Phase 1
Completed N=16
Study to Evaluate the Effect of GSK3640254 on the Pharmacokinetics of Tenofovir Alafenamide/Emtricitabine
Source: ClinicalTrials.gov NCT03836729 ↗Enrolled (actual)
16
Serious AEs
0.0%
Results posted
Apr 2020
Primary outcomePrimary: Period 1: Area Under the Plasma Concentration-time Curve From Time 0 to the End of the Dosing Interval at Steady State (AUC [0-tau]) of TAF — 250.4 Hours*nanogram per milliliter
Summary
Human immunodeficiency virus (HIV) infection frequently involves combination drug therapy for its treatment; hence, it is important to understand their interactions and resulting changes in exposure which are associated with medications. This is a Phase-1, open-label, fixed-sequence 2-period, one-way drug interaction study to assess the pharmacokinetic (PK), safety, and tolerability of GSK3640254 and Tenofovir alafenamide/emtricitabine (TAF/FTC) when administered alone and in combination in healthy subjects. The study will consist of a screening period of 28 days before the first dose of study intervention followed by 2 sequential treatment periods. Subjects will be administered TAF/FTC 25/200 milligram (mg) once daily (QD) on Days 1 to 14 of Period 1 followed by co-administration of TAF/FTC 25/200 mg QD with GSK3640254 200 mg QD on Days 1 to 7 of Period 2.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Period 1: Area Under the Plasma Concentration-time Curve From Time 0 to the End of the Dosing Interval at Steady State (AUC [0-tau]) of TAF |
250.4 | — |
| PRIMARY Period 2: AUC (0-tau) of TAF |
215.4 | — |
| PRIMARY Period 1: Maximum Observed Concentration (Cmax) of TAF |
203.4 | — |
| PRIMARY Period 2: Cmax of TAF |
175.1 | — |
| PRIMARY Period 1: AUC (0-tau) of FTC |
9787.5 | — |
| PRIMARY Period 2: AUC (0-tau) of FTC |
9421.0 | — |
| PRIMARY Period 1:Cmax of FTC |
1811 | — |
| PRIMARY Period 2:Cmax of FTC |
1701 | — |
| PRIMARY Period 1: Plasma Concentration at the End of the Dosing Interval (Ctau) of FTC |
71.81 | — |
| PRIMARY Period 2: Ctau of FTC |
82.92 | — |
| PRIMARY Period 1: AUC (0-tau) of Tenofovir (TFV) |
221.9 | — |
| PRIMARY Period 2: AUC (0-tau) of TFV |
229.1 | — |
| PRIMARY Period 1: Cmax of TFV |
13.14 | — |
| PRIMARY Period 2: Cmax of TFV |
13.30 | — |
| PRIMARY Period 1: Ctau of TFV |
7.688 | — |
| PRIMARY Period 2: Ctau of TFV |
8.244 | — |
| SECONDARY Number of Participants With Non-serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAE) |
9; 3; 0; 0 | — |
| SECONDARY Period 1: Change From Baseline in Hematology Parameter of Platelet Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils and Basophils |
-0.005; -0.006; -0.021; -0.020; 0.014; 0.049 | — |
| SECONDARY Period 2: Change From Baseline in Hematology Parameter of Platelet Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils and Basophils |
-0.004; -0.002; 0.003; -0.023; -0.039; -0.043 | — |
| SECONDARY Period 1: Absolute Values of the Hematology Parameter of Platelet Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils and Basophils |
0.046; 0.041; 0.040; 0.225; 0.204; 0.205 | — |
