CompletedNCT04488770Updated Feb 17, 2023Results posted

Safety, Tolerability and Pharmacokinetic Investigation of GSK3882347 in Healthy Participants.

A Phase 1 interventional study of GSK3882347 and Placebo in Urinary Tract Infections, sponsored by GlaxoSmithKline. Completed at 1 site in United Kingdom. Open to participants aged 18 Years to 50 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2023-02-17.

Sponsored by GlaxoSmithKline · Phase 1, Interventional, and Treatment

Phase: Phase 1
Study type: Interventional
Enrollment: 61
Allocation: Randomized
Ages: 18 Years to 50 Years
Sex: All

Study summary

This is a phase 1, 2-part, double-blind (sponsor-unblinded), randomized, placebo-controlled, first time in human (FTIH) study, that includes both single-ascending and multiple-ascending dose phase to assess the safety, tolerability, and pharmacokinetics (PK) of GSK3882347 in healthy adult men and Woman of Non Childbearing Potential (WONCBP). Part 1 will be the single ascending dose (SAD) phase and Part 2 will be the multiple ascending dose (MAD) phase. Each participant in the SAD cohort will receive a single dose of GSK3882347 or placebo (PBO) in 3:1 ratio and in Part 2 (MAD), participants will be randomized in a 4:1 ratio to receive active treatment and placebo. Part 1 will consist of two cohorts with a maximum of four-period for each cohort, the food effect evaluation will be conducted in last period (Period 4) in only one of the cohorts based on the observed human pharmacokinetics (PK). Part 2 will consist of maximum of four cohorts for each of the MAD dose or placebo.

Conditions studied

Urinary Tract Infections

Browse trials for

Urinary Tract Infections 779

Keywords

SAD
MAD
FTIH
Pharmacokinetics
Urinary Tract Infections
GSK3882347

In context

Urinary Tract Infections

779 studies on the registry are indexed under Urinary Tract Infections; 132 are open to participants now.

This study's enrollment of 61 is below the median of 130 across 544 interventional studies indexed under Urinary Tract Infections.

Browse Urinary Tract Infections studies →

Lead sponsor

GlaxoSmithKline is the lead sponsor of 3,647 studies on the registry; 118 are open to participants now.

Of its 264 completed or terminated interventional studies of FDA-regulated products, 239 (91%) have results posted.

Browse GlaxoSmithKline studies →

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years to 50 Years
Sexes eligible: All
Accepts healthy volunteers: Yes

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

Participant must be 18 to 50 years of age inclusive, at the time of signing the informed consent.
Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring. A participant with a clinical abnormality or laboratory parameter(s) not specifically listed in the exclusion or exclusion criteria that is outside the reference range for the population being studied may be included only if the investigator, in consultation with the Medical Monitor (if required), agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
Participants with Body weight at least 50.0 kilograms (kg) (110 pound [lbs]) for males and 45.0 kg (99 lbs.) for females; and body mass index (BMI) within the range 18.5 - 32.0 kilograms per meter square (kg/m\^2) (inclusive).
Male and female participants; a female participant is eligible to participate if she is of WONCBP; Male participants are eligible to participate if they agree to the following during the intervention period for at least five days, corresponding to time needed to eliminate study intervention(s) (e.g. 5 terminal half-lives) after the last dose of study intervention), refrain from donating sperm, be abstinent from heterosexual or homosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent; must agree to use contraception/barrier, agree to use a male condom.
Capable of giving signed informed consent as described in which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.

Exclusion criteria

Exclusion Criteria:

Participants with history or presence of cardiovascular, respiratory, hepatic, urological, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study intervention; or interfering with the interpretation of data
Alanine transaminase (ALT) greater than 1.5 times upper limit of normal (ULN).
Bilirubin greater than 1.5 times ULN (isolated bilirubin greater than1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin is less than 35%)
Current or chronic history of liver disease or known hepatic or biliary abnormalities (except for Gilbert's syndrome or asymptomatic gallstones).
Medical history of cardiac arrhythmias or cardiac disease or a family or personal history of long QT syndrome.
Male participants with heart rate of less than 45 or greater than 100 beats per minute (bpm), females with less than 50 or greater than 100 bpm.
Participants with PR interval less than 120 or greater than 220 milliseconds (msec); QRS duration less than 70 msec or greater than 120 msec; QTcF interval greater than 450 msec.
Evidence of previous myocardial infarction on ECG (does not include ST segment changes associated with re-polarization).
Any conduction abnormality (including but not specific to left or right complete bundle branch block, atrioventricular (AV) block [2nd degree or higher], Wolff-Parkinson-White [WPW] syndrome).
Sinus Pauses greater than 3 seconds.
Any significant arrhythmia which, in the opinion of the Investigator or GSK Medical Monitor, will interfere with the safety for the individual participant.
Non-sustained or sustained ventricular tachycardia (3 consecutive ventricular ectopic beats).
Current or history of renal disease, or estimated creatinine clearance \<90 milliliter (mL)/minute/1.73meter\^2 or serum creatinine greater than ULN at screening.
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) before the first dose of study intervention, unless in the opinion of the Investigator and the GSK medical monitor, the medication will not interfere with the study procedures or compromise participant safety.
Use of a systemic antimicrobial within 30 days of screening.
Participation in the study would result in loss of blood or blood products in excess of 500 mL within 56 days.
Exposure to more than 4 new chemical entities within 12 months prior to the first dosing day.
Current enrolment or past participation within the last 30 days before signing of consent in any other clinical study involving an investigational study intervention or any other type of medical research.
Positive human immunodeficiency virus (HIV) antibody test.
Presence of Hepatitis B surface antigen (HBsAg) at screening or within 3 months prior to first dose of study intervention.
Positive Hepatitis C antibody test result at screening or within 3 months prior to first dose of study intervention.
Positive Hepatitis C ribonucleic acid (RNA) test result at screening or within 3 months prior to first dose of study intervention.
Positive pre-study drug/alcohol screen.
Any history of substance abuse or a positive test for drugs of abuse at screening or admission.
A positive highly sensitive pregnancy test (urine or serum as required by local regulations) at screening.
A positive laboratory confirmation of COVID-19 infection, or high clinical index of suspicion for COVID-19.
Part 1 (Food Effect): Participant must have no dietary restrictions (e.g., lactose intolerance) or inability to eat a high fat meal.
Regular alcohol consumption within 6 months prior to the study defined as: An average weekly intake of greater than 21 units for males or greater than 14 units for females. One unit is equivalent to approximately (250 mL) of beer, (100 mL) of wine or (35 mL) measure of spirits.
Positive smoke breathalyzer indicative of smoking history at screening and each in-house admission to the clinical research unit or regular use of tobacco- or nicotine-containing products (e.g. nicotine patches or vaporizing devices) within 6 months prior to screening.
Hypersensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates participation in the study.

Study design

Phase: Phase 1
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover assignment
Masking: Double (Participant, Investigator)
Enrollment: 61 participants (actual)

Study arms

Experimental
Part 1 (SAD) Cohort 1:Participants receiving GSK3882347
In this single ascending dose phase, participants will receive GSK3882347 50 milligram (mg), 150 mg and 250 mg orally on Day 1 of period 1, 2 and 3 respectively. Period 4 will be conducted to assess food effect based on the observed human PK.
Drug: GSK3882347
Placebo comparator
Part 1 (SAD),Cohort 1:Participants receiving Placebo
In this single ascending dose phase, participants will receive matching Placebo orally on Day 1 of period 1, 2 and 3. Period 4 will be conducted to assess food effect based on the observed human PK.
Drug: Placebo
Experimental
Part 1 (SAD),Cohort 2: Participants receiving GSK3882347
In this single ascending dose phase, participants will receive GSK3882347 500 mg, 15 mg and 900 mg orally on Day 1 of period 1, 3 and 2 respectively.
Drug: GSK3882347
Placebo comparator
Part 1 (SAD),Cohort 2: Participants receiving Placebo
In this single ascending dose phase, participants will receive matching Placebo orally on Day 1 of period 1, 3 and 2.
Drug: Placebo
Experimental
Part 2 (MAD),Cohort 3: Participants receiving GSK3882347 50mg
In this multiple ascending dose phase, participants will receive GSK3882347 50 mg orally on Day 1 to Day 7 of the study. The dose to be administered may be changed based on clinical safety, tolerability and PK findings in Part 1.
Drug: GSK3882347
Placebo comparator
Part 2 (MAD),Cohort 3: Participants receiving Placebo
In this multiple ascending dose phase, participants will receive matching Placebo orally on Day 1 to Day 7 of the study.
Drug: Placebo
Experimental
Part 2 (MAD),Cohort 4: Participants receiving GSK3882347 150mg
GSK3882347 150 mg will be administered orally to the participants on Day 1 to day 7 of the study. This is a projected dose. The dose administered in Part 2, Cohort 4 will be based on PK/PD results from preceding dosing cohorts.
Drug: GSK3882347
Placebo comparator
Part 2 (MAD),Cohort 4: Participants receiving Placebo
In this multiple ascending dose phase, participants will receive matching Placebo orally on Day 1 to Day 7 of the study.
Drug: Placebo
Experimental
Part 2(MAD),Cohort 5: Participants receiving GSK3882347 500mg
GSK3882347 500 mg will be administered orally to the participants on Day 1 to day 7 of the study. This is a projected dose. The dose administered in Part 2, Cohort 5 will be based on PK/PD results from preceding dosing cohorts.
Drug: GSK3882347
Placebo comparator
Part 2 (MAD),Cohort 5: Participants receiving Placebo
In this multiple ascending dose phase, participants will receive matching Placebo orally on Day 1 to Day 7 of the study.
Drug: Placebo
Experimental
Part 2(MAD),Cohort 6: Participants receiving GSK3882347 900mg
GSK3882347 900 mg will be administered orally to the participants on Day 1 to day 7 of the study. This is a projected dose. The dose administered in Part 2, Cohort 6 will be based on PK/PD results from preceding dosing cohorts.
Drug: GSK3882347
Placebo comparator
Part 2(MAD),Cohort 6: Participants receiving Placebo
In this multiple ascending dose phase, participants will receive matching Placebo orally on Day 1 to Day 7 of the study.
Drug: Placebo

Interventions

DrugGSK3882347
Capsule of 10-200mg dose strength will be provided in labelled High Density Polyethylene (HDPE) bottles.
DrugPlacebo
Matching strength placebo capsules will be provided

