December 3, 2019
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December 5, 2019
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May 29, 2023
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July 18, 2023
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July 18, 2023
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April 23, 2020
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December 1, 2022 (Final data collection date for primary outcome measure)
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- 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) [ Time Frame: 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.
- 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 [ Time Frame: 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.
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Number of participants with therapeutic response at the Test-of-Cure (TOC) visit [ Time Frame: Up to Day 13 ] 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.
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- Number of Participants With Clinical Outcome at the TOC Visit - Micro-ITT NTF-S Population [ Time Frame: TOC visit (Days 9 to 16) ]
Clinical outcomes at TOC were categorized as clinical resolution, clinical improvement, clinical worsening and unable to determine. Clinical resolution at TOC was defined as resolution of signs and symptoms of acute cystitis present at baseline (BL) (and no symptoms) without receiving any other AB before the TOC visit. Clinical improvement at TOC was defined as improvement (but not complete resolution) in total symptom score (CSS) from BL, without receiving any other AB before the TOC visit. Clinical worsening at TOC was defined as worsening or no change in CSS from BL or received other AB for the current infection (uUTI) before or on the date of the TOC visit. Unable to determine outcome criteria were: BL score is missing (and thus improvement/worsening cannot be determined), TOC assessment is missing, or receipt of other AB not for the current infection before the TOC visit (unless clinical worsening outcome criteria were met).
- Number of Participants With Clinical Response at the TOC Visit - Micro-ITT NTF-S Population [ Time Frame: TOC visit (Days 9 to 16) ]
Clinical response at TOC was categorized as clinical success and clinical failure. Clinical success at TOC was defined as resolution of symptoms of acute cystitis present at BL (and no new symptoms), without receiving any other AB before the TOC visit. Lack of resolution, including receipt of an AB for uUTI at the TOC visit, or a missing outcome assessment was defined as Clinical Failure at TOC.
- Number of Participants With Microbiological Outcome (MO) at the TOC Visit - Micro-ITT NTF-S Population [ Time Frame: TOC Visit (Days 9 to 16) ]
Participant-level MOs at TOC were categorized as microbiological eradication (ME), microbiological persistence (MP), microbiological recurrence (MR) and unable to determine (UTD). ME at TOC was defined as all baseline qualifying uropathogens (QUP) have an outcome of eradication at TOC (i.e., <10^3 CFU/mL without the participant receiving other systemic antimicrobials before the TOC Visit). MP at TOC was defined as at least 1 QUP has an outcome of persistence (≥10^3 CFU/mL) at TOC. MR at TOC was defined as at least 1 QUP had an outcome of recurrence and none have an outcome of persistence at TOC. UTD at TOC was defined as all QUP outcomes are UTD at TOC.
- Number of Participants With Microbiological Response at the TOC Visit - Micro-ITT NTF-S Population [ Time Frame: TOC visit (Days 9 to 16) ]
Participant-level microbiological response at TOC was categorized as microbiological success and microbiological failure. Microbiological success at TOC was defined as all baseline qualifying uropathogens (QUP)s had a microbiological outcome of eradication at TOC visit. Microbiological failure was defined as lack of microbiological success, including those participants with UTD outcomes.
- 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 [ Time Frame: FU visit (Days 21 to 31) ]
TR at FU was categorized as therapeutic success and therapeutic failure. A therapeutic success at FU referred to participants who have been deemed both a microbiological success (reduction of all QUPs recovered at BL to <10^3 CFU/mL, following microbiological eradication at the TOC visit, without receiving other AB before the FU visit) and a clinical success (resolution of signs and symptoms of acute cystitis demonstrated at the TOC visit persist at the FU visit and no new signs and symptoms, without receiving other AB before the FU visit [or AB for uUTI on day of FU visit]). Lack of clinical or microbiological success (including missing outcome assessments) was considered as therapeutic failure.
- Number of Participants With Clinical Outcome at the Follow up (FU) Visit - Micro-ITT NTF-S Population [ Time Frame: FU visit (Days 21 to 31) ]
Clinical outcomes at FU were categorized as SCR, DCR, CI, CW, CR and UTD. SCR at FU was resolution of symptoms of acute cystitis demonstrated at the TOC persist at the FU (and no symptoms), without receiving other AB before the FU. DCR at FU was resolution of symptoms of acute cystitis present at BL after clinical failure at TOC without receiving AB before FU. CI at FU was improvement in CSS from BL, but not complete resolution without receiving AB before FU. CW at FU was worsening or no change in CSS at FU compared to BL after clinical failure at TOC or receiving other AB for the current infection (uUTI) before or on the date of the FU. CR at FU was symptoms of acute cystitis reoccur at FU after clinical success at TOC. Unable to determine outcome criteria at FU were BL score missing, FU assessment missing or received other AB not for the current infection (uUTI) prior to the assessment (unless CS or CR outcome criteria were met).
