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

NCT04187144 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: 2123902020-000553-27
• Study Type: interventional
• Target: 1,606
• Locations: 6 countries
• Sites: 113

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)

  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 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)

• 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 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 at a unit dose strength of 750mg. Participants will administer two 750 mg tablets, BID. Each dose will 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. Participants will administer 1 capsule BID. Each dose should be taken with water after consumption of food.

Gepotidacin

Nitrofurantoin DRUG

Nitrofurantoin will be available as over-encapsulated 100 mg capsules containing 25 mg nitrofurantoin macrocrystals and 75 mg nitrofurantoin. Participants will administer one 100 mg capsule, BID. 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. Participants will administer two tablets, BID. 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:

• The participant is \>=12 years of age at the time of signing the informed consent/assent and has a body weight \>=40 kilogram (kg).
• The participant has 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.
• The participant has nitrite or pyuria (greater than \[\>\]15 white blood cell \[WBC\]/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.
• The participant is capable of giving signed informed consent/assent.

You may not qualify if:

• The participant resides in a nursing home or dependent care type-facility.
• The participant has a body mass index \>=40.0 kilogram per meter square (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.
• The participant has a history of sensitivity to the study treatment, 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.
• The participant is immunocompromised or has altered immune defenses that may predispose the participant to a higher risk of treatment failure and/or complications.
• The 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 intervention .
• The participant has a known glucose-6 phosphate dehydrogenase deficiency.
• The 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.
• The 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.
• The 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.
• The 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).
• The participant has an indwelling catheter, nephrostomy, ureter stent, or other foreign material in the urinary tract.
• The 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 degree Fahrenheit (\>=38 Degrees Celsius \[C\]), flank pain, chills, or any other manifestations suggestive of upper UTI.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (113)

