Phase 1
Completed N=23
A Relative Bioavailability and Food-Effect Study of the Fixed Dose Combination of GSK3640254 and Dolutegravir (DTG) in Healthy Participants
Source: ClinicalTrials.gov NCT04857892 ↗Enrolled (actual)
23
Serious AEs
0.0%
Results posted
Mar 2024
Primary outcomePrimary: Part 1: Area Under the Plasma Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC[0-inf]) of GSK3640254 — 22.13; 21.93; 22.63 Hours*microgram per milliliter
Summary
This is a two part study to compare the relative bioavailability (BA) of 2 fixed dose combinations (FDCs) of GSK3640254/DTG with GSK3640254 and DTG administered together as single agents (Part 1) and to assess the effect of food on the pharmacokinetic (PK) of the selected FDC of GSK3640254/DTG (Part 2).
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Part 1: Area Under the Plasma Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC[0-inf]) of GSK3640254 |
22.13; 21.93; 22.63 | — |
| PRIMARY Part 1: Area Under the Plasma Concentration-time Curve From Time 0 to Time t (AUC[0-t]) of GSK3640254 |
17.62; 19.14; 18.69 | — |
| PRIMARY Part 1: Maximum Observed Concentration (Cmax) of GSK3640254 |
0.7382; 0.7610; 0.7579 | — |
| PRIMARY Part 1: AUC(0-inf) of DTG |
74.18; 82.13; 80.53 | — |
| PRIMARY Part 1: AUC(0-t) of DTG |
68.91; 77.89; 73.44 | — |
| PRIMARY Part 1: Cmax of DTG |
4.182; 4.432; 4.264 | — |
| PRIMARY Part 2: AUC(0-inf) of GSK3640254 |
21.39; 6.622 | — |
| PRIMARY Part 2: AUC(0-t) of GSK3640254 |
19.33; 6.027 | — |
| PRIMARY Part 2: Cmax of GSK3640254 |
0.6093; 0.2193 | — |
| PRIMARY Part 2: AUC(0-inf) of DTG |
85.07; 64.61 | — |
| PRIMARY Part 2: AUC(0-t) of DTG |
83.18; 63.17 | — |
| PRIMARY Part 2: Cmax of DTG |
4.000; 3.273 | — |
| SECONDARY Part 1: Number of Participants With Non-Serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAEs) |
0; 0; 1; 0; 0; 0 | — |
| SECONDARY Part 2: Number of Participants With Non-SAEs and SAEs |
1; 2; 0; 0 | — |
| SECONDARY Part 1: Absolute Values for Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets |
0.035; 0.036; 0.036; 0.036; 0.036; 0.037 | — |
| SECONDARY Part 2: Absolute Values for Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets |
0.046; 0.041; 0.038; 0.041; 0.051; 0.037 | — |
| SECONDARY Part 1: Absolute Values for Hematology Parameter: Hemoglobin |
139.8; 142.7; 138.8; 141.1; 143.1; 139.2 | — |
| SECONDARY Part 2: Absolute Values for Hematology Parameter: Hemoglobin |
139.8; 138.4; 141.0; 140.7; 143.1; 135.6 | — |
| SECONDARY Part 1: Absolute Values for Hematology Parameter: Erythrocytes Mean Corpuscular Volume |
86.45; 86.33; 86.94; 86.26; 86.51; 86.99 | — |
| SECONDARY Part 2: Absolute Values for Hematology Parameter: Erythrocytes Mean Corpuscular Volume |
84.55; 84.89; 84.30; 84.74; 84.33; 84.50 | — |
| SECONDARY Part 1: Absolute Values for Hematology Parameter: Erythrocytes |
4.757; 4.850; 4.686; 4.822; 4.855; 4.700 | — |
| SECONDARY Part 2: Absolute Values for Hematology Parameter: Erythrocytes |
4.914; 4.853; 4.958; 4.913; 4.976; 4.787 | — |
| SECONDARY Part 1: Absolute Values for Hematology Parameters: Hematocrit |
0.4110; 0.4181; 0.4070; 0.4156; 0.4195; 0.4087 | — |
| SECONDARY Part 2: Absolute Values for Hematology Parameters: Hematocrit |
0.4145; 0.4106; 0.4173; 0.4153; 0.4183; 0.4044 | — |
| SECONDARY Part 1: Absolute Values for Hematology Parameters: Erythrocytes Mean Corpuscular Hemoglobin |