- Number of Participants With Clinical Response at the Follow up (FU) Visit - Micro-ITT NTF-S Population [ Time Frame: FU visit (Days 21 to 31) ]
Clinical response at FU was categorized as clinical success and clinical failure. Clinical success at FU was defined as resolution of symptoms of acute cystitis demonstrated at TOC persist at the FU visit (and no new symptoms), without receiving other AB before the FU visit. Lack of sustained clinical resolution or a missing outcome assessment was defined as clinical failure.
- Number of Participants With Microbiological Outcome (MO) at the Follow up (FU) Visit - Micro-ITT NTF-S Population [ Time Frame: FU visit (Days 21 to 31) ]
Participant-level MOs at FU were categorized as sustained microbiological eradication (SME), microbiological recurrence (MR), microbiological persistence (MP), delayed microbiological eradication (DME) and unable to determine (UTD). SME at FU was defined as all baseline QUPs had an outcome of sustained eradication at FU (i.e., <10^3 CFU/mL without the participant receiving other systemic antimicrobials before the FU Visit). MR at FU was defined as at least one QUP had an outcome of recurrence (≥10^3 CFU/mL) and none had an outcome of persistence at FU. MP at FU was defined as at least one QUP had an outcome of persistence at FU. DME at FU was defined as at least one QUP had an outcome of delayed eradication and none had an outcome of persistence or recurrence at FU. UTD at FU was defined as all QUP outcomes were unable to determine at FU.
- Number of Participants With Microbiological Response at the Follow up (FU) Visit - Micro-ITT NTF-S Population [ Time Frame: FU visit (Days 21 to 31) ]
Participant- level microbiological response at FU was categorized as microbiological success and microbiological failure. Microbiological success at FU was defined as all baseline QUPs had a microbiological outcome of sustained eradication at FU visit. Microbiological failure at FU was defined as not meeting criteria of microbiological success including those participants with UTD outcome.
- Number of Participants With Clinical Outcome at the TOC Visit - Intent-to-Treat (ITT) Population [ Time Frame: TOC visit (Days 9 to 16) ]
Clinical outcomes at TOC were categorized as clinical resolution, clinical improvement, clinical worsening and unable to determine. Clinical resolution at TOC was defined as resolution symptoms of acute cystitis present at baseline (BL) (and no symptoms) without receiving any other AB before the TOC visit. Clinical improvement at TOC was defined as improvement (but not complete resolution) in CSS from BL, without receiving any other AB before the TOC visit. Clinical worsening at TOC was defined as worsening or no change in CSS from BL or received other AB for the current infection (uUTI) before or on the date of the TOC visit. Unable to determine outcome criteria were: BL score is missing (and thus improvement/worsening cannot be determined), TOC assessment is missing, or receipt of other AB not for the current infection before the TOC visit (unless clinical worsening outcome criteria were met).
- Number of Participants With Clinical Response at the TOC Visit - Intent-to-Treat (ITT) Population [ Time Frame: TOC visit (Days 9 to 16) ]
Clinical response at TOC was categorized as clinical success and clinical failure. Clinical success at TOC was defined as resolution of signs and symptoms of acute cystitis present at BL (and no new symptoms), without receiving any other AB before the TOC visit. Lack of resolution, including receipt of an AB for uUTI at the TOC visit, or a missing outcome assessment was defined as Clinical Failure.
- Number of Participants With Clinical Outcome at the Follow up (FU) Visit - Intent-to-Treat (ITT) Population [ Time Frame: FU visit (Days 21 to 31) ]
Clinical outcomes at FU were categorized as Sustained Clinical Response (SCR), Delayed Clinical Response (DCR), CI, CW, Clinical Recurrence (CR) and UTD. SCR at FU was resolution of symptoms of acute cystitis demonstrated at TOC persist at the FU (and no symptoms), without receiving other AB before the FU. DCR at FU was resolution of symptoms of acute cystitis present at BL after clinical failure at TOC without receiving AB before FU. CI at FU was improvement in CSS from BL, but not complete resolution without receiving AB before FU. CW at FU was worsening or no change in CSS at FU compared to BL after clinical failure at TOC or receiving other AB for the current infection (uUTI) before or on the date of the FU. CR at FU was symptoms of acute cystitis reoccur at FU after clinical success at TOC. UTD outcome criteria at FU were BL score missing, FU assessment missing or received other AB not for current infection (uUTI) prior to assessment (unless CS or CR outcome criteria were met).
