HIV InfectionsPhase 1NCT03836729
Study to Evaluate the Effect of GSK3640254 on the Pharmacokinetics of Tenofovir Alafenamide/Emtricitabine
A Phase 1 study testing Tenofovir alafenamide/emtricitabine and GSK3640254 in people with HIV Infections, run by ViiV Healthcare at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- HIV Infections
- What is being tested?
- Tenofovir alafenamide/emtricitabine and GSK3640254
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- 11 Feb 2019to 30 Apr 2019
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- 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 (<6 months) without inpatient treatment and are currently well-controlled clinically or resolved may be considered for entry after discussion and agreement with the ViiV Medical Monitor.
- Any pre-existing physical or other psychiatric condition (including alcohol or drug abuse), which, in the opinion of the investigator (with or without psychiatric evaluation), could interfere with the subject's ability to comply with the dosing schedule and protocol evaluations or which might compromise the safety of the subject.
- Medical history of cardiac arrhythmias or cardiac disease or a family or personal history of long QT syndrome.
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- History of any kidney disease or current or chronic history of impaired renal function as indicated by an estimated creatinine clearance <80 milliliters per minute (mL/min). Creatinine clearance (CrCL) is estimated by either of the following methods: (a) The Modification of Diet in Renal Disease (MDRD) equation: estimated glomerular filtration rate (eGFR) (milliliter [mL]/minute [min]/1.73 meter square [m^2]) = 175 x (SCr)^-1.154 x (Age)^-0.203 x 0.742 [if female] x 1.212 [if African American] glomerular filtration rate (GFR) is expressed in mL/min/1.73 m^2, SCr is serum creatinine expressed in milligrams per deciliter (mg/dL), and age is expressed in years. (b)The Cockcroft-Gault equation: CrCL(mL/min) ={((l40-age) x weight)/(72xSCr)}x 0.85 (if female) CrCL is expressed in mL/min, age is expressed in years, weight is expressed in kg, and SCr is serum creatinine expressed in mg/dL.
- Presence of Hepatitis B surface antigen (HBsAg) at Screening or within 3 months prior to starting study intervention.
- Positive Hepatitis C antibody test result at Screening or within 3 months prior to starting study intervention AND positive on reflex to Hepatitis C ribonucleic acid (RNA).
- Positive HIV-1 and -2 antigen/antibody immunoassay at Screening.
- ALT >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 <35%).
- Any acute laboratory abnormality at Screening which, in the opinion of the investigator, should preclude participation in the study of an investigational compound.
- Any Grade 2 to 4 laboratory abnormality at Screening, with the exception of creatine phosphokinase (CPK) and lipid abnormalities (e.g., total cholesterol, triglycerides, etc), and ALT (described above), will exclude a subject from the study unless the investigator can provide a compelling explanation for the laboratory result(s) and has the assent of the sponsor. A single repeat of any laboratory abnormality is allowed within a single screening period to determine eligibility.
- A positive test result for drugs of abuse (including marijuana), alcohol, or cotinine (indicating active current smoking) at Screening or before the first dose of study intervention.
- Unable to refrain from the use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication and for the duration of the study.
- Treatment with any vaccine within 30 days prior to receiving study intervention.
- Unwillingness to abstain from excessive consumption of any food or drink containing grapefruit and grapefruit juice, Seville oranges, blood oranges, or pomelos or their fruit juices within 7 days prior to the first dose of study intervention(s) until the end of the study.
- Participation in another concurrent clinical study or prior clinical study (with the exception of imaging trials) prior to the first dosing day in the current study: 30 days, 5 half-lives, or twice the duration of the biological effect of the study intervention (whichever is longer).
- Where participation in the study would result in donation of blood or blood products in excess of 500 mL within 56 days.
- 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, sinoatrial pauses, bundle branch block, or conduction abnormality) which, in the opinion of the investigator or VH/GSK Medical Monitor, will interfere with the safety for the individual subject.
- Exclusion criteria for screening ECG (a single repeat is allowed for eligibility determination): Heart rate for male: <45 or >100 beats per minute (bpm) and for females: <50 or >100 bpm; PR interval: <120 or >200 milliseconds (msec); QRS duration: <70 or >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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Open-Label One-way Interaction Clinical Trial to Evaluate the Pharmacokinetic Interactions Between GSK3640254 and Tenofovir Alafenamide/Emtricitabine in Healthy Subjects
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.
- Conditions
- HIV Infections
- Being tested
- Tenofovir alafenamide/emtricitabine, GSK3640254
- Keywords
- Human immunodeficiency virus, Sequential, Tenofovir alafenamide, Emtricitabine, GSK3640254
- Medical subject headings
- HIV Infections, Acquired Immunodeficiency Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tenofovir alafenamide/emtricitabineDrug
TAF/FTC will be available as 25/200 milligrams (mg) tablet. Subjects will be administered TAF/FTC 25/200 mg QD via the oral route.
GSK3640254Drug
GSK3640254 will be available as 100 mg capsule. Subjects will be administered GSK3640254 200 mg capsule QD via the oral route.
| Study group | Role | What they receive |
|---|---|---|
| TAF/FTC followed by TAF/FTC + GSK3640254 | Experimental | Subjects will receive TAF/FTC 25/200 mg QD on Days 1 through 14 in Treatment Period 1. Subjects will be co-administered TAF/FTC 25/200 mg QD with GSK3640254 200 mg QD on Days 1 through 7 in Treatment Period 2. Receives: Drug: Tenofovir alafenamide/emtricitabine; Drug: GSK3640254 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Blood samples were collected at indicated time-points for analysis of AUC (0-tau). Pharmacokinetic (PK) parameters were calculated by standard non-compartmental analysis. PK Parameter Population included all participants who underwent plasma PK sampling and had evaluable PK parameters estimated.
Measured: Pre-dose, 15, 30, 45 minutes, 1 hour, 1 hour 30 minutes, 2, 3, 4, 5, 6, 8, 12 and 24 hours in Period 1 Day 14
Period 2: AUC (0-tau) of TAF
Blood samples were collected at indicated time-points for analysis of AUC (0-tau). PK parameters were calculated by standard non-compartmental analysis.
Measured: Pre-dose, 15, 30, 45 minutes, 1 hour, 1 hour 30 minutes, 2, 3, 4, 5, 6, 8, 12 and 24 hours in Period 2 Day 7
Period 1: Maximum Observed Concentration (Cmax) of TAF
Blood samples were collected at indicated time-points for analysis of Cmax. PK parameters were calculated by standard non-compartmental analysis.
Measured: Pre-dose, 15, 30, 45 minutes, 1 hour, 1 hour 30 minutes, 2, 3, 4, 5, 6, 8, 12 and 24 hours in Period 1 Day 14
Period 2: Cmax of TAF
Blood samples were collected at indicated time-points for analysis of Cmax. PK parameters were calculated by standard non-compartmental analysis.
Measured: Pre-dose, 15, 30, 45 minutes, 1 hour, 1 hour 30 minutes, 2, 3, 4, 5, 6, 8, 12 and 24 hours in Period 2 Day 7
Period 1: AUC (0-tau) of FTC
Blood samples were collected at indicated time-points for analysis of AUC (0-tau). PK parameters were calculated by standard non-compartmental analysis.
