Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics Investigation of GSK3335065 Intravenous (IV) Infusion in Healthy Adults
- Conditions
- Pancreatitis, Acute Necrotizing
- Interventions
- Drug: GSK3335065Drug: Placebo
- Registration Number
- NCT03245619
- Lead Sponsor
- GlaxoSmithKline
- Brief Summary
GSK3335065 is being developed as a treatment for acute pancreatitis with the intent of reducing 3-hydroxykynurenine (3HK) levels to the normal range (or lower) and maintaining them at this level throughout the treatment period. This study will utilize an adaptive design and is divided into 3 parts. Part A will consist of 8 cohorts (1-8) and is Single Ascending Dose (SAD) of GSK3335065 by IV bolus in males. Part B will be initiated after completion of dosing in Part A. It will involve ascending IV bolus doses of GSK3335065 followed by IV constant infusion for 7 days in males and will consist of four cohorts (9-12). Part C consists of a single dose of GSK3335065 by IV bolus (cohort 13), and a single dose followed by continuous infusion over 7 days (cohort 14) in females of non-child bearing potential (WONCBP). Total 64 subjects will be evaluated in the study of which Part A will include 16 healthy male subjects, Part B will include 32 healthy male subjects and Part C will include 16 WONCBP. In Part A, cohorts 1 and 2 will last up to 19 weeks and cohorts 3 to 8 will last up to 7 weeks and Part B will last up to 13 weeks. In Part C cohort 7 will last up to 7 weeks and cohort 8 will last for 13 weeks.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 18
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Subjects receiving GSK3335065 (Cohorts 1 to 8) in Part A GSK3335065 Male subjects will be assigned to Cohorts 1 to 8. In each cohort, six subjects will be randomized to receive alternating and escalated doses of GSK3335065. Subjects receiving Placebo (Cohort 9 to 12) in Part B Placebo Male subjects will be assigned to one of four cohorts (9, 10, 11 or 12). In each cohort, two subjects will be randomized to receive placebo. Subjects receiving Placebo (Cohorts 1 to 8) in Part A Placebo Male subjects will be assigned to Cohort 1 and 2. In each cohort, two subjects will be randomized to receive placebo. Subjects receiving Placebo (Cohort 13) in Part C Placebo WONCBP will be assigned to cohort 13. Two subjects will be randomized to receive placebo. Subjects receiving GSK3335065 (Cohort 9 to 12) in Part B GSK3335065 Male subjects will be assigned to one of four cohorts (9, 10, 11 or 12). In each cohort, six subjects will be randomized to receive GSK3335065. In all cohorts each dose level will consist of an IV bolus on Day 1 subsequently followed by a continuous IV infusion for seven days. Subjects receiving GSK3335065 (Cohort 13) in Part C GSK3335065 WONCBP will be assigned to cohort 13. Six subjects will be randomized to receive a single IV dose of GSK3335065. Subjects receiving GSK3335065 (Cohort 14) in Part C GSK3335065 WONCBP will be assigned to cohort 14. Six subjects will be randomized to receive a continuous IV infusion over 7 days of GSK3335065. Subjects receiving Placebo (Cohort 14) in Part C Placebo WONCBP will be assigned to cohort 14. Two subjects will be randomized to receive placebo.
- Primary Outcome Measures
Name Time Method Number of Participants With Hematological Parameters of Potential Clinical Importance-Part A Up to Day 22 Blood samples were collected for the assessment of hematology parameters. The clinical concern range for the parameters were: hematocrit (high: \>0.54 proportion of red blood cells in blood); hemoglobin (high: \>180 grams per liter \[g/L\]), lymphocytes (low: \<0.8x10\^9 cells per liter \[cells/L\]); neutrophil count (low: \<1.5x10\^9 cells/L); platelet count (low: \<100x10\^9 cells/L and high: \>550x10\^9 cells/L); white blood cells count (low: \<3x10\^9 cells/L and high: \>20x10\^9 cells/L). Data for worst-case post-Baseline is presented. Baseline was defined as the latest pre-dose assessment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
Number of Participants With Hematological Parameters of Potential Clinical Importance-Part B Up to Day 34 Blood samples were planned to be collected for the assessment of hematology parameters.
Number of Participants With Hematological Parameters of Potential Clinical Importance-Part C Up to Day 34 Blood samples were planned to be collected for the assessment of hematology parameters.
