Outcome
Type |
Measure |
Description |
Time frame |
Safety issue |
Primary |
Parts 1: Number of Participants With Adverse Events (AEs) |
An AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. |
Up to Day 17 |
|
Primary |
Parts 2: Number of Participants With Adverse Events (AEs) |
An AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. |
Up to Day 29 |
|
Primary |
Part 1: Number of Participants With Worst Case Chemistry Results by Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline |
Blood samples were collected for analysis of chemistry parameters. PCI ranges were >2*Upper limit of normal (ULN) units per liter (U/L)(Alanine Aminotransferase [ALT]), >2*ULN (U/L) (Aspartate Aminotransferase ([AST]), >2*ULN (Alkaline Phosphatase [ALP]) (U/L), >1.5*ULN (micromoles per liter) (bilirubin), <2 or >2.75 millimoles/liter (L) (mmol/L)(calcium), <3 or >7.5 mmol/L (glucose), <3 or >5.3 mmol/L (potassium), <130 or >149 mmol/L (sodium). Participants were counted in worst case category that their value changes to (low, within [w/in] range or no change [NC], or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, are recorded in 'To within Range No Change' category. Participants were counted twice if participant had values that changed 'To Low' and 'To High', so percentages may not add to 100 percentage (%). |
Up to Week 10 |
|
Primary |
Part 1: Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline |
Blood samples were collected for analysis of hematology parameters. The ranges for hematology parameters are as follows: Hematocrit[>51 percent(%)-male, >45%-female], Hemoglobin [Higher: >175 grams/Liter(g/L) in male, >150g/L in female and Low: less than(<) 100g/L in male, <95g/L in female], Lymphocytes[<0.97 10^9/L], Neutrophils[<1.5 10^9/L], Platelets[High: >550 10^9/ L and Low: <100 10^9/ L], White blood cells[High:>18 10^9/L Low:<2 10^9/L], Red blood cells[Low: <3.0 10^12/L in male, <2.5 10^12/L]. Participants were counted in worst case category that their value changes to (low, within range [W/in] or no change or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (for example-High to High), or whose value became within range, were recorded in "To within Range or No Change" category. Participants were counted twice if participant has values that changed 'To Low' & 'To High', so the percentages may not add to 100%. |
Up to Week 10 |
|
Primary |
Part 1: Number of Participants With Worst Case Urinalysis Results by Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline |
Urine samples were collected to assess urine glucose, protein and ketones using dipstick method. The dipstick test gave results in a semi-quantitative manner, and results for urinalysis parameters were recorded as negative, trace, 1+, 2+, 3+ indicating proportional concentrations in the urine sample. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date. Result for urinalysis parameters were recorded as no change/decreased and any increase. |
Up to Week 10 |
|
Primary |
Part 1: Number of Participants With Clinically Significant Changes in Hepatobiliary Laboratory Values |
Blood samples were collected to evaluate hepatobiliary abnormalities. Number of participants with Bilirubin (BIL), Alkaline phosphatase (ALP), Alanine Aminotransferase (ALT)/combination of these with levels more than the defined hepatobiliary abnormality criteria were presented. Hepatocellular injury is defined as ([ALT/ALT ULN]/[ALP/ALP ULN]) >= 5 and ALT >=3xULN. |
Up to Week 10 |
|
Primary |
Part 1: Number of Participants With Clinically Significant Changes in 12-lead Electrocardiogram (ECG) Laboratory Values |
Twelve lead ECG was obtained using an ECG machine that automatically calculated the heart rate and measured QTc, PR, QRS intervals. Abnormal findings were categorized as clinically significant and not clinically significant. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Data for number of participants with worst case post-Baseline abnormal ECG findings have been presented. |
Up to Week 10 |
|
Primary |
Part 1: Number of Participants With Worst Case Vital Signs Results by Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline |
Vital signs included diastolic blood pressure (DBP), systolic blood pressure (SBP), pulse rate (PR), body temperature, respiratory rate (RR) and were measured after resting for at least 5 minutes in semi-supine position. PCI ranges were, SBP (millimeters of mercury[mmHg]): <85 (low) or >160 (high), DBP (mmHg): <45 (low) or >100 (high), heart rate (beats per minute): <40 (low) or >110 (high), respiration rate (breaths per minute):<=8 (low) or >20 (high) and body temperature (degrees Celsius) <=35.5 (low) or >38.0 (high). Participants were counted in worst case category that their value changes to (low, within range or no change, or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, are recorded in 'To W/in Range No Change' category. Participants were counted twice if participant had values that changed 'To Low' and 'To High', so percentages may not add to 100%. |
