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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT04187144
Ethics application status
Date submitted
3/12/2019
Date registered
5/12/2019
Date last updated
10/12/2020

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
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 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 at the Test-of-Cure (TOC) visit - A therapeutic success refers to participants who have been deemed both a "microbiological success" and a "clinical success". All other combinations (other than clinical success + microbiological success) will be deemed failures for therapeutic response.
Timepoint [1] 0 0
Up to Day 13
Secondary outcome [1] 0 0
Number of participants with clinical outcome at the TOC visit - The clinical signs and symptoms score for acute cystitis will be determined by the investigator and used to programmatically determine the clinical outcome.
Timepoint [1] 0 0
Up to Day 13
Secondary outcome [2] 0 0
Number of participants with clinical outcome at the follow up visit - The clinical signs and symptoms score for acute cystitis will be determined by the investigator and used to programmatically determine the clinical outcome.
Timepoint [2] 0 0
Up to Day 31
Secondary outcome [3] 0 0
Number of participants with clinical response at the TOC visit - The clinical signs and symptoms score for acute cystitis will be determined by the investigator and used to programmatically determine the clinical response.
Timepoint [3] 0 0
Up to Day 13
Secondary outcome [4] 0 0
Number of participants with clinical response at the follow up visit - The clinical signs and symptoms score for acute cystitis will be determined by the investigator and used to programmatically determine the clinical response.
Timepoint [4] 0 0
Up to Day 31
Secondary outcome [5] 0 0
Number of participants with microbiological outcome at the TOC visit - The microbiological outcome to study intervention will be determined by pre-specified programmed algorithm for each participant or uropathogen. The microbiological outcome by Baseline qualifying uropathogen will be determined by comparing the baseline culture results to the culture results at each subsequent visit.
Timepoint [5] 0 0
Up to Day 13
Secondary outcome [6] 0 0
Number of participants with microbiological outcome at the follow up visit - The microbiological outcome to study intervention will be determined by pre-specified programmed algorithm for each participant or uropathogen. The microbiological outcome by baseline qualifying uropathogen will be determined by comparing the baseline culture results to the culture results at each subsequent visit.
Timepoint [6] 0 0
Up to Day 31
Secondary outcome [7] 0 0
Number of participants with microbiological response at the TOC visit - The microbiological response to study intervention will be determined by pre-specified programmed algorithm for each participant or uropathogen.
Timepoint [7] 0 0
Up to Day 13
Secondary outcome [8] 0 0
Number of participants with microbiological response at the follow up visit - The microbiological response to study intervention will be determined by pre-specified programmed algorithm for each participant or uropathogen
Timepoint [8] 0 0
Up to Day 31
Secondary outcome [9] 0 0
Number of participants with therapeutic response at the follow up visit - A therapeutic success refers to participants who have been deemed both a "microbiological success" and a "clinical success". All other combinations (other than clinical success + microbiological success) will be deemed failures for therapeutic response.
Timepoint [9] 0 0
Up to Day 31
Secondary outcome [10] 0 0
Number of participants with treatment-emergent adverse events (AEs) and serious adverse events (SAEs) - An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose; results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect, any other situation that require medical or scientific judgment.
Timepoint [10] 0 0
Up to Day 31
Secondary outcome [11] 0 0
Change from Baseline in neutrophil count, lymphocyte count, monocyte count, eosinophil count, basophil count and platelet count (Giga cells per Liter) - Blood samples will be collected for the assessment of neutrophil count, lymphocyte count, monocyte count, eosinophil count, basophil count and platelet count.
Timepoint [11] 0 0
Baseline and up to Day 13
Secondary outcome [12] 0 0
Change from Baseline in hemoglobin level (grams per deciliter) - Blood samples will be collected for the assessment of hemoglobin level.
Timepoint [12] 0 0
Baseline and up to Day 13
Secondary outcome [13] 0 0
Change from Baseline in hematocrit level (Proportion of red blood cells in blood) - Blood samples will be collected for the assessment of hematocrit level
Timepoint [13] 0 0
Baseline and up to Day 13
Secondary outcome [14] 0 0
Change from Baseline in red blood cell (RBC) count (Trillion cells per liter) - Blood samples will be collected for the assessment of RBC count.
Timepoint [14] 0 0
Baseline and up to Day 13
Secondary outcome [15] 0 0
Change from Baseline in mean corpuscular hemoglobin (MCH) (Picograms) - Blood samples will be collected for the assessment of MCH
Timepoint [15] 0 0
Baseline and up to Day 13
Secondary outcome [16] 0 0
Change from Baseline in mean corpuscular volume (MCV) (Femtoliters) - Blood samples will be collected for the assessment of MCV.
Timepoint [16] 0 0
Baseline and up to Day 13
Secondary outcome [17] 0 0
Change from Baseline in blood urea nitrogen (BUN), glucose non-fasting, calcium, chloride, sodium, magnesium, phosphorus, and potassium levels (millimoles per liter) - Blood samples will be collected for the assessment of BUN, glucose non-fasting, calcium, chloride, magnesium, phosphorus, sodium and potassium levels.
Timepoint [17] 0 0
Baseline and up to Day 13
Secondary outcome [18] 0 0
Change from Baseline in total bilirubin, direct bilirubin and creatinine levels (micromoles per Liter) - Blood samples will be collected for the assessment of total bilirubin, direct bilirubin and creatinine levels.
Timepoint [18] 0 0
Baseline and up to Day 13
Secondary outcome [19] 0 0
Change from Baseline in albumin and total protein levels (gram per Liter) - Blood samples will be collected for the assessment of albumin and total protein levels.
Timepoint [19] 0 0
Baseline and up to Day 13
Secondary outcome [20] 0 0
Change from Baseline in aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase levels (International units per Liter) - Blood samples will be collected for the assessment of AST, ALT and alkaline phosphatase levels.
Timepoint [20] 0 0
Baseline and up to Day 13
Secondary outcome [21] 0 0
Number of participants with abnormal urinalysis Dipstick results - Urine samples will be collected to assess pH, glucose, protein, nitrite, leukocyte esterase, blood and ketones by Dipstick method. Microscopic examination will be performed if blood or protein will be abnormal.
Timepoint [21] 0 0
Up to Day 13
Secondary outcome [22] 0 0
Change from Baseline in specific gravity of urine - Urine samples will be collected for the measurement of specific gravity.
Timepoint [22] 0 0
Baseline and up to Day 13
Secondary outcome [23] 0 0
Change from Baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP) - SBP and DBP will be assessed in a semi-supine position after 5 minutes rest.
Timepoint [23] 0 0
Baseline and up to Day 13
Secondary outcome [24] 0 0
Change from Baseline in pulse rate - Pulse rate will be assessed in a semi-supine position after 5 minutes rest.
Timepoint [24] 0 0
Baseline and up to Day 13
Secondary outcome [25] 0 0
Change from Baseline in body temperature - Changes in body temperature from Baseline will be assessed.
Timepoint [25] 0 0
Baseline and up to Day 13
Secondary outcome [26] 0 0
Change from Baseline in PR, QRS, QT, and corrected QT interval (QTc) intervals (milliseconds [msec]) - Twelve lead electrocardiograms (ECG) will be obtained using an ECG machine that will automatically measure the PR, QRS, QT and QTc intervals.
Timepoint [26] 0 0
Baseline and up to Day 4

