Safety, Tolerability, Pharmacokinetic and Microbiological Investigation of GSK3882347 in Female Participants With Urinary Tract Infections

A Double-Blind, Double Dummy, Randomized, Phase 1b, Nitrofurantoin Controlled, Repeat Oral Dose Study to Investigate the Safety, Tolerability, Pharmacokinetics and Microbiological Response of GSK3882347 in Female Participants With Acute Uncomplicated Urinary Tract Infection

This phase 1b study is a double-blind, double-dummy, nitrofurantoin-controlled study designed to evaluate microbiological response at the test of cure (ToC) visit along with safety, tolerability and pharmacokinetic (PK) response following oral dosing for 5 days of GSK3882347 in an adult female with uncomplicated urinary tract infections (uUTI). Comparator nitrofurantoin will be included in the study to ensure unbiased reporting of safety events. The study will be separated into 2 cohorts. Cohort 1 consists of an inpatient treatment period and PK analysis at frequent timepoints. Cohort 2 includes an outpatient treatment period and PK analysis conducted less frequently, at key trough timepoints.

Study Overview

• Status: Completed
• Conditions: Urinary Tract Infections; Uncomplicated Urinary Tract Infections
• Intervention / Treatment: Drug: GSK3882347; Drug: Placebo; Drug: Nitrofurantoin

• Study Type: Interventional
• Enrollment (Actual): 140
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Anniston, Alabama, United States, 36207
      • GSK Investigational Site
  • California
    • Lomita, California, United States, 90717
      • GSK Investigational Site
    • Modesto, California, United States, 95350-5365
      • GSK Investigational Site
  • Florida
    • Doral, Florida, United States, 33166
      • GSK Investigational Site
    • Miami, Florida, United States, 33186
      • GSK Investigational Site
    • Miami Lakes, Florida, United States, 33016-1507
      • GSK Investigational Site
    • Palmetto Bay, Florida, United States, 33157
      • GSK Investigational Site
    • Sweetwater, Florida, United States, 33172
      • GSK Investigational Site
  • Illinois
    • Chicago, Illinois, United States, 60643
      • GSK Investigational Site
  • New York
    • The Bronx, New York, United States, 10456
      • GSK Investigational Site
  • Pennsylvania
    • Smithfield, Pennsylvania, United States, 15478
      • GSK Investigational Site
  • Texas
    • Austin, Texas, United States, 78705
      • GSK Investigational Site
    • Dallas, Texas, United States, 75230
      • GSK Investigational Site
    • Houston, Texas, United States, 77061
      • GSK Investigational Site
    • Missouri City, Texas, United States, 77459
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 66 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participants must be greater than or equal to (>=)18 years of age and less than or equal to (<=)70 years
• The participant has 2 or more of the following clinical signs and symptoms of uncomplicated urinary tract infections (uUTI) with onset less than (<) 96 hours of the screening assessment: dysuria, frequency, urgency, or lower abdominal pain
• Participant has nitrite OR pyuria (≥ 10 white blood cells/ cubic millimeter [WBC/mm^3], OR > 5 WBC/high power field [HPF]) OR the presence of 2+ leukocyte esterase from a pre-treatment clean-catch midstream urine sample
• Participants with body mass index (BMI) >= 19.0 kilograms per square meter (kg/m^2)
• A female participant is eligible to participate who is not pregnant (as confirmed by a highly sensitive pregnancy test before the first dose of study intervention) or breastfeeding and one of the following conditions apply: 1) Woman participant of non-childbearing potential (WONCBP) Or 2) Woman participant of childbearing potential (WOCBP) using a contraceptive method that is highly effective, with a failure rate of < 1 percentage (%), during the study intervention period and up to 5 days post intervention
• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and protocol.

Exclusion Criteria:

• The participant has a BMI >= 40.0 kg/ m^2 or a BMI >=35.0 kg/ m^2 with obesity related health conditions such as high blood pressure or uncontrolled diabetes (non-fasting glucose value >300 milligram/deciliter [mg/dL])
• The participant is immunocompromised or has altered immune defenses that may predispose the participant to a higher risk of treatment failure and/or complications
• The participant has symptoms known or suspected to be caused by another disease process, such as asymptomatic bacteriuria, overactive bladder, chronic incontinence, or chronic interstitial cystitis
• The participant has an anatomical or physiological anomaly that predisposes the participant to UTIs or may be a source of persistent bacterial colonization, including calculi, obstruction of the urinary tract, primary renal disease, or neurogenic bladder, or the participant has a history of anatomical or functional abnormalities of the urinary tract
• The participant has an indwelling catheter, nephrostomy, ureteral stent, or other foreign material in the urinary tract
• The participant who, in the opinion of the investigator, has an otherwise complicated UTI, an active upper UTI (e.g., pyelonephritis, urosepsis), signs and symptoms onset >=96 hours before the screening assessment, or a temperature >=101-degree Fahrenheit (°F) (>=38 degree Celsius [°C]), flank pain, chills, or any other manifestations suggestive of upper UTI
• The participant has anuria, oliguria, or significant impairment of renal function
• The participant presents at enrollment with a suspected sexually transmitted infection
• A positive confirmation of Coronavirus Disease 2019 (COVID-19) infection, or high clinical index of suspicion for COVID-19
• The participant has received treatment with other systemic antimicrobials or systemic antifungals within 1 week or 10 weeks for dalbavancin or oritavancin before study entry.
• Regular alcohol consumption within 6 months prior to the study with an average weekly intake of >14 units for females and one unit is equivalent to approximately 8 g of alcohol: a half-pint (250 mL) of beer, one glass (125 mL) of wine or one (35 mL) measure of spirits
• Unable to take nitrofurantoin. E.g. hypersensitivity to the active substance

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GSK3882347+ Placebo; Participants received GSK3882347 oral capsules plus placebo oral capsules from Day 1 to Day 5.	Drug: GSK3882347; GSK3882347 was administered.; Drug: Placebo; Placebo matching GSK3882347 or Nitrofurantoin was administered.
Active Comparator: Nitrofurantoin + Placebo; Participants received 100 milligrams (mg) of nitrofurantoin oral capsules plus placebo oral capsules from Day 1 to Day 5.	Drug: Placebo; Placebo matching GSK3882347 or Nitrofurantoin was administered.; Drug: Nitrofurantoin; Nitrofurantoin was administered.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Microbiological Response at the Test of Cure (ToC) Visit	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).	Day 10 to Day 13 (ToC Visit)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events (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.	From the first dose of study intervention up to Follow-up Visit (up to Day 31)
Number of Participants With Serious AEs (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 or incapacity; is a congenital anomaly or birth defect; or any other situation according to the medical or scientific judgment of the investigator.	From the signing of informed consent up to Follow-up Visit (up to Day 31)
Number of Participants With Clinically Significant Changes in Vital Signs Findings	Vital signs included tympanic-measured temperature, pulse and respiratory rate, systolic and diastolic blood pressure. Blood pressure and pulse measurements were assessed in a semi-supine or seated position with a completely automated device and were measured after at least 10 minutes of rest for the participant in a quiet setting without distractions. Clinical significance of any change in vital signs was determined by the investigator.	Up to Day 31
Number of Participants With Clinically Significant Changes in Electrocardiograms (ECG) Findings	Twelve-lead ECGs were obtained using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and corrected QT (QTc) intervals. Clinical significance of any change in ECG findings was determined by the investigator.	Up to Day 31
Number of Participants With Clinically Significant Changes in Hematology Parameters	Blood samples were collected for hematology parameters including platelet count, red blood cell (RBC) count, hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, reticulocytes, white blood cell (WBC) count (neutrophils, lymphocytes, monocytes, eosinophils, basophils). Clinical significance of any change in hematology parameters was determined by the investigator.	Up to Day 31
Number of Participants With Clinically Significant Changes in Chemistry Parameters	Blood samples were collected for chemistry parameters including blood urea nitrogen (BUN), creatinine (including estimated glomerular filtration rate [eGFR]), glucose (non-fasting), potassium, sodium, calcium, total and direct bilirubin, total protein, aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT), alanine aminotransferase (ALT)/serum glutamic-pyruvic transaminase (SGPT), and alkaline phosphatase. Clinical significance of any change in clinical chemistry parameters was determined by the investigator.	Up to Day 31
Number of Participants With Clinically Significant Changes in Urinalysis Parameters	Urine samples were collected for the analysis of urine parameters including specific gravity, potential of hydrogen (pH), glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, leukocyte esterase, microscopic examination (if blood or protein was abnormal), and protein/creatinine ratio. Clinical significance of any change in urinalysis parameters was determined by the investigator.	Up to Day 31
Cohort 1: Plasma Concentration at the End of the Dosing Interval Tau (Ctau) of GSK3882347 Post-dose on Day 1 and Day 5		24 hours post-dose on Day 1 and Day 5
Cohort 1: Urine Concentration of GSK3882347 at 22-24-hour (h) Interval Collection Post-dose on Day 1 and Day 5		22-24 hour interval post-dose on Day 1 and Day 5
Cohort 2: Plasma Ctau of GSK3882347 Post-dose on Day 1 and Day 5		24 hours post-dose on Day 1 and Day 5
Cohort 2: Urine Concentration of GSK3882347 at 22-24h Interval Collection Post-dose on Day 1 and Day 5		22-24 hour interval post-dose on Day 1 and Day 5

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Clinical Symptom Score Outcome	Clinical symptom score (CSS) measures 4 uncomplicated urinary tract infection (uUTI) symptoms: dysuria, frequency, urgency, and lower abdominal/suprapubic pain. Each symptom is scored from 0 (no symptoms) to 3 (severe). Individual symptom scores are added for a cumulative total score (range 0-12), with higher scores indicating greater severity. Clinical outcome for a visit is categorized based on change of total score from baseline (BL): Clinical Resolution (CR) - Total score decreases from BL to 0; Clinical Improvement (CI) - Total score decreases from BL but is greater than (>) 0; Clinical Worsening (CW) - Total score increases or has no change from BL; or Indeterminate (Ind) - Participant (par.) failed to attend the visit, achieved CR/CI but received systemic antibacterials between BL and the visit day being assessed, or BL score is missing. For a clinical outcome of CR/CI, the par. must not have received another systemic antibacterials between BL and the visit being assessed.	Day 2 to Day 6
Number of Participants With Clinical Symptom Score Response at the ToC Visit	CSS measures 4 uUTI symptoms: dysuria, frequency, urgency, and lower abdominal/suprapubic pain. Each symptom is scored from 0 (no symptoms) to 3 (severe). Individual symptom scores are added for a cumulative total score (range 0-12), with higher scores indicating greater severity. Clinical outcome at ToC is categorized based on change of total score from BL: CR - Total score decreases from BL to 0; CI - Total score decreases from BL but is >0; CW - Total score increases or has no change from BL; Ind - Par. refused a clinical examination, failed to attend the ToC visit, achieved CR or CI but received another systemic antibacterial before ToC, or BL score is missing. For a clinical outcome of CR or CI, the par. must not have received another systemic antibacterial between BL and ToC visit. Clinical response at ToC is defined as "Clinical Success" for an outcome of CR, and "Clinical Failure" for any other outcome (CI, CW, or Ind).	Day 10 to Day 13 (ToC Visit)
Number of Participants With Clinical Symptom Score Response at the Follow-up (FU) Visit	CSS measures 4 uUTI symptoms: dysuria, frequency, urgency, and lower abdominal/suprapubic pain. Individual symptoms (each scored 0 to 3) are added for a total score (0-12), with higher scores indicating greater severity. Clinical outcome at FU is categorized based on change of total score from ToC: Sustained CR (SCR) - ToC and FU=0; Delayed CR (DCR) - FU=0, after >0 at ToC; CI - Total score at FU and ToC>0, with score at FU<ToC; CW - Total score at FU and ToC>0, with score at FU>ToC; Clinical Recurrence (CRr) - Total score >0 at FU after ToC=0; Ind - Par. refused a clinical exam, failed to attend FU, achieved SCR/DCR/CI but received another systemic antibacterials before ToC, or BL score is missing. For a clinical outcome of SCR/DCR/CI, the par. must not have received any systemic antibacterials between BL and FU. Clinical response at FU is defined as "Clinical Success" for an outcome of SCR, and "Clinical Failure" for any other outcome (DCR, CI, CW, CRr, or Ind).	Day 25 to Day 31 (Follow-up Visit)
Number of Participants With Clinical Resolution Response Outcome	The investigators were asked to record their impression of the clinical status of the participant with regard to the presenting uUTI (resolved/unresolved). Clinical resolution outcome was reported as Clinically Resolved if, in the opinion of the investigator, there was resolution of signs and symptoms of the uUTI present at Baseline (and no worsening and no new signs and symptoms) and no requirement for the use of other antibacterial therapy. Refusal to consent to a clinical examination at a required in-person visit or failure to attend the visit had an outcome of Indeterminate.	Day 2 to Day 6
Number of Participants With Clinical Resolution Response at the ToC Visit	The investigators were asked to record their impression of the clinical status of the participant with regard to the presenting uUTI (resolved/unresolved). Clinical resolution response at ToC visit was defined as "Clinical Resolution Success (CRS)" when, in the opinion of the investigator, there was resolution of signs and symptoms of the uUTI present at Baseline (and no worsening and no new signs and symptoms) and no requirement for the use of other antibacterial therapy. "Clinical Resolution Failure (CRF)" was defined when investigator's assessment was Clinically Unresolved/Clinical Worsening or Indeterminate at ToC. Indeterminate was defined as refusal to consent to a clinical examination or failure to attend the ToC visit.	Day 10 to Day 13 (ToC Visit)
Number of Participants With Clinical Resolution Response at the Follow-up (FU) Visit	The investigators were asked to record their impression of the clinical status of the participant with regard to the presenting uUTI (resolved/unresolved). Clinical resolution response at FU was defined as "CRS" when investigator's assessment was Clinically Resolved at both ToC and FU (SCR), i.e., resolution of signs and symptoms of the uUTI present at BL (and no worsening and no new signs and symptoms) and no requirement for the use of other antibacterials. "CRF" was defined when investigator's assessment was: Clinically Unresolved at ToC but Clinically Resolved at FU (DCR); Clinically Resolved at ToC but Clinically Unresolved at FU (CRr); Clinically Unresolved at both ToC and FU (CU/CW); or when participants refused to consent to a clinical exam, failed to attend the FU, or achieved SCR/DCR but received other systemic antibacterials before FU (Ind).	Day 25 to Day 31 (Follow-up Visit)

Collaborators and Investigators

• Sponsor: GlaxoSmithKline
• Investigators: Study Director: GSK Clinical Trials, GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (Actual): May 18, 2022
• Primary Completion (Actual): December 3, 2024
• Study Completion (Actual): December 3, 2024

Study Registration Dates

• First Submitted: November 15, 2021
• First Submitted That Met QC Criteria: November 15, 2021
• First Posted (Actual): December 1, 2021

Study Record Updates

• Last Update Posted (Actual): March 13, 2026
• Last Update Submitted That Met QC Criteria: February 20, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Nitrofurantoin; Microbiological response; Urinary tract infections (UTI); GSK3882347; Escherichia coli (E. coli)
• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Negative Bacterial Infections; Enterobacteriaceae Infections; Urinary Tract Infections; Escherichia coli Infections; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nitro Compounds; Furans; Nitrofurans; Nitrofurantoin
• Other Study ID Numbers: 212943

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
• IPD Sharing Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, a key secondary endpoints and safety data of the study.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No