29.37; 29.47; 29.65; 29.28; 29.51; 29.63 | — |
| SECONDARY Part 2: Absolute Values for Hematology Parameters: Erythrocytes Mean Corpuscular Hemoglobin |
28.51; 28.62; 28.49; 28.68; 28.84; 28.32 | — |
| SECONDARY Part 1: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets |
0.000; 0.000; 0.002; 0.003; 0.002; -0.007 | — |
| SECONDARY Part 2: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets |
-0.004; -0.001; -0.010; 0.003; 0.000; 0.008 | — |
| SECONDARY Part 1: Change From Baseline in Hematology Parameter: Hemoglobin |
1.2; 0.4; 0.4; 0.5; -2.7; -1.3 | — |
| SECONDARY Part 2: Change From Baseline in Hematology Parameter: Hemoglobin |
1.4; 2.2; -1.4; 1.2; -1.2; 1.7 | — |
| SECONDARY Part 1: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume |
-0.06; 0.18; 0.05; 0.32; 0.42; 0.13 | — |
| SECONDARY Part 2: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume |
-0.05; -0.16; -0.31; 0.13; -0.11; -0.13 | — |
| SECONDARY Part 1: Change From Baseline in Hematology Parameter: Erythrocytes |
0.052; 0.005; 0.014; 0.020; -0.097; -0.062 | — |
| SECONDARY Part 2: Change From Baseline in Hematology Parameter: Erythrocytes |
0.034; 0.061; -0.024; 0.027; -0.077; -0.003 | — |
| SECONDARY Part 1: Change From Baseline in Hematology Parameter: Hematocrit |
0.0042; 0.0013; 0.0017; 0.0027; -0.0067; -0.0048 | — |
| SECONDARY Part 2: Change From Baseline in Hematology Parameter: Hematocrit |
0.0029; 0.0047; -0.0038; 0.0040; -0.0074; -0.0007 | — |
| SECONDARY Part 1: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin |
-0.02; 0.04; -0.02; 0.05; 0.07; 0.17 | — |
| SECONDARY Part 2: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin |
0.07; 0.06; -0.13; 0.00; 0.21; 0.34 | — |
| SECONDARY Part 1: Absolute Values for Clinical Chemistry Parameters: Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Gamma Glutamyl Transferase (GGT), Lactate Dehydrogenase (LDH), Creatinine Kinase (CK) |
16.4; 19.1; 18.9; 16.3; 17.4; 18.4 | — |
| SECONDARY Part 2: Absolute Values of Clinical Chemistry Parameters: ALT, ALP, AST, GGT, LDH, CK |
18.9; 18.8; 18.6; 18.9; 18.5; 25.2 | — |
| SECONDARY Part 1: Absolute Values of Clinical Chemistry Parameters: Calcium, Carbon-dioxide (CO2), Chloride, Glucose, Potassium, Sodium, Urea Nitrogen, Phosphorus, Triglycerides, Cholesterol, and Anion Gap |
2.357; 2.366; 2.347; 2.371; 2.377; 2.379 | — |
| SECONDARY Part 2: Absolute Values of Clinical Chemistry Parameters: Calcium, CO2, Chloride, Glucose, Potassium, Sodium, Urea Nitrogen, Phosphorus, Triglycerides, Cholesterol, and Anion Gap |
2.356; 2.354; 2.343; 2.362; 2.315; 2.381 | — |
| SECONDARY Part 1: Absolute Values for Chemistry Parameters: Serum Lipase, Serum Amylase |
32.5; 34.6; 31.1; 32.1; 40.4; 34.2 | — |
| SECONDARY Part 2: Absolute Values for Chemistry Parameters: Serum Lipase, Serum Amylase |
32.1; 30.2; 30.5; 30.4; 28.6; 40.3 | — |
| SECONDARY Part 1: Absolute Values of Clinical Chemistry Parameters: Albumin, Globulin and Protein |
43.8; 43.8; 43.8; 44.6; 44.5; 44.5 | — |
| SECONDARY Part 2: Absolute Values of Clinical Chemistry Parameters: Albumin, Globulin and Protein |
42.9; 43.1; 43.3; 43.2; 44.4; 44.9 | — |
| SECONDARY Part 1: Absolute Values of Clinical Chemistry Parameters: Creatinine, Direct Bilirubin, Bilirubin, and Urate |
74.58; 77.79; 75.32; 82.89; 84.90; 81.47 | — |
