Phase 1
Completed N=27
GSK3739937 First-Time-In-Human (FTIH) Study in Healthy Volunteers
Source: ClinicalTrials.gov NCT04493684 ↗Enrolled (actual)
27
Serious AEs
0.0%
Results posted
Aug 2023
Primary outcomePrimary: Part 1 - Number of Any Adverse Events (AEs) and Serious Adverse Events (SAEs) — 7; 1; 3; 3 Events
Summary
This study is a Phase 1, double-blind (sponsor-unblinded), randomized, placebo-controlled, single- and repeat-dose escalation study including a weekly oral dose (MAD) cohort and a relative bioavailability (RBA) and food effect (FE) cohort to investigate the safety, tolerability and PK of VH3739937 in healthy participants. This is a three part study. Part 1 and Part 2 is designed to gain information on the safety, tolerability, and pharmacokinetic (PK) properties of GSK3739937 when administered as powder-in-a-bottle (PiB). Part 3 will evaluate the RBA of the GSK3739937 PiB and GSK3739937 Tablet and the safety, tolerability and PK parameters of the tablet formulation when administered under fasting and fed conditions.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Part 1 - Number of Any Adverse Events (AEs) and Serious Adverse Events (SAEs) |
7; 1; 3; 3; 0; 2 | — |
| PRIMARY Part 2 - Number of Any AEs and SAEs |
3; 0; 2; 5; 0; 4 | — |
| PRIMARY Part 3 - Number of Any AEs and SAEs |
2; 4; 6; 0; 0; 0 | — |
| PRIMARY Part 1 - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets |
-0.01; 0; 0; 0; -0.02; 0 | — |
| PRIMARY Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets |
0; 0; 0.03; -0.02; 0.03; -0.03 | — |
| PRIMARY Part 2 (QW PBO and Cohort 6) - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets |
0; 0; 0.03; -0.01; 0.23; 0.04 | — |
| PRIMARY Part 3 - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets |
0.01; 0; 0; -0.05; -0.05; -0.05 | — |
| PRIMARY Part 1 - Change From Baseline in Hematology Parameters - Erythrocytes Count |
0.079; 0.17; 0.197; 0.245; 0.048; 0.11 | — |
| PRIMARY Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameters - Erythrocytes Count |
-0.06; 0.017; -0.227; 0.037 | — |
| PRIMARY Part 2 (QW PBO and Cohort 6) - Change From Baseline in Hematology Parameters - Erythrocytes Count |
-0.060; -0.014 | — |
| PRIMARY Part 3 - Change From Baseline in Hematology Parameters - Erythrocytes Count |
0.229; 0.197; 0.189 | — |
| PRIMARY Part 1 - Change From Baseline in Hematology Parameter - Erythrocytes Mean Corpuscular Hemoglobin (MCH) |
0.09; -0.5; 0.33; -0.08; -0.13; -0.13 | — |
| PRIMARY Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameter - Erythrocytes Mean Corpuscular Hemoglobin (MCH) |
0.02; -0.3; 0.16; -0.08 | — |
| PRIMARY Part 2 (QW PBO and Cohort 6) - Change From Baseline in Hematology Parameter - Erythrocytes Mean Corpuscular Hemoglobin (MCH) |
-0.87; -0.83 | — |
| PRIMARY Part 3 - Change From Baseline in Hematology Parameter - Erythrocytes Mean Corpuscular Hemoglobin (MCH) |
0; -0.24; 0.05 | — |
| PRIMARY Part 1 - Change From Baseline in Hematology Parameter - Hematocrit |
0.0083; 0.014; 0.015; 0.0237; 0.0012; 0.0047 | — |
| PRIMARY Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameter - Hematocrit |
-0.0081; 0.0066; -0.0217; 0.0043 | — |
| PRIMARY Part 2 (QW PBO and Cohort 6) - Change From Baseline in Hematology Parameter - Hematocrit |
-0.0120; -0.0094 | — |
| PRIMARY Part 3 - Change From Baseline in Hematology Parameter - Hematocrit |
0.0182; 0.013; 0.0159 | — |
