EFFICACY & SAFETY

 

BLUJEPA was studied in 2 randomized, double-blind, double-dummy, phase 3, noninferiority trials vs the current standard of care, nitrofurantoin1,2

 

EAGLE-2 and EAGLE-3 were phase 3, randomized, double-blind, double-dummy, noninferiority trials comparing BLUJEPA with nitrofurantoin (NTF) in the treatment of uncomplicated urinary tract infections (uUTIs).2

Trial design: EAGLE-2 and EAGLE-32

ITT population

3136 patients randomized across 2 clinical trials

(EAGLE-2: N=1531; EAGLE-3: N=1605)

Trial design diagram showing two clinical trials comparing oral BLUJEPA to oral nitrofurantoin over a 5-day treatment period with primary efficacy assessment
  • Patients were randomized to receive either BLUJEPA (n=1572) or NTF (n=1564) orally twice daily for 5 days2
  • Randomization was stratified by age group (<18 years, 18-50 years, >50 years) and history of recurrent uUTIs2
  • *

    Placebo matched the comparator.2

  • †

    Both trials stopped early on the basis of a pre-specified interim analysis for efficacy.2

IA=interim analysis; ITT=intent-to-treat; micro=microbiological; NTF=nitrofurantoin; NTF-S=nitrofurantoin-susceptible.

Inclusion and exclusion criteria

Key inclusion criteria icon

Key inclusion criteria1,3:

  • Nonpregnant females ≥12 years of age
  • Body weight ≥40 kg
  • ≥2 symptoms consistent with uUTI (dysuria, frequency, urgency, or lower abdominal pain)
  • Evidence of urinary nitrate and/or pyuria
Key exclusion criteria icon

Key exclusion criteria1,3:

  • Any medical condition or presentation suggestive of a complicated UTI, or an upper UTI (eg, pyelonephritis, urosepsis)
  • Significant renal impairment (creatinine clearance <60 mL/min)
  • Patients with a body mass index ≥40 kg/m2 or a body mass index ≥35 kg/m2 and experiencing obesity-related health conditions
  • Compromised immunity increasing risk for treatment failure or complications
  • Residency in care facilities
  • Certain urinary, renal, urogenital, cardiac, or hepatic conditions

See full trial patient demographics

Primary endpoint

The primary endpoint assessed therapeutic response (success or failure), a composite of clinical response + microbiological response in the micro ITT NTF-S (IA) population.2
Two women smiling and looking forward, dressed in white and yellow tops on a blue background
  • Therapeutic success required both2:
    • Clinical success: complete resolution of the baseline signs and symptoms of acute cystitis (dysuria, urgency, frequency, lower abdominal pain) without additional antibiotic use, and no new signs/symptoms
    • Microbiological success: eradication of qualifying uropathogens (reduction from ≥105 CFU/mL to <103 CFU/mL) without additional antibiotic use
  • Treatment was considered therapeutic failure in patients with microbiological and/or clinical failure, or with missing outcomes data.2
SEE PRIMARY ENDPOINT RESULTS

Interim analysis

 

The interim analysis was conducted when at least 60% of 884 patients (ie, the maximum target sample size) in the primary analysis population for each trial had the opportunity to reach the test-of-cure visit or were known to not have attained therapeutic success before the test-of-cure visit. Noninferiority was assessed in this population. Testing for superiority occurred only if noninferiority was achieved.2

Trial populations

Two groups icon

Intent-to-treat (ITT) population

The ITT population comprised the patients in each trial who were randomized into either the BLUJEPA treatment group or the NTF treatment group.2

Microscope icon

Micro ITT NTF-S population

The micro ITT NTF-S population included all randomized patients who2:

  • received ≥1 dose of study treatment, and
  • had 1 or 2 qualifying uropathogens (≥105 CFU/mL) at baseline that were susceptible to NTF
Group icon

Micro ITT NTF-S (IA set)

The primary analysis population was the micro ITT NTF-S (IA set), which comprised patients who, at the time of interim analysis data cutoff, had reached the test-of-cure visit or were known to not have attained therapeutic success before the test-of-cure visit.2 

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Learn about the safety profile of BLUJEPA.

Review the most common adverse reactions.