Up to Week 10 |
|
Primary |
Part 1: Number of Participants With Clinically Significant Changes in Continuous Telemetry |
Continuous cardiac telemetry was performed in a supine position after at least 5 minutes of rest. Number of participants who had abnormal findings upon cardiac telemetry assessment have been presented. |
Upto Day 3 |
|
Primary |
Part 2: Cohorts 4: Number of Participants With Worst Case Chemistry Results by Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline |
Blood samples were collected for analysis of chemistry parameters. PCI ranges were >=2*Upper limit of normal (ULN) units per liter (U/L)(Alanine Aminotransferase [ALT]), >=2*ULN (U/L) (Aspartate Aminotransferase ([AST]), >=2*ULN (Alkaline Phosphatase [ALP]) (U/L), >=1.5*ULN (micromoles per liter) (bilirubin), <2 or >2.75 millimoles/liter (L) (mmol/L)(calcium), <3 or >11 mmol/L (glucose), <3 or >5.5 mmol/L (potassium), <130 or >150 mmol/L (sodium),<50 or >85 grams/liter (protein). Participants were counted in worst case category that their value changes to (low, within [w/in] range or no change [NC], or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, are recorded in 'To within Range No Change' category. Participants were counted twice if participant had values that changed 'To Low' and 'To High', so percentages may not add to 100 percentage (%) |
Upto Week 9 |
|
Primary |
Part 2: Cohorts 4: Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline |
Blood samples were collected for analysis of hematology parameters. The ranges for hematology parameters are as follows: Hematocrit[>51 % in male, >45% in female], Haemoglobin[Higher: > 175 grams/Litre (g/L) in male, >150 g/L in female and Low: less than (<) 100 g/L in male, <95 g/L in female], Lymphocytes[<0.97 10^9/L], Neutrophils[<1.5 10^9/L], Platelets[High: > 550 10^9/ L and Low: < 100 10^9/ L], White blood cells[High:>18 10^9/L Low:<2 10^9/L], Red blood cells[Low: <3.0 10^12/L in male, <2.5 10^12/L]. Participants were counted in worst case category that their value changes to (low, within range or no change or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (for example [e.g.], High to High), or whose value became within range, were recorded in "To within Range or No Change" category. Participants were counted twice if participant has values that changed 'To Low' & 'To High', so the percentages may not add to 100%. |
Upto Week 9 |
|
Primary |
Part 2: Cohorts 4: Number of Participants With Worst Case Urinalysis Results by Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline |
Urine samples were collected to assess urine glucose, protein, occult blood and ketones using dipstick method. The dipstick test gave results in a semi-quantitative manner, and results for urinalysis parameters were recorded as negative, trace, 1+, 2+, 3+ indicating proportional concentrations in the urine sample. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date. Result for urinalysis parameters were recorded as no change/decreased and any increase. |
Upto Week 9 |
|
Primary |
Part 2: Cohorts 4: Number of Participants With Clinically Significant Changes in Hepatobiliary Laboratory Values |
Blood samples were collected to evaluate hepatobiliary abnormalities. Number of participants with Bilirubin (BIL), Alkaline phosphatase (ALP), Alanine Aminotransferase (ALT) in combination of these with levels more than the defined hepatobiliary abnormality criteria were presented. Hepatocellular injury is defined as ([ALT/ALT ULN]/[ALP/ALP ULN]) greater than or equal to (>=) 5 and ALT >=3xULN. |
Upto Week 9 |
|
Primary |
Part 2: Cohorts 4: Number of Participants With Clinically Significant Changes in 12-lead ECG Laboratory Values |
Twelve lead ECG was obtained using an ECG machine that automatically calculated the heart rate and measured QTc, PR, QRS intervals. Abnormal findings were categorized as clinically significant and not clinically significant. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Data for number of participants with worst case post-Baseline abnormal ECG findings have been presented. |
Upto Week 9 |
|
Primary |
Part 2: Cohorts 4: Number of Participants With Worst Case Vital Signs Results by Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline |
Vital signs included diastolic blood pressure (DBP), systolic blood pressure (SBP), pulse rate (PR), body temperature, respiratory rate (RR) and were measured after resting for at least 5 minutes in semi-supine position. PCI ranges were, SBP (millimeters of mercury[mmHg]): <85 (low) or >160 (high), DBP (mmHg): <45 (low) or >100 (high), heart rate (beats per minute): <40 (low) or >110 (high), respiration rate (breaths per minute):<=8 (low) or >20 (high) and body temperature (degrees Celsius) <=35.5 (low) or >38.0 (high). Participants were counted in worst case category that their value changes to (low, within range or no change, or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, are recorded in 'To W/in Range No Change' category. Participants were counted twice if participant had values that changed 'To Low' and 'To High', so percentages may not add to 100%. |
Upto Week 9 |
|
Primary |
Part 2: Cohorts 4: Number of Participants With Clinically Significant Changes in Echocardiogram |
Echocardiography was performed at screening and Part 2 of the study using sound waves. |
Upto Week 9 |
|
Primary |
Part 2: Cohorts 4: Number of Participants With Clinically Significant Changes in Continuous Telemetry |
Continuous cardiac telemetry was performed in a supine position after at least 5 minutes of rest. Number of participants who had abnormal findings upon cardiac telemetry assessment have been presented. |
Upto Day 14 |
|
Primary |
Part 1: Area Under the Plasma Concentration Curve From Time Zero to Last Time of Quantifiable Concentration (AUC[0-t]) of GSK3884464 Following Single Dose Administration |
Blood samples were collected at indicated time points for pharmacokinetic analysis of AUC[0-t]. |
Day 1 pre-dose,15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 18, 24, 36, 48, 72, 96, and 120 hours post-dose |
|
Primary |
Part 1: AUC From Time Zero to Infinity (AUC[0-inf]) of GSK3884464 Following Single Dose Administration |
Blood samples were collected at indicated time points for pharmacokinetic analysis of AUC[0-t]. |
Day 1 pre-dose,15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 18, 24, 36, 48, 72, 96, and 120 hours post-dose |
|
Primary |
Part 1: Maximum Observed Plasma Concentration (Cmax) of GSK3884464 Following Single Dose Administration |
Blood samples were collected at indicated time points for pharmacokinetic analysis of Cmax. |
Day 1 pre-dose,15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 18, 24, 36, 48, 72, 96, and 120 hours post-dose |
|
Primary |
Part 1: Time to Maximum Observed Plasma Drug Concentration (Tmax) of GSK3884464 Following Single Dose Administration |
Blood samples were collected at indicated time points for pharmacokinetic analysis of Tmax. |
Day 1 pre-dose,15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 18, 24, 36, 48, 72, 96, and 120 hours post-dose |
|
Primary |
Part 1: Terminal Half-life (T1/2) of GSK3884464 Following Single Dose Administration |
Blood samples were collected at indicated time points for pharmacokinetic analysis of T1/2. |
Day 1 pre-dose,15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 18, 24, 36, 48, 72, 96, and 120 hours post-dose |
|
Primary |
Part 2: Cohorts 4: AUC Over the Dosing Interval (AUC[Tau]) of GSK3884464 Following Repeat Dose Administration |
Blood samples were collected at indicated time points for pharmacokinetic analysis of AUC [tau] for repeat dose administration. NA indicates geometric coefficient of variation could not be calculated for single participant. |
Day 1: pre-dose, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24 hours post-dose; Day 4 and Day 11: pre-dose; Day 7: pre-dose, 6 and 12 hours post-dose; Day 14: pre-dose, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 72, 96 and 120 hours post-dose |
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Primary |
Part 2: Cohorts 4: Cmax of GSK3884464 Following Repeat Dose Administration |
Blood samples were collected at indicated time points for pharmacokinetic analysis of Cmax for repeat dose administration. NA indicates geometric coefficient of variation could not be calculated for single participant. |
Day 1: pre-dose, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24 hours post-dose; Day 4 and Day 11: pre-dose; Day 7: pre-dose, 6 and 12 hours post-dose; Day 14: pre-dose, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 72, 96 and 120 hours post-dose |
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Primary |
Part 2: Cohorts 4: Trough Plasma Concentration (Ctau) of GSK3884464 Following Repeat Dose Administration |
