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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04187144




Registration number
NCT04187144
Ethics application status
Date submitted
3/12/2019
Date registered
5/12/2019

Titles & IDs
Public title
Comparative Study to Evaluate Efficacy and Safety of Gepotidacin to Nitrofurantoin in Treatment of Uncomplicated Urinary Tract Infection (UTI)
Scientific title
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)
Secondary ID [1] 0 0
2020-000553-27
Secondary ID [2] 0 0
212390
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Urinary Tract Infections 0 0
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

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

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

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


Treatment: Drugs: Gepotidacin
Gepotidacin will be available as tablets at a unit dose strength of 750mg. Participants will administer two 750 mg tablets, BID. Each dose will be taken with water after consumption of food.

Treatment: Drugs: Placebo matching nitrofurantoin
Placebo matching nitrofurantoin will be available as over-encapsulated unit-dose capsules. Participants will administer 1 capsule BID. Each dose should be taken with water after consumption of food.

Treatment: Drugs: Nitrofurantoin
Nitrofurantoin will be available as over-encapsulated 100 mg capsules containing 25 mg nitrofurantoin macrocrystals and 75 mg nitrofurantoin. Participants will administer one 100 mg capsule, BID. Each dose should be taken with water after consumption of food.

Treatment: Drugs: Placebo matching gepotidacin
Placebo matching gepotidacin will be available as unit-dose gepotidacin placebo-to-match tablet. Participants will administer two tablets, BID. Each dose should be taken with water after consumption of food.