| SECONDARY Period 2: Absolute Values of the Hematology Parameter of Platelet Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils and Basophils |
0.040; 0.036; 0.038; 0.043; 0.208; 0.185 | — |
| SECONDARY Period 1: Change From Baseline in Hematology Parameter of Hematocrit |
0.0121; 0.0189 | — |
| SECONDARY Period 2: Change From Baseline in Hematology Parameter of Hematocrit |
-0.0147; -0.0007; -0.0204 | — |
| SECONDARY Period 1: Absolute Values of the Hematology Parameter: Hematocrit |
0.4264; 0.4384; 0.4453 | — |
| SECONDARY Period 2: Absolute Values of the Hematology Parameter: Hematocrit |
0.4453; 0.4306; 0.4444; 0.4247 | — |
| SECONDARY Period 1: Change From Baseline in Hematology Parameter of Hemoglobin |
6.1; 8.4 | — |
| SECONDARY Period 2: Change From Baseline in Hematology Parameter of Hemoglobin |
-3.9; -1.1; -6.4 | — |
| SECONDARY Period 1: Absolute Values of the Hematology Parameter: Hemoglobin |
142.0; 148.1; 150.4 | — |
| SECONDARY Period 2: Absolute Values of the Hematology Parameter: Hemoglobin |
150.4; 146.4; 149.1; 143.9 | — |
| SECONDARY Period 1: Change From Baseline in Hematology Parameter of Mean Corpuscle Hemoglobin (MCH) |
0.13; 0.36 | — |
| SECONDARY Period 2: Change From Baseline in Hematology Parameter of MCH |
-0.11; -0.21; -0.17 | — |
| SECONDARY Period 1: Absolute Values of the Hematology Parameter: MCH |
28.63; 28.75; 28.98 | — |
| SECONDARY Period 2: Absolute Values of the Hematology Parameter: MCH |
28.98; 28.88; 28.83; 28.87 | — |
| SECONDARY Period 1: Change From Baseline in Hematology Parameter of Mean Corpuscle Volume (MCV) |
-0.83; -0.07 | — |
| SECONDARY Period 2: Change From Baseline in Hematology Parameter of MCV |
-1.02; -0.17; -0.82 | — |
| SECONDARY Period 1: Absolute Values of the Hematology Parameter: MCV |
85.92; 85.09; 85.85 | — |
| SECONDARY Period 2: Absolute Values of the Hematology Parameter: MCV |
85.85; 84.83; 85.85; 85.20 | — |
| SECONDARY Period 1: Change From Baseline in Hematology Parameter of Erythrocytes |
0.189; 0.226 | — |
| SECONDARY Period 2: Change From Baseline in Hematology Parameter of Erythrocytes |
-0.113; 0.000; -0.189 | — |
| SECONDARY Period 1: Absolute Values of the Hematology Parameter: Erythrocytes |
4.977; 5.166; 5.203 | — |
| SECONDARY Period 2: Absolute Values of the Hematology Parameter: Erythrocytes |
5.203; 5.090; 5.190; 5.001 | — |
| SECONDARY Period 1: Change From Baseline in Clinical Chemistry Parameter of Glucose, Anion Gap, Cholesterol, Calcium, Potassium, Sodium, Blood Urea Nitrogen (BUN), Carbon Dioxide (CO2), Chloride and Phosphorus |
-0.160; -0.320; -0.004; -0.389; 1.9; 2.2 | — |
| SECONDARY Period 2: Change From Baseline in Clinical Chemistry Parameter of Glucose, Anion Gap, Cholesterol, Calcium, Potassium, Sodium, BUN, CO2, Chloride and Phosphorus |
0.236; 0.315; 0.136; 0.011; 0.102; 0.030 | — |
| SECONDARY Period 1: Absolute Values of Clinical Chemistry Parameter of Glucose, Anion Gap, Cholesterol, Calcium, Potassium, Sodium, BUN, CO2, Chloride and Phosphorus |
5.111; 4.951; 4.791; 4.253; 4.249; 3.864 | — |
| SECONDARY Period 2: Absolute Values of Clinical Chemistry Parameter of Glucose, Anion Gap, Cholesterol, Calcium, Potassium, Sodium, BUN, CO2, Chloride and Phosphorus |