Measured: Pre-dose, 15, 30, 45 minutes, 1 hour, 1 hour 30 minutes, 2, 3, 4, 5, 6, 8, 12 and 24 hours in Period 1 Day 14
Period 2: AUC (0-tau) of FTC
Blood samples were collected at indicated time-points for analysis of AUC (0-tau). PK parameters were calculated by standard non-compartmental analysis.
Measured: Pre-dose, 15, 30, 45 minutes, 1 hour, 1 hour 30 minutes, 2, 3, 4, 5, 6, 8, 12 and 24 hours in Period 2 Day 7
Period 1:Cmax of FTC
Blood samples were collected at indicated time-points for analysis of Cmax. PK parameters were calculated by standard non-compartmental analysis.
Measured: Pre-dose, 15, 30, 45 minutes, 1 hour, 1 hour 30 minutes, 2, 3, 4, 5, 6, 8, 12 and 24 hours in Period 1 Day 14
Period 2:Cmax of FTC
Blood samples were collected at indicated time-points for analysis of Cmax. PK parameters were calculated by standard non-compartmental analysis.
Measured: Pre-dose, 15, 30, 45 minutes, 1 hour, 1 hour 30 minutes, 2, 3, 4, 5, 6, 8, 12 and 24 hours in Period 2 Day 7
Period 1: Plasma Concentration at the End of the Dosing Interval (Ctau) of FTC
Blood samples were collected at indicated time-points for analysis of Ctau. PK parameters were calculated by standard non-compartmental analysis.
Measured: Pre-dose, 15, 30, 45 minutes, 1 hour, 1 hour 30 minutes, 2, 3, 4, 5, 6, 8, 12 and 24 hours in Period 1 Day 14
Period 2: Ctau of FTC
Blood samples were collected at indicated time-points for analysis of Ctau. PK parameters were calculated by standard non-compartmental analysis.
Measured: Pre-dose, 15, 30, 45 minutes, 1 hour, 1 hour 30 minutes, 2, 3, 4, 5, 6, 8, 12 and 24 hours in Period 2 Day 7
Period 1: AUC (0-tau) of Tenofovir (TFV)
Blood samples were collected at indicated time-points for analysis of AUC (0-tau). PK parameters were calculated by standard non-compartmental analysis.
Measured: Pre-dose, 15, 30, 45 minutes, 1 hour, 1 hour 30 minutes, 2, 3, 4, 5, 6, 8, 12 and 24 hours in Period 1 Day 14
Period 2: AUC (0-tau) of TFV
Blood samples were collected at indicated time-points for analysis of AUC (0-tau). PK parameters were calculated by standard non-compartmental analysis.
Measured: Pre-dose, 15, 30, 45 minutes, 1 hour, 1 hour 30 minutes, 2, 3, 4, 5, 6, 8, 12 and 24 hours in Period 2 Day 7
Period 1: Cmax of TFV
Blood samples were collected at indicated time-points for analysis of Cmax. PK parameters were calculated by standard non-compartmental analysis.
Measured: Pre-dose, 15, 30, 45 minutes, 1 hour, 1 hour 30 minutes, 2, 3, 4, 5, 6, 8, 12 and 24 hours in Period 1 Day 14
Period 2: Cmax of TFV
Blood samples were collected at indicated time-points for analysis of Cmax. PK parameters were calculated by standard non-compartmental analysis.
Measured: Pre-dose, 15, 30, 45 minutes, 1 hour, 1 hour 30 minutes, 2, 3, 4, 5, 6, 8, 12 and 24 hours in Period 2 Day 7
Period 1: Ctau of TFV
Blood samples were collected at indicated time-points for analysis of Ctau. PK parameters were calculated by standard non-compartmental analysis.
Measured: Pre-dose, 15, 30, 45 minutes, 1 hour, 1 hour 30 minutes, 2, 3, 4, 5, 6, 8, 12 and 24 hours in Period 1 Day 14
Period 2: Ctau of TFV
Blood samples were collected at indicated time-points for analysis of Ctau. PK parameters were calculated by standard non-compartmental analysis.
Measured: Pre-dose, 15, 30, 45 minutes, 1 hour, 1 hour 30 minutes, 2, 3, 4, 5, 6, 8, 12 and 24 hours in Period 2 Day 7
Secondary outcomes (91)
Number of Participants With Non-serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAE)
An adverse events (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
Measured: Up to Day 24
Period 1: Change From Baseline in Hematology Parameter of Platelet Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils and Basophils
Blood samples were collected at indicated timepoints for analysis of hematology parameters like platelet count, neutrophils, lymphocytes, monocytes, eosinophils and basophils. Baseline was defined as Day -1 for Period 1. Change from Baseline was defined as post-dose visit value minus Baseline value.
Measured: Baseline and at Days 7, and 14
Period 2: Change From Baseline in Hematology Parameter of Platelet Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils and Basophils
Blood samples were collected at indicated timepoints for analysis for hematology parameters like platelet count, neutrophils, lymphocytes, monocytes, eosinophils and basophils. Baseline was defined as Period 1 Day 14 for Period 2. Change from Baseline was defined as post-dose visit value minus Baseline value.
Measured: Baseline and at Days 3, 7, 9
Period 1: Absolute Values of the Hematology Parameter of Platelet Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils and Basophils
Blood samples were collected at indicated timepoints for analysis of hematology parameters like platelet count, neutrophils, lymphocytes, monocytes, eosinophils and basophils. Baseline was defined as Day -1 for Period 1.
Measured: Baseline and at Days 7, and 14
Period 2: Absolute Values of the Hematology Parameter of Platelet Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils and Basophils
Blood samples were collected at indicated timepoints for analysis of hematology parameters like platelet count, neutrophils, lymphocytes, monocytes, eosinophils and basophils. Baseline was defined as Period 1 Day 14 for Period 2.
Measured: Baseline and at Days 3, 7, 9
Period 1: Change From Baseline in Hematology Parameter of Hematocrit
Blood samples were collected at indicated timepoints for analysis of hematology parameter like hematocrit. Baseline was defined as Day -1 for Period 1. Change from Baseline was defined as post-dose visit value minus Baseline value.
Measured: Baseline and at Days 7, 14
Period 2: Change From Baseline in Hematology Parameter of Hematocrit
Blood samples were collected at indicated time-points for analysis for hematology parameter like hematocrit. Baseline was defined as Period 1 Day 14 for Period 2. Change from Baseline was defined as post-dose visit value minus Baseline value.
Measured: Baseline and at Days 3, 7, 9
Period 1: Absolute Values of the Hematology Parameter: Hematocrit
Blood samples were collected at indicated time points for analysis for hematology parameter like hematocrit. Baseline was defined as Day -1 for Period 1.
Measured: Baseline and at Days 7, 14
Period 2: Absolute Values of the Hematology Parameter: Hematocrit
Blood samples were collected at indicated time-points for analysis for hematology parameter like hematocrit. Baseline was defined as Period 1 Day 14 for Period 2.
Measured: Baseline and at Days 3, 7, 9
Period 1: Change From Baseline in Hematology Parameter of Hemoglobin
Blood samples were collected at indicated timepoints for analysis for hematology parameter like hemoglobin. Baseline was defined as Day -1 for Period 1. Change from Baseline was defined as post-dose visit value minus Baseline value.
