The FTIH study with GSK3439171A will evaluate the safety of GSK3439171A in healthy subjects in order to avoid confounding factors due to the disease or concomitant drugs in patients. The study design is based on pre-clinical findings for GSK3439171A, contributing to the frequency, type and duration of safety assessment and monitoring during treatment periods in each cohort. The single dose assessments in Part A will be conducted to determine safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of the study intervention in individuals before progressing to doses explored further in other parts of the study and will allow for any adjustments needed based on emerging safety, tolerability, and PK information. Part A will also serve to identify a dose for use in examining the effect of food on GSK3439171A exposure in Part C. In Part B, a single dose safety, tolerability and PK will be collected followed by progression of these subjects to the repeat dose portion of the study. The up to 14-day dosing was chosen as it is thought to provide sufficient safety and tolerability data to bridge to longer duration studies. The dosing period can be adjusted depending on PK and PD data collected in Part A of the study. Part B will involve more detailed PK/PD/metabolite assessments to better understand the impact of GSK3439171A on target engagement and metabolism in humans. Approximately 150 subjects will be screened to achieve 75 randomly assigned to study intervention. Duration for Part A, B and C will be approximately 10 weeks, 9 weeks and 8 weeks respectively.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
66
Oral solution with doses 0.5 mg up to 4.5 mg and capsule for doses 5 mg and upwards
Placebo oral solution to match with doses 0.5 mg up to 4.5 mg and capsule for doses 5 mg and upwards
GSK Investigational Site
Baltimore, Maryland, United States
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)-Part A
An AE is 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. 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.
Time frame: Up to Day 40
Number of Participants With AEs and SAEs-Part B
An AE is 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. 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.
Time frame: Up to Day 34
Number of Participants With AEs and SAEs-Part C
An AE is 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. 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.
Time frame: Up to Day 29
Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance-Part A
Blood samples were collected for the assessment of clinical chemistry parameters. The clinical concern range for the parameters were: albumin (low: \<30 grams per liter \[g/L\]); 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 millimoles (mmol)/L and high: \>2.75 mmol/L); creatinine (high: change from Baseline \>44.2 micromoles/L); glucose (low: \<3 mmol/L and high: \>9 mmol/L); magnesium (low: 0.5 mmol/L and high: 1.23 mmol/L); phosphorus (low: 0.8 mmol/L and high: 1.6 mmol/L); potassium (low: \<3 mmol/L and high: \>5.5 mmol/L); sodium (low: \<130 mmol/L and high: \>150 mmol/L) and creatine kinase (high: \>500 units per liter). The number of participants with any clinical chemistry abnormality of potential clinical importance is reported.
Time frame: Up to Day 40
Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance-Part B
Blood samples were collected for the assessment of clinical chemistry parameters. The clinical concern range for the parameters were: albumin (low: \<30 g/L); ALT (high: \>=2xULN); AST (high: \>=2xULN); ALP (high: \>=2xULN); total bilirubin (high: \>=1.5xULN); calcium (low: \<2 mmol/L and high: \>2.75 mmol/L); creatinine (high: change from Baseline \>44.2 micromoles/L); glucose (low: \<3 mmol/L and high: \>9 mmol/L); magnesium (low: 0.5 mmol/L and high: 1.23 mmol/L); phosphorus (low: 0.8 mmol/L and high: 1.6 mmol/L); potassium (low: \<3 mmol/L and high: \>5.5 mmol/L); sodium (low: \<130 mmol/L and high: \>150 mmol/L) and creatine kinase (high: \>500 units per liter). The number of participants with any clinical chemistry abnormality of potential clinical importance is reported.
Time frame: Up to Day 34
Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance-Part C
Blood samples were collected for the assessment of clinical chemistry parameters. The clinical concern range for the parameters were: albumin (low: \<30 g/L); ALT (high: \>=2xULN); AST (high: \>=2xULN); ALP (high: \>=2xULN); total bilirubin (high: \>=1.5xULN); calcium (low: \<2 mmol/L and high: \>2.75 mmol/L); creatinine (high: change from Baseline \>44.2 micromoles/L); glucose (low: \<3 mmol/L and high: \>9 mmol/L); magnesium (low: 0.5 mmol/L and high: 1.23 mmol/L); phosphorus (low: 0.8 mmol/L and high: 1.6 mmol/L); potassium (low: \<3 mmol/L and high: \>5.5 mmol/L); sodium (low: \<130 mmol/L and high: \>150 mmol/L) and creatine kinase (high: \>500 units per liter). The number of participants with any clinical chemistry abnormality of potential clinical importance is reported.
