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

NCT ID: NCT05138822

Last Updated: 2025-01-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 140 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-05-18
• Study Completion Date: 2024-12-03

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 daily 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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

GSK3882347 + Placebo

Participants will be administered GSK3882347 plus placebo.

Group Type: EXPERIMENTAL

GSK3882347

Intervention Type: DRUG

GSK3882347 will be administered on each dosing day.

Placebo

Intervention Type: DRUG

Placebo matching study drug (GSK3882347) or Nitrofurantoin will be administered on each dosing day.

Nitrofurantoin+ Placebo

Participants will be administered nitrofurantoin plus placebo.

Group Type: ACTIVE_COMPARATOR

Nitrofurantoin

Intervention Type: DRUG

Nitrofurantoin will be administered on each dosing day.

Placebo

Intervention Type: DRUG

Placebo matching study drug (GSK3882347) or Nitrofurantoin will be administered on each dosing day.

Interventions

GSK3882347

GSK3882347 will be administered on each dosing day.

Intervention Type: DRUG

Nitrofurantoin

Nitrofurantoin will be administered on each dosing day.

Intervention Type: DRUG

Placebo

Placebo matching study drug (GSK3882347) or Nitrofurantoin will be administered on each dosing day.

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Anniston, Alabama, United States

GSK Investigational Site

Lomita, California, United States

GSK Investigational Site

Modesto, California, United States

GSK Investigational Site

Doral, Florida, United States

GSK Investigational Site

Miami, Florida, United States

GSK Investigational Site

Miami Lakes, Florida, United States

GSK Investigational Site

Palmetto Bay, Florida, United States

GSK Investigational Site

Sweetwater, Florida, United States

GSK Investigational Site

Chicago, Illinois, United States

GSK Investigational Site

The Bronx, New York, United States

GSK Investigational Site

Smithfield, Pennsylvania, United States

GSK Investigational Site

Austin, Texas, United States

GSK Investigational Site

Dallas, Texas, United States

GSK Investigational Site

Houston, Texas, United States

GSK Investigational Site

Missouri City, Texas, United States

Countries

United States

Other Identifiers

212943

Identifier Type: -

Identifier Source: org_study_id