| SECONDARY Part 2: Absolute Values of Clinical Chemistry Parameters: Creatinine, Direct Bilirubin, Bilirubin, and Urate |
81.02; 83.19; 88.29; 90.17; 85.31; 83.79 | — |
| SECONDARY Part 1: Change From Baseline in Chemistry Parameters: ALT, ALP, AST, GGT, LDH, CK |
-0.1; -1.7; -0.5; -1.7; -0.2; -3.0 | — |
| SECONDARY Part 2: Change From Baseline in Chemistry Parameters: ALT, ALP, AST, GGT, LDH, CK |
-0.7; 0.1; 1.1; 3.4; 1.6; 2.2 | — |
| SECONDARY Part 1: Change From Baseline in Clinical Chemistry Parameters: Calcium, CO2, Chloride, Glucose, Potassium, Sodium, Urea Nitrogen, Phosphorus, Triglycerides, Cholesterol, and Anion Gap |
0.014; 0.011; 0.033; -0.007; 0.013; 0.007 | — |
| SECONDARY Part 2: Change From Baseline in Clinical Chemistry Parameters: Calcium, CO2, Chloride, Glucose, Potassium, Sodium, Urea Nitrogen, Phosphorus, Triglycerides, Cholesterol, and Anion Gap |
-0.008; 0.007; -0.033; 0.019; -0.002; -0.007 | — |
| SECONDARY Part 1: Change From Baseline in Clinical Chemistry Parameters: Lipase and Amylase |
-0.4; 5.8; 3.2; 3.3; 1.3; 2.0 | — |
| SECONDARY Part 2: Change From Baseline in Clinical Chemistry Parameters: Lipase and Amylase |
-1.6; 0.3; 2.3; 5.3; -2.2; -0.1 | — |
| SECONDARY Part 1: Change From Baseline in Clinical Chemistry Parameters: Albumin, Globulin and Protein |
0.8; 0.7; 0.7; -0.8; 0.2; -0.2 | — |
| SECONDARY Part 2: Change From Baseline in Clinical Chemistry Parameters: Albumin, Globulin and Protein |
0.6; 0.2; 0.9; 1.6; 0.9; 0.4 | — |
| SECONDARY Part 1: Change From Baseline in Clinical Chemistry Parameters: Creatinine, Direct Bilirubin, Bilirubin, and Urate |
8.31; 7.12; 6.15; 3.10; 3.38; 1.92 | — |
| SECONDARY Part 2: Change From Baseline in Clinical Chemistry Parameters: Creatinine, Direct Bilirubin, Bilirubin, and Urate |
7.73; 6.97; 3.54; 1.28; 2.16; -0.98 | — |
| SECONDARY Part 1: Absolute Values for Urinalysis Parameter: Specific Gravity |
1.0138; 1.0168; 1.0153; 1.0137; 1.0150; 1.0151 | — |
| SECONDARY Part 2 : Absolute Values for Urinalysis Parameter: Specific Gravity |
1.0146; 1.0164; 1.0157; 1.0182; 1.0123; 1.0142 | — |
| SECONDARY Part 1: Absolute Values for Urinalysis Parameters: Potential of Hydrogen (pH) |
6.18; 5.95; 5.88; 6.16; 6.12; 6.20 | — |
| SECONDARY Part 1: Absolute Values for Urinalysis Parameter: Potential of Hydrogen |
6.12; 6.08; 6.12; 6.17; 6.13; 6.28 | — |
| SECONDARY Part 1: Number of Participants With Urinalysis Dipstick Results: Glucose |
22; 21; 20; 22; 21; 20 | — |
| SECONDARY Part 2: Number of Participants With Urinalysis Dipstick Results: Glucose |
17; 18; 17; 18; 8; 9 | — |
| SECONDARY Part 1: Number of Participants With Urinalysis Dipstick Results: Protein |
22; 21; 20; 22; 21; 20 | — |
| SECONDARY Part 2: Number of Participants With Urinalysis Dipstick Results: Protein |
17; 18; 17; 18; 8; 9 | — |
| SECONDARY Part 1: Number of Participants With Urinalysis Dipstick Results: Occult Blood |
20; 18; 18; 1; 2; 2 | — |
| SECONDARY Part 2: Number of Participants With Urinalysis Dipstick Results: Occult Blood |
15; 16; 1; 0; 0; 1 | — |
| SECONDARY Part 1: Number of Participants With Urinalysis Dipstick Results: Ketones |
22; 20; 20; 0; 1; 0 | — |
| SECONDARY Part 2: Number of Participants With Urinalysis Dipstick Results: Ketones |
17; 17; 0; 1; 17; 17 | — |
| SECONDARY Part 1: Number of Participants With Urinalysis Dipstick Results: Bilirubin and Nitrite |
22; 21; 20; 22; 21; 20 | — |