Time frame: Up to Day 29
Number of Participants With Hematology Abnormalities of Potential Clinical Importance-Part A
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 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). The number of participants with any hematology abnormality of potential clinical importance is reported.
Time frame: Up to Day 40
Number of Participants With Hematology Abnormalities of Potential Clinical Importance-Part B
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 g/L), lymphocytes (low: \<0.8x10\^9 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). The number of participants with any hematology abnormality of potential clinical importance is reported.
Time frame: Up to Day 34
Number of Participants With Hematology Abnormalities of Potential Clinical Importance-Part C
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 g/L), lymphocytes (low: \<0.8x10\^9 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). The number of participants with any hematology abnormality of potential clinical importance is reported.
Time frame: Up to Day 29
Number of Participants With Abnormal Urinalysis Dipstick Results-Part A
Urine samples were taken for the assessment of following urine parameters: glucose, ketones, occult blood (OB) and protein by dipstick method. The dipstick test gives results in a semi-quantitative manner, and results can be read as Trace, 1+, 2+ indicating proportional concentrations in the urine sample.
Time frame: 8 hours, 24 hours, 48 hours and 72 hours in Periods 1, 2 and 3
Number of Participants With Urinalysis Dipstick Results for Potential of Hydrogen (pH)-Part A
Urine samples were taken for the assessment of urine pH. Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acid pH (5.0 to 6.0). Dipstick test results for pH were presented as number of participants having pH value as 5, 6, 7, 8 or 9.
Time frame: 8 hours, 24 hours, 48 hours and 72 hours in Periods 1, 2 and 3
Number of Participants With Abnormal Urinalysis Dipstick Results-Part B
Urine samples were taken for the assessment of following urine parameters: glucose, ketones, OB and protein by dipstick method. The dipstick test gives results in a semi-quantitative manner, and results can be read as Trace, 1+, 2+ indicating proportional concentrations in the urine sample.
Time frame: Day 2 (24 hours); Day 3 (48 hours); Days 4, 13 and 20 (72 hours); pre-dose on Days 7, 10, 11 and 17
Number of Participants With Urinalysis Dipstick Results (pH)-Part B
Urine samples were taken for the assessment of urine pH. Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acid pH (5.0 to 6.0). Dipstick test results for pH were presented as number of participants having pH value as 5, 6, 7, 8 or 9.
Time frame: Day 2 (24 hours); Day 3 (48 hours); Days 4, 13 and 20 (72 hours); pre-dose on Days 7, 10, 11 and 17
Number of Participants With Abnormal Urinalysis Dipstick Results-Part C
Urine samples were taken for the assessment of following urine parameters: glucose, ketones, OB and protein by dipstick method. The dipstick test gives results in a semi-quantitative manner, and results can be read as Trace, 1+, 2+ indicating proportional concentrations in the urine sample.
Time frame: 8 hours, 24 hours, 48 hours and 72 hours in Period 1 and Period 2
Number of Participants With Urinalysis Dipstick Results (pH)-Part C
Urine samples were taken for the assessment of urine pH. Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acid pH (5.0 to 6.0). Dipstick test results for pH were presented as number of participants having pH value as 5, 6, 7, 8 or 9.
Time frame: 8 hours, 24 hours, 48 hours and 72 hours in Period 1 and Period 2
Number of Participants With Vital Signs of Potential Clinical Importance-Part A
Vital signs were measured in a supine position after five minutes of rest and included temperature, systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate and respiratory rate. The clinical concern range for the parameters included: SBP (low: \<85 millimeters of mercury \[mmHg\] and high: \>160 mmHg), DBP (low: \<45 mmHg and high: \>100 mmHg) and heart rate (low: \<40 beats per minute \[bpm\] and high: \>110 bpm). Number of participants with any vital signs of potential clinical importance is reported.
Time frame: Up to Day 40
Number of Participants With Vital Signs of Potential Clinical Importance-Part B
Vital signs were measured in a supine position after five minutes of rest and included temperature, SBP, DBP, heart rate and respiratory rate. The clinical concern range for the parameters included: SBP (low: \<85 mmHg and high: \>160 mmHg), DBP (low: \<45 mmHg and high: \>100 mmHg) and heart rate (low: \<40 bpm and high: \>110 bpm). Number of participants with any vital signs of potential clinical importance is reported.
