Last updated: 02/19/2024 06:11:19
Comparative study to evaluate efficacy and safety of Gepotidacin to nitrofurantoin in treatment of uncomplicated urinary tract infection (UTI)
EudraCT ID
EU CT Number
Not applicable
Trial status
Study complete
Study complete
Trial overview
Official title: A Phase III, Randomized, Multicenter, Parallel-Group, Double-Blind, Double-Dummy Study in Adolescent and Adult Female Participants Comparing the Efficacy and Safety of Gepotidacin to Nitrofurantoin in the Treatment of Uncomplicated Urinary Tract Infection (Acute Cystitis)
Trial description: 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.
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Allocation:
Randomized
Primary outcomes:
Number of participants with therapeutic response (combined per participant clinical and microbiological response) at the Test-of-Cure (TOC) visit
Timeframe: Days 10 to 13
Secondary outcomes:
Number of participants with clinical outcome and response at the TOC visit
Timeframe: Days 10 to 13
Number of participants with clinical outcome and response at the follow up visit
Timeframe: Days 25 to 31
Number of participants with per participant microbiological outcome and response at the TOC visit
Timeframe: Days 10 to 13
Number of participants with per participant microbiological outcome and response at the follow up visit
Timeframe: Days 25 to 31
Number of participants with therapeutic response (combined per participant clinical and microbiological response) at the follow up visit
Timeframe: Days 25 to 31
Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)
Timeframe: Up to Day 31
Change from Baseline in hematology parameters: neutrophil count, lymphocyte count, monocyte count, eosinophil count, basophil count and platelet count (Giga cells per Liter)
Timeframe: Baseline, On-Therapy (Days 2 to 4), and Test of cure (Days 10 to 13)
Change from Baseline in hematology parameter: hemoglobin level
Timeframe: Baseline, On-Therapy (Days 2 to 4), and Test of cure (Days 10 to 13)
Change from Baseline in hematology parameter: hematocrit level
Timeframe: Baseline, On-Therapy (Days 2 to 4), and Test of cure (Days 10 to 13)
Change from Baseline in hematology parameter: Red blood cell (RBC) count
Timeframe: Baseline, On-Therapy (Days 2 to 4), and Test of cure (Days 10 to 13)
Change from Baseline in hematology parameter: Mean corpuscular hemoglobin (MCH)
Timeframe: Baseline, On-Therapy (Days 2 to 4), and Test of cure (Days 10 to 13)
Change from Baseline in hematology parameter: Mean corpuscular volume (MCV)
Timeframe: Baseline, On-Therapy (Days 2 to 4), and Test of cure (Days 10 to 13)
Change from Baseline in clinical chemistry parameters: Blood urea nitrogen (BUN), glucose non-fasting, calcium, chloride, sodium, magnesium, phosphorus, and potassium levels (millimoles per liter)
Timeframe: Baseline, On-Therapy (Days 2 to 4), and Test of cure (Days 10 to 13)
Change from Baseline in clinical chemistry parameters: Total bilirubin, direct bilirubin and creatinine levels (micromoles per Liter)
Timeframe: Baseline, On-Therapy (Days 2 to 4), and Test of cure (Days 10 to 13)
Change from Baseline in clinical chemistry parameters: albumin and total protein levels (gram per Liter)
Timeframe: Baseline, On-Therapy (Days 2 to 4), and Test of cure (Days 10 to 13)
Change from Baseline in clinical chemistry parameters: Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase levels (International units per Liter)
Timeframe: Baseline, On-Therapy (Days 2 to 4), and Test of cure (Days 10 to 13)
Number of participants with abnormal urinalysis Dipstick results
Timeframe: Days 10 to 13
Change from Baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP) (Millimeters of mercury [mmHg])
Timeframe: Baseline, On-Therapy (Days 2 to 4), and Test of cure (Days 10 to 13)
Change from Baseline in pulse rate
Timeframe: Baseline, On-Therapy (Days 2 to 4), and Test of cure (Days 10 to 13)
Change from Baseline in body temperature
Timeframe: Baseline, On-Therapy (Days 2 to 4), and Test of cure (Days 10 to 13)
Change from Baseline in Electrocardiograms (ECG) parameters: QT interval corrected for heart rate according to Bazett’s formula (QTcB) and QT interval corrected for heart rate according to Fridericia’s formula (QTcF) (milliseconds [msec])
Timeframe: Baseline, On-Therapy (Days 2 to 4), and Test of cure (Days 10 to 13)
Interventions:
Enrollment:
1606
Primary completion date:
2022-01-12
Observational study model:
Not applicable
Time perspective:
Not applicable
Clinical publications:
Breton J, Butler D, Dennison J, Hooton T, Janmohamed S, Jarvis E, et al. . Oral gepotidacin versus nitrofurantoin in patients with uncomplicated urinary tract infection: results from two randomised, double-blind, double-dummy, phase 3, non-inferiority trials (EAGLE-2 and EAGLE-3). Lancet.