Measured: Baseline and at Days 7, 14
Period 2: Change From Baseline in Hematology Parameter of Hemoglobin
Blood samples were collected at indicated timepoints for analysis of hematology parameter like hemoglobin. Baseline was defined as Period 1 Day 14 for Period 2. Change from Baseline was defined as post-dose visit value minus Baseline value.
Measured: Baseline and at Days 3, 7, 9
Period 1: Absolute Values of the Hematology Parameter: Hemoglobin
Blood samples were collected at indicated time-points for analysis for hematology parameter like hemoglobin. Baseline was defined as Day -1 for Period 1.
Measured: Baseline and at Days 7, 14
Period 2: Absolute Values of the Hematology Parameter: Hemoglobin
Blood samples were collected at indicated time-points for analysis for hematology parameter like hemoglobin. Baseline was defined as Period 1 Day 14 for Period 2.
Measured: Baseline and at Days 3, 7, 9
Period 1: Change From Baseline in Hematology Parameter of Mean Corpuscle Hemoglobin (MCH)
Blood samples were collected at indicated timepoints for analysis of hematology parameter like MCH. Baseline was defined as Day -1 for Period 1. Change from Baseline was defined as post-dose visit value minus Baseline value.
Measured: Baseline and at Days 7, 14
Period 2: Change From Baseline in Hematology Parameter of MCH
Blood samples were collected at indicated timepoints for analysis for hematology parameter like MCH. Baseline was defined as Period 1 Day 14 for Period 2. Change from Baseline was defined as post-dose visit value minus Baseline value.
Measured: Baseline and at Days 3, 7, 9
Period 1: Absolute Values of the Hematology Parameter: MCH
Blood samples were collected at indicated time-points for analysis for hematology parameter like MCH. Baseline was defined as Day -1 for Period 1.
Measured: Baseline and at Days 7, 14
Period 2: Absolute Values of the Hematology Parameter: MCH
Blood samples were collected at indicated time-points for analysis of hematology parameter like MCH. Baseline was defined as Period 1 Day 14 for Period 2.
Measured: Baseline and at Days 3, 7, 9
Period 1: Change From Baseline in Hematology Parameter of Mean Corpuscle Volume (MCV)
Blood samples were collected at indicated time-points for analysis for hematology parameter like MCV. Baseline was defined as Day -1 for Period 1. Change from Baseline was defined as post-dose visit value minus Baseline value.
Measured: Baseline and at Days 7, 14
Period 2: Change From Baseline in Hematology Parameter of MCV
Blood samples were collected at indicated timepoints for analysis for hematology parameter like MCV. Baseline was defined as Period 1 Day 14 for Period 2. Change from Baseline was defined as post-dose visit value minus Baseline value.
Measured: Baseline and at Days 3, 7, 9
Period 1: Absolute Values of the Hematology Parameter: MCV
Blood samples were collected at indicated time-points for analysis for hematology parameter like MCV. Baseline was defined as Day -1 for Period 1.
Measured: Baseline and at Days 7, 14
Period 2: Absolute Values of the Hematology Parameter: MCV
Blood samples were collected at indicated time-points for analysis for hematology parameter like MCV. Baseline was defined as Period 1 Day 14 for Period 2.
Measured: Baseline and at Days 3, 7, 9
Period 1: Change From Baseline in Hematology Parameter of Erythrocytes
Blood samples were collected at indicated time-points for analysis for hematology parameter like erythrocytes. Baseline was defined as Day -1 for Period 1. Change from Baseline was defined as post-dose visit value minus Baseline value.
Measured: Baseline and at Days 7, 14
Period 2: Change From Baseline in Hematology Parameter of Erythrocytes
Blood samples were collected at indicated time-points for analysis for hematology parameter like erythrocytes. Baseline was defined as Period 1 Day 14 for Period 2. Change from Baseline was defined as post-dose visit value minus Baseline value.
Measured: Baseline and at Days 3, 7, 9
Period 1: Absolute Values of the Hematology Parameter: Erythrocytes
Blood samples were collected at indicated time-points for analysis for hematology parameter like erythrocytes. Baseline was defined as Day -1 for Period 1.
Measured: Baseline and at Days 7, 14
Period 2: Absolute Values of the Hematology Parameter: Erythrocytes
Blood samples were collected at indicated time-points for analysis for hematology parameter like erythrocytes. Baseline was defined as Period 1 Day 14 for Period 2.
Measured: Baseline and at Days 3, 7, 9
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
Blood samples were collected at indicated time-points for analysis for clinical chemistry parameter of glucose, calcium, potassium, sodium, BUN, anion gap, CO2, chloride and phosphorus. Baseline was defined as Day -1 for Period 1. Change from Baseline was defined as post-dose visit value minus Baseline value.
Measured: Baseline and at Days 7, 14
Period 2: Change From Baseline in Clinical Chemistry Parameter of Glucose, Anion Gap, Cholesterol, Calcium, Potassium, Sodium, BUN, CO2, Chloride and Phosphorus
Blood samples were collected at indicated time-points for analysis for clinical chemistry parameter of glucose, calcium, potassium, sodium, BUN, anion gap, CO2, chloride and phosphorus. Baseline was defined as Period 1 Day 14 for Period 2. Change from Baseline was defined as post-dose visit value minus Baseline value.
Measured: Baseline and at Days 3, 7, 9
Period 1: Absolute Values of Clinical Chemistry Parameter of Glucose, Anion Gap, Cholesterol, Calcium, Potassium, Sodium, BUN, CO2, Chloride and Phosphorus
Blood samples were collected at indicated time-points for analysis of clinical chemistry parameter of glucose, calcium, potassium, sodium, BUN, anion gap, CO2, chloride and phosphorus. Baseline was defined as Day -1 for Period 1.
Measured: Baseline and at Days 7, 14
Period 2: Absolute Values of Clinical Chemistry Parameter of Glucose, Anion Gap, Cholesterol, Calcium, Potassium, Sodium, BUN, CO2, Chloride and Phosphorus
Blood samples were collected at indicated time-points for analysis for clinical chemistry parameter of glucose, calcium, potassium, sodium, BUN, anion gap, CO2, chloride and phosphorus. Baseline was defined as Period 1 Day 14 for Period 2.
Measured: Baseline and at Days 3, 7, 9
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)
Blood samples were collected at indicated time-points for analysis of clinical chemistry parameter like alkaline phosphatase, ALT, AST, LDH, GGT and CK. Baseline was defined as Day -1 for Period 1. Change from Baseline was defined as post-dose visit value minus Baseline value.
Measured: Baseline and at Days 7, 14
Period 2: Change From Baseline in Clinical Chemistry Parameter of Alkaline Phosphatase, ALT, AST, LDH, GGT, and CK
Blood samples were collected at indicated time-points for analysis for clinical chemistry parameter of alkaline phosphatase, ALT, AST, LDH, GGT and CK. Baseline was defined as Period 1 Day 14 for Period 2. Change from Baseline was defined as post-dose visit value minus Baseline value.
Measured: Baseline and at Days 3, 7, 9
Period 1: Absolute Values of Clinical Chemistry Parameter of Alkaline Phosphatase, ALT, AST, LDH, GGT, and CK
Blood samples were collected at indicated time-points for analysis for clinical chemistry parameter of alkaline phosphatase, ALT, AST, LDH, GGT and CK. Baseline was defined as Day -1 for Period 1.