Blood samples were collected at indicated time points for pharmacokinetic analysis of Ctau for repeat dose administration. NA indicates geometric coefficient of variation could not be calculated for single participant. |
Day 1: pre-dose, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24 hours post-dose; Day 4 and Day 11: pre-dose; Day 7: pre-dose, 6 and 12 hours post-dose; Day 14: pre-dose, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 72, 96 and 120 hours post-dose |
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Primary |
Part 2: Cohorts 4: Tmax of GSK3884464 Following Repeat Dose Administration |
Blood samples were collected at indicated time points for pharmacokinetic analysis of Tmax for repeat dose administration. NA indicates full range could not be calculated for single participant. |
Day 1: pre-dose, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24 hours post-dose; Day 4 and Day 11: pre-dose; Day 7: pre-dose, 6 and 12 hours post-dose; Day 14: pre-dose, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 72, 96 and 120 hours post-dose |
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Primary |
Part 2: Cohorts 4: T1/2 of GSK3884464 Following Repeat Dose Administration |
Blood samples were collected at indicated time points for pharmacokinetic analysis of T1/2 for repeat dose administration. NA indicates full range could not be calculated for single participant. |
Day 1: pre-dose, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24 hours post-dose; Day 4 and Day 11: pre-dose; Day 7: pre-dose, 6 and 12 hours post-dose; Day 14: pre-dose, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 72, 96 and 120 hours post-dose |
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Primary |
Part 2: Cohorts 4: Accumulation Ratio Based on AUC(Tau) (RAUC) of GSK3884464 Following Repeat Dose Administration |
Blood samples were collected at indicated time points for pharmacokinetic analysis of RAUC for repeat dose administration. NA indicates geometric coefficient of variation could not be calculated for single participant. |
Day 1: pre-dose, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24 hours post-dose; Day 4 and Day 11: pre-dose; Day 7: pre-dose, 6 and 12 hours post-dose; Day 14: pre-dose, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 72, 96 and 120 hours post-dose |
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Primary |
Part 2: Cohorts 4: Accumulation Ratio Based on Cmax (RCmax) of GSK3884464 Following Repeat Dose Administration |
Blood samples were collected at indicated time points for pharmacokinetic analysis of RCmax for repeat dose administration. NA indicates geometric coefficient of variation could not be calculated for single participant. |
Day 1: pre-dose, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24 hours post-dose; Day 4 and Day 11: pre-dose; Day 7: pre-dose, 6 and 12 hours post-dose; Day 14: pre-dose, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 72, 96 and 120 hours post-dose |
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Primary |
Part 2: Cohorts 4: Accumulation Ratio Based on Ctau (RCtau) of GSK3884464 Following Repeat Dose Administration |
Blood samples were collected at indicated time points for pharmacokinetic analysis of RCtau for repeat dose administration. NA indicates geometric coefficient of variation could not be calculated for single participant. |
Day 1: pre-dose, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24 hours post-dose; Day 4 and Day 11: pre-dose; Day 7: pre-dose, 6 and 12 hours post-dose; Day 14: pre-dose, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 72, 96 and 120 hours post-dose |
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Secondary |
Part 1: Change From Baseline in NAD(P)H Dehydrogenase Quinone 1 (NQO1) Messenger Ribonucleic Acid (mRNA) in Whole Blood Post Treatment With GSK3884464 |
Blood samples were collected at indicated time points for pharmacodynamic analysis of NQO1 mRNA. |
Day1: pre-dose,30 minutes,1,1.5,2,3,4,6, 8,12,18,24 hours post-dose |
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Secondary |
Part 2: Cohorts 4: Change From Baseline in NQO1 mRNA in Whole Blood Post Treatment With GSK3884464 |
Blood samples were collected at indicated time points for pharmacodynamic analysis of NQO1 mRNA for repeat dose administration. NA indicates standard deviation could not be calculated for single participant. |
Day 1: pre-dose, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24 hours post-dose; Day 4 and Day 11: pre-dose; Day 7: pre-dose, 6 and 12 hours post-dose; Day 14: pre-dose, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 72, 96 and 120 hours post-dose |
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