Number of Participants With Clinical Chemistry Parameters of Potential Clinical Importance-Part A Up to Day 22 Blood samples were collected for the assessment of clinical chemistry parameters. The clinical concern range for the parameters were: albumin (low: \<30 millimoles per liter \[mmol/L\]); alanine aminotransferase (ALT) (high: \>=2xupper limit of normal \[ULN\]); aspartate aminotransferase (AST) (high: \>=2xULN); alkaline phosphatase (ALP) (high: \>=2xULN); total bilirubin (high: \>=1.5xULN); calcium (low: \<2 mmol/L and high: \>2.75 mmol/L); glucose (low: \<3 mmol/L and high: \>9 mmol/L); potassium (low: \<3 mmol/L and high: \>5.5 mmol/L) and sodium (low: \<130 mmol/L and high: \>150 mmol/L). Data for worst-case post-Baseline is presented. Baseline was defined as the latest pre-dose assessment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
Number of Participants With Clinical Chemistry Parameters of Potential Clinical Importance-Part B Up to Day 34 Blood samples were planned to be collected for the assessment of clinical chemistry parameters.
Number of Participants With Clinical Chemistry Parameters of Potential Clinical Importance-Part C Up to Day 34 Blood samples were planned to be collected for the assessment of clinical chemistry parameters.
Number of Participants With Abnormal Urine Parameters-Part A Up to Day 22 Urine samples were taken for the assessment of following urine parameters: specific gravity, potential of hydrogen (pH), glucose, protein, blood and ketones by dipstick method. Microscopic examination was performed and collected for any abnormal dipstick results. Number of participants with abnormal urine parameters any time post-Baseline is presented. Baseline was defined as the latest pre-dose assessment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
Number of Participants With Abnormal Urine Parameters-Part B Up to Day 34 Urine samples were planned to be collected for the assessment of urine parameters.
Number of Participants With Abnormal Urine Parameters-Part C Up to Day 34 Urine samples were planned to be collected for the assessment of urine parameters.
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)-Part A Up to Day 22 An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; is a congenital anomaly/birth defect; other important medical events that may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed before. All Subject Population comprised of all participants randomized to treatment who received at least one dose of study treatment. AEs and SAEs were collected from admission until follow-up. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
Number of Participants With AEs and SAEs-Part B Up to Day 34 An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; is a congenital anomaly/birth defect; other important medical events that may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed before. AEs and SAEs were planned to be collected from admission until follow-up.
Number of Participants With AEs and SAEs-Part C Up to Day 34 An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; is a congenital anomaly/birth defect; other important medical events that may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed before. AEs and SAEs were planned to be collected from admission until follow-up.
Number of Participants With Abnormal Electrocardiogram (ECG) Findings-Part A Up to Day 22 Triplicate 12-lead ECGs were obtained using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT, QT interval corrected using Fridericia's formula (QTcF) and Bazett's QT interval corrected for heart rate (QTcB). ECG measurements were preceded by at least 5 minutes rest for the participant in a semi-recumbent position. Number of participants with abnormal-clinically significant and abnormal-not clinically significant ECG findings at worst case post-Baseline is presented. Baseline was defined as the latest pre-dose assessment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
Number of Participants With Abnormal ECG Findings-Part B Up to Day 34 Triplicate 12-lead ECGs were planned to be obtained using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT, QTcF and QTcB intervals.
Number of Participants With Abnormal ECG Findings-Part C Up to Day 34 Triplicate 12-lead ECGs were planned to be obtained using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT, QTcF and QTcB intervals.
Number of Participants With Abnormal Vital Signs-Part A Up to Day 22 Vital signs including systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate, respiration rate and temperature were measured in a semi-recumbent position with a completely automated device preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Participants are counted in the worst case category that their value changes to (low, normal or high), unless there is no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the "To Normal or No Change" category. Data for worst case post-Baseline relative to Baseline is presented. Baseline was defined as the latest pre-dose assessment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
Number of Participants With Abnormal Vital Signs-Part B Up to Day 34 Vital signs including SBP, DBP, heart rate, respiration rate and temperature were planned to be measured in a semi-recumbent position with a completely automated device preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions.
Number of Participants With Abnormal Vital Signs-Part C Up to Day 34 Vital signs including SBP, DBP, heart rate, respiration rate and temperature were planned to be measured in a semi-recumbent position with a completely automated device preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions.