| PRIMARY Part 1 - Change From Baseline in Hematology Parameter - Reticulocytes |
0.0008; 0.002; -0.0045; -0.0008; -0.0007; -0.0015 | — |
| PRIMARY Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameter - Reticulocytes |
-0.0017; -0.0011; 0.0010; -0.0012 | — |
| PRIMARY Part 2 (QW PBO and Cohort 6) - Change From Baseline in Hematology Parameter - Reticulocytes |
0.0003; -0.0001 | — |
| PRIMARY Part 3 - Change From Baseline in Hematology Parameter - Reticulocytes |
-0.0011; -0.0009; -0.0012 | — |
| PRIMARY Part 1 - Change From Baseline in Hematology Parameter - Hemoglobin (Hb) |
2.8; 2; 7.5; 6.7; 1; 2.7 | — |
| PRIMARY Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameter - Hemoglobin (Hb) |
-1.6; -1; -5.7; 0.5 | — |
| PRIMARY Part 2 (QW PBO and Cohort 6) - Change From Baseline in Hematology Parameter - Hemoglobin (Hb) |
-5.7; -4.3 | — |
| PRIMARY Part 3 - Change From Baseline in Hematology Parameter - Hemoglobin (Hb) |
6.7; 4.5; 5.7 | — |
| PRIMARY Part 1 - Change From Baseline in Clinical Chemistry Parameter - Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphate (ALP) and Serum Creatine Phosphokinase (CPK) |
4.6; 5; 8.3; 6.7; 3; 6.2 | — |
| PRIMARY Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameter - ALT, AST, ALP and Serum CPK |
-0.4; -4.6; 5.9; 3.0; -3.1; -5.9 | — |
| PRIMARY Part 2 (QW PBO and Cohort 6) - Change From Baseline in Clinical Chemistry Parameter -ALT, AST, ALP and Serum CPK |
0.0; 1.9; -2.3; -3.1; -3.0; -3 | — |
| PRIMARY Part 3 - Change From Baseline in Clinical Chemistry Parameter - ALT, AST, ALP and CPK |
5.9; 5.4; 5.2; 1.3; -0.2; -0.4 | — |
| PRIMARY Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides |
-0.29; -0.499; -0.3147; -0.1387; -0.157; -0.379 | — |
| PRIMARY Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides |
-0.2773; -0.6027; 0.0319; -0.3978; -1; -1.4 | — |
| PRIMARY Part 2 (QW PBO and Cohort 6) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides |
-0.2590; -0.3014; -0.7; -0.3; -0.0913; -0.0391 | — |
| PRIMARY Part 3 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides Edit Properties | Duplicate Measure |
-0.2033; -0.3755; -0.2145; 1.5; 0.4; 1.5 | — |
| PRIMARY Part 1 - Change From Baseline in Clinical Chemistry Parameters - Amylase and Lipase |
-1.2; 12; -0.7; -0.7; 3.7; 5.8 | — |
| PRIMARY Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameters - Amylase and Lipase |
3.7; -18.3; 0.3; 7.2; 3.8; -6.3 | — |
| PRIMARY Part 2 (QW PBO and Cohort 6) - Change From Baseline in Clinical Chemistry Parameters - Amylase and Lipase |
2.7; -10; -2.0; -1.9 | — |
| PRIMARY Part 3 - Change From Baseline in Clinical Chemistry Parameters - Amylase and Lipase |
0.5; 1.2; 5.1; 0.4; -0.6; 2.7 | — |
| PRIMARY Part 1 - Change From Baseline in Clinical Chemistry Parameter - Total Bilirubin, Direct Bilirubin and Creatinine |
-0.2839; 0; -0.1995; 0.4895; -0.285; 0.2565 | — |
| PRIMARY Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameter - Total Bilirubin, Direct Bilirubin and Creatinine |
-0.6058; 0.5863; -0.8061; 0.2817; 0.19; 0.244 | — |
| PRIMARY Part 2 (QW PBO and Cohort 6) - Change From Baseline in Clinical Chemistry Parameter - Total Bilirubin, Direct Bilirubin and Creatinine |
0.5700; 1.4671; -1.140; 1.71; -1.1787; 2.2731 | — |
| PRIMARY Part 3 - Change From Baseline in Clinical Chemistry Parameter - Total Bilirubin, Direct Bilirubin and Creatinine |