DOI: 10.1016/S0140-6736(23)02196-7
PMID: 38342126
Medical condition
Urinary Tract Infections
Product
nitrofurantoin
Collaborators
Not applicable
Study date(s)
April 2020 to December 2022
Type
Interventional
Phase
3
Participation criteria
Sex
Female
Age
12+ years
Accepts healthy volunteers
No
- 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 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.
Inclusion and exclusion criteria
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: a) Poorly controlled asthma or chronic obstructive pulmonary disease; Acute severe pain,; Active peptic ulcer disease; Parkinson disease; Myasthenia gravis; Or b) Known acute porphyria. c) 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.
Trial location(s)
Location
GSK Investigational Site
Brooklyn, New York, United States, 11229
Status
Study Complete
Location
GSK Investigational Site
Cary, North Carolina, United States, 27518
Status
Study Complete
Location
GSK Investigational Site
Cincinnati, Ohio, United States, 45215
Status
Study Complete
Location
GSK Investigational Site
Hialeah, Florida, United States, 33013
Status
Study Complete
Location
GSK Investigational Site
Missouri City, Texas, United States, 77459
Status
Study Complete
Location
GSK Investigational Site
San Antonio, Texas, United States, 78209
Status
Study Complete
Location
GSK Investigational Site
San Antonio, Texas, United States, 78251
Status
Study Complete
Location
GSK Investigational Site
St. George, Utah, United States, 84790
Status
Study Complete
Location
GSK Investigational Site
Winston Salem, North Carolina, United States, 27103
Status
Study Complete
Location
GSK Investigational Site
La Mesa, California, United States, 91942
Status
Study Complete
Location
GSK Investigational Site
Lake Worth, Florida, United States, 33461
Status
Study Complete
Location
GSK Investigational Site
Lawrenceville, New Jersey, United States, 08648
Status
Study Complete
Location
GSK Investigational Site
Sacramento, California, United States, 95821
Status
Study Complete
Location
GSK Investigational Site
San Antonio, North Carolina, United States, 78229
Status
Study Complete
Location
GSK Investigational Site
Blackfoot, Idaho, United States, 83221
Status
Study Complete
Location
GSK Investigational Site
Boynton Beach, Florida, United States, 33435
Status
Study Complete
Location
GSK Investigational Site
Fargo, North Dakota, United States, 58104
Status
Study Complete
Location
GSK Investigational Site
Greenville, South Carolina, United States, 29615
Status
Study Complete
Location
GSK Investigational Site
New Tazewell, Tennessee, United States, 37824-1409
Status
Study Complete
Location
GSK Investigational Site
North Richland Hills, Texas, United States, 76180
Status
Study Complete
Location
GSK Investigational Site
Salt Lake City, Utah, United States, 84107
Status
Study Complete
Location
GSK Investigational Site
Sweetwater, Florida, United States, 33172
Status
Study Complete
Location
GSK Investigational Site
Union, South Carolina, United States, 29379
Status
Study Complete
Location
GSK Investigational Site
West Palm Beach, Florida, United States, 33409
Status
Study Complete
Location
GSK Investigational Site
Clearwater, Florida, United States, 33761
Status
Study Complete
Location
GSK Investigational Site
Huntsville, Alabama, United States, 35801
Status
Study Complete
Location
GSK Investigational Site
Leesburg, Florida, United States, 34748
Status
Study Complete
Location
GSK Investigational Site
Milan, Tennessee, United States, 38358
Status
Study Complete
Location
GSK Investigational Site
Ormond Beach, Florida, United States, 32174
Status
Study Complete
Location
GSK Investigational Site
Richmond, Virginia, United States, 23225
Status
Study Complete
Location
GSK Investigational Site
Richmond, Virginia, United States, 23235
Status
Study Complete
Location
GSK Investigational Site
Washington, District of Columbia, United States, 20011
