Comparative Study to Evaluate Efficacy and Safety of Gepotidacin to Nitrofurantoin in Treatment of Uncomplicated Urinary Tract Infection (UTI)

• ClinicalTrials.gov Identifier: NCT04187144
• Recruitment Status: Completed
• First Posted: December 5, 2019
• Results First Posted: July 18, 2023
• Last Update Posted: July 18, 2023
• Sponsor: GlaxoSmithKline
• Information provided by (Responsible Party): GlaxoSmithKline

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Urinary Tract Infections
• Interventions: Drug: Gepotidacin; Drug: Placebo matching nitrofurantoin; Drug: Nitrofurantoin; Drug: Placebo matching gepotidacin
• Enrollment: 1606

Participant Flow

Recruitment Details	1605 unique participants were enrolled in the study including one participant that was randomized twice in error. This participant signed two different informed consent forms, therefore that participant was counted as enrolling twice.
Pre-assignment Details

Arm/Group Title	Gepotidacin	Nitrofurantoin
Arm/Group Description	Participants with uncomplicated urinary tract infection (uUTI) (acute cystitis) randomized to receive gepotidacin 1500 milligram (mg) (2*750 mg, tablets), twice daily (BID), orally on Day 1 to Day 5. The total daily dose of gepotidacin received was 3000 mg. Participants also received 1 capsule of placebo matched with nitrofurantoin BID, orally on Day 1 to Day 5. All doses were administered after food consumption and with water.	Participants with uncomplicated urinary tract infection (acute cystitis) randomized to receive nitrofurantoin 100 mg capsule, BID, orally on Day 1 to Day 5. The total daily dose of nitrofurantoin received was 200 mg. Participants also received 2 tablets of placebo matched with gepotidacin BID, orally on Day 1 to Day 5. All doses were administered after food consumption and with water.
Period Title: Overall Study
Started [1]	805	800
Safety Population [2]	804	798
Microbiological ITT (Micro ITT) Population [3]	331	324
Micro-ITT NTF-S Population [4]	292	275
Micro-ITT NTF-S (IA Set) Population [5]	277	264
Completed	748	759
Not Completed	57	41
Reason Not Completed
Lost to Follow-up	12	11
Withdrawal by Subject	20	18
Adverse Event	19	4
Physician Decision	5	3
Screening Failure due to creatinine clearance and body mass index	0	1
Protocol Deviation	1	4
[1] Participants randomly assigned to the study treatment were included in Intent-to-Treat (ITT) population; [2] Safety population included all randomized participants who receive at least 1 dose of study treatment.; [3] Microbiological ITT (micro-ITT) population included all participants randomly assigned to study treatment who receive at least 1 dose of study treatment and have a qualifying baseline uropathogen [10^5 CFU/mL] from a quantitative bacteriological culture of a pretreatment clean catch midstream urine specimen.; [4] Micro-ITT NTF-S population is defined as all participants in the micro-ITT population whose baseline qualifying uropathogens [10^5 CFU/mL] are all susceptible to nitrofurantoin (NTF-S).; [5] Microbiological intent-to-treat susceptible to nitrofurantoin (micro-ITT NTF-S) (IA Set) population included participants in the micro ITT NTF-S who per the interim analysis data had the opportunity to reach their Test of Cure (TOC) visit, or had not yet reached their TOC visit, but were already known to be failures.

Baseline Characteristics

Arm/Group Title		Gepotidacin	Nitrofurantoin	Total
Arm/Group Description		Participants with uncomplicated urinary tract infection (acute cystitis) randomized to receive gepotidacin 1500 milligram (mg) (2*750 mg, tablets), twice daily (BID), orally on Day 1 to Day 5. The total daily dose of gepotidacin received was 3000 mg. Participants also received 1 capsule of placebo matched with nitrofurantoin BID, orally on Day 1 to Day 5. All doses were administered after food consumption and with water.	Participants with uncomplicated urinary tract infection (acute cystitis) randomized to receive nitrofurantoin 100 mg capsule, BID, orally on Day 1 to Day 5. The total daily dose of nitrofurantoin received was 200 mg. Participants also received 2 tablets of placebo matched with gepotidacin BID, orally on Day 1 to Day 5. All doses were administered after food consumption and with water.	Total of all reporting groups
Overall Number of Baseline Participants		805	800	1605
Baseline Analysis Population Description		Participants randomly assigned to the study treatment were included in the ITT population.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	805 participants	800 participants	1605 participants
		48.2 (17.84)	48.4 (17.72)	48.3 (17.77)
Age, Customized; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	805 participants	800 participants	1605 participants
Less than (<) 18 years		8 1.0%	3 0.4%	11 0.7%
More than or equal to (>=) 18 years to 50 years		427 53.0%	430 53.8%	857 53.4%
More than (>) 50 years		370 46.0%	367 45.9%	737 45.9%
Sex/Gender, Customized; Measure Type: Count of Participants; Unit of measure: Participants
Female	Number Analyzed	805 participants	800 participants	1605 participants
		805 100.0%	800 100.0%	1605 100.0%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	805 participants	800 participants	1605 participants
	Hispanic or Latino	246 30.6%	232 29.0%	478 29.8%
	Not Hispanic or Latino	559 69.4%	568 71.0%	1127 70.2%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	805 participants	800 participants	1605 participants
	American Indian or Alaska Native	2 0.2%	1 0.1%	3 0.2%
	Asian	51 6.3%	65 8.1%	116 7.2%
	Native Hawaiian or Other Pacific Islander	1 0.1%	0 0.0%	1 0.1%
	Black or African American	74 9.2%	62 7.8%	136 8.5%
	White	674 83.7%	668 83.5%	1342 83.6%
	More than one race	2 0.2%	4 0.5%	6 0.4%
	Unknown or Not Reported	1 0.1%	0 0.0%	1 0.1%
Baseline Acute Cystitis Recurrence [1]; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	805 participants	800 participants	1605 participants
Recurrent Infection		334 41.5%	338 42.3%	672 41.9%
Non-Recurrent Infection		471 58.5%	462 57.8%	933 58.1%
		[1] Measure Description: Recurrent infection was defined as a confirmed infection with at least 1 episode within the past 3 months, at least 2 episodes within the past 6 months, or at least 3 episodes within the past 12 months before study entry.

Outcome Measures

1. Primary Outcome

Title	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)
Description	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.
Time Frame	TOC visit (Days 9 to 16)

Outcome Measure Data

Analysis Population Description

Microbiological intent-to-treat susceptible to nitrofurantoin - (Micro-ITT NTF-S) (Interim Analysis [IA] Set) population included participants in the micro ITT NTF-S who per the interim analysis data had the opportunity to reach their Test of Cure (TOC) visit, or had not yet reached their TOC visit, but were already known to be failures.