Measured: Baseline and at Days 7, 14
Period 2: Absolute Values of Clinical Chemistry Parameter of Alkaline Phosphatase, ALT, AST, LDH, GGT, and CK
Blood samples were collected at indicated time-points for analysis for clinical chemistry parameter of alkaline phosphatase, ALT, AST, LDH, GGT and CK. Baseline was defined as Period 1 Day 14 for Period 2.
Measured: Baseline and at Days 3, 7, 9
Period 1: Change From Baseline in Clinical Chemistry Parameter of Lipase and Amylase
Blood samples were collected at indicated time-points for analysis for clinical chemistry parameter of lipase and amylase. Baseline was defined as Day -1 for Period 1. Change from Baseline was defined as post-dose visit value minus Baseline value.
Measured: Baseline and at Days 7, 14
Period 2: Change From Baseline in Clinical Chemistry Parameter of Lipase and Amylase
Blood samples were collected at indicated time-points for analysis for clinical chemistry parameter of lipase and amylase. Baseline was defined as Period 1 Day 14 for Period 2. Change from Baseline was defined as post-dose visit value minus Baseline value.
Measured: Baseline and at Days 3, 7, 9
Period 1: Absolute Values of Chemistry Parameters of Lipase and Amylase
Blood samples were collected at indicated time-points for analysis for clinical chemistry parameter of lipase and amylase. Baseline was defined as Day -1 for Period 1.
Measured: Baseline and at Days 7, 14
Period 2: Absolute Values of Chemistry Parameters of Lipase and Amylase
Blood samples were collected at indicated time-points for analysis for clinical chemistry parameter of lipase and amylase. Baseline was defined as Period 1 Day 14 for Period 2.
Measured: Baseline and at Days 3, 7, 9
Period 1: Change From Baseline in Clinical Chemistry Parameter of Total Bilirubin, Direct Bilirubin, and Creatinine
Blood samples were collected at indicated time-points for analysis for clinical chemistry parameter of total bilirubin, direct bilirubin, and creatinine. Baseline was defined as Day -1 for Period 1. Change from Baseline was defined as post-dose visit value minus Baseline value.
Measured: Baseline and at Days 7, 14
Period 2: Change From Baseline in Clinical Chemistry Parameter of Total Bilirubin, Direct Bilirubin, and Creatinine
Blood samples were collected at indicated time-points for analysis for clinical chemistry parameter of total bilirubin, direct bilirubin, and creatinine. Baseline was defined as Period 1 Day 14 for Period 2. Change from Baseline was defined as post-dose visit value minus Baseline value.
Measured: Baseline and at Days 3, 7, 9
Period 1: Absolute Values of Clinical Chemistry Parameter of Total Bilirubin, Direct Bilirubin, and Creatinine
Blood samples were collected at indicated time-points for analysis for clinical chemistry parameter of total bilirubin, direct bilirubin, and creatinine. Baseline was defined as Day -1 for Period 1.
Measured: Baseline and at Days 7, 14
Period 2: Absolute Values of Clinical Chemistry Parameter of Total Bilirubin, Direct Bilirubin, and Creatinine
Blood samples were collected at indicated time-points for analysis for clinical chemistry parameter of total bilirubin, direct bilirubin, creatinine and uric acid. Baseline was defined as Period 1 Day 14 for Period 2.
Measured: Baseline and at Days 3, 7, 9
Period 1: Change From Baseline in Clinical Chemistry Parameter of Total Protein, Albumin and Globulin
Blood samples were collected at indicated time-points for analysis for clinical chemistry parameter of of total protein, albumin and globulin. Baseline was defined as Day -1 for Period 1. Change from Baseline was defined as post-dose visit value minus Baseline value.
Measured: Baseline and at Days 7, 14
Period 2: Change From Baseline in Clinical Chemistry Parameter of Total Protein, Albumin and Globulin
Blood samples were collected at indicated time-points for analysis for clinical chemistry parameter of total protein, albumin and globulin. Baseline was defined as Period 1 Day 14 for Period 2. Change from Baseline was defined as post-dose visit value minus Baseline value.
Measured: Baseline and at Days 3, 7, 9
Period 1: Absolute Values of Clinical Chemistry Parameter of Total Protein, Albumin and Globulin
Blood samples were collected at indicated time-points for analysis for clinical chemistry parameter of total protein, albumin and globulin. Baseline was defined as Day -1 for Period 1.
Measured: Baseline and at Days 7, 14
Period 2: Absolute Values of Clinical Chemistry Parameter of Total Protein, Albumin and Globulin
Blood samples were collected at indicated time-points for analysis for clinical chemistry parameter of total bilirubin, direct bilirubin, creatinine and uric acid. Baseline was defined as Period 1 Day 14 for Period 2.
Measured: Baseline and at Days 3, 7, 9
Period 1: Change From Baseline in Specific Gravity of Urine
Urine samples were collected at indicated time points for the assessment of specific gravity. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine. The concentration of the excreted molecules determines the urine's specific gravity. Baseline was defined as Day -1 for Period 1. Change from Baseline was defined as post-dose visit value minus Baseline value.
Measured: Baseline and at Days 7, 14
Period 2: Change From Baseline in Specific Gravity of Urine
Urine samples were collected at indicated time points for the assessment of specific gravity. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine. The concentration of the excreted molecules determines the urine's specific gravity. Baseline was defined as Period 1 Day 14 for Period 2. Change from Baseline was defined as post-dose visit value minus Baseline value.
Measured: Baseline and at Days 3, 7, 9
Period 1: Absolute Values of Specific Gravity of Urine
Urine samples were collected at indicated time points for the assessment of specific gravity. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine. The concentration of the excreted molecules determines the urine's specific gravity. Baseline was defined as Day -1 for Period 1.
Measured: Baseline and at Days 7, 14
Period 2: Absolute Values of Specific Gravity of Urine
Urine samples were collected at indicated time points for the assessment of specific gravity. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine. The concentration of the excreted molecules determines the urine's specific gravity. Baseline was defined as Period 1 Day 14 for Period 2.
Measured: Baseline and at Days 3, 7, 9
Period 1: Change From Baseline in Potential of Hydrogen (pH) of Urine
Urine samples were collected at indicated time points for the assessment of Urinary 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 - 6.0). Baseline was defined as Day -1 for Period 1. Change from Baseline was defined as post-dose visit value minus Baseline value.
Measured: Baseline and at Days 7, 14
Period 2: Change From Baseline in pH of Urine
Urine samples were collected at indicated time points for the assessment of Urinary 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 - 6.0). Baseline was defined as Period 1 Day 14 for Period 2. Change from Baseline was defined as post-dose visit value minus Baseline value.
Measured: Baseline and at Days 3, 7, 9
Period 1: Absolute Values of pH of Urine
Urine samples were collected at indicated time points for the assessment of Urinary 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 - 6.0). Baseline was defined as Day -1 for Period 1.
Measured: Baseline and at Days 7, 14
Period 2: Absolute Values of pH of Urine
Urine samples were collected at indicated time points for the assessment of Urinary 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 - 6.0). Baseline was defined as Period 1 Day 14 for Period 2.
Measured: Baseline and at Days 3, 7, 9
Period 1: Change From Baseline in Urine Urobilinogen
Urine samples were collected at indicated time points for the assessment of urine urobilinogen. Baseline was defined as Day -1 for Period 1. Change from Baseline was defined as post-dose visit value minus Baseline value.
