Urinary Tract InfectionsPhase 1NCT04488770

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

A Phase 1 study testing GSK3882347 in people with Urinary Tract Infections, run by GlaxoSmithKline at 1 site in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 50 yearsHealthy volunteers can take part
Conditions the study is for: Urinary Tract Infections
What is being tested?: GSK3882347
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 61 participants
Where: 1 siteUnited Kingdom
Study dates: 24 Aug 2020to 14 May 2021
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 50 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

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.

Who cannot join

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.

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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.

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

GSK Investigational Site
Cambridge, CB2 2GG

Other trials in United Kingdom

About this study

Official title: A Double-Blind Randomized, Placebo-Controlled, Single and Repeated Oral Dose Escalation Study to Investigate the Safety, Tolerability, Pharmacokinetics (Including Food Effect) of GSK3882347 in Healthy Participants

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: Urinary Tract Infections
Being tested: GSK3882347, Placebo
Keywords: SAD, MAD, FTIH, Pharmacokinetics, Urinary Tract Infections, GSK3882347
Medical subject headings: Urinary Tract Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

GSK3882347Drug
Capsule of 10-200mg dose strength will be provided in labelled High Density Polyethylene (HDPE) bottles.
PlaceboDrug
Matching strength placebo capsules will be provided

Study groups in NCT04488770
Study group	Role	What they receive
Part 1 (SAD) Cohort 1:Participants receiving GSK3882347	Experimental	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. Receives: Drug: GSK3882347
Part 1 (SAD),Cohort 1:Participants receiving Placebo	Placebo comparator	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. Receives: Drug: Placebo
Part 1 (SAD),Cohort 2: Participants receiving GSK3882347	Experimental	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. Receives: Drug: GSK3882347
Part 1 (SAD),Cohort 2: Participants receiving Placebo	Placebo comparator	In this single ascending dose phase, participants will receive matching Placebo orally on Day 1 of period 1, 3 and 2. Receives: Drug: Placebo
Part 2 (MAD),Cohort 3: Participants receiving GSK3882347 50mg	Experimental	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. Receives: Drug: GSK3882347
Part 2 (MAD),Cohort 3: Participants receiving Placebo	Placebo comparator	In this multiple ascending dose phase, participants will receive matching Placebo orally on Day 1 to Day 7 of the study. Receives: Drug: Placebo
Part 2 (MAD),Cohort 4: Participants receiving GSK3882347 150mg	Experimental	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. Receives: Drug: GSK3882347
Part 2 (MAD),Cohort 4: Participants receiving Placebo	Placebo comparator	In this multiple ascending dose phase, participants will receive matching Placebo orally on Day 1 to Day 7 of the study. Receives: Drug: Placebo
Part 2(MAD),Cohort 5: Participants receiving GSK3882347 500mg	Experimental	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. Receives: Drug: GSK3882347
Part 2 (MAD),Cohort 5: Participants receiving Placebo	Placebo comparator	In this multiple ascending dose phase, participants will receive matching Placebo orally on Day 1 to Day 7 of the study. Receives: Drug: Placebo
Part 2(MAD),Cohort 6: Participants receiving GSK3882347 900mg	Experimental	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. Receives: Drug: GSK3882347
Part 2(MAD),Cohort 6: Participants receiving Placebo	Placebo comparator	In this multiple ascending dose phase, participants will receive matching Placebo orally on Day 1 to Day 7 of the study. Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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 (%).
Measured: 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%.
Measured: 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)
Measured: 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).
Measured: 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 (21)

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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 32, 48, 72 and 96 hours post-dose

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

24 Aug 202014 May 2021

First posted28 Jul 2020
Study start24 Aug 2020
Primary completion14 May 2021
Study completion14 May 2021

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Urinary Tract InfectionsStudies of the same condition, open and under way.
More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Model description: Part 1 will consist of two cohorts (Cohorts 1 and 2) with a maximum of four periods in a cross-over design conducted in two separate cohorts. Part 2 consists of a maximum of four ascending repeat-dose cohorts (Cohorts 3 to 6) for which participants, will receive a single oral dose of GSK3882347 or placebo for 7 days.
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 61 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04488770
Sponsor's protocol ID: 212148
Other IDs: 2020-000680-23
Status last verified: May 2022
First submitted: 23 Jul 2020
Last updated: 17 Feb 2023
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: Yes: IPD for this study will be made available via the Clinical Study Data Request site.

