GSK3882347 for Urinary Tract Infection (UTI)

No longer recruiting at 18 trial locations

Overseen By US GSK Clinical Trials Call Center

Age: 18+

Sex: Female

Travel: May Be Covered

Trial Phase: Phase 1

Sponsor: GlaxoSmithKline

Must not be taking: Systemic antimicrobials, Systemic antifungals

Disqualifiers: Obesity, Immunocompromised, Anatomical anomalies, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: 5 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines a new medication, GSK3882347, to assess its effectiveness in treating uncomplicated urinary tract infections (uUTIs) in adult women. Researchers aim to compare it to an existing antibiotic, nitrofurantoin, to evaluate its effectiveness and safety. Participants will take the medication for 5 days, with their response closely monitored. Women who have recently developed uUTI symptoms, such as pain while urinating or frequent trips to the bathroom, might be suitable for this trial. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new medication.

Do I have to stop taking my current medications for this trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have taken other systemic antimicrobials or systemic antifungals within 1 week (or 10 weeks for dalbavancin or oritavancin) before joining the study.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have taken other systemic antimicrobials or systemic antifungals within 1 week before the study, or 10 weeks for certain drugs like dalbavancin or oritavancin.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that GSK3882347 is currently being tested for safety and tolerance in people. Early studies have examined how the body processes both single and multiple doses of this drug. Specific safety results are not yet available, as researchers are still collecting basic safety information in this early trial phase.

In contrast, nitrofurantoin is a well-known medication that has been used successfully for a long time to treat urinary tract infections. It is generally considered safe, but like all medications, it can have side effects. Common side effects include nausea and headache. More serious side effects are rare but can include lung or liver problems, especially in individuals with existing health conditions.

Overall, nitrofurantoin has a long history of safe use, while information on GSK3882347 is still being gathered. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for urinary tract infections?

Unlike the standard antibiotics used for urinary tract infections (UTIs), like nitrofurantoin, GSK3882347 has a unique mechanism of action that targets the bacteria in a different way. This new drug is designed to disrupt the bacterial processes essential for their survival, offering a novel approach to treatment. Researchers are excited about GSK3882347 because it has the potential to be more effective against antibiotic-resistant strains of bacteria, which are becoming increasingly common and harder to treat with existing medications.

What evidence suggests that this trial's treatments could be effective for uncomplicated urinary tract infections?

Research has shown that nitrofurantoin, which participants in this trial may receive, effectively treats simple urinary tract infections (uUTIs), with about 79% of patients achieving a clinical cure. It is often the first choice for treating uUTIs due to its safety and effectiveness. In contrast, GSK3882347, another treatment option in this trial, is a newer antibiotic with limited human data. It belongs to a new group of antibiotics that may help with bladder infections like uUTIs. This treatment targets the specific bacteria causing these infections, suggesting it could be a promising new option. Early results from similar treatments in this group are encouraging, but more data is needed to confirm its effectiveness. ^{1 3 4 6 7}

Who Is on the Research Team?

GSK Clinical Trials

Principal Investigator

GlaxoSmithKline

Are You a Good Fit for This Trial?

This trial is for adult women aged 18-70 with uncomplicated urinary tract infections (uUTI), not pregnant or breastfeeding, and using effective contraception. They must have symptoms like pain during urination, frequent urge to urinate, or lower abdominal pain. Women with immune issues, other diseases causing similar symptoms, urinary anomalies, severe kidney problems, recent antimicrobial treatment or high alcohol intake are excluded.

Inclusion Criteria

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

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: Woman participant of non-childbearing potential (WONCBP) Or 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

You have a weakened immune system that may increase the risk of treatment failure or complications.

You have symptoms that may be caused by a different medical condition, such as chronic bladder issues or asymptomatic bacteriuria.

You have a physical condition that increases your risk of developing urinary tract infections, such as blockages or abnormalities in your urinary tract or a history of such conditions.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive daily oral dosing of GSK3882347 or nitrofurantoin for 5 days

5 days

Inpatient for Cohort 1, Outpatient for Cohort 2

Test of Cure (ToC)

Microbiological response is evaluated at the test of cure visit

Day 10 to Day 13

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to Day 31

What Are the Treatments Tested in This Trial?