Measured: Baseline and at Days 7, 14
Period 2: Change From Baseline in Urine Urobilinogen
Urine samples were collected at indicated time points for the assessment of urine urobilinogen. Baseline was defined as Period 1 Day 14 for Period 2. Change from Baseline was defined as post-dose visit value minus Baseline value.
Measured: Baseline and at Days 3, 7, 9
Period 1: Absolute Values of Urine Urobilinogen
Urine samples were collected at indicated time points for the assessment of urine urobilinogen. Baseline was defined as Day -1 for Period 1.
Measured: Baseline and at Days 7, 14
Period 2: Absolute Values of Urine Urobilinogen
Urine samples were collected at indicated time points for the assessment of urine urobilinogen. Baseline was defined as Period 1 Day 14 for Period 2.
Measured: Baseline and at Days 3, 7, 9
Period 1: Change From Baseline in Heart Rate
Urine samples were collected at indicated time points for the assessment of urine urobilinogen. Baseline was defined as Day -1 for Period 1. Change from Baseline was defined as post-dose visit value minus Baseline value.
Measured: Baseline and at Day 1, 2 and 4 hours post-dose
Period 2: Change From Baseline in Heart Rate
Twelve-lead ECGs was performed with the participant in a supine or semi-supine position after a rest of at least 10 minutes using an automated ECG machine to measure heart rate. Baseline was defined as Day 1 (Pre-dose) for each Period. Change from Baseline was defined as post-dose visit value minus Baseline value.
Measured: Baseline and at Day 1, 2 and 4 hours post-dose; Day 4, Pre-dose, 2 and 4 hours post-dose; Day 7, Pre-dose, 2 and 4 hours post-dose; Day 9 post-dose
Period 1: Absolute Values of Heart Rate
Twelve-lead ECGs was performed with the participant in a supine or semi-supine position after a rest of at least 10 minutes using an automated ECG machine to measure heart rate. Baseline was defined as Day 1 (Pre-dose) for each Period. Change from Baseline was defined as post-dose visit value minus Baseline value.
Measured: Baseline and at Day 1, 2 and 4 hours post-dose
Period 2: Absolute Values of Heart Rate
Twelve-lead ECGs was performed with the participant in a supine or semi-supine position after a rest of at least 10 minutes using an automated ECG machine to measure heart rate. Baseline was defined as Day 1 (Pre-dose) for each Period.
Measured: Baseline and at Day 1, 2 and 4 hours post-dose; Day 4, Pre-dose, 2 and 4 hours post-dose; Day 7, Pre-dose, 2 and 4 hours post-dose; Day 9 post-dose
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
Twelve-lead ECGs was performed with the participant in a supine or semi-supine position after a rest of at least 10 minutes using an automated ECG machine to measure PR interval, QRS duration, QT Interal, QTcF Interval and QTcB interval. Baseline was defined as Day 1 (Pre-dose) for each Period. Change from Baseline was defined as post-dose visit value minus Baseline value.
Measured: Baseline and at Day 1, 2 and 4 hours post-dose
Period 2: Change From Baseline in ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF Interval, and QTcB Interval
Twelve-lead ECGs was performed with the participant in a supine or semi-supine position after a rest of at least 10 minutes using an automated ECG machine to measure PR interval, QRS duration, QT Interal, QTcF Interval and QTcB interval. Baseline was defined as Day 1 (Pre-dose) for each Period. Change from Baseline was defined as post-dose visit value minus Baseline value.
Measured: Baseline and at Day 1, 2 and 4 hours post-dose; Day 4, Pre-dose, 2 and 4 hours post-dose; Day 7, Pre-dose, 2 and 4 hours post-dose; Day 9 post-dose
Period 1: Absolute Values of ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF Interval, and QTcB Interval
Twelve-lead ECGs was performed with the participant in a supine or semi-supine position after a rest of at least 10 minutes using an automated ECG machine to measure PR interval, QRS duration, QT Interval, QTcF Interval and QTcB interval. Baseline was defined as Day 1 (Pre-dose) for each Period.
Measured: Baseline and at Day 1, 2 and 4 hours post-dose
Period 2: Absolute Values of ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF Interval, and QTcB Interval
Twelve-lead ECGs was performed with the participant in a supine or semi-supine position after a rest of at least 10 minutes using an automated ECG machine to measure PR interval, QRS duration, QT Interval, QTcF Interval and QTcB interval. Baseline was defined as Day 1 (Pre-dose) for each Period.
Measured: Baseline and at Day 1, 2 and 4 hours post-dose; Day 4, Pre-dose, 2 and 4 hours post-dose; Day 7, Pre-dose, 2 and 4 hours post-dose; Day 9 post-dose
Period 1: Change From Baseline in Temperature
Temperature was assessed at indicated time-points. Baseline was defined as Day 1 (Pre-dose) for each Period. Change from Baseline was defined as post-dose visit value minus Baseline value.
Measured: Baseline and at Days 2, 3, 4, 5 and 7
Period 2: Change From Baseline in Temperature
Temperature was assessed at indicated time-points. Baseline was defined as Day 1 (Pre-dose) for each Period. Change from Baseline was defined as post-dose visit value minus Baseline value.
Measured: Baseline and at Days 4, 7, 9, and 10
Period 1: Absolute Values of Temperature
Temperature was assessed at indicated time-points. Baseline was defined as Day 1 (Pre-dose) for each Period.
Measured: Baseline and at Days 2, 3, 4, 5 and 7
Period 2: Absolute Values of Temperature
Temperature was assessed at indicated time-points. Baseline was defined as Day 1 (Pre-dose) for each Period.
Measured: Baseline and at Days 4, 7, 9, and 10
Period 1: Change From Baseline in Pulse Rate
Pulse rate was assessed in the semi-recumbent position with a completely automated device at indicated time-points. Baseline was defined as Day 1 (Pre-dose) for each Period. Change from Baseline was defined as post-dose visit value minus Baseline value.
Measured: Baseline and at Days 2, 3, 4, 5 and 7
Period 2: Change From Baseline in Pulse Rate
Pulse rate was assessed in the semi-recumbent position with a completely automated device at indicated time-points. Baseline was defined as Day 1 (Pre-dose) for each Period. Change from Baseline was defined as post-dose visit value minus Baseline value.
Measured: Baseline and at Days 4, 7, 9, and 10
Period 1: Absolute Values of Pulse Rate
Pulse rate was assessed in the semi-recumbent position with a completely automated device at indicated time-points. Baseline was defined as Day 1 (Pre-dose) for each Period.
Measured: Baseline and at Days 2, 3, 4, 5 and 7
Period 2: Absolute Values of Pulse Rate
Pulse rate was assessed in the semi-recumbent position with a completely automated device at indicated time-points. Baseline was defined as Day 1 (Pre-dose) for each Period.
Measured: Baseline and at Days 4, 7, 9, and 10
Period 1: Change From Baseline in Respiratory Rate
Respiratory rate was assessed at indicated time-points. Baseline was defined as Day 1 (Pre-dose) for each Period. Change from Baseline was defined as post-dose visit value minus Baseline value.
Measured: Baseline and at Days 2, 3, 4, 5 and 7
Period 2: Change From Baseline in Respiratory Rate
Respiratory rate was assessed at indicated time-points. Baseline was defined as Day 1 (Pre-dose) for each Period. Change from Baseline was defined as post-dose visit value minus Baseline value.