| SECONDARY Part 2: Number of Participants With Urinalysis Dipstick Results: Bilirubin and Nitrite |
17; 18; 17; 18; 8; 9 | — |
| SECONDARY Part 1: Number of Participants With Urinalysis Dipstick Results: Leukocyte Esterase |
21; 19; 20; 1; 2; 0 | — |
| SECONDARY Part 2: Number of Participants With Urinalysis Dipstick Results: Leukocyte Esterase |
17; 17; 0; 1; 15; 17 | — |
| SECONDARY Part 1: Change From Baseline in Urinalysis Parameter: Specific Gravity |
0.0000; -0.0017; -0.0002; 0.0033; 0.0043; 0.0030 | — |
| SECONDARY Part 2: Change From Baseline in Urinalysis Parameter: Specific Gravity |
0.0011; 0.0018; -0.0005; -0.0019; -0.0001; -0.0022 | — |
| SECONDARY Part 1: Change From Baseline for Urinalysis Parameter: Potential of Hydrogen |
-0.02; 0.17; 0.33; -0.58; -0.08; -0.08 | — |
| SECONDARY Part 2: Change From Baseline for Urinalysis Parameter: Potential of Hydrogen |
0.00; 0.08; 0.13; 0.11; -0.06; -0.06 | — |
| SECONDARY Part 1: Number of Participants With Worst Case Urine Parameter: Glucose Results by Maximum Grade Increase Post-Baseline Relative to Baseline |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Part 2: Number of Participants With Worst Case Urine Parameter: Glucose Results by Maximum Grade Increase Post-Baseline Relative to Baseline |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Part 1: Number of Participants With Worst Case Urine Parameter: Protein Results by Maximum Grade Increase Post-Baseline Relative to Baseline |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Part 2: Number of Participants With Worst Case Urine Parameter: Protein Results by Maximum Grade Increase Post-Baseline Relative to Baseline |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Part 1: Number of Participants With Worst Case Urine Parameter: Erythrocytes Results by Maximum Grade Increase Post-Baseline Relative to Baseline |
1; 0; 0; 0; 0; 0 | — |
| SECONDARY Part 2: Number of Participants With Worst Case Urine Parameter: Erythrocytes Results by Maximum Grade Increase Post-Baseline Relative to Baseline |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Part 1: Absolute Values of Electrocardiogram (ECG) Parameters: PR Interval, QRS Duration, QT Interval and QT Interval Corrected by Fridericia's Formula (QTcF) |
162.8; 162.8; 163.1; 159.0; 158.0; 157.7 | — |
| SECONDARY Part 2: Absolute Values of ECG Parameters: PR Interval, QRS Duration, QT Interval and QTcF |
168.8; 170.9; 160.6; 167.0; 162.6; 167.4 | — |
| SECONDARY Part 1: Change From Baseline in ECG Parameters: PR Interval, QRS Duration, QT Interval and QTcF Interval |
-3.8; -4.7; -5.5; -3.6; -2.8; -3.3 | — |
| SECONDARY Part 2: Change From Baseline in ECG Parameters: PR Interval, QRS Duration, QT Interval and QTcF Interval |
-8.1; -3.9; -6.1; -3.4; -6.5; -9.9 | — |
| SECONDARY Part 1: Absolute Values of Vital Sign Parameters: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) |
61.5; 63.2; 63.2; 60.9; 63.1; 63.0 | — |
| SECONDARY Part 2: Absolute Values of Vital Signs: DBP and SBP |
65.1; 65.7; 64.0; 62.9; 61.8; 61.1 | — |
| SECONDARY Part 1: Absolute Values of Vital Signs: Pulse Rate |
64.9; 66.06; 67.4; 61.7; 68.6; 64.8 | — |
| SECONDARY Part 2: Absolute Values of Vital Signs: Pulse Rate |
64.4; 64.2; 65.7; 67.3; 66.9; 69.1 | — |
| SECONDARY Part 1: Absolute Values of Vital Signs: Oral Temperature |
36.38; 36.43; 36.52; 36.47; 36.55; 36.60 | — |