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 <=72 hours prior to study entry: dysuria, frequency, urgency, or
lower abdominal pain

- The participant has nitrite or pyuria (>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.

- 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.

- Additional requirements for pregnancy testing during and after study intervention
are specified.

- 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.

- 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 protocol.
Minimum age
12 Years
Maximum age
No limit
Gender
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 high blood pressure or uncontrolled diabetes.

- The participant has a history of sensitivity to the study interventions, 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
(e.g., uncontrolled diabetes, renal transplant recipients, participants with
clinically significant persistent granulocytopenia [absolute neutrophil count
<1000/microliter (µL)], and participants receiving immunosuppressive therapy,
including corticosteroid therapy [>40 milligrams (mg)/day prednisolone or equivalent
for >1 week, >=20 mg/day prednisolone or equivalent for >2 weeks, or prednisolone or
equivalent >=10 mg/day for >6 weeks]). Participants with a known cluster of
differentiation 4 (CD4) count of <200 cells per cubic millimeter (cells/mm^3) should
not be enrolled.

- The participant has any of the following: Medical condition that requires medication
that may be impacted by inhibition of acetylcholinesterase, such as;

- 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 intervention
(e.g., ileostomy or malabsorption syndrome)

- 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 Enterobacteriaceae (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.

- 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
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 degree Fahrenheit, 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 or a strong P-glycoprotein (P-gp) inhibitor.

- For any participant >=12 to <18 years of age, the participant has an abnormal ECG
reading at Baseline or during the study intervention.

- 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 × upper limit of normal (ULN).

- The participant has a known bilirubin value >1.5 × ULN (isolated bilirubin >1.5 × ULN
is acceptable if bilirubin is fractionated and direct bilirubin <35%).

- 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.

- The participant must agree not to use the medications or nondrug therapies from the
Baseline Visit through the TOC Visit

- The participant has been previously enrolled in this study or has previously been
treated with gepotidacin.

- The participant has participated in a clinical trial and has received an
investigational product within 30 days or 5 half-lives, whichever is longer.