- Number of Participants With Clinical Response at the Follow up (FU) Visit - Intent-to-Treat (ITT) Population [ Time Frame: FU visit (Days 21 to 31) ]
Clinical response at FU was categorized as clinical success and clinical failure. Clinical success at FU was defined as resolution of symptoms of acute cystitis demonstrated at TOC persist at the FU visit (and no new symptoms), without receiving other AB before the FU visit. Lack of sustained clinical resolution or a missing outcome assessment was defined as clinical failure.
- Number of Participants With Treatment-emergent Adverse Events (TEAEs) [ Time Frame: From the time of first dose (Day 1) through the final follow-up visit (Day 21-31) ]
An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment.
- Number of Participants With Serious Adverse Events (SAEs) [ Time Frame: From the time of first dose (Day 1) through the final follow-up visit (Day 21-31) ]
An SAE is defined as any untoward medical occurrence that, at any dose may result in death or is life-threatening or requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity or is a congenital anomaly/birth defect or any other situation according to medical or scientific judgment or is associated with liver injury and impaired liver function.
- 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 [ Time Frame: Baseline (on or before Day 1), On-Therapy (Days 2 to 5), and Test of cure (Days 9 to 16) ]
Blood samples were collected for the analysis of hematology parameters: neutrophil count, lymphocyte count, monocyte count, eosinophil count, basophil count and platelet count. Baseline is defined as the latest pre-dose assessment with a non-missing value.
- Change From Baseline in Hematology Parameter: Hemoglobin Level [ Time Frame: Baseline (on or before Day 1), On-Therapy (Days 2 to 5), and Test of cure (Days 9 to 16) ]
Blood samples were collected for the analysis of hemoglobin level. Baseline is defined as the latest pre-dose assessment with a non-missing value.
- Change From Baseline in Hematology Parameter: Hematocrit Level [ Time Frame: Baseline (on or before Day 1), On-Therapy (Days 2 to 5), and Test of cure (Days 9 to 16) ]
Blood samples were collected for the analysis of hematocrit level. Baseline is defined as the latest pre-dose assessment with a non-missing value.
- Change From Baseline in Hematology Parameter: Erythrocytes (RBC) Count [ Time Frame: Baseline (on or before Day 1), On-Therapy (Days 2 to 5), and Test of cure (Days 9 to 16) ]
Blood samples were collected for the analysis of erythrocytes count. Baseline is defined as the latest pre-dose assessment with a non-missing value.
- Change From Baseline in Hematology Parameter: Mean Corpuscular Hemoglobin (MCH) [ Time Frame: Baseline (on or before Day 1), On-Therapy (Days 2 to 5), and Test of cure (Days 9 to 16) ]
Blood samples were collected for the analysis of MCH. Baseline is defined as the latest pre-dose assessment with a non-missing value.
- Change From Baseline in Hematology Parameter: Mean Corpuscular Volume (MCV) [ Time Frame: Baseline (on or before Day 1), On-Therapy (Days 2 to 5), and Test of cure (Days 9 to 16) ]
Blood samples were collected for the analysis of MCV. Baseline is defined as the latest pre-dose assessment with a non-missing value.
- Change From Baseline in Clinical Chemistry Parameters: Serum Blood Urea Nitrogen (BUN), Glucose Non-fasting, Calcium, Chloride, Sodium, Magnesium, Phosphate, and Potassium Levels [ Time Frame: Baseline (on or before Day 1), On-Therapy (Days 2 to 5), and Test of cure (Days 9 to 16) ]
Blood samples were collected for the analysis of clinical chemistry parameters. Baseline is defined as the latest pre-dose assessment with a non-missing value.
- Change From Baseline in Clinical Chemistry Parameters: Total Bilirubin, Direct Bilirubin and Creatinine Levels [ Time Frame: Baseline (on or before Day 1), On-Therapy (Days 2 to 5), and Test of cure (Days 9 to 16) ]
Blood samples were collected for the analysis of clinical chemistry parameters. Baseline is defined as the latest pre-dose assessment with a non-missing value.
