Phase 1
N=18
A Relative Bioavailability and Food-Effect Study of GSK3640254 Tablet and Capsule Formulations in Healthy Participants
HIV Infections
Bottom Line
View on ClinicalTrials.gov: NCT04263142 ↗Enrolled (actual)
18
Serious AEs
0.0%
Results posted
Mar 2021
Primary outcome: Primary: Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC[0 to Inf]) for GSK3640254-Part 1 — 36.94; 36.88 Hours*microgram per milliliter
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- GSK3640254 Tablet (Drug); GSK3640254 Capsule (Drug)
- Age
- Adult · 18+ yrs
- Sex
- All
- Sponsor
- ViiV Healthcare
- Primary completion
- Mar 2020
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC[0 to Inf]) for GSK3640254-Part 1 |
36.94; 36.88 | — |
| PRIMARY Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Time t (AUC[0 to t]) for GSK3640254-Part 1 |
33.72; 33.80 | — |
| PRIMARY Maximum Observed Concentration (Cmax) for GSK3640254-Part 1 |
1.201; 1.313 | — |
| PRIMARY Time of Maximum Observed Concentration for GSK3640254-Part 1 |
5.000; 4.000 | — |
| PRIMARY AUC(0 to Inf) for GSK3640254-Part 2 |
41.00; 13.46; 36.92 | — |
| PRIMARY AUC(0 to t) for GSK3640254-Part 2 |
37.91; 11.37; 34.08 | — |
| PRIMARY Cmax for GSK3640254-Part 2 |
1.425; 0.3544; 1.082 | — |
| PRIMARY Time of Maximum Observed Concentration for GSK3640254-Part 2 |
5.000; 4.000; 5.000 | — |
| SECONDARY Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)-Part 1 |
0; 1; 0; 0 | — |
| SECONDARY Number of Participants With AEs and SAEs-Part 2 |
0; 0; 5; 0; 0; 0 | — |
| SECONDARY Absolute Values of Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils and Platelets-Part 1 |
0.032; 0.032; 0.030; 0.030; 0.027; 0.030 | — |
| SECONDARY Absolute Values for Erythrocytes Count-Part 1 |
4.801; 4.801; 4.937; 4.983; 5.009; 5.061 | — |
| SECONDARY Absolute Values for Hemoglobin-Part 1 |
142.2; 142.2; 146.4; 148.3; 150.3; 150.3 | — |
| SECONDARY Absolute Values for Hematocrit-Part 1 |
0.4252; 0.4252; 0.4346; 0.4405; 0.4410; 0.4430 | — |
| SECONDARY Absolute Values for Erythrocyte Mean Corpuscular Volume-Part 1 |
88.80; 88.80; 88.21; 88.61; 88.17; 87.63 | — |
| SECONDARY Absolute Values for Erythrocyte Mean Corpuscular Hemoglobin-Part 1 |
29.68; 29.68; 29.69; 29.83; 30.08; 29.74 | — |
| SECONDARY Absolute Values of Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils and Platelets-Part 2 |
0.042; 0.042; 0.042; 0.041; 0.040; 0.043 | — |
| SECONDARY Absolute Values for Erythrocytes Count-Part 2 |
4.613; 4.613; 4.613; 4.893; 4.899; 4.850 | — |
| SECONDARY Absolute Values for Hemoglobin-Part 2 |
134.0; 134.0; 134.0; 140.6; 141.1; 140.0 | — |
| SECONDARY Absolute Values for Hematocrit-Part 2 |
0.4010; 0.4010; 0.4010; 0.4207; 0.4219; 0.4176 | — |
| SECONDARY Absolute Values for Erythrocyte Mean Corpuscular Volume-Part 2 |
86.98; 86.98; 86.98; 86.37; 86.52; 86.57 | — |
| SECONDARY Absolute Values for Erythrocyte Mean Corpuscular Hemoglobin-Part 2 |
29.05; 29.05; 29.05; 28.87; 28.92; 28.99 | — |
| SECONDARY Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils and Platelets-Part 1 |