Arm/Group Title	Gepotidacin	Nitrofurantoin
Arm/Group Description:	Participants with uncomplicated urinary tract infection (acute cystitis) randomized to receive gepotidacin 1500 milligram (mg) (2*750 mg, tablets), twice daily (BID), orally on Day 1 to Day 5. The total daily dose of gepotidacin received was 3000 mg. Participants also received 1 capsule of placebo matched with nitrofurantoin BID, orally on Day 1 to Day 5. All doses were administered after food consumption and with water.	Participants with uncomplicated urinary tract infection (acute cystitis) randomized to receive nitrofurantoin 100 mg capsule, BID, orally on Day 1 to Day 5. The total daily dose of nitrofurantoin received was 200 mg. Participants also received 2 tablets of placebo matched with gepotidacin BID, orally on Day 1 to Day 5. All doses were administered after food consumption and with water.
Overall Number of Participants Analyzed	277	264
Measure Type: Count of Participants; Unit of Measure: Participants
Therapeutic Success	162 58.5%	115 43.6%
Therapeutic Failure	115 41.5%	149 56.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gepotidacin, Nitrofurantoin
	Comments	[Not Specified]
	Type of Statistical Test	Non-Inferiority
	Comments	The difference in success rate between treatment groups (gepotidacin - nitrofurantoin) was calculated using Miettinen-Nurminen Summary Score Method adjusted for age group and acute cystitis recurrence strata combinations. Criteria for non-inferiority is if the Z-statistic for non-inferiority is greater than the 2.098 Z-statistic boundary.
Method of Estimation	Estimation Parameter	Adjusted Difference in Percent
	Estimated Value	14.6
	Confidence Interval	(2-Sided) 95%; 6.4 to 22.8
	Estimation Comments	[Not Specified]
Other Statistical Analysis		Observed Z statistic value for Noninferiority was 5.8838.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Gepotidacin, Nitrofurantoin
	Comments	The difference in success rate between treatment groups (gepotidacin - nitrofurantoin) was calculated using Miettinen-Nurminen Summary Score Method adjusted for age group and acute cystitis recurrence strata combinations. Criteria for superiority is if the one-sided p-value is less than the 0.018 p-value boundary
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0003
	Comments	[Not Specified]
	Method	1-sided p-value for Test of Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Adjusted difference in Percent
	Estimated Value	14.6
	Confidence Interval	(2-Sided) 95%; 6.4 to 22.8
	Estimation Comments	[Not Specified]

2. Primary Outcome

Title	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
Description	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.
Time Frame	TOC visit (Days 9 to 16)

Outcome Measure Data

Analysis Population Description

Micro-ITT NTF-S population

Arm/Group Title	Gepotidacin	Nitrofurantoin
Arm/Group Description:	Participants with uncomplicated urinary tract infection (acute cystitis) randomized to receive gepotidacin 1500 milligram (mg) (2*750 mg, tablets), twice daily (BID), orally on Day 1 to Day 5. The total daily dose of gepotidacin received was 3000 mg. Participants also received 1 capsule of placebo matched with nitrofurantoin BID, orally on Day 1 to Day 5. All doses were administered after food consumption and with water.	Participants with uncomplicated urinary tract infection (acute cystitis) randomized to receive nitrofurantoin 100 mg capsule, BID, orally on Day 1 to Day 5. The total daily dose of nitrofurantoin received was 200 mg. Participants also received 2 tablets of placebo matched with gepotidacin BID, orally on Day 1 to Day 5. All doses were administered after food consumption and with water.
Overall Number of Participants Analyzed	292	275
Measure Type: Count of Participants; Unit of Measure: Participants
Therapeutic Success	172 58.9%	121 44.0%
Therapeutic Failure	120 41.1%	154 56.0%

3. Secondary Outcome

Title	Number of Participants With Clinical Outcome at the TOC Visit - Micro-ITT NTF-S Population
Description	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).
Time Frame	TOC visit (Days 9 to 16)

Outcome Measure Data

Analysis Population Description

Micro-ITT NTF-S population

Arm/Group Title	Gepotidacin	Nitrofurantoin
Arm/Group Description:	Participants with uncomplicated urinary tract infection (acute cystitis) randomized to receive gepotidacin 1500 milligram (mg) (2*750 mg, tablets), twice daily (BID), orally on Day 1 to Day 5. The total daily dose of gepotidacin received was 3000 mg. Participants also received 1 capsule of placebo matched with nitrofurantoin BID, orally on Day 1 to Day 5. All doses were administered after food consumption and with water.	Participants with uncomplicated urinary tract infection (acute cystitis) randomized to receive nitrofurantoin 100 mg capsule, BID, orally on Day 1 to Day 5. The total daily dose of nitrofurantoin received was 200 mg. Participants also received 2 tablets of placebo matched with gepotidacin BID, orally on Day 1 to Day 5. All doses were administered after food consumption and with water.
Overall Number of Participants Analyzed	292	275
Measure Type: Count of Participants; Unit of Measure: Participants
Clinical Resolution	199 68.2%	175 63.6%
Clinical Improvement (CI)	51 17.5%	68 24.7%
Clinical Worsening (CW)	20 6.8%	17 6.2%
Unable to Determine	22 7.5%	15 5.5%

4. Secondary Outcome

Title	Number of Participants With Clinical Response at the TOC Visit - Micro-ITT NTF-S Population
Description	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.
Time Frame	TOC visit (Days 9 to 16)

Outcome Measure Data

Analysis Population Description

Micro-ITT NTF-S population.

Arm/Group Title	Gepotidacin	Nitrofurantoin
Arm/Group Description:	Participants with uncomplicated urinary tract infection (acute cystitis) randomized to receive gepotidacin 1500 milligram (mg) (2*750 mg, tablets), twice daily (BID), orally on Day 1 to Day 5. The total daily dose of gepotidacin received was 3000 mg. Participants also received 1 capsule of placebo matched with nitrofurantoin BID, orally on Day 1 to Day 5. All doses were administered after food consumption and with water.	Participants with uncomplicated urinary tract infection (acute cystitis) randomized to receive nitrofurantoin 100 mg capsule, BID, orally on Day 1 to Day 5. The total daily dose of nitrofurantoin received was 200 mg. Participants also received 2 tablets of placebo matched with gepotidacin BID, orally on Day 1 to Day 5. All doses were administered after food consumption and with water.
Overall Number of Participants Analyzed	292	275
Measure Type: Count of Participants; Unit of Measure: Participants
Clinical Success	199 68.2%	175 63.6%
Clinical Failure	93 31.8%	100 36.4%

5. Secondary Outcome

Title	Number of Participants With Microbiological Outcome (MO) at the TOC Visit - Micro-ITT NTF-S Population
Description	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.
Time Frame	TOC Visit (Days 9 to 16)

Outcome Measure Data

Analysis Population Description

Micro-ITT NTF-S population.