- Secondary Outcome Measures
Name Time Method Area Under the Plasma Concentration-time Curve From Time 0 to Last Quantifiable Concentration (AUC[0-t]) for GSK3335065-Part A (Cohorts 1 and 2) 1 hour pre-dose, 6, 12, 15, 20, and 30 minutes, 1, 2, 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 60 and 72 hours post-dose Blood samples for pharmacokinetic (PK) analysis of GSK3335065 were collected at the indicated time points. PK parameters were calculated using standard non-compartmental analysis. PK Parameter Population comprised of all active participants whose PK sample was obtained and analyzed and who provided PK parameters.
AUC(0-t) for GSK3335065-Part A (Cohorts 3 to 8) 1 hour pre-dose, 6, 12, 15, 20, and 30 minutes, 1, 2, 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-dose Blood samples for PK analysis of GSK3335065 were collected at the indicated time points. PK parameters were calculated using standard non-compartmental analysis.
AUC(0-t) for GSK3335065-Part B Day1 (Pre-dose, 6, 15, 30 minutes, 1, 2, 3, 4.5, 6, 9, 12, 18hours post-infusion), Days2 to 7 (pre-dose), Day8 (end of infusion, 6 and 12 hours post-infusion), Day9 (18, 24, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-infusion) Blood samples for PK analysis of GSK3335065 were planned to be collected at the indicated time points.
AUC(0-t) for GSK3335065-Part C (Cohort 13) 1 hour pre-dose, 6, 12, 15, 20, and 30 minutes, 1, 2, 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-dose Blood samples for PK analysis of GSK3335065 were planned to be collected at the indicated time points.
AUC(0-t) for GSK3335065-Part C (Cohort 14) Day1 (Pre-dose, 6, 15, 30 minutes, 1, 2, 3, 4.5, 6, 9, 12, 18hours post-infusion), Days2 to 7 (pre-dose), Day8 (end of infusion, 6 and 12 hours post-infusion), Day9 (18, 24, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-infusion) Blood samples for PK analysis of GSK3335065 were planned to be collected at the indicated time points.
Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC[0-Inf]) for GSK3335065-Part A (Cohorts 1 and 2) 1 hour pre-dose, 6, 12, 15, 20, and 30 minutes, 1, 2, 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 60 and 72 hours post-dose Blood samples for PK analysis of GSK3335065 were collected at the indicated time points. PK parameters were calculated using standard non-compartmental analysis. Data for Cohort 1 is derived only from time points up to 3 hours as later data in this participant was below limit of quantification.
AUC(0-Inf) for GSK3335065-Part A (Cohorts 3 to 8) 1 hour pre-dose, 6, 12, 15, 20, and 30 minutes, 1, 2, 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-dose Blood samples for PK analysis of GSK3335065 were collected at the indicated time points. PK parameters were calculated using standard non-compartmental analysis.
AUC(0-Inf) for GSK3335065-Part B Day1 (Pre-dose, 6, 15, 30 minutes, 1, 2, 3, 4.5, 6, 9, 12, 18hours post-infusion), Days2 to 7 (pre-dose), Day8 (end of infusion, 6 and 12 hours post-infusion), Day9 (18, 24, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-infusion) Blood samples for PK analysis of GSK3335065 were planned to be collected at the indicated time points.
AUC(0-Inf) for GSK3335065-Part C (Cohort 13) 1 hour pre-dose, 6, 12, 15, 20, and 30 minutes, 1, 2, 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-dose Blood samples for PK analysis of GSK3335065 were planned to be collected at the indicated time points.
AUC(0-Inf) for GSK3335065-Part C (Cohort 14) Day1 (Pre-dose, 6, 15, 30 minutes, 1, 2, 3, 4.5, 6, 9, 12, 18hours post-infusion), Days2 to 7 (pre-dose), Day8 (end of infusion, 6 and 12 hours post-infusion), Day9 (18, 24, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-infusion) Blood samples for PK analysis of GSK3335065 were planned to be collected at the indicated time points.
Time of the Last Measurable Concentration (Tlast) of GSK3335065-Part A (Cohorts 1 and 2) 1 hour pre-dose, 6, 12, 15, 20, and 30 minutes, 1, 2, 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 60 and 72 hours post-dose Blood samples for pharmacokinetic PK analysis of GSK3335065 were collected at the indicated time points. PK parameters were calculated using standard non-compartmental analysis.