- Change From Baseline in Clinical Chemistry Parameters: Albumin and Protein Levels [ Time Frame: Baseline (on or before Day 1), On-Therapy (Days 2 to 5), and Test of cure (Days 9 to 16) ]
Blood samples were collected for the analysis of clinical chemistry parameters. Baseline is defined as the latest pre-dose assessment with a non-missing value.
- Change From Baseline in Clinical Chemistry Parameters: Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) and Alkaline Phosphatase (ALP) Levels [ Time Frame: Baseline (on or before Day 1), On-Therapy (Days 2 to 5), and Test of cure (Days 9 to 16) ]
Blood samples were collected for the analysis of clinical chemistry parameters. Baseline is defined as the latest pre-dose assessment with a non-missing value.
- Number of Participants With Urinalysis Dipstick Results [ Time Frame: Baseline (on or before Day 1), On-Therapy (Days 2 to 5), and Test of cure (Days 9 to 16) ]
Urine samples were collected for urinalysis: Urine Glucose (GLU), Urine Protein (PRO), Urine Occult Blood (BLO), Urine Ketones (KET), Urine Nitrite (NIT) and Urine Leukocyte Esterase (LEU). Baseline is defined as the latest pre-dose assessment with a non-missing value. The dipstick test gives results in a semi-quantitative manner, and results can be read as Negative, Trace, Small, Moderate, Large, Positive, 50 milligram per deciliter (mg/dL), 150 mg/dL, >=500 mg/dL, 30 mg/dL, 100 mg/dL, 200 mg/dL, 5 mg/dL, 20 mg/dL, >=80 mg/dL indicating concentrations in the urine sample. In the row title (GLU, Baseline, Negative), GLU indicates parameter, Baseline is the visit and Negative indicates the concentration in the urine sample. Data is presented in similar way for others parameters.
- Absolute Mean Values of Urine Specific Gravity [ Time Frame: Baseline (on or before Day 1), On-Therapy (Days 2 to 5), and Test of cure (Days 9 to 16) ]
Urine samples were collected from participants to assess urine specific gravity. Baseline is defined as the latest pre-dose assessment with a non-missing value.
- Absolute Mean Values of Urine Potential of Hydrogen (pH) [ Time Frame: Baseline (on or before Day 1), On-Therapy (Days 2 to 5), and Test of cure (Days 9 to 16) ]
Urine samples were collected from participants to assess urine pH levels. Baseline is defined as the latest pre-dose assessment with a non-missing value.
- Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at On-Therapy and Test of Cure Visit [ Time Frame: Baseline (on or before Day 1), On-Therapy (Days 2 to 5), and Test of cure (Days 9 to 16) ]
SBP and DBP were measured in a semi-supine position after 5 minutes rest. Baseline is defined as the latest pre-dose assessment with a non-missing value.
- Change From Baseline in Pulse Rate at On Therapy and Test of Cure Visit [ Time Frame: Baseline (on or before Day 1), On-Therapy (Days 2 to 5), and Test of cure (Days 9 to 16) ]
Pulse rate was measured in a semi-supine position after 5 minutes rest. Baseline is defined as the latest pre-dose assessment with a non-missing value.
- Change From Baseline in Body Temperature [ Time Frame: Baseline (on or before Day 1), On-Therapy (Days 2 to 5), and Test of cure (Days 9 to 16) ]
Temperature was measured in a semi-supine position after 5 minutes rest. Baseline is defined as the latest pre-dose assessment with a non-missing value.
- 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 [ Time Frame: Up to Day 31 ]
Triplicate 12-lead ECGs (over an approximate 5- to 10-minute period) were performed using an ECG machine. Baseline is defined as the latest pre-dose assessment with a non-missing value. The row titles <=450, >450 to <=480, >480 to <=500 millisecond (msec) are the values at baseline. The category titles <= 30, 31-60, >60 msec are the maximum change from baseline values. The maximum change from baseline value category was determined by comparing the baseline value category to the worst-case post-baseline value category for each participant, which considered unscheduled and out of visit window assessments. Data of number of participants with any change at worst-case post-baseline (maximum grade increase post-baseline) is presented.