Measured: Baseline and at Days 4, 7, 9, and 10
Period 1: Absolute Values of Respiratory Rate
Respiratory rate was assessed at indicated time-points. Baseline was defined as Day 1 (Pre-dose) for each Period.
Measured: Baseline and at Days 2, 3, 4, 5 and 7
Period 2: Absolute Values of Respiratory Rate
Respiratory rate was assessed at indicated time-points. Baseline was defined as Day 1 (Pre-dose) for each Period.
Measured: Baseline and at Days 4, 7, 9, and 10
Period 1: Change From Baseline in Blood Pressure
Systolic blood pressure (SBP) and diastolic blood pressure (DBP) was assessed in the semi-recumbent position with a completely automated device at indicated time-points. Baseline was defined as Day 1 (Pre-dose) for each Period. Change from Baseline was defined as post-dose visit value minus Baseline value.
Measured: Baseline and at Days 2, 3, 4, 5 and 7
Period 2: Change From Baseline in Blood Pressure
SBP and DBP was assessed in the semi-recumbent position with a completely automated device at indicated time-points. Baseline was defined as Day 1 (Pre-dose) for each Period. Change from Baseline was defined as post-dose visit value minus Baseline value.
Measured: Baseline and at Days 4, 7, 9, and 10
Period 1: Absolute Values of Blood Pressure
SBP and DBP was assessed in the semi-recumbent position with a completely automated device at indicated time-points. Baseline was defined as Day 1 (Pre-dose) for each Period.
Measured: Baseline and at Days 2, 3, 4, 5 and 7
Period 2: Absolute Values of Blood Pressure
SBP and DBP was assessed in the semi-recumbent position with a completely automated device at indicated time-points. Baseline was defined as Day 1 (Pre-dose) for each Period.
Measured: Baseline and at Days 4, 7, 9, and 10
Period 2: AUC (0-tau) of GSK3640254
Blood samples were collected at indicated time-points for analysis of AUC (0-tau). PK parameters were calculated by standard non-compartmental analysis.
Measured: Pre-dose, 1 and 2hours, 2 hours 30 minutes, 3 and 3 hour 30 minutes, 4 and 4 hour 30 minutes, 5, 6, 8, 12 and 24 hours in Period 2 Day 7
Period 2: Cmax of GSK3640254
Blood samples were collected at indicated time-points for analysis of Cmax. PK parameters were calculated by standard non-compartmental analysis.
Measured: Pre-dose, 1 and 2hours, 2 hours 30 minutes, 3 and 3 hour 30 minutes, 4 and 4 hour 30 minutes, 5, 6, 8, 12 and 24 hours in Period 2 Day 7
Period 2: Ctau of GSK3640254
Blood samples were collected at indicated time-points for analysis of Ctau. PK parameters were calculated by standard non-compartmental analysis.
Measured: Pre-dose, 1 and 2 hours, 2 hours 30 minutes, 3 and 3 hour 30 minutes, 4 and 4 hour 30 minutes, 5, 6, 8, 12 and 24 hours in Period 2 Day 7
Period 2: Time of Maximum Observed Concentration (Tmax) of GSK3640254
Blood samples were collected at indicated time-points for analysis of Tmax. PK parameters were calculated by standard non-compartmental analysis.
Measured: Pre-dose, 1 and 2hours, 2 hours 30 minutes, 3 and 3 hour 30 minutes, 4 and 4 hour 30 minutes, 5, 6, 8, 12 and 24 hours in Period 2 Day 7
Period 1: Tmax of TAF
Blood samples were collected at indicated time-points for analysis of Tmax. PK parameters were calculated by standard non-compartmental analysis.
Measured: Pre-dose, 15, 30, 45 minutes, 1 hour, 1 hour 30 minutes, 2, 3, 4, 5, 6, 8, 12 and 24 hours in Period 1 Day 14
Period 2: Tmax of TAF
Blood samples were collected at indicated time-points for analysis of Tmax. PK parameters were calculated by standard non-compartmental analysis.
Measured: Pre-dose, 15, 30, 45 minutes, 1 hour, 1 hour 30 minutes, 2, 3, 4, 5, 6, 8, 12 and 24 hours in Period 2 Day 7
Period 1: Tmax of FTC
Blood samples were collected at indicated time-points for analysis of Tmax. PK parameters were calculated by standard non-compartmental analysis.
Measured: Pre-dose, 15, 30, 45 minutes, 1 hour, 1 hour 30 minutes, 2, 3, 4, 5, 6, 8, 12 and 24 hours in Period 1 Day 14
Period 2: Tmax of FTC
Blood samples were collected at indicated time-points for analysis of Tmax. PK parameters were calculated by standard non-compartmental analysis.
Measured: Pre-dose, 15, 30, 45 minutes, 1 hour, 1 hour 30 minutes, 2, 3, 4, 5, 6, 8, 12 and 24 hours in Period 2 Day 7
Period 1: Tmax of TFV
Blood samples were collected at indicated time-points for analysis of Tmax. PK parameters were calculated by standard non-compartmental analysis.
Measured: Pre-dose, 15, 30, 45 minutes, 1 hour, 1 hour 30 minutes, 2, 3, 4, 5, 6, 8, 12 and 24 hours in Period 1 Day 14
Period 2: Tmax of TFV
Blood samples were collected at indicated time-points for analysis of Tmax. PK parameters were calculated by standard non-compartmental analysis.
Measured: Pre-dose, 15, 30, 45 minutes, 1 hour, 1 hour 30 minutes, 2, 3, 4, 5, 6, 8, 12 and 24 hours in Period 2 Day 7
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Feb 2019
- Study start11 Feb 2019
- Primary completion30 Mar 2019
- Study completion30 Apr 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- More trials run by ViiV HealthcareThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Intervention model
- Sequential
- Model description
- This is a fixed-sequence 2-period, one-way drug interaction study
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- ViiV Healthcare
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, ViiV Healthcare
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03836729
- Sponsor's protocol ID
- 208134
- Status last verified
- Apr 2020
- First submitted
- 7 Feb 2019
- Last updated
- 21 Apr 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: IPD for this study will be made available via the Clinical Study Data Request site.
Publications
Pene Dumitrescu T, Joshi SR, Xu J, Zhan J, Johnson M, Butcher L, Zimmerman E, Webster L, Davidson AM, Lataillade M, Min S. A Phase I Evaluation of the Pharmacokinetics and Tolerability of the HIV-1 Maturation Inhibitor GSK3640254 and Tenofovir Alafenamide/Emtricitabine in Healthy Participants. Antimicrob Agents Chemother. 2021 May 18;65(6):e02173-20. doi: 10.1128/AAC.02173-20. Print 2021 May 18.
