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

NCT04020341 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: 2049892018-001801-98
• Study Type: interventional
• Target: 1,531
• Locations: 12 countries
• Sites: 103

Brief Summary

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.

Conditions

Urinary Tract Infections

Keywords

Acute cystitis; Efficacy; Gepotidacin; Nitrofurantoin; Urinary Tract Infection; Simple cystitis

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Therapeutic Response (TR) (Combined Per Participant Clinical and Microbiological Response) at the Test-of-Cure (TOC) Visit - Micro-ITT NTF-S (IA Set)

  Therapeutic response (success/failure) is a measure of the overall efficacy response. A therapeutic success referred to participants who had been deemed both a "microbiological success"(reduction of all qualifying bacterial uropathogens \[greater than or equal to {\>=}10\^5 colony-forming units per milliliter {CFU/mL}\] recovered at Baseline to less than (\<)10\^3 CFU/mL as observed on quantitative urine culture without the participant receiving other systemic antimicrobials before the TOC Visit) and a "clinical success" (resolution of signs and symptoms of acute cystitis present at Baseline \[and no new signs and symptoms\] without the participant receiving other systemic antimicrobials before the TOC Visit). Lack of clinical or microbiological success (including missing outcome assessments) was considered as therapeutic failure.

  TOC visit (Days 9 to 16)

• Number of Participants With Therapeutic Response (TR) (Combined Per Participant Clinical and Microbiological Response) at the Test-of-Cure (TOC) Visit - Micro-ITT NTF-S Population

  TR at TOC (success/failure) is a measure of the overall efficacy response. A therapeutic success at TOC referred to participant who have been deemed both a microbiological success (reduction of all qualifying bacterial uropathogens recovered at Baseline \[BL\] to \<10\^3 colony forming units per milliliter \[CFU/mL\] without receiving other systemic antimicrobials \[AB\] before the TOC visit) and a clinical success (resolution of symptoms of acute cystitis present at BL and no new symptoms without receiving other AB before the TOC visit \[or AB for uUTI on day of TOC visit\]). Lack of clinical or microbiological success (including missing outcome assessments) was considered as therapeutic failure.

  TOC visit (Days 9 to 16)

Secondary Outcomes (33)

• Number of Participants With Clinical Outcome at the TOC Visit - Micro-ITT NTF-S Population

  TOC visit (Days 9 to 16)

• Number of Participants With Clinical Response at the TOC Visit - Micro-ITT NTF-S Population

  TOC visit (Days 9 to 16)

• Number of Participants With Microbiological Outcome (MO) at the TOC Visit - Micro-ITT NTF-S Population

  TOC Visit (Days 9 to 16)

• Number of Participants With Microbiological Response at the TOC Visit - Micro-ITT NTF-S Population

  TOC visit (Days 9 to 16)

• Number of Participants With Therapeutic Response (TR) (Combined Per Participant Clinical and Microbiological Response) at the Follow up (FU) Visit-Micro-ITT NTF-S Population

  FU visit (Days 21 to 31)

Study Arms (2)

Gepotidacin

EXPERIMENTAL

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

Drug: Gepotidacin; Drug: Placebo matching nitrofurantoin

Nitrofurantoin

ACTIVE COMPARATOR

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

Drug: Nitrofurantoin; Drug: Placebo matching gepotidacin

Interventions

Gepotidacin DRUG

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

Gepotidacin

Placebo matching nitrofurantoin DRUG

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

Gepotidacin

Nitrofurantoin 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.

Nitrofurantoin

Placebo matching gepotidacin 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.