What researchers measure

Primary outcomes

Part 1: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs)
An 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 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 or any other situation according to medical or scientific judgment. Number of participants with common (greater than or equal to \[\>=\]5 percent \[%\]) non-serious AEs is presented.
Time frame: Up to 3 months
Part 2: Number of Participants With Non-serious AEs and SAEs
An 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 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 or any other situation according to medical or scientific judgment. Number of participants with common (\>=5%) non-serious AEs is presented.
Time frame: Up to 26 days
Part 1: Number of Participants With Treatment Related AEs
An 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. Number of participants with treatment related AEs is presented.
Time frame: Up to 3 months
Part 2: Number of Participants With Treatment Related AEs
An 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. Number of participants with treatment related AEs is presented.
Time frame: Up to 26 days
Part 1: Number of Participants With Worst-case Hematology Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline
Blood samples were collected to analyze hematocrit,hemoglobin,leukocytes,lymphocytes,neutrophils and platelets. PCI ranges were \<0.075 or \>0.54 proportion of red blood cells in blood for hematocrit, \<25 or \>180 grams per liter(g/L) for hemoglobin,\<3 or \>20 x10\^9 cells per liter(cells/L) for leukocytes,\<0.8 x10\^9 cells/L for lymphocytes,\<1.5 x10\^9 cells/L for neutrophils and \<100 or \>550 x10\^9 cells/L for platelets.Participants were counted in worst case category that their value changes to(low,within range or no change or high),unless there is no change in their category.Participants whose laboratory value category was unchanged(for example\[e.g.\],High to High),or whose value became within range, were recorded in"To within Range or No Change" category.Participants were counted twice if the participant has values that changed 'To Low' and 'To High',so the percentages may not add to 100%.Baseline=latest pre-dose assessment with a non-missing value, including those from unscheduled visits
Time frame: Up to 3 months
Part 2: Number of Participants With Worst-case Hematology Results Relative to PCI Criteria Post-Baseline Relative to Baseline
Blood samples were collected to analyze hematocrit,hemoglobin,leukocytes,lymphocytes,neutrophils and platelets. PCI ranges were \<0.075 or \>0.54 proportion of red blood cells in blood for hematocrit, \<25 or \>180 grams per liter(g/L) for hemoglobin,\<3 or \>20 x10\^9 cells per liter(cells/L) for leukocytes,\<0.8 x10\^9 cells/L for lymphocytes,\<1.5 x10\^9 cells/L for neutrophils and \<100 or \>550 x10\^9 cells/L for platelets.Participants were counted in worst case category that their value changes to(low,within range or no change or high),unless there is no change in their category.Participants whose laboratory value category was unchanged(e.g.,High to High),or whose value became within range, were recorded in"To within Range or No Change" category.Participants were counted twice if the participant has values that changed 'To Low' and 'To High',so the percentages may not add to 100%.Baseline=latest pre-dose assessment with a non-missing value, including those from unscheduled visits
Time frame: Up to 26 days
Part 1: Number of Participants With Worst-case Clinical Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline
Blood samples were collected to analyze PCI ranges: \>=2 times Upper limit of Normal(ULN) Units per Liter(U/L) for Alanine aminotransferase(ALT),\>=2 times ULN U/L for alkaline phosphatase(ALP), \>=2 times ULN U/L for aspartate aminotransferase(AST),\>=1.5 times ULN micromoles/L for bilirubin,\<2 or \>2.75 millimoles/L (mmol/L) for calcium,\<3 or \>9 mmol/L for glucose,\<3 or \>5.5 mmol/L for potassium and \<130 or \>150 mmol/L for sodium.Participants were counted in worst case category that their value changes to(low,within range or no change or high),unless there is no change in their category.Participants whose laboratory value category was unchanged(e.g.,High to High),or whose value became within range,were recorded in"To within Range or No Change" category.Participants were counted twice if the participant has values that changed 'To Low' and 'To High',so the percentages may not add to 100%.Baseline=latest pre-dose assessment with a non-missing value,including those from unscheduled visits
Time frame: Up to 3 months
Part 2: Number of Participants With Worst-case Clinical Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline
Blood samples were collected to analyze PCI ranges: \>=2 times ULN U/L for Alanine aminotransferase(ALT),\>=2 times ULN U/L for alkaline phosphatase(ALP), \>=2 times ULN U/L for aspartate aminotransferase(AST),\>=1.5 times ULN micromoles/L for bilirubin,\<2 or \>2.75 mmol/L for calcium,\<3 or \>9 mmol/L for glucose,\<3 or \>5.5 mmol/L for potassium and \<130 or \>150 mmol/L for sodium.Participants were counted in worst case category that their value changes to(low,within range or no change or high),unless there is no change in their category.Participants whose laboratory value category was unchanged(e.g.,High to High),or whose value became within range,were recorded in"To within Range or No Change" category.Participants were counted twice if the participant has values that changed 'To Low' and 'To High',so the percentages may not add to 100%.Baseline=latest pre-dose assessment with a non-missing value,including those from unscheduled visits.
Time frame: Up to 26 days
Part 1: Number of Participants With Worst Case Urinalysis Results Post Baseline Relative to Baseline
Urine samples were collected for the analysis of urine parameters including occult blood and protein by dipstick. The dipstick test gave results in a semi-quantitative manner, and results for urinalysis parameters were recorded as no change/decreased, increase to positive for urine occult blood and protein indicating proportional concentrations in the urine sample. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Number of participants with worst case urinalysis results Post Baseline relative to Baseline is presented.
Time frame: Up to 3 months
Part 2: Number of Participants With Worst Case Urinalysis Results Post Baseline Relative to Baseline
Urine samples were collected for the analysis of urine parameters including occult blood and protein by dipstick. The dipstick test gave results in a semi-quantitative manner (proportional concentrations in urine samples), and results for urinalysis parameters were recorded as no change/decreased, increase to positive for urine occult blood and protein. 'No change/decreased' indicates no change from Baseline results or decreased in results from Baseline including change in negative results. 'Increase to positive' indicates increase in result from Baseline. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Number of participants with worst case urinalysis results Post Baseline relative to Baseline is presented.
Time frame: Up to 26 days
Part 1: Number of Participants With Worst Case Vital Signs Results Relative to PCI Criteria Post Baseline Relative to Baseline
Vital signs were assessed including Systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse rate (PR). PCI ranges were \<85 (Low), 85-160 (Normal) and \>160 (High) for SBP; \<45 (Low), 45-100 (Normal), \>100 (High) for DBP; \<40 (Low), 40-110 (Normal), \>110 (High) for pulse rate. Participants were counted in worst case category that their value changes to(low,within range or no change, high),unless there is no change in their category.Participants whose laboratory value category was unchanged(e.g.,High to High),or whose value became within range, were recorded in"To within Range or No Change" category.Participants were counted twice if the participant has values that changed 'To Low' and 'To High',so the percentages may not add to 100%.Baseline was defined as latest pre-dose assessment with a non-missing value, including those from unscheduled visits
Time frame: Up to 3 months
Part 2: Number of Participants With Worst Case Vital Signs Results Relative to PCI Criteria Post Baseline Relative to Baseline
Vital signs were assessed including Systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse rate (PR). PCI ranges were \<85 (Low), 85-160 (Normal) and \>160 (High) for SBP; \<45 (Low), 45-100 (Normal), \>100 (High) for DBP; \<40 (Low), 40-110 (Normal), \>110 (High) for pulse rate. Participants were counted in worst case category that their value changes to(low,within range or no change, high),unless there is no change in their category.Participants whose laboratory value category was unchanged(e.g.,High to High),or whose value became within range, were recorded in"To within Range or No Change" category.Participants were counted twice if the participant has values that changed 'To Low' and 'To High',so the percentages may not add to 100%.Baseline was defined as latest pre-dose assessment with a non-missing value, including those from unscheduled visits
Time frame: Up to 26 days
Part 1: Number of Participants With Worst Case Abnormal Electrocardiogram (ECG) Results Post Baseline Relative to Baseline
A 12-lead ECG was recorded with the participant in a semi-supine position after a rest of at least 10 minutes. Twelve lead ECGs were obtained by using an automated ECG machine that measured PR, QRS, QT, and corrected QT (QTc) intervals and calculated heart rate. Data for abnormal not clinically significant (NCS) and clinically significant (CS) ECG findings are presented. CS abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Baseline was defined as latest pre-dose assessment with a non-missing value, including those from unscheduled visits.
Time frame: Up to 3 months
Part 2: Number of Participants With Worst Case Abnormal ECG Results Post Baseline Relative to Baseline
A 12-lead ECG was recorded with the participant in a semi-supine position after a rest of at least 10 minutes. Twelve lead ECGs were obtained by using an automated ECG machine that measured PR, QRS, QT, and corrected QT (QTc) intervals and calculated heart rate. Data for abnormal not clinically significant (NCS) and clinically significant (CS) ECG findings are presented. CS abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Baseline was defined as latest pre-dose assessment with a non-missing value, including those from unscheduled visits.
Time frame: Up to 26 days
Part 1: Area Under the Concentration-time Curve From Time Zero to 24 Hours (AUC[0-24]) After Single Dose Administration of GSK3882347
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16 and 24 hours post-dose in each treatment period
Part 1: Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUC[0-t]) After Single Dose Administration of GSK3882347
Blood samples were collected at indicated time points for PK analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 32, 48, 72 and 96 hours post-dose in each treatment period
Part 1: Area Under the Concentration-time Curve Extrapolated From Time Zero to Infinity (AUC[0-infinity]) After Single Dose Administration of GSK3882347
Blood samples were collected at indicated time points for PK analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 32, 48, 72 and 96 hours post-dose in each treatment period
Part 1: Maximum Plasma Concentration (Cmax) After Single Dose Administration of GSK3882347
Blood samples were collected at indicated time points for PK analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 32, 48, 72 and 96 hours post-dose in each treatment period
Part 1: Plasma Concentrations at 24 Hours (C24h) After Single Dose Administration of GSK3882347
Blood samples were collected at indicated time points for PK analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16 and 24 hours post-dose in each treatment period
Part 1: Time to Cmax (Tmax) After Single Dose Administration of GSK3882347
Blood samples were collected at indicated time points for PK analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 32, 48, 72 and 96 hours post-dose in each treatment period
Part 1: Lag Time for Absorption (Tlag) After Single Dose Administration of GSK3882347
Blood samples were collected at indicated time points for PK analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 32, 48, 72 and 96 hours post-dose in each treatment period
Part 1: Terminal Elimination Half-life (T1/2) After Single Dose Administration of GSK3882347
Blood samples were collected at indicated time points for PK analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 32, 48, 72 and 96 hours post-dose in each treatment period
Part 2: Area Under the Concentration-time Curve Over the Dosing Interval Tau (AUC[0-tau]) After Repeat Dose Administration of GSK3882347
Blood samples were collected at indicated time points for PK analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Days 1 and 7: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16, 24 hours post-dose
Part 2: Cmax After Repeat Dose Administration of GSK3882347
Blood samples were collected at indicated time points for PK analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Days 1 and 7: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16, 24 hours post-dose
Part 2: Tmax After Repeat Dose Administration of GSK3882347
Blood samples were collected at indicated time points for PK analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Days 1 and 7: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16, 24 hours post-dose
Part 2: Plasma Concentrations Over the Dosing Interval (Ctau) After Repeat Dose Administration of GSK3882347
Blood samples were collected at indicated time points for PK analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Days 1 and 7: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16, 24 hours post-dose
Part 1: Urine Concentration Between 22-24 Hours (C22-24) After Single Dose Administration of GSK3882347
Urine samples were collected at indicated time points for PK analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Day 1: 22-24 hours post-dose in each treatment period
Part 2: Urine Concentration Between 22-24 Hours (C22-24) After Repeat Dose Administration of GSK3882347
Urine samples were collected at indicated time points for PK analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Day 1 and Day 7: 22-24 hours post-dose
Part 1: Amount of Drug Excreted in Urine of Unchanged Drug (Ae Total) After Single Dose Administration of GSK3882347
Urine samples were collected at indicated time points for PK analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: At 0-2, 2-4, 4-6, 6-8, 8-10, 10-12, 12-22, 22-24, 24-26, 26-32, 32-38, 38-48, 48-60, 60-72, 72-84, 84-96 hours post-dose in each treatment period
Part 2: Amount of Drug Excreted in Urine of Unchanged Drug (Ae Total) After Repeat Dose Administration of GSK3882347
Urine samples were collected at indicated time points for PK analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Days 1 and 7: At 0-2, 2-4, 4-6, 6-8, 8-10, 10-12, 12-22, 22-24 hours post-dose
Part 1: Percentage of the Given Dose of Drug Excreted in Urine (%fe Total) After Single Dose Administration of GSK3882347
Urine samples were collected at indicated time points for PK analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis. %fe was calculated as: (Ae total/Dose)\*100 percent (%).
Time frame: At 0-2, 2-4, 4-6, 6-8, 8-10, 10-12, 12-22, 22-24, 24-26, 26-32, 32-38, 38-48, 48-60, 60-72, 72-84, 84-96 hours post-dose in each treatment period
Part 2: Percentage of the Given Dose of Drug Excreted in Urine (%fe Total) After Single Dose Administration of GSK3882347
Urine samples were collected at indicated time points for PK analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis. %fe was calculated as: (Ae total/Dose)\*100%.
Time frame: Day 1 and Day 7: At 0-2, 2-4, 4-6, 6-8, 8-10, 10-12, 12-22, 22-24 hours post-dose
Part 1: Renal Clearance of Drug (CLr) After Single Dose Administration of GSK3882347
Urine samples were collected at indicated time points for PK analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis. CLr was calculated as: Ae total/AUC(0-t)
Time frame: At 0-2, 2-4, 4-6, 6-8, 8-10, 10-12, 12-22, 22-24, 24-26, 26-32, 32-38, 38-48, 48-60, 60-72, 72-84, 84-96 hours post-dose in each treatment period
Part 2: Renal Clearance of Drug (CLr) After Repeat Dose Administration of GSK3882347
Urine samples were collected at indicated time points for PK analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis. CLr was calculated as: Ae total/AUC(0-t).
Time frame: Day 1 and Day 7: At 0-2, 2-4, 4-6, 6-8, 8-10, 10-12, 12-22, 22-24 hours post-dose

Secondary outcomes

Part 1: Area Under the Concentration-time Curve From Time Zero to 12 Hours (AUC[0-12]) After Single Dose Administration of GSK3882347
Blood samples were collected at indicated time points for PK analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8 and 12 hours post-dose in each treatment period
Part 1: Plasma Concentrations at 12 Hours (C12) After Single Dose Administration of GSK3882347
Blood samples were collected at indicated time points for PK analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8 and 12 hours post-dose in each treatment period
Part 1: Apparent Oral Clearance (CL/F) After Single Dose Administration of GSK3882347
Blood samples were collected at indicated time points for PK analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 32, 48, 72 and 96 hours post-dose in each treatment period
Part 1: Apparent Volume of Distribution After Oral Administration (Vz/F) After Single Dose Administration of GSK3882347
Blood samples were collected at indicated time points for PK analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 32, 48, 72 and 96 hours post-dose in each treatment period
Part 1: Mean Residence Time (MRT) After Single Dose Administration of GSK3882347
Blood samples were collected at indicated time points for PK analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 32, 48, 72 and 96 hours post-dose in each treatment period
Part 2: Area Under the Concentration-time Curve From Time Zero to 12 Hours (AUC[0-12]) After Repeat Dose Administration of GSK3882347
Blood samples were collected at indicated time points for PK analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Days 1 and 7: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8 and 12 hours post-dose
Part 2: Plasma Concentrations at 12 Hours (C12) After Repeat Dose Administration of GSK3882347
Blood samples were collected at indicated time points for PK analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Days 1 and 7: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8 and 12 hours post-dose
Part 1: Dose Proportionality of GSK3882347 for Dose Levels 15 mg to 900 mg Using AUC(0-infinity) After Single Dose Administration of GSK3882347 Under Fasted Condition
Blood samples were collected at indicated time points for PK analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis. Dose proportionality was assessed using Power model. Log-e(dose) was fitted as fixed effect and participant was fitted as random effect. Kenward and Roger method and unstructured covariance structure was used. Slope and 90% confidence interval (CI) for the slope are presented. The SD 250 mg fed treatment was not considered in the analysis.
Time frame: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 32, 48, 72 and 96 hours post-dose in each treatment period
Part 1: Dose Proportionality of GSK3882347 for Dose Levels 15 mg to 900 mg Using Cmax After Single Dose Administration of GSK3882347 Under Fasted Condition
Blood samples were collected at indicated time points for PK analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis. Dose proportionality was assessed using Power model. Log-e(dose) was fitted as fixed effect and participant was fitted as random effect. Kenward and Roger method and unstructured covariance structure was used. Slope and 90% CI for the slope are presented. The SD 250 mg fed treatment was not considered in the analysis.
Time frame: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 32, 48, 72 and 96 hours post-dose in each treatment period
Part 2: Dose Proportionality of GSK3882347 for Dose Levels 50 mg to 900 mg Using AUC(0-tau) After Repeat Dose Administration of GSK3882347
Blood samples were collected at indicated time points for PK analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis. Dose proportionality was assessed using Power model. Log-e(dose) was fitted as fixed effect and participant was fitted as random effect. Kenward and Roger method and unstructured covariance structure was used. Slope and 90% CI for the slope are presented.
Time frame: Day 1 and Day 7: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16, 24 hours post-dose
Part 2: Dose Proportionality of GSK3882347 for Dose Levels 50 mg to 900 mg Using Cmax After Repeat Dose Administration of GSK3882347
Blood samples were collected at indicated time points for PK analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis. Dose proportionality was assessed using Power model. Log-e(dose) was fitted as fixed effect and participant was fitted as random effect. Kenward and Roger method and unstructured covariance structure was used. Slope and 90% CI for the slope are presented.
Time frame: Day 1 and Day 7: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16, 24 hours post-dose
Part 2: Observed Accumulation Ratio (Ro) Using AUC(0-tau) After Repeat Dose Administration of GSK3882347
Blood samples were collected at indicated time points for PK analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis. Accumulation ratio was calculated as AUC(0-tau) at Day 7 divided by AUC(0-tau) at Day 1 for GSK3882347. Mixed effect model was used to assess accumulation ratio for the log transformed parameters. Treatment, day and the interaction of treatment and day were fitted as fixed effect. Participant was fitted as random effect. Kenward and Roger method and unstructured covariance structure was used.
Time frame: Day 1 and Day 7: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16, 24 hours post-dose
Part 2: Time Invariance of GSK3882347
Blood samples were collected at indicated time points for the analysis of time invariance. Time invariance was calculated as AUC(0-tau) at Day 7 divided by AUC(0-infinity) at Day 1 for GSK3882347. Mixed effect ANOVA model was used to assess time invariance for the log transformed parameters. Treatment, day and the interaction of treatment and day were fitted as fixed effect. Participant was fitted as random effect. Kenward and Roger method and unstructured covariance structure was used.
Time frame: Day 1 and Day 7: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16, 24 hours post-dose
Part 2: Pre-dose Plasma Concentrations After Repeat Dose Administration of GSK3882347 From Days 3 to 7
Blood samples were collected at indicated time points for PK analysis of GSK3882347.
Time frame: Days 3, 4, 5, 6 and 7: Pre-dose
Part 1: Area Under the Concentration-time Curve From Time Zero to 24 Hours (AUC[0-24]) After Single Dose Administration of GSK3882347 250 mg Under Fasted and Fed Conditions for Assessment of Food Effect
Blood samples were collected at indicated time points for PK analysis of GSK3882347 250 mg under fasted and fed conditions for assessment of food effect. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16 and 24 hours post-dose
Part 1: Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUC [0-t]) After Single Dose Administration of GSK3882347 250 mg Under Fasted and Fed Conditions for Assessment of Food Effect
Blood samples were collected at indicated time points for PK analysis of GSK3882347 250 mg under fasted and fed conditions for assessment of food effect. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 32, 48, 72 and 96 hours post-dose
Part 1: Area Under the Concentration-time Curve Extrapolated From Time Zero to Infinity (AUC [0-infinity]) After Single Dose Administration of GSK3882347 250 mg Under Fasted and Fed Conditions for Assessment of Food Effect
Blood samples were collected at indicated time points for PK analysis of GSK3882347 250 mg under fasted and fed conditions for assessment of food effect. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 32, 48, 72 and 96 hours post-dose
Part 1: Maximum Plasma Concentration (Cmax) After Single Dose Administration of GSK3882347 250 mg Under Fasted and Fed Conditions for Assessment of Food Effect
Blood samples were collected at indicated time points for PK analysis of GSK3882347 250 mg under fasted and fed conditions for assessment of food effect. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 32, 48, 72 and 96 hours post-dose
Part 1: Plasma Concentrations at 24 Hours (C24h) After Single Dose Administration of GSK3882347 250 mg Under Fasted and Fed Conditions for Assessment of Food Effect
Blood samples were collected at indicated time points for PK analysis of GSK3882347 250 mg under fasted and fed conditions for assessment of food effect. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16 and 24 hours post-dose
Part 1: Tmax After Single Dose Administration of GSK3882347 250 mg Under Fasted and Fed Conditions for Assessment of Food Effect
Blood samples were collected at indicated time points for PK analysis of GSK3882347 250 mg under fasted and fed conditions for assessment of food effect. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 32, 48, 72 and 96 hours post-dose
Part 1: Tlag After Single Dose Administration of GSK3882347 250 mg Under Fasted and Fed Conditions for Assessment of Food Effect
Blood samples were collected at indicated time points for PK analysis of GSK3882347 250 mg under fasted and fed conditions for assessment of food effect. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 32, 48, 72 and 96 hours post-dose