4.791; 5.027; 5.129; 4.950; 3.864; 3.875 | — |
| SECONDARY Period 1: Change From Baseline in Clinical Chemistry Parameter of Alkaline Phosphatase, Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH), Gamma-glutamyl Transferase (GGT), and Creatine Phosphokinase (CK) |
-2.6; 2.4; -6.2; -6.9; -2.1; -6.2 | — |
| SECONDARY Period 2: Change From Baseline in Clinical Chemistry Parameter of Alkaline Phosphatase, ALT, AST, LDH, GGT, and CK |
3.7; 2.6; -1.0; -1.4; -0.5; -0.1 | — |
| SECONDARY Period 1: Absolute Values of Clinical Chemistry Parameter of Alkaline Phosphatase, ALT, AST, LDH, GGT, and CK |
60.9; 58.3; 63.4; 24.6; 18.4; 17.6 | — |
| SECONDARY Period 2: Absolute Values of Clinical Chemistry Parameter of Alkaline Phosphatase, ALT, AST, LDH, GGT, and CK |
63.4; 67.1; 65.4; 61.8; 17.6; 16.2 | — |
| SECONDARY Period 1: Change From Baseline in Clinical Chemistry Parameter of Lipase and Amylase |
-2.3; -2.8; -4.0; -5.3 | — |
| SECONDARY Period 2: Change From Baseline in Clinical Chemistry Parameter of Lipase and Amylase |
3.3; -1.9; 1.1; 7.7; 0.0; 3.5 | — |
| SECONDARY Period 1: Absolute Values of Chemistry Parameters of Lipase and Amylase |
56.4; 54.1; 53.6; 22.2; 18.2; 16.9 | — |
| SECONDARY Period 2: Absolute Values of Chemistry Parameters of Lipase and Amylase |
53.6; 56.8; 52.7; 55.7; 16.9; 24.6 | — |
| SECONDARY Period 1: Change From Baseline in Clinical Chemistry Parameter of Total Bilirubin, Direct Bilirubin, and Creatinine |
5.69; 7.36; 2.25; 2.10; 0.15; 0.64 | — |
| SECONDARY Period 2: Change From Baseline in Clinical Chemistry Parameter of Total Bilirubin, Direct Bilirubin, and Creatinine |
-2.34; 3.53; 0.28; -0.82; -0.26; -1.91 | — |
| SECONDARY Period 1: Absolute Values of Clinical Chemistry Parameter of Total Bilirubin, Direct Bilirubin, and Creatinine |
80.16; 85.85; 87.52; 9.64; 11.89; 11.74 | — |
| SECONDARY Period 2: Absolute Values of Clinical Chemistry Parameter of Total Bilirubin, Direct Bilirubin, and Creatinine |
87.52; 85.18; 91.53; 88.27; 11.44; 10.62 | — |
| SECONDARY Period 1: Change From Baseline in Clinical Chemistry Parameter of Total Protein, Albumin and Globulin |
2.6; 2.9; 2.5; 2.8; 0.1; 0.1 | — |
| SECONDARY Period 2: Change From Baseline in Clinical Chemistry Parameter of Total Protein, Albumin and Globulin |
0.1; 3.1; 0.8; 0.2; 2.3; 0.2 | — |
| SECONDARY Period 1: Absolute Values of Clinical Chemistry Parameter of Total Protein, Albumin and Globulin |
69.8; 72.4; 72.6; 25.9; 28.4; 28.7 | — |
| SECONDARY Period 2: Absolute Values of Clinical Chemistry Parameter of Total Protein, Albumin and Globulin |
72.6; 72.8; 75.7; 73.3; 28.7; 28.9 | — |
| SECONDARY Period 1: Change From Baseline in Specific Gravity of Urine |
0.0007; 0.0011 | — |
| SECONDARY Period 2: Change From Baseline in Specific Gravity of Urine |
0.0031; 0.0024; 0.0005 | — |
| SECONDARY Period 1: Absolute Values of Specific Gravity of Urine |
1.0136; 1.0143; 1.0147 | — |
| SECONDARY Period 2: Absolute Values of Specific Gravity of Urine |
1.0147; 1.0178; 1.0170; 1.0151 | — |
| SECONDARY Period 1: Change From Baseline in Potential of Hydrogen (pH) of Urine |
