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临床试验/NCT04187144
NCT04187144已完成3 期

A Phase III, Randomized, Multicenter, Parallel-Group, Double-Blind, Double-Dummy Study in Adolescent and Adult Female Participants Comparing the Efficacy and Safety of Gepotidacin to Nitrofurantoin in the Treatment of Uncomplicated Urinary Tract Infection (Acute Cystitis)

GlaxoSmithKline1 个研究点 分布在 1 个国家目标入组 1,606 人开始时间: 2020年4月23日最近更新:
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试验速览

阶段
3 期
状态
已完成
入组人数
1,606
试验地点
1
主要终点
Number of Participants With Therapeutic Response (TR) (Combined Per Participant Clinical and Microbiological Response) at the Test-of-Cure (TOC) Visit - Micro-ITT NTF-S Population
研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

The study will be conducted to evaluate the therapeutic response (combined per participant microbiological and clinical response) of oral gepotidacin compared to oral nitrofurantoin for treatment of uncomplicated UTI (acute cystitis) in adolescent and adult female participants.

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 is >=12 years of age at the time of signing the informed consent/assent and has a body weight >=40 kilogram (kg).
  • •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.
  • •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 female.
  • •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 has a history of sensitivity to the study treatment, or components thereof, or a history of a drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates her participation.
  • •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; 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 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.
  • •The participant has acute 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 Escherichia 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 (for example [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 vesico-ureteral 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 >=101.4 degree Fahrenheit (>=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 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.
  • •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 ALT value >2 times upper limit of normal (ULN).
  • •The participant has a known 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

Gepotidacin

Experimental

Participants will be administered oral doses of 1500 milligrams (mg) gepotidacin plus nitrofurantoin matching placebo BID; approximately every 12 hours for 5 days.

干预措施: Gepotidacin (Drug)

Gepotidacin

Experimental

Participants will be administered oral doses of 1500 milligrams (mg) gepotidacin plus nitrofurantoin matching placebo BID; approximately every 12 hours for 5 days.

干预措施: Placebo matching nitrofurantoin (Drug)

Nitrofurantoin

Active Comparator

Participants will be administered oral doses of 100 mg nitrofurantoin plus gepotidacin matching placebo BID; approximately every 12 hours for 5 days.

干预措施: Nitrofurantoin (Drug)

Nitrofurantoin

Active Comparator

Participants will be administered oral doses of 100 mg nitrofurantoin plus gepotidacin matching placebo BID; approximately every 12 hours for 5 days.

干预措施: Placebo matching gepotidacin (Drug)

结局指标

主要结局

Number of Participants With Therapeutic Response (TR) (Combined Per Participant Clinical and Microbiological Response) at the Test-of-Cure (TOC) Visit - Micro-ITT NTF-S Population

时间窗: 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 Baseline \[BL\] 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.

Number of Participants With Therapeutic Response (TR) (Combined Per Participant Clinical and Microbiological Response) at the Test-of-Cure (TOC) Visit - Micro-ITT NTF-S (IA Set)