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 administering the treatment/s
The people assessing the outcomes
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
Recruiting
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)
ACT,NSW,QLD
Recruitment hospital [1] 0 0
GSK Investigational Site - Bruce
Recruitment hospital [2] 0 0
GSK Investigational Site - Blacktown
Recruitment hospital [3] 0 0
GSK Investigational Site - Darlinghurst, Sydney
Recruitment hospital [4] 0 0
GSK Investigational Site - Kanwal
Recruitment hospital [5] 0 0
GSK Investigational Site - Maroubra
Recruitment hospital [6] 0 0
GSK Investigational Site - Sydney
Recruitment hospital [7] 0 0
GSK Investigational Site - Tarragindi
Recruitment hospital [8] 0 0
GSK Investigational Site - Herston
Recruitment postcode(s) [1] 0 0
2617 - Bruce
Recruitment postcode(s) [2] 0 0
2148 - Blacktown
Recruitment postcode(s) [3] 0 0
2010 - Darlinghurst, Sydney
Recruitment postcode(s) [4] 0 0
2259 - Kanwal
Recruitment postcode(s) [5] 0 0
2035 - Maroubra
Recruitment postcode(s) [6] 0 0
2010 - Sydney
Recruitment postcode(s) [7] 0 0
4121 - Tarragindi
Recruitment postcode(s) [8] 0 0
4029 - Herston
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
Georgia
Country [7] 0 0
United States of America
State/province [7] 0 0
Idaho
Country [8] 0 0
United States of America
State/province [8] 0 0
Iowa
Country [9] 0 0
United States of America
State/province [9] 0 0
Kansas
Country [10] 0 0
United States of America
State/province [10] 0 0
Maryland
Country [11] 0 0
United States of America
State/province [11] 0 0
Massachusetts
Country [12] 0 0
United States of America
State/province [12] 0 0
Michigan
Country [13] 0 0
United States of America
State/province [13] 0 0
Montana
Country [14] 0 0
United States of America
State/province [14] 0 0
New Jersey
Country [15] 0 0
United States of America
State/province [15] 0 0
New Mexico
Country [16] 0 0
United States of America
State/province [16] 0 0
New York
Country [17] 0 0
United States of America
State/province [17] 0 0
North Carolina
Country [18] 0 0
United States of America
State/province [18] 0 0
North Dakota
Country [19] 0 0
United States of America
State/province [19] 0 0
Ohio
Country [20] 0 0
United States of America
State/province [20] 0 0
Oregon
Country [21] 0 0
United States of America
State/province [21] 0 0
Pennsylvania
Country [22] 0 0
United States of America
State/province [22] 0 0
South Carolina
Country [23] 0 0
United States of America
State/province [23] 0 0
Tennessee
Country [24] 0 0
United States of America
State/province [24] 0 0
Texas
Country [25] 0 0
United States of America
State/province [25] 0 0
Utah
Country [26] 0 0
United States of America
State/province [26] 0 0
Virginia
Country [27] 0 0
Bulgaria
State/province [27] 0 0
Gabrovo
Country [28] 0 0
Bulgaria
State/province [28] 0 0
Haskovo
Country [29] 0 0
Bulgaria
State/province [29] 0 0
Kyustendil
Country [30] 0 0
Bulgaria
State/province [30] 0 0
Montana
Country [31] 0 0
Bulgaria
State/province [31] 0 0
Pleven
Country [32] 0 0
Bulgaria
State/province [32] 0 0
Ruse
Country [33] 0 0
Bulgaria
State/province [33] 0 0
Shumen
Country [34] 0 0
Bulgaria
State/province [34] 0 0
Sofia
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Bulgaria
State/province [35] 0 0
Stara Zagora
Country [36] 0 0
Bulgaria
State/province [36] 0 0
Targovisthe

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
GlaxoSmithKline
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Urinary tract infections (UTIs; acute cystitis) are very common, with approximately 11
percentage of women (>18 years of age) reporting at least 1 episode of acute cystitis per
year. The purpose of this study to evaluate the therapeutic response (combined
microbiological and clinical efficacy per participant) of oral gepotidacin compared to oral
nitrofurantoin for acute cystitis in adolescent and adult female participants. In this study,
participants will be randomly assigned in a 1:1 ratio to receive either oral gepotidacin or
oral nitrofurantoin. The study will enroll approximately 2000 participants with uncomplicated
UTI. The duration of the study will be approximately 28 days with 4 planned study visits.
Trial website
https://clinicaltrials.gov/show/NCT04187144
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
US GSK Clinical Trials Call Center
Address 0 0
Country 0 0
Phone 0 0
877-379-3718
Fax 0 0
Email 0 0
GSKClinicalSupportHD@gsk.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04187144