Time frame: Up to Day 34
Number of Participants With Vital Signs of Potential Clinical Importance-Part C
Vital signs were measured in a supine position after five minutes of rest and included temperature, SBP, DBP, heart rate and respiratory rate. The clinical concern range for the parameters included: SBP (low: \<85 mmHg and high: \>160 mmHg), DBP (low: \<45 mmHg and high: \>100 mmHg) and heart rate (low: \<40 bpm and high: \>110 bpm). Number of participants with any vital signs of potential clinical importance is reported.
Time frame: Up to Day 29
Number of Participants With Abnormal Electrocardiogram (ECG) Findings-Part A
Twelve-lead ECGs were recorded with the participants in a supine position using an ECG machine that automatically calculated heart rate and measured PR, QRS, QT and corrected QT (QTc) intervals. Clinically significant (CS) and not clinically significant (NCS) abnormal ECG findings have been presented. CS 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 worst case post-Baseline is presented. Baseline value is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.
Time frame: Up to Day 40
Number of Participants With Abnormal ECG Findings-Part B
Twelve-lead ECGs were recorded with the participants in a supine position using an ECG machine that automatically calculated heart rate and measured PR, QRS, QT and QTc intervals. CS and NCS abnormal ECG findings have been presented. CS 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 worst case post-Baseline is presented. Baseline value is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.
Time frame: Up to Day 34
Number of Participants With Abnormal ECG Findings-Part C
Twelve-lead ECGs were recorded with the participants in a supine position using an ECG machine that automatically calculated heart rate and measured PR, QRS, QT and QTc intervals. CS and NCS abnormal ECG findings have been presented. CS 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 worst case post-Baseline is presented. Baseline value is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.
Time frame: Up to Day 29
Area Under Tha Plasma Drug Concentration Versus Time Curve From Time Zero to Time of Last Quantifiable Concentration (AUC[0 to t]) of GSK3439171A Following Single Dose-Part A (GSK3439171A 5 mg Only)
Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Time frame: pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36 and 48 hours post-dose
AUC(0 to t) of GSK3439171A Following Single Dose-Part A (GSK3439171A 10 mg, 30 mg, 60 mg, 120 mg and 180 mg)
Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Time frame: pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose
AUC(0 to t) of GSK3439171A Following Single Dose-Part B (GSK3439171A 5 mg and 11 mg)
Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Time frame: Day 1 (pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose)
AUC(0 to t) of GSK3439171A Following Repeat Dose-Part B (GSK3439171A 5 mg and 11 mg)
Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Time frame: Day 17 (pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose)
AUC(0 to t) of GSK3439171A Following Single Dose-Part B (GSK3439171A 40 mg Only)
Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Time frame: Day 1 (pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose)
AUC(0 to t) of GSK3439171A Following Repeat Dose-Part B (GSK3439171A 40 mg Only)
Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Time frame: Day 10 (pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose)
Area Under the Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC[0 to Inf]) of GSK3439171A Following Single Dose-Part A (GSK3439171A 5 mg Only)
Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Time frame: pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36 and 48 hours post-dose
AUC(0 to Inf) of GSK3439171A Following Single Dose-Part A (GSK3439171A 10 mg, 30 mg, 60 mg, 120 mg and 180 mg)
Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Time frame: pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose
AUC(0 to Inf) of GSK3439171A Following Single Dose-Part B (GSK3439171A 5 mg and 11 mg)
Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Time frame: Day 1 (pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose)
AUC(0 to Inf) of GSK3439171A Following Repeat Dose-Part B (GSK3439171A 5 mg and 11 mg)
Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Time frame: Day 17 (pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose)
AUC(0 to Inf) of GSK3439171A Following Single Dose-Part B (GSK3439171A 40 mg Only)
Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Time frame: Day 1 (pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose)
AUC(0 to Inf) of GSK3439171A Following Repeat Dose-Part B (GSK3439171A 40 mg Only)
Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Time frame: Day 10 (pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose)
Maximum Observed Plasma Concentration (Cmax) of GSK3439171A Following Single Dose-Part A (GSK3439171A 5 mg Only)
Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Time frame: pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36 and 48 hours post-dose
Cmax of GSK3439171A Following Single Dose-Part A (GSK3439171A 10 mg, 30 mg, 60 mg, 120 mg and 180 mg)
Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Time frame: pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose
Cmax of GSK3439171A Following Single Dose-Part B (GSK3439171A 5 mg and 11 mg)
Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Time frame: Day 1 (pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose)
Cmax of GSK3439171A Following Repeat Dose-Part B (GSK3439171A 5 mg and 11 mg)
Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Time frame: Day 17 (pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose)
Cmax of GSK3439171A Following Single Dose-Part B (GSK3439171A 40 mg Only)
Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Time frame: Day 1 (pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose)
Cmax of GSK3439171A Following Repeat Dose-Part B (GSK3439171A 40 mg Only)
Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Time frame: Day 10 (pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose)
Time to Maximum Observed Plasma Concentration (Tmax) of GSK3439171A Following Single Dose-Part A (GSK3439171A 5 mg Only)
Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Time frame: pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36 and 48 hours post-dose
Tmax of GSK3439171A Following Single Dose-Part A (GSK3439171A 10 mg, 30 mg, 60 mg, 120 mg and 180 mg)
Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Time frame: pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose
Tmax of GSK3439171A Following Single Dose-Part B (GSK3439171A 5 mg and 11 mg)
Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Time frame: Day 1 (pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose)
Tmax of GSK3439171A Following Repeat Dose-Part B (GSK3439171A 5 mg and 11 mg)
Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Time frame: Day 17 (pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose)
Tmax of GSK3439171A Following Single Dose-Part B (GSK3439171A 40 mg Only)
Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Time frame: Day 1 (pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose)
Tmax of GSK3439171A Following Repeat Dose-Part B (GSK3439171A 40 mg Only)
Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Time frame: Day 10 (pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose)
Apparent Terminal Half-life (T1/2) of GSK3439171A Following Single Dose-Part A (GSK3439171A 5 mg Only)
Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Time frame: pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36 and 48 hours post-dose
T1/2 of GSK3439171A Following Single Dose-Part A (GSK3439171A 10 mg, 30 mg, 60 mg, 120 mg and 180 mg)
Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Time frame: pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose
T1/2 of GSK3439171A Following Single Dose-Part B (GSK3439171A 5 mg and 11 mg)
Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Time frame: Day 1 (pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose)
T1/2 of GSK3439171A Following Repeat Dose-Part B (GSK3439171A 5 mg and 11 mg)
Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Time frame: Day 17 (pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose)
T1/2 of GSK3439171A Following Single Dose-Part B (GSK3439171A 40 mg Only)
Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Time frame: Day 1 (pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose)
T1/2 of GSK3439171A Following Repeat Dose-Part B (GSK3439171A 40 mg Only)
Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Time frame: Day 10 (pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose)
AUC(0 to t) of GSK3439171A (Food Effect)-Part C
Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Time frame: pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose
AUC(0 to Inf) of GSK3439171A (Food Effect)-Part C
Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Time frame: pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose
Cmax for GSK3439171A (Food Effect)-Part C
Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Time frame: pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose
Tmax for GSK3439171A-Part C
Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Time frame: pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose
T1/2 for GSK3439171A-Part C
Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Time frame: pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose
Dose Proportionality of GSK3439171A Using AUC(0 to t) Following a Single Dose-Part A
Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis. Dose proportionality was assessed using Power model with fixed effects of logarithm of treatment and participant as random effect. Slope and 90% confidence interval for the slope are presented.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Time frame: pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose
Dose Proportionality of GSK3439171A Using AUC(0 to Inf) Following a Single Dose-Part A
Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis. Dose proportionality was assessed using Power model with fixed effects of logarithm of treatment and participant as random effect. Slope and 90 % confidence interval for the slope are presented.
Time frame: pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose
Dose Proportionality of GSK3439171A Using Cmax Following a Single Dose-Part A
Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis. Dose proportionality was assessed using Power model with fixed effects of logarithm of treatment and participant as random effect. Slope and 90% confidence interval for the slope are presented.
Time frame: pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose
Dose Proportionality of GSK3439171A Using AUC(0 to Tau) Following Repeat Dose-Part B
Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis. Dose proportionality was assessed using Power model with fixed effects of logarithm of treatment and participant as random effect. Slope and 90% confidence interval for the slope are presented.
Time frame: Days 10 and 17 (pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose)
Dose Proportionality of GSK3439171A Using Cmax Following Repeat Dose-Part B
Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis. Dose proportionality was assessed using Power model with fixed effects of logarithm of treatment and participant as random effect. Slope and 90% confidence interval for the slope are presented.
Time frame: Days 10 and 17 (pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose)
Observed Accumulation Ratio for AUC (AUC[Ro])-Part B (GSK3439171A 5 mg and 11 mg)
Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis. AUC(Ro) was calculated as Day17 AUC(0 to tau) divided by Day 1 AUC (0 to tau). Analysis was performed using Mixed effect model with AUC (0 to tau) as the response variable. Treatment, visit and treatment-by-visit interaction are added as fixed effects and participant as random effect. Ratio and 90% confidence interval of the ratio is presented.