Tlast of GSK3335065-Part A (Cohorts 3 to 8) 1 hour pre-dose, 6, 12, 15, 20, and 30 minutes, 1, 2, 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-dose Blood samples for PK analysis of GSK3335065 were collected at the indicated time points. PK parameters were calculated using standard non-compartmental analysis.
Tlast of GSK3335065-Part B Day1 (Pre-dose, 6, 15, 30 minutes, 1, 2, 3, 4.5, 6, 9, 12, 18hours post-infusion), Days2 to 7 (pre-dose), Day8 (end of infusion, 6 and 12 hours post-infusion), Day9 (18, 24, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-infusion) Blood samples for PK analysis of GSK3335065 were planned to be collected at the indicated time points.
Tlast of GSK3335065-Part C (Cohort 13) 1 hour pre-dose, 6, 12, 15, 20, and 30 minutes, 1, 2, 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-dose Blood samples for PK analysis of GSK3335065 were planned to be collected at the indicated time points.
Tlast of GSK3335065-Part C (Cohort 14) Day1 (Pre-dose, 6, 15, 30 minutes, 1, 2, 3, 4.5, 6, 9, 12, 18hours post-infusion), Days2 to 7 (pre-dose), Day8 (end of infusion, 6 and 12 hours post-infusion), Day9 (18, 24, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-infusion) Blood samples for PK analysis of GSK3335065 were planned to be collected at the indicated time points.
Maximum Observed Concentration (Cmax) of GSK3335065-Part A (Cohorts 1 and 2) 1 hour pre-dose, 6, 12, 15, 20, and 30 minutes, 1, 2, 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 60 and 72 hours post-dose Blood samples for pharmacokinetic PK analysis of GSK3335065 were collected at the indicated time points. PK parameters were calculated using standard non-compartmental analysis.
Cmax of GSK3335065-Part A (Cohorts 3 to 8) 1 hour pre-dose, 6, 12, 15, 20, and 30 minutes, 1, 2, 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-dose Blood samples for PK analysis of GSK3335065 were collected at the indicated time points. PK parameters were calculated using standard non-compartmental analysis.
Cmax of GSK3335065-Part B Day1 (Pre-dose, 6, 15, 30 minutes, 1, 2, 3, 4.5, 6, 9, 12, 18hours post-infusion), Days2 to 7 (pre-dose), Day8 (end of infusion, 6 and 12 hours post-infusion), Day9 (18, 24, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-infusion) Blood samples for PK analysis of GSK3335065 were planned to be collected at the indicated time points.
Cmax of GSK3335065-Part C (Cohort 13) 1 hour pre-dose, 6, 12, 15, 20, and 30 minutes, 1, 2, 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-dose Blood samples for PK analysis of GSK3335065 were planned to be collected at the indicated time points.
Cmax of GSK3335065-Part C (Cohort 14) Day1 (Pre-dose, 6, 15, 30 minutes, 1, 2, 3, 4.5, 6, 9, 12, 18hours post-infusion), Days2 to 7 (pre-dose), Day8 (end of infusion, 6 and 12 hours post-infusion), Day9 (18, 24, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-infusion) Blood samples for PK analysis of GSK3335065 were planned to be collected at the indicated time points.
Time to Reach Maximum Concentration (Tmax) for GSK3335065-Part A (Cohorts 1 and 2) 1 hour pre-dose, 6, 12, 15, 20, and 30 minutes, 1, 2, 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 60 and 72 hours post-dose Blood samples for pharmacokinetic PK analysis of GSK3335065 were collected at the indicated time points. PK parameters were calculated using standard non-compartmental analysis.
Tmax of GSK3335065-Part A (Cohorts 3 to 8) 1 hour pre-dose, 6, 12, 15, 20, and 30 minutes, 1, 2, 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-dose Blood samples for PK analysis of GSK3335065 were collected at the indicated time points. PK parameters were calculated using standard non-compartmental analysis.
Tmax of GSK3335065-Part B Day1 (Pre-dose, 6, 15, 30 minutes, 1, 2, 3, 4.5, 6, 9, 12, 18hours post-infusion), Days2 to 7 (pre-dose), Day8 (end of infusion, 6 and 12 hours post-infusion), Day9 (18, 24, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-infusion) Blood samples for PK analysis of GSK3335065 were planned to be collected at the indicated time points.