-0.002; -0.002; -0.002; -0.004; 0.016; 0.022 | — |
| SECONDARY Change From Baseline in Erythrocytes Count-Part 1 |
0.136; 0.182; 0.253; 0.214 | — |
| SECONDARY Change From Baseline in Hemoglobin-Part 1 |
4.2; 6.1; 8.7; 7.6 | — |
| SECONDARY Change From Baseline in Hematocrit-Part 1 |
0.0094; 0.0153; 0.0189; 0.0147 | — |
| SECONDARY Change From Baseline in Erythrocyte Mean Corpuscular Volume-Part 1 |
-0.59; -0.19; -0.84; -0.96 | — |
| SECONDARY Change From Baseline in Erythrocyte Mean Corpuscular Hemoglobin-Part 1 |
0.01; 0.14; 0.26; 0.20 | — |
| SECONDARY Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils and Platelets-Part 2 |
-0.001; -0.003; 0.001; 0.000; 0.006; 0.000 | — |
| SECONDARY Change From Baseline in Erythrocytes Count-Part 2 |
0.256; 0.247; 0.237; 0.231; 0.172; 0.077 | — |
| SECONDARY Change From Baseline in Hemoglobin-Part 2 |
6.5; 6.3; 6.0; 7.0; 4.2; 2.4 | — |
| SECONDARY Change From Baseline in Hematocrit-Part 2 |
0.0187; 0.0182; 0.0166; 0.0179; 0.0106; 0.0046 | — |
| SECONDARY Change From Baseline in Erythrocyte Mean Corpuscular Volume-Part 2 |
-0.35; -0.28; -0.41; -0.06; -0.02; -0.33 | — |
| SECONDARY Change From Baseline in Erythrocyte Mean Corpuscular Hemoglobin-Part 2 |
-0.05; -0.05; -0.06; 0.10; 0.18; 0.13 | — |
| SECONDARY Absolute Values for Chemistry Parameters: Creatinine, Total Bilirubin, Direct Bilirubin and Urate-Part 1 |
78.68; 78.68; 80.87; 80.11; 79.57; 80.33 | — |
| SECONDARY Absolute Values for Chemistry Parameters: Calcium, Glucose, Potassium, Sodium, Chloride, Phosphate, Blood Urea Nitrogen (BUN), Triglycerides, Cholesterol, Anion Gap, Carbon Dioxide-Part 1 |
2.327; 2.327; 2.352; 2.378; 2.343; 2.313 | — |
| SECONDARY Absolute Values for Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Gamma-glutamyl Transferase (GGT), Creatine Kinase (CK), Lactate Dehydrogenase (LDH)-Part 1 |
22.1; 22.1; 21.8; 18.4; 20.6; 19.6 | — |
| SECONDARY Absolute Values for Chemistry Parameters: Albumin, Globulin and Protein-Part 1 |
43.7; 43.7; 43.8; 44.4; 45.1; 44.2 | — |
| SECONDARY Absolute Values for Chemistry Parameters: Amylase and Lipase-Part 1 |
43.3; 43.3; 46.7; 47.7; 44.3; 47.6 | — |
| SECONDARY Absolute Values for Chemistry Parameters: Creatinine, Total Bilirubin, Direct Bilirubin and Urate-Part 2 |
74.00; 74.00; 74.00; 81.95; 83.34; 80.18 | — |
| SECONDARY Absolute Values for Chemistry Parameters: Calcium, Glucose, Potassium, Sodium, Chloride, Phosphate, BUN, Triglycerides, Cholesterol, Anion Gap, Carbon Dioxide-Part 2 |
2.312; 2.312; 2.312; 2.408; 2.369; 2.390 | — |
| SECONDARY Absolute Values for Chemistry Parameters: ALT, ALP, AST, GGT, CK, LDH-Part 2 |
19.0; 19.0; 19.0; 14.4; 17.3; 16.8 | — |
| SECONDARY Absolute Values for Chemistry Parameters: Albumin, Globulin and Protein-Part 2 |
43.8; 43.8; 43.8; 45.6; 45.4; 45.7 | — |
| SECONDARY Absolute Values for Chemistry Parameters: Amylase and Lipase-Part 2 |
49.3; 49.3; 49.3; 48.3; 49.4; 50.1 | — |
| SECONDARY Change From Baseline Chemistry Parameters: Creatinine, Total Bilirubin, Direct Bilirubin and Urate-Part 1 |
2.19; 1.43; 3.64; -1.10; 0.89; 0.36 | — |