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 17 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Double-Blind Randomized, Placebo-Controlled, Single and Repeated Oral Dose Escalation Study to Investigate the Safety, Tolerability, Pharmacokinetics (Including Food Effect) of GSK3882347 in Healthy Participants
ClinicalTrials.gov ID: NCT04488770
Acronym / sponsor ID: 212148
Conditions: Urinary Tract Infections
Keywords: SAD, MAD, FTIH, Pharmacokinetics, Urinary Tract Infections, GSK3882347
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 61 participants (actual)
Lead sponsor: GlaxoSmithKlineIndustry (pharma, biotech, devices)
Collaborators: Department of Health and Human Services, Wellcome Trust
Study start: 24 Aug 2020 (actual)
Primary completion: 14 May 2021 (actual)
Study completion: 14 May 2021 (actual)
First posted: 28 Jul 2020 (actual)
Results: Posted 17 Feb 2023

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind (participant, investigator)
Number of arms: 12
Model description: Part 1 will consist of two cohorts (Cohorts 1 and 2) with a maximum of four periods in a cross-over design conducted in two separate cohorts. Part 2 consists of a maximum of four ascending repeat-dose cohorts (Cohorts 3 to 6) for which participants, will receive a single oral dose of GSK3882347 or placebo for 7 days.

Arm	Type	Receives
Part 1 (SAD) Cohort 1:Participants receiving GSK3882347	Experimental	Drug: GSK3882347In 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.
Part 1 (SAD),Cohort 1:Participants receiving Placebo	Placebo comparator	Drug: PlaceboIn 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.
Part 1 (SAD),Cohort 2: Participants receiving GSK3882347	Experimental	Drug: GSK3882347In 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.
Part 1 (SAD),Cohort 2: Participants receiving Placebo	Placebo comparator	Drug: PlaceboIn this single ascending dose phase, participants will receive matching Placebo orally on Day 1 of period 1, 3 and 2.
Part 2 (MAD),Cohort 3: Participants receiving GSK3882347 50mg	Experimental	Drug: GSK3882347In 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.
Part 2 (MAD),Cohort 3: Participants receiving Placebo	Placebo comparator	Drug: PlaceboIn this multiple ascending dose phase, participants will receive matching Placebo orally on Day 1 to Day 7 of the study.
Part 2 (MAD),Cohort 4: Participants receiving GSK3882347 150mg	Experimental	Drug: GSK3882347GSK3882347 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.
Part 2 (MAD),Cohort 4: Participants receiving Placebo	Placebo comparator	Drug: PlaceboIn this multiple ascending dose phase, participants will receive matching Placebo orally on Day 1 to Day 7 of the study.
Part 2(MAD),Cohort 5: Participants receiving GSK3882347 500mg	Experimental	Drug: GSK3882347GSK3882347 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.
Part 2 (MAD),Cohort 5: Participants receiving Placebo	Placebo comparator	Drug: PlaceboIn this multiple ascending dose phase, participants will receive matching Placebo orally on Day 1 to Day 7 of the study.
Part 2(MAD),Cohort 6: Participants receiving GSK3882347 900mg	Experimental	Drug: GSK3882347GSK3882347 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.
Part 2(MAD),Cohort 6: Participants receiving Placebo	Placebo comparator	Drug: PlaceboIn this multiple ascending dose phase, participants will receive matching Placebo orally on Day 1 to Day 7 of the study.

Who may qualify

Ages: 18 to 50 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (5 listed)

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.

Key exclusion criteria (30 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
GSK3882347Capsule of 10-200mg dose strength will be provided in labelled High Density Polyethylene (HDPE) bottles.	Drug	Part 1 (SAD) Cohort 1:Participants receiving GSK3882347, Part 1 (SAD),Cohort 2: Participants receiving GSK3882347, Part 2 (MAD),Cohort 3: Participants receiving GSK3882347 50mg, Part 2 (MAD),Cohort 4: Participants receiving GSK3882347 150mg, Part 2(MAD),Cohort 5: Participants receiving GSK3882347 500mg, Part 2(MAD),Cohort 6: Participants receiving GSK3882347 900mg
PlaceboMatching strength placebo capsules will be provided	Drug	Part 1 (SAD),Cohort 1:Participants receiving Placebo, Part 1 (SAD),Cohort 2: Participants receiving Placebo, Part 2 (MAD),Cohort 3: Participants receiving Placebo, Part 2 (MAD),Cohort 4: Participants receiving Placebo, Part 2 (MAD),Cohort 5: Participants receiving Placebo, Part 2(MAD),Cohort 6: Participants receiving Placebo

