Urinary Tract Infection (Acute Cystitis) MedDRA version: 20.0 Level: PT Classification code 10011781 Term: Cystitis System Organ Class: 10021881 - Infections and infestations
Conditions
Interventions
Product Name: Gepotidacin
Product Code: GSK2140944
Pharmaceutical Form: Tablet
INN or Proposed INN: Gepotidacin
CAS Number: 1075236-89-3
Other descriptive name: GSK2140944
Concentration unit: mg milli
Sponsors
GlaxoSmithKline Research & Development Limited
Eligibility
Sex/Gender
All
Inclusion 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 kg. Note: Although participants as young as 12 years may enroll in the study, study sites must follow their institutional ethics committee and local country/national regulatory guidelines and enrollment will be contingent upon such approvals regarding the allowed lower age limit for clinical study participants. -The participant has 2 or more of the following clinical signs and symptoms of acute cystitis with onset =72 hours prior to study entry: dysuria, frequency, urgency, or lower abdominal pain -The participant has nitrite or pyuria (>15WBC/HPFor the presence of 3+/large leukocyte esterase)from a pretreatment clean-catch midstream urine sample based on local laboratory procedures. -The participant is female. A female participant is eligible to participate if she is a woman of childbearing potential (WOCBP) who is not pregnant as confirmed by high sensitivity urine pregnancy test at Baseline (day 1) regardless of current or prior contraception or abstinence, is not breastfeeding, or is not a WOCBP (note: pregnancy test requirements, contraceptive guidance and WOCBP definitions are provided in Appendix 6 of Protocol). - The participant is capable of giving signed informed consent/assent,which includes compliance with the requirements and restrictions listed in the informed consent form (ICF)/assent form and in this protocol. Are the trial subjects under 18? yes Number of subjects for this age range: 120 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 1200 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 120
Exclusion criteria
Exclusion criteria: -The participant resides in a nursing home or dependent care type-facility AND has a body mass index =40.0 kg/m2 or a body mass index =35.0kg/m2 and is experiencing obesity-related health conditions such as 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, 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, and participants receiving immunosuppressive therapy, including corticosteroid therapy. -Participants with a known CD4 count of <200 cells/mm3 should not be enrolled. -Participant has any of the following: /Medical condition that requires medication that may be impacted by inhibition of acetylcholinesterase, such as: Poorly controlled asthma or chronic obstructive pulmonary disease at Baseline and, in the opinion of the investigator, not stable on current therapy/Acute severe pain, uncontrolled with conventional medical management/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 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 and in the judgment of the investigator, would not be able or willing to comply with the protocol or complete study follow-up. -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 -Participant has symptoms known or suspected to be caused by another disease process,ex overactive bladder, chronic incontinence, or chronic interstitial cystitis, that interfere with the clinical efficacy assessments. -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, or neurogenic bladder, or the participant has a history of anatomical or functional abnormalities of the urinary tract -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, signs and symptom onset =96hours before study entry, or a temperature =101°F, flank pain, chills, or any other manifestations suggestive of upper UTI. -Participant has known anuria, oliguria, or significant impairment of renal function or presents with vaginal discharge at Baseline. -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 OR has a recent history of vasovagal syncopeor episodes of symptomatic bradycardia or brady arrhythmia within the last 12 months. -Participant is taking QT-pro
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the combined clinical and microbiological efficacy of gepotidacin compared tonitrofurantoin, at the Test-of-Cure (TOC) Visit,in female participants with acute cystitisin the MicrobiologicalIntent-to-Treat nitrofurantoin-Susceptible (micro-ITT NTF-S) Population ;Secondary Objective: - To assess the clinical efficacy of gepotidacin compared tonitrofurantoin, at the TOC and Follow-up Visits,in female participants with acute cystitis in the Intent-to-Treat Population -To assess the microbiological efficacy of gepotidacin compared tonitrofurantoin, at the TOC and Follow-up Visits,in female participants with acute cystitis in the micro-ITT NTF-S Population - To assess the therapeutic response of acute cystitis after treatment with gepotidacin or nitrofurantoin, at the Follow-up Visit,in female participants with acute cystitis in themicro-ITT NTF-S Population- -To determine the plasma and urine pharmacokinetic(PK) concentrations of gepotidacin in female participants with acute cystitis -To assess the safety and tolerability of gepotidacin comparedtonitrofurantoin in female participants with acute cystitis ;Primary end point(s): Therapeutic response (combined per-participant microbiological and clinical response) at the TOC Visit ;Timepoint(s) of evaluation of this end point: The primary efficacy endpoint will be the therapeutic response (combined per-participant microbiological and clinical response) at the TOC Visit (i.e., 10 to 13 days after randomization, which is also 5 to 8 days after completion of study treatment) in participants who have a qualifying bacterial uropathogen at Baseline | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): -Clinical outcome and response at the TOC and Follow-up Visits. -Microbiological outcome and response at the TOC and Follow-up Visits. -Therapeutic response (combined per-participant microbiological and clinical response) at the Follow-up Visit. -Gepotidacin plasma and urine concentrations(peak and trough). -Treatment-emergent AEs and serious AEs (SAEs) and change from baseline results for clinical laboratory tests and vital sign measurements. -Gram stain, quantitative bacteriology culture, and in vitro antimicrobial susceptibility test results at the Baseline, On-therapy, TOC, and Follow-up Visits -Therapeutic response (combined per-participant microbiological and clinical response), clinical outcome and response, and microbiological outcome and response at each visit in participants who have a qualifying bacterial uropathogen at Baseline, including participants with a subset of isolates resistant to other antimicrobials. -Gepotidacin exposure and clinical and microbiological response at the TOC Visit, if data permit. -Microbiological outcome at the On-therapy Visit -Clinical outcome at the On-therapy Visit -Urinary tract infection Activity Impairment Assessment (AIA) scores at the Baseline, On-therapy, TOC, and Follow-up Visits;Timepoint(s) of evaluation of this end point: Participants will return to the study site on Day 28 (±3) for a Follow-up Visit. | — |
Countries
Bulgaria, Germany, Greece, Hungary, India, Mexico, Romania, Spain, United Kingdom, United States
Contacts
Public ContactClinical Trials Helpdesk
GlaxoSmithKline Research & Development Ltd.
Outcome results
None listed