Results

Posted Feb 17, 2023

Participant flow

This was a 2-part, first-time-in-human (FTIH), dose-escalation, placebo (PBO)-controlled, single dose (SD) (Part 1) and repeat dose (RD) (Part 2) study to determine the safety, tolerability and pharmacokinetic (PK) profile of GSK3882347 in healthy participants. The study was conducted at a single center in the United Kingdom.

Part 1-Cohort 1: Period 1 (Up to 5 Days)

Participant flow — Part 1-Cohort 1: Period 1 (Up to 5 Days)
Milestone	Part1-Cohort1:GSK3882347 SD 50mg/SD 150mg/SD 250 mg/SD PBO	Part1-Cohort1:GSK3882347 SD 50mg/SD 150mg/SD PBO/SD 250mg Fed	Part1-Cohort1: GSK3882347 SD 50mg/SD PBO/SD 250mg/SD 250mg Fed	Part1-Cohort1:SD PBO/GSK3882347 SD 150mg/SD 250mg/SD 250mg Fed
Started	2	2	2	2
Completed	2	2	2	1
Not completed	0	0	0	1
Withdrew: Adverse event	0	0	0	1

Part 1-Cohort 1: Period 2 (Up to 5 Days)

Participant flow — Part 1-Cohort 1: Period 2 (Up to 5 Days)
Milestone	Part1-Cohort1:GSK3882347 SD 50mg/SD 150mg/SD 250 mg/SD PBO	Part1-Cohort1:GSK3882347 SD 50mg/SD 150mg/SD PBO/SD 250mg Fed	Part1-Cohort1: GSK3882347 SD 50mg/SD PBO/SD 250mg/SD 250mg Fed	Part1-Cohort1:SD PBO/GSK3882347 SD 150mg/SD 250mg/SD 250mg Fed
Started	2	2	2	2
Completed	2	2	2	2
Not completed	0	0	0	0

Part 1-Cohort 1: Period 3 (Up to 5 Days)

Participant flow — Part 1-Cohort 1: Period 3 (Up to 5 Days)
Milestone	Part1-Cohort1:GSK3882347 SD 50mg/SD 150mg/SD 250 mg/SD PBO	Part1-Cohort1:GSK3882347 SD 50mg/SD 150mg/SD PBO/SD 250mg Fed	Part1-Cohort1: GSK3882347 SD 50mg/SD PBO/SD 250mg/SD 250mg Fed	Part1-Cohort1:SD PBO/GSK3882347 SD 150mg/SD 250mg/SD 250mg Fed
Started	2	2	2	2
Completed	1	2	2	2
Not completed	1	0	0	0
Withdrew: Adverse event	1	0	0	0

Part 1-Cohort 1: Period 4 (Up to 5 Days)

Participant flow — Part 1-Cohort 1: Period 4 (Up to 5 Days)
Milestone	Part1-Cohort1:GSK3882347 SD 50mg/SD 150mg/SD 250 mg/SD PBO	Part1-Cohort1:GSK3882347 SD 50mg/SD 150mg/SD PBO/SD 250mg Fed	Part1-Cohort1: GSK3882347 SD 50mg/SD PBO/SD 250mg/SD 250mg Fed	Part1-Cohort1:SD PBO/GSK3882347 SD 150mg/SD 250mg/SD 250mg Fed
Started	2	2	2	2
Completed	2	2	2	2
Not completed	0	0	0	0

Part 1-Cohort 2: Period 1 (Up to 5 Days)

Participant flow — Part 1-Cohort 2: Period 1 (Up to 5 Days)
Milestone	Part 1-Cohort 2: SD PBO/GSK3882347 SD 900 mg/SD 15 mg	Part 1-Cohort 2: GSK3882347 SD 500 mg/SD PBO/SD 15 mg	Part 1-Cohort 2: GSK3882347 SD 500 mg/SD 900 mg/SD PBO	Part 1-Cohort 2: GSK3882347 SD 500 mg/SD 900 mg/SD 15 mg
Started	2	2	2	2
Completed	2	1	1	2
Not completed	0	1	1	0
Withdrew: Withdrawal by subject	0	1	1	0

Part 1-Cohort 2: Period 2 (Up to 5 Days)

Participant flow — Part 1-Cohort 2: Period 2 (Up to 5 Days)
Milestone	Part 1-Cohort 2: SD PBO/GSK3882347 SD 900 mg/SD 15 mg	Part 1-Cohort 2: GSK3882347 SD 500 mg/SD PBO/SD 15 mg	Part 1-Cohort 2: GSK3882347 SD 500 mg/SD 900 mg/SD PBO	Part 1-Cohort 2: GSK3882347 SD 500 mg/SD 900 mg/SD 15 mg
Started	2	2	2	2
Completed	1	2	2	2
Not completed	1	0	0	0
Withdrew: Physician decision	1	0	0	0

Part 1-Cohort 2: Period 3 (Up to 5 Days)

Participant flow — Part 1-Cohort 2: Period 3 (Up to 5 Days)
Milestone	Part 1-Cohort 2: SD PBO/GSK3882347 SD 900 mg/SD 15 mg	Part 1-Cohort 2: GSK3882347 SD 500 mg/SD PBO/SD 15 mg	Part 1-Cohort 2: GSK3882347 SD 500 mg/SD 900 mg/SD PBO	Part 1-Cohort 2: GSK3882347 SD 500 mg/SD 900 mg/SD 15 mg
Started	2	2	2	2
Completed	2	2	2	2
Not completed	0	0	0	0

Part 2 (Up to 26 Days)

Participant flow — Part 2 (Up to 26 Days)
Milestone	Part 2: Repeat Dose Placebo	Part 2: Repeat Dose GSK3882347 50 mg	Part 2: Repeat Dose GSK3882347 150 mg	Part 2: Repeat Dose GSK3882347 500 mg	Part 2: Repeat Dose GSK3882347 900 mg
Started	8	8	8	8	8
Completed	8	8	8	8	8
Not completed	0	0	0	0	0

Outcome measures

PrimaryPart 1: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs)

An 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 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 or any other situation according to medical or scientific judgment. Number of participants with common (greater than or equal to \[\>=\]5 percent \[%\]) non-serious AEs is presented.

Time frame:: Up to 3 months
Reported as:: Count of participants · Participants

Part 1: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs)
Participants	Part 1: Single Dose Placebo	Part 1: Single Dose GSK3882347 15 mg	Part 1: Single Dose GSK3882347 50 mg	Part 1: Single Dose GSK3882347 150 mg	Part 1: Single Dose GSK3882347 250 mg	Part 1: Single Dose GSK3882347 250 mg Fed	Part 1: Single Dose GSK3882347 500 mg	Part 1: Single Dose GSK3882347 900 mg
Non-serious AEs	7	1	2	2	3	2	3	2
SAEs	0	0	0	0	0	0	0	0

PrimaryPart 2: Number of Participants With Non-serious AEs and SAEs

Time frame:: Up to 26 days
Reported as:: Count of participants · Participants

Part 2: Number of Participants With Non-serious AEs and SAEs
Participants	Part 2: Repeat Dose Placebo	Part 2: Repeat Dose GSK3882347 50 mg	Part 2: Repeat Dose GSK3882347 150 mg	Part 2: Repeat Dose GSK3882347 500 mg	Part 2: Repeat Dose GSK3882347 900 mg
Non-serious AEs	5	4	2	7	7
SAEs	0	0	0	0	0

PrimaryPart 1: Number of Participants With Treatment Related AEs

Time frame:: Up to 3 months
Reported as:: Count of participants · Participants

Part 1: Number of Participants With Treatment Related AEs
Participants	Part 1: Single Dose Placebo	Part 1: Single Dose GSK3882347 15 mg	Part 1: Single Dose GSK3882347 50 mg	Part 1: Single Dose GSK3882347 150 mg	Part 1: Single Dose GSK3882347 250 mg	Part 1: Single Dose GSK3882347 250 mg Fed	Part 1: Single Dose GSK3882347 500 mg	Part 1: Single Dose GSK3882347 900 mg
Part 1: Number of Participants With Treatment Related AEs	0	0	0	0	0	0	0	0

PrimaryPart 2: Number of Participants With Treatment Related AEs

Time frame:: Up to 26 days
Reported as:: Count of participants · Participants

Part 2: Number of Participants With Treatment Related AEs
Participants	Part 2: Repeat Dose Placebo	Part 2: Repeat Dose GSK3882347 50 mg	Part 2: Repeat Dose GSK3882347 150 mg	Part 2: Repeat Dose GSK3882347 500 mg	Part 2: Repeat Dose GSK3882347 900 mg
Part 2: Number of Participants With Treatment Related AEs	1	2	0	0	0

PrimaryPart 1: Number of Participants With Worst-case Hematology Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline

Blood samples were collected to analyze hematocrit,hemoglobin,leukocytes,lymphocytes,neutrophils and platelets. PCI ranges were \<0.075 or \>0.54 proportion of red blood cells in blood for hematocrit, \<25 or \>180 grams per liter(g/L) for hemoglobin,\<3 or \>20 x10\^9 cells per liter(cells/L) for leukocytes,\<0.8 x10\^9 cells/L for lymphocytes,\<1.5 x10\^9 cells/L for neutrophils and \<100 or \>550 x10\^9 cells/L for platelets.Participants were counted in worst case category that their value changes to(low,within range or no change or high),unless there is no change in their category.Participants whose laboratory value category was unchanged(for example\[e.g.\],High to High),or whose value became within range, were recorded in"To within Range or No Change" category.Participants were counted twice if the participant has values that changed 'To Low' and 'To High',so the percentages may not add to 100%.Baseline=latest pre-dose assessment with a non-missing value, including those from unscheduled visits

Time frame:: Up to 3 months
Reported as:: Count of participants · Participants

Part 1: Number of Participants With Worst-case Hematology Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline
Participants	Part 1: Single Dose Placebo	Part 1: Single Dose GSK3882347 15 mg	Part 1: Single Dose GSK3882347 50 mg	Part 1: Single Dose GSK3882347 150 mg	Part 1: Single Dose GSK3882347 250 mg	Part 1: Single Dose GSK3882347 250 mg Fed	Part 1: Single Dose GSK3882347 500 mg	Part 1: Single Dose GSK3882347 900 mg
Hematocrit: To Low	2	2	0	0	1	1	1	1
Hematocrit: To within Range or No Change	12	4	6	6	5	5	5	5
Hematocrit: To High	0	0	0	0	0	0	0	0
Hemoglobin: To Low	0	0	0	0	0	0	0	0
Hemoglobin: To within Range or No Change	14	6	6	6	6	6	6	6
Hemoglobin: To High	0	0	0	0	0	0	0	0
Leukocytes: To Low	0	0	0	0	0	0	0	0
Leukocytes: To within Range or No Change	14	6	6	6	6	6	6	6
Leukocytes: To High	0	0	0	0	0	0	0	0
Lymphocytes: To Low	0	0	0	0	0	0	0	0
Lymphocytes: To within Range or No Change	14	6	6	6	6	6	6	6
Lymphocytes: To High	0	0	0	0	0	0	0	0
Neutrophils: To Low	0	0	0	0	0	0	0	0
Neutrophils: To within Range or No Change	14	6	6	6	6	6	6	6
Neutrophils: To High	0	0	0	0	0	0	0	0
Platelets: To Low	0	0	0	0	0	0	0	0
Platelets: To within Range or No Change	14	6	6	6	6	6	6	6
Platelets: To High	0	0	0	0	0	0	0	0