Nitrofurantoin

Eligibility Criteria

• Age: 12 Years+
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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:
• Poorly controlled asthma or chronic obstructive pulmonary disease; acute severe pain; active peptic ulcer disease; Parkinson disease; myasthenia gravis; Or
• Known acute porphyria.
• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (103)

GSK Investigational Site

Birmingham, Alabama, 35205, United States

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GSK Investigational Site

Phoenix, Arizona, 85051, United States

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GSK Investigational Site

Tucson, Arizona, 85712, United States

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GSK Investigational Site

Beverly Hills, California, 90211-2921, United States

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GSK Investigational Site

Chula Vista, California, 91911, United States

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GSK Investigational Site

La Mesa, California, 91942, United States

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GSK Investigational Site

Lomita, California, 90717, United States

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GSK Investigational Site

Long Beach, California, 90806, United States

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GSK Investigational Site

Northridge, California, 91324-3331, United States

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GSK Investigational Site

Northridge, California, 91324-3528, United States

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GSK Investigational Site

Palm Springs, California, 92264, United States

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GSK Investigational Site

San Diego, California, 92120, United States

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GSK Investigational Site

DeLand, Florida, 32720, United States

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Hialeah, Florida, 33016, United States

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Miami, Florida, 33144, United States

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GSK Investigational Site

Miami Springs, Florida, 33166, United States

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Orlando, Florida, 32806, United States

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Pompano Beach, Florida, 33060, United States

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Atlanta, Georgia, 30328, United States

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GSK Investigational Site

Columbus, Georgia, 31901-2561, United States

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Fayetteville, Georgia, 31204, United States

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Wichita, Kansas, 67226-3007, United States

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New Orleans, Louisiana, 70115, United States

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Shreveport, Louisiana, 71106, United States

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Watertown, Massachusetts, 02472, United States

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Dearborn Heights, Michigan, 48127-3163, United States

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Norfolk, Nebraska, 68701-2669, United States

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East Brunswick, New Jersey, 08816-1407, United States

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Albuquerque, New Mexico, 87109, United States

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Endwell, New York, 13760, United States

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Fayetteville, North Carolina, 28304, United States

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Scottdale, Pennsylvania, 15683, United States

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Smithfield, Pennsylvania, 15478, United States

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Clarksville, Tennessee, 37043-1524, United States

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Memphis, Tennessee, 38120, United States

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Arlington, Texas, 76014, United States

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GSK Investigational Site

Austin, Texas, 78705, United States

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Corpus Christi, Texas, 78414, United States

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GSK Investigational Site

Forney, Texas, 75126, United States

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GSK Investigational Site

Houston, Texas, 77055, United States

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GSK Investigational Site

Houston, Texas, 77065-5597, United States

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Blagoevgrad, 2700, Bulgaria

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Dupnitsa, 2600, Bulgaria

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GSK Investigational Site

Pernik, 5800, Bulgaria

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Pleven, 5800, Bulgaria

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Plovdiv, 4000, Bulgaria

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Sliven, 8800, Bulgaria

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Smolyan, 4700, Bulgaria

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Sofia, 1000, Bulgaria

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Sofia, 1408, Bulgaria

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Sofia, 1431, Bulgaria

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GSK Investigational Site

Yambol, 8600, Bulgaria

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GSK Investigational Site

Bory, 305 99, Czechia

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Kromeríž, 767 01, Czechia

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Prague, 120 00, Czechia

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GSK Investigational Site

Giessen, Hesse, 35385, Germany

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GSK Investigational Site

Essen, North Rhine-Westphalia, 45355, Germany

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GSK Investigational Site

Mülheim, North Rhine-Westphalia, 45468, Germany

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GSK Investigational Site

Berlin, 10439, Germany

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Hamburg, 20146, Germany

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Heraklion, 71110, Greece

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Larissa, 41110, Greece

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Thessaloniki, 546 42, Greece

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GSK Investigational Site

Thessaloniki, 54635, Greece

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Thessaloniki, 56403, Greece

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GSK Investigational Site

Ballószög, 6035, Hungary

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GSK Investigational Site

Csongrád, 6640, Hungary

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GSK Investigational Site

Nyíregyháza, 4400, Hungary

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Orosháza-Szentetornya, 5905, Hungary