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

Outcomes
Primary outcome [1] 0 0
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)
Timepoint [1] 0 0
TOC visit (Days 9 to 16)
Primary outcome [2] 0 0
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
Timepoint [2] 0 0
TOC visit (Days 9 to 16)
Secondary outcome [1] 0 0
Number of Participants With Clinical Outcome at the TOC Visit - Micro-ITT NTF-S Population
Timepoint [1] 0 0
TOC visit (Days 9 to 16)
Secondary outcome [2] 0 0
Number of Participants With Clinical Response at the TOC Visit - Micro-ITT NTF-S Population
Timepoint [2] 0 0
TOC visit (Days 9 to 16)
Secondary outcome [3] 0 0
Number of Participants With Microbiological Outcome (MO) at the TOC Visit - Micro-ITT NTF-S Population
Timepoint [3] 0 0
TOC Visit (Days 9 to 16)
Secondary outcome [4] 0 0
Number of Participants With Microbiological Response at the TOC Visit - Micro-ITT NTF-S Population
Timepoint [4] 0 0
TOC visit (Days 9 to 16)
Secondary outcome [5] 0 0
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
Timepoint [5] 0 0
FU visit (Days 21 to 31)
Secondary outcome [6] 0 0
Number of Participants With Clinical Outcome at the Follow up (FU) Visit - Micro-ITT NTF-S Population
Timepoint [6] 0 0
FU visit (Days 21 to 31)
Secondary outcome [7] 0 0
Number of Participants With Clinical Response at the Follow up (FU) Visit - Micro-ITT NTF-S Population
Timepoint [7] 0 0
FU visit (Days 21 to 31)
Secondary outcome [8] 0 0
Number of Participants With Microbiological Outcome (MO) at the Follow up (FU) Visit - Micro-ITT NTF-S Population
Timepoint [8] 0 0
FU visit (Days 21 to 31)
Secondary outcome [9] 0 0
Number of Participants With Microbiological Response at the Follow up (FU) Visit - Micro-ITT NTF-S Population
Timepoint [9] 0 0
FU visit (Days 21 to 31)
Secondary outcome [10] 0 0
Number of Participants With Clinical Outcome at the TOC Visit - Intent-to-Treat (ITT) Population
Timepoint [10] 0 0
TOC visit (Days 9 to 16)
Secondary outcome [11] 0 0
Number of Participants With Clinical Response at the TOC Visit - Intent-to-Treat (ITT) Population
Timepoint [11] 0 0
TOC visit (Days 9 to 16)
Secondary outcome [12] 0 0
Number of Participants With Clinical Outcome at the Follow up (FU) Visit - Intent-to-Treat (ITT) Population
Timepoint [12] 0 0
FU visit (Days 21 to 31)
Secondary outcome [13] 0 0
Number of Participants With Clinical Response at the Follow up (FU) Visit - Intent-to-Treat (ITT) Population
Timepoint [13] 0 0
FU visit (Days 21 to 31)
Secondary outcome [14] 0 0
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Timepoint [14] 0 0
From the time of first dose (Day 1) through the final follow-up visit (Day 21-31)
Secondary outcome [15] 0 0
Number of Participants With Serious Adverse Events (SAEs)
Timepoint [15] 0 0
From the time of first dose (Day 1) through the final follow-up visit (Day 21-31)
Secondary outcome [16] 0 0
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
Timepoint [16] 0 0
Baseline (on or before Day 1), On-Therapy (Days 2 to 5), and Test of cure (Days 9 to 16)
Secondary outcome [17] 0 0
Change From Baseline in Hematology Parameter: Hemoglobin Level
Timepoint [17] 0 0
Baseline (on or before Day 1), On-Therapy (Days 2 to 5), and Test of cure (Days 9 to 16)
Secondary outcome [18] 0 0
Change From Baseline in Hematology Parameter: Hematocrit Level
Timepoint [18] 0 0
Baseline (on or before Day 1), On-Therapy (Days 2 to 5), and Test of cure (Days 9 to 16)
Secondary outcome [19] 0 0
Change From Baseline in Hematology Parameter: Erythrocytes (RBC) Count
Timepoint [19] 0 0
Baseline (on or before Day 1), On-Therapy (Days 2 to 5), and Test of cure (Days 9 to 16)
Secondary outcome [20] 0 0
Change From Baseline in Hematology Parameter: Mean Corpuscular Hemoglobin (MCH)
Timepoint [20] 0 0
Baseline (on or before Day 1), On-Therapy (Days 2 to 5), and Test of cure (Days 9 to 16)
Secondary outcome [21] 0 0
Change From Baseline in Hematology Parameter: Mean Corpuscular Volume (MCV)
Timepoint [21] 0 0
Baseline (on or before Day 1), On-Therapy (Days 2 to 5), and Test of cure (Days 9 to 16)
Secondary outcome [22] 0 0
Change From Baseline in Clinical Chemistry Parameters: Serum Blood Urea Nitrogen (BUN), Glucose Non-fasting, Calcium, Chloride, Sodium, Magnesium, Phosphate, and Potassium Levels
Timepoint [22] 0 0
Baseline (on or before Day 1), On-Therapy (Days 2 to 5), and Test of cure (Days 9 to 16)
Secondary outcome [23] 0 0
Change From Baseline in Clinical Chemistry Parameters: Total Bilirubin, Direct Bilirubin and Creatinine Levels
Timepoint [23] 0 0
Baseline (on or before Day 1), On-Therapy (Days 2 to 5), and Test of cure (Days 9 to 16)
Secondary outcome [24] 0 0
Change From Baseline in Clinical Chemistry Parameters: Albumin and Protein Levels
Timepoint [24] 0 0
Baseline (on or before Day 1), On-Therapy (Days 2 to 5), and Test of cure (Days 9 to 16)
Secondary outcome [25] 0 0
Change From Baseline in Clinical Chemistry Parameters: Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) and Alkaline Phosphatase (ALP) Levels
Timepoint [25] 0 0
Baseline (on or before Day 1), On-Therapy (Days 2 to 5), and Test of cure (Days 9 to 16)
Secondary outcome [26] 0 0
Number of Participants With Urinalysis Dipstick Results
Timepoint [26] 0 0
Baseline (on or before Day 1), On-Therapy (Days 2 to 5), and Test of cure (Days 9 to 16)
Secondary outcome [27] 0 0
Absolute Mean Values of Urine Specific Gravity
Timepoint [27] 0 0
Baseline (on or before Day 1), On-Therapy (Days 2 to 5), and Test of cure (Days 9 to 16)
Secondary outcome [28] 0 0
Absolute Mean Values of Urine Potential of Hydrogen (pH)
Timepoint [28] 0 0
Baseline (on or before Day 1), On-Therapy (Days 2 to 5), and Test of cure (Days 9 to 16)
Secondary outcome [29] 0 0
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at On-Therapy and Test of Cure Visit
Timepoint [29] 0 0
Baseline (on or before Day 1), On-Therapy (Days 2 to 5), and Test of cure (Days 9 to 16)
Secondary outcome [30] 0 0
Change From Baseline in Pulse Rate at On Therapy and Test of Cure Visit
Timepoint [30] 0 0
Baseline (on or before Day 1), On-Therapy (Days 2 to 5), and Test of cure (Days 9 to 16)
Secondary outcome [31] 0 0
Change From Baseline in Body Temperature
Timepoint [31] 0 0
Baseline (on or before Day 1), On-Therapy (Days 2 to 5), and Test of cure (Days 9 to 16)
Secondary outcome [32] 0 0
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
Timepoint [32] 0 0
Up to Day 31
Secondary outcome [33] 0 0
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
Timepoint [33] 0 0
Up to Day 31

Eligibility
Key inclusion criteria
* 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.
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 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:

1. Poorly controlled asthma or chronic obstructive pulmonary disease; Acute severe pain,; Active peptic ulcer disease; Parkinson disease; Myasthenia gravis; Or
2. Known acute porphyria.
3. 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.