Primary outcome

Part 1: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: Up to 3 months
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.
Part 2: Number of Participants With Non-serious AEs and SAEs
Time frame: Up to 26 days
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.
Part 1: Number of Participants With Treatment Related AEs
Time frame: Up to 3 months
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.
Part 2: Number of Participants With Treatment Related AEs
Time frame: Up to 26 days
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.
Part 1: Number of Participants With Worst-case Hematology Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline
Time frame: Up to 3 months
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
Part 2: Number of Participants With Worst-case Hematology Results Relative to PCI Criteria Post-Baseline Relative to Baseline
Time frame: Up to 26 days
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
Part 1: Number of Participants With Worst-case Clinical Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline
Time frame: Up to 3 months
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
Part 2: Number of Participants With Worst-case Clinical Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline
Time frame: Up to 26 days
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.
Part 1: Number of Participants With Worst Case Urinalysis Results Post Baseline Relative to Baseline
Time frame: Up to 3 months
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.
Part 2: Number of Participants With Worst Case Urinalysis Results Post Baseline Relative to Baseline
Time frame: Up to 26 days
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.
Part 1: Number of Participants With Worst Case Vital Signs Results Relative to PCI Criteria Post Baseline Relative to Baseline
Time frame: Up to 3 months
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
Part 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
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
Part 1: Number of Participants With Worst Case Abnormal Electrocardiogram (ECG) Results Post Baseline Relative to Baseline
Time frame: Up to 3 months
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.
Part 2: Number of Participants With Worst Case Abnormal ECG Results Post Baseline Relative to Baseline
Time frame: Up to 26 days
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.
Part 1: Area Under the Concentration-time Curve From Time Zero to 24 Hours (AUC[0-24]) After Single Dose Administration of GSK3882347
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
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis.
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
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
Blood samples were collected at indicated time points for PK analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis.
Part 1: Area Under the Concentration-time Curve Extrapolated From Time Zero to Infinity (AUC[0-infinity]) After Single Dose Administration of GSK3882347
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
Blood samples were collected at indicated time points for PK analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis.
Part 1: Maximum Plasma Concentration (Cmax) After Single Dose Administration of GSK3882347
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
Blood samples were collected at indicated time points for PK analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis.
Part 1: Plasma Concentrations at 24 Hours (C24h) After Single Dose Administration of GSK3882347
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
Blood samples were collected at indicated time points for PK analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis.
Part 1: Time to Cmax (Tmax) After Single Dose Administration of GSK3882347
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
Blood samples were collected at indicated time points for PK analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis.
Part 1: Lag Time for Absorption (Tlag) After Single Dose Administration of GSK3882347
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
Blood samples were collected at indicated time points for PK analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis.
Part 1: Terminal Elimination Half-life (T1/2) After Single Dose Administration of GSK3882347
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
Blood samples were collected at indicated time points for PK analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis.
Part 2: Area Under the Concentration-time Curve Over the Dosing Interval Tau (AUC[0-tau]) After Repeat Dose Administration of GSK3882347
Time frame: Days 1 and 7: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16, 24 hours post-dose
Blood samples were collected at indicated time points for PK analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis.
Part 2: Cmax After Repeat Dose Administration of GSK3882347
Time frame: Days 1 and 7: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16, 24 hours post-dose
Blood samples were collected at indicated time points for PK analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis.
Part 2: Tmax After Repeat Dose Administration of GSK3882347
Time frame: Days 1 and 7: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16, 24 hours post-dose
Blood samples were collected at indicated time points for PK analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis.
Part 2: Plasma Concentrations Over the Dosing Interval (Ctau) After Repeat Dose Administration of GSK3882347
Time frame: Days 1 and 7: Pre-dose, 15, 30 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16, 24 hours post-dose
Blood samples were collected at indicated time points for PK analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis.
Part 1: Urine Concentration Between 22-24 Hours (C22-24) After Single Dose Administration of GSK3882347
Time frame: Day 1: 22-24 hours post-dose in each treatment period
Urine samples were collected at indicated time points for PK analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis.
Part 2: Urine Concentration Between 22-24 Hours (C22-24) After Repeat Dose Administration of GSK3882347
Time frame: Day 1 and Day 7: 22-24 hours post-dose
Urine samples were collected at indicated time points for PK analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis.
Part 1: Amount of Drug Excreted in Urine of Unchanged Drug (Ae Total) After Single Dose Administration of GSK3882347
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
Urine samples were collected at indicated time points for PK analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis.
Part 2: Amount of Drug Excreted in Urine of Unchanged Drug (Ae Total) After Repeat Dose Administration of GSK3882347
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
Urine samples were collected at indicated time points for PK analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis.
Part 1: Percentage of the Given Dose of Drug Excreted in Urine (%fe Total) After Single Dose Administration of GSK3882347
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
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 (%).
Part 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
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%.
Part 1: Renal Clearance of Drug (CLr) After Single Dose Administration of GSK3882347
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
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)
Part 2: Renal Clearance of Drug (CLr) After Repeat 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
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).