PrimaryPart 2: Number of Participants With Worst-case Hematology Results Relative to PCI Criteria Post-Baseline Relative to Baseline

Blood samples were collected to analyze hematocrit,hemoglobin,leukocytes,lymphocytes,neutrophils and platelets. PCI ranges were \<0.075 or \>0.54 proportion of red blood cells in blood for hematocrit, \<25 or \>180 grams per liter(g/L) for hemoglobin,\<3 or \>20 x10\^9 cells per liter(cells/L) for leukocytes,\<0.8 x10\^9 cells/L for lymphocytes,\<1.5 x10\^9 cells/L for neutrophils and \<100 or \>550 x10\^9 cells/L for platelets.Participants were counted in worst case category that their value changes to(low,within range or no change or high),unless there is no change in their category.Participants whose laboratory value category was unchanged(e.g.,High to High),or whose value became within range, were recorded in"To within Range or No Change" category.Participants were counted twice if the participant has values that changed 'To Low' and 'To High',so the percentages may not add to 100%.Baseline=latest pre-dose assessment with a non-missing value, including those from unscheduled visits

Time frame:: Up to 26 days
Reported as:: Count of participants · Participants

Part 2: Number of Participants With Worst-case Hematology Results Relative to PCI Criteria Post-Baseline Relative to Baseline
Participants	Part 2: Repeat Dose Placebo	Part 2: Repeat Dose GSK3882347 50 mg	Part 2: Repeat Dose GSK3882347 150 mg	Part 2: Repeat Dose GSK3882347 500 mg	Part 2: Repeat Dose GSK3882347 900 mg
Hematocrit: To Low	2	2	1	0	1
Hematocrit: To within Range or No Change	6	6	7	8	7
Hematocrit: To High	0	0	0	0	0
Hemoglobin: To Low	0	1	0	0	0
Hemoglobin: To within Range or No Change	8	7	8	8	8
Hemoglobin: To High	0	0	0	0	0
Leukocytes: To Low	1	0	0	0	0
Leukocytes: To within Range or No Change	7	8	8	8	8
Leukocytes: To High	0	0	0	0	0
Lymphocytes: To Low	0	0	0	0	0
Lymphocytes: To within Range or No Change	8	8	8	8	8
Lymphocytes: To High	0	0	0	0	0
Neutrophils: To Low	0	0	1	0	0
Neutrophils: To within Range or No Change	8	8	7	8	8
Neutrophils: To High	0	0	0	0	0
Platelets: To Low	0	0	0	0	0
Platelets: To within Range or No Change	8	8	8	8	8
Platelets: To High	0	0	0	0	0

PrimaryPart 1: Number of Participants With Worst-case Clinical Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline

Blood samples were collected to analyze PCI ranges: \>=2 times Upper limit of Normal(ULN) Units per Liter(U/L) for Alanine aminotransferase(ALT),\>=2 times ULN U/L for alkaline phosphatase(ALP), \>=2 times ULN U/L for aspartate aminotransferase(AST),\>=1.5 times ULN micromoles/L for bilirubin,\<2 or \>2.75 millimoles/L (mmol/L) for calcium,\<3 or \>9 mmol/L for glucose,\<3 or \>5.5 mmol/L for potassium and \<130 or \>150 mmol/L for sodium.Participants were counted in worst case category that their value changes to(low,within range or no change or high),unless there is no change in their category.Participants whose laboratory value category was unchanged(e.g.,High to High),or whose value became within range,were recorded in"To within Range or No Change" category.Participants were counted twice if the participant has values that changed 'To Low' and 'To High',so the percentages may not add to 100%.Baseline=latest pre-dose assessment with a non-missing value,including those from unscheduled visits

Time frame:: Up to 3 months
Reported as:: Count of participants · Participants

Part 1: Number of Participants With Worst-case Clinical Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline
Participants	Part 1: Single Dose Placebo	Part 1: Single Dose GSK3882347 15 mg	Part 1: Single Dose GSK3882347 50 mg	Part 1: Single Dose GSK3882347 150 mg	Part 1: Single Dose GSK3882347 250 mg	Part 1: Single Dose GSK3882347 250 mg Fed	Part 1: Single Dose GSK3882347 500 mg	Part 1: Single Dose GSK3882347 900 mg
ALT: To Low	0	0	0	0	0	0	0	0
ALT: To within Range or No Change	14	6	6	6	6	6	6	6
ALT: To High	0	0	0	0	0	0	0	0
ALP: To Low	0	0	0	0	0	0	0	0
ALP: To within Range or No Change	14	6	6	6	6	6	6	6
ALP: To High	0	0	0	0	0	0	0	0
AST: To Low	0	0	0	0	0	0	0	0
AST: To within Range or No Change	14	6	6	6	6	6	6	6
AST: To High	0	0	0	0	0	0	0	0
Bilirubin: To Low	0	0	0	0	0	0	0	0
Bilirubin: To within Range or No Change	14	6	6	6	6	6	6	6
Bilirubin: To High	0	0	0	0	0	0	0	0
Calcium: To Low	0	0	0	0	0	0	0	0
Calcium: To within Range or No Change	14	6	6	6	6	6	6	6
Calcium: To High	0	0	0	0	0	0	0	0
Glucose: To Low	0	0	0	0	0	0	0	0
Glucose: To within Range or No Change	14	6	6	6	6	6	6	6
Glucose: To High	0	0	0	0	0	0	0	0
Potassium: To Low	0	0	0	0	0	0	0	0
Potassium: To within Range or No Change	14	6	6	6	6	6	6	6
Potassium: To High	0	0	0	0	0	0	0	0
Sodium: To Low	0	0	0	0	0	0	0	0
Sodium: To within Range or No Change	14	6	6	6	6	6	6	6
Sodium: To High	0	0	0	0	0	0	0	0

PrimaryPart 2: Number of Participants With Worst-case Clinical Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline

Blood samples were collected to analyze PCI ranges: \>=2 times ULN U/L for Alanine aminotransferase(ALT),\>=2 times ULN U/L for alkaline phosphatase(ALP), \>=2 times ULN U/L for aspartate aminotransferase(AST),\>=1.5 times ULN micromoles/L for bilirubin,\<2 or \>2.75 mmol/L for calcium,\<3 or \>9 mmol/L for glucose,\<3 or \>5.5 mmol/L for potassium and \<130 or \>150 mmol/L for sodium.Participants were counted in worst case category that their value changes to(low,within range or no change or high),unless there is no change in their category.Participants whose laboratory value category was unchanged(e.g.,High to High),or whose value became within range,were recorded in"To within Range or No Change" category.Participants were counted twice if the participant has values that changed 'To Low' and 'To High',so the percentages may not add to 100%.Baseline=latest pre-dose assessment with a non-missing value,including those from unscheduled visits.

Time frame:: Up to 26 days
Reported as:: Count of participants · Participants

Part 2: Number of Participants With Worst-case Clinical Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline
Participants	Part 2: Repeat Dose Placebo	Part 2: Repeat Dose GSK3882347 50 mg	Part 2: Repeat Dose GSK3882347 150 mg	Part 2: Repeat Dose GSK3882347 500 mg	Part 2: Repeat Dose GSK3882347 900 mg
ALT: To Low	0	0	0	0	0
ALT: To within Range or No Change	8	8	8	8	8
ALT: To High	0	0	0	0	0
ALP: To Low	0	0	0	0	0
ALP: To within Range or No Change	8	8	8	8	8
ALP: To High	0	0	0	0	0
AST: To Low	0	0	0	0	0
AST: To within Range or No Change	8	8	8	8	8
AST: To High	0	0	0	0	0
Bilirubin: To Low	0	0	0	0	0
Bilirubin:To within Range or No Change	7	8	8	8	8
Bilirubin: To High	1	0	0	0	0
Calcium: To Low	0	0	0	0	0
Calcium: To within Range or No Change	8	8	8	8	8
Calcium: To High	0	0	0	0	0
Glucose: To Low	0	0	0	—	—
Glucose: To within Range or No Change	4	8	8	—	—
Glucose: To High	0	0	0	—	—
Potassium: To Low	0	0	0	0	0
Potassium:To within Range or No Change	8	8	8	8	8
Potassium: To High	0	0	0	0	0
Sodium: To Low	0	0	0	0	0
Sodium: To within Range or No Change	8	8	8	8	8
Sodium: To High	0	0	0	0	0

PrimaryPart 1: Number of Participants With Worst Case Urinalysis Results Post Baseline Relative to Baseline

Urine samples were collected for the analysis of urine parameters including occult blood and protein by dipstick. The dipstick test gave results in a semi-quantitative manner, and results for urinalysis parameters were recorded as no change/decreased, increase to positive for urine occult blood and protein indicating proportional concentrations in the urine sample. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Number of participants with worst case urinalysis results Post Baseline relative to Baseline is presented.

Time frame:: Up to 3 months
Reported as:: Count of participants · Participants

Part 1: Number of Participants With Worst Case Urinalysis Results Post Baseline Relative to Baseline
Participants	Part 1: Single Dose Placebo	Part 1: Single Dose GSK3882347 15 mg	Part 1: Single Dose GSK3882347 50 mg	Part 1: Single Dose GSK3882347 150 mg	Part 1: Single Dose GSK3882347 250 mg	Part 1: Single Dose GSK3882347 250 mg Fed	Part 1: Single Dose GSK3882347 500 mg	Part 1: Single Dose GSK3882347 900 mg
Occult Blood, No change/decreased	14	6	6	6	6	6	6	5
Occult blood, Increase to positive	0	0	0	0	0	0	0	1
Protein, No change/decreased	14	6	6	6	6	6	6	6
Protein, Increase to positive	0	0	0	0	0	0	0	0

PrimaryPart 2: Number of Participants With Worst Case Urinalysis Results Post Baseline Relative to Baseline

Urine samples were collected for the analysis of urine parameters including occult blood and protein by dipstick. The dipstick test gave results in a semi-quantitative manner (proportional concentrations in urine samples), and results for urinalysis parameters were recorded as no change/decreased, increase to positive for urine occult blood and protein. 'No change/decreased' indicates no change from Baseline results or decreased in results from Baseline including change in negative results. 'Increase to positive' indicates increase in result from Baseline. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Number of participants with worst case urinalysis results Post Baseline relative to Baseline is presented.

Time frame:: Up to 26 days
Reported as:: Count of participants · Participants

Part 2: Number of Participants With Worst Case Urinalysis Results Post Baseline Relative to Baseline
Participants	Part 2: Repeat Dose Placebo	Part 2: Repeat Dose GSK3882347 50 mg	Part 2: Repeat Dose GSK3882347 150 mg	Part 2: Repeat Dose GSK3882347 500 mg	Part 2: Repeat Dose GSK3882347 900 mg
Occult Blood, No change/decreased	8	8	7	8	8
Occult blood, Increase to positive	0	0	1	0	0
Protein, No change/decreased	7	8	8	8	8
Protein, Increase to trace	1	0	0	0	0

PrimaryPart 1: Number of Participants With Worst Case Vital Signs Results Relative to PCI Criteria Post Baseline Relative to Baseline

Vital signs were assessed including Systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse rate (PR). PCI ranges were \<85 (Low), 85-160 (Normal) and \>160 (High) for SBP; \<45 (Low), 45-100 (Normal), \>100 (High) for DBP; \<40 (Low), 40-110 (Normal), \>110 (High) for pulse rate. Participants were counted in worst case category that their value changes to(low,within range or no change, high),unless there is no change in their category.Participants whose laboratory value category was unchanged(e.g.,High to High),or whose value became within range, were recorded in"To within Range or No Change" category.Participants were counted twice if the participant has values that changed 'To Low' and 'To High',so the percentages may not add to 100%.Baseline was defined as latest pre-dose assessment with a non-missing value, including those from unscheduled visits

Time frame:: Up to 3 months
Reported as:: Count of participants · Participants

Part 1: Number of Participants With Worst Case Vital Signs Results Relative to PCI Criteria Post Baseline Relative to Baseline
Participants	Part 1: Single Dose Placebo	Part 1: Single Dose GSK3882347 15 mg	Part 1: Single Dose GSK3882347 50 mg	Part 1: Single Dose GSK3882347 150 mg	Part 1: Single Dose GSK3882347 250 mg	Part 1: Single Dose GSK3882347 250 mg Fed	Part 1: Single Dose GSK3882347 500 mg	Part 1: Single Dose GSK3882347 900 mg
SBP: To Low	0	0	0	0	0	0	0	0
SBP: To within Range or No Change	14	6	6	6	6	6	6	6
SBP: To High	0	0	0	0	0	0	0	0
DBP: To Low	0	0	0	0	0	0	0	0
DBP: To within Range or No Change	14	6	6	6	6	6	6	6
DBP: To High	0	0	0	0	0	0	0	0
PR: To Low	0	0	0	0	0	0	0	0
PR: To within Range or No Change	14	6	6	6	6	6	6	6
PR: To High	0	0	0	0	0	0	0	0

PrimaryPart 2: Number of Participants With Worst Case Vital Signs Results Relative to PCI Criteria Post Baseline Relative to Baseline

Time frame:: Up to 26 days
Reported as:: Count of participants · Participants

Part 2: Number of Participants With Worst Case Vital Signs Results Relative to PCI Criteria Post Baseline Relative to Baseline
Participants	Part 2: Repeat Dose Placebo	Part 2: Repeat Dose GSK3882347 50 mg	Part 2: Repeat Dose GSK3882347 150 mg	Part 2: Repeat Dose GSK3882347 500 mg	Part 2: Repeat Dose GSK3882347 900 mg
SBP: To Low	0	0	0	0	0
SBP: To within Range or No Change	8	8	8	8	8
SBP: To High	0	0	0	0	0
DBP: To Low	0	0	0	0	0
DBP: To within Range or No Change	8	8	8	8	8
DBP: To High	0	0	0	0	0
PR: To Low	1	0	1	0	0
PR: To within Range or No Change	7	8	7	8	8
PR: To High	0	0	0	0	0

PrimaryPart 1: Number of Participants With Worst Case Abnormal Electrocardiogram (ECG) Results Post Baseline Relative to Baseline

A 12-lead ECG was recorded with the participant in a semi-supine position after a rest of at least 10 minutes. Twelve lead ECGs were obtained by using an automated ECG machine that measured PR, QRS, QT, and corrected QT (QTc) intervals and calculated heart rate. Data for abnormal not clinically significant (NCS) and clinically significant (CS) ECG findings are presented. CS abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Baseline was defined as latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

Time frame:: Up to 3 months
Reported as:: Count of participants · Participants

Part 1: Number of Participants With Worst Case Abnormal Electrocardiogram (ECG) Results Post Baseline Relative to Baseline
Participants	Part 1: Single Dose Placebo	Part 1: Single Dose GSK3882347 15 mg	Part 1: Single Dose GSK3882347 50 mg	Part 1: Single Dose GSK3882347 150 mg	Part 1: Single Dose GSK3882347 250 mg	Part 1: Single Dose GSK3882347 250 mg Fed	Part 1: Single Dose GSK3882347 500 mg	Part 1: Single Dose GSK3882347 900 mg
Abnormal: NCS	3	1	1	0	0	2	1	1
Abnormal: CS	0	0	0	0	0	0	0	0

PrimaryPart 2: Number of Participants With Worst Case Abnormal ECG Results Post Baseline Relative to Baseline

Time frame:: Up to 26 days
Reported as:: Count of participants · Participants

Part 2: Number of Participants With Worst Case Abnormal ECG Results Post Baseline Relative to Baseline
Participants	Part 2: Repeat Dose Placebo	Part 2: Repeat Dose GSK3882347 50 mg	Part 2: Repeat Dose GSK3882347 150 mg	Part 2: Repeat Dose GSK3882347 500 mg	Part 2: Repeat Dose GSK3882347 900 mg
Abnormal: NCS	3	3	6	6	3
Abnormal: CS	0	0	0	0	0

PrimaryPart 1: Area Under the Concentration-time Curve From Time Zero to 24 Hours (AUC[0-24]) After Single Dose Administration of GSK3882347

Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis.