0.3306; 0.4124; 0.2059; 0.456; 0.905; 1.026 | — |
| PRIMARY Part 1 - Change From Baseline in Clinical Chemistry Parameter - Total Protein |
3.2; 2; 4.5; 6.3; 1; 3.7 | — |
| PRIMARY Part 2 - (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameter - Total Protein |
-3.7; -7.1; -5.4; 2.0 | — |
| PRIMARY Part 2 (QW PBO and Cohort 6) - Change From Baseline in Clinical Chemistry Parameter - Total Protein |
-1.7; -2.1 | — |
| PRIMARY Part 3 - Change From Baseline in Clinical Chemistry Parameter - Total Protein |
5.1; 5.4; 4.5 | — |
| PRIMARY Part 1 - Number of Participants With Abnormal Urinalysis Parameters |
4; 0; 1; 1; 2; 3 | — |
| PRIMARY Part 2 - Number of Participants With Abnormal Urinalysis Parameters |
2; 1; 3; 0; 1; 3 | — |
| PRIMARY Part 3 - Number of Participants With Abnormal Urinalysis Parameters |
1; 1; 1; 4; 2; 2 | — |
| PRIMARY Part 1 - Change From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) |
5.3; 0.5; -0.1; 4.6; 2.3; 1.3 | — |
| PRIMARY Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Vital Signs - Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) |
-6.0; -2.1; -2.1; -0.8; -3.4; 0.8 | — |
| PRIMARY Part 2 (QW PBO and Cohort 6) - Change From Baseline in Vital Signs - Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) |
1.0; 1.5; 4.2; 0.9 | — |
| PRIMARY Part 3 - Change From Baseline in Vital Signs - Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) |
6.2; 3.8; 9.3; 2.3; 3.4; 4.4 | — |
| PRIMARY Part 1 - Change From Baseline in Vital Signs - Pulse Rate |
1.5; 15.7; 3.5; -0.2; 5.9; 4.8 | — |
| PRIMARY Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Vital Signs - Pulse Rate |
1.1; -2.8; 5.0; 3.0 | — |
| PRIMARY Part 2 (QW PBO and Cohort 6) - Change From Baseline in Vital Signs - Pulse Rate |
0.9; 5.2 | — |
| PRIMARY Part 3 - Change From Baseline in Vital Signs - Pulse Rate |
6.2; 7.4; 6.6 | — |
| PRIMARY Part 1 - Change From Baseline in Vital Signs - Body Temperature |
-0.06; -0.10; 0.12; -0.05; 0.10; 0.02 | — |
| PRIMARY Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Vital Signs - Body Temperature |
0.16; -0.07; 0.09; -0.08 | — |
| PRIMARY Part 2 (QW PBO and Cohort 6) - Change From Baseline in Vital Signs - Body Temperature |
-0.07; -0.06 | — |
| PRIMARY Part 3 - Change From Baseline in Vital Signs - Body Temperature |
0.08; 0.06; 0.15 | — |
| PRIMARY Part 1 - Change From Baseline in Vital Signs - Respiratory Rate |
0.7; -5.0; -3.0; 3.7; 0.7; 0.3 | — |
| PRIMARY Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Vital Signs - Respiratory Rate |
-0.4; -3.4; 0.0; 1.2 | — |
| PRIMARY Part 2 (QW PBO and Cohort 6) - Change From Baseline in Vital Signs - Respiratory Rate |
0.0; -1.4 | — |
| PRIMARY Part 3 - Change From Baseline in Vital Signs - Respiratory Rate |
0.4; -0.3; 1.2 | — |
| PRIMARY Part 1 - Number of Participants With Worst Case Post-Baseline Electrocardiogram (ECG) Findings |
1; 2; 0; 0; 0; 1 | — |
| PRIMARY Part 2 - Number of Participants With Worst Case Post-Baseline ECG Findings |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Part 3 - Number of Participants With Worst Case Post-Baseline ECG Findings |
1; 1; 1; 14; 16; 14 | — |
| PRIMARY Part 3 - Area Under the Plasma Concentration Time Curve (AUC) From Zero to 24 Hours (AUC[0-24]) of GSK3739937 |
6455.362; 8646.757; 3522.969 | — |
| PRIMARY Part 3 - AUC From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC[0-inf]) of GSK3739937 |