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
Completed
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)
NSW,QLD
Recruitment hospital [1] 0 0
GSK Investigational Site - Maroubra
Recruitment hospital [2] 0 0
GSK Investigational Site - Sydney
Recruitment hospital [3] 0 0
GSK Investigational Site - Tarragindi
Recruitment postcode(s) [1] 0 0
2035 - Maroubra
Recruitment postcode(s) [2] 0 0
2010 - Sydney
Recruitment postcode(s) [3] 0 0
4121 - Tarragindi
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
District of Columbia
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Idaho
Country [7] 0 0
United States of America
State/province [7] 0 0
Maryland
Country [8] 0 0
United States of America
State/province [8] 0 0
Massachusetts
Country [9] 0 0
United States of America
State/province [9] 0 0
Montana
Country [10] 0 0
United States of America
State/province [10] 0 0
Nebraska
Country [11] 0 0
United States of America
State/province [11] 0 0
New Jersey
Country [12] 0 0
United States of America
State/province [12] 0 0
New York
Country [13] 0 0
United States of America
State/province [13] 0 0
North Carolina
Country [14] 0 0
United States of America
State/province [14] 0 0
North Dakota
Country [15] 0 0
United States of America
State/province [15] 0 0
Ohio
Country [16] 0 0
United States of America
State/province [16] 0 0
Oregon
Country [17] 0 0
United States of America
State/province [17] 0 0
Pennsylvania
Country [18] 0 0
United States of America
State/province [18] 0 0
South Carolina
Country [19] 0 0
United States of America
State/province [19] 0 0
Tennessee
Country [20] 0 0
United States of America
State/province [20] 0 0
Texas
Country [21] 0 0
United States of America
State/province [21] 0 0
Utah
Country [22] 0 0
United States of America
State/province [22] 0 0
Virginia
Country [23] 0 0
Bulgaria
State/province [23] 0 0
Gabrovo
Country [24] 0 0
Bulgaria
State/province [24] 0 0
Haskovo
Country [25] 0 0
Bulgaria
State/province [25] 0 0
Kyustendil
Country [26] 0 0
Bulgaria
State/province [26] 0 0
Montana
Country [27] 0 0
Bulgaria
State/province [27] 0 0
Pleven
Country [28] 0 0
Bulgaria
State/province [28] 0 0
Ruse
Country [29] 0 0
Bulgaria
State/province [29] 0 0
Shumen
Country [30] 0 0
Bulgaria
State/province [30] 0 0
Sofia
Country [31] 0 0
Bulgaria
State/province [31] 0 0
Stara Zagora
Country [32] 0 0
Bulgaria
State/province [32] 0 0
Targovisthe
Country [33] 0 0
India
State/province [33] 0 0
Aurangabad
Country [34] 0 0
India
State/province [34] 0 0
Chandrapur
Country [35] 0 0
India
State/province [35] 0 0
Hyderabad
Country [36] 0 0
India
State/province [36] 0 0
Mumbai
Country [37] 0 0
India
State/province [37] 0 0
Nagpur
Country [38] 0 0
India
State/province [38] 0 0
Nashik
Country [39] 0 0
India
State/province [39] 0 0
New Delhi
Country [40] 0 0
India
State/province [40] 0 0
Pune
Country [41] 0 0
India
State/province [41] 0 0
Rajkot
Country [42] 0 0
India
State/province [42] 0 0
Surat
Country [43] 0 0
Korea, Republic of
State/province [43] 0 0
Ansan-si
Country [44] 0 0
Korea, Republic of
State/province [44] 0 0
Goyang-si, Gyeonggi-do
Country [45] 0 0
Korea, Republic of
State/province [45] 0 0
Hwasun-gun, Jeollanam-do
Country [46] 0 0
Korea, Republic of
State/province [46] 0 0
Incheon
Country [47] 0 0
Korea, Republic of
State/province [47] 0 0
Seoul
Country [48] 0 0
Korea, Republic of
State/province [48] 0 0
Suwon
Country [49] 0 0
Poland
State/province [49] 0 0
Katowice
Country [50] 0 0
Poland
State/province [50] 0 0
Ostrowiec Swietokrzyski
Country [51] 0 0
Poland
State/province [51] 0 0
Swidnik
Country [52] 0 0
Poland
State/province [52] 0 0
Warszawa

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
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
IPD for this study will be made available via the Clinical Study Data Request site.

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Informed consent form (ICF), Clinical study report (CSR)
When will data be available (start and end dates)?
IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.
Available to whom?
Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: http://clinicalstudydatarequest.com


What supporting documents are/will be available?

Results publications and other study-related documents

No documents have been uploaded by study researchers.