Arm/Group Title	Gepotidacin	Nitrofurantoin
Arm/Group Description:	Participants with uncomplicated urinary tract infection (acute cystitis) randomized to receive gepotidacin 1500 milligram (mg) (2*750 mg, tablets), twice daily (BID), orally on Day 1 to Day 5. The total daily dose of gepotidacin received was 3000 mg. Participants also received 1 capsule of placebo matched with nitrofurantoin BID, orally on Day 1 to Day 5. All doses were administered after food consumption and with water.	Participants with uncomplicated urinary tract infection (acute cystitis) randomized to receive nitrofurantoin 100 mg capsule, BID, orally on Day 1 to Day 5. The total daily dose of nitrofurantoin received was 200 mg. Participants also received 2 tablets of placebo matched with gepotidacin BID, orally on Day 1 to Day 5. All doses were administered after food consumption and with water.
Overall Number of Participants Analyzed	292	275
Measure Type: Count of Participants; Unit of Measure: Participants
Microbiological Eradication (ME)	213 72.9%	158 57.5%
Microbiological Persistence (MP)	13 4.5%	31 11.3%
Microbiological Recurrence (MR)	19 6.5%	52 18.9%
Unable to Determine (UTD)	47 16.1%	34 12.4%

6. Secondary Outcome

Title	Number of Participants With Microbiological Response at the TOC Visit - Micro-ITT NTF-S Population
Description	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.
Time Frame	TOC visit (Days 9 to 16)

Outcome Measure Data

Analysis Population Description

Micro-ITT NTF-S population.

Arm/Group Title	Gepotidacin	Nitrofurantoin
Arm/Group Description:	Participants with uncomplicated urinary tract infection (acute cystitis) randomized to receive gepotidacin 1500 milligram (mg) (2*750 mg, tablets), twice daily (BID), orally on Day 1 to Day 5. The total daily dose of gepotidacin received was 3000 mg. Participants also received 1 capsule of placebo matched with nitrofurantoin BID, orally on Day 1 to Day 5. All doses were administered after food consumption and with water.	Participants with uncomplicated urinary tract infection (acute cystitis) randomized to receive nitrofurantoin 100 mg capsule, BID, orally on Day 1 to Day 5. The total daily dose of nitrofurantoin received was 200 mg. Participants also received 2 tablets of placebo matched with gepotidacin BID, orally on Day 1 to Day 5. All doses were administered after food consumption and with water.
Overall Number of Participants Analyzed	292	275
Measure Type: Count of Participants; Unit of Measure: Participants
Microbiological Success	213 72.9%	158 57.5%
Microbiological Failure	79 27.1%	117 42.5%

7. Secondary Outcome

Title	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
Description	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.
Time Frame	FU visit (Days 21 to 31)

Outcome Measure Data

Analysis Population Description

Micro-ITT NTF-S population.

Arm/Group Title	Gepotidacin	Nitrofurantoin
Arm/Group Description:	Participants with uncomplicated urinary tract infection (acute cystitis) randomized to receive gepotidacin 1500 milligram (mg) (2*750 mg, tablets), twice daily (BID), orally on Day 1 to Day 5. The total daily dose of gepotidacin received was 3000 mg. Participants also received 1 capsule of placebo matched with nitrofurantoin BID, orally on Day 1 to Day 5. All doses were administered after food consumption and with water.	Participants with uncomplicated urinary tract infection (acute cystitis) randomized to receive nitrofurantoin 100 mg capsule, BID, orally on Day 1 to Day 5. The total daily dose of nitrofurantoin received was 200 mg. Participants also received 2 tablets of placebo matched with gepotidacin BID, orally on Day 1 to Day 5. All doses were administered after food consumption and with water.
Overall Number of Participants Analyzed	292	275
Measure Type: Count of Participants; Unit of Measure: Participants
Therapeutic Success	126 43.2%	95 34.5%
Therapeutic Failure	166 56.8%	180 65.5%

8. Secondary Outcome

Title	Number of Participants With Clinical Outcome at the Follow up (FU) Visit - Micro-ITT NTF-S Population
Description	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).
Time Frame	FU visit (Days 21 to 31)

Outcome Measure Data

Analysis Population Description

Micro-ITT NTF-S population

Arm/Group Title	Gepotidacin	Nitrofurantoin
Arm/Group Description:	Participants with uncomplicated urinary tract infection (acute cystitis) randomized to receive gepotidacin 1500 milligram (mg) (2*750 mg, tablets), twice daily (BID), orally on Day 1 to Day 5. The total daily dose of gepotidacin received was 3000 mg. Participants also received 1 capsule of placebo matched with nitrofurantoin BID, orally on Day 1 to Day 5. All doses were administered after food consumption and with water.	Participants with uncomplicated urinary tract infection (acute cystitis) randomized to receive nitrofurantoin 100 mg capsule, BID, orally on Day 1 to Day 5. The total daily dose of nitrofurantoin received was 200 mg. Participants also received 2 tablets of placebo matched with gepotidacin BID, orally on Day 1 to Day 5. All doses were administered after food consumption and with water.
Overall Number of Participants Analyzed	292	275
Measure Type: Count of Participants; Unit of Measure: Participants
Sustained Clinical Resolution (SCR)	168 57.5%	154 56.0%
Delayed Clinical Resolution (DCR)	34 11.6%	35 12.7%
Clinical Improvement (CI)	15 5.1%	19 6.9%
Clinical Worsening (CW)	26 8.9%	32 11.6%
Clinical Recurrence (CR)	8 2.7%	7 2.5%
Unable to Determine (UTD)	41 14.0%	28 10.2%

9. Secondary Outcome

Title	Number of Participants With Clinical Response at the Follow up (FU) Visit - Micro-ITT NTF-S Population
Description	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.
Time Frame	FU visit (Days 21 to 31)

Outcome Measure Data

Analysis Population Description

Micro-ITT NTF-S population

Arm/Group Title	Gepotidacin	Nitrofurantoin
Arm/Group Description:	Participants with uncomplicated urinary tract infection (acute cystitis) randomized to receive gepotidacin 1500 milligram (mg) (2*750 mg, tablets), twice daily (BID), orally on Day 1 to Day 5. The total daily dose of gepotidacin received was 3000 mg. Participants also received 1 capsule of placebo matched with nitrofurantoin BID, orally on Day 1 to Day 5. All doses were administered after food consumption and with water.	Participants with uncomplicated urinary tract infection (acute cystitis) randomized to receive nitrofurantoin 100 mg capsule, BID, orally on Day 1 to Day 5. The total daily dose of nitrofurantoin received was 200 mg. Participants also received 2 tablets of placebo matched with gepotidacin BID, orally on Day 1 to Day 5. All doses were administered after food consumption and with water.
Overall Number of Participants Analyzed	292	275
Measure Type: Count of Participants; Unit of Measure: Participants
Clinical Success	168 57.5%	154 56.0%
Clinical Failure	124 42.5%	121 44.0%

10. Secondary Outcome

Title	Number of Participants With Microbiological Outcome (MO) at the Follow up (FU) Visit - Micro-ITT NTF-S Population
Description	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.
Time Frame	FU visit (Days 21 to 31)

Outcome Measure Data

Analysis Population Description

Micro-ITT NTF-S population.