Tmax of GSK3335065-Part C (Cohort 13) 1 hour pre-dose, 6, 12, 15, 20, and 30 minutes, 1, 2, 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-dose Blood samples for PK analysis of GSK3335065 were planned to be collected at the indicated time points.
Tmax of GSK3335065-Part C (Cohort 14) Day1 (Pre-dose, 6, 15, 30 minutes, 1, 2, 3, 4.5, 6, 9, 12, 18hours post-infusion), Days2 to 7 (pre-dose), Day8 (end of infusion, 6 and 12 hours post-infusion), Day9 (18, 24, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-infusion) Blood samples for PK analysis of GSK3335065 were planned to be collected at the indicated time points.
Clearance for GSK3335065-Part A (Cohorts 1 and 2) 1 hour pre-dose, 6, 12, 15, 20, and 30 minutes, 1, 2, 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 60 and 72 hours post-dose Blood samples for PK analysis of GSK3335065 were collected at the indicated time points. PK parameters were calculated using standard non-compartmental analysis. Data for Cohort 1 is derived only from time points up to 3 hours as later data in this participant was below limit of quantification.
Clearance for GSK3335065-Part A (Cohorts 3 to 8) 1 hour pre-dose, 6, 12, 15, 20, and 30 minutes, 1, 2, 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-dose Blood samples for PK analysis of GSK3335065 were collected at the indicated time points. PK parameters were calculated using standard non-compartmental analysis.
Clearance for GSK3335065-Part B Day1 (Pre-dose, 6, 15, 30 minutes, 1, 2, 3, 4.5, 6, 9, 12, 18hours post-infusion), Days2 to 7 (pre-dose), Day8 (end of infusion, 6 and 12 hours post-infusion), Day9 (18, 24, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-infusion) Blood samples for PK analysis of GSK3335065 were planned to be collected at the indicated time points.
Clearance for GSK3335065-Part C (Cohort 13) 1 hour pre-dose, 6, 12, 15, 20, and 30 minutes, 1, 2, 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-dose Blood samples for PK analysis of GSK3335065 were planned to be collected at the indicated time points.
Clearance for GSK3335065-Part C (Cohort 14) Day1 (Pre-dose, 6, 15, 30 minutes, 1, 2, 3, 4.5, 6, 9, 12, 18hours post-infusion), Days2 to 7 (pre-dose), Day8 (end of infusion, 6 and 12 hours post-infusion), Day9 (18, 24, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-infusion) Blood samples for PK analysis of GSK3335065 were planned to be collected at the indicated time points.
Volume of Distribution for GSK3335065-Part A (Cohorts 1 and 2) 1 hour pre-dose, 6, 12, 15, 20, and 30 minutes, 1, 2, 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 60 and 72 hours post-dose Blood samples for PK analysis of GSK3335065 were collected at the indicated time points. PK parameters were calculated using standard non-compartmental analysis. Data for Cohort 1 is derived only from time points up to 3 hours as later data in this participant was below limit of quantification.
Volume of Distribution for GSK3335065-Part A (Cohorts 3 to 8) 1 hour pre-dose, 6, 12, 15, 20, and 30 minutes, 1, 2, 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-dose Blood samples for PK analysis of GSK3335065 were collected at the indicated time points. PK parameters were calculated using standard non-compartmental analysis.
Volume of Distribution for GSK3335065-Part B Day1 (Pre-dose, 6, 15, 30 minutes, 1, 2, 3, 4.5, 6, 9, 12, 18hours post-infusion), Days2 to 7 (pre-dose), Day8 (end of infusion, 6 and 12 hours post-infusion), Day9 (18, 24, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-infusion) Blood samples for PK analysis of GSK3335065 were planned to be collected at the indicated time points.
Volume of Distribution for GSK3335065-Part C (Cohort 13) 1 hour pre-dose, 6, 12, 15, 20, and 30 minutes, 1, 2, 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-dose Blood samples for PK analysis of GSK3335065 were planned to be collected at the indicated time points.
Volume of Distribution for GSK3335065-Part C (Cohort 14) Day1 (Pre-dose, 6, 15, 30 minutes, 1, 2, 3, 4.5, 6, 9, 12, 18hours post-infusion), Days2 to 7 (pre-dose), Day8 (end of infusion, 6 and 12 hours post-infusion), Day9 (18, 24, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-infusion) Blood samples for PK analysis of GSK3335065 were planned to be collected at the indicated time points.
