Gepotidacin for Urinary Tract Infections

(SIS Trial)

No longer recruiting at 30 trial locations

Overseen By EU GSK Clinical Trials Call Center

Age: Any Age

Sex: Female

Trial Phase: Phase 3

Sponsor: GlaxoSmithKline

Must not be taking: QT-prolonging drugs, Strong CYP3A4 inhibitors

Disqualifiers: Obesity, Immunocompromised, Seizure disorder, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 4 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new oral medication, gepotidacin, to determine its effectiveness and safety in treating uncomplicated urinary tract infections (UTIs) in females. The focus is on females experiencing at least two symptoms, such as painful urination, frequent urination, sudden urges to urinate, or lower abdominal pain, beginning less than four days ago. Participants should not have complicated UTIs or other medical conditions that might interfere with the treatment. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, especially those that prolong the QT interval or are strong inhibitors of specific enzymes, from the start of the trial until a specified visit. If you're on such medications, you may need to discontinue them to participate.

Is there any evidence suggesting that gepotidacin is likely to be safe for humans?

Research has shown that gepotidacin is generally safe for treating simple urinary tract infections (UTIs). In earlier studies, common side effects included nausea, diarrhea, and headache, occurring in less than 10% of patients. The FDA has approved this treatment for simple UTIs in females, including teenagers and adults, indicating strong evidence of its safety. Overall, the data indicates that side effects are usually mild and manageable for most people. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for UTIs?

Unlike the standard antibiotics used for urinary tract infections, such as nitrofurantoin or trimethoprim-sulfamethoxazole, gepotidacin works differently by targeting bacterial enzymes in a unique way. Researchers are excited about gepotidacin because it belongs to a new class of antibiotics called triazaacenaphthylene bacterial topoisomerase inhibitors, which means it can potentially overcome resistance that limits the effectiveness of current treatments. This fresh mechanism of action offers hope for more effective and reliable treatment options, especially as antibiotic resistance continues to rise.

What evidence suggests that gepotidacin might be an effective treatment for uncomplicated UTI?

Research has shown that gepotidacin effectively treats uncomplicated urinary tract infections (UTIs). In studies, gepotidacin outperformed nitrofurantoin, a common UTI treatment. Specifically, one study found that 50.6% of patients taking gepotidacin experienced significant symptom improvement. Gepotidacin, a new type of antibiotic, fights bacteria differently, offering promise for UTIs, especially when other antibiotics may be less effective. Participants in this trial will receive gepotidacin to further evaluate its effectiveness. ^{4 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for adolescent and adult female participants who are experiencing symptoms of an uncomplicated urinary tract infection (acute cystitis). Specific eligibility criteria details were not provided, so it's important to contact the study organizers for more information.

Inclusion Criteria

I am female.

My urine test showed signs of infection.

I have had symptoms like pain when urinating, needing to urinate often, a strong need to urinate, or lower belly pain in the last 4 days.

Exclusion Criteria

I have a condition that makes me more prone to urinary tract infections.

Participants residing in a nursing home or dependent care type-facility

Participants with a history of sensitivity to the study treatment, or components thereof, or a history of a drug or other allergy that contraindicates participation

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive oral gepotidacin for treatment of uncomplicated UTI (acute cystitis)

4 days

Daily monitoring for symptom improvement

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 week

What Are the Treatments Tested in This Trial?

Interventions

• Gepotidacin

Trial Overview

The trial is testing the effectiveness and safety of a medication called Gepotidacin. This oral drug is being studied to see if it can improve symptoms in females with uncomplicated UTI.

How Is the Trial Designed?

Group I: Gepotidacin Experimental Treatment 1 Intervention

Single Arm

Gepotidacin is already approved in United States for the following indications:

Approved in United States as Gepotidacin for:

• Uncomplicated Urinary Tract Infections (Acute Cystitis)

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

Gepotidacin, a new antibiotic for treating uncomplicated urinary tract infections and gonorrhea, showed dose proportionality in plasma exposure across different doses (1500 to 3000 mg) and conditions (fed and fasted) in healthy participants, indicating consistent pharmacokinetics.

The study found that while Japanese participants had slightly higher plasma concentrations of gepotidacin compared to non-Japanese participants, the overall safety profile was acceptable, with gastrointestinal side effects being the most common, which improved when the drug was taken with food.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic, Safety, and Tolerability Evaluations of Gepotidacin (GSK2140944) in Healthy Japanese Participants. Barth, A., Hossain, M., Perry, CR., et al.[2023]

Gepotidacin is a novel antibiotic that works by inhibiting bacterial DNA replication, targeting specific bacterial enzymes, and is currently being evaluated for treating uncomplicated urinary tract infections (uUTIs).

A 1,500-mg oral dose of gepotidacin taken twice daily for 5 days has been selected for phase III clinical trials involving adolescent and adult females, aiming to assess its safety and efficacy compared to standard treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose Selection for Phase III Clinical Evaluation of Gepotidacin (GSK2140944) in the Treatment of Uncomplicated Urinary Tract Infections. Scangarella-Oman, NE., Hossain, M., Hoover, JL., et al.[2022]

Gepotidacin is a novel oral antibiotic that works by inhibiting bacterial DNA replication, potentially offering a new treatment option for uncomplicated urinary tract infections (UTIs) and urogenital gonorrhoea, especially in the context of rising antimicrobial resistance.

Phase II clinical trial data for gepotidacin show promising results, and if approved, it will be the first new oral antibiotic for UTIs in over 20 years, suggesting it could play a significant role in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gepotidacin: a novel, oral, 'first-in-class' triazaacenaphthylene antibiotic for the treatment of uncomplicated urinary tract infections and urogenital gonorrhoea. Watkins, RR., Thapaliya, D., Lemonovich, TL., et al.[2023]

In a phase 2a study involving 22 female participants with uncomplicated urinary tract infections, gepotidacin demonstrated a favorable safety profile with no treatment-limiting adverse events and significant clinical success rates of 86% at test-of-cure and 82% at follow-up.