Arm/Group Title	Gepotidacin	Nitrofurantoin
Arm/Group Description:	Participants with uncomplicated urinary tract infection (acute cystitis) randomized to receive gepotidacin 1500 milligram (mg) (2*750 mg, tablets), twice daily (BID), orally on Day 1 to Day 5. The total daily dose of gepotidacin received was 3000 mg. Participants also received 1 capsule of placebo matched with nitrofurantoin BID, orally on Day 1 to Day 5. All doses were administered after food consumption and with water.	Participants with uncomplicated urinary tract infection (acute cystitis) randomized to receive nitrofurantoin 100 mg capsule, BID, orally on Day 1 to Day 5. The total daily dose of nitrofurantoin received was 200 mg. Participants also received 2 tablets of placebo matched with gepotidacin BID, orally on Day 1 to Day 5. All doses were administered after food consumption and with water.
Overall Number of Participants Analyzed	292	275
Measure Type: Count of Participants; Unit of Measure: Participants
Sustained Microbiological Eradication (SME)	154 52.7%	119 43.3%
Microbiological Persistence (MP)	19 6.5%	44 16.0%
Microbiological Recurrence (MR)	29 9.9%	23 8.4%
Delayed Microbiological Eradication (DME)	20 6.8%	28 10.2%
Unable to Determine (UTD)	70 24.0%	61 22.2%

11. Secondary Outcome

Title	Number of Participants With Microbiological Response at the Follow up (FU) Visit - Micro-ITT NTF-S Population
Description	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.
Time Frame	FU visit (Days 21 to 31)

Outcome Measure Data

Analysis Population Description

Micro-ITT NTF-S population.

Arm/Group Title	Gepotidacin	Nitrofurantoin
Arm/Group Description:	Participants with uncomplicated urinary tract infection (acute cystitis) randomized to receive gepotidacin 1500 milligram (mg) (2*750 mg, tablets), twice daily (BID), orally on Day 1 to Day 5. The total daily dose of gepotidacin received was 3000 mg. Participants also received 1 capsule of placebo matched with nitrofurantoin BID, orally on Day 1 to Day 5. All doses were administered after food consumption and with water.	Participants with uncomplicated urinary tract infection (acute cystitis) randomized to receive nitrofurantoin 100 mg capsule, BID, orally on Day 1 to Day 5. The total daily dose of nitrofurantoin received was 200 mg. Participants also received 2 tablets of placebo matched with gepotidacin BID, orally on Day 1 to Day 5. All doses were administered after food consumption and with water.
Overall Number of Participants Analyzed	292	275
Measure Type: Count of Participants; Unit of Measure: Participants
Microbiological Success	154 52.7%	119 43.3%
Microbiological Failure	138 47.3%	156 56.7%

12. Secondary Outcome

Title	Number of Participants With Clinical Outcome at the TOC Visit - Intent-to-Treat (ITT) Population
Description	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).
Time Frame	TOC visit (Days 9 to 16)

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) population included all participants randomly assigned to study treatment.

Arm/Group Title	Gepotidacin	Nitrofurantoin
Arm/Group Description:	Participants with uncomplicated urinary tract infection (acute cystitis) randomized to receive gepotidacin 1500 milligram (mg) (2*750 mg, tablets), twice daily (BID), orally on Day 1 to Day 5. The total daily dose of gepotidacin received was 3000 mg. Participants also received 1 capsule of placebo matched with nitrofurantoin BID, orally on Day 1 to Day 5. All doses were administered after food consumption and with water.	Participants with uncomplicated urinary tract infection (acute cystitis) randomized to receive nitrofurantoin 100 mg capsule, BID, orally on Day 1 to Day 5. The total daily dose of nitrofurantoin received was 200 mg. Participants also received 2 tablets of placebo matched with gepotidacin BID, orally on Day 1 to Day 5. All doses were administered after food consumption and with water.
Overall Number of Participants Analyzed	805	800
Measure Type: Count of Participants; Unit of Measure: Participants
Clinical Resolution	549 68.2%	517 64.6%
Clinical Improvement	153 19.0%	199 24.9%
Clinical Worsening	36 4.5%	39 4.9%
Unable to Determine	67 8.3%	45 5.6%

13. Secondary Outcome

Title	Number of Participants With Clinical Response at the TOC Visit - Intent-to-Treat (ITT) Population
Description	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.
Time Frame	TOC visit (Days 9 to 16)

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) population

Arm/Group Title	Gepotidacin	Nitrofurantoin
Arm/Group Description:	Participants with uncomplicated urinary tract infection (acute cystitis) randomized to receive gepotidacin 1500 milligram (mg) (2*750 mg, tablets), twice daily (BID), orally on Day 1 to Day 5. The total daily dose of gepotidacin received was 3000 mg. Participants also received 1 capsule of placebo matched with nitrofurantoin BID, orally on Day 1 to Day 5. All doses were administered after food consumption and with water.	Participants with uncomplicated urinary tract infection (acute cystitis) randomized to receive nitrofurantoin 100 mg capsule, BID, orally on Day 1 to Day 5. The total daily dose of nitrofurantoin received was 200 mg. Participants also received 2 tablets of placebo matched with gepotidacin BID, orally on Day 1 to Day 5. All doses were administered after food consumption and with water.
Overall Number of Participants Analyzed	805	800
Measure Type: Count of Participants; Unit of Measure: Participants
Clinical Success	549 68.2%	517 64.6%
Clinical Failure	256 31.8%	283 35.4%

14. Secondary Outcome

Title	Number of Participants With Clinical Outcome at the Follow up (FU) Visit - Intent-to-Treat (ITT) Population
Description	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).
Time Frame	FU visit (Days 21 to 31)

