Gepotidacin for Urinary Tract Infections

(SIS Trial)

Recruiting at 29 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

97 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug gepotidacin for treating urinary tract infections?

Research shows that gepotidacin is effective against bacteria causing urinary tract infections, like E. coli and Staphylococcus saprophyticus, even those resistant to other antibiotics. In a study, it successfully inhibited 98% of E. coli and 100% of Staphylococcus saprophyticus strains, suggesting it could be a promising treatment option. ^{1 2 3 4 5}

Is gepotidacin safe for humans?

Gepotidacin has been tested in several studies and generally shows an acceptable safety profile in humans, with most side effects being mild and related to the stomach. It has been evaluated in healthy participants and those with urinary tract infections, showing no treatment-limiting adverse events. ^{2 4 5 6 7}

How is the drug gepotidacin different from other treatments for urinary tract infections?

Gepotidacin is a new type of antibiotic that works by a unique method to stop bacteria from replicating their DNA, making it effective against many bacteria that are resistant to current antibiotics. This makes it a promising option for treating urinary tract infections, especially as antibiotic resistance becomes more common. ^{1 2 4 5 6}

What is the purpose of this trial?

The study will be conducted to evaluate the clinical symptom improvement and safety of oral gepotidacin for treatment of uncomplicated UTI (acute cystitis) in adolescent and adult female participants.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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 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 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]

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]

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]

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]

References

1. United States 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. [2023]

2. United States 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). [2023]

3. England 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. [2023]

4. New Zealand 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. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Pharmacokinetic, Safety, and Tolerability Evaluations of Gepotidacin (GSK2140944) in Healthy Japanese Participants. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Dose Selection for Phase III Clinical Evaluation of Gepotidacin (GSK2140944) in the Treatment of Uncomplicated Urinary Tract Infections. [2022]

7. United States 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). [2021]