Time frame:: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16 and 24 hours post-dose in each treatment period
Reported as:: Geometric mean · Hours*nanograms per milliliter

Part 1: Area Under the Concentration-time Curve From Time Zero to 24 Hours (AUC[0-24]) After Single Dose Administration of GSK3882347
Hours*nanograms per milliliter	Part 1: Single Dose GSK3882347 15 mg	Part 1: Single Dose GSK3882347 50 mg	Part 1: Single Dose GSK3882347 150 mg	Part 1: Single Dose GSK3882347 250 mg	Part 1: Single Dose GSK3882347 250 mg Fed	Part 1: Single Dose GSK3882347 500 mg	Part 1: Single Dose GSK3882347 900 mg
Part 1: Area Under the Concentration-time Curve From Time Zero to 24 Hours (AUC[0-24]) After Single Dose Administration of GSK3882347	1671.7 ± 20.9	6514.1 ± 12.3	17717.9 ± 18.0	28472.2 ± 27.9	21456.4 ± 7.8	48381.2 ± 26.9	65150.2 ± 28.3

PrimaryPart 1: Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUC[0-t]) After Single Dose Administration of GSK3882347

Blood samples were collected at indicated time points for PK analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis.

Time frame:: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 32, 48, 72 and 96 hours post-dose in each treatment period
Reported as:: Geometric mean · Hours*nanograms per milliliter

Part 1: Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUC[0-t]) After Single Dose Administration of GSK3882347
Hours*nanograms per milliliter	Part 1: Single Dose GSK3882347 15 mg	Part 1: Single Dose GSK3882347 50 mg	Part 1: Single Dose GSK3882347 150 mg	Part 1: Single Dose GSK3882347 250 mg	Part 1: Single Dose GSK3882347 250 mg Fed	Part 1: Single Dose GSK3882347 500 mg	Part 1: Single Dose GSK3882347 900 mg
Part 1: Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUC[0-t]) After Single Dose Administration of GSK3882347	1954.3 ± 24.7	8249.8 ± 18.2	22266.9 ± 16.9	36561.0 ± 26.7	29091.9 ± 10.6	63052.2 ± 26.1	88901.9 ± 31.8

PrimaryPart 1: Area Under the Concentration-time Curve Extrapolated From Time Zero to Infinity (AUC[0-infinity]) After Single Dose Administration of GSK3882347

Blood samples were collected at indicated time points for PK analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis.

Time frame:: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 32, 48, 72 and 96 hours post-dose in each treatment period
Reported as:: Geometric mean · Hours*nanograms per milliliter

Part 1: Area Under the Concentration-time Curve Extrapolated From Time Zero to Infinity (AUC[0-infinity]) After Single Dose Administration of GSK3882347
Hours*nanograms per milliliter	Part 1: Single Dose GSK3882347 15 mg	Part 1: Single Dose GSK3882347 50 mg	Part 1: Single Dose GSK3882347 150 mg	Part 1: Single Dose GSK3882347 250 mg	Part 1: Single Dose GSK3882347 250 mg Fed	Part 1: Single Dose GSK3882347 500 mg	Part 1: Single Dose GSK3882347 900 mg
Part 1: Area Under the Concentration-time Curve Extrapolated From Time Zero to Infinity (AUC[0-infinity]) After Single Dose Administration of GSK3882347	2167.0 ± 23.4	8425.5 ± 18.1	22433.7 ± 16.8	36768.0 ± 26.5	29316.1 ± 10.5	63377.3 ± 26.1	89424.5 ± 32.1

PrimaryPart 1: Maximum Plasma Concentration (Cmax) After Single Dose Administration of GSK3882347

Blood samples were collected at indicated time points for PK analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis.

Time frame:: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 32, 48, 72 and 96 hours post-dose in each treatment period
Reported as:: Geometric mean · Nanograms per milliliter

Part 1: Maximum Plasma Concentration (Cmax) After Single Dose Administration of GSK3882347
Nanograms per milliliter	Part 1: Single Dose GSK3882347 15 mg	Part 1: Single Dose GSK3882347 50 mg	Part 1: Single Dose GSK3882347 150 mg	Part 1: Single Dose GSK3882347 250 mg	Part 1: Single Dose GSK3882347 250 mg Fed	Part 1: Single Dose GSK3882347 500 mg	Part 1: Single Dose GSK3882347 900 mg
Part 1: Maximum Plasma Concentration (Cmax) After Single Dose Administration of GSK3882347	165.7 ± 22.3	661.7 ± 14.8	1825.8 ± 21.2	3126.7 ± 31.3	1834.5 ± 13.4	4671.3 ± 27.4	5771.6 ± 24.6

PrimaryPart 1: Plasma Concentrations at 24 Hours (C24h) After Single Dose Administration of GSK3882347

Blood samples were collected at indicated time points for PK analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis.

Time frame:: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16 and 24 hours post-dose in each treatment period
Reported as:: Geometric mean · Nanograms per milliliter

Part 1: Plasma Concentrations at 24 Hours (C24h) After Single Dose Administration of GSK3882347
Nanograms per milliliter	Part 1: Single Dose GSK3882347 15 mg	Part 1: Single Dose GSK3882347 50 mg	Part 1: Single Dose GSK3882347 150 mg	Part 1: Single Dose GSK3882347 250 mg	Part 1: Single Dose GSK3882347 250 mg Fed	Part 1: Single Dose GSK3882347 500 mg	Part 1: Single Dose GSK3882347 900 mg
Part 1: Plasma Concentrations at 24 Hours (C24h) After Single Dose Administration of GSK3882347	27.32 ± 29.7	106.70 ± 39.5	283.18 ± 24.7	500.35 ± 28.8	453.82 ± 13.6	853.98 ± 35.0	1291.37 ± 41.0

PrimaryPart 1: Time to Cmax (Tmax) After Single Dose Administration of GSK3882347

Blood samples were collected at indicated time points for PK analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis.

Time frame:: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 32, 48, 72 and 96 hours post-dose in each treatment period
Reported as:: Median · Hours

Part 1: Time to Cmax (Tmax) After Single Dose Administration of GSK3882347
Hours	Part 1: Single Dose GSK3882347 15 mg	Part 1: Single Dose GSK3882347 50 mg	Part 1: Single Dose GSK3882347 150 mg	Part 1: Single Dose GSK3882347 250 mg	Part 1: Single Dose GSK3882347 250 mg Fed	Part 1: Single Dose GSK3882347 500 mg	Part 1: Single Dose GSK3882347 900 mg
Part 1: Time to Cmax (Tmax) After Single Dose Administration of GSK3882347	3.000 (2.00 to 4.00)	4.000 (2.00 to 4.18)	4.000 (2.00 to 6.00)	4.000 (2.00 to 6.00)	4.000 (2.00 to 8.00)	4.000 (2.00 to 4.00)	4.000 (2.00 to 8.00)

PrimaryPart 1: Lag Time for Absorption (Tlag) After Single Dose Administration of GSK3882347

Blood samples were collected at indicated time points for PK analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis.

Time frame:: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 32, 48, 72 and 96 hours post-dose in each treatment period
Reported as:: Median · Hours

Part 1: Lag Time for Absorption (Tlag) After Single Dose Administration of GSK3882347
Hours	Part 1: Single Dose GSK3882347 15 mg	Part 1: Single Dose GSK3882347 50 mg	Part 1: Single Dose GSK3882347 150 mg	Part 1: Single Dose GSK3882347 250 mg	Part 1: Single Dose GSK3882347 250 mg Fed	Part 1: Single Dose GSK3882347 500 mg	Part 1: Single Dose GSK3882347 900 mg
Part 1: Lag Time for Absorption (Tlag) After Single Dose Administration of GSK3882347	0.375 (0.25 to 0.50)	0.250 (0 to 0.50)	0.250 (0 to 0.50)	0.250 (0 to 0.25)	0.250 (0.25 to 1.50)	0.250 (0.25 to 0.50)	0.250 (0.25 to 0.50)

PrimaryPart 1: Terminal Elimination Half-life (T1/2) After Single Dose Administration of GSK3882347

Blood samples were collected at indicated time points for PK analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis.

Time frame:: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 32, 48, 72 and 96 hours post-dose in each treatment period
Reported as:: Geometric mean · Hours

Part 1: Terminal Elimination Half-life (T1/2) After Single Dose Administration of GSK3882347
Hours	Part 1: Single Dose GSK3882347 15 mg	Part 1: Single Dose GSK3882347 50 mg	Part 1: Single Dose GSK3882347 150 mg	Part 1: Single Dose GSK3882347 250 mg	Part 1: Single Dose GSK3882347 250 mg Fed	Part 1: Single Dose GSK3882347 500 mg	Part 1: Single Dose GSK3882347 900 mg
Part 1: Terminal Elimination Half-life (T1/2) After Single Dose Administration of GSK3882347	11.407 ± 17.7	12.269 ± 14.5	11.538 ± 10.1	12.277 ± 16.0	12.984 ± 10.3	12.630 ± 11.6	12.690 ± 13.8

PrimaryPart 2: Area Under the Concentration-time Curve Over the Dosing Interval Tau (AUC[0-tau]) After Repeat Dose Administration of GSK3882347

Blood samples were collected at indicated time points for PK analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis.

Time frame:: Days 1 and 7: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16, 24 hours post-dose
Reported as:: Geometric mean · Hours*nanograms per milliliter

Part 2: Area Under the Concentration-time Curve Over the Dosing Interval Tau (AUC[0-tau]) After Repeat Dose Administration of GSK3882347
Hours*nanograms per milliliter	Part 2: Repeat Dose GSK3882347 50 mg	Part 2: Repeat Dose GSK3882347 150 mg	Part 2: Repeat Dose GSK3882347 500 mg	Part 2: Repeat Dose GSK3882347 900 mg
Day 1	5862.9 ± 16.2	20191.4 ± 25.6	45400.0 ± 38.8	53753.9 ± 27.8
Day 7	6144.9 ± 8.7	21109.5 ± 27.9	61202.0 ± 27.4	82351.1 ± 22.7

PrimaryPart 2: Cmax After Repeat Dose Administration of GSK3882347

Blood samples were collected at indicated time points for PK analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis.

Time frame:: Days 1 and 7: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16, 24 hours post-dose
Reported as:: Geometric mean · Nanograms per milliliter

Part 2: Cmax After Repeat Dose Administration of GSK3882347
Nanograms per milliliter	Part 2: Repeat Dose GSK3882347 50 mg	Part 2: Repeat Dose GSK3882347 150 mg	Part 2: Repeat Dose GSK3882347 500 mg	Part 2: Repeat Dose GSK3882347 900 mg
Day 1	586.0 ± 20.8	2179.1 ± 29.5	4409.4 ± 34.2	4933.1 ± 24.0
Day 7	600.4 ± 21.9	2007.4 ± 31.7	5370.3 ± 21.2	6575.2 ± 28.6

PrimaryPart 2: Tmax After Repeat Dose Administration of GSK3882347

Blood samples were collected at indicated time points for PK analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis.

Time frame:: Days 1 and 7: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16, 24 hours post-dose
Reported as:: Median · Hours

Part 2: Tmax After Repeat Dose Administration of GSK3882347
Hours	Part 2: Repeat Dose GSK3882347 50 mg	Part 2: Repeat Dose GSK3882347 150 mg	Part 2: Repeat Dose GSK3882347 500 mg	Part 2: Repeat Dose GSK3882347 900 mg
Day 1	4.000 (2.00 to 6.00)	3.000 (1.50 to 4.00)	4.000 (4.00 to 6.00)	4.008 (4.00 to 6.00)
Day 7	4.000 (2.00 to 6.00)	4.000 (2.00 to 6.00)	4.000 (2.00 to 6.00)	4.000 (2.00 to 6.00)

PrimaryPart 2: Plasma Concentrations Over the Dosing Interval (Ctau) After Repeat Dose Administration of GSK3882347

Blood samples were collected at indicated time points for PK analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis.

Time frame:: Days 1 and 7: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16, 24 hours post-dose
Reported as:: Geometric mean · Nanograms per milliliter

Part 2: Plasma Concentrations Over the Dosing Interval (Ctau) After Repeat Dose Administration of GSK3882347
Nanograms per milliliter	Part 2: Repeat Dose GSK3882347 50 mg	Part 2: Repeat Dose GSK3882347 150 mg	Part 2: Repeat Dose GSK3882347 500 mg	Part 2: Repeat Dose GSK3882347 900 mg
Day 1	90.98 ± 46.8	292.53 ± 22.2	789.85 ± 46.7	1084.55 ± 31.8
Day 7	109.28 ± 26.8	368.34 ± 29.7	1170.62 ± 39.2	1864.47 ± 23.1

PrimaryPart 1: Urine Concentration Between 22-24 Hours (C22-24) After Single Dose Administration of GSK3882347

Urine samples were collected at indicated time points for PK analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis.