Time frame: Days 1 and 17 (pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose)
Observed Accumulation Ratio for AUC (AUC[Ro])-Part B (GSK3439171A 40 mg Only)
Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis. AUC(Ro) was calculated as Day10 AUC(0 to tau) divided by Day 1 AUC (0 to tau). Analysis was performed using Mixed effect model with AUC (0 to tau) as the response variable. Treatment, visit and treatment-by-visit interaction are added as fixed effects and participant as random effect. Ratio and 90% confidence interval of the ratio is presented.
Time frame: Days 1 and 10 (pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose)
Observed Accumulation Ratio for Cmax (RCmax)-Part B (GSK3439171A 5 mg and 11 mg)
Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis. RCmax was calculated as Day17 Cmax divided by Day 1 Cmax. Analysis was performed using Mixed effect model with Cmax as the response variable. Treatment, visit and treatment-by-visit interaction are added as fixed effects and participant as random effect. Ratio and 90% confidence interval of the ratio is presented.
Time frame: Days 1 and 17 (pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose)
Observed Accumulation Ratio for Cmax (RCmax)-Part B (GSK3439171A 40 mg Only)
Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis. RCmax was calculated as Day10 Cmax divided by Day 1 Cmax. Analysis was performed using Mixed effect model with Cmax as the response variable. Treatment, visit and treatment-by-visit interaction are added as fixed effects and participant as random effect. Ratio and 90% confidence interval of the ratio is presented.
Time frame: Days 1 and 10 (pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose)
Steady State Accumulation Ratio (Rss)-Part B (GSK3439171A 5 mg and 11 mg)
Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis. Rss was calculated as Day 17 AUC(0-tau) divided by Day 1 AUC(0-inf). Analysis was performed using Mixed Effect Model, with AUC(0-tau) and AUC(0-inf) as the response variables. Treatment, visit, parameter and parameter-by-treatment-by-visit interaction are added as fixed effects and participant as random effect. Ratio and 90% confidence interval of the ratio is presented.
Time frame: Days 1 and 17 (pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose)
Steady State Accumulation Ratio (Rss)-Part B (GSK3439171A 40 mg Only)
Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis. Rss was calculated as Day 10 AUC(0-tau) divided by Day 1 AUC(0-inf). Analysis was performed using Mixed Effect Model, with AUC(0-tau) and AUC(0-inf) as the response variables. Treatment, visit, parameter and parameter-by-treatment-by-visit interaction are added as fixed effects and participant as random effect. Ratio and 90% confidence interval of the ratio is presented.
Time frame: Days 1 and 10 (pre-dose, 0.083, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 60 and 72 hours post-dose)
Trough Plasma Concentrations at the End of Dosing Interval for Repeat Doses on Days 6, 7, 9, 10, 11, 15, 16 and 17-Part B (GSK3439171A 5 mg and 11 mg)
Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Time frame: pre-dose on Days 6, 7, 9, 10, 11, 15, 16 and 17
Trough Plasma Concentrations at the End of Dosing Interval for Repeat Doses on Days 6, 7, 9 and 10-Part B (GSK3439171A 40 mg Only)
Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.
Time frame: pre-dose on Days 6, 7, 9 and 10
Steady State Assessment Using Trough Plasma Concentration at the End of Dosing Interval for Repeat Dose-Part B (GSK3439171A 5 mg and 11 mg)
Blood samples were collected at indicated time points for pharmacokinetic analysis. The slope estimate of the day effect was obtained from Mixed Effect Model, with visit as the fixed effect and participant as random effect. The analysis was done separately for each treatment. "Variance Component" covariance structure was used. The back transformed slope and 90% confidence interval for the slope is presented.
Time frame: pre-dose on Days 6, 7, 9, 10, 11, 15, 16 and 17
Steady State Assessment Using Trough Plasma Concentration at the End of Dosing Interval for Repeat Dose-Part B (GSK3439171A 40 mg Only)
Blood samples were collected at indicated time points for pharmacokinetic analysis. The slope estimate of the day effect was obtained from Mixed Effect Model, with visit as the fixed effect and participant as random effect. The analysis was done separately for each treatment. "Variance Component" covariance structure is used. The back transformed slope and 90% confidence interval for the slope is presented.
Time frame: pre-dose on Days 6, 7, 9 and 10