PubMed 33753329
Study at a glance
From the registry record, last updated by the sponsor on 21 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label One-way Interaction Clinical Trial to Evaluate the Pharmacokinetic Interactions Between GSK3640254 and Tenofovir Alafenamide/Emtricitabine in Healthy Subjects
- ClinicalTrials.gov ID
- NCT03836729
- Acronym / sponsor ID
- 208134
- Conditions
- HIV Infections
- Keywords
- Human immunodeficiency virus, Sequential, Tenofovir alafenamide, Emtricitabine, GSK3640254
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- ViiV HealthcareIndustry (pharma, biotech, devices)
- Study start
- 11 Feb 2019 (actual)
- Primary completion
- 30 Mar 2019 (actual)
- Study completion
- 30 Apr 2019 (actual)
- First posted
- 11 Feb 2019 (actual)
- Results
- Posted 2 Apr 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- This is a fixed-sequence 2-period, one-way drug interaction study
| Arm | Type | Receives |
|---|---|---|
| TAF/FTC followed by TAF/FTC + GSK3640254 | Experimental | Drug: Tenofovir alafenamide/emtricitabine, Drug: GSK3640254Subjects will receive TAF/FTC 25/200 mg QD on Days 1 through 14 in Treatment Period 1. Subjects will be co-administered TAF/FTC 25/200 mg QD with GSK3640254 200 mg QD on Days 1 through 7 in Treatment Period 2. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (26 listed)
- 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 (<6 months) without inpatient treatment and are currently well-controlled clinically or resolved may be considered for entry after discussion and agreement with the ViiV Medical Monitor.
- Any pre-existing physical or other psychiatric condition (including alcohol or drug abuse), which, in the opinion of the investigator (with or without psychiatric evaluation), could interfere with the subject's ability to comply with the dosing schedule and protocol evaluations or which might compromise the safety of the subject.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tenofovir alafenamide/emtricitabineTAF/FTC will be available as 25/200 milligrams (mg) tablet. Subjects will be administered TAF/FTC 25/200 mg QD via the oral route. | Drug | TAF/FTC followed by TAF/FTC + GSK3640254 |
| GSK3640254GSK3640254 will be available as 100 mg capsule. Subjects will be administered GSK3640254 200 mg capsule QD via the oral route. | Drug | TAF/FTC followed by TAF/FTC + GSK3640254 |
Primary outcome
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
Time frame: Pre-dose, 15, 30, 45 minutes, 1 hour, 1 hour 30 minutes, 2, 3, 4, 5, 6, 8, 12 and 24 hours in Period 1 Day 14
Blood samples were collected at indicated time-points for analysis of AUC (0-tau). Pharmacokinetic (PK) parameters were calculated by standard non-compartmental analysis. PK Parameter Population included all participants who underwent plasma PK sampling and had evaluable PK parameters estimated.
Period 2: AUC (0-tau) of TAF
Time frame: Pre-dose, 15, 30, 45 minutes, 1 hour, 1 hour 30 minutes, 2, 3, 4, 5, 6, 8, 12 and 24 hours in Period 2 Day 7
Blood samples were collected at indicated time-points for analysis of AUC (0-tau). PK parameters were calculated by standard non-compartmental analysis.
Period 1: Maximum Observed Concentration (Cmax) of TAF
Time frame: Pre-dose, 15, 30, 45 minutes, 1 hour, 1 hour 30 minutes, 2, 3, 4, 5, 6, 8, 12 and 24 hours in Period 1 Day 14
Blood samples were collected at indicated time-points for analysis of Cmax. PK parameters were calculated by standard non-compartmental analysis.
Period 2: Cmax of TAF
Time frame: Pre-dose, 15, 30, 45 minutes, 1 hour, 1 hour 30 minutes, 2, 3, 4, 5, 6, 8, 12 and 24 hours in Period 2 Day 7
Blood samples were collected at indicated time-points for analysis of Cmax. PK parameters were calculated by standard non-compartmental analysis.
Period 1: AUC (0-tau) of FTC
Time frame: Pre-dose, 15, 30, 45 minutes, 1 hour, 1 hour 30 minutes, 2, 3, 4, 5, 6, 8, 12 and 24 hours in Period 1 Day 14
Blood samples were collected at indicated time-points for analysis of AUC (0-tau). PK parameters were calculated by standard non-compartmental analysis.
Period 2: AUC (0-tau) of FTC
Time frame: Pre-dose, 15, 30, 45 minutes, 1 hour, 1 hour 30 minutes, 2, 3, 4, 5, 6, 8, 12 and 24 hours in Period 2 Day 7
Blood samples were collected at indicated time-points for analysis of AUC (0-tau). PK parameters were calculated by standard non-compartmental analysis.
Period 1:Cmax of FTC
Time frame: Pre-dose, 15, 30, 45 minutes, 1 hour, 1 hour 30 minutes, 2, 3, 4, 5, 6, 8, 12 and 24 hours in Period 1 Day 14
Blood samples were collected at indicated time-points for analysis of Cmax. PK parameters were calculated by standard non-compartmental analysis.
Period 2:Cmax of FTC
Time frame: Pre-dose, 15, 30, 45 minutes, 1 hour, 1 hour 30 minutes, 2, 3, 4, 5, 6, 8, 12 and 24 hours in Period 2 Day 7
Blood samples were collected at indicated time-points for analysis of Cmax. PK parameters were calculated by standard non-compartmental analysis.
Period 1: Plasma Concentration at the End of the Dosing Interval (Ctau) of FTC
Time frame: Pre-dose, 15, 30, 45 minutes, 1 hour, 1 hour 30 minutes, 2, 3, 4, 5, 6, 8, 12 and 24 hours in Period 1 Day 14
Blood samples were collected at indicated time-points for analysis of Ctau. PK parameters were calculated by standard non-compartmental analysis.
Period 2: Ctau of FTC
Time frame: Pre-dose, 15, 30, 45 minutes, 1 hour, 1 hour 30 minutes, 2, 3, 4, 5, 6, 8, 12 and 24 hours in Period 2 Day 7
Blood samples were collected at indicated time-points for analysis of Ctau. PK parameters were calculated by standard non-compartmental analysis.
Period 1: AUC (0-tau) of Tenofovir (TFV)
Time frame: Pre-dose, 15, 30, 45 minutes, 1 hour, 1 hour 30 minutes, 2, 3, 4, 5, 6, 8, 12 and 24 hours in Period 1 Day 14
Blood samples were collected at indicated time-points for analysis of AUC (0-tau). PK parameters were calculated by standard non-compartmental analysis.
Period 2: AUC (0-tau) of TFV
Time frame: Pre-dose, 15, 30, 45 minutes, 1 hour, 1 hour 30 minutes, 2, 3, 4, 5, 6, 8, 12 and 24 hours in Period 2 Day 7
Blood samples were collected at indicated time-points for analysis of AUC (0-tau). PK parameters were calculated by standard non-compartmental analysis.
Period 1: Cmax of TFV
Time frame: Pre-dose, 15, 30, 45 minutes, 1 hour, 1 hour 30 minutes, 2, 3, 4, 5, 6, 8, 12 and 24 hours in Period 1 Day 14
Blood samples were collected at indicated time-points for analysis of Cmax. PK parameters were calculated by standard non-compartmental analysis.
Period 2: Cmax of TFV
Time frame: Pre-dose, 15, 30, 45 minutes, 1 hour, 1 hour 30 minutes, 2, 3, 4, 5, 6, 8, 12 and 24 hours in Period 2 Day 7
Blood samples were collected at indicated time-points for analysis of Cmax. PK parameters were calculated by standard non-compartmental analysis.