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) population

Arm/Group Title	Gepotidacin	Nitrofurantoin
Arm/Group Description:	Participants with uncomplicated urinary tract infection (acute cystitis) randomized to receive gepotidacin 1500 milligram (mg) (2*750 mg, tablets), twice daily (BID), orally on Day 1 to Day 5. The total daily dose of gepotidacin received was 3000 mg. Participants also received 1 capsule of placebo matched with nitrofurantoin BID, orally on Day 1 to Day 5. All doses were administered after food consumption and with water.	Participants with uncomplicated urinary tract infection (acute cystitis) randomized to receive nitrofurantoin 100 mg capsule, BID, orally on Day 1 to Day 5. The total daily dose of nitrofurantoin received was 200 mg. Participants also received 2 tablets of placebo matched with gepotidacin BID, orally on Day 1 to Day 5. All doses were administered after food consumption and with water.
Overall Number of Participants Analyzed	805	800
Measure Type: Count of Participants; Unit of Measure: Participants
Sustained Clinical Resolution (SCR)	478 59.4%	443 55.4%
Delayed Clinical Resolution (DCR)	108 13.4%	116 14.5%
Clinical Improvement (CI)	40 5.0%	52 6.5%
Clinical Worsening (CW)	51 6.3%	65 8.1%
Clinical Recurrence (CR)	25 3.1%	28 3.5%
Unable to Determine (UTD)	103 12.8%	96 12.0%

15. Secondary Outcome

Title	Number of Participants With Clinical Response at the Follow up (FU) Visit - Intent-to-Treat (ITT) Population
Description	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.
Time Frame	FU visit (Days 21 to 31)

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) population

Arm/Group Title	Gepotidacin	Nitrofurantoin
Arm/Group Description:	Participants with uncomplicated urinary tract infection (acute cystitis) randomized to receive gepotidacin 1500 milligram (mg) (2*750 mg, tablets), twice daily (BID), orally on Day 1 to Day 5. The total daily dose of gepotidacin received was 3000 mg. Participants also received 1 capsule of placebo matched with nitrofurantoin BID, orally on Day 1 to Day 5. All doses were administered after food consumption and with water.	Participants with uncomplicated urinary tract infection (acute cystitis) randomized to receive nitrofurantoin 100 mg capsule, BID, orally on Day 1 to Day 5. The total daily dose of nitrofurantoin received was 200 mg. Participants also received 2 tablets of placebo matched with gepotidacin BID, orally on Day 1 to Day 5. All doses were administered after food consumption and with water.
Overall Number of Participants Analyzed	805	800
Measure Type: Count of Participants; Unit of Measure: Participants
Clinical Success	478 59.4%	443 55.4%
Clinical Failure	327 40.6%	357 44.6%

16. Secondary Outcome

Title	Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Description	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.
Time Frame	From the time of first dose (Day 1) through the final follow-up visit (Day 21-31)

Outcome Measure Data

Analysis Population Description

Safety population included all randomized participants who receive at least 1 dose of study treatment.

Arm/Group Title	Gepotidacin	Nitrofurantoin
Arm/Group Description:	Participants with uncomplicated urinary tract infection (acute cystitis) randomized to receive gepotidacin 1500 milligram (mg) (2*750 mg, tablets), twice daily (BID), orally on Day 1 to Day 5. The total daily dose of gepotidacin received was 3000 mg. Participants also received 1 capsule of placebo matched with nitrofurantoin BID, orally on Day 1 to Day 5. All doses were administered after food consumption and with water.	Participants with uncomplicated urinary tract infection (acute cystitis) randomized to receive nitrofurantoin 100 mg capsule, BID, orally on Day 1 to Day 5. The total daily dose of nitrofurantoin received was 200 mg. Participants also received 2 tablets of placebo matched with gepotidacin BID, orally on Day 1 to Day 5. All doses were administered after food consumption and with water.
Overall Number of Participants Analyzed	804	798
Measure Type: Count of Participants; Unit of Measure: Participants
	285 35.4%	200 25.1%

17. Secondary Outcome

Title	Number of Participants With Serious Adverse Events (SAEs)
Description	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.
Time Frame	From the time of first dose (Day 1) through the final follow-up visit (Day 21-31)

Outcome Measure Data

Analysis Population Description

Safety population included all randomized participants who receive at least 1 dose of study treatment.

Arm/Group Title	Gepotidacin	Nitrofurantoin
Arm/Group Description:	Participants with uncomplicated urinary tract infection (acute cystitis) randomized to receive gepotidacin 1500 milligram (mg) (2*750 mg, tablets), twice daily (BID), orally on Day 1 to Day 5. The total daily dose of gepotidacin received was 3000 mg. Participants also received 1 capsule of placebo matched with nitrofurantoin BID, orally on Day 1 to Day 5. All doses were administered after food consumption and with water.	Participants with uncomplicated urinary tract infection (acute cystitis) randomized to receive nitrofurantoin 100 mg capsule, BID, orally on Day 1 to Day 5. The total daily dose of nitrofurantoin received was 200 mg. Participants also received 2 tablets of placebo matched with gepotidacin BID, orally on Day 1 to Day 5. All doses were administered after food consumption and with water.
Overall Number of Participants Analyzed	804	798
Measure Type: Count of Participants; Unit of Measure: Participants
	5 0.6%	5 0.6%

18. Secondary Outcome

Title	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
Description	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.
Time Frame	Baseline (on or before Day 1), On-Therapy (Days 2 to 5), and Test of cure (Days 9 to 16)

Outcome Measure Data

Analysis Population Description

Safety population. Only those participants with data available at the specified data points were analyzed.

