Safety, Tolerability, Pharmacokinetic and Microbiological Investigation of GSK3882347 in Female Participants With Urinary Tract Infections
- Conditions
- Uncomplicated Urinary Tract InfectionsUrinary Tract Infections
- Interventions
- Registration Number
- NCT05138822
- Lead Sponsor
- GlaxoSmithKline
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 140
- 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.
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description GSK3882347 + Placebo GSK3882347 Participants will be administered GSK3882347 plus placebo. GSK3882347 + Placebo Placebo Participants will be administered GSK3882347 plus placebo. Nitrofurantoin+ Placebo Nitrofurantoin Participants will be administered nitrofurantoin plus placebo. Nitrofurantoin+ Placebo Placebo Participants will be administered nitrofurantoin plus placebo.
- Primary Outcome Measures
Name Time Method Numbers of participants with microbiological response (responder/non-responder of GSK3882347) at the test of cure (TOC) visit Day 10 to Day 13 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
- Secondary Outcome Measures
Name Time Method Number of participants with adverse events (AEs) and serious adverse events (SAEs) Up to Day 31 AEs and SAEs will be collected.
Number of participants with clinically significant change from baseline in hematology parameters Baseline (Day 1) and up to Day 31 Blood samples will be collected for the assessment of hematology parameters.
Number of participants with clinically significant change from baseline in urinalysis Baseline (Day 1) and up to Day 31 Blood samples will be collected for the assessment of urinalysis parameters.
Urine concentration of GSK3882347 at 22-24-hour (h) interval collection post-dose Up to Day 5 Urine samples will be collected for the concentrations of GSK3882347.
Number of participants with clinically significant change from baseline in clinical chemistry Baseline (Day 1) and up to Day 31 Blood samples will be collected for the assessment of chemistry parameters.
Number of participants with clinically significant change from baseline in vital signs Baseline (Day 1) and up to Day 31 Number of participants with clinically significant change from baseline in 12- lead Electrocardiogram (ECG) findings Baseline (Day 1) and up to Day 31 Plasma concentration of GSK3882347 single dose Up to Day 5 Blood samples will be collected for the concentrations of GSK3882347.
Trial Locations
- Locations (1)
GSK Investigational Site
🇺🇸Missouri City, Texas, United States