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: 1624306-20-2
Other descriptive name: GSK2140944
Concentration unit: mg milli
Sponsors
GlaxoSmithKline Research & Development Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Otherwise healthy participants are eligible to be included in the study only if all of the following criteria apply: Age 1.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. Type of Participant and Disease Characteristics 2.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 (see Appendix 5). 3.The participant has nitrite or pyuria (>15 WBC/HPF or the presence of 3+/large leukocyte esterase) from a pretreatment clean-catch midstream urine sample based on local laboratory procedures. Sex 4. The participant is female. Contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. A female participant is eligible to participate if she is a woman of childbearing potential (WOCBP) who is not pregnant as confirmed by a high sensitivity urine pregnancy test at Baseline (Day 1) regardless of current or prior contraception use or abstinence, is not breastfeeding, or is not a WOCBP. Note: Pregnancy testing requirements, contraceptive guidance, and WOCBP definitions are provided in Appendix 2 and Appendix 6. Additional requirements for pregnancy testing during and after study intervention are located in Appendix 6. The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy. Informed Consent 5.The participant is capable of giving signed informed consent/assent as described in Appendix 3 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 960 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 typefacility 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 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, 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/known Acute porphyria/any surgical or medical condition 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 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, 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- (=38°C), 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-prolongin
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the combined clinical and microbiological efficacy of gepotidacin compared to nitrofurantoin, at the Test-of-Cure (TOC) Visit, in female participants with acute cystitis with qualifying bacterial uropathogen(s) at Baseline that all are susceptible to nitrofurantoin.;Secondary Objective: To assess the: •clinical efficacy of gepotidacin compared to nitrofurantoin, at TOC and Follow-up Visits, in female participants with acute cystitis with qualifying bacterial uropathogen(s) at Baseline that all are susceptible to nitrofurantoin •microbiological efficacy of gepotidacin compared to nitrofurantoin, at the TOC and Follow-up Visits, in female participants with acute cystitis with qualifying bacterial uropathogen(s) at Baseline that all are susceptible to nitrofurantoin •the combined clinical and microbiological efficacy of gepotidacin compared to nitrofurantoin, at Follow-up Visit, in female participants with acute cystitis with qualifying bacterial uropathogen(s) at Baseline that all are susceptible to nitrofurantoin •safety and tolerability of gepotidacin compared to nitrofurantoin 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 • Treatment-emergent adverse events and serious adverse events and change from baseline results for clinical laboratory tests, electrocardiograms, and vital sign measurements • Gram stain, quantitative bacteriology culture, and in vitro antimicrobial susceptibility test results at the Baseline, On-therapy, TOC, and Followup Visits • Therapeutic response (combined microbiological and clinical response), clinical outcome and response, and microbiological outcome and response by uropathogen at each visit • Microbiological outcome at the On-therapy Visit • Clinical outcome at the On-therapy Visit • Investigator assessment of clinical response at the TOC and Follow-up Visits, as data permits • 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
Australia, Bulgaria, India, Poland, United States
Contacts
Public ContactClinical Trials Helpdesk
GlaxoSmithKline Research & Development Ltd.
Outcome results
None listed