时间窗: 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 Baseline \[BL\] 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 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 Microbiological Outcome (MO) at the TOC Visit - Micro-ITT NTF-S Population(TOC Visit (Days 9 to 16))
  • Number of Participants With Clinical Outcome at the TOC Visit - Micro-ITT NTF-S Population(TOC visit (Days 9 to 16))
  • Number of Participants With Clinical Response at the TOC Visit - Micro-ITT NTF-S Population(TOC visit (Days 9 to 16))
  • Absolute Mean Values of Urine Potential of Hydrogen (pH)(Baseline (on or before Day 1), On-Therapy (Days 2 to 5), and Test of cure (Days 9 to 16))
  • Number of Participants With Microbiological Response at the TOC Visit - Micro-ITT NTF-S Population(TOC visit (Days 9 to 16))
  • Number of Participants With Therapeutic Response (TR) (Combined Per Participant Clinical and Microbiological Response) at the Follow up (FU) Visit - Micro-ITT NTF-S Population(FU visit (Days 21 to 31))
  • Change From Baseline in Body Temperature(Baseline (on or before Day 1), On-Therapy (Days 2 to 5), and Test of cure (Days 9 to 16))
  • Number of Participants With Clinical Outcome at the Follow up (FU) Visit - Micro-ITT NTF-S Population(FU visit (Days 21 to 31))
  • Number of Participants With Clinical Response at the Follow up (FU) Visit - Micro-ITT NTF-S Population(FU visit (Days 21 to 31))
  • Number of Participants With Microbiological Outcome (MO) at the Follow up (FU) Visit - Micro-ITT NTF-S Population(FU visit (Days 21 to 31))
  • Number of Participants With Microbiological Response at the Follow up (FU) Visit - Micro-ITT NTF-S Population(FU visit (Days 21 to 31))
  • Number of Participants With Clinical Outcome at the TOC Visit - Intent-to-Treat (ITT) Population(TOC visit (Days 9 to 16))
  • Number of Participants With Clinical Response at the TOC Visit - Intent-to-Treat (ITT) Population(TOC visit (Days 9 to 16))
  • Number of Participants With Clinical Outcome at the Follow up (FU) Visit - Intent-to-Treat (ITT) Population(FU visit (Days 21 to 31))
  • Number of Participants With Clinical Response at the Follow up (FU) Visit - Intent-to-Treat (ITT) Population(FU visit (Days 21 to 31))
  • Number of Participants With Treatment-emergent Adverse Events (TEAEs)(From the time of first dose (Day 1) through the final follow-up visit (Day 21-31))
  • Number of Participants With Serious Adverse Events (SAEs)(From the time of first dose (Day 1) through the final follow-up visit (Day 21-31))
  • Change From Baseline in Hematology Parameters: Neutrophil Count, Lymphocyte Count, Monocyte Count, Eosinophil Count, Basophil Count and Platelet Count at On Therapy and Test of Cure Visit(Baseline (on or before Day 1), On-Therapy (Days 2 to 5), and Test of cure (Days 9 to 16))
  • Change From Baseline in Hematology Parameter: Hemoglobin Level(Baseline (on or before Day 1), On-Therapy (Days 2 to 5), and Test of cure (Days 9 to 16))
  • Number of Participants With Urinalysis Dipstick Results(Baseline (on or before Day 1), On-Therapy (Days 2 to 5), and Test of cure (Days 9 to 16))
  • Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at On-Therapy and Test of Cure Visit(Baseline (on or before Day 1), On-Therapy (Days 2 to 5), and Test of cure (Days 9 to 16))
  • Change From Baseline in Pulse Rate at On Therapy and Test of Cure Visit(Baseline (on or before Day 1), On-Therapy (Days 2 to 5), and Test of cure (Days 9 to 16))
  • Number of Participants With Maximum Change From Baseline in Electrocardiograms (ECG) Parameter: QT Interval Corrected for Heart Rate According to Bazett's Formula (QTcB) at Worst-case Post-baseline(Up to Day 31)
  • Change From Baseline in Hematology Parameter: Hematocrit Level(Baseline (on or before Day 1), On-Therapy (Days 2 to 5), and Test of cure (Days 9 to 16))
  • Change From Baseline in Hematology Parameter: Erythrocytes (RBC) Count(Baseline (on or before Day 1), On-Therapy (Days 2 to 5), and Test of cure (Days 9 to 16))
  • Change From Baseline in Hematology Parameter: Mean Corpuscular Hemoglobin (MCH)(Baseline (on or before Day 1), On-Therapy (Days 2 to 5), and Test of cure (Days 9 to 16))
  • Change From Baseline in Hematology Parameter: Mean Corpuscular Volume (MCV)(Baseline (on or before Day 1), On-Therapy (Days 2 to 5), and Test of cure (Days 9 to 16))
  • Change From Baseline in Clinical Chemistry Parameters: Serum Blood Urea Nitrogen (BUN), Glucose Non-fasting, Calcium, Chloride, Sodium, Magnesium, Phosphate, and Potassium Levels(Baseline (on or before Day 1), On-Therapy (Days 2 to 5), and Test of cure (Days 9 to 16))
  • Change From Baseline in Clinical Chemistry Parameters: Total Bilirubin, Direct Bilirubin and Creatinine Levels(Baseline (on or before Day 1), On-Therapy (Days 2 to 5), and Test of cure (Days 9 to 16))
  • Change From Baseline in Clinical Chemistry Parameters: Albumin and Protein Levels(Baseline (on or before Day 1), On-Therapy (Days 2 to 5), and Test of cure (Days 9 to 16))
  • Absolute Mean Values of Urine Specific Gravity(Baseline (on or before Day 1), On-Therapy (Days 2 to 5), and Test of cure (Days 9 to 16))
  • Change From Baseline in Clinical Chemistry Parameters: Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) and Alkaline Phosphatase (ALP) Levels(Baseline (on or before Day 1), On-Therapy (Days 2 to 5), and Test of cure (Days 9 to 16))
  • Number of Participants With Maximum Change From Baseline in Electrocardiograms (ECG) Parameter- QT Interval Corrected for Heart Rate According to Fridericia's Formula (QTcF) at Worst-case Post-baseline(Up to Day 31)

研究者

申办方类型
Industry
责任方
Sponsor

研究点 (1)

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