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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05630833




Registration number
NCT05630833
Ethics application status
Date submitted
23/11/2022
Date registered
30/11/2022
Date last updated
10/02/2023

Titles & IDs
Public title
A Study to Investigate the Efficacy and Safety With Gepotidacin in Japanese Female Participants With Uncomplicated Urinary Tract Infection (Acute Cystitis)
Scientific title
A Phase III, Multicenter, Randomized, Active Reference, Double Blind, Double-dummy Study in Japanese Female Participants to Evaluate the Efficacy and Safety of Gepotidacin in the Treatment of Uncomplicated Urinary Tract Infection (Acute Cystitis)
Secondary ID [1] 0 0
214144
Universal Trial Number (UTN)
Trial acronym
EAGLE-J
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Condition category
Condition code
Infection 0 0 0 0
Studies of infection and infectious agents
Infection 0 0 0 0
Other infectious diseases
Infection 0 0 0 0
Sexually transmitted infections
Renal and Urogenital 0 0 0 0
Other renal and urogenital disorders
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Gepotidacin
Treatment: Drugs - Nitrofurantoin
Treatment: Drugs - Placebo

Experimental: Gepotidacin + Placebo -

Active Comparator: Nitrofurantoin + Placebo -


Treatment: Drugs: Gepotidacin
Gepotidacin will be administered.

Treatment: Drugs: Nitrofurantoin
Nitrofurantoin will be administered.

