NCT05630833已完成3 期
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)
适应症
干预措施
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 380
- 试验地点
- 1
- 主要终点
- Number of Participants With Therapeutic Response (TR) (Combined Per-participant Microbiological and Clinical Success) for Gepotidacin at the Test of Cure (TOC) Visit
研究概览
简要总结
The purpose of this study is to evaluate the consistency of therapeutic response of gepotidacin in female participants with acute uncomplicated cystitis with qualifying bacterial uropathogen(s) at baseline that all are susceptible to nitrofurantoin in Japan, with that from global studies (Studies 204989 [NCT04020341] and 212390 [NCT04187144]).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Nitrofurantoin + Placebo
Active Comparator
干预措施: Nitrofurantoin (Drug)
Gepotidacin + Placebo
Experimental
干预措施: Gepotidacin (Drug)
Gepotidacin + Placebo
Experimental
干预措施: Placebo (Drug)
Nitrofurantoin + Placebo
Active Comparator
干预措施: Placebo (Drug)
结局指标
主要结局
Number of Participants With Therapeutic Response (TR) (Combined Per-participant Microbiological and Clinical Success) for Gepotidacin at the Test of Cure (TOC) Visit
时间窗: At TOC visit (Days 9 to 16)
TR at TOC (success/failure) is a measure of the overall efficacy response. A therapeutic success at TOC referred to participant who have been deemed both a microbiological success (reduction of all qualifying bacterial uropathogens recovered at BL to \<10\^3 colony forming units per milliliter \[CFU/mL\] without receiving other systemic antimicrobials \[AB\] before the TOC visit) and a clinical success (resolution of symptoms of acute cystitis present at BL and no new symptoms without receiving other AB before the TOC visit \[or AB for uUTI on day of TOC visit\]). Lack of clinical or microbiological success (including missing outcome assessments) was considered as therapeutic failure.
次要结局
- Number of Participants With Therapeutic Response (TR) of Gepotidacin Compared to Nitrofurantoin at the Test of Cure (TOC) Visit - Micro-ITT NTF-S Population(At TOC visit (Days 9 to 16))
- Number of Participants With Clinical Outcome at the TOC Visit - Micro-ITT NTF-S Population(At TOC visit (Days 9 to 16))
- Number of Participants With Clinical Response at the TOC Visit - Micro-ITT NTF-S Population(At TOC visit (Days 9 to 16))
- Number of Participants With Microbiological Outcome (MO) at the TOC Visit -Micro-ITT NTF-S Population(At TOC visit (Days 9 to 16))
- Number of Participants With Microbiological Response at the TOC Visit -Micro-ITT NTF-S Population(At TOC visit (Days 9 to 16))
- Number of Participants With Therapeutic Response (TR) at the TOC Visit(At TOC visit (Days 9 to 16))
- Number of Participants With Clinical Outcome at the TOC Visit(At TOC visit (Days 9 to 16))
- Number of Participants With Clinical Response at the TOC Visit(At TOC visit (Days 9 to 16))
- Number of Participants With Microbiological Outcome at the TOC Visit(At TOC visit (Days 9 to 16))
- Number of Participants With Microbiological Response at the TOC Visit(At TOC visit (Days 9 to 16))
- Number of Participants With Investigator Assessed Clinical Response(At TOC visit (Days 9 to 16))
- Number of Participants With Treatment-emergent Adverse Events (TEAEs)(From first dose (Day 1) to Follow-up visit (Days 21 to 31))
- Number of Participants With Serious AEs (SAEs) and Adverse Events of Special Interest (AESIs)(From first dose (Day 1) to Follow-up visit (Days 21 to 31))
- Number of Participants With Urinalysis Dipstick Results(Baseline (Day 1), On-Therapy (Days 2 to 5), and at TOC visit (Days 9 to 16))
- Change From Baseline (CFB) in Electrocardiograms (ECGs): Heart Rate(Baseline (Day 1), On-Therapy (Days 2 to 5), and at TOC visit (Days 9 to 16))