Arm/Group Title		Gepotidacin	Nitrofurantoin
Arm/Group Description:		Participants with uncomplicated urinary tract infection (acute cystitis) randomized to receive gepotidacin 1500 milligram (mg) (2*750 mg, tablets), twice daily (BID), orally on Day 1 to Day 5. The total daily dose of gepotidacin received was 3000 mg. Participants also received 1 capsule of placebo matched with nitrofurantoin BID, orally on Day 1 to Day 5. All doses were administered after food consumption and with water.	Participants with uncomplicated urinary tract infection (acute cystitis) randomized to receive nitrofurantoin 100 mg capsule, BID, orally on Day 1 to Day 5. The total daily dose of nitrofurantoin received was 200 mg. Participants also received 2 tablets of placebo matched with gepotidacin BID, orally on Day 1 to Day 5. All doses were administered after food consumption and with water.
Overall Number of Participants Analyzed		736	737
Mean (Standard Deviation); Unit of Measure: Giga cells per Liter (10^9 cells/L)
Eosinophils, Baseline	Number Analyzed	702 participants	698 participants
		0.161 (0.1350)	0.163 (0.1331)
Eosinophils, On-Therapy	Number Analyzed	622 participants	606 participants
		0.006 (0.0841)	0.013 (0.0814)
Eosinophils, Test of Cure	Number Analyzed	608 participants	599 participants
		0.015 (0.0906)	0.018 (0.1081)
Basophils, Baseline	Number Analyzed	642 participants	668 participants
		0.054 (0.0227)	0.053 (0.0228)
Basophils, On-Therapy	Number Analyzed	533 participants	550 participants
		-0.001 (0.0195)	0.001 (0.0194)
Basophils, Test of Cure	Number Analyzed	528 participants	551 participants
		0.000 (0.0209)	0.001 (0.0183)
Lymphocytes, Baseline	Number Analyzed	736 participants	737 participants
		2.091 (0.6954)	2.121 (0.7122)
Lymphocytes, On-Therapy	Number Analyzed	661 participants	657 participants
		-0.018 (0.4523)	-0.076 (0.5051)
Lymphocytes, Test of Cure	Number Analyzed	641 participants	651 participants
		-0.010 (0.5292)	0.059 (0.5839)
Monocytes, Baseline	Number Analyzed	736 participants	737 participants
		0.529 (0.1803)	0.525 (0.1790)
Monocytes, On-Therapy	Number Analyzed	661 participants	657 participants
		-0.020 (0.1487)	0.003 (0.1711)
Monocytes, Test of Cure	Number Analyzed	641 participants	651 participants
		-0.029 (0.1731)	-0.012 (0.1778)
Neutrophils, Baseline	Number Analyzed	736 participants	737 participants
		4.582 (1.8893)	4.755 (1.8821)
Neutrophils, On-Therapy	Number Analyzed	661 participants	656 participants
		-0.490 (1.6201)	-0.453 (1.7453)
Neutrophils, Test of Cure	Number Analyzed	641 participants	651 participants
		-0.534 (2.0207)	-0.494 (1.9072)
Platelets, Baseline	Number Analyzed	723 participants	729 participants
		280.3 (68.46)	287.2 (73.51)
Platelets, On-Therapy	Number Analyzed	649 participants	648 participants
		-1.1 (33.03)	-2.5 (36.67)
Platelets, Test of Cure	Number Analyzed	626 participants	637 participants
		6.8 (42.12)	5.5 (58.04)

19. Secondary Outcome

Title	Change From Baseline in Hematology Parameter: Hemoglobin Level
Description	Blood samples were collected for the analysis of hemoglobin level. Baseline is defined as the latest pre-dose assessment with a non-missing value.
Time Frame	Baseline (on or before Day 1), On-Therapy (Days 2 to 5), and Test of cure (Days 9 to 16)

Outcome Measure Data

Analysis Population Description

Safety population. Only those participants with data available at the specified data points were analyzed.

Arm/Group Title		Gepotidacin	Nitrofurantoin
Arm/Group Description:		Participants with uncomplicated urinary tract infection (acute cystitis) randomized to receive gepotidacin 1500 milligram (mg) (2*750 mg, tablets), twice daily (BID), orally on Day 1 to Day 5. The total daily dose of gepotidacin received was 3000 mg. Participants also received 1 capsule of placebo matched with nitrofurantoin BID, orally on Day 1 to Day 5. All doses were administered after food consumption and with water.	Participants with uncomplicated urinary tract infection (acute cystitis) randomized to receive nitrofurantoin 100 mg capsule, BID, orally on Day 1 to Day 5. The total daily dose of nitrofurantoin received was 200 mg. Participants also received 2 tablets of placebo matched with gepotidacin BID, orally on Day 1 to Day 5. All doses were administered after food consumption and with water.
Overall Number of Participants Analyzed		739	737
Mean (Standard Deviation); Unit of Measure: Gram per Liter (g/L)
Baseline	Number Analyzed	739 participants	737 participants
		132.5 (13.25)	131.7 (14.28)
On-Therapy	Number Analyzed	665 participants	657 participants
		-1.5 (6.74)	-1.9 (6.82)
Test of Cure	Number Analyzed	643 participants	653 participants
		-1.3 (7.44)	-1.4 (8.33)

20. Secondary Outcome

Title	Change From Baseline in Hematology Parameter: Hematocrit Level
Description	Blood samples were collected for the analysis of hematocrit level. Baseline is defined as the latest pre-dose assessment with a non-missing value.
Time Frame	Baseline (on or before Day 1), On-Therapy (Days 2 to 5), and Test of cure (Days 9 to 16)

Outcome Measure Data

Analysis Population Description

Safety population. Only those participants with data available at the specified data points were analyzed.

Arm/Group Title		Gepotidacin	Nitrofurantoin
Arm/Group Description:		Participants with uncomplicated urinary tract infection (acute cystitis) randomized to receive gepotidacin 1500 milligram (mg) (2*750 mg, tablets), twice daily (BID), orally on Day 1 to Day 5. The total daily dose of gepotidacin received was 3000 mg. Participants also received 1 capsule of placebo matched with nitrofurantoin BID, orally on Day 1 to Day 5. All doses were administered after food consumption and with water.	Participants with uncomplicated urinary tract infection (acute cystitis) randomized to receive nitrofurantoin 100 mg capsule, BID, orally on Day 1 to Day 5. The total daily dose of nitrofurantoin received was 200 mg. Participants also received 2 tablets of placebo matched with gepotidacin BID, orally on Day 1 to Day 5. All doses were administered after food consumption and with water.
Overall Number of Participants Analyzed		739	737
Mean (Standard Deviation); Unit of Measure: Percentage of hematocrit
Baseline	Number Analyzed	739 participants	737 participants
		0.4314 (0.04146)	0.4292 (0.04348)
On-Therapy	Number Analyzed	665 participants	657 participants
		-0.0033 (0.02832)	-0.0041 (0.02715)
Test of Cure	Number Analyzed	643 participants	653 participants
		-0.0045 (0.02806)	-0.0029 (0.03194)

21. Secondary Outcome

Title	Change From Baseline in Hematology Parameter: Erythrocytes (RBC) Count
Description	Blood samples were collected for the analysis of erythrocytes count. Baseline is defined as the latest pre-dose assessment with a non-missing value.
Time Frame	Baseline (on or before Day 1), On-Therapy (Days 2 to 5), and Test of cure (Days 9 to 16)

Outcome Measure Data

Analysis Population Description

Safety population. Only those participants with data available at the specified data points were analyzed.