- 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 [ Time Frame: Up to Day 31 ]
Triplicate 12-lead ECGs (over an approximate 5- to 10-minute period) were performed using an ECG machine. Baseline is defined as the latest pre-dose assessment with a non-missing value. The row titles <=450 msec, >450 msec to <=480 msec are the values at baseline. The category titles <= 30, 31-60, >60 msec are the maximum change from baseline values. The maximum change from baseline value category was determined by comparing the baseline value category to the worst-case post-baseline value category for each participant, which considered unscheduled and out of visit window assessments. Data of number of participants with any change at worst-case post-baseline (maximum grade increase post-baseline) is presented.
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- Number of participants with clinical outcome at the TOC visit [ Time Frame: Up to Day 13 ]
The clinical signs and symptoms score for acute cystitis will be determined by the investigator and used to programmatically determine the clinical outcome.
- Number of participants with clinical outcome at the follow up visit [ Time Frame: Up to Day 31 ]
The clinical signs and symptoms score for acute cystitis will be determined by the investigator and used to programmatically determine the clinical outcome.
- Number of participants with clinical response at the TOC visit [ Time Frame: Up to Day 13 ]
The clinical signs and symptoms score for acute cystitis will be determined by the investigator and used to programmatically determine the clinical response.
- Number of participants with clinical response at the follow up visit [ Time Frame: Up to Day 31 ]
The clinical signs and symptoms score for acute cystitis will be determined by the investigator and used to programmatically determine the clinical response.
- Number of participants with microbiological outcome at the TOC visit [ Time Frame: Up to Day 13 ]
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.
- Number of participants with microbiological outcome at the follow up visit [ Time Frame: Up to Day 31 ]
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.
- Number of participants with microbiological response at the TOC visit [ Time Frame: Up to Day 13 ]
The microbiological response to study intervention will be determined by pre-specified programmed algorithm for each participant or uropathogen.
- Number of participants with microbiological response at the follow up visit [ Time Frame: Up to Day 31 ]
The microbiological response to study intervention will be determined by pre-specified programmed algorithm for each participant or uropathogen
- Number of participants with therapeutic response at the follow up visit [ Time Frame: Up to Day 31 ]
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.
- Number of participants with treatment-emergent adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: Up to Day 31 ]
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.
- Change from Baseline in neutrophil count, lymphocyte count, monocyte count, eosinophil count, basophil count and platelet count (Giga cells per Liter) [ Time Frame: Baseline and up to Day 13 ]
Blood samples will be collected for the assessment of neutrophil count, lymphocyte count, monocyte count, eosinophil count, basophil count and platelet count.
- Change from Baseline in hemoglobin level (grams per deciliter) [ Time Frame: Baseline and up to Day 13 ]
Blood samples will be collected for the assessment of hemoglobin level.
- Change from Baseline in hematocrit level (Proportion of red blood cells in blood) [ Time Frame: Baseline and up to Day 13 ]
Blood samples will be collected for the assessment of hematocrit level
- Change from Baseline in red blood cell (RBC) count (Trillion cells per liter) [ Time Frame: Baseline and up to Day 13 ]
Blood samples will be collected for the assessment of RBC count.
- Change from Baseline in mean corpuscular hemoglobin (MCH) (Picograms) [ Time Frame: Baseline and up to Day 13 ]
Blood samples will be collected for the assessment of MCH
- Change from Baseline in mean corpuscular volume (MCV) (Femtoliters) [ Time Frame: Baseline and up to Day 13 ]
Blood samples will be collected for the assessment of MCV.
- Change from Baseline in blood urea nitrogen (BUN), glucose non-fasting, calcium, chloride, sodium, magnesium, phosphorus, and potassium levels (millimoles per liter) [ Time Frame: Baseline and up to Day 13 ]
Blood samples will be collected for the assessment of BUN, glucose non-fasting, calcium, chloride, magnesium, phosphorus, sodium and potassium levels.
- Change from Baseline in total bilirubin, direct bilirubin and creatinine levels (micromoles per Liter) [ Time Frame: Baseline and up to Day 13 ]
Blood samples will be collected for the assessment of total bilirubin, direct bilirubin and creatinine levels.
- Change from Baseline in albumin and total protein levels (gram per Liter) [ Time Frame: Baseline and up to Day 13 ]
Blood samples will be collected for the assessment of albumin and total protein levels.
- Change from Baseline in aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase levels (International units per Liter) [ Time Frame: Baseline and up to Day 13 ]
Blood samples will be collected for the assessment of AST, ALT and alkaline phosphatase levels.
- Number of participants with abnormal urinalysis Dipstick results [ Time Frame: Up to Day 13 ]
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.