| SECONDARY Change From Baseline in Chemistry Parameters: Calcium, Glucose, Potassium, Sodium, Chloride, Phosphate, BUN, Triglycerides, Cholesterol, Anion Gap, Carbon Dioxide-Part 1 |
0.025; 0.051; 0.019; -0.016; -0.145; -0.281 | — |
| SECONDARY Change From Baseline in Chemistry Parameters: ALT, ALP, AST, GGT, CK, LDH-Part 1 |
-0.2; -3.6; 1.3; -5.3; -2.4; -2.5 | — |
| SECONDARY Change From Baseline in Chemistry Parameters: Albumin, Globulin and Protein-Part 1 |
0.1; 0.7; 0.9; 1.0; -0.6; 0.3 | — |
| SECONDARY Change From Baseline in Chemistry Parameters: Amylase and Lipase-Part 1 |
3.3; 4.3; 1.0; 4.2; 2.7; 2.2 | — |
| SECONDARY Change From Baseline in Chemistry Parameters: Creatinine, Total Bilirubin, Direct Bilirubin and Urate-Part 2 |
7.25; 7.41; 6.18; 10.10; 8.86; 7.19 | — |
| SECONDARY Change From Baseline in Chemistry Parameters: Calcium, Glucose, Potassium, Sodium, Chloride, Phosphate, BUN, Triglycerides, Cholesterol, Anion Gap, Carbon Dioxide-Part 2 |
0.098; 0.063; 0.078; 0.097; 0.068; 0.067 | — |
| SECONDARY Change From Baseline in Chemistry Parameters: ALT, ALP, AST, GGT, CK, LDH-Part 2 |
-4.9; -2.5; -2.2; -9.7; -3.4; 5.7 | — |
| SECONDARY Change From Baseline in Chemistry Parameters: Albumin, Globulin and Protein-Part 2 |
2.0; 1.8; 1.9; 3.4; 1.8; 1.1 | — |
| SECONDARY Change From Baseline in Chemistry Parameters: Amylase and Lipase-Part 2 |
0.7; 1.8; 0.8; 4.4; -1.8; -4.4 | — |
| SECONDARY Absolute Values for Urine Parameter: Specific Gravity-Part 1 |
1.0120; 1.0120; 1.0152; 1.0158; 1.0201; 1.0161 | — |
| SECONDARY Absolute Values for Urine Parameter: Urobilinogen-Part 1 |
4.1384; 4.1384; 3.3860; 4.1384; 3.3860; 3.3860 | — |
| SECONDARY Absolute Values for Urine Parameter: Potential of Hydrogen (pH)-Part 1 |
6.03; 6.03; 6.14; 6.25; 5.72; 5.89 | — |
| SECONDARY Absolute Values for Urine Parameter: Specific Gravity-Part 2 |
1.0080; 1.0080; 1.0080; 1.0166; 1.0151; 1.0163 | — |
| SECONDARY Absolute Values for Urine Parameter: Urobilinogen-Part 2 |
4.6759; 4.6759; 4.6759; 4.0632; 3.3860; 3.3860 | — |
| SECONDARY Absolute Values for Urine Parameter: pH-Part 2 |
6.36; 6.36; 6.36; 6.15; 6.08; 6.10 | — |
| SECONDARY Change From Baseline in Urine Parameter: Specific Gravity-Part 1 |
0.0032; 0.0038; 0.0088; 0.0034 | — |
| SECONDARY Change From Baseline in Urine Parameter: Urobilinogen-Part 1 |
-0.7524; 0.0000; 0.0000; -1.5049 | — |
| SECONDARY Change From Baseline in Urine Parameter: pH-Part 1 |
0.11; 0.22; -0.17; -0.28 | — |
| SECONDARY Change From Baseline in Urine Parameter: Specific Gravity-Part 2 |
0.0084; 0.0066; 0.0083; 0.0109; 0.0140; 0.0091 | — |
| SECONDARY Change From Baseline in Urine Parameter: Urobilinogen-Part 2 |
-0.6772; -1.4275; -1.2899; 0.0000; -2.7088; 1.9349 | — |
| SECONDARY Change From Baseline in Urine Parameter: pH-Part 2 |
-0.18; -0.18; -0.26; -0.43; -0.80; 0.07 | — |
| SECONDARY Number of Participants With Abnormal Urine Dipstick Results-Part 1 |
0; 1; 1; 0; 0; 1 | — |
| SECONDARY Number of Participants With Abnormal Urine Dipstick Results-Part 2 |
1; 0; 0; 0; 0; 1 | — |