Apparent Terminal Half Life (T1/2) for GSK3335065-Part A (Cohorts 1 and 2) 1 hour pre-dose, 6, 12, 15, 20, and 30 minutes, 1, 2, 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 60 and 72 hours post-dose Blood samples for PK analysis of GSK3335065 were collected at the indicated time points. PK parameters were calculated using standard non-compartmental analysis. Data for Cohort 1 is derived only from time points up to 3 hours as later data in this participant was below limit of quantification.
T1/2 for GSK3335065-Part A (Cohorts 3 to 8) 1 hour pre-dose, 6, 12, 15, 20, and 30 minutes, 1, 2, 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-dose Blood samples for PK analysis of GSK3335065 were collected at the indicated time points. PK parameters were calculated using standard non-compartmental analysis.
T1/2 for GSK3335065-Part B Day1 (Pre-dose, 6, 15, 30 minutes, 1, 2, 3, 4.5, 6, 9, 12, 18hours post-infusion), Days2 to 7 (pre-dose), Day8 (end of infusion, 6 and 12 hours post-infusion), Day9 (18, 24, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-infusion) Blood samples for PK analysis of GSK3335065 were planned to be collected at the indicated time points.
T1/2 for GSK3335065-Part C (Cohort 13) 1 hour pre-dose, 6, 12, 15, 20, and 30 minutes, 1, 2, 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-dose Blood samples for PK analysis of GSK3335065 were planned to be collected at the indicated time points.
T1/2 for GSK3335065-Part C (Cohort 14) Day1 (Pre-dose, 6, 15, 30 minutes, 1, 2, 3, 4.5, 6, 9, 12, 18hours post-infusion), Days2 to 7 (pre-dose), Day8 (end of infusion, 6 and 12 hours post-infusion), Day9 (18, 24, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-infusion) Blood samples for PK analysis of GSK3335065 were planned to be collected at the indicated time points.
Change From Baseline in Levels of Tryptophan Metabolites-Part A (Cohort 1 and 2) Baseline, 6, 15 and 30 minutes, 1, 1.5, 2, 3, 4.5, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 60 and 72 hours post-dose Blood samples were collected to measure the kynurenine-3-monooxygenase (KMO) enzyme inhibition by determining the levels of the biomarkers Kynurenine (Kyn) and 3-hydroxykynurenine (3-HK). Baseline was the average of all pre-dose measurements (Day 1 \[pre-dose at 1 hour and 30 minutes\]). Change from Baseline was calculated as value at the specified time point minus the Baseline value.
Change From Baseline in Levels of Tryptophan Metabolites-Part A (Cohorts 3 to 8) Baseline, 6, 15 and 30 minutes, 1, 1.5, 2, 3, 4.5, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-dose Blood samples were collected to measure the KMO enzyme inhibition by determining the levels of the biomarkers Kyn and 3-HK. Baseline was the average of all pre-dose measurements (Day -1 \[pre-dose at 16 hours, 14 hours, 12 hours and 10 hours\] and Day 1 \[pre-dose at 30 minutes and 2 hours\]). Change from Baseline was calculated as value at the specified time point minus the Baseline value.
Change From Baseline in Levels of Tryptophan Metabolites-Part B Day1 (Pre-dose, 6, 15, 30 minutes, 1, 2, 3, 4.5, 6, 9, 12, 18 hours post-infusion), Days2 to 7 (pre-dose), Day8 (6 and 12 hours post-infusion), Day9 (18, 24, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168 and 180 hours post-infusion) Blood samples were planned to be collected to measure the KMO enzyme inhibition by determining the levels of the biomarkers Kyn and 3-HK.
Change From Baseline in Levels of Tryptophan Metabolites-Part C Day1 (Pre-dose, 6, 15, 30 minutes, 1, 2, 3, 4.5, 6, 9, 12, 18 hours post-infusion), Days2 to 7 (pre-dose), Day8 (6 and 12 hours post-infusion), Day9 (18, 24, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168 and 180 hours post-infusion) Blood samples were planned to be collected to measure the KMO enzyme inhibition by determining the levels of the biomarkers Kyn and 3-HK.
Trial Locations
- Locations (1)
GSK Investigational Site
🇬🇧Cambridge, United Kingdom