GSK Investigational Site

Birmingham, Alabama, 35205, United States

Location

GSK Investigational Site

Homewood, Alabama, 35209, United States

Location

GSK Investigational Site

Huntsville, Alabama, 35801, United States

Location

GSK Investigational Site

Gilbert, Arizona, 85296, United States

Location

GSK Investigational Site

Peoria, Arizona, 85381-3689, United States

Location

GSK Investigational Site

Phoenix, Arizona, 85015-1104, United States

Location

GSK Investigational Site

La Mesa, California, 91942, United States

Location

GSK Investigational Site

Modesto, California, 95350-5365, United States

Location

GSK Investigational Site

Northridge, California, 91324, United States

Location

GSK Investigational Site

Sacramento, California, 95821, United States

Location

GSK Investigational Site

Valencia, California, 91355-5319, United States

Location

GSK Investigational Site

Washington D.C., District of Columbia, 20011, United States

Location

GSK Investigational Site

Apollo Beach, Florida, 33572, United States

Location

GSK Investigational Site

Boynton Beach, Florida, 33435, United States

Location

GSK Investigational Site

Clearwater, Florida, 33761, United States

Location

GSK Investigational Site

Coconut Creek, Florida, 33063, United States

Location

GSK Investigational Site

Gainesville, Florida, 32607, United States

Location

GSK Investigational Site

Hialeah, Florida, 33013, United States

Location

GSK Investigational Site

Lake Worth, Florida, 33461, United States

Location

GSK Investigational Site

Leesburg, Florida, 34748, United States

Location

GSK Investigational Site

Miami, Florida, 33126, United States

Location

GSK Investigational Site

Miami, Florida, 33135, United States

Location

GSK Investigational Site

Miami, Florida, 33155, United States

Location

GSK Investigational Site

Miami, Florida, 33186-2178, United States

Location

GSK Investigational Site

Orlando, Florida, 32810, United States

Location

GSK Investigational Site

Ormond Beach, Florida, 32174, United States

Location

GSK Investigational Site

Palm Springs, Florida, 33406, United States

Location

GSK Investigational Site

Pembroke Pines, Florida, 33026-4383, United States

Location

GSK Investigational Site

Plant City, Florida, 33563, United States

Location

GSK Investigational Site

Sweetwater, Florida, 33172, United States

Location

GSK Investigational Site

Tampa, Florida, 33614, United States

Location

GSK Investigational Site

West Palm Beach, Florida, 33409, United States

Location

GSK Investigational Site

Blackfoot, Idaho, 83221, United States

Location

GSK Investigational Site

Boise, Idaho, 83704, United States

Location

GSK Investigational Site

Meridian, Idaho, 83642, United States

Location

GSK Investigational Site

Hanover, Maryland, 21076, United States

Location

GSK Investigational Site

Fall River, Massachusetts, 02723, United States

Location

GSK Investigational Site

Butte, Montana, 59701, United States

Location

GSK Investigational Site

Lincoln, Nebraska, 68510, United States

Location

GSK Investigational Site

East Orange, New Jersey, 07018-1502, United States

Location

GSK Investigational Site

Lawrenceville, New Jersey, 08648, United States

Location

GSK Investigational Site

Mount Laurel, New Jersey, 08054, United States

Location

GSK Investigational Site

Brooklyn, New York, 11229, United States

Location

GSK Investigational Site

New York, New York, 10016-7313, United States

Location

GSK Investigational Site

New York, New York, 10016, United States

Location

GSK Investigational Site

The Bronx, New York, 10456, United States

Location

GSK Investigational Site

Cary, North Carolina, 27518, United States

Location

GSK Investigational Site

Wilmington, North Carolina, 28412, United States

Location

GSK Investigational Site

Winston-Salem, North Carolina, 27103, United States

Location

GSK Investigational Site

Fargo, North Dakota, 58104, United States

Location

GSK Investigational Site

Cincinnati, Ohio, 45215, United States

Location

GSK Investigational Site

Columbus, Ohio, 43213, United States

Location

GSK Investigational Site

Columbus, Ohio, 43214, United States

Location

GSK Investigational Site

Columbus, Ohio, 43231, United States

Location

GSK Investigational Site

Dayton, Ohio, 45424, United States

Location

GSK Investigational Site

Eugene, Oregon, 97404, United States

Location

GSK Investigational Site

Bala-Cynwyd, Pennsylvania, 19004, United States

Location

GSK Investigational Site

Philadelphia, Pennsylvania, 19107, United States

Location

GSK Investigational Site

Greenville, South Carolina, 29615, United States

Location

GSK Investigational Site

Lancaster, South Carolina, 29720, United States

Location

GSK Investigational Site

Union, South Carolina, 29379, United States

Location

GSK Investigational Site

Milan, Tennessee, 38358, United States

Location

GSK Investigational Site

New Tazewell, Tennessee, 37824-1409, United States

Location

GSK Investigational Site

Austin, Texas, 78735, United States

Location

GSK Investigational Site

Austin, Texas, 78744 -1645, United States

Location

GSK Investigational Site

Houston, Texas, 77087, United States

Location

GSK Investigational Site

Katy, Texas, 77450, United States

Location

GSK Investigational Site

Mesquite, Texas, 75149, United States

Location

GSK Investigational Site

Missouri City, Texas, 77459, United States

Location

GSK Investigational Site

North Richland Hills, Texas, 76180, United States

Location

GSK Investigational Site

Plano, Texas, 75024, United States

Location

GSK Investigational Site

San Antonio, Texas, 78209, United States

Location

GSK Investigational Site

San Antonio, Texas, 78229, United States

Location

GSK Investigational Site

San Antonio, Texas, 78251, United States

Location

GSK Investigational Site

Bountiful, Utah, 84010, United States

Location

GSK Investigational Site

Salt Lake City, Utah, 84107, United States

Location

GSK Investigational Site

St. George, Utah, 84790, United States

Location

GSK Investigational Site

Richmond, Virginia, 23225, United States

Location

GSK Investigational Site

Richmond, Virginia, 23235, United States

Location

GSK Investigational Site

Maroubra, New South Wales, 2035, Australia

Location

GSK Investigational Site

Sydney, New South Wales, 2010, Australia

Location

GSK Investigational Site

Tarragindi, Queensland, 4121, Australia

Location

GSK Investigational Site

Gabrovo, 5300, Bulgaria

Location

GSK Investigational Site

Haskovo, 6300, Bulgaria

Location

GSK Investigational Site

Kyustendil, 2500, Bulgaria

Location

GSK Investigational Site

Montana, 3400, Bulgaria

Location

GSK Investigational Site

Pleven, 5800, Bulgaria

Location

GSK Investigational Site

Rousse, 7000, Bulgaria

Location

GSK Investigational Site

Shumen, 9700, Bulgaria

Location

GSK Investigational Site

Sofia, 1606, Bulgaria

Location

GSK Investigational Site

Stara Zagora, 6000, Bulgaria

Location

GSK Investigational Site

Targovisthe, 7700, Bulgaria

Location

GSK Investigational Site

Aurangabad, 431001, India

Location

GSK Investigational Site

Chandrapur, 442402, India

Location

GSK Investigational Site

Hyderabad, 500004, India

Location

GSK Investigational Site

Mumbai, 400022, India

Location

GSK Investigational Site

Nagpur, 440003, India

Location

GSK Investigational Site

Nagpur, 440015, India

Location

GSK Investigational Site

Nashik, 422101, India

Location

GSK Investigational Site

New Delhi, 110062, India

Location

GSK Investigational Site

Pune, 411016, India

Location

GSK Investigational Site

Rajkot, 360005, India

Location

GSK Investigational Site

Surat, 395010, India

Location

GSK Investigational Site

Katowice, 40-748, Poland

Location

GSK Investigational Site

Ostrowiec Świętokrzyski, 27-400, Poland

Location

GSK Investigational Site

Świdnik, 21-040, Poland

Location

GSK Investigational Site

Warsaw, 02798, Poland

Location

GSK Investigational Site

Ansan-si, 15355, South Korea

Location

GSK Investigational Site

Goyang-si, Gyeonggi-do, 10326, South Korea

Location

GSK Investigational Site

Hwasun-gun, Jeollanam-do, 58128, South Korea

Location

GSK Investigational Site

Incheon, 21565, South Korea

Location

GSK Investigational Site

Seoul, 06973, South Korea

Location

GSK Investigational Site

Suwon, 16247, South Korea

Location

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: December 3, 2019
• First Posted: December 5, 2019
• Study Start: April 23, 2020
• Primary Completion: December 1, 2022
• Study Completion: December 1, 2022
• Last Updated: July 18, 2023
• Results First Posted: July 18, 2023

Record last verified: 2023-07

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

KR (6); BU (10); US (79); AU (3); PL (4); IN (11)