21 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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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 and safety

Results posted to the registry on 17 Feb 2023, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Part1-Cohort1:GSK3882347 SD 50mg/SD 150mg/SD 250 mg/SD PBO	2	2
Part1-Cohort1:GSK3882347 SD 50mg/SD 150mg/SD PBO/SD 250mg Fed	2	2
Part1-Cohort1: GSK3882347 SD 50mg/SD PBO/SD 250mg/SD 250mg Fed	2	2
Part1-Cohort1:SD PBO/GSK3882347 SD 150mg/SD 250mg/SD 250mg Fed	2	1
Part 1-Cohort 2: SD PBO/GSK3882347 SD 900 mg/SD 15 mg	0	0
Part 1-Cohort 2: GSK3882347 SD 500 mg/SD PBO/SD 15 mg	0	0
Part 1-Cohort 2: GSK3882347 SD 500 mg/SD 900 mg/SD PBO	0	0
Part 1-Cohort 2: GSK3882347 SD 500 mg/SD 900 mg/SD 15 mg	0	0
Part 2: Repeat Dose Placebo	0	0
Part 2: Repeat Dose GSK3882347 50 mg	0	0
Part 2: Repeat Dose GSK3882347 150 mg	0	0
Part 2: Repeat Dose GSK3882347 500 mg	0	0
Part 2: Repeat Dose GSK3882347 900 mg	0	0

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

Time frame: Up to 3 months. Count of participants. Unit: Participants

Measure	Part 1: Single Dose Placebo n = 14	Part 1: Single Dose GSK3882347 15 mg n = 6	Part 1: Single Dose GSK3882347 50 mg n = 6	Part 1: Single Dose GSK3882347 150 mg n = 6	Part 1: Single Dose GSK3882347 250 mg n = 6	Part 1: Single Dose GSK3882347 250 mg Fed n = 6	Part 1: Single Dose GSK3882347 500 mg n = 6	Part 1: Single Dose GSK3882347 900 mg n = 6
Non-serious AEs	7	1	2	2	3	2	3	2
SAEs	0	0	0	0	0	0	0	0

Population analysed: Safety Population comprised of all participants who received at least one dose of study intervention.

Primary outcome: Part 2: Number of Participants With Non-serious AEs and SAEs

Time frame: Up to 26 days. Count of participants. Unit: Participants

Measure	Part 2: Repeat Dose Placebo n = 8	Part 2: Repeat Dose GSK3882347 50 mg n = 8	Part 2: Repeat Dose GSK3882347 150 mg n = 8	Part 2: Repeat Dose GSK3882347 500 mg n = 8	Part 2: Repeat Dose GSK3882347 900 mg n = 8
Non-serious AEs	5	4	2	7	7
SAEs	0	0	0	0	0

Population analysed: Safety Population.

Primary outcome: Part 1: Number of Participants With Treatment Related AEs

Time frame: Up to 3 months. Count of participants. Unit: Participants

Measure	Part 1: Single Dose Placebo n = 14	Part 1: Single Dose GSK3882347 15 mg n = 6	Part 1: Single Dose GSK3882347 50 mg n = 6	Part 1: Single Dose GSK3882347 150 mg n = 6	Part 1: Single Dose GSK3882347 250 mg n = 6	Part 1: Single Dose GSK3882347 250 mg Fed n = 6	Part 1: Single Dose GSK3882347 500 mg n = 6	Part 1: Single Dose GSK3882347 900 mg n = 6
Value	0	0	0	0	0	0	0	0

Population analysed: Safety Population

Primary outcome: Part 2: Number of Participants With Treatment Related AEs

Time frame: Up to 26 days. Count of participants. Unit: Participants

Measure	Part 2: Repeat Dose Placebo n = 8	Part 2: Repeat Dose GSK3882347 50 mg n = 8	Part 2: Repeat Dose GSK3882347 150 mg n = 8	Part 2: Repeat Dose GSK3882347 500 mg n = 8	Part 2: Repeat Dose GSK3882347 900 mg n = 8
Value	1	2	0	0	0

Population analysed: Safety Population.

21 secondary outcomes are reported in the full results.

Adverse events

Time frame: 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. Other adverse events reported at 5% frequency or more

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

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 17 Feb 2023.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: Yes. IPD for this study will be made available via the Clinical Study Data Request site.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

GSK Clinical Trials study director

GlaxoSmithKline

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing GSK3882347 in people with Urinary Tract Infections, run by GlaxoSmithKline at 1 site in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 17 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 17 Feb 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Part 1: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) (time frame: Up to 3 months). The study lists 34 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04488770.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Feb 2023.