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
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
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:
Enrollment:
1531
Primary completion date:
2022-30-11
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
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
Showing 1 - 6 of 101 Results
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
2022-30-11
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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