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)

GSK study ID
212390
See study documents
Clinicaltrials.gov ID
NCT04187144
See results summary
EudraCT ID
2020-000553-27
EU CT Number
Not applicable
Trial status
Study complete
Study complete
Overview
Eligibility
Locations
Study documents
Results summary
Plain language summaries
Additional information

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:
  • Drug: Gepotidacin
  • Drug: Placebo matching nitrofurantoin
  • Drug: Nitrofurantoin
  • Drug: Placebo matching gepotidacin
    • 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
    Status
    Contact us
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    Location
    GSK Investigational Site
    Columbus, Ohio, United States, 43231
    Status
    Study Complete
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    Location
    GSK Investigational Site
    Mesquite, Texas, United States, 75149
    Status
    Study Complete
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    Location
    GSK Investigational Site
    Bountiful, Utah, United States, 84010
    Status
    Study Complete
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    Location
    GSK Investigational Site
    Brooklyn, New York, United States, 11229
    Status
    Study Complete
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    Location
    GSK Investigational Site
    Cary, North Carolina, United States, 27518
    Status
    Study Complete
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    Location
    GSK Investigational Site
    Cincinnati, Ohio, United States, 45215
    Status
    Study Complete
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    Study documents

    Protocol
    Available language(s): English
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    Statistical analysis plan
    Available language(s): English
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    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
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    To view plain language summaries on trialsummaries.com click here.

    Additional information about the trial

    Additional information
    Not applicable
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