A Study to Evaluate Efficacy and Safety of Gepotidacin in the Treatment of Uncomplicated Urinary Tract Infection (UTI)

NCT ID: NCT04020341

Last Updated: 2023-06-22

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

1531 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-10-17

Study Completion Date

2022-11-30

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

The study will be conducted to evaluate the therapeutic response (combined per participant microbiological and clinical response) of oral gepotidacin compared to oral nitrofurantoin for treatment of uncomplicated UTI (acute cystitis) in adolescent and adult female participants.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Urinary Tract Infections

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Gepotidacin

Participants will be administered oral doses of 1500 milligrams (mg) gepotidacin plus nitrofurantoin matching placebo twice daily (BID); approximately every 12 hours for 5 days

Group Type EXPERIMENTAL

Gepotidacin

Intervention Type DRUG

Gepotidacin will be available as tablets containing 750 mg gepotidacin. Each dose should be taken with water after consumption of food.

Placebo matching nitrofurantoin

Intervention Type DRUG

Placebo matching nitrofurantoin will be available as over-encapsulated unit-dose capsules. Each dose should be taken with water after consumption of food.

Nitrofurantoin

Participants will be administered oral doses of 100 mg nitrofurantoin plus gepotidacin matching placebo BID; approximately every 12 hours for 5 days.

Group Type ACTIVE_COMPARATOR

Nitrofurantoin

Intervention Type DRUG

Nitrofurantoin will be available as over-encapsulated capsules containing 25 mg nitrofurantoin macrocrystals and 75 mg nitrofurantoin. Each dose should be taken with water after consumption of food.

Placebo matching gepotidacin

Intervention Type DRUG

Placebo matching gepotidacin will be available as unit-dose gepotidacin placebo-to-match tablet. Each dose should be taken with water after consumption of food.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Gepotidacin

Gepotidacin will be available as tablets containing 750 mg gepotidacin. Each dose should be taken with water after consumption of food.

Intervention Type DRUG

Placebo matching nitrofurantoin

Placebo matching nitrofurantoin will be available as over-encapsulated unit-dose capsules. Each dose should be taken with water after consumption of food.

Intervention Type DRUG

Nitrofurantoin

Nitrofurantoin will be available as over-encapsulated capsules containing 25 mg nitrofurantoin macrocrystals and 75 mg nitrofurantoin. Each dose should be taken with water after consumption of food.

Intervention Type DRUG

Placebo matching gepotidacin

Placebo matching gepotidacin will be available as unit-dose gepotidacin placebo-to-match tablet. Each dose should be taken with water after consumption of food.

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* Participants having \>=12 years of age at the time of signing the informed consent/assent and have a body weight \>=40 kilograms (kg).
* Participants having 2 or more of the following clinical signs and symptoms of acute cystitis with onset \<96 hours prior to study entry: dysuria, frequency, urgency, or lower abdominal pain.
* Participants having nitrite or pyuria (greater than \[\>\]15 white blood cells \[WBC\]/high power field \[HPF\] or the presence of 3 plus \[+\]/large leukocyte esterase) from a pretreatment clean-catch midstream urine sample based on local laboratory procedures.
* The participant is female.
* Participant is capable of giving signed informed consent/assent.

Exclusion Criteria

* Participant resides in a nursing home or dependent care type-facility.
* Participant has a body mass index \>=40.0 kilogram per square meter (kg/m\^2) or a body mass index \>=35.0 kg/m\^2 and is experiencing obesity-related health conditions such as uncontrolled high blood pressure or uncontrolled diabetes.
* Participant has a history of sensitivity to the study treatments, or components thereof, or a history of a drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates her participation.
* Participant is immunocompromised or has altered immune defenses that may predispose the participant to a higher risk of treatment failure and/or complications.
* Participant has any of the following:

1. Poorly controlled asthma or chronic obstructive pulmonary disease; acute severe pain; active peptic ulcer disease; Parkinson disease; myasthenia gravis; Or
2. Known acute porphyria.
3. Any surgical or medical condition (active or chronic) that may interfere with drug absorption, distribution, metabolism, or excretion of the study treatment.
* Participant has a known glucose-6-phosphate dehydrogenase deficiency.
* Participant has a serious underlying disease that could be imminently life-threatening, or the participant is unlikely to survive for the duration of the study period.
* Participant has acute cystitis that is known or suspected to be due to fungal, parasitic, or viral pathogens; or known or suspected to be due to Pseudomonas aeruginosa or Enterobacterales (other than Escherichia coli) as the contributing pathogen.
* 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, that may interfere with the clinical efficacy assessments or preclude complete resolution of acute cystitis symptoms.
* 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 or stricture of the urinary tract, primary renal disease (for example \[e.g.\], polycystic renal disease), or neurogenic bladder, or the participant has a history of anatomical or functional abnormalities of the urinary tract (e.g., chronic vesico-ureteral reflux, detrusor insufficiency).
* Participant has an indwelling catheter, nephrostomy, ureter stent, or other foreign material in the urinary tract.
* Participant who, in the opinion of the investigator, has an otherwise complicated UTI, an active upper UTI (e.g., pyelonephritis, urosepsis), signs and symptom onset \>=96 hours before study entry, or a temperature \>=101.4 Degrees Fahrenheit (F) (\>=38 Degrees Celsius \[C\]), flank pain, chills, or any other manifestations suggestive of upper UTI.
* Participant has known anuria, oliguria, or significant impairment of renal function (creatinine clearance \<60 milliliter per minute \[mL/min\] or clinically significant elevated serum creatinine as determined by the investigator).
* Participant presents with vaginal discharge at Baseline (e.g., suspected sexually transmitted disease).
* Participant has congenital long QT syndrome or known prolongation of the corrected QT (QTc) interval.
* Participant has uncompensated heart failure.
* Participant has severe left ventricular hypertrophy.
* Participant has a family history of QT prolongation or sudden death.
* Participant has a recent history of vasovagal syncope or episodes of symptomatic bradycardia or brady-arrhythmia within the last 12 months.
* Participant is taking QT-prolonging drugs or drugs known to increase the risk of torsades de pointes (TdP) per the www.crediblemeds.org. "Known Risk of TdP" category at the time of her Baseline Visit, which cannot be safely discontinued from the Baseline Visit to the TOC Visit; or the participant is taking a strong cytochrome P450 enzyme 3A4 (CYP3A4) inhibitor.
* For any participant \>=12 to \<18 years of age, the participant has an abnormal electrocardiogram (ECG) reading.
* Participant has a QTc \>450 millisecond (msec) or a QTc \>480 msec for participants with bundle-branch block.
* Participant has a documented or recent history of uncorrected hypokalemia within the past 3 months.
* Participant has a known alanine aminotransferase (ALT) value \>2 times upper limit of normal (ULN).
* Participant has a known bilirubin value \>1.5 times ULN (isolated bilirubin \>1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin \<35 percent \[%\]).
* Participant has a current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones), including symptomatic viral hepatitis or moderate-to-severe liver insufficiency (Child Pugh class B or C).
* Participant has a previous history of cholestatic jaundice or hepatic dysfunction associated with nitrofurantoin.
* Participant has received treatment with other systemic antimicrobials or systemic antifungals within 1 week before study entry.
Minimum Eligible Age