Arm/Group Title		Gepotidacin	Nitrofurantoin
Arm/Group Description:		Participants with uncomplicated urinary tract infection (acute cystitis) randomized to receive gepotidacin 1500 milligram (mg) (2*750 mg, tablets), twice daily (BID), orally on Day 1 to Day 5. The total daily dose of gepotidacin received was 3000 mg. Participants also received 1 capsule of placebo matched with nitrofurantoin BID, orally on Day 1 to Day 5. All doses were administered after food consumption and with water.	Participants with uncomplicated urinary tract infection (acute cystitis) randomized to receive nitrofurantoin 100 mg capsule, BID, orally on Day 1 to Day 5. The total daily dose of nitrofurantoin received was 200 mg. Participants also received 2 tablets of placebo matched with gepotidacin BID, orally on Day 1 to Day 5. All doses were administered after food consumption and with water.
Overall Number of Participants Analyzed		739	737
Mean (Standard Deviation); Unit of Measure: Tera cells per Liter (10^12 cells/L)
Baseline	Number Analyzed	739 participants	737 participants
		4.539 (0.4211)	4.539 (0.4379)
On-Therapy	Number Analyzed	665 participants	657 participants
		-0.046 (0.2309)	-0.060 (0.2513)
Test of Cure	Number Analyzed	643 participants	653 participants
		-0.038 (0.2634)	-0.049 (0.3052)

22. Secondary Outcome

Title	Change From Baseline in Hematology Parameter: Mean Corpuscular Hemoglobin (MCH)
Description	Blood samples were collected for the analysis of MCH. Baseline is defined as the latest pre-dose assessment with a non-missing value.
Time Frame	Baseline (on or before Day 1), On-Therapy (Days 2 to 5), and Test of cure (Days 9 to 16)

Outcome Measure Data

Analysis Population Description

Safety population. Only those participants with data available at the specified data points were analyzed.

Arm/Group Title		Gepotidacin	Nitrofurantoin
Arm/Group Description:		Participants with uncomplicated urinary tract infection (acute cystitis) randomized to receive gepotidacin 1500 milligram (mg) (2*750 mg, tablets), twice daily (BID), orally on Day 1 to Day 5. The total daily dose of gepotidacin received was 3000 mg. Participants also received 1 capsule of placebo matched with nitrofurantoin BID, orally on Day 1 to Day 5. All doses were administered after food consumption and with water.	Participants with uncomplicated urinary tract infection (acute cystitis) randomized to receive nitrofurantoin 100 mg capsule, BID, orally on Day 1 to Day 5. The total daily dose of nitrofurantoin received was 200 mg. Participants also received 2 tablets of placebo matched with gepotidacin BID, orally on Day 1 to Day 5. All doses were administered after food consumption and with water.
Overall Number of Participants Analyzed		739	737
Mean (Standard Deviation); Unit of Measure: Picogram (pg)
Baseline	Number Analyzed	739 participants	737 participants
		29.28 (2.537)	29.09 (2.644)
On-Therapy	Number Analyzed	665 participants	657 participants
		-0.02 (0.795)	-0.02 (0.820)
Test of Cure	Number Analyzed	643 participants	653 participants
		-0.04 (0.780)	0.02 (0.917)

23. Secondary Outcome

Title	Change From Baseline in Hematology Parameter: Mean Corpuscular Volume (MCV)
Description	Blood samples were collected for the analysis of MCV. Baseline is defined as the latest pre-dose assessment with a non-missing value.
Time Frame	Baseline (on or before Day 1), On-Therapy (Days 2 to 5), and Test of cure (Days 9 to 16)

Outcome Measure Data

Analysis Population Description

Safety population. Only those participants with data available at the specified data points were analyzed.

Arm/Group Title		Gepotidacin	Nitrofurantoin
Arm/Group Description:		Participants with uncomplicated urinary tract infection (acute cystitis) randomized to receive gepotidacin 1500 milligram (mg) (2*750 mg, tablets), twice daily (BID), orally on Day 1 to Day 5. The total daily dose of gepotidacin received was 3000 mg. Participants also received 1 capsule of placebo matched with nitrofurantoin BID, orally on Day 1 to Day 5. All doses were administered after food consumption and with water.	Participants with uncomplicated urinary tract infection (acute cystitis) randomized to receive nitrofurantoin 100 mg capsule, BID, orally on Day 1 to Day 5. The total daily dose of nitrofurantoin received was 200 mg. Participants also received 2 tablets of placebo matched with gepotidacin BID, orally on Day 1 to Day 5. All doses were administered after food consumption and with water.
Overall Number of Participants Analyzed		739	737
Mean (Standard Deviation); Unit of Measure: Femtolitre (fL)
Baseline	Number Analyzed	739 participants	737 participants
		95.30 (7.191)	94.82 (7.511)
On-Therapy	Number Analyzed	665 participants	657 participants
		0.26 (4.287)	0.35 (4.303)
Test of Cure	Number Analyzed	643 participants	653 participants
		-0.15 (4.049)	0.39 (4.730)

24. Secondary Outcome

Title	Change From Baseline in Clinical Chemistry Parameters: Serum Blood Urea Nitrogen (BUN), Glucose Non-fasting, Calcium, Chloride, Sodium, Magnesium, Phosphate, and Potassium Levels
Description	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.
Time Frame	Baseline (on or before Day 1), On-Therapy (Days 2 to 5), and Test of cure (Days 9 to 16)

Outcome Measure Data

Analysis Population Description

Safety population. Only those participants with data available at the specified data points were analyzed.

