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

NCT ID: NCT04187144

Last Updated: 2023-07-18

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

1606 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-04-23

Study Completion Date

2022-12-01

Brief Summary

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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

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Conditions

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Urinary Tract Infections

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Gepotidacin

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

Group Type EXPERIMENTAL

Gepotidacin

Intervention Type 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.

Placebo matching nitrofurantoin

Intervention Type 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.

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 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.

Placebo matching gepotidacin

Intervention Type 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.

Interventions

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Gepotidacin

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.

Intervention Type DRUG

Placebo matching nitrofurantoin

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.

Intervention Type DRUG

Nitrofurantoin

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.

Intervention Type DRUG

Placebo matching gepotidacin

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.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 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.

Exclusion Criteria

* 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:

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 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.
* The participant has known anuria, oliguria, or significant impairment of renal function (creatinine clearance \<60 milliliters per minute (mL/min) or clinically significant elevated serum creatinine as determined by the investigator).
* The participant presents with vaginal discharge at Baseline (e.g., suspected sexually transmitted disease).
* The participant has congenital long QT syndrome or known prolongation of the QTc interval.
* The participant has uncompensated heart failure.
* The participant has severe left ventricular hypertrophy.
* The participant has a family history of QT prolongation or sudden death.
* The participant has a recent history of vasovagal syncope or episodes of symptomatic bradycardia or brady arrhythmia within the last 12 months.
* The 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 ECG reading.
* The participant has a QTc \>450 msec or a QTc \>480 msec for participants with bundle-branch block.
* The participant has a documented or recent history of uncorrected hypokalemia within the past 3 months.
* The participant has a known ALT value \>2 times upper limit of normal (ULN).
* The 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 \[%\]).
* The participant has cirrhosis or current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice.
* The participant has a previous history of cholestatic jaundice/hepatic dysfunction associated with nitrofurantoin.
* The 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

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GlaxoSmithKline

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

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GSK Investigational Site

Birmingham, Alabama, United States

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Homewood, Alabama, United States

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Huntsville, Alabama, United States

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Gilbert, Arizona, United States

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Peoria, Arizona, United States

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Phoenix, Arizona, United States

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La Mesa, California, United States

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Modesto, California, United States

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Northridge, California, United States

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Sacramento, California, United States

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Valencia, California, United States

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

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Apollo Beach, Florida, United States

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Boynton Beach, Florida, United States

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Clearwater, Florida, United States

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Coconut Creek, Florida, United States

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Gainesville, Florida, United States

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Hialeah, Florida, United States

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Lake Worth, Florida, United States

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Leesburg, Florida, United States

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Miami, Florida, United States

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Miami, Florida, United States

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Miami, Florida, United States

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Miami, Florida, United States

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Orlando, Florida, United States

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Ormond Beach, Florida, United States

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Palm Springs, Florida, United States

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Pembroke Pines, Florida, United States

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Plant City, Florida, United States

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Sweetwater, Florida, United States

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Tampa, Florida, United States

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West Palm Beach, Florida, United States

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Blackfoot, Idaho, United States

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Boise, Idaho, United States

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Meridian, Idaho, United States

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Hanover, Maryland, United States

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Fall River, Massachusetts, United States

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Butte, Montana, United States

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Lincoln, Nebraska, United States

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East Orange, New Jersey, United States

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Lawrenceville, New Jersey, United States

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Mount Laurel, New Jersey, United States

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Brooklyn, New York, United States

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New York, New York, United States

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New York, New York, United States

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The Bronx, New York, United States

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Cary, North Carolina, United States

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Wilmington, North Carolina, United States

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Winston-Salem, North Carolina, United States

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Fargo, North Dakota, United States

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Cincinnati, Ohio, United States

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Columbus, Ohio, United States

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Columbus, Ohio, United States

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Columbus, Ohio, United States

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Dayton, Ohio, United States

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Eugene, Oregon, United States

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Bala-Cynwyd, Pennsylvania, United States

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Philadelphia, Pennsylvania, United States

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Greenville, South Carolina, United States

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Lancaster, South Carolina, United States

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Union, South Carolina, United States

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Milan, Tennessee, United States

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New Tazewell, Tennessee, United States

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Austin, Texas, United States

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Austin, Texas, United States

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Houston, Texas, United States

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Katy, Texas, United States

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Mesquite, Texas, United States

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Missouri City, Texas, United States

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North Richland Hills, Texas, United States

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Plano, Texas, United States

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San Antonio, Texas, United States

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San Antonio, Texas, United States

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San Antonio, Texas, United States

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Bountiful, Utah, United States

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Salt Lake City, Utah, United States

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St. George, Utah, United States

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Richmond, Virginia, United States

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Richmond, Virginia, United States

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Maroubra, New South Wales, Australia

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Sydney, New South Wales, Australia

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Tarragindi, Queensland, Australia

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Gabrovo, , Bulgaria

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Haskovo, , Bulgaria

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Kyustendil, , Bulgaria

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Montana, , Bulgaria

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Pleven, , Bulgaria

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Rousse, , Bulgaria

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Shumen, , Bulgaria

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Sofia, , Bulgaria

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Stara Zagora, , Bulgaria

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Targovisthe, , Bulgaria

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Aurangabad, , India

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Chandrapur, , India

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Hyderabad, , India

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Mumbai, , India

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Nagpur, , India

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Nagpur, , India

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Nashik, , India

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New Delhi, , India

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Pune, , India

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Rajkot, , India

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Surat, , India

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Katowice, , Poland

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Ostrowiec Świętokrzyski, , Poland

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Świdnik, , Poland

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Warsaw, , Poland

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Ansan-si, , South Korea

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Goyang-si, Gyeonggi-do, , South Korea

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Hwasun-gun, Jeollanam-do, , South Korea

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Incheon, , South Korea

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Seoul, , South Korea

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Suwon, , South Korea

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Countries

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United States Australia Bulgaria India Poland South Korea

References

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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

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2020-000553-27

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

212390

Identifier Type: -

Identifier Source: org_study_id

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