-0.34; -0.19 | — |
| SECONDARY Period 2: Change From Baseline in pH of Urine |
0.19; 0.10; 0.10 | — |
| SECONDARY Period 1: Absolute Values of pH of Urine |
6.22; 5.88; 6.03 | — |
| SECONDARY Period 2: Absolute Values of pH of Urine |
6.03; 6.22; 6.07; 6.07 | — |
| SECONDARY Period 1: Change From Baseline in Urine Urobilinogen |
-2.5395; -2.5395 | — |
| SECONDARY Period 2: Change From Baseline in Urine Urobilinogen |
0.0000; 0.0000; 0.0000 | — |
| SECONDARY Period 1: Absolute Values of Urine Urobilinogen |
5.9255; 3.3860; 3.3860 | — |
| SECONDARY Period 2: Absolute Values of Urine Urobilinogen |
3.3860; 3.3860; 3.3860; 3.3860 | — |
| SECONDARY Period 1: Change From Baseline in Heart Rate |
1.5; -3.3 | — |
| SECONDARY Period 2: Change From Baseline in Heart Rate |
5.0; 2.8; -0.5; 3.3; -0.3; 0.3 | — |
| SECONDARY Period 1: Absolute Values of Heart Rate |
67.6; 69.1; 64.4 | — |
| SECONDARY Period 2: Absolute Values of Heart Rate |
66.5; 71.5; 69.3; 65.1; 68.9; 65.3 | — |
| SECONDARY Period 1: Change From Baseline in ECG Parameters: PR Interval, QRS Duration, QT Interval, Fridericia QT Correction Formula (QTcF) Interval, and Bazett QT Correction Formula (QTcB) Interval |
1.5; -1.9; -1.1; 0.3; -7.5; 5.8 | — |
| SECONDARY Period 2: Change From Baseline in ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF Interval, and QTcB Interval |
-6.8; -3.7; -0.5; -6.9; -3.9; -2.7 | — |
| SECONDARY Period 1: Absolute Values of ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF Interval, and QTcB Interval |
161.3; 162.8; 159.4; 91.0; 89.9; 91.3 | — |
| SECONDARY Period 2: Absolute Values of ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF Interval, and QTcB Interval |
167.3; 160.4; 163.6; 167.1; 160.7; 163.7 | — |
| SECONDARY Period 1: Change From Baseline in Temperature |
-0.16; -0.15; -0.09; -0.15; -0.24 | — |
| SECONDARY Period 2: Change From Baseline in Temperature |
-0.10; -0.07; -0.01; 0.07 | — |
| SECONDARY Period 1: Absolute Values of Temperature |
36.49; 36.33; 36.34; 36.41; 36.34; 36.25 | — |
| SECONDARY Period 2: Absolute Values of Temperature |
36.49; 36.37; 36.40; 36.46; 36.53 | — |
| SECONDARY Period 1: Change From Baseline in Pulse Rate |
-1.2; -3.8; -4.0; -1.6; -7.6 | — |
| SECONDARY Period 2: Change From Baseline in Pulse Rate |
2.4; 1.9; -0.3; 9.5 | — |
| SECONDARY Period 1: Absolute Values of Pulse Rate |
73.9; 72.8; 70.1; 69.9; 72.3; 66.3 | — |
| SECONDARY Period 2: Absolute Values of Pulse Rate |
70.5; 71.9; 71.4; 69.2; 79.0 | — |
| SECONDARY Period 1: Change From Baseline in Respiratory Rate |
-1.5; -0.5; -0.5; 1.3; 0.6 | — |
| SECONDARY Period 2: Change From Baseline in Respiratory Rate |
-3.2; -2.4; -0.8; -1.5 | — |
| SECONDARY Period 1: Absolute Values of Respiratory Rate |
14.0; 12.5; 13.5; 13.5; 15.3; 14.6 | — |
| SECONDARY Period 2: Absolute Values of Respiratory Rate |
15.6; 12.5; 13.3; 14.9; 14.3 | — |
| SECONDARY Period 1: Change From Baseline in Blood Pressure |
1.4; -1.8; -2.7; -2.3; 0.8; 0.1 | — |
| SECONDARY Period 2: Change From Baseline in Blood Pressure |
-0.3; 1.1; -1.7; 4.1; 0.1; 3.7 | — |