Time frame:: Day 1: 22-24 hours post-dose in each treatment period
Reported as:: Geometric mean · Micrograms per milliliter

Part 1: Urine Concentration Between 22-24 Hours (C22-24) After Single Dose Administration of GSK3882347
Micrograms per milliliter	Part 1: Single Dose GSK3882347 15 mg	Part 1: Single Dose GSK3882347 50 mg	Part 1: Single Dose GSK3882347 150 mg	Part 1: Single Dose GSK3882347 250 mg	Part 1: Single Dose GSK3882347 250 mg Fed	Part 1: Single Dose GSK3882347 500 mg	Part 1: Single Dose GSK3882347 900 mg
Part 1: Urine Concentration Between 22-24 Hours (C22-24) After Single Dose Administration of GSK3882347	1.55 ± 71.3	2.99 ± 95.9	11.27 ± 146.7	15.26 ± 133.9	11.42 ± 148.0	48.54 ± 161.8	33.50 ± 75.0

PrimaryPart 2: Urine Concentration Between 22-24 Hours (C22-24) After Repeat Dose Administration of GSK3882347

Urine samples were collected at indicated time points for PK analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis.

Time frame:: Day 1 and Day 7: 22-24 hours post-dose
Reported as:: Geometric mean · Micrograms per milliliter

Part 2: Urine Concentration Between 22-24 Hours (C22-24) After Repeat Dose Administration of GSK3882347
Micrograms per milliliter	Part 2: Repeat Dose GSK3882347 50 mg	Part 2: Repeat Dose GSK3882347 150 mg	Part 2: Repeat Dose GSK3882347 500 mg	Part 2: Repeat Dose GSK3882347 900 mg
Day 1	2.95 ± 52.5	11.98 ± 64.8	18.15 ± 42.8	38.43 ± 90.6
Day 7	2.56 ± 84.4	16.50 ± 26.7	23.60 ± 69.6	57.15 ± 75.2

PrimaryPart 1: Amount of Drug Excreted in Urine of Unchanged Drug (Ae Total) After Single Dose Administration of GSK3882347

Urine samples were collected at indicated time points for PK analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis.

Time frame:: At 0-2, 2-4, 4-6, 6-8, 8-10, 10-12, 12-22, 22-24, 24-26, 26-32, 32-38, 38-48, 48-60, 60-72, 72-84, 84-96 hours post-dose in each treatment period
Reported as:: Geometric mean · Milligrams

Part 1: Amount of Drug Excreted in Urine of Unchanged Drug (Ae Total) After Single Dose Administration of GSK3882347
Milligrams	Part 1: Single Dose GSK3882347 15 mg	Part 1: Single Dose GSK3882347 50 mg	Part 1: Single Dose GSK3882347 150 mg	Part 1: Single Dose GSK3882347 250 mg	Part 1: Single Dose GSK3882347 250 mg Fed	Part 1: Single Dose GSK3882347 500 mg	Part 1: Single Dose GSK3882347 900 mg
Part 1: Amount of Drug Excreted in Urine of Unchanged Drug (Ae Total) After Single Dose Administration of GSK3882347	11.16 ± 15.7	32.01 ± 9.4	106.86 ± 25.5	146.43 ± 20.5	95.17 ± 9.2	306.93 ± 20.8	430.03 ± 22.5

PrimaryPart 2: Amount of Drug Excreted in Urine of Unchanged Drug (Ae Total) After Repeat Dose Administration of GSK3882347

Urine samples were collected at indicated time points for PK analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis.

Time frame:: Days 1 and 7: At 0-2, 2-4, 4-6, 6-8, 8-10, 10-12, 12-22, 22-24 hours post-dose
Reported as:: Geometric mean · Milligrams

Part 2: Amount of Drug Excreted in Urine of Unchanged Drug (Ae Total) After Repeat Dose Administration of GSK3882347
Milligrams	Part 2: Repeat Dose GSK3882347 50 mg	Part 2: Repeat Dose GSK3882347 150 mg	Part 2: Repeat Dose GSK3882347 500 mg	Part 2: Repeat Dose GSK3882347 900 mg
Day 1	24.77 ± 17.6	88.30 ± 14.2	188.49 ± 32.5	267.16 ± 18.4
Day 7	26.71 ± 19.0	108.20 ± 17.4	258.08 ± 18.7	390.10 ± 13.0

PrimaryPart 1: Percentage of the Given Dose of Drug Excreted in Urine (%fe Total) After Single Dose Administration of GSK3882347

Urine samples were collected at indicated time points for PK analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis. %fe was calculated as: (Ae total/Dose)\*100 percent (%).

Time frame:: At 0-2, 2-4, 4-6, 6-8, 8-10, 10-12, 12-22, 22-24, 24-26, 26-32, 32-38, 38-48, 48-60, 60-72, 72-84, 84-96 hours post-dose in each treatment period
Reported as:: Geometric mean · Percent dose excreted

Part 1: Percentage of the Given Dose of Drug Excreted in Urine (%fe Total) After Single Dose Administration of GSK3882347
Percent dose excreted	Part 1: Single Dose GSK3882347 15 mg	Part 1: Single Dose GSK3882347 50 mg	Part 1: Single Dose GSK3882347 150 mg	Part 1: Single Dose GSK3882347 250 mg	Part 1: Single Dose GSK3882347 250 mg Fed	Part 1: Single Dose GSK3882347 500 mg	Part 1: Single Dose GSK3882347 900 mg
Part 1: Percentage of the Given Dose of Drug Excreted in Urine (%fe Total) After Single Dose Administration of GSK3882347	74.43 ± 15.7	64.02 ± 9.4	71.24 ± 25.5	58.57 ± 20.5	38.07 ± 9.2	61.39 ± 20.8	47.78 ± 22.5

PrimaryPart 2: Percentage of the Given Dose of Drug Excreted in Urine (%fe Total) After Single Dose Administration of GSK3882347

Time frame:: Day 1 and Day 7: At 0-2, 2-4, 4-6, 6-8, 8-10, 10-12, 12-22, 22-24 hours post-dose
Reported as:: Geometric mean · Percent dose excreted

Part 2: Percentage of the Given Dose of Drug Excreted in Urine (%fe Total) After Single Dose Administration of GSK3882347
Percent dose excreted	Part 2: Repeat Dose GSK3882347 50 mg	Part 2: Repeat Dose GSK3882347 150 mg	Part 2: Repeat Dose GSK3882347 500 mg	Part 2: Repeat Dose GSK3882347 900 mg
Day 1	49.54 ± 17.6	58.87 ± 14.2	37.70 ± 32.5	29.68 ± 18.4
Day 7	53.42 ± 19.0	72.13 ± 17.4	51.62 ± 18.7	43.34 ± 13.0

PrimaryPart 1: Renal Clearance of Drug (CLr) After Single Dose Administration of GSK3882347

Urine samples were collected at indicated time points for PK analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis. CLr was calculated as: Ae total/AUC(0-t)

Time frame:: At 0-2, 2-4, 4-6, 6-8, 8-10, 10-12, 12-22, 22-24, 24-26, 26-32, 32-38, 38-48, 48-60, 60-72, 72-84, 84-96 hours post-dose in each treatment period
Reported as:: Geometric mean · Liters per hour

Part 1: Renal Clearance of Drug (CLr) After Single Dose Administration of GSK3882347
Liters per hour	Part 1: Single Dose GSK3882347 15 mg	Part 1: Single Dose GSK3882347 50 mg	Part 1: Single Dose GSK3882347 150 mg	Part 1: Single Dose GSK3882347 250 mg	Part 1: Single Dose GSK3882347 250 mg Fed	Part 1: Single Dose GSK3882347 500 mg	Part 1: Single Dose GSK3882347 900 mg
Part 1: Renal Clearance of Drug (CLr) After Single Dose Administration of GSK3882347	5.71 ± 31.7	3.88 ± 25.8	4.80 ± 30.9	4.00 ± 19.1	3.27 ± 14.2	4.87 ± 17.5	4.84 ± 22.7

PrimaryPart 2: Renal Clearance of Drug (CLr) After Repeat Dose Administration of GSK3882347

Urine samples were collected at indicated time points for PK analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis. CLr was calculated as: Ae total/AUC(0-t).

Time frame:: Day 1 and Day 7: At 0-2, 2-4, 4-6, 6-8, 8-10, 10-12, 12-22, 22-24 hours post-dose
Reported as:: Geometric mean · Liters per hour

Part 2: Renal Clearance of Drug (CLr) After Repeat Dose Administration of GSK3882347
Liters per hour	Part 2: Repeat Dose GSK3882347 50 mg	Part 2: Repeat Dose GSK3882347 150 mg	Part 2: Repeat Dose GSK3882347 500 mg	Part 2: Repeat Dose GSK3882347 900 mg
Day 1	4.24 ± 20.8	4.38 ± 28.6	4.16 ± 28.7	4.98 ± 19.1
Day 7	4.34 ± 16.9	5.12 ± 19.8	4.22 ± 28.6	4.73 ± 18.0

SecondaryPart 1: Area Under the Concentration-time Curve From Time Zero to 12 Hours (AUC[0-12]) After Single Dose Administration of GSK3882347

Blood samples were collected at indicated time points for PK analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis.

Time frame:: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8 and 12 hours post-dose in each treatment period
Reported as:: Geometric mean · Hours*nanogram per milliliter

Part 1: Area Under the Concentration-time Curve From Time Zero to 12 Hours (AUC[0-12]) After Single Dose Administration of GSK3882347
Hours*nanogram per milliliter	Part 1: Single Dose GSK3882347 15 mg	Part 1: Single Dose GSK3882347 50 mg	Part 1: Single Dose GSK3882347 150 mg	Part 1: Single Dose GSK3882347 250 mg	Part 1: Single Dose GSK3882347 250 mg Fed	Part 1: Single Dose GSK3882347 500 mg	Part 1: Single Dose GSK3882347 900 mg
Part 1: Area Under the Concentration-time Curve From Time Zero to 12 Hours (AUC[0-12]) After Single Dose Administration of GSK3882347	1181.6 ± 20.3	4609.1 ± 10.2	12519.7 ± 19.7	20127.1 ± 29.1	14009.0 ± 10.1	33030.8 ± 26.8	42353.5 ± 26.6

SecondaryPart 1: Plasma Concentrations at 12 Hours (C12) After Single Dose Administration of GSK3882347

Blood samples were collected at indicated time points for PK analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis.

Time frame:: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8 and 12 hours post-dose in each treatment period
Reported as:: Geometric mean · Nanograms per milliliter

Part 1: Plasma Concentrations at 12 Hours (C12) After Single Dose Administration of GSK3882347
Nanograms per milliliter	Part 1: Single Dose GSK3882347 15 mg	Part 1: Single Dose GSK3882347 50 mg	Part 1: Single Dose GSK3882347 150 mg	Part 1: Single Dose GSK3882347 250 mg	Part 1: Single Dose GSK3882347 250 mg Fed	Part 1: Single Dose GSK3882347 500 mg	Part 1: Single Dose GSK3882347 900 mg
Part 1: Plasma Concentrations at 12 Hours (C12) After Single Dose Administration of GSK3882347	58.73 ± 26.7	232.96 ± 17.1	636.41 ± 18.5	947.62 ± 27.5	857.73 ± 9.5	1806.50 ± 33.9	2714.12 ± 43.9

SecondaryPart 1: Apparent Oral Clearance (CL/F) After Single Dose Administration of GSK3882347

Blood samples were collected at indicated time points for PK analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis.

Time frame:: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 32, 48, 72 and 96 hours post-dose in each treatment period
Reported as:: Geometric mean · Liters per hour

Part 1: Apparent Oral Clearance (CL/F) After Single Dose Administration of GSK3882347
Liters per hour	Part 1: Single Dose GSK3882347 15 mg	Part 1: Single Dose GSK3882347 50 mg	Part 1: Single Dose GSK3882347 150 mg	Part 1: Single Dose GSK3882347 250 mg	Part 1: Single Dose GSK3882347 250 mg Fed	Part 1: Single Dose GSK3882347 500 mg	Part 1: Single Dose GSK3882347 900 mg
Part 1: Apparent Oral Clearance (CL/F) After Single Dose Administration of GSK3882347	6.92 ± 23.4	5.93 ± 18.1	6.69 ± 16.8	6.80 ± 26.5	8.53 ± 10.5	7.89 ± 26.1	10.06 ± 32.1

SecondaryPart 1: Apparent Volume of Distribution After Oral Administration (Vz/F) After Single Dose Administration of GSK3882347

Blood samples were collected at indicated time points for PK analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis.

Time frame:: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 32, 48, 72 and 96 hours post-dose in each treatment period
Reported as:: Geometric mean · Liters

Part 1: Apparent Volume of Distribution After Oral Administration (Vz/F) After Single Dose Administration of GSK3882347
Liters	Part 1: Single Dose GSK3882347 15 mg	Part 1: Single Dose GSK3882347 50 mg	Part 1: Single Dose GSK3882347 150 mg	Part 1: Single Dose GSK3882347 250 mg	Part 1: Single Dose GSK3882347 250 mg Fed	Part 1: Single Dose GSK3882347 500 mg	Part 1: Single Dose GSK3882347 900 mg
Part 1: Apparent Volume of Distribution After Oral Administration (Vz/F) After Single Dose Administration of GSK3882347	113.92 ± 22.8	105.04 ± 6.7	111.30 ± 22.7	120.43 ± 34.3	159.74 ± 11.3	143.76 ± 30.1	184.26 ± 24.1

SecondaryPart 1: Mean Residence Time (MRT) After Single Dose Administration of GSK3882347

Blood samples were collected at indicated time points for PK analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis.