| SECONDARY Absolute Values of Electrocardiogram (ECG) Parameters: PR Interval, QRS Duration, QT Interval and QT Interval Corrected by Fridericia's Formula (QTcF)-Part 1 |
164.1; 162.3; 166.3; 158.7; 160.6; 158.9 | — |
| SECONDARY Absolute Values of ECG Parameters: PR Interval, QRS Duration, QT Interval and QTcF Interval-Part 2 |
166.4; 166.2; 166.8; 163.9; 166.8; 161.7 | — |
| SECONDARY Change From Baseline in ECG Parameters: PR Interval, QRS Duration, QT Interval and QTcF Interval-Part 1 |
2.2; -3.6; -3.6; -3.3; -0.9; 3.2 | — |
| SECONDARY Change From Baseline in ECG Parameters: PR Interval, QRS Duration, QT Interval and QTcF Interval-Part 2 |
-2.5; 0.7; -5.0; -1.2; -0.4; -4.2 | — |
| SECONDARY Absolute Values for Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)-Part 1 |
118.3; 117.4; 113.8; 115.1; 113.6; 113.3 | — |
| SECONDARY Absolute Values for Vital Sign: Pulse Rate-Part 1 |
65.7; 66.2; 66.7; 68.4; 67.4; 68.6 | — |
| SECONDARY Absolute Values for Vital Sign: Respiratory Rate-Part 1 |
14.0; 14.9; 13.1; 13.9; 14.7; 15.2 | — |
| SECONDARY Absolute Values for Vital Sign: Temperature-Part 1 |
36.24; 36.37; 36.22; 36.39; 36.33; 36.22 | — |
| SECONDARY Absolute Values for Vital Signs: DBP and SBP-Part 2 |
120.8; 115.2; 117.4; 117.4; 116.6; 115.7 | — |
| SECONDARY Absolute Values for Vital Sign: Pulse Rate-Part 2 |
65.4; 64.1; 63.8; 66.9; 64.0; 64.1 | — |
| SECONDARY Absolute Values for Vital Sign: Respiratory Rate-Part 2 |
14.8; 15.3; 13.8; 14.3; 15.4; 14.2 | — |
| SECONDARY Absolute Values for Vital Sign: Temperature-Part 2 |
36.24; 36.50; 36.37; 36.29; 36.40; 36.27 | — |
| SECONDARY Change From Baseline in Vital Signs: SBP and DBP-Part 1 |
-4.5; -2.3; -4.7; -4.1; -6.1; -3.4 | — |
| SECONDARY Change From Baseline in Vital Sign: Pulse Rate-Part 1 |
1.1; 2.2; 1.8; 2.4; 1.7; -0.6 | — |
| SECONDARY Change From Baseline in Vital Sign: Respiratory Rate-Part 1 |
-1.1; -0.8; 0.6; 0.3; -0.1; -0.2 | — |
| SECONDARY Change From Baseline in Vital Sign: Temperature-Part 1 |
-0.03; 0.02; 0.09; -0.15; 0.13; -0.02 | — |
| SECONDARY Change From Baseline in Vital Signs: SBP and DBP-Part 2 |
-3.5; 1.5; -1.7; -5.1; 2.1; -0.9 | — |
| SECONDARY Change From Baseline in Vital Sign: Pulse Rate-Part 2 |
1.5; -0.1; 0.3; 1.3; 0.9; 3.7 | — |
| SECONDARY Change From Baseline in Vital Sign: Respiratory Rate-Part 2 |
-0.5; 0.1; 0.4; 0.2; -0.7; 0.4 | — |
| SECONDARY Change From Baseline in Vital Sign: Temperature-Part 2 |
0.05; -0.10; -0.10; 0.09; -0.13; -0.08 | — |
| SECONDARY Lag Time for Absorption (Tlag) for GSK3640254-Part 1 |
0.528; 0.139 | — |
| SECONDARY Apparent Terminal Phase Half-life (t1/2) for GSK3640254-Part 1 |
26.247; 26.185 | — |
| SECONDARY Apparent Oral Clearance (CL/F) for GSK3640254-Part 1 |
5.413; 5.423 | — |
| SECONDARY Apparent Volume of Distribution (Vz/F) for GSK3640254-Part 1 |
205.0; 204.9 | — |
| SECONDARY Plasma Concentration of GSK3640254-Part 1 |
1.910; 1.580; 6.795; 81.90; 26.40; 291.0 | — |
| SECONDARY Tlag for GSK3640254-Part 2 |
0.050; 0.000; 0.048 | — |
| SECONDARY T1/2 for GSK3640254-Part 2 |
24.921; 25.669; 24.833 | — |
| SECONDARY CL/F for GSK3640254-Part 2 |
