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

NCT04488770 | Completed Phase 1 Results

• 2 other identifiers: 2121482020-000680-23
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 1

Brief 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

Urinary Tract Infections

Keywords

SAD; MAD; FTIH; Pharmacokinetics; Urinary Tract Infections; GSK3882347

Outcome Measures

Primary Outcomes (34)

• 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.

  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.

  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.

  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.

  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

  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

  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

  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.

  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.

  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.

  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

  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

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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 (%).

  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%.

  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)

  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).

  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

  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

  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

  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

  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

  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

Study Arms (12)

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Drug: Placebo

Interventions

GSK3882347 DRUG

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

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

Placebo DRUG

Matching strength placebo capsules will be provided

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

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Participant must be 18 to 50 years of age inclusive, at the time of signing the informed consent.

You may not qualify if:

• 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.
• 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).

Sponsors & Collaborators

• GlaxoSmithKline: lead
• Department of Health and Human Services: collaborator
• Wellcome Trust: collaborator

Study Sites (1)

GSK Investigational Site

Cambridge, CB2 2GG, United Kingdom

Location

MeSH Terms

Conditions

Urinary Tract Infections

Condition Hierarchy (Ancestors)

Infections; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

8664357343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: This will be a double-blind study with participants and the site staff blinded.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: July 23, 2020
• First Posted: July 28, 2020
• Study Start: August 24, 2020
• Primary Completion: May 14, 2021
• Study Completion: May 14, 2021
• Last Updated: February 17, 2023
• Results First Posted: February 17, 2023

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• 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.

Locations

GB (1)