12 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

GlaxoSmithKline

INDUSTRY

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

GSK Investigational Site

Birmingham, Alabama, United States

Site Status

GSK Investigational Site

Phoenix, Arizona, United States

Site Status

GSK Investigational Site

Tucson, Arizona, United States

Site Status

GSK Investigational Site

Beverly Hills, California, United States

Site Status

GSK Investigational Site

Chula Vista, California, United States

Site Status

GSK Investigational Site

La Mesa, California, United States

Site Status

GSK Investigational Site

Lomita, California, United States

Site Status

GSK Investigational Site

Long Beach, California, United States

Site Status

GSK Investigational Site

Northridge, California, United States

Site Status

GSK Investigational Site

Northridge, California, United States

Site Status

GSK Investigational Site

Palm Springs, California, United States

Site Status

GSK Investigational Site

San Diego, California, United States

Site Status

GSK Investigational Site

DeLand, Florida, United States

Site Status

GSK Investigational Site

Hialeah, Florida, United States

Site Status

GSK Investigational Site

Miami, Florida, United States

Site Status

GSK Investigational Site

Miami Springs, Florida, United States

Site Status

GSK Investigational Site

Orlando, Florida, United States

Site Status

GSK Investigational Site

Pompano Beach, Florida, United States

Site Status

GSK Investigational Site

Atlanta, Georgia, United States

Site Status

GSK Investigational Site

Columbus, Georgia, United States

Site Status

GSK Investigational Site

Fayetteville, Georgia, United States

Site Status

GSK Investigational Site

Wichita, Kansas, United States

Site Status

GSK Investigational Site

New Orleans, Louisiana, United States

Site Status

GSK Investigational Site

Shreveport, Louisiana, United States

Site Status

GSK Investigational Site

Watertown, Massachusetts, United States

Site Status

GSK Investigational Site

Dearborn Heights, Michigan, United States

Site Status

GSK Investigational Site

Norfolk, Nebraska, United States

Site Status

GSK Investigational Site

East Brunswick, New Jersey, United States

Site Status

GSK Investigational Site

Albuquerque, New Mexico, United States

Site Status

GSK Investigational Site

Endwell, New York, United States

Site Status

GSK Investigational Site

Fayetteville, North Carolina, United States

Site Status

GSK Investigational Site

Scottdale, Pennsylvania, United States

Site Status

GSK Investigational Site

Smithfield, Pennsylvania, United States

Site Status

GSK Investigational Site

Clarksville, Tennessee, United States

Site Status

GSK Investigational Site

Memphis, Tennessee, United States

Site Status

GSK Investigational Site

Arlington, Texas, United States

Site Status

GSK Investigational Site

Austin, Texas, United States

Site Status

GSK Investigational Site

Corpus Christi, Texas, United States

Site Status

GSK Investigational Site

Forney, Texas, United States

Site Status

GSK Investigational Site

Houston, Texas, United States

Site Status

GSK Investigational Site

Houston, Texas, United States

Site Status

GSK Investigational Site

Blagoevgrad, , Bulgaria

Site Status

GSK Investigational Site

Dupnitsa, , Bulgaria

Site Status

GSK Investigational Site

Pernik, , Bulgaria

Site Status

GSK Investigational Site

Pleven, , Bulgaria

Site Status

GSK Investigational Site

Plovdiv, , Bulgaria

Site Status

GSK Investigational Site

Sliven, , Bulgaria

Site Status

GSK Investigational Site

Smolyan, , Bulgaria

Site Status

GSK Investigational Site

Sofia, , Bulgaria

Site Status

GSK Investigational Site

Sofia, , Bulgaria

Site Status

GSK Investigational Site

Sofia, , Bulgaria

Site Status

GSK Investigational Site

Yambol, , Bulgaria

Site Status

GSK Investigational Site

Bory, , Czechia

Site Status

GSK Investigational Site

Kromeríž, , Czechia

Site Status

GSK Investigational Site

Prague, , Czechia

Site Status

GSK Investigational Site

Giessen, Hesse, Germany

Site Status

GSK Investigational Site

Essen, North Rhine-Westphalia, Germany

Site Status

GSK Investigational Site

Mülheim, North Rhine-Westphalia, Germany

Site Status

GSK Investigational Site

Berlin, , Germany

Site Status

GSK Investigational Site

Hamburg, , Germany

Site Status

GSK Investigational Site

Heraklion, , Greece

Site Status

GSK Investigational Site

Larissa, , Greece

Site Status

GSK Investigational Site

Thessaloniki, , Greece

Site Status

GSK Investigational Site

Thessaloniki, , Greece

Site Status

GSK Investigational Site

Thessaloniki, , Greece

Site Status

GSK Investigational Site

Ballószög, , Hungary

Site Status

GSK Investigational Site

Csongrád, , Hungary

Site Status

GSK Investigational Site

Nyíregyháza, , Hungary

Site Status

GSK Investigational Site

Orosháza-Szentetornya, , Hungary

Site Status

GSK Investigational Site

Ahmedabad, , India

Site Status

GSK Investigational Site

Surat, , India

Site Status

GSK Investigational Site

Varanasi, , India

Site Status

GSK Investigational Site

Ciudad de Mexico, Campeche, Mexico

Site Status

GSK Investigational Site

Guadalajara, Jalisco, Mexico

Site Status

GSK Investigational Site

Guadalajara, Jalisco, Mexico

Site Status

GSK Investigational Site

Monterrey, Nuevo León, Mexico

Site Status

GSK Investigational Site

Monterrey, Nuevo León, Mexico

Site Status

GSK Investigational Site

San Juan del Río, Querétaro, Mexico

Site Status

GSK Investigational Site

Jalisco, , Mexico

Site Status

GSK Investigational Site

Bucharest, , Romania

Site Status

GSK Investigational Site

Bucharest, , Romania

Site Status

GSK Investigational Site

Bucharest, , Romania

Site Status

GSK Investigational Site

Iași, , Romania

Site Status

GSK Investigational Site

Oradea, , Romania

Site Status

GSK Investigational Site

Timișoara, , Romania

Site Status

GSK Investigational Site

Bratislava, , Slovakia

Site Status

GSK Investigational Site

Košice, , Slovakia

Site Status

GSK Investigational Site

Nitra, , Slovakia

Site Status

GSK Investigational Site

Pruské, , Slovakia

Site Status

GSK Investigational Site

Šaľa, , Slovakia

Site Status

GSK Investigational Site

Trenčín, , Slovakia

Site Status

GSK Investigational Site

Trenčín, , Slovakia

Site Status

GSK Investigational Site

Alicante, , Spain

Site Status

GSK Investigational Site

Córdoba, , Spain

Site Status

GSK Investigational Site

Madrid, , Spain

Site Status

GSK Investigational Site

Madrid, , Spain

Site Status

GSK Investigational Site

Madrid, , Spain

Site Status

GSK Investigational Site

Madrid, , Spain

Site Status

GSK Investigational Site

Valencia, , Spain

Site Status

GSK Investigational Site

Vic, , Spain

Site Status

GSK Investigational Site

Crownhill, Plymouth, , United Kingdom

Site Status

GSK Investigational Site

Liskeard, , United Kingdom

Site Status

GSK Investigational Site

Peterborough, , United Kingdom

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States Bulgaria Czechia Germany Greece Hungary India Mexico Romania Slovakia Spain United Kingdom

References

Explore related publications, articles, or registry entries linked to this study.