Gepotidacin showed promising pharmacokinetics, achieving steady-state plasma concentrations by day 3 and effective urinary exposure, indicating its potential efficacy in treating uUTI, warranting further evaluation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 2a Pharmacokinetic, Safety, and Exploratory Efficacy Evaluation of Oral Gepotidacin (GSK2140944) in Female Participants with Uncomplicated Urinary Tract Infection (Acute Uncomplicated Cystitis). Overcash, JS., Tiffany, CA., Scangarella-Oman, NE., et al.[2021]

Gepotidacin showed remarkable efficacy against urinary tract infection (UTI) pathogens, inhibiting 98% of E. coli and 100% of Staphylococcus saprophyticus isolates at low concentrations, indicating its potential as a strong treatment option.

Importantly, gepotidacin remained effective against E. coli strains that were resistant to other common antibiotics, including those with extended-spectrum β-lactamase production and multidrug resistance, suggesting it could be a valuable alternative for difficult-to-treat infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antimicrobial Activity of Gepotidacin Tested against Escherichia coli and Staphylococcus saprophyticus Isolates Causing Urinary Tract Infections in Medical Centers Worldwide (2019 to 2020). Arends, SJR., Butler, D., Scangarella-Oman, N., et al.[2023]

Gepotidacin, a new treatment for gonorrhea and urinary tract infections, showed minimal impact from urine on its effectiveness against bacteria, with only slight increases in minimum inhibitory concentrations (MICs) for certain strains.

In comparison, levofloxacin also demonstrated minimal changes in MICs due to urine, suggesting that both antibiotics maintain their efficacy in the presence of urine, although further research is needed to fully understand these interactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of the effect of urine on the in vitro activity of gepotidacin and levofloxacin against Escherichia coli, Staphylococcus epidermidis, and Staphylococcus saprophyticus. Koeth, LM., DiFranco-Fisher, JM., Scangarella-Oman, NE.[2023]

Gepotidacin is a novel antibiotic that works by inhibiting bacterial DNA replication, showing promise against common uUTI pathogens, including antibiotic-resistant strains.

The ongoing phase III trials (EAGLE-2 and EAGLE-3) aim to evaluate the efficacy and safety of gepotidacin compared to nitrofurantoin in about 5000 women with uUTIs, focusing on its potential as a new treatment option in the face of rising antibiotic resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Design of Two Phase III, Randomized, Multicenter Studies Comparing Gepotidacin with Nitrofurantoin for the Treatment of Uncomplicated Urinary Tract Infection in Female Participants. Perry, C., Hossain, M., Powell, M., et al.[2022]

Citations

1.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/40924001/

Efficacy and in vitro activity of gepotidacin against bacterial ...

Two recent Phase 3 trials demonstrated the efficacy of gepotidacin compared with nitrofurantoin to treat uncomplicated urinary tract infections ...

2.

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 ...

3.

journals.asm.org

journals.asm.org/doi/10.1128/aac.00199-20

Phase 2a Pharmacokinetic, Safety, and Exploratory Efficacy ...

This phase 2a study in female participants with uUTI evaluated the pharmacokinetics (primary objective), safety, and exploratory efficacy of gepotidacin.

4.

clinicaltrials.gov

clinicaltrials.gov/study/NCT03568942

Pharmacokinetic Study of Oral Gepotidacin (GSK2140944) ...

Pharmacokinetic Study of Oral Gepotidacin (GSK2140944) in Subjects With Uncomplicated Urinary Tract Infection (Acute Cystitis). ClinicalTrials.gov ID ...

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cidrap.umn.edu

cidrap.umn.edu/antimicrobial-stewardship/trial-data-show-efficacy-safety-first-class-antibiotic-uncomplicated

Trial data show efficacy, safety of first-in-class antibiotic for ...

In the EAGLE-2 trial, 162 (50.6%) of 320 patients in the gepotidacin group had therapeutic success, compared with 135 (47.0%) of 287 patients ...

6.

accessdata.fda.gov

accessdata.fda.gov/drugsatfda_docs/label/2025/218230s000lbl.pdf

BLUJEPA (gepotidacin) tablets, for oral use - accessdata.fda.gov

Adverse Reactions Occurring in ≥1% of Uncomplicated Urinary Tract Infection Patients. Treated with BLUJEPA (Trials 1 and 2 Pooled Data; Safety Population).

7.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10678935/

2831. Efficacy and Safety of Gepotidacin for Uncomplicated ...

Gepotidacin generally demonstrated consistent therapeutic efficacy in patient subgroups, including patients aged > 50 years and those with a history of ...

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gsk.com

gsk.com/en-gb/media/press-releases/gepotidacin-accepted-for-priority-review-by-us-fda-for-treatment-of-uncomplicated-urinary-tract-infections-in-female-adults-and-adolescents/

Gepotidacin accepted for priority review by US FDA ...

Gepotidacin accepted for priority review by US FDA for treatment of uncomplicated urinary tract infections in female adults and adolescents.

9.

dig.pharmacy.uic.edu

dig.pharmacy.uic.edu/faqs/2025-2/june-2025-faqs/what-information-is-available-on-the-new-drug-gepotidacin-for-treatment-of-uncomplicated-urinary-tract-infections/

What information is available on the new drug gepotidacin for ...

Gepotidacin is currently approved to treat uncomplicated UTIs in female adults and pediatric patients who are aged ≥12 years and weigh ≥40 kg.