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

Uncomplicated Urinary Tract Infections Clinical Trial

Official title:

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

Clinical Trial Details — Status: Suspended

Administrative data

• NCT number: NCT05138822
• Other study ID #: 212943
• Status: Suspended
• Phase: Phase 1
• Start date: May 18, 2022
• Est. completion date: July 16, 2024

Study information

• Verified date: October 2023
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Suspended
• Enrollment: 80
• Est. completion date: July 16, 2024
• Est. primary completion date: July 16, 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Communicable Diseases
• Infections
• Uncomplicated Urinary Tract Infections
• Urinary Tract Infections

Intervention

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

Locations

Country	Name	City	State
United States	GSK Investigational Site	Anniston	Alabama
United States	GSK Investigational Site	Arlington	Texas
United States	GSK Investigational Site	Austin	Texas
United States	GSK Investigational Site	Bronx	New York
United States	GSK Investigational Site	Chicago	Illinois
United States	GSK Investigational Site	Dallas	Texas
United States	GSK Investigational Site	Doral	Florida
United States	GSK Investigational Site	Houston	Texas
United States	GSK Investigational Site	La Mesa	California
United States	GSK Investigational Site	Lomita	California
United States	GSK Investigational Site	Miami Lakes	Florida
United States	GSK Investigational Site	Missouri City	Texas
United States	GSK Investigational Site	Modesto	California
United States	GSK Investigational Site	Ormond Beach	Florida
United States	GSK Investigational Site	Saint George	Utah

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Numbers of participants with microbiological response (responder/non-responder of GSK3882347) at the test of cure (TOC) visit	Microbiological response is defined as the response of less than (<)10^3 colony forming unit (CFU)/milliliter (mL) for all qualifying Escherichia coli (identified at baseline urine microbiology visit) at TOC visit, without receiving other systemic antimicrobials (rescue medications) prior to TOC	Day 10 to Day 13
Secondary	Number of participants with adverse events (AEs) and serious adverse events (SAEs)	AEs and SAEs will be collected.	Up to Day 31
Secondary	Number of participants with clinically significant change from baseline in hematology parameters	Blood samples will be collected for the assessment of hematology parameters.	Baseline (Day 1) and up to Day 31
Secondary	Number of participants with clinically significant change from baseline in clinical chemistry	Blood samples will be collected for the assessment of chemistry parameters.	Baseline (Day 1) and up to Day 31
Secondary	Number of participants with clinically significant change from baseline in urinalysis	Blood samples will be collected for the assessment of urinalysis parameters.	Baseline (Day 1) and up to Day 31
Secondary	Number of participants with clinically significant change from baseline in vital signs		Baseline (Day 1) and up to Day 31
Secondary	Number of participants with clinically significant change from baseline in 12- lead Electrocardiogram (ECG) findings		Baseline (Day 1) and up to Day 31
Secondary	Plasma concentration of GSK3882347 single dose	Blood samples will be collected for the concentrations of GSK3882347.	Up to Day 5
Secondary	Urine concentration of GSK3882347 at 22-24-hour (h) interval collection post-dose	Urine samples will be collected for the concentrations of GSK3882347.	Up to Day 5