| SECONDARY Part 2: Absolute Values of Vital Signs: Oral Temperature |
36.28; 36.30; 36.42; 36.33; 36.42; 36.32 | — |
| SECONDARY Part 1: Absolute Values of Vital Signs: Respiratory Rate |
14.1; 13.6; 13.9; 13.8; 13.8; 14.8 | — |
| SECONDARY Part 2: Absolute Values of Vital Signs: Respiratory Rate |
12.7; 12.9; 14.5; 13.9; 13.1; 13.8 | — |
| SECONDARY Part 1: Change From Baseline in Vital Signs: DBP and SBP |
-0.6; -0.1; 13.9; -2.4; -2.5; -2.4 | — |
| SECONDARY Part 2: Change From Baseline in Vital Signs: DBP and SBP |
-1.1; -2.8; -3.3; -4.6; -0.3; -1.8 | — |
| SECONDARY Part 1: Change From Baseline in Vital Signs: Pulse Rate |
-3.2; 2.6; -2.7; -0.7; -1.4; -2.8 | — |
| SECONDARY Part 2: Change From Baseline in Vital Signs: Pulse Rate |
1.3; 3.1; 2.5; 4.9; 7.0; 3.4 | — |
| SECONDARY Part 1: Change From Baseline in Vital Signs: Oral Temperature |
0.09; 0.11; 0.08; 0.15; 0.05; 0.11 | — |
| SECONDARY Part 2: Change From Baseline in Vital Signs: Oral Temperature |
0.14; 0.03; 0.14; 0.02; 0.12; 0.01 | — |
| SECONDARY Part 1: Change From Baseline in Vital Signs: Respiratory Rate |
-0.3; 0.2; 0.9; 0.9; -0.8; 0.5 | — |
| SECONDARY Part 2: Change From Baseline in Vital Signs: Respiratory Rate |
1.8; 1.0; 0.4; 0.9; -1.0; -1.3 | — |
Eligibility Criteria
Inclusion Criteria
- Participant must be 18 to 65 years of age inclusive, at the time of signing the informed consent.
- Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring (history and ECG).
- Participants capable of giving signed informed consent.
Exclusion Criteria
- Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- A pre-existing condition interfering with normal gastro intestinal anatomy or motility (for example [e.g.], gastroesophageal reflux disease, gastric ulcers, gastritis) or hepatic and/or renal function that could interfere with the absorption, metabolism, and/or excretion of the study intervention or render the participant unable to take oral study intervention.
- Prior cholecystectomy surgery (prior appendectomy is acceptable).
- Clinically significant illness, including viral syndromes within 3 weeks of dosing.
- Participant with known or suspected active Coronavirus disease (COVID)-19 infection or contact with an individual with known COVID-19, within 14 days of study enrollment.
- Current enrollment or past participation within the last 30 days before signing of consent in any other clinical study involving an investigational study intervention (including an investigational COVID vaccine) or any other type of medical research.
- Prior exposure to GSK3640254 or prior intolerance to DTG in this or another clinical study.
- Any positive (abnormal) response confirmed by the investigator on a screening clinician- or qualified designee-administered Columbia Suicide Severity Rating Scale (C-SSRS).
- Any significant arrhythmia or ECG finding (e.g., prior myocardial infarction in the past 3 months, symptomatic bradycardia, non-sustained or sustained atrial arrhythmias, non-sustained or sustained ventricular tachycardia, any degree of atrioventricular block, or conduction abnormality) which, in the opinion of the investigator or ViiV Healthcare (VH)/GlaxoSmithKline (GSK) medical monitor, will interfere with the safety for the individual participant.
Data sourced from ClinicalTrials.gov (NCT04857892). 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.