Status
Study Complete
Location
GSK Investigational Site
Wi1mingion, North Carolina, United States, 28412
Status
Study Complete
Location
GSK Investigational Site
Bala Cynwyd, Pennsylvania, United States, 19004
Status
Study Complete
Location
GSK Investigational Site
Gilbert, Arizona, United States, 85296
Status
Study Complete
Location
GSK Investigational Site
Homewood, Alabama, United States, 35209
Status
Study Complete
Location
GSK Investigational Site
Maroubra, New South Wales, Australia, 2035
Status
Study Complete
Location
GSK Investigational Site
Mount Laurel, New Jersey, United States, 8054
Status
Study Complete
Location
GSK Investigational Site
New York, New York, United States, 10016
Status
Study Complete
Location
GSK Investigational Site
Sydney, New South Wales, Australia, 2010
Status
Study Complete
Location
GSK Investigational Site
Fall River, Massachusetts, United States, 2723
Status
Study Complete
Location
GSK Investigational Site
Hanover, Maryland, United States, 21076
Status
Study Complete
Location
GSK Investigational Site
Orlando, Florida, United States, 32810
Status
Study Complete
Location
GSK Investigational Site
Palm Springs, Florida, United States, 33406
Status
Study Complete
Location
GSK Investigational Site
Tarragindi, Queensland, Australia, 4121
Status
Study Complete
Location
GSK Investigational Site
Philadelphia, Pennsylvania, United States, 19107
Status
Study Complete
Location
GSK Investigational Site
Lancaster, South Carolina, United States, 29720
Status
Study Complete
Location
GSK Investigational Site
Apollo Beach, Florida, United States, 33572
Status
Study Complete
Location
GSK Investigational Site
Austin, Texas, United States, 78744 -1645
Status
Study Complete
Location
GSK Investigational Site
East Orange, New Jersey, United States, 07018-1502
Status
Study Complete
Location
GSK Investigational Site
Goyang-si, Gyeonggi-do, South Korea, 10326
Status
Study Complete
Location
GSK Investigational Site
Hwasun-gun, Jeollanam-do, South Korea, 58128
Status
Study Complete
Location
GSK Investigational Site
Lincoln, Nebraska, United States, 68510
Status
Study Complete
Location
GSK Investigational Site
Northridge, California, United States, 91324
Status
Study Complete
Location
GSK Investigational Site
Ostrowiec Swietokrzyski, Poland, 27-400
Status
Study Complete
Location
GSK Investigational Site
Pembroke Pines, Florida, United States, 33026-4383
Status
Study Complete
Location
GSK Investigational Site
Phoenix, Arizona, United States, 85015-1104
Status
Study Complete
Location
GSK Investigational Site
Valencia, California, United States, 91355-5319
Status
Study Complete
Location
GSK Investigational Site
Birmingham, Alabama, United States, 35205
Status
Study Complete
Location
GSK Investigational Site
Coconut Creek, Florida, United States, 33063
Status
Study Complete
Location
GSK Investigational Site
Gainesville, Florida, United States, 32607
Status
Study Complete
Location
GSK Investigational Site
Miami, Florida, United States, 33186-2178
Status
Study Complete
Location
GSK Investigational Site
Modesto, California, United States, 95350-5365
Status
Study Complete
Location
GSK Investigational Site
Peoria, Arizona, United States, 85381-3689
Status
Study Complete
Location
GSK Investigational Site
Plant City, Florida, United States, 33563
Status
Study Complete
Study documents
Protocol
Available language(s): English
Statistical analysis plan
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
Study complete
Actual primary completion date
2022-01-12
Actual study completion date
2022-01-12
Plain language summaries
Summary of results in plain language
Available language(s): English, Bulgarian, Gujarati, Hindi, Korean, Marathi, Polish, Spanish (United States), Telugu
To view plain language summaries on trialsummaries.com click here.
Additional information about the trial
Additional information
Not applicable
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