- Change From Baseline (CFB) in Electrocardiograms (ECGs): PR, QRS, QT and QTcF(Baseline (Day 1), On-Therapy (Days 2 to 5), and at TOC visit (Days 9 to 16))
- Change From Baseline (CFB) in Vital Sign: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)(Baseline (Day 1), On-Therapy (Days 2 to 5), and at TOC visit (Days 9 to 16))
- Change From Baseline (CFB) in Vital Sign: Temperature(Baseline (Day 1), On-Therapy (Days 2 to 5), and at TOC visit (Days 9 to 16))
- Change From Baseline (CFB) in Vital Sign: Pulse Rate(Baseline (Day 1), On-Therapy (Days 2 to 5), and at TOC visit (Days 9 to 16))
- Plasma Concentrations of Gepotidacin(Baseline (Day 1 at 0-2h & >2h Post dose), Day 2 to 5 at Pre-dose, 0-2h & >2h Post Dose)
- Urine Concentrations of Gepotidacin(Baseline (Day 1 at 0-2h & >2h Post dose), Day 2 to 5 at Pre-dose, 0-2h & >2h Post Dose)
- Change From Baseline (CFB) in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, and Platelets at On Therapy and Test of Cure Visit(Baseline (Day 1), On-Therapy (Days 2 to 5), and at TOC visit (Days 9 to 16))
- Change From Baseline (CFB) in Hematology Parameter-Hemoglobin Level at On Therapy and Test of Cure Visit(Baseline (Day 1), On-Therapy (Days 2 to 5), and at TOC visit (Days 9 to 16))
- Change From Baseline (CFB) in Hematology Parameter- Hematocrit Level at On Therapy and Test of Cure Visit(Baseline (Day 1), On-Therapy (Days 2 to 5), and at TOC visit (Days 9 to 16))
- Change From Baseline (CFB) in Hematology Parameter- Erythrocytes Count at On Therapy and Test of Cure Visit(Baseline (Day 1), On-Therapy (Days 2 to 5), and at TOC visit (Days 9 to 16))
- Change From Baseline (CFB) in Hematology Parameter - Mean Corpuscular Hemoglobin (MCH) at On Therapy and Test of Cure Visit(Baseline (Day 1), On-Therapy (Days 2 to 5), and at TOC visit (Days 9 to 16))
- Change From Baseline (CFB) in Hematology Parameter - Mean Corpuscular Volume (MCV) at On Therapy and Test of Cure Visit(Baseline (Day 1), On-Therapy (Days 2 to 5), and at TOC visit (Days 9 to 16))
- Change From Baseline (CFB) in Clinical Chemistry Parameters - Calcium, Glucose, Potassium, Magnesium, Phosphate, Sodium, and Urea Nitrogen Levels at On Therapy and Test of Cure Visit(Baseline (Day 1), On-Therapy (Days 2 to 5), and at TOC visit (Days 9 to 16))
- Change From Baseline (CFB) in Clinical Chemistry Parameters - Serum Chloride at On Therapy and Test of Cure Visit(Baseline (Day 1), On-Therapy (Days 2 to 5), and at TOC visit (Days 9 to 16))
- Change From Baseline (CFB) in Clinical Chemistry Parameters - Direct Bilirubin, Total Bilirubin and Creatinine Levels at On Therapy and Test of Cure Visit(Baseline (Day 1), On-Therapy (Days 2 to 5), and at TOC visit (Days 9 to 16))
- Change From Baseline (CFB) in Clinical Chemistry Parameters - Creatinine Clearance at On Therapy and Test of Cure Visit(Baseline (Day 1), On-Therapy (Days 2 to 5), and at TOC visit (Days 9 to 16))
- Change From Baseline (CFB) in Clinical Chemistry Parameters - Albumin and Protein Levels at On Therapy and Test of Cure Visit(Baseline (Day 1), On-Therapy (Days 2 to 5), and at TOC visit (Days 9 to 16))
- Change From Baseline (CFB) in Clinical Chemistry Parameters - Alkaline Phosphatase (ALP) and Alanine Aminotransferase (ALT) Levels at On Therapy and Test of Cure Visit(Baseline (Day 1), On-Therapy (Days 2 to 5), and at TOC visit (Days 9 to 16))
- Change From Baseline (CFB) in Clinical Chemistry Parameter - Aspartate Aminotransferase (AST) Levels at On Therapy and Test of Cure Visit(Baseline (Day 1), On-Therapy (Days 2 to 5), and at TOC visit (Days 9 to 16))
研究者
研究点 (1)
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