Interventions

• GSK3882347
• Nitrofurantoin
• Placebo

Trial Overview The study tests GSK3882347's safety and effectiveness against uUTI compared to Nitrofurantoin and a placebo over 5 days. It includes two groups: one staying in the hospital for detailed daily checks (Cohort 1) and another treated as outpatients with less frequent checks (Cohort 2).

How Is the Trial Designed?

Group I: GSK3882347 + Placebo Experimental Treatment 2 Interventions

Participants will be administered GSK3882347 plus placebo.

Group II: Nitrofurantoin+ Placebo Active Control 2 Interventions

Participants will be administered nitrofurantoin plus placebo.

Who Is Running the Clinical Trial?

GlaxoSmithKline

Lead Sponsor

Trials

4,834

Recruited

8,389,000+

Headquarters

London, UK

Known For

Vaccines & Medicines

Top Products

**Advair (salmeterol, fluticasone propionate)**, **Shingrix (shingles vaccine)**, **Augmentin (amoxicillin/clavulanate potassium)**, **Ventolin (salbutamol sulfate)

Dame Emma Walmsley

GlaxoSmithKline

Chief Executive Officer since 2017

MA in Classics and Modern Languages from Oxford University

Dr. Hal Barron

GlaxoSmithKline

Chief Medical Officer since 2018

MD from Harvard Medical School

Published Research Related to This Trial

A retrospective analysis of 91 pregnancies treated with nitrofurantoin macrocrystals for urinary tract infections found no significant increase in adverse outcomes for the fetus compared to the general U.S. population.

The study concluded that nitrofurantoin macrocrystals do not appear to be toxic to the fetus, suggesting it is a safe option for treating urinary tract infections in pregnant women.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Foetal safety of nitrofurantoin macrocrystals therapy during pregnancy: a retrospective analysis. Hailey, FJ., Fort, H., Williams, JC., et al.[2017]

In a study involving 65 hospitalized patients with acute urinary tract infections, treatment with a nitrofurantoin/sulphadiazine compound showed therapeutic effectiveness, highlighting its potential as a reliable antibacterial option.

The study emphasized the importance of monitoring for iatrogenic infections, as these patients were already severely ill, indicating a need for careful management to minimize additional risks during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treatment of acute urinary tract infection with a nitrofurantoin-sulphadiazine compound preparation (author's transl)]. Griendl, W.[2013]

In studies involving rats and rabbits, nitrofurantoin macrocrystals were administered at doses up to six times the human therapeutic dose, showing no adverse effects on maternal health, fetal development, or neonatal survival.

The results suggest that nitrofurantoin macrocrystals are a safe option for treating urinary tract infections in pregnant women, as they did not cause any reproductive or developmental toxicity in the animal models tested.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

General reproduction, perinatal-postnatal, and teratology studies of nitrofurantoin macrocrystals in rats and rabbits. Prytherch, JP., Sutton, ML., Denine, EP.[2013]

Nitrofurantoin, while generally safe for treating lower urinary tract infections, can cause rare but serious adverse effects, such as systemic inflammatory response syndrome, as demonstrated in a case involving a 66-year-old woman.

The patient's symptoms resolved completely after discontinuing nitrofurantoin, highlighting the importance of monitoring for adverse reactions and educating patients about potential side effects of this antibiotic.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systemic Inflammatory Response Syndrome from Nitrofurantoin: A Case Report. O'Connor, RA., Patel, V., Lang, V., et al.[2022]

In a study of over 29,000 women, nitrofurantoin was found to be equally effective in treating urinary tract infections (UTIs) in those with moderate renal impairment compared to those without, showing no increased risk of treatment ineffectiveness.

However, women with more severe renal impairment (less than 50 ml/min) had a significantly higher risk of serious pulmonary adverse events leading to hospitalization when treated with nitrofurantoin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ineffectiveness and adverse events of nitrofurantoin in women with urinary tract infection and renal impairment in primary care. Geerts, AF., Eppenga, WL., Heerdink, R., et al.[2021]

In a study of 105 type 2 diabetic women aged 50-70, nitrofurantoin was found to be an effective treatment for recurrent urinary tract infections (UTIs), showing similar efficacy to cotrimoxazole over a 12-month observation period.