SEE SAFETY DATA

Indication & Important Safety Info

Indication

Important Safety Information

Indication

BLUJEPA is indicated for the treatment of female adult and pediatric patients 12 years of age and older weighing at least 40 kilograms (kg) with uncomplicated urinary tract infections (uUTI) caused by the following susceptible microorganisms: Escherichia coli, Klebsiella pneumoniae, Citrobacter freundii complex, Staphylococcus saprophyticus, and Enterococcus faecalis.

Usage to Reduce Development of Drug-Resistant Bacteria

To reduce the development of drug-resistant bacteria and maintain the effectiveness of BLUJEPA and other antibacterial drugs, BLUJEPA should be used only to treat infections that are proven or strongly suspected to be caused by bacteria.

Important Safety Information

CONTRAINDICATIONS

BLUJEPA is contraindicated in patients with a history of severe hypersensitivity to BLUJEPA.

WARNINGS AND PRECAUTIONS

QTc Prolongation

  • A dose and concentration-dependent prolongation of the QTc interval has been observed with BLUJEPA. Avoid use of BLUJEPA in patients with a history of QTc prolongation or with relevant pre-existing cardiac disease, patients taking antiarrhythmic agents, and in patients receiving drugs that prolong the QT interval. Due to an increase in BLUJEPA exposure, avoid concomitant administration of BLUJEPA with strong CYP3A4 inhibitors, in patients with severe hepatic impairment (Child-Pugh Class C), and in patients with severe renal impairment (estimated glomerular filtration rate [eGFR] <30 mL/min).

Acetylcholinesterase Inhibition

  • Dysarthria and other adverse reactions potentially attributed to acetylcholinesterase inhibition have been reported with BLUJEPA, an acetylcholinesterase inhibitor. Increased cholinergic effects can be associated with severe adverse effects, including atrioventricular block, bradycardia, bronchospasm, seizures/convulsions, and vasovagal syncope. Monitor patients with underlying medical conditions that may be exacerbated by acetylcholinesterase inhibition and patients receiving succinylcholine-type neuromuscular blocking agents, systemic anticholinergic medications, or non-depolarizing neuromuscular blocking agents.

Hypersensitivity Reactions

  • Hypersensitivity reactions, including anaphylaxis, have been reported in patients receiving BLUJEPA. If an allergic reaction to BLUJEPA occurs, discontinue the drug and institute appropriate supportive measures.

Clostridioides difficile-Associated Diarrhea

  • Clostridioides difficile infection (CDI) has been reported with nearly all systemic antibacterial agents, including BLUJEPA. Evaluate patients who develop diarrhea.
ADVERSE REACTIONS
  • The most common adverse reactions occurring in ≥1% of patients are diarrhea, nausea, abdominal pain, flatulence, headache, soft feces, dizziness, vomiting, and vulvovaginal candidiasis.
DRUG INTERACTIONS
  • CYP3A4 Inhibitors: Avoid coadministration of BLUJEPA with strong CYP3A4 inhibitors due to increased gepotidacin exposure.
  • CYP3A4 Inducers: Avoid coadministration of BLUJEPA with strong CYP3A4 inducers due to decreased gepotidacin exposure.
  • CYP3A4 Substrates: Avoid coadministration of BLUJEPA with drugs that are extensively metabolized by CYP3A4 and have a narrow therapeutic window.
  • Digoxin: Due to an increase in digoxin exposures, consider monitoring digoxin serum concentration, as appropriate, with concomitant administration of BLUJEPA.
USE IN SPECIFIC POPULATIONS
  • Renal Impairment: Avoid use of BLUJEPA in patients with severe renal impairment with eGFR <30 mL/min, including those receiving dialysis.
  • Hepatic Impairment: Avoid use of BLUJEPA in patients with severe hepatic impairment (Child-Pugh Class C).

Please see accompanying Prescribing Information, including Medication Guide, for BLUJEPA. 

To report SUSPECTED ADVERSE REACTIONS, contact GSK at gsk.public.reportum.com or 1-888-825-5249 or
FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

References

  1. BLUJEPA (gepotidacin) tablets. Prescribing Information. GSK; 2025.

  2. Wagenlehner F, Perry CR, Hooton TM, et al. 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;403(10428):741-755. doi:10.1016/S0140-6736(23)02196-7

  3. Wagenlehner F, Perry CR, Hooton TM, et al. 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. Supplementary appendix. Lancet. 2024;403(10428):1-33. doi:10.1016/S0140-6736(23)02196-7