Time frame:: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 32, 48, 72 and 96 hours post-dose in each treatment period
Reported as:: Median · Hours

Part 1: Mean Residence Time (MRT) After Single Dose Administration of GSK3882347
Hours	Part 1: Single Dose GSK3882347 15 mg	Part 1: Single Dose GSK3882347 50 mg	Part 1: Single Dose GSK3882347 150 mg	Part 1: Single Dose GSK3882347 250 mg	Part 1: Single Dose GSK3882347 250 mg Fed	Part 1: Single Dose GSK3882347 500 mg	Part 1: Single Dose GSK3882347 900 mg
Part 1: Mean Residence Time (MRT) After Single Dose Administration of GSK3882347	15.775 (12.76 to 23.46)	16.843 (12.45 to 19.61)	15.614 (13.38 to 19.62)	16.262 (14.36 to 19.84)	18.818 (16.57 to 20.73)	17.259 (15.41 to 19.89)	18.630 (15.32 to 22.90)

SecondaryPart 2: Area Under the Concentration-time Curve From Time Zero to 12 Hours (AUC[0-12]) After Repeat Dose Administration of GSK3882347

Blood samples were collected at indicated time points for PK analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis.

Time frame:: Days 1 and 7: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8 and 12 hours post-dose
Reported as:: Geometric mean · Hours*nanogram per milliliter

Part 2: Area Under the Concentration-time Curve From Time Zero to 12 Hours (AUC[0-12]) After Repeat Dose Administration of GSK3882347
Hours*nanogram per milliliter	Part 2: Repeat Dose GSK3882347 50 mg	Part 2: Repeat Dose GSK3882347 150 mg	Part 2: Repeat Dose GSK3882347 500 mg	Part 2: Repeat Dose GSK3882347 900 mg
Day 1	4076.3 ± 16.4	14411.9 ± 28.9	30660.3 ± 37.1	35231.6 ± 26.3
Day 7	4222.8 ± 11.0	14506.3 ± 28.9	41187.1 ± 24.1	53121.9 ± 23.9

SecondaryPart 2: Plasma Concentrations at 12 Hours (C12) After Repeat Dose Administration of GSK3882347

Blood samples were collected at indicated time points for PK analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis.

Time frame:: Days 1 and 7: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8 and 12 hours post-dose
Reported as:: Geometric mean · Nanograms per milliliter

Part 2: Plasma Concentrations at 12 Hours (C12) After Repeat Dose Administration of GSK3882347
Nanograms per milliliter	Part 2: Repeat Dose GSK3882347 50 mg	Part 2: Repeat Dose GSK3882347 150 mg	Part 2: Repeat Dose GSK3882347 500 mg	Part 2: Repeat Dose GSK3882347 900 mg
Day 1	214.4 ± 23.5	709.1 ± 19.9	1704.8 ± 42.1	2068.2 ± 36.0
Day 7	221.5 ± 11.8	776.1 ± 28.3	2360.8 ± 30.6	3218.5 ± 21.6

SecondaryPart 1: Dose Proportionality of GSK3882347 for Dose Levels 15 mg to 900 mg Using AUC(0-infinity) After Single Dose Administration of GSK3882347 Under Fasted Condition

Blood samples were collected at indicated time points for PK analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis. Dose proportionality was assessed using Power model. Log-e(dose) was fitted as fixed effect and participant was fitted as random effect. Kenward and Roger method and unstructured covariance structure was used. Slope and 90% confidence interval (CI) for the slope are presented. The SD 250 mg fed treatment was not considered in the analysis.

Time frame:: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 32, 48, 72 and 96 hours post-dose in each treatment period
Reported as:: Number · Slope of log dose

Part 1: Dose Proportionality of GSK3882347 for Dose Levels 15 mg to 900 mg Using AUC(0-infinity) After Single Dose Administration of GSK3882347 Under Fasted Condition
Slope of log dose	Part 1: GSK3882347 SD 15 mg to 900 mg
Part 1: Dose Proportionality of GSK3882347 for Dose Levels 15 mg to 900 mg Using AUC(0-infinity) After Single Dose Administration of GSK3882347 Under Fasted Condition	0.919 (0.889 to 0.949)

SecondaryPart 1: Dose Proportionality of GSK3882347 for Dose Levels 15 mg to 900 mg Using Cmax After Single Dose Administration of GSK3882347 Under Fasted Condition

Blood samples were collected at indicated time points for PK analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis. Dose proportionality was assessed using Power model. Log-e(dose) was fitted as fixed effect and participant was fitted as random effect. Kenward and Roger method and unstructured covariance structure was used. Slope and 90% CI for the slope are presented. The SD 250 mg fed treatment was not considered in the analysis.

Time frame:: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 32, 48, 72 and 96 hours post-dose in each treatment period
Reported as:: Number · Slope of log dose

Part 1: Dose Proportionality of GSK3882347 for Dose Levels 15 mg to 900 mg Using Cmax After Single Dose Administration of GSK3882347 Under Fasted Condition
Slope of log dose	Part 1: GSK3882347 SD 15 mg to 900 mg
Part 1: Dose Proportionality of GSK3882347 for Dose Levels 15 mg to 900 mg Using Cmax After Single Dose Administration of GSK3882347 Under Fasted Condition	0.903 (0.865 to 0.941)

SecondaryPart 2: Dose Proportionality of GSK3882347 for Dose Levels 50 mg to 900 mg Using AUC(0-tau) After Repeat Dose Administration of GSK3882347

Time frame:: Day 1 and Day 7: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16, 24 hours post-dose
Reported as:: Number · Slope of log dose

Part 2: Dose Proportionality of GSK3882347 for Dose Levels 50 mg to 900 mg Using AUC(0-tau) After Repeat Dose Administration of GSK3882347
Slope of log dose	Part 2: GSK3882347 RD 50 mg to 900 mg
Day 1	0.770 (0.684 to 0.857)
Day 7	0.908 (0.841 to 0.976)

SecondaryPart 2: Dose Proportionality of GSK3882347 for Dose Levels 50 mg to 900 mg Using Cmax After Repeat Dose Administration of GSK3882347

Time frame:: Day 1 and Day 7: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16, 24 hours post-dose
Reported as:: Number · Slope of log dose

Part 2: Dose Proportionality of GSK3882347 for Dose Levels 50 mg to 900 mg Using Cmax After Repeat Dose Administration of GSK3882347
Slope of log dose	Part 2: GSK3882347 RD 50 mg to 900 mg
Day 1	0.736 (0.644 to 0.829)
Day 7	0.841 (0.763 to 0.920)

SecondaryPart 2: Observed Accumulation Ratio (Ro) Using AUC(0-tau) After Repeat Dose Administration of GSK3882347

Blood samples were collected at indicated time points for PK analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis. Accumulation ratio was calculated as AUC(0-tau) at Day 7 divided by AUC(0-tau) at Day 1 for GSK3882347. Mixed effect model was used to assess accumulation ratio for the log transformed parameters. Treatment, day and the interaction of treatment and day were fitted as fixed effect. Participant was fitted as random effect. Kenward and Roger method and unstructured covariance structure was used.

Time frame:: Day 1 and Day 7: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16, 24 hours post-dose
Reported as:: Number · Ratio

Part 2: Observed Accumulation Ratio (Ro) Using AUC(0-tau) After Repeat Dose Administration of GSK3882347
Ratio	Part 2: Repeat Dose GSK3882347 50 mg	Part 2: Repeat Dose GSK3882347 150 mg	Part 2: Repeat Dose GSK3882347 500 mg	Part 2: Repeat Dose GSK3882347 900 mg
Part 2: Observed Accumulation Ratio (Ro) Using AUC(0-tau) After Repeat Dose Administration of GSK3882347	1.05 (0.93 to 1.18)	1.05 (0.93 to 1.18)	1.35 (1.20 to 1.52)	1.53 (1.36 to 1.72)

SecondaryPart 2: Time Invariance of GSK3882347

Blood samples were collected at indicated time points for the analysis of time invariance. Time invariance was calculated as AUC(0-tau) at Day 7 divided by AUC(0-infinity) at Day 1 for GSK3882347. Mixed effect ANOVA model was used to assess time invariance for the log transformed parameters. Treatment, day and the interaction of treatment and day were fitted as fixed effect. Participant was fitted as random effect. Kenward and Roger method and unstructured covariance structure was used.

Time frame:: Day 1 and Day 7: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16, 24 hours post-dose
Reported as:: Number · Ratio

Part 2: Time Invariance of GSK3882347
Ratio	Part 2: Repeat Dose GSK3882347 50 mg	Part 2: Repeat Dose GSK3882347 150 mg	Part 2: Repeat Dose GSK3882347 500 mg	Part 2: Repeat Dose GSK3882347 900 mg
Part 2: Time Invariance of GSK3882347	0.83 (0.74 to 0.94)	0.87 (0.77 to 0.99)	1.07 (0.95 to 1.20)	1.13 (1.00 to 1.28)

SecondaryPart 2: Pre-dose Plasma Concentrations After Repeat Dose Administration of GSK3882347 From Days 3 to 7

Blood samples were collected at indicated time points for PK analysis of GSK3882347.

Time frame:: Days 3, 4, 5, 6 and 7: Pre-dose
Reported as:: Mean · Nanograms per milliliter

Part 2: Pre-dose Plasma Concentrations After Repeat Dose Administration of GSK3882347 From Days 3 to 7
Nanograms per milliliter	Part 2: Repeat Dose GSK3882347 50 mg	Part 2: Repeat Dose GSK3882347 150 mg	Part 2: Repeat Dose GSK3882347 500 mg	Part 2: Repeat Dose GSK3882347 900 mg
Day 3: Pre-dose	99.48 ± 19.360	326.89 ± 81.306	1157.589 ± 432.3864	1578.14 ± 328.085
Day 4: Pre-dose	96.66 ± 16.722	344.56 ± 112.891	1212.368 ± 438.9076	1883.90 ± 560.646
Day 5: Pre-dose	96.16 ± 15.683	329.37 ± 88.100	1166.770 ± 369.9656	1724.07 ± 524.054
Day 6: Pre-dose	97.50 ± 21.275	339.83 ± 100.604	1157.068 ± 384.6052	1776.54 ± 513.638
Day 7: Pre-dose	92.46 ± 14.390	300.16 ± 75.925	1105.470 ± 464.5923	1769.40 ± 618.929

SecondaryPart 1: Area Under the Concentration-time Curve From Time Zero to 24 Hours (AUC[0-24]) After Single Dose Administration of GSK3882347 250 mg Under Fasted and Fed Conditions for Assessment of Food Effect

Blood samples were collected at indicated time points for PK analysis of GSK3882347 250 mg under fasted and fed conditions for assessment of food effect. PK parameters were analyzed using standard non-compartmental analysis.

Time frame:: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16 and 24 hours post-dose
Reported as:: Geometric mean · Hours*nanogram per milliliter

Part 1: Area Under the Concentration-time Curve From Time Zero to 24 Hours (AUC[0-24]) After Single Dose Administration of GSK3882347 250 mg Under Fasted and Fed Conditions for Assessment of Food Effect
Hours*nanogram per milliliter	Part 1: Single Dose GSK3882347 250 mg	Part 1: Single Dose GSK3882347 250 mg Fed
Part 1: Area Under the Concentration-time Curve From Time Zero to 24 Hours (AUC[0-24]) After Single Dose Administration of GSK3882347 250 mg Under Fasted and Fed Conditions for Assessment of Food Effect	28472.2 ± 0.08	21456.4 ± 0.08

Statistical analysis

Part 1: Single Dose GSK3882347 250 mg vs Part 1: Single Dose GSK3882347 250 mg Fed · Ratio of geometric mean: 0.75 · 90% CI 0.61 to 0.93Mixed Effect Model has been used to assess Food Effect for the log transformed parameter AUC(0-24). Treatment in the fed/fasted state is fitted as Fixed Effect. Participant is fitted as Random Effect. Unstructured covariance structure is used.

SecondaryPart 1: Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUC [0-t]) After Single Dose Administration of GSK3882347 250 mg Under Fasted and Fed Conditions for Assessment of Food Effect

Time frame:: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 32, 48, 72 and 96 hours post-dose
Reported as:: Geometric mean · Hours*nanogram per milliliter

Part 1: Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUC [0-t]) After Single Dose Administration of GSK3882347 250 mg Under Fasted and Fed Conditions for Assessment of Food Effect
Hours*nanogram per milliliter	Part 1: Single Dose GSK3882347 250 mg	Part 1: Single Dose GSK3882347 250 mg Fed
Part 1: Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUC [0-t]) After Single Dose Administration of GSK3882347 250 mg Under Fasted and Fed Conditions for Assessment of Food Effect	36561.0 ± 0.08	29091.9 ± 0.08

Statistical analysis

Part 1: Single Dose GSK3882347 250 mg vs Part 1: Single Dose GSK3882347 250 mg Fed · Ratio of geometric mean: 0.80 · 90% CI 0.65 to 0.98Mixed Effect Model was used to assess Food Effect for the log transformed parameter AUC(0-t). Treatment in the fed/fasted state was fitted as Fixed Effect. Participant was fitted as Random Effect. Unstructured covariance structure was used.

SecondaryPart 1: Area Under the Concentration-time Curve Extrapolated From Time Zero to Infinity (AUC [0-infinity]) After Single Dose Administration of GSK3882347 250 mg Under Fasted and Fed Conditions for Assessment of Food Effect

Time frame:: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 32, 48, 72 and 96 hours post-dose
Reported as:: Geometric mean · Hours*nanogram per milliliter

Part 1: Area Under the Concentration-time Curve Extrapolated From Time Zero to Infinity (AUC [0-infinity]) After Single Dose Administration of GSK3882347 250 mg Under Fasted and Fed Conditions for Assessment of Food Effect
Hours*nanogram per milliliter	Part 1: Single Dose GSK3882347 250 mg	Part 1: Single Dose GSK3882347 250 mg Fed
Part 1: Area Under the Concentration-time Curve Extrapolated From Time Zero to Infinity (AUC [0-infinity]) After Single Dose Administration of GSK3882347 250 mg Under Fasted and Fed Conditions for Assessment of Food Effect	36768.0 ± 0.08	29316.1 ± 0.08

Statistical analysis

Part 1: Single Dose GSK3882347 250 mg vs Part 1: Single Dose GSK3882347 250 mg Fed · Ratio of geometric mean: 0.80 · 90% CI 0.65 to 0.98Mixed Effect Model was used to assess Food Effect for log transformed parameter AUC(0-infinity). Treatment in the fed/fasted state was fitted as Fixed Effect. Participant was fitted as Random Effect. Unstructured covariance structure was used.