Arm/Group Title		Gepotidacin	Nitrofurantoin
Arm/Group Description:		Participants with uncomplicated urinary tract infection (acute cystitis) randomized to receive gepotidacin 1500 milligram (mg) (2*750 mg, tablets), twice daily (BID), orally on Day 1 to Day 5. The total daily dose of gepotidacin received was 3000 mg. Participants also received 1 capsule of placebo matched with nitrofurantoin BID, orally on Day 1 to Day 5. All doses were administered after food consumption and with water.	Participants with uncomplicated urinary tract infection (acute cystitis) randomized to receive nitrofurantoin 100 mg capsule, BID, orally on Day 1 to Day 5. The total daily dose of nitrofurantoin received was 200 mg. Participants also received 2 tablets of placebo matched with gepotidacin BID, orally on Day 1 to Day 5. All doses were administered after food consumption and with water.
Overall Number of Participants Analyzed		781	777
Mean (Standard Deviation); Unit of Measure: millimoles per liter (mmol/L)
Serum Urea Nitrogen, Baseline	Number Analyzed	780 participants	776 participants
		4.742 (2.1107)	4.724 (1.8645)
Serum Urea Nitrogen, On- Therapy	Number Analyzed	714 participants	721 participants
		-0.056 (1.4269)	-0.018 (1.1663)
Serum Urea Nitrogen, Test of Cure	Number Analyzed	703 participants	716 participants
		0.022 (1.4000)	0.131 (1.4826)
Serum Calcium, Baseline	Number Analyzed	776 participants	773 participants
		2.363 (0.1196)	2.362 (0.1083)
Serum Calcium, On-Therapy	Number Analyzed	705 participants	717 participants
		-0.010 (0.0950)	-0.018 (0.0944)
Serum Calcium, Test of Cure	Number Analyzed	698 participants	712 participants
		-0.014 (0.1070)	-0.016 (0.0981)
Serum Chloride, Baseline	Number Analyzed	780 participants	776 participants
		101.0 (3.27)	100.9 (3.27)
Serum Chloride, On-Therapy	Number Analyzed	713 participants	721 participants
		0.3 (2.80)	0.1 (2.85)
Serum Chloride, Test of Cure	Number Analyzed	701 participants	716 participants
		0.4 (2.93)	0.4 (3.02)
Serum Glucose, Baseline	Number Analyzed	777 participants	774 participants
		5.590 (1.9980)	5.719 (2.1915)
Serum Glucose, On-Therapy	Number Analyzed	705 participants	719 participants
		0.230 (1.5120)	0.328 (1.9380)
Serum Glucose, Test of Cure	Number Analyzed	698 participants	709 participants
		0.215 (1.4412)	0.266 (1.6667)
Serum Magnesium, Baseline	Number Analyzed	776 participants	773 participants
		0.839 (0.0749)	0.835 (0.0802)
Serum Magnesium, On-Therapy	Number Analyzed	706 participants	717 participants
		-0.001 (0.0635)	-0.015 (0.0616)
Serum Magnesium, Test of Cure	Number Analyzed	698 participants	712 participants
		-0.011 (0.0674)	-0.015 (0.0689)
Serum Potassium, Baseline	Number Analyzed	776 participants	772 participants
		4.32 (0.414)	4.27 (0.415)
Serum Potassium, On-Therapy	Number Analyzed	701 participants	717 participants
		-0.04 (0.417)	-0.03 (0.428)
Serum Potassium, Test of Cure	Number Analyzed	696 participants	710 participants
		-0.03 (0.438)	0.00 (0.461)
Serum Phosphate, Baseline	Number Analyzed	778 participants	774 participants
		1.141 (0.1828)	1.139 (0.1725)
Serum Phosphate, On-Therapy	Number Analyzed	704 participants	719 participants
		-0.005 (0.1782)	-0.027 (0.1836)
Serum Phosphate, Test of Cure	Number Analyzed	699 participants	711 participants
		0.002 (0.1851)	-0.004 (0.1939)
Serum Sodium, Baseline	Number Analyzed	781 participants	777 participants
		138.8 (2.64)	138.8 (2.76)
Serum Sodium, On-Therapy	Number Analyzed	714 participants	724 participants
		0.0 (2.64)	-0.2 (2.64)
Serum Sodium, Test of Cure	Number Analyzed	702 participants	717 participants
		0.2 (2.91)	0.1 (2.91)

25. Secondary Outcome

Title	Change From Baseline in Clinical Chemistry Parameters: Total Bilirubin, Direct Bilirubin and Creatinine Levels
Description	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.
Time Frame	Baseline (on or before Day 1), On-Therapy (Days 2 to 5), and Test of cure (Days 9 to 16)

Outcome Measure Data

Analysis Population Description

Safety population. Only those participants with data available at the specified data points were analyzed.

Arm/Group Title		Gepotidacin	Nitrofurantoin
Arm/Group Description:		Participants with uncomplicated urinary tract infection (acute cystitis) randomized to receive gepotidacin 1500 milligram (mg) (2*750 mg, tablets), twice daily (BID), orally on Day 1 to Day 5. The total daily dose of gepotidacin received was 3000 mg. Participants also received 1 capsule of placebo matched with nitrofurantoin BID, orally on Day 1 to Day 5. All doses were administered after food consumption and with water.	Participants with uncomplicated urinary tract infection (acute cystitis) randomized to receive nitrofurantoin 100 mg capsule, BID, orally on Day 1 to Day 5. The total daily dose of nitrofurantoin received was 200 mg. Participants also received 2 tablets of placebo matched with gepotidacin BID, orally on Day 1 to Day 5. All doses were administered after food consumption and with water.
Overall Number of Participants Analyzed		779	776
Mean (Standard Deviation); Unit of Measure: micromoles per Liter (umol/L)
Serum Direct Bilirubin, Baseline	Number Analyzed	93 participants	84 participants
		4.61 (1.669)	4.47 (1.128)
Serum Direct Bilirubin, On- Therapy	Number Analyzed	50 participants	41 participants
		-0.18 (1.192)	-0.18 (1.114)
Serum Direct Bilirubin, Test of Cure	Number Analyzed	46 participants	38 participants
		-0.19 (1.059)	0.15 (1.288)
Serum Total Bilirubin, Baseline	Number Analyzed	751 participants	742 participants
		6.57 (3.940)	6.56 (3.518)
Serum Total Bilirubin, On-Therapy	Number Analyzed	655 participants	670 participants
		-0.28 (2.510)	-0.42 (2.672)
Serum Total Bilirubin, Test of Cure	Number Analyzed	652 participants	656 participants
		-0.01 (2.976)	-0.29 (3.230)
Serum Creatinine, Baseline	Number Analyzed	779 participants	776 participants
		58.8 (30.59)	58.1 (17.22)
Serum Creatinine, On-Therapy	Number Analyzed	712 participants	721 participants
		0.8 (30.31)	0.3 (10.31)
Serum Creatinine, Test of Cure	Number Analyzed	703 participants	715 participants
		1.7 (14.00)	1.5 (13.40)

26. Secondary Outcome

Title	Change From Baseline in Clinical Chemistry Parameters: Albumin and Protein Levels
Description	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.
Time Frame	Baseline (on or before Day 1), On-Therapy (Days 2 to 5), and Test of cure (Days 9 to 16)

Outcome Measure Data

Analysis Population Description

Safety population. Only those participants with data available at the specified data points were analyzed.

Arm/Group Title		Gepotidacin	Nitrofurantoin
Arm/Group Description:		Participants with uncomplicated urinary tract infection (acute cystitis) randomized to receive gepotidacin 1500 milligram (mg) (2*750 mg, tablets), twice daily (BID), orally on Day 1 to Day 5. The total daily dose of gepotidacin received was 3000 mg. Participants also received 1 capsule of placebo matched with nitrofurantoin BID, orally on Day 1 to Day 5. All doses were administered after food consumption and with water.	Participants with uncomplicated urinary tract infection (acute cystitis) randomized to receