 |
| 89Zr-GSK3128349 | Mean Volume of ROI for Each Organ at All Time Points | Thyroid gland: PET scan 4; n=7 | 4.137 Milliliter (mL) | Standard Deviation 2.0853 |
| 89Zr-GSK3128349 | Mean Volume of ROI for Each Organ at All Time Points | Testis: PET scan 1; n=8 | 13.223 Milliliter (mL) | Standard Deviation 6.7226 |
| 89Zr-GSK3128349 | Mean Volume of ROI for Each Organ at All Time Points | Testis: PET scan 2; n=8 | 12.010 Milliliter (mL) | Standard Deviation 6.5955 |
| 89Zr-GSK3128349 | Mean Volume of ROI for Each Organ at All Time Points | Bladder: PET scan 1; n=8 | 84.228 Milliliter (mL) | Standard Deviation 69.2024 |
| 89Zr-GSK3128349 | Mean Volume of ROI for Each Organ at All Time Points | Bladder: PET scan 2; n=8 | 60.669 Milliliter (mL) | Standard Deviation 26.7843 |
| 89Zr-GSK3128349 | Mean Volume of ROI for Each Organ at All Time Points | Bladder: PET scan 3; n=7 | 54.771 Milliliter (mL) | Standard Deviation 26.2373 |
| 89Zr-GSK3128349 | Mean Volume of ROI for Each Organ at All Time Points | Bladder: PET scan 4; n=7 | 66.291 Milliliter (mL) | Standard Deviation 47.1061 |
| 89Zr-GSK3128349 | Mean Volume of ROI for Each Organ at All Time Points | Kidney: PET scan 1; n=8 | 144.093 Milliliter (mL) | Standard Deviation 32.8834 |
| 89Zr-GSK3128349 | Mean Volume of ROI for Each Organ at All Time Points | Kidney: PET scan 2; n=8 | 162.578 Milliliter (mL) | Standard Deviation 55.1273 |
| 89Zr-GSK3128349 | Mean Volume of ROI for Each Organ at All Time Points | Parotid gland: PET scan 1; n=8 | 8.304 Milliliter (mL) | Standard Deviation 3.5772 |
| 89Zr-GSK3128349 | Mean Volume of ROI for Each Organ at All Time Points | Parotid gland: PET scan 2; n=8 | 9.391 Milliliter (mL) | Standard Deviation 4.2224 |
| 89Zr-GSK3128349 | Mean Volume of ROI for Each Organ at All Time Points | Spleen: PET scan 1; n=8 | 62.238 Milliliter (mL) | Standard Deviation 20.6549 |
| 89Zr-GSK3128349 | Mean Volume of ROI for Each Organ at All Time Points | Spleen: PET scan 2; n=8 | 67.160 Milliliter (mL) | Standard Deviation 21.9034 |
| 89Zr-GSK3128349 | Mean Volume of ROI for Each Organ at All Time Points | Spleen: PET scan 3; n=7 | 54.544 Milliliter (mL) | Standard Deviation 13.4153 |
| 89Zr-GSK3128349 | Mean Volume of ROI for Each Organ at All Time Points | Brain: PET scan 2; n=8 | 510.614 Milliliter (mL) | Standard Deviation 139.8124 |
| 89Zr-GSK3128349 | Mean Volume of ROI for Each Organ at All Time Points | Brain: PET scan 3; n=7 | 471.550 Milliliter (mL) | Standard Deviation 152.8605 |
| 89Zr-GSK3128349 | Mean Volume of ROI for Each Organ at All Time Points | Lung: PET scan 2; n=8 | 329.374 Milliliter (mL) | Standard Deviation 162.8302 |
| 89Zr-GSK3128349 | Mean Volume of ROI for Each Organ at All Time Points | Lung: PET scan 3; n=7 | 328.794 Milliliter (mL) | Standard Deviation 115.2736 |
| 89Zr-GSK3128349 | Mean Volume of ROI for Each Organ at All Time Points | Lung: PET scan 4; n=7 | 308.494 Milliliter (mL) | Standard Deviation 77.7344 |
| 89Zr-GSK3128349 | Mean Volume of ROI for Each Organ at All Time Points | Aorta: PET scan 1; n=8 | 6.388 Milliliter (mL) | Standard Deviation 2.9532 |
| 89Zr-GSK3128349 | Mean Volume of ROI for Each Organ at All Time Points | Aorta: PET scan 2; n=8 | 8.171 Milliliter (mL) | Standard Deviation 3.5471 |
| 89Zr-GSK3128349 | Mean Volume of ROI for Each Organ at All Time Points | Aorta: PET scan 3; n=7 | 7.887 Milliliter (mL) | Standard Deviation 3.178 |
| 89Zr-GSK3128349 | Mean Volume of ROI for Each Organ at All Time Points | Aorta: PET scan 4; n=7 | 8.199 Milliliter (mL) | Standard Deviation 3.5405 |
| 89Zr-GSK3128349 | Mean Volume of ROI for Each Organ at All Time Points | Heart: PET scan 1; n=8 | 135.013 Milliliter (mL) | Standard Deviation 74.5105 |
| 89Zr-GSK3128349 | Mean Volume of ROI for Each Organ at All Time Points | Heart: PET scan 2; n=8 | 111.133 Milliliter (mL) | Standard Deviation 53.4101 |
| 89Zr-GSK3128349 | Mean Volume of ROI for Each Organ at All Time Points | Kidney, cortex: PET scan 1; n=8 | 5.483 Milliliter (mL) | Standard Deviation 3.0342 |
| 89Zr-GSK3128349 | Mean Volume of ROI for Each Organ at All Time Points | Kidney, cortex: PET scan 2; n=8 | 5.728 Milliliter (mL) | Standard Deviation 2.7257 |
| 89Zr-GSK3128349 | Mean Volume of ROI for Each Organ at All Time Points | Kidney, cortex: PET scan 3; n=7 | 6.770 Milliliter (mL) | Standard Deviation 1.2609 |
| 89Zr-GSK3128349 | Mean Volume of ROI for Each Organ at All Time Points | Kidney, cortex: PET scan 4; n=7 | 7.229 Milliliter (mL) | Standard Deviation 3.5309 |
| 89Zr-GSK3128349 | Mean Volume of ROI for Each Organ at All Time Points | Kidney, medulla: PET scan 1; n=8 | 4.646 Milliliter (mL) | Standard Deviation 2.1984 |
| 89Zr-GSK3128349 | Mean Volume of ROI for Each Organ at All Time Points | Kidney, medulla: PET scan 2; n=8 | 4.885 Milliliter (mL) | Standard Deviation 2.3112 |
| 89Zr-GSK3128349 | Mean Volume of ROI for Each Organ at All Time Points | Kidney, medulla: PET scan 3; n=7 | 6.104 Milliliter (mL) | Standard Deviation 1.4927 |
| 89Zr-GSK3128349 | Mean Volume of ROI for Each Organ at All Time Points | Kidney, medulla: PET scan 4; n=7 | 6.661 Milliliter (mL) | Standard Deviation 3.3183 |
| 89Zr-GSK3128349 | Mean Volume of ROI for Each Organ at All Time Points | Body: PET scan 1; n=8 | 103654.675 Milliliter (mL) | Standard Deviation 29591.971 |
| 89Zr-GSK3128349 | Mean Volume of ROI for Each Organ at All Time Points | Body: PET scan 2; n=8 | 106925.973 Milliliter (mL) | Standard Deviation 32398.3328 |
| 89Zr-GSK3128349 | Mean Volume of ROI for Each Organ at All Time Points | Body: PET scan 3; n=7 | 96034.243 Milliliter (mL) | Standard Deviation 22195.6206 |
| 89Zr-GSK3128349 | Mean Volume of ROI for Each Organ at All Time Points | Body: PET scan 4; n=7 | 100291.249 Milliliter (mL) | Standard Deviation 27671.1649 |
Secondary
Apparent Terminal Phase Half-life (t1/2) and Mean Residence Time (MRT) of 89Zr-GSK3128349 and GSK3128349
PK parameters included t1/2 and MRT. t1/2 and MRT for 89Zr-GSK3128349 was calculated from the whole blood and plasma concentration-time data, measured by scintillation counting. t1/2 and MRT for GSK3128349 was calculated from the whole blood and plasma concentration-time data, measured by mass spectrometry.
Time frame: Pre-dose, 1 h, 3 h, 6 h, 8h, 24 h post-dose, Day 4, Day 6, Day 14, Day 22, Day 33 and Day 45
Population: PK Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 89Zr-GSK3128349 | Apparent Terminal Phase Half-life (t1/2) and Mean Residence Time (MRT) of 89Zr-GSK3128349 and GSK3128349 | 89Zr-GSK3128349: t1/2 | 279.3697 Hours | Geometric Coefficient of Variation 40.6517 |
| 89Zr-GSK3128349 | Apparent Terminal Phase Half-life (t1/2) and Mean Residence Time (MRT) of 89Zr-GSK3128349 and GSK3128349 | GSK3128349: t1/2 | 420.6105 Hours | Geometric Coefficient of Variation 9.2835 |
| 89Zr-GSK3128349 | Apparent Terminal Phase Half-life (t1/2) and Mean Residence Time (MRT) of 89Zr-GSK3128349 and GSK3128349 | 89Zr-GSK3128349: MRT | 404.8882 Hours | Geometric Coefficient of Variation 36.4904 |
| 89Zr-GSK3128349 | Apparent Terminal Phase Half-life (t1/2) and Mean Residence Time (MRT) of 89Zr-GSK3128349 and GSK3128349 | GSK3128349: MRT | 562.3356 Hours | Geometric Coefficient of Variation 9.7841 |
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
PK parameters included AUC (0-t) and AUC (0-inf). AUC (0-t) and AUC (0-inf) for 89Zr-GSK3128349 was calculated from the whole blood and plasma concentration-time data, measured by scintillation counting. AUC (0-t) and AUC (0-inf) for GSK3128349 was calculated from the whole blood and plasma concentration-time data, measured by mass spectrometry.
Time frame: Pre-dose, 1 hour (h), 3 h, 6 h, 8h, 24 h post-dose, Day 4, Day 6, Day 14, Day 22, Day 33 and Day 45
Population: PK Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 89Zr-GSK3128349 | 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 | 89Zr-GSK3128349: AUC (0-t) | 461526.5722 (Becquerel [Bq] per mL)*h | Geometric Coefficient of Variation 11.1647 |
| 89Zr-GSK3128349 | 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 | 89Zr-GSK3128349: AUC (0-inf) | 930260.1961 (Becquerel [Bq] per mL)*h | Geometric Coefficient of Variation 19.4399 |
| 89Zr-GSK3128349 | 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 | GSK3128349: AUC (0-t) | 82177.6360 (Becquerel [Bq] per mL)*h | Geometric Coefficient of Variation 19.0961 |
| 89Zr-GSK3128349 | 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 | GSK3128349: AUC (0-inf) | 104257.7700 (Becquerel [Bq] per mL)*h | Geometric Coefficient of Variation 16.5839 |
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
PK parameters included AUMC (0-inf) and AUMC (0-t). AUMC (0-inf) and AUMC (0-t) for 89Zr-GSK3128349 was calculated from the whole blood and plasma concentration-time data, measured by scintillation counting.
Time frame: Pre-dose, 1 h, 3 h, 6 h, 8h, 24 h post-dose, Day 4, Day 6, Day 14, Day 22, Day 33 and Day 45
Population: PK Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 89Zr-GSK3128349 | 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 | 89Zr-GSK3128349: AUMC (0-inf) | 376651413.6839 (Bq/mL)*h^2) | Geometric Coefficient of Variation 56.6074 |
| 89Zr-GSK3128349 | 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 | 89Zr-GSK3128349: AUMC (0-t) | 53242134.4377 (Bq/mL)*h^2) | Geometric Coefficient of Variation 10.0977 |
Secondary
AUMC (0-inf) and AUMC (0-t) of GSK3128349
PK parameters included AUMC (0-inf) and AUMC (0-t). AUMC (0-inf) and AUMC (0-t) for GSK3128349 was calculated from the whole blood and plasma concentration-time data, measured by mass spectrometry.
Time frame: Pre-dose, 1 h, 3 h, 6 h, 8h, 24 h post-dose, Day 4, Day 6, Day 14, Day 22, Day 33 and Day 45
Population: PK Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 89Zr-GSK3128349 | AUMC (0-inf) and AUMC (0-t) of GSK3128349 | GSK3128349: AUMC (0-t) | 25366300.3864 (ng/mL)*h^2 | Geometric Coefficient of Variation 31.7095 |
| 89Zr-GSK3128349 | AUMC (0-inf) and AUMC (0-t) of GSK3128349 | GSK3128349: AUMC (0-inf) | 58627561.8533 (ng/mL)*h^2 | Geometric Coefficient of Variation 23.8246 |
Secondary
Clearance of 89Zr-GSK3128349 and GSK3128349
PK parameters included clearance. Clearance for 89Zr-GSK3128349 was calculated from the whole blood and plasma concentration-time data, measured by scintillation counting. Clearance for GSK3128349 was calculated from the whole blood and plasma concentration-time data, measured by mass spectrometry.
Time frame: Pre-dose, 1 h, 3 h, 6 h, 8h, 24 h post-dose, Day 4, Day 6, Day 14, Day 22, Day 33 and Day 45
Population: PK Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 89Zr-GSK3128349 | Clearance of 89Zr-GSK3128349 and GSK3128349 | 89Zr-GSK3128349: Clearance | 13.4371 mL/h | Geometric Coefficient of Variation 19.4399 |
| 89Zr-GSK3128349 | Clearance of 89Zr-GSK3128349 and GSK3128349 | GSK3128349: Clearance | 9.5918 mL/h | Geometric Coefficient of Variation 16.5657 |
Secondary
Cmax of GSK3128349
PK parameters included Cmax. Cmax for GSK3128349 was calculated from the whole blood and plasma concentration-time data, measured by mass spectrometry.
Time frame: Pre-dose, 1 h, 3 h, 6 h, 8h, 24 h post-dose, Day 4, Day 6, Day 14, Day 22, Day 33 and Day 45
Population: PK Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 89Zr-GSK3128349 | Cmax of GSK3128349 | 374.3868 Nanogram (ng) per mL | Geometric Coefficient of Variation 10.4183 |
Secondary
Elimination Rate Constant (Lambda-z) of 89Zr-GSK3128349
PK parameters included lambda-z. Cmax for 89Zr-GSK3128349 was calculated from the whole blood and plasma concentration-time data, measured by scintillation counting.
Time frame: Pre-dose, 1 h, 3 h, 6 h, 8h, 24 h post-dose, Day 4, Day 6, Day 14, Day 22, Day 33 and Day 45
Population: PK Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 89Zr-GSK3128349 | Elimination Rate Constant (Lambda-z) of 89Zr-GSK3128349 | 0.0025 1 per h | Geometric Coefficient of Variation 40.6517 |
Secondary
Maximum Observed Plasma Concentration (Cmax) of 89Zr-GSK3128349
PK parameters included Cmax. Cmax for 89Zr-GSK3128349 was calculated from the whole blood and plasma concentration-time data, measured by scintillation counting.
Time frame: Pre-dose, 1 h, 3 h, 6 h, 8h, 24 h post-dose, Day 4, Day 6, Day 14, Day 22, Day 33 and Day 45
Population: PK Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 89Zr-GSK3128349 | Maximum Observed Plasma Concentration (Cmax) of 89Zr-GSK3128349 | 3872.7027 Bq per mL | Geometric Coefficient of Variation 8.6104 |
Secondary
Mean Organ and Effective Dose
Organ dose was defined as the amount of radiation delivered to a particular organ. Effective dose was defined as the tissue-weighted sum of the organ doses in all specified tissues and organs of the human body. The organ and effective dose is a fraction of milliSievert (mSv) and MegaBecquerel (MBq). The mean relative uptake of 89Zr-GSK3128349 in different organs for all participants across all PET scans is presented.
Time frame: Up to Day 7
Population: PK Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 89Zr-GSK3128349 | Mean Organ and Effective Dose | Bone marrow | 0.3407 mSv/MBq | Standard Deviation 0.03146 |
| 89Zr-GSK3128349 | Mean Organ and Effective Dose | Spleen | 0.7314 mSv/MBq | Standard Deviation 0.08562 |
| 89Zr-GSK3128349 | Mean Organ and Effective Dose | Thymus gland | 0.3457 mSv/MBq | Standard Deviation 0.03229 |
| 89Zr-GSK3128349 | Mean Organ and Effective Dose | Lung | 0.8413 mSv/MBq | Standard Deviation 0.17595 |
| 89Zr-GSK3128349 | Mean Organ and Effective Dose | Heart | 0.6721 mSv/MBq | Standard Deviation 0.14849 |
| 89Zr-GSK3128349 | Mean Organ and Effective Dose | Liver | 0.7909 mSv/MBq | Standard Deviation 0.15549 |
| 89Zr-GSK3128349 | Mean Organ and Effective Dose | Pancreas | 0.5701 mSv/MBq | Standard Deviation 0.09391 |
| 89Zr-GSK3128349 | Mean Organ and Effective Dose | Thyroid gland | 0.4004 mSv/MBq | Standard Deviation 0.09722 |
| 89Zr-GSK3128349 | Mean Organ and Effective Dose | Testis | 0.4827 mSv/MBq | Standard Deviation 0.03345 |
| 89Zr-GSK3128349 | Mean Organ and Effective Dose | Bladder | 0.2889 mSv/MBq | Standard Deviation 0.02315 |
| 89Zr-GSK3128349 | Mean Organ and Effective Dose | Kidney | 1.3871 mSv/MBq | Standard Deviation 0.30625 |
| 89Zr-GSK3128349 | Mean Organ and Effective Dose | Brain | 0.1431 mSv/MBq | Standard Deviation 0.04001 |
| 89Zr-GSK3128349 | Mean Organ and Effective Dose | Body | 0.4480 mSv/MBq | Standard Deviation 0.03811 |
Secondary
Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)
AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For marketed medicinal products, this also includes failure to produce expected benefits (i.e., lack of efficacy), abuse or misuse. SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant or is associated with liver injury or impaired liver function.
Time frame: Up to 45 days
Population: Safety Population which comprised of all participants who received a dose of 89Zr-GSK3128349.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 89Zr-GSK3128349 | Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) | AE | 2 Participants |
| 89Zr-GSK3128349 | Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) | SAE | 0 Participants |
Secondary
Number of Participants With Clinical Chemistry Data of Potential Clinical Concern
The potential clinical concern range for clinical chemistry parameters were: glucose (low: \< 3 millimole \[mmol\]/L and high: \> 9 mmol/L), creatinine (high: Change from Baseline or Day 1 should be positive and \> 44.2 mmol/L), phosphorous (low: \< 0.8 mmol/L and high: \> 1.6 mmol/L), magnesium (low: \< 0.5 mmol/L and high: \> 1.23 mmol/L), calcium (low: \<2 mmoL/L and high: \> 2.75 mmol/L), carbon dioxide content (low: \< 18 mmol/L and high: \> 32 mmol/L), albumin (low: \< 30 mmol/L), potassium (low: \< 3.0 mmol/L and high: \> 5.5 mmol/L) and sodium (low: \< 130 mmol/L and high: \> 130 mmol/L). Number of participants with clinical chemistry abnormalities of potential clinical importance are presented
Time frame: Up to 45 days
Population: Safety Population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 89Zr-GSK3128349 | Number of Participants With Clinical Chemistry Data of Potential Clinical Concern | 0 Participants |
Secondary
Number of Participants With Electrocardiogram (ECG) Values of Potential Clinical Concern
ECG measurements were made with the participant in a supine position having rested in this position for at least 5 minutes before each reading. Triplicate 12-lead ECGS were obtained pre dose at Day 1 and single 12-lead ECGs will be obtained at other time points during the study. The potential clinical concern range for ECG parameters was as follows: Absolute corrected QT (QTc) interval (lower: \>450 milliseconds \[msec\], \>450 msec, \>=480 msec and \>=500 msec) and (higher: \<=479 msec and \<=499 msec); absolute PR interval (lower: \<110 and higher \>220 msec) and absolute QRS interval (lower: \<75 msec and \>110 msec). Number of participants with ECG values of potential clinical concern are presented.
Time frame: Pre-dose on Day 1, 1 h and 24 h post-dose on Day 1 and Day 45
Population: Safety Population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 89Zr-GSK3128349 | Number of Participants With Electrocardiogram (ECG) Values of Potential Clinical Concern | QT interval corrected by Bazett's formula | 0 Participants |
| 89Zr-GSK3128349 | Number of Participants With Electrocardiogram (ECG) Values of Potential Clinical Concern | QRS duration | 1 Participants |
| 89Zr-GSK3128349 | Number of Participants With Electrocardiogram (ECG) Values of Potential Clinical Concern | Heart rate | 0 Participants |
| 89Zr-GSK3128349 | Number of Participants With Electrocardiogram (ECG) Values of Potential Clinical Concern | PR interval | 0 Participants |
| 89Zr-GSK3128349 | Number of Participants With Electrocardiogram (ECG) Values of Potential Clinical Concern | RR interval | 0 Participants |
| 89Zr-GSK3128349 | Number of Participants With Electrocardiogram (ECG) Values of Potential Clinical Concern | QT interval | 0 Participants |
| 89Zr-GSK3128349 | Number of Participants With Electrocardiogram (ECG) Values of Potential Clinical Concern | QT interval corrected by Fridericia formula | 0 Participants |
Secondary
Number of Participants With Hematology Data of Potential Clinical Concern
The potential clinical concern range for hematology parameters were: Hemoglobin (low: \> 25 gram per Liter change from Baseline/Day 1 and high: \> 180 gram per Liter), lymphocytes (low: \< 0.8 gigacells/L), hematocrit (low: \> 0.075 ratio change from Baseline and high: \> 0.54 ratio), neutrophil count (low: \< 1.5\*10\^9/Liter), platelet count (low: \< 100 gigacells/L and high: \> 550 gigacells/L), white blood cell (WBC) count (low: \< 3 gigacells/L and high: \> 20 gigacells/L). Number of participants with hematology abnormalities of potential clinical importance are presented.
Time frame: Up to 45 days
Population: Safety Population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 89Zr-GSK3128349 | Number of Participants With Hematology Data of Potential Clinical Concern | 0 Participants |
Secondary
Number of Participants With Positive Anti-GSK3128349 Antibody Assay
Blood samples for testing antibodies against GSK3128349 will be collected on Day 1 (pre-dose) and on Day 43. The actual date and time of each blood sample collection was recorded. The first blood sample was taken pre-dose on Day 1 to determine the presence, if any, of pre-existing Anti Drug Antibodies (ADAs). The presence of such antibodies was assessed using an electrochemiluminescent (ECL) immuno assay. If sera contain anti-GSK3128349 antibodies, they were further analyzed for the antibody specificity and titres. Number of participants who were found to have anti-GSK3128349 antibodies are presented.
Time frame: Pre-dose on Day 1 and Day 43
Population: Safety Population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 89Zr-GSK3128349 | Number of Participants With Positive Anti-GSK3128349 Antibody Assay | 1 Participants |
Secondary
Number of Participants With Vital Signs of Potential Clinical Concern
Vital signs included pulse rate, systolic and diastolic blood pressure and body temperature. All vital sign measurements were made with the participant in a supine position and rested in this position for at least 5 minutes before each reading. The potential clinical concern range for systolic blood pressure: \<85 and \>160 millimeters of mercury (mmHg), for diastolic: \<45 and \>100 mmHg and heart rate: \<40 and \>110 beats per minute. Number of participants with vital signs of potential clinical concern are presented.