SecondaryPart 1: Maximum Plasma Concentration (Cmax) After Single Dose Administration of GSK3882347 250 mg Under Fasted and Fed Conditions for Assessment of Food Effect

Time frame:: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 32, 48, 72 and 96 hours post-dose
Reported as:: Geometric mean · Nanograms per milliliter

Part 1: Maximum Plasma Concentration (Cmax) After Single Dose Administration of GSK3882347 250 mg Under Fasted and Fed Conditions for Assessment of Food Effect
Nanograms per milliliter	Part 1: Single Dose GSK3882347 250 mg	Part 1: Single Dose GSK3882347 250 mg Fed
Part 1: Maximum Plasma Concentration (Cmax) After Single Dose Administration of GSK3882347 250 mg Under Fasted and Fed Conditions for Assessment of Food Effect	3126.7 ± 0.10	1834.5 ± 0.10

Statistical analysis

Part 1: Single Dose GSK3882347 250 mg vs Part 1: Single Dose GSK3882347 250 mg Fed · Ratio of geometric mean: 0.59 · 90% CI 0.46 to 0.75Mixed Effect Model was used to assess Food Effect for the log transformed parameter Cmax. Treatment in the fed/fasted state was fitted as Fixed Effect. Participant was fitted as Random Effect. Unstructured covariance structure was used.

SecondaryPart 1: Plasma Concentrations at 24 Hours (C24h) After Single Dose Administration of GSK3882347 250 mg Under Fasted and Fed Conditions for Assessment of Food Effect

Time frame:: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16 and 24 hours post-dose
Reported as:: Geometric mean · Nanograms per milliliter

Part 1: Plasma Concentrations at 24 Hours (C24h) After Single Dose Administration of GSK3882347 250 mg Under Fasted and Fed Conditions for Assessment of Food Effect
Nanograms per milliliter	Part 1: Single Dose GSK3882347 250 mg	Part 1: Single Dose GSK3882347 250 mg Fed
Part 1: Plasma Concentrations at 24 Hours (C24h) After Single Dose Administration of GSK3882347 250 mg Under Fasted and Fed Conditions for Assessment of Food Effect	494.7 ± 0.09	449.2 ± 0.09

Statistical analysis

Part 1: Single Dose GSK3882347 250 mg vs Part 1: Single Dose GSK3882347 250 mg Fed · Ratio of geometric mean: 0.91 · 90% CI 0.74 to 1.11Mixed Effect Model was used to assess Food Effect for the log transformed parameter C24h. Treatment in the fed/fasted state was fitted as Fixed Effect. Participant was fitted as Random Effect. Unstructured covariance structure was used.

SecondaryPart 1: Tmax After Single Dose Administration of GSK3882347 250 mg Under Fasted and Fed Conditions for Assessment of Food Effect

Time frame:: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 32, 48, 72 and 96 hours post-dose
Reported as:: Median · Hours

Part 1: Tmax After Single Dose Administration of GSK3882347 250 mg Under Fasted and Fed Conditions for Assessment of Food Effect
Hours	Part 1: Single Dose GSK3882347 250 mg	Part 1: Single Dose GSK3882347 250 mg Fed
Part 1: Tmax After Single Dose Administration of GSK3882347 250 mg Under Fasted and Fed Conditions for Assessment of Food Effect	4.000 (2.00 to 6.00)	4.000 (2.00 to 8.00)

Statistical analysis

Part 1: Single Dose GSK3882347 250 mg vs Part 1: Single Dose GSK3882347 250 mg Fed · Median difference (net): 0.000 · 90% CI 0.000 to 2.000Wilcoxon matched pair test was used to assess Food Effect for the parameter Tmax.

SecondaryPart 1: Tlag After Single Dose Administration of GSK3882347 250 mg Under Fasted and Fed Conditions for Assessment of Food Effect

Time frame:: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 32, 48, 72 and 96 hours post-dose
Reported as:: Median · Hours

Part 1: Tlag After Single Dose Administration of GSK3882347 250 mg Under Fasted and Fed Conditions for Assessment of Food Effect
Hours	Part 1: Single Dose GSK3882347 250 mg	Part 1: Single Dose GSK3882347 250 mg Fed
Part 1: Tlag After Single Dose Administration of GSK3882347 250 mg Under Fasted and Fed Conditions for Assessment of Food Effect	0.250 (0 to 0.25)	0.250 (0.25 to 1.50)

Statistical analysis

Part 1: Single Dose GSK3882347 250 mg vs Part 1: Single Dose GSK3882347 250 mg Fed · Median difference (net): 0.000 · 90% CI 0.000 to 0.250Wilcoxon matched pair test was used to assess Food Effect for the parameter Tlag.

Adverse events

Collected over All-cause mortality, SAEs and Non-SAEs were collected from the start of study treatment up to 3 months for Part 1 and up to 26 days for Part 2. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Part 1: Single Dose Placebo	0/14 (0%)	0/14 (0%)	7/14 (50%)
Part 1: Single Dose GSK3882347 15 mg	0/6 (0%)	0/6 (0%)	1/6 (16.7%)
Part 1: Single Dose GSK3882347 50 mg	0/6 (0%)	0/6 (0%)	2/6 (33.3%)
Part 1: Single Dose GSK3882347 150 mg	0/6 (0%)	0/6 (0%)	2/6 (33.3%)
Part 1: Single Dose GSK3882347 250 mg	0/6 (0%)	0/6 (0%)	3/6 (50%)
Part 1: Single Dose GSK3882347 250 mg Fed	0/6 (0%)	0/6 (0%)	2/6 (33.3%)
Part 1: Single Dose GSK3882347 500 mg	0/6 (0%)	0/6 (0%)	3/6 (50%)
Part 1: Single Dose GSK3882347 900 mg	0/6 (0%)	0/6 (0%)	2/6 (33.3%)
Part 2: Repeat Dose Placebo	0/8 (0%)	0/8 (0%)	5/8 (62.5%)
Part 2: Repeat Dose GSK3882347 50 mg	0/8 (0%)	0/8 (0%)	4/8 (50%)
Part 2: Repeat Dose GSK3882347 150 mg	0/8 (0%)	0/8 (0%)	2/8 (25%)
Part 2: Repeat Dose GSK3882347 500 mg	0/8 (0%)	0/8 (0%)	7/8 (87.5%)
Part 2: Repeat Dose GSK3882347 900 mg	0/8 (0%)	0/8 (0%)	7/8 (87.5%)

Most frequent other events

Showing 10 of 39

Most frequent other events
Event	Part 1: Single Dose Placebo	Part 1: Single Dose GSK3882347 15 mg	Part 1: Single Dose GSK3882347 50 mg	Part 1: Single Dose GSK3882347 150 mg	Part 1: Single Dose GSK3882347 250 mg	Part 1: Single Dose GSK3882347 250 mg Fed	Part 1: Single Dose GSK3882347 500 mg	Part 1: Single Dose GSK3882347 900 mg	Part 2: Repeat Dose Placebo	Part 2: Repeat Dose GSK3882347 50 mg	Part 2: Repeat Dose GSK3882347 150 mg	Part 2: Repeat Dose GSK3882347 500 mg	Part 2: Repeat Dose GSK3882347 900 mg
Dermatitis contactSkin and subcutaneous tissue disorders	1/14	0/6	0/6	0/6	0/6	0/6	0/6	2/6	1/8	0/8	1/8	1/8	0/8
ContusionInjury, poisoning and procedural complications	2/14	0/6	0/6	0/6	0/6	0/6	0/6	0/6	1/8	1/8	0/8	2/8	1/8
FlatulenceGastrointestinal disorders	0/14	0/6	0/6	0/6	0/6	0/6	0/6	0/6	1/8	0/8	0/8	2/8	1/8
HeadacheNervous system disorders	2/14	1/6	1/6	0/6	0/6	1/6	1/6	0/6	1/8	0/8	0/8	0/8	1/8
Burning sensationNervous system disorders	0/14	0/6	0/6	0/6	0/6	0/6	1/6	0/6	0/8	0/8	0/8	0/8	0/8
DizzinessNervous system disorders	0/14	0/6	0/6	0/6	1/6	0/6	0/6	0/6	1/8	0/8	0/8	0/8	0/8
PresyncopeNervous system disorders	0/14	1/6	0/6	0/6	0/6	0/6	0/6	0/6	0/8	0/8	0/8	0/8	0/8
Abdominal painGastrointestinal disorders	0/14	0/6	1/6	0/6	0/6	0/6	0/6	0/6	0/8	1/8	0/8	0/8	0/8
Abdominal pain lowerGastrointestinal disorders	0/14	0/6	0/6	0/6	0/6	0/6	1/6	0/6	0/8	0/8	0/8	0/8	0/8
Mouth ulcerationGastrointestinal disorders	0/14	0/6	0/6	1/6	0/6	0/6	0/6	0/6	0/8	0/8	0/8	0/8	0/8

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)	Part1-Cohort1:GSK3882347 SD 50mg/SD 150mg/SD 250 mg/SD PBO	Part1-Cohort1:GSK3882347 SD 50mg/SD 150mg/SD PBO/SD 250mg Fed	Part1-Cohort1: GSK3882347 SD 50mg/SD PBO/SD 250mg/SD 250mg Fed	Part1-Cohort1:SD PBO/GSK3882347 SD 150mg/SD 250mg/SD 250mg Fed	Part 1-Cohort 2: SD PBO/GSK3882347 SD 900 mg/SD 15 mg	Part 1-Cohort 2: GSK3882347 SD 500 mg/SD PBO/SD 15 mg	Part 1-Cohort 2: GSK3882347 SD 500 mg/SD 900 mg/SD PBO	Part 1-Cohort 2: GSK3882347 SD 500 mg/SD 900 mg/SD 15 mg	Part 2: Repeat Dose Placebo	Part 2: Repeat Dose GSK3882347 50 mg	Part 2: Repeat Dose GSK3882347 150 mg	Part 2: Repeat Dose GSK3882347 500 mg	Part 2: Repeat Dose GSK3882347 900 mg	Total
<=18 years	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Between 18 and 65 years	3	2	2	3	3	3	3	2	8	8	8	8	8	61
>=65 years	0	0	0	0	0	0	0	0	0	0	0	0	0	0

Sex: Female, Male
Sex: Female, Male(Participants)	Part1-Cohort1:GSK3882347 SD 50mg/SD 150mg/SD 250 mg/SD PBO	Part1-Cohort1:GSK3882347 SD 50mg/SD 150mg/SD PBO/SD 250mg Fed	Part1-Cohort1: GSK3882347 SD 50mg/SD PBO/SD 250mg/SD 250mg Fed	Part1-Cohort1:SD PBO/GSK3882347 SD 150mg/SD 250mg/SD 250mg Fed	Part 1-Cohort 2: SD PBO/GSK3882347 SD 900 mg/SD 15 mg	Part 1-Cohort 2: GSK3882347 SD 500 mg/SD PBO/SD 15 mg	Part 1-Cohort 2: GSK3882347 SD 500 mg/SD 900 mg/SD PBO	Part 1-Cohort 2: GSK3882347 SD 500 mg/SD 900 mg/SD 15 mg	Part 2: Repeat Dose Placebo	Part 2: Repeat Dose GSK3882347 50 mg	Part 2: Repeat Dose GSK3882347 150 mg	Part 2: Repeat Dose GSK3882347 500 mg	Part 2: Repeat Dose GSK3882347 900 mg	Total
Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Male	3	2	2	3	3	3	3	2	8	8	8	8	8	61

Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)	Part1-Cohort1:GSK3882347 SD 50mg/SD 150mg/SD 250 mg/SD PBO	Part1-Cohort1:GSK3882347 SD 50mg/SD 150mg/SD PBO/SD 250mg Fed	Part1-Cohort1: GSK3882347 SD 50mg/SD PBO/SD 250mg/SD 250mg Fed	Part1-Cohort1:SD PBO/GSK3882347 SD 150mg/SD 250mg/SD 250mg Fed	Part 1-Cohort 2: SD PBO/GSK3882347 SD 900 mg/SD 15 mg	Part 1-Cohort 2: GSK3882347 SD 500 mg/SD PBO/SD 15 mg	Part 1-Cohort 2: GSK3882347 SD 500 mg/SD 900 mg/SD PBO	Part 1-Cohort 2: GSK3882347 SD 500 mg/SD 900 mg/SD 15 mg	Part 2: Repeat Dose Placebo	Part 2: Repeat Dose GSK3882347 50 mg	Part 2: Repeat Dose GSK3882347 150 mg	Part 2: Repeat Dose GSK3882347 500 mg	Part 2: Repeat Dose GSK3882347 900 mg	Total
Black or African American	0	0	0	1	0	1	0	0	1	0	1	0	1	5
Asian- South East Asian Heritage	0	0	1	0	0	0	0	0	0	0	1	0	1	3
White- White/Caucasian/European Heritage	3	2	1	2	3	2	3	2	6	8	6	7	6	51
Mixed race	0	0	0	0	0	0	0	0	1	0	0	1	0	2

Study locations

1 site

GSK Investigational Site
Cambridge, CB2 2GG, United Kingdom

References and documents

Study documents

Study protocol · Oct 21, 2020
Statistical analysis plan · May 24, 2021

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — IPD for this study will be made available via the Clinical Study Data Request site.

Supporting information: Study protocol, Statistical analysis plan, Informed consent form, Clinical study report

Time frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.

Access criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

Data sharing details ↗ · clinicalstudydatarequest.com

Timeline

Tracking since Sep 25, 2026

ElapsedEstimatedEstimated, not yet reached

Ran from Aug 2020 to primary completion in May 2021, 8 months.

Results were first posted in Feb 2023, 1 year 9 months after primary completion.

How these figures are worked out, and which studies are left out of them.

Registered: Jul 23, 2020
First posted: Jul 28, 2020
StartActual: Aug 24, 2020
Primary completionActual: May 14, 2021
CompletionActual: May 14, 2021
Results first posted: Feb 17, 2023
Last update: Feb 17, 2023

What these dates mean

Start.: When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.: When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.: When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.: Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.

No changes since tracking began. The registry record was last updated on Feb 17, 2023, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT04488770
Lead sponsor: GlaxoSmithKline
Collaborators: Department of Health and Human Services, Wellcome Trust
Responsible party: Sponsor
First posted: Jul 28, 2020
Start date: Aug 24, 2020
Primary completion: May 14, 2021
Completion: May 14, 2021
Results posted: Feb 17, 2023
Last update: Feb 17, 2023

Study contacts

GSK Clinical Trials

study director · GlaxoSmithKline

Oversight

Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in May 2022. You cannot join it, but the record below documents what was studied.

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Discussion

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Urinary Tract Infections

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