4.878; 14.85; 5.417 | — |
| SECONDARY Vz/F for GSK3640254-Part 2 |
175.4; 550.1; 194.1 | — |
| SECONDARY Plasma Concentration of GSK3640254-Part 2 |
6.370; 0; NA; 39.25; 38.70; 92.30 | — |
Summary
This is an open-label, 2 part, single-dose and crossover study conducted to assess the relative bioavailability of a tablet compared to a capsule of GSK3640254 and to assess the effect of food on the GSK3640254 tablet in healthy participants. This study will also evaluate the effect of food (fasted, moderate fat meal, and high fat meal) on the pharmacokinetics of the GSK3640254 mesylate tablet formulation. In Part 1, participants will be randomly assigned to 1 of 2 treatment sequences (AB or BA) in two sequential treatment periods; and in Part 2, participants will be randomly assigned to 1 of 3 treatment sequences (CDE, DEC, or ECD) in three sequential treatment periods. Participants will be randomized to receive a single dose of GSK3640254 200 milligram (mg) capsules under moderate fat conditions and GSK3640254 200 mg tablets under moderate fat, fasted and high fat conditions in each treatment period. Approximately 30 participants will be enrolled.
Eligibility Criteria
Inclusion Criteria
- Participants must be 18 to 55 years of age inclusive, at the time of signing the informed consent.
- Participants who are 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).
- Body weight >=50.0 kilogram (kg) (110 pounds [lbs]) for men and >=45.0 kg (99 lbs) for women and body mass index within the range 18.5 to 31.0 kg per square meter (kg/m^2) (inclusive).
- Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Male participants: Males shall not engage in intercourse while confined in the clinic. There is no need for an extended period of double barrier use or prolonged abstinence after study discharge. Female participants: 1. A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least 1 of the following conditions applies: a. not a woman of childbearing potential (WOCBP); or Is a WOCBP and using a nonhormonal contraceptive method that is highly effective, with a failure rate of 6 months) outpatient treatment. Participants with other conditions such as adjustment disorder or dysthymia that have required shorter term medical therapy ( 1.5 times upper limit of normal (ULN). A single repeat of ALT is allowed within a single Screening period to determine eligibility.
- Bilirubin >1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin 100 beats per minute and QTcF interval: >450 millisecond.
- History of regular alcohol consumption within 6 months of the study defined as an average weekly intake of >14 units. One unit is equivalent to 8 grams of alcohol: a half pint (approximately 240 mL) of beer, 1 glass (125 mL) of wine, or 1 (25 mL) measure of spirits.
- Unable to refrain from tobacco or nicotine-containing products within 3 months prior to Screening.
- History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates their participation.
Data sourced from ClinicalTrials.gov (NCT04263142). 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.