Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
GSK3882347 · 3 trials · 2 indications
Microbiological response (success/failure) is used to measure microbiological efficacy. Microbiological success was defined as a reduction in E. coli count to less than (\<) 10\^3 colony-forming units (CFU) per milliliter (CFU/mL) for any E. coli at the ToC visit. Microbiological failure included all other microbiological outcomes (for example but not limited to \>=10\^3 CFU/mL for any E. coli identified at ToC visit, use of rescue medication prior to ToC, lost to follow-up before ToC, missing/unevaluable samples at ToC, etc).
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.
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.
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.
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.
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
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
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
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.
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.
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.
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
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
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.
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.
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis.
Blood samples were collected at indicated time points for PK analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis.
Blood samples were collected at indicated time points for PK analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis.
Blood samples were collected at indicated time points for PK analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis.
Blood samples were collected at indicated time points for PK analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis.
Blood samples were collected at indicated time points for PK analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis.
Blood samples were collected at indicated time points for PK analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis.
Blood samples were collected at indicated time points for PK analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis.
Blood samples were collected at indicated time points for PK analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis.
Blood samples were collected at indicated time points for PK analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis.
Blood samples were collected at indicated time points for PK analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis.
Blood samples were collected at indicated time points for PK analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis.
Urine samples were collected at indicated time points for PK analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis.
Urine samples were collected at indicated time points for PK analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis.
Urine samples were collected at indicated time points for PK analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis.
Urine samples were collected at indicated time points for PK analysis of GSK3882347. PK parameters were analyzed using standard non-compartmental analysis.
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 (%).
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%.
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)
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).
| Arm | Type | Description |
|---|---|---|
| GSK3882347 and MDZ | EXPERIMENTAL | Period 1: Participants will receive MDZ on Day 1. Period 2: Participants will receive 14-days of repeat dosing of GSK3882347 Followed by one dose of MDZ co-administered with GSK3882347 on Day 15. |
| GSK3882347+ Placebo | EXPERIMENTAL | Participants received GSK3882347 oral capsules plus placebo oral capsules from Day 1 to Day 5. |
| Nitrofurantoin + Placebo | ACTIVE_COMPARATOR | Participants received 100 milligrams (mg) of nitrofurantoin oral capsules plus placebo oral capsules from Day 1 to Day 5. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| Name | Type | Description |
|---|---|---|
| Midazolam | DRUG | Midazolam will be administered. |
| GSK3882347 | DRUG | GSK3882347 will be administered. |
| Nitrofurantoin | DRUG | Nitrofurantoin was administered. |
| Placebo | DRUG | Placebo matching GSK3882347 or Nitrofurantoin was administered. |
Inclusion criteria: * 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 ...
GSK3882347 is an investigational small molecule being developed for the treatment of Urinary Tract Infections (UTIs), including Uncomplicated Urinary Tract Infections. It is currently in Phase 1 clinical development and has not been approved by regulatory authorities.
GSK3882347 is being developed by GSK plc, a global biopharma company listed on the London Stock Exchange under the ticker GSK. The company is conducting Phase 1 clinical trials to evaluate the safety, tolerability, and pharmacokinetics of this investigational drug.
GSK3882347 is in Phase 1 clinical development. It is an investigational drug and has not received regulatory approval. GSK plc is conducting early-stage trials to assess its safety, tolerability, and pharmacokinetic profile in healthy participants and in female patients with urinary tract infections.
GSK3882347 has been studied in three completed Phase 1 trials: NCT04488770 in healthy participants in the UK, NCT05138822 in female participants with urinary tract infections in the US, and NCT05760261, a drug interaction study in healthy participants in the UK. All trials are completed.
GSK3882347 is the sole name provided for this investigational drug. No alternative names or aliases have been reported. It is a small molecule being developed by GSK plc for urinary tract infections.