- Change from Baseline in specific gravity of urine [ Time Frame: Baseline and up to Day 13 ]
Urine samples will be collected for the measurement of specific gravity.
- Change from Baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP) [ Time Frame: Baseline and up to Day 13 ]
SBP and DBP will be assessed in a semi-supine position after 5 minutes rest.
- Change from Baseline in pulse rate [ Time Frame: Baseline and up to Day 13 ]
Pulse rate will be assessed in a semi-supine position after 5 minutes rest.
- Change from Baseline in body temperature [ Time Frame: Baseline and up to Day 13 ]
Changes in body temperature from Baseline will be assessed.
- Change from Baseline in PR, QRS, QT, and corrected QT interval (QTc) intervals (milliseconds [msec]) [ Time Frame: Baseline and up to Day 4 ]
Twelve lead electrocardiograms (ECG) will be obtained using an ECG machine that will automatically measure the PR, QRS, QT and QTc intervals.
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Not Provided
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Not Provided
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Comparative Study to Evaluate Efficacy and Safety of Gepotidacin to Nitrofurantoin in Treatment of Uncomplicated Urinary Tract Infection (UTI)
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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)
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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.
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Not Provided
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Interventional
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Phase 3
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Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double (Participant, Investigator) Primary Purpose: Treatment
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Urinary Tract Infections
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- Drug: 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.
- Drug: 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.
- Drug: 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.
- Drug: 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.
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- 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.
Interventions:
- Drug: Gepotidacin
- Drug: Placebo matching nitrofurantoin
- 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.
Interventions:
- Drug: Nitrofurantoin
- Drug: Placebo matching gepotidacin
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- Perry C, Hossain M, Powell M, Raychaudhuri A, Scangarella-Oman N, Tiffany C, Xu S, Dumont E, Janmohamed S. Design of Two Phase III, Randomized, Multicenter Studies Comparing Gepotidacin with Nitrofurantoin for the Treatment of Uncomplicated Urinary Tract Infection in Female Participants. Infect Dis Ther. 2022 Dec;11(6):2297-2310. doi: 10.1007/s40121-022-00706-9. Epub 2022 Oct 21.
- Fishman C, Caverly Rae JM, Posobiec LM, Laffan SB, Lerman SA, Pearson N, Janmohamed S, Dumont E, Nunn-Floyd D, Stanislaus DJ. Novel Bacterial Topoisomerase Inhibitor Gepotidacin Demonstrates Absence of Fluoroquinolone-Like Arthropathy in Juvenile Rats. Antimicrob Agents Chemother. 2022 Nov 15;66(11):e0048322. doi: 10.1128/aac.00483-22. Epub 2022 Oct 18.
- Scangarella-Oman NE, Hossain M, Hoover JL, Perry CR, Tiffany C, Barth A, Dumont EF. Dose Selection for Phase III Clinical Evaluation of Gepotidacin (GSK2140944) in the Treatment of Uncomplicated Urinary Tract Infections. Antimicrob Agents Chemother. 2022 Mar 15;66(3):e0149221. doi: 10.1128/AAC.01492-21. Epub 2022 Jan 3.
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Completed
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1606
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1200
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December 1, 2022
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December 1, 2022 (Final data collection date for primary outcome measure)
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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.
Exclusion Criteria:
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Sexes Eligible for Study: |
Female |
Gender Based Eligibility: |
Yes |
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12 Years and older (Child, Adult, Older Adult)
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No
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Contact information is only displayed when the study is recruiting subjects
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Australia, Bulgaria, India, Korea, Republic of, Poland, United States
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NCT04187144
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212390 2020-000553-27 ( EudraCT Number )
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Yes
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Studies a U.S. FDA-regulated Drug Product: |
Yes |
Studies a U.S. FDA-regulated Device Product: |
No |
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Plan to Share IPD: |
Yes |
Plan Description: |
IPD for this study will be made available via the Clinical Study Data Request site. |
Supporting Materials: |
Study Protocol |
Supporting Materials: |
Statistical Analysis Plan (SAP) |
Supporting Materials: |
Informed Consent Form (ICF) |
Supporting Materials: |
Clinical Study Report (CSR) |
Time Frame: |
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. |
Access Criteria: |
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. |
URL: |
http://clinicalstudydatarequest.com |
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GlaxoSmithKline
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Same as current
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GlaxoSmithKline
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Same as current
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Not Provided
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Study Director: |
GSK Clinical Trials |
GlaxoSmithKline |
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GlaxoSmithKline
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July 2023
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