43323.02; 58892.29; 27326.99 | — |
| PRIMARY Part 3 - Maximum Observed Concentration (Cmax) of GSK3739937 |
389.81; 524.99; 227.88 | — |
| SECONDARY Part 1 (Cohort 1 and 2) - AUC(0-24) of GSK3739937 |
637.8486; 1976.944; 5027.183; 9490.296; 13743.02; 23829.99 | — |
| SECONDARY Part 1 (Cohort 1 and 2) - AUC From Zero (Pre-dose) to Time of the Last Quantifiable Concentration (t) (AUC [0-t]) of GSK3739937 |
2486.061; 11441.28; 33650.11; 64937.76; 90730.34; 158068.4 | — |
| SECONDARY Part 1 (Cohort 1 and 2) - AUC(0-inf) of GSK3739937 |
NA; 12788.34; 40287.05; 75181.6; 107211.7; 190803.9 | — |
| SECONDARY Part 1 (Cohort 1 and 2) - Apparent Terminal Phase Half-life (T1/2) of GSK3739937 |
NA; 75.8706; 79.0711; 91.8314; 96.7684; 82.6113 | — |
| SECONDARY Part 1 (Cohort 1 and 2) - Apparent Oral Clearance (CL/F) of GSK3739937 |
NA; 2.3459; 1.9857; 2.1282; 2.9847; 3.3542 | — |
| SECONDARY Part 1 (Cohort 1 and 2) - Cmax of GSK3739937 |
39.22; 127.3; 310.43; 528.63; 1014.31; 1458.44 | — |
| SECONDARY Part 1 (Cohort 1 and 2) - Concentration of GSK3739937 at 24 Hours (C24) of GSK3739937 |
29.46; 85.3; 247.73; 429.55; 612.15; 1126.32 | — |
| SECONDARY Part 1 (Cohort 1 and 2) - Last Quantifiable Concentration (Clast) of GSK3739937 |
15.09; 14.41; 18.24; 39.54; 51.33; 78.7 | — |
| SECONDARY Part 1 (Cohort 1 and 2 ) - Time of Occurrence of Cmax (Tmax) of GSK3739937 |
6.98; 8; 7.98; 7.95; 6.99; 7 | — |
| SECONDARY Part 1 (Cohort 1 and 2) - Lag Time (Tlag) of GSK3739937 |
3.47; 1.99; 1.23; 1; 1; 0.5 | — |
| SECONDARY Part 1 (Cohort 1 and 2) - Time to Reach Clast (Tlast) of GSK3739937 |
95.7; 261.967; 359.967; 358.942; 359.642; 359.9 | — |
| SECONDARY Part 2 (Cohort 3, 4 and 5) - AUC (0-24) of GSK3739937 on Day 1 |
1888.173; 3559.102; 5893.917 | — |
| SECONDARY Part 2 (Cohort 3, 4 and 5) - Cmax of GSK3739937 on Day 1 |
132.12; 232.07; 375.26 | — |
| SECONDARY Part 2 (Cohort 3, 4 and 5) - C24 of GSK3739937 on Day 1 |
89.33; 188.65; 271.59 | — |
| SECONDARY Part 2 (Cohort 3, 4 and 5) - Tmax of GSK3739937 on Day 1 |
9; 8; 9 | — |
| SECONDARY Part 2 (Cohort 3, 4 and 5) - Tlag of GSK3739937 on Day 1 |
2; 2; 1.03 | — |
| SECONDARY Part 2 (Cohort 3 and 4) - Tmax of GSK3739937 on Day 14 |
6.95; 7.03 | — |
| SECONDARY Part 2 (Cohort 3 and 4) - Cmax of GSK3739937 on Day 14 |
766.32; 1149.32 | — |
| SECONDARY Part 2 (Cohort 3 and 4) - AUC From Pre-dose to the End of the Dosing Interval at Steady State (AUC[0-tau]) of GSK3739937 on Day 14 |
14592.19; 24888.49 | — |
| SECONDARY Part 2 (Cohort 3 and 4) - Plasma Trough Concentration (Ctau) of GSK3739937 on Day 14 |
588.1557; 990.3205 | — |
| SECONDARY Part 2 (Cohort 3 and 4) - T1/2 of GSK3739937 on Day 14 |
85.7725; 72.2484 | — |
| SECONDARY Part 2 (Cohort 3 and 4) - CL/F of GSK3739937 on Day 14 |
1.7132; 2.009 | — |
| SECONDARY Part 2 (Cohort 5) - Tmax of GSK3739937 on Day 18 |
9.01 | — |
| SECONDARY Part 2 (Cohort 5) - Cmax of GSK3739937 on Day 18 |
2748 | — |
| SECONDARY Part 2 (Cohort 5) - AUC From Pre-dose to the End of the Dosing Interval at Steady State (AUC[0-tau]) on Day 18 |
58417.64 | — |
| SECONDARY Part 2 (Cohort 5) - Plasma Trough Concentration (Ctau) of GSK3739937 on Day 18 |
2458.275 | — |
| SECONDARY Part 2 (Cohort 5) - T1/2 of GSK3739937 on Day 18 |
78.5264 | — |
| SECONDARY Part 2 (Cohort 5) - CL/F of GSK3739937 on Day 18 |
1.7118 | — |