Period 1: Ctau of TFV
Time frame: Pre-dose, 15, 30, 45 minutes, 1 hour, 1 hour 30 minutes, 2, 3, 4, 5, 6, 8, 12 and 24 hours in Period 1 Day 14
Blood samples were collected at indicated time-points for analysis of Ctau. PK parameters were calculated by standard non-compartmental analysis.
Period 2: Ctau of TFV
Time frame: Pre-dose, 15, 30, 45 minutes, 1 hour, 1 hour 30 minutes, 2, 3, 4, 5, 6, 8, 12 and 24 hours in Period 2 Day 7
Blood samples were collected at indicated time-points for analysis of Ctau. PK parameters were calculated by standard non-compartmental analysis.
91 secondary outcomes
Number of Participants With Non-serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAE)
Time frame: Up to Day 24
Period 1: Change From Baseline in Hematology Parameter of Platelet Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils and Basophils
Time frame: Baseline and at Days 7, and 14
Period 2: Change From Baseline in Hematology Parameter of Platelet Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils and Basophils
Time frame: Baseline and at Days 3, 7, 9
Period 1: Absolute Values of the Hematology Parameter of Platelet Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils and Basophils
Time frame: Baseline and at Days 7, and 14
Period 2: Absolute Values of the Hematology Parameter of Platelet Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils and Basophils
Time frame: Baseline and at Days 3, 7, 9
Period 1: Change From Baseline in Hematology Parameter of Hematocrit
Time frame: Baseline and at Days 7, 14
Period 2: Change From Baseline in Hematology Parameter of Hematocrit
Time frame: Baseline and at Days 3, 7, 9
Period 1: Absolute Values of the Hematology Parameter: Hematocrit
Time frame: Baseline and at Days 7, 14
Period 2: Absolute Values of the Hematology Parameter: Hematocrit
Time frame: Baseline and at Days 3, 7, 9
Period 1: Change From Baseline in Hematology Parameter of Hemoglobin
Time frame: Baseline and at Days 7, 14
Period 2: Change From Baseline in Hematology Parameter of Hemoglobin
Time frame: Baseline and at Days 3, 7, 9
Period 1: Absolute Values of the Hematology Parameter: Hemoglobin
Time frame: Baseline and at Days 7, 14
Period 2: Absolute Values of the Hematology Parameter: Hemoglobin
Time frame: Baseline and at Days 3, 7, 9
Period 1: Change From Baseline in Hematology Parameter of Mean Corpuscle Hemoglobin (MCH)
Time frame: Baseline and at Days 7, 14
Period 2: Change From Baseline in Hematology Parameter of MCH
Time frame: Baseline and at Days 3, 7, 9
Period 1: Absolute Values of the Hematology Parameter: MCH
Time frame: Baseline and at Days 7, 14
Period 2: Absolute Values of the Hematology Parameter: MCH
Time frame: Baseline and at Days 3, 7, 9
Period 1: Change From Baseline in Hematology Parameter of Mean Corpuscle Volume (MCV)
Time frame: Baseline and at Days 7, 14
Period 2: Change From Baseline in Hematology Parameter of MCV
Time frame: Baseline and at Days 3, 7, 9
Period 1: Absolute Values of the Hematology Parameter: MCV
Time frame: Baseline and at Days 7, 14
Period 2: Absolute Values of the Hematology Parameter: MCV
Time frame: Baseline and at Days 3, 7, 9
Period 1: Change From Baseline in Hematology Parameter of Erythrocytes
Time frame: Baseline and at Days 7, 14
Period 2: Change From Baseline in Hematology Parameter of Erythrocytes
Time frame: Baseline and at Days 3, 7, 9
Period 1: Absolute Values of the Hematology Parameter: Erythrocytes
Time frame: Baseline and at Days 7, 14
Period 2: Absolute Values of the Hematology Parameter: Erythrocytes
Time frame: Baseline and at Days 3, 7, 9
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
Time frame: Baseline and at Days 7, 14
Period 2: Change From Baseline in Clinical Chemistry Parameter of Glucose, Anion Gap, Cholesterol, Calcium, Potassium, Sodium, BUN, CO2, Chloride and Phosphorus
Time frame: Baseline and at Days 3, 7, 9
Period 1: Absolute Values of Clinical Chemistry Parameter of Glucose, Anion Gap, Cholesterol, Calcium, Potassium, Sodium, BUN, CO2, Chloride and Phosphorus
Time frame: Baseline and at Days 7, 14
Period 2: Absolute Values of Clinical Chemistry Parameter of Glucose, Anion Gap, Cholesterol, Calcium, Potassium, Sodium, BUN, CO2, Chloride and Phosphorus
Time frame: Baseline and at Days 3, 7, 9
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)
Time frame: Baseline and at Days 7, 14
Period 2: Change From Baseline in Clinical Chemistry Parameter of Alkaline Phosphatase, ALT, AST, LDH, GGT, and CK
Time frame: Baseline and at Days 3, 7, 9
Period 1: Absolute Values of Clinical Chemistry Parameter of Alkaline Phosphatase, ALT, AST, LDH, GGT, and CK
Time frame: Baseline and at Days 7, 14
Period 2: Absolute Values of Clinical Chemistry Parameter of Alkaline Phosphatase, ALT, AST, LDH, GGT, and CK
Time frame: Baseline and at Days 3, 7, 9
Period 1: Change From Baseline in Clinical Chemistry Parameter of Lipase and Amylase
Time frame: Baseline and at Days 7, 14
Period 2: Change From Baseline in Clinical Chemistry Parameter of Lipase and Amylase
Time frame: Baseline and at Days 3, 7, 9
Period 1: Absolute Values of Chemistry Parameters of Lipase and Amylase
Time frame: Baseline and at Days 7, 14
Period 2: Absolute Values of Chemistry Parameters of Lipase and Amylase
Time frame: Baseline and at Days 3, 7, 9
Period 1: Change From Baseline in Clinical Chemistry Parameter of Total Bilirubin, Direct Bilirubin, and Creatinine
Time frame: Baseline and at Days 7, 14
Period 2: Change From Baseline in Clinical Chemistry Parameter of Total Bilirubin, Direct Bilirubin, and Creatinine
Time frame: Baseline and at Days 3, 7, 9
Period 1: Absolute Values of Clinical Chemistry Parameter of Total Bilirubin, Direct Bilirubin, and Creatinine
Time frame: Baseline and at Days 7, 14
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Apr 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 33753329Pene Dumitrescu T, Joshi SR, Xu J, Zhan J, Johnson M, Butcher L, Zimmerman E, Webster L, Davidson AM, Lataillade M, Min S. A Phase I Evaluation of the Pharmacokinetics and Tolerability of the HIV-1 Maturation Inhibitor GSK3640254 and Tenofovir Alafenamide/Emtricitabine in Healthy Participants. Antimicrob Agents Chemother. 2021 May 18;65(6):e02173-20. doi: 10.1128/AAC.02173-20. Print 2021 May 18.
- Individual participant dataSharing planned: Yes. IPD for this study will be made available via the Clinical Study Data Request site.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
ViiV Healthcare
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Tenofovir alafenamide/emtricitabine and GSK3640254 in people with HIV Infections, run by ViiV Healthcare at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Apr 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 (time frame: Pre-dose, 15, 30, 45 minutes, 1 hour, 1 hour 30 minutes, 2, 3, 4, 5, 6, 8, 12 and 24 hours in Period 1 Day 14). The study lists 16 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03836729, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Apr 2020.