Treatment: Drugs: Placebo
Placebo will be administered.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of participants with therapeutic response (combined per participant clinical and microbiological response) at the TOC Visit
Timepoint [1] 0 0
Days 10 to 13
Secondary outcome [1] 0 0
Number of participants with therapeutic response to gepotidacin compared to nitrofurantoin at the TOC Visit
Timepoint [1] 0 0
Days 10 to 13
Secondary outcome [2] 0 0
Number of participants with clinical outcome and response at the TOC visit
Timepoint [2] 0 0
Days 10 to 13
Secondary outcome [3] 0 0
Number of participants with per participant microbiological outcome and response at the TOC visit
Timepoint [3] 0 0
Days 10 to 13
Secondary outcome [4] 0 0
Number of participants with therapeutic response in female participants with acute uncomplicated cystitis who have qualifying uropathogen(s) resistant to two or more specific classes of antimicrobials
Timepoint [4] 0 0
Days 10 to 13
Secondary outcome [5] 0 0
Number of participants with clinical outcome and response in female participants with acute uncomplicated cystitis who have qualifying uropathogen(s) resistant to two or more specific classes of antimicrobials
Timepoint [5] 0 0
Days 10 to 13
Secondary outcome [6] 0 0
Number of participants with microbiological outcome and response in female participants with acute uncomplicated cystitis who have qualifying uropathogen(s) resistant to two or more specific classes of antimicrobials
Timepoint [6] 0 0
Days 10 to 13
Secondary outcome [7] 0 0
Number of participants with Investigator assessment of clinical response at the TOC Visit
Timepoint [7] 0 0
Days 10 to 13
Secondary outcome [8] 0 0
Number of participants with Treatment-Emergent Adverse Events (TEAEs)
Timepoint [8] 0 0
Up to Day 31
Secondary outcome [9] 0 0
Number of participants with Serious Adverse Events (SAEs)
Timepoint [9] 0 0
Up to Day 31
Secondary outcome [10] 0 0
Number of participants with Adverse Events of Special Interest (AESIs)
Timepoint [10] 0 0
Up to Day 31
Secondary outcome [11] 0 0
Change from baseline in hematology parameters: neutrophil count, lymphocyte count, monocyte count, eosinophil count, basophil count and platelet count (Giga cells per liter)
Timepoint [11] 0 0
Baseline, On-Therapy (Days 2 to 4), and TOC (Days 10 to 13)
Secondary outcome [12] 0 0
Change from baseline in hematology parameter: Red Blood Cell (RBC) count (Trillion cells per liter)
Timepoint [12] 0 0
Baseline, On-Therapy (Days 2 to 4), and TOC (Days 10 to 13)
Secondary outcome [13] 0 0
Change from baseline in hematology parameter: Hemoglobin (Hb) (Grams per liter)
Timepoint [13] 0 0
Baseline, On-Therapy (Days 2 to 4), and TOC (Days 10 to 13)
Secondary outcome [14] 0 0
Change from baseline in hematology parameter: Hematocrit (Proportion of red blood cells in blood)
Timepoint [14] 0 0
Baseline, On-Therapy (Days 2 to 4), and TOC (Days 10 to 13)
Secondary outcome [15] 0 0
Change from baseline in hematology parameter: Mean Corpuscular Volume (MCV) (Femtoliters)
Timepoint [15] 0 0
Baseline, On-Therapy (Days 2 to 4), and TOC (Days 10 to 13)
Secondary outcome [16] 0 0
Change from baseline in hematology parameter: Mean Corpuscular Hemoglobin (MCH) (Picograms)
Timepoint [16] 0 0
Baseline, On-Therapy (Days 2 to 4), and TOC (Days 10 to 13)
Secondary outcome [17] 0 0
Change from baseline in clinical chemistry parameters: Blood urea nitrogen [BUN], glucose [non-fasting], calcium, chloride, sodium, magnesium, phosphate, and potassium levels (Millimoles per liter)
Timepoint [17] 0 0
Baseline, On-Therapy (Days 2 to 4), and TOC (Days 10 to 13)
Secondary outcome [18] 0 0
Change from baseline in clinical chemistry parameters: Total bilirubin, direct bilirubin and creatinine levels (Micromoles per liter)
Timepoint [18] 0 0
Baseline, On-Therapy (Days 2 to 4), and TOC (Days 10 to 13)
Secondary outcome [19] 0 0
Change from baseline in clinical chemistry parameters: albumin and total protein levels (Gram per liter)
Timepoint [19] 0 0
Baseline, On-Therapy (Days 2 to 4), and TOC (Days 10 to 13)
Secondary outcome [20] 0 0
Change from baseline in clinical chemistry parameters: Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase levels (International units per liter)
Timepoint [20] 0 0
Baseline, On-Therapy (Days 2 to 4), and TOC (Days 10 to 13)
Secondary outcome [21] 0 0
Change from Baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP) (Millimeters of mercury [mmHg])
Timepoint [21] 0 0
Baseline, On-Therapy (Days 2 to 4), and TOC (Days 10 to 13)
Secondary outcome [22] 0 0
Change from baseline in pulse rate (Beats per minute)
Timepoint [22] 0 0
Baseline, On-Therapy (Days 2 to 4), and TOC (Days 10 to 13)
Secondary outcome [23] 0 0
Change from baseline in body temperature (Degrees Celsius)
Timepoint [23] 0 0
Baseline, On-Therapy (Days 2 to 4), and TOC (Days 10 to 13)
Secondary outcome [24] 0 0
Change from baseline in heart rate (Beats per minute)
Timepoint [24] 0 0
Baseline, On-Therapy (Days 2 to 4), and TOC (Days 10 to 13)
Secondary outcome [25] 0 0
Change from baseline in electrocardiogram parameters: PR Interval, QRS Duration, QT Interval, QT interval corrected for heart rate according Fridericia's formula (QTcF) and Bazett's formula (QTcB) (Milliseconds [msec])
Timepoint [25] 0 0
Baseline, On-Therapy (Days 2 to 4), and TOC (Days 10 to 13)
Secondary outcome [26] 0 0
Plasma concentration of gepotidacin
Timepoint [26] 0 0
Up to Day 4
Secondary outcome [27] 0 0
Urine concentration of gepotidacin
Timepoint [27] 0 0
Up to Day 4

Eligibility
Key inclusion criteria
- The participant has a body weight >=40 kilograms (kg).

- The participant has 2 or more of the following clinical signs and symptoms of acute
cystitis with onset less than (<) 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 capable of giving signed informed consent/assent.
Minimum age
12 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key 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 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:

- Poorly controlled asthma or chronic obstructive pulmonary disease; Acute severe
pain; Active peptic ulcer disease; Parkinson disease; Myasthenia gravis; a
history of seizure disorder requiring medications for control (this does not
include a history of childhood febrile seizures); Or

- Known acute porphyria.

- 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, in the judgment of the investigator, would not be able or willing to
comply with the protocol or complete study follow-up.

- The participant has acute uncomplicated 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 E. 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 (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
vesicoureteral 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 >=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 corrected
QT (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 at Baseline.

- 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 alanine aminotransferase (ALT) value >2 times upper limit
of normal (ULN).

- The participant has a known total 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
Japan
State/province [1] 0 0
Ibaraki
Country [2] 0 0
Japan
State/province [2] 0 0
Osaka
Country [3] 0 0
Japan
State/province [3] 0 0
Saitama

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
GlaxoSmithKline
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
GlaxoSmithKline
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
US GSK Clinical Trials Call Center
Address 0 0
Country 0 0
Phone 0 0
877-379-3718
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.