| SECONDARY Part 2 (Cohort 6) - AUC From Zero to 168 Hours (AUC[0-168]) of GSK3739937 From Day 1 |
96434.63 | — |
| SECONDARY Part 2 (Cohort 6) - Cmax of GSK3739937 on Day 1 |
1106.61 | — |
| SECONDARY Part 2 (Cohort 6) - Concentration of GSK3739937 at 168 Hours (C168) From Day 1 |
250.62 | — |
| SECONDARY Part 2 (Cohort 6) - Tmax of GSK3739937 on Day 1 |
9.88 | — |
| SECONDARY Part 2 (Cohort 6) - Tlag of GSK3739937 on Day 1 |
— | — |
| SECONDARY Part 2 (Cohort 6 ) - AUC(0-t) of GSK3739937 on Day 15 |
169693.1 | — |
| SECONDARY Part 2 (Cohort 6) - Cmax of GSK3739937 on Day 15 |
1855.67 | — |
| SECONDARY Part 2 (Cohort 6) - Ctau of GSK3739937 on Day 15 |
455.4447 | — |
| SECONDARY Part 2 (Cohort 6) - Tmax of GSK3739937 on Day 15 |
10 | — |
| SECONDARY Part 2 (Cohort 6) - T1/2 of GSK3739937 on Day 15 |
74.5404 | — |
| SECONDARY Part 2 (Cohort 6) - CL/F of GSK3739937 on Day 15 |
2.9465 | — |
| SECONDARY Part 3 (Cohort 7) - C24 of GSK3739937 |
316.7; 407.5; 153.97 | — |
| SECONDARY Part 3 (Cohort 7) Clast of GSK3739937 |
19.76; 25.09; 15.44 | — |
| SECONDARY Part 3 (Cohort 7) - Tmax of GSK3739937 |
9; 8.42; 6 | — |
| SECONDARY Part 3 (Cohort 7) - Tlag of GSK3739937 |
1; 2; 0.98 | — |
| SECONDARY Part 3 (Cohort 7) - Tlast of GSK3739937 |
336.75; 360.067; 267.4 | — |
| SECONDARY Part 3 (Cohort 7) - T1/2 of GSK3739937 |
74.7429; 72.9842; 72.8066 | — |
| SECONDARY Part 3 (Cohort 7) - CL/F of GSK3739937 |
2.3082; 1.698; 3.6594 | — |
| SECONDARY Part 1 - Dose Proportionality of GSK3739937 for Dose Levels 30 mg to 800 mg Using AUC(0-infinity) After Single Dose Administration of GSK3739937 |
0.882 | — |
| SECONDARY Part 1 - Dose Proportionality of GSK3739937 for Dose Levels 10 mg to 800 mg Using Cmax After Single Dose Administration of GSK3739937 |
0.914 | — |
| SECONDARY Part 2 - Dose Proportionality of GSK3739937 for Dose Levels 25 mg to 100 mg Using AUC(0-24) After Repeated Dose Administration of GSK3739937 |
0.997 | — |
| SECONDARY Part 2 - Dose Proportionality of GSK3739937 for Dose Levels 25 mg to 100 mg Using Cmax After Repeated Dose Administration of GSK3739937 |
0.914 | — |
| SECONDARY Part 2 - Dose Proportionality of GSK3739937 for Dose Levels 25 mg to 100 mg Using Ctau After Repeated Dose Administration of GSK3739937 |
1.023 | — |
| SECONDARY Part 2 (Cohort 3 and 4) - Accumulation Ratio of AUC(0-tau) (R [AUC{0-TAU}]) |
7.728; 6.993 | — |
| SECONDARY Part 2 (Cohort 5) - Accumulation Ratio of AUC(0-tau) (R [AUC{0-TAU}]) |
9.943 | — |
| SECONDARY Part 2 (Cohort 6) - Accumulation Ratio of AUC(0-tau) (R [AUC{0-TAU}]) |
1.76 | — |
| SECONDARY Part 2 (Cohort 3 and 4) - Accumulation Ratio of Cmax (R [CMAX]) |
5.8; 4.952 | — |
| SECONDARY Part 2 (Cohort 5) - Accumulation Ratio of Cmax (R [CMAX]) |
7.325 | — |
| SECONDARY Part 2 (Cohort 6) - Accumulation Ratio of Cmax (R [CMAX]) |
1.677 | — |
| SECONDARY Part 2 (Cohort 3 and 4) - Accumulation Ratio of C(Tau) (R[CTAU]) |
6.584; 5.25 | — |
| SECONDARY Part 2 (Cohort 5) - Accumulation Ratio of C(Tau) (R[CTAU]) |
9.133 | — |
| SECONDARY Part 2 (Cohort 6) - Accumulation Ratio of C(Tau) (R[CTAU]) |
1.817 | — |
| SECONDARY Part 2 (Cohort 3 and 4) - Pre-dose Concentration of GSK3739937 |
37.1872; 57.1056 | — |
| SECONDARY Part 2 (Cohort 5) - Pre-dose Concentration of GSK3739937 |
114.9742 | — |
Eligibility Criteria
Inclusion Criteria
- Participant must be 18 to 55 years of age inclusive, at the time of signing the informed consent.