Scangarella-Oman NE, Butler DL, Breton J, Brown D, Kasapidis C, Sheets AJ. Efficacy and in vitro activity of gepotidacin against bacterial uropathogens, including subsets with molecularly characterized resistance mechanisms and genotypes/epidemiological clones, in females with uncomplicated urinary tract infections: results from two global, pivotal, phase 3 trials (EAGLE-2 and EAGLE-3). Antimicrob Agents Chemother. 2025 Oct;69(10):e0163924. doi: 10.1128/aac.01639-24. Epub 2025 Sep 9.

Reference Type DERIVED
PMID: 40924012 (View on PubMed)

Scangarella-Oman NE, Butler DL, Breton J, Brown D, Kasapidis C, Millns H, Huang C, Perry CR, Sheets AJ, Dennison J, Janmohamed S. Efficacy and in vitro activity of gepotidacin against bacterial uropathogens, including drug-resistant phenotypes, in females with uncomplicated urinary tract infections: results from two global, pivotal, phase 3 trials (EAGLE-2 and EAGLE-3). Antimicrob Agents Chemother. 2025 Oct;69(10):e0164024. doi: 10.1128/aac.01640-24. Epub 2025 Sep 9.

Reference Type DERIVED
PMID: 40924001 (View on PubMed)

Hackel MA, Karlowsky JA, Sahm DF, West JM, Scangarella-Oman NE. In vitro activity of gepotidacin against urinary tract infection isolates of Enterobacterales, Enterococcus faecalis, and Staphylococcus saprophyticus. Antimicrob Agents Chemother. 2025 Jun 4;69(6):e0029625. doi: 10.1128/aac.00296-25. Epub 2025 May 15.

Reference Type DERIVED
PMID: 40372095 (View on PubMed)

Wagenlehner F, Perry CR, Hooton TM, Scangarella-Oman NE, Millns H, Powell M, Jarvis E, Dennison J, Sheets A, Butler D, Breton J, Janmohamed S. Oral gepotidacin versus nitrofurantoin in patients with uncomplicated urinary tract infection (EAGLE-2 and EAGLE-3): two randomised, controlled, double-blind, double-dummy, phase 3, non-inferiority trials. Lancet. 2024 Feb 24;403(10428):741-755. doi: 10.1016/S0140-6736(23)02196-7. Epub 2024 Feb 8.

Reference Type DERIVED
PMID: 38342126 (View on PubMed)

Perry C, Hossain M, Powell M, Raychaudhuri A, Scangarella-Oman N, Tiffany C, Xu S, Dumont E, Janmohamed S. Design of Two Phase III, Randomized, Multicenter Studies Comparing Gepotidacin with Nitrofurantoin for the Treatment of Uncomplicated Urinary Tract Infection in Female Participants. Infect Dis Ther. 2022 Dec;11(6):2297-2310. doi: 10.1007/s40121-022-00706-9. Epub 2022 Oct 21.

Reference Type DERIVED
PMID: 36271314 (View on PubMed)

Fishman C, Caverly Rae JM, Posobiec LM, Laffan SB, Lerman SA, Pearson N, Janmohamed S, Dumont E, Nunn-Floyd D, Stanislaus DJ. Novel Bacterial Topoisomerase Inhibitor Gepotidacin Demonstrates Absence of Fluoroquinolone-Like Arthropathy in Juvenile Rats. Antimicrob Agents Chemother. 2022 Nov 15;66(11):e0048322. doi: 10.1128/aac.00483-22. Epub 2022 Oct 18.

Reference Type DERIVED
PMID: 36255258 (View on PubMed)

Scangarella-Oman NE, Hossain M, Hoover JL, Perry CR, Tiffany C, Barth A, Dumont EF. Dose Selection for Phase III Clinical Evaluation of Gepotidacin (GSK2140944) in the Treatment of Uncomplicated Urinary Tract Infections. Antimicrob Agents Chemother. 2022 Mar 15;66(3):e0149221. doi: 10.1128/AAC.01492-21. Epub 2022 Jan 3.

Reference Type DERIVED
PMID: 34978887 (View on PubMed)

Provided Documents

Download supplemental materials such as informed consent forms, study protocols, or participant manuals.

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

2018-001801-98

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

204989

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

Gentamicin Bladder Instillation Trial
NCT01884467 UNKNOWN PHASE4