Last updated: 02/19/2024 06:10:30
A study to evaluate efficacy and safety of Gepotidacin in the treatment of uncomplicated urinary tract infection (UTI)
EudraCT ID
EU CT Number
Not applicable
Trial status
Completed
Completed
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
Plasma concentration of gepotidacin
Timeframe: Up to Day 5
Urine concentration of gepotidacin
Timeframe: Up to Day 5
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)
Interventions:
Drug: Gepotidacin
Drug: Placebo matching nitrofurantoin
Drug: Nitrofurantoin
Drug: Placebo matching gepotidacin
Enrollment:
1531
Observational study model:
Not applicable
Primary completion date:
2022-30-11
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
gepotidacin, nitrofurantoin
Collaborators
Not applicable
Study date(s)
October 2019 to November 2022
Type
Interventional
Phase
3
Participation criteria
Sex
Female
Age
12+ years
Accepts healthy volunteers
No
- 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.
- 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.
Inclusion and exclusion criteria
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: 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 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.
Trial location(s)
Location
GSK Investigational Site
Shreveport, Louisiana, United States, 71106
Status
Study Complete
Location
GSK Investigational Site
Arlington, Texas, United States, 76014
Status
Study Complete
Location
GSK Investigational Site
Chula Vista, California, United States, 91911
Status
Study Complete
Location
GSK Investigational Site
Corpus Christi, Texas, United States, 78414
Status
Study Complete
Location
GSK Investigational Site
Hialeah, Florida, United States, 33016
Status
Study Complete
Location
GSK Investigational Site
La Mesa, California, United States, 91942
Status
Study Complete
Location
GSK Investigational Site
Lomita, California, United States, 90717
Status
Study Complete
Location
GSK Investigational Site
Long Beach, California, United States, 90806
Status
Study Complete
Location
GSK Investigational Site
Memphis, Tennessee, United States, 38120
Status
Study Complete
Location
GSK Investigational Site
Miami Springs, Florida, United States, 33166
Status
Study Complete
Location
GSK Investigational Site
Orlando, Florida, United States, 32806
Status
Study Complete
Location
GSK Investigational Site
Watertown, Massachusetts, United States, 02472
Status
Study Complete
Location
GSK Investigational Site
Albuquerque, New Mexico, United States, 87109
Status
Study Complete
Location
GSK Investigational Site
Atlanta, Georgia, United States, 30328
Status
Study Complete
Location
GSK Investigational Site
Birmingham, Alabama, United States, 35205
Status
Study Complete
Location
GSK Investigational Site
Endwell, New York, United States, 13760
Status
Study Complete
Location
GSK Investigational Site
Essen, Nordrhein-Westfalen, Germany, 45355
Status
Study Complete
Location
GSK Investigational Site
Fayetteville, North Carolina, United States, 28304
Status
Study Complete
Location
GSK Investigational Site
New Orleans, Louisiana, United States, 70115
Status
Study Complete
Location
GSK Investigational Site
Pompano Beach, Florida, United States, 33060
Status
Study Complete
Location
GSK Investigational Site
San Diego, California, United States, 92120
Status
Study Complete
Location
GSK Investigational Site
Scottdale, Pennsylvania, United States, 15683
Status
Study Complete
Location
GSK Investigational Site
Smithfield, Pennsylvania, United States, 15478
Status
Study Complete
Location
GSK Investigational Site
Palm Springs, California, United States, 92264
Status
Study Complete
Location
GSK Investigational Site
Phoenix, Arizona, United States, 85051
Status
Study Complete
Location
GSK Investigational Site
Crownhill, Plymouth, United Kingdom, PL5 3JB
Status
Study Complete
Location
GSK Investigational Site
Muelheim an der Ruhr, Nordrhein-Westfalen, Germany, 45468
Status
Study Complete
Location
GSK Investigational Site
San Juan del Río, Querétaro, Mexico, 76800
Status
Study Complete
Location
GSK Investigational Site
Ciudad de Mexico, Campeche, Mexico, ?06100
Status
Study Complete
Location
GSK Investigational Site
Beverly Hills, California, United States, 90211-2921
Status
Study Complete
Location
GSK Investigational Site
Clarksville, Tennessee, United States, 37043-1524
Status
Study Complete
Location
GSK Investigational Site
Columbus, Georgia, United States, 31901-2561
Status
Study Complete
Location
GSK Investigational Site
Dearborn Heights, Michigan, United States, 48127-3163
Status
Study Complete
Location
GSK Investigational Site
East Brunswick, New Jersey, United States, 08816-1407
Status
Study Complete
Location
GSK Investigational Site
Fayetteville, Georgia, United States, 31204
Status
Study Complete
Location
GSK Investigational Site
Norfolk, Nebraska, United States, 68701-2669
Status
Study Complete
Location
GSK Investigational Site
Northridge, California, United States, 91324-3331
Status
Study Complete
Location
GSK Investigational Site
Wichita, Kansas, United States, 67226-3007
Status
Study Complete
Location
GSK Investigational Site
Houston, Texas, United States, 77065-5597
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
Completed
Actual primary completion date
2022-30-11
Actual study completion date
2022-30-11
Plain language summaries
Summary of results in plain language
Available language(s): English, Bulgarian, Czech, German, Greek, Gujarati, Hindi, Hungarian, Marathi, Romanian, Slovak, Spanish (Mexico), Spanish, Spanish (United States)
To view plain language summaries on trialsummaries.com click here.
Additional information about the trial
Additional information
Not applicable
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