| SECONDARY Period 1: Absolute Values of Blood Pressure |
123.3; 124.7; 121.5; 120.6; 121.0; 124.1 | — |
| SECONDARY Period 2: Absolute Values of Blood Pressure |
120.4; 119.3; 120.8; 117.9; 123.7; 74.4 | — |
| SECONDARY Period 2: AUC (0-tau) of GSK3640254 |
24.53 | — |
| SECONDARY Period 2: Cmax of GSK3640254 |
1.411 | — |
| SECONDARY Period 2: Ctau of GSK3640254 |
0.7883 | — |
| SECONDARY Period 2: Time of Maximum Observed Concentration (Tmax) of GSK3640254 |
5.000 | — |
| SECONDARY Period 1: Tmax of TAF |
1.00 | — |
| SECONDARY Period 2: Tmax of TAF |
1.000 | — |
| SECONDARY Period 1: Tmax of FTC |
1.500 | — |
| SECONDARY Period 2: Tmax of FTC |
1.500 | — |
| SECONDARY Period 1: Tmax of TFV |
3.000 | — |
| SECONDARY Period 2: Tmax of TFV |
3.000 | — |
Eligibility Criteria
Inclusion Criteria
- Subject must be 18 to 55 years of age inclusive, at the time of signing the informed consent.
- Subjects 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 kilograms (kg) (110 pound [lbs]) for men and >=45.0 kilograms [kg] (99 lbs) for women and body mass index (BMI) within the range 18.5 to 31.0 kilograms per meter square (kg/m^2) (inclusive).
- Male or female; A female subject is eligible to participate if she is not pregnant, not breastfeeding and not a woman of childbearing potential (WOCBP).
- Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and protocol.
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 gastrointestinal (GI) anatomy or motility (e.g.,gastroesophageal reflux disease, gastric ulcers, gastritis), hepatic and/or renal function, that could interfere with the absorption, metabolism and/or excretion of the study drugs or render the subject unable to take oral study intervention.
- Any history of significant underlying psychiatric disorder including, but not limited to, schizophrenia, bipolar disorder with or without psychotic symptoms, other psychotic disorders, or schizotypal (personality) disorder.
- Any history of major depressive disorder with or without suicidal features or anxiety disorders, that required medical intervention (pharmacologic or not) such as hospitalization or other inpatient treatment and/or chronic (>6 months) outpatient treatment. Subjects with other conditions such as adjustment disorder or dysthymia that have required shorter term medical therapy ( 1.5 × upper limit of normal (ULN). A single repeat of ALT is allowed within a single screening period to determine eligibility.
- Bilirubin >1.5 × ULN (isolated bilirubin >1.5 × ULN is acceptable if bilirubin is fractionated and direct bilirubin 100 beats per minute (bpm) and for females: 100 bpm; PR interval: 200 milliseconds (msec); QRS duration: 110 msec and QTcF interval for male: >450 msec and for female: >470 msec. A heart rate from 100 to 110 bpm can be rechecked by ECG or vital signs within 30 minutes to verify eligibility.
- 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 (equivalent to 240 mL) of beer, 1 glass (125 mL) of wine, or 1 (25 mL) measure of spirits.
- Regular use of 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 (NCT03836729). 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.