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GSK Investigational Site

Ahmedabad, 380016, India

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GSK Investigational Site

Surat, 395002, India

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GSK Investigational Site

Varanasi, 221010, India

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GSK Investigational Site

Ciudad de Mexico, Campeche, 06100, Mexico

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GSK Investigational Site

Guadalajara, Jalisco, 44160, Mexico

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GSK Investigational Site

Guadalajara, Jalisco, 44280, Mexico

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GSK Investigational Site

Monterrey, Nuevo León, 64000, Mexico

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GSK Investigational Site

Monterrey, Nuevo León, 64460, Mexico

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GSK Investigational Site

San Juan del Río, Querétaro, 76800, Mexico

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GSK Investigational Site

Jalisco, 44130, Mexico

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GSK Investigational Site

Bucharest, 021105, Romania

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GSK Investigational Site

Bucharest, 022328, Romania

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GSK Investigational Site

Bucharest, 050653, Romania

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GSK Investigational Site

Iași, 700116, Romania

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GSK Investigational Site

Oradea, 410469, Romania

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GSK Investigational Site

Timișoara, 300736, Romania

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GSK Investigational Site

Bratislava, 851 05, Slovakia

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GSK Investigational Site

Košice, 040 01, Slovakia

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GSK Investigational Site

Nitra, 949 01, Slovakia

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GSK Investigational Site

Pruské, 018 52, Slovakia

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GSK Investigational Site

Šaľa, 927 01, Slovakia

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GSK Investigational Site

Trenčín, 911 01, Slovakia

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GSK Investigational Site

Trenčín, 911 05, Slovakia

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GSK Investigational Site

Alicante, 03010, Spain

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GSK Investigational Site

Córdoba, 140044, Spain

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GSK Investigational Site

Madrid, 28023, Spain

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GSK Investigational Site

Madrid, 28041, Spain

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GSK Investigational Site

Madrid, 28044, Spain

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GSK Investigational Site

Madrid, 28050, Spain

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GSK Investigational Site

Valencia, 46026, Spain

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GSK Investigational Site

Vic, 08500, Spain

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GSK Investigational Site

Crownhill, Plymouth, PL5 3JB, United Kingdom

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GSK Investigational Site

Liskeard, PL14 3XA, United Kingdom

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GSK Investigational Site

Peterborough, PE8 6PL, United Kingdom

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Related Publications (8)

• Wagenlehner F, Kaye KS, Talan DA, Sheets AJ, Scangarella-Oman NE, Jarvis E, Dennison J, Janmohamed S, Helgeson M, Perry C. Impact of updated regulatory guidelines on study results in contemporary uncomplicated urinary tract infection clinical trials and implications for trial conduct and drug development: a comparative analysis with EAGLE-2 and EAGLE-3. Contemp Clin Trials Commun. 2025 Nov 18;48:101572. doi: 10.1016/j.conctc.2025.101572. eCollection 2025 Dec.

  PMID: 41399629 DERIVED

• 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.

  PMID: 40924012 DERIVED

• 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.

  PMID: 40924001 DERIVED

• 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.

  PMID: 40372095 DERIVED

• 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.

  PMID: 38342126 DERIVED

• 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.

  PMID: 36271314 DERIVED

• 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.

  PMID: 36255258 DERIVED

• 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.

  PMID: 34978887 DERIVED

MeSH Terms

Conditions

Urinary Tract Infections

Interventions

gepotidacin; Nitrofurantoin

Condition Hierarchy (Ancestors)

Infections; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Nitrofurans; Nitro Compounds; Organic Chemicals; Furans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 11, 2019
• First Posted: July 16, 2019
• Study Start: October 17, 2019
• Primary Completion: November 30, 2022
• Study Completion: November 30, 2022
• Last Updated: June 22, 2023
• Results First Posted: June 22, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

Locations

ME (7); SL (7); US (41); DE (5); RO (6); BU (11); CZ (3); HU (4); GB (3); GR (5); ES (8); IN (3)