Both nitrofurantoin and cotrimoxazole resulted in comparable rates of clinical cure and bacteriological eradication, indicating that nitrofurantoin is a viable option for managing recurrent UTIs in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy of nitrofurantoin in the treatment of chronic urinary tract infections in patients with type 2 diabetes mellitus]. Mozdzan, M., Ruxer, J., Siejka, A., et al.[2020]

The study identified that a nitrofurantoin suspension with glycerin (0.2%) and sodium citrate (0.3%) significantly improved physical stability, making it a promising formulation for treating urinary tract infections.

The optimal formulation, which included Veegum (1%), sodium carboxyl methyl cellulose (1%), glycerin, sodium citrate, and sorbitol (20%), exhibited pseudoplastic behavior, indicating good flow properties and ease of use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influence of flocculating agents and structural vehicles on the physical stability and rheological behavior of nitrofurantoin suspension. Moghimipour, E., Salimi, A., Rezaee, S., et al.[2022]

Nitrofurantoin remains an effective treatment for uncomplicated urinary tract infections (UTIs), particularly against common pathogens like E. coli, despite its long history of use and potential side effects.

Recent studies indicate that short-term nitrofurantoin therapy is well-tolerated and effective, making it a recommended first-line treatment in current guidelines, although it is contraindicated in late pregnancy and for patients with renal impairment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Nitrofurantoin--clinical relevance in uncomplicated urinary tract infections]. Stock, I.[2014]

Nitrofurantoin is a broad-spectrum antibiotic effective against both Gram-negative and Gram-positive bacteria, making it a valuable option for treating acute lower urinary tract infections, especially in the context of rising antibiotic resistance.

Recent data suggest that nitrofurantoin is particularly useful for managing urinary tract infections caused by multidrug-resistant pathogens, highlighting its importance as a treatment option when other oral antibiotics are limited.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of Old Antibiotics in the Era of Antibiotic Resistance. Highlighted Nitrofurantoin for the Treatment of Lower Urinary Tract Infections. Munoz-Davila, MJ.[2020]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05138822

Study Details | NCT05138822 | Safety, Tolerability, ... This phase 1b study is a double-blind, double-dummy, nitrofurantoin-controlled study designed to evaluate microbiological response at the test of cure (ToC) ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38342126/

Oral gepotidacin versus nitrofurantoin in patients with ... We aimed to compare the efficacy and safety of oral gepotidacin with that of nitrofurantoin in adolescent and adult female individuals with uncomplicated ...

3. withpower.com withpower.com/trial/phase-1-communicable-diseases-11-2021-2dc29

GSK3882347 for Urinary Tract Infection · Info for Participants Recent studies suggest that short-term use of nitrofurantoin is as effective as other standard treatments, and it is recommended as a first-choice treatment for ...

4. isrctn.com isrctn.com/pdf/16147016

Drug interaction assessment of GSK3882347 in healthy ... The GSK drug (GSK3882347) tested in this study was made to potentially treat or prevent bladder infections, also known as acute cystitis or ...

5. gsk.com gsk.com/en-gb/media/press-releases/gepotidacin-s-positive-phase-iii-data-shows-potential-to-be-the-first-in-a-new-class-of-oral-antibiotics-for-uncomplicated-urinary-tract-infections/

Gepotidacin's positive phase III data shows potential to be ... Gepotidacin's positive phase III data shows potential to be the first in a new class of oral antibiotics for uncomplicated urinary tract ...

6. hra.nhs.uk hra.nhs.uk/planning-and-improving-research/application-summaries/research-summaries/gsk3882347-first-time-in-human-study/

GSK3882347 First time in human study The main objective of this study is to understand the safety, tolerability and blood levels of GSK3882347 when given in single and multiple doses.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05760261

Drug Interaction Assessment of GSK3882347 in Healthy ... The objective of this study is to determine the magnitude and clinical relevance of a potential drug-drug interaction of GSK3882347 with midazolam (MDZ) in ...