- Participants who are overtly healthy as determined by the investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring (history and ECG).
- Participants who are negative on two consecutive tests for severe acute respiratory syndrome coronavirus-2 (SARs-CoV-2), performed at Screening and on admission and (re-)admission to the Phase I unit, using an approved molecular test polymerase chain reaction (PCR).
- Participants who are able to understand and comply with protocol requirements and timetables, instructions, and protocol-stated restrictions.
- Body weight >=50.0 kilograms (kg) (110 pound [lbs]) for men and >=45.0 kg (99 lbs) for women and body mass index within the range 18.5 to 32.0 kilogram per square meter (kg/m^2).
- Male participants are eligible to participate if they agree to use contraceptive methods
- A female participant is eligible to participate if she is not pregnant or breastfeeding, and is not a woman of childbearing potential (WOCBP). - Capable of giving signed informed consent
Exclusion Criteria
- Signs and symptoms which in the opinion of the investigator are suggestive of coronavirus disease 2019 (COVID-19) (i.e. fever, cough etc) within 14 days of inpatient admission.
- Contact with known COVID-19 positive persons in the 14 days prior to inpatient admission.
- History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, distribution, metabolism, or elimination of drugs; constituting a risk when taking the study intervention or interfering with the interpretation of data.
- Pre-existing clinically relevant, in the opinion of the principal investigator (PI), gastro-intestinal pathology or diagnosis - e.g. irritable bowel syndrome, inflammatory bowel disease, and/or significant baseline signs and symptoms.
- Medical history of cardiac arrhythmias or cardiac disease or a family and personal history of long QT syndrome.
- Any known or suspected pre-existing psychiatric condition
- Any positive (abnormal) response confirmed by the investigator or clinician (or qualified designee) administered Columbia Suicide Severity Rating Scale (CSSRS) at screening .
- Any other clinical condition (including but not limited to active substance use) or prior therapy that, in the opinion of the Investigator, would make the participant unsuitable for the study; unable to comply with dosing requirements; or unable to comply with study visits; or a condition that could affect the absorption, distribution, metabolism or excretion of the drug.
- Estimated glomerular filtration rate (eGFR) 1.1 x upper limit of normal (ULN).
- Hemoglobin 1.1x ULN.
- Bilirubin >1.1 x ULN (isolated bilirubin >1.1 x ULN is acceptable if bilirubin is fractionated and direct bilirubin =3 consecutive ventricular ectopic beats), second-degree atrioventricular (AV) block Mobitz Type II, third-degree atrioventricular block, complete heart block, or conduction abnormality (including but not specific to left or right complete bundle branch; AV block [2nd degree or higher]; Wolff-Parkinson-White [WPW] syndrome), Sinus Pauses > 3 seconds, which, in the opinion of the investigator or ViiV Healthcare (VH)/ GlaxoSmithKline (GSK) Medical Monitor, will interfere with the safety for the individual participant.
- Exclusion criteria for Screening ECG. Heart rate 100 beats per minute (bpm) for males and 100 bpm for females; PR interval 220 millisecond (msec); QRS duration 120 msec; the Fridericia's QT correction formula (QTcF) interval >450 msec.
- Past or intended use of over-the-counter or prescription medication [including cytochrome p450 enzyme inducers or inhibitors, vitamins, herbal and dietary supplements ] within
Data sourced from ClinicalTrials.gov (NCT04493684). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.