Time frame: Up to 45 days
Population: Safety Population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 89Zr-GSK3128349 | Number of Participants With Vital Signs of Potential Clinical Concern | 0 Participants |
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
PK parameters included AUCex and AUMCex. AUCex and AUMCex for 89Zr-GSK3128349 was calculated from the whole blood and plasma concentration-time data, measured by scintillation counting. AUCex and AUMCex for GSK3128349 was calculated from the whole blood and plasma concentration-time data, measured by mass spectrometry.
Time frame: Pre-dose, 1 h, 3 h, 6 h, 8h, 24 h post-dose, Day 4, Day 6, Day 14, Day 22, Day 33 and Day 45
Population: PK Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 89Zr-GSK3128349 | 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 | 89Zr-GSK3128349: Percent AUCex | 48.5838 Percentage area under the curve | Geometric Coefficient of Variation 20.4243 |
| 89Zr-GSK3128349 | 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 | 89Zr-GSK3128349: Percent AUMCex | 84.0346 Percentage area under the curve | Geometric Coefficient of Variation 8.3187 |
| 89Zr-GSK3128349 | 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 | GSK3128349: Percent AUCex | 20.7353 Percentage area under the curve | Geometric Coefficient of Variation 19.8191 |
| 89Zr-GSK3128349 | 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 | GSK3128349: Percent AUMCex | 55.9698 Percentage area under the curve | Geometric Coefficient of Variation 11.654 |
Secondary
Serum Titers of Anti-GSK3128349 Antibodies
Blood samples for testing antibodies against GSK3128349 will be collected on Day 1 (pre-dose) and on Day 43. The actual date and time of each blood sample collection was recorded. The first blood sample was taken pre-dose on Day 1 to determine the presence, if any, of pre-existing ADAs. The presence of such antibodies and serum titers of anti-GSK3128349 antibodies was assessed using an ECL immuno-assay. If sera contain anti-GSK3128349 antibodies, they were further analyzed for the antibody specificity and titers.
Time frame: Pre-dose on Day 1 and Day 43
Population: Safety Population. Only those participants with positive anti-GSK3128349 antibody assay were analyzed.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| 89Zr-GSK3128349 | Serum Titers of Anti-GSK3128349 Antibodies | Day 1, pre-dose | 80 Titers |
| 89Zr-GSK3128349 | Serum Titers of Anti-GSK3128349 Antibodies | Day 43 | 40 Titers |
Secondary
Volume of Distribution at a Steady State (Vss) and Volume of Distribution in the Terminal Phase (Vz) of 89Zr-GSK3128349 and GSK3128349
PK parameters included Vss and Vz. Vss and Vz for 89Zr-GSK3128349 was calculated from the whole blood and plasma concentration-time data, measured by scintillation counting. Vss and Vz for GSK3128349 was calculated from the whole blood and plasma concentration-time data, measured by mass spectrometry.
Time frame: Pre-dose, 1 h, 3 h, 6 h, 8h, 24 h post-dose, Day 4, Day 6, Day 14, Day 22, Day 33 and Day 45
Population: PK Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 89Zr-GSK3128349 | Volume of Distribution at a Steady State (Vss) and Volume of Distribution in the Terminal Phase (Vz) of 89Zr-GSK3128349 and GSK3128349 | 89Zr-GSK3128349: Vss | 5440.5241 mL | Geometric Coefficient of Variation 21.7532 |
| 89Zr-GSK3128349 | Volume of Distribution at a Steady State (Vss) and Volume of Distribution in the Terminal Phase (Vz) of 89Zr-GSK3128349 and GSK3128349 | 89Zr-GSK3128349: Vz | 5415.7602 mL | Geometric Coefficient of Variation 25.5996 |
| 89Zr-GSK3128349 | Volume of Distribution at a Steady State (Vss) and Volume of Distribution in the Terminal Phase (Vz) of 89Zr-GSK3128349 and GSK3128349 | GSK3128349: Vss | 5393.6763 mL | Geometric Coefficient of Variation 13.5175 |
| 89Zr-GSK3128349 | Volume of Distribution at a Steady State (Vss) and Volume of Distribution in the Terminal Phase (Vz) of 89Zr-GSK3128349 and GSK3128349 | GSK3128349: Vz | 5820.3069 mL | Geometric Coefficient of Variation 13.919 |