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

NCT05138822 | Completed Phase 1 Results FDA Drug

• 1 other identifier: 212943
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 15

Brief Summary

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.

Conditions

Uncomplicated Urinary Tract Infections; Urinary Tract Infections

Keywords

Microbiological response; Urinary tract infections (UTI); GSK3882347; Nitrofurantoin; Pharmacokinetics; Escherichia coli (E. coli)

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (11)

• Number of Participants With Adverse Events (AEs)

  From the first dose of study intervention up to Follow-up Visit (up to Day 31)

• Number of Participants With Serious AEs (SAEs)

  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

  Up to Day 31

• Number of Participants With Clinically Significant Changes in Electrocardiograms (ECG) Findings

  Up to Day 31

• Number of Participants With Clinically Significant Changes in Hematology Parameters

  Up to Day 31

Other Outcomes (6)

• Number of Participants With Clinical Symptom Score Outcome

  Day 2 to Day 6

• Number of Participants With Clinical Symptom Score Response at the ToC Visit

  Day 10 to Day 13 (ToC Visit)

• Number of Participants With Clinical Symptom Score Response at the Follow-up (FU) Visit

  Day 25 to Day 31 (Follow-up Visit)

Study Arms (2)

GSK3882347+ Placebo

EXPERIMENTAL

Participants received GSK3882347 oral capsules plus placebo oral capsules from Day 1 to Day 5.

Drug: GSK3882347; Drug: Placebo

Nitrofurantoin + Placebo

ACTIVE COMPARATOR

Participants received 100 milligrams (mg) of nitrofurantoin oral capsules plus placebo oral capsules from Day 1 to Day 5.

Drug: Nitrofurantoin; Drug: Placebo

Interventions

GSK3882347 DRUG

GSK3882347 was administered.

GSK3882347+ Placebo

Nitrofurantoin DRUG

Nitrofurantoin was administered.

Nitrofurantoin + Placebo

Placebo DRUG

Placebo matching GSK3882347 or Nitrofurantoin was administered.

GSK3882347+ Placebo; Nitrofurantoin + Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Gender Eligibility Details: An adult female participant with 2 or more clinical signs and symptoms of acute urinary tract infections are included in this study activity.
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (15)

GSK Investigational Site

Anniston, Alabama, 36207, United States

Location

GSK Investigational Site

Lomita, California, 90717, United States

Location

GSK Investigational Site

Modesto, California, 95350-5365, United States

Location

GSK Investigational Site

Doral, Florida, 33166, United States

Location

GSK Investigational Site

Miami, Florida, 33186, United States

Location

GSK Investigational Site

Miami Lakes, Florida, 33016-1507, United States

Location

GSK Investigational Site

Palmetto Bay, Florida, 33157, United States

Location

GSK Investigational Site

Sweetwater, Florida, 33172, United States

Location

GSK Investigational Site

Chicago, Illinois, 60643, United States

Location

GSK Investigational Site

The Bronx, New York, 10456, United States

Location

GSK Investigational Site

Smithfield, Pennsylvania, 15478, United States

Location

GSK Investigational Site

Austin, Texas, 78705, United States

Location

GSK Investigational Site

Dallas, Texas, 75230, United States

Location

GSK Investigational Site

Houston, Texas, 77061, United States

Location

GSK Investigational Site

Missouri City, Texas, 77459, United States

Location

MeSH Terms

Conditions

Urinary Tract Infections; Escherichia coli Infections

Interventions

Nitrofurantoin

Condition Hierarchy (Ancestors)

Infections; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Enterobacteriaceae Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses

Intervention Hierarchy (Ancestors)

Nitrofurans; Nitro Compounds; Organic Chemicals; Furans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

Due to potential data quality issues, 14 participants were excluded from the analyses presented. Only 1 out of these 14 participants was in the defined Micro-MPP analysis set. Hence, any analysis presented here using the Micro-MPP analysis set excludes this 1 participant.

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

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 randomized double-blind study with both participants and site staff blinded.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This will be a randomized double-blind study and participants will be randomized to receive either GSK3882347 or nitrofurantoin in a 3:1 allocation ratio using an interactive response technology (IRT).

Study Record Dates

• First Submitted: November 15, 2021
• First Posted: December 1, 2021
• Study Start: May 18, 2022
• Primary Completion: December 3, 2024
• Study Completion: December 3, 2024
• Last Updated: March 13, 2026
• Results First Posted: March 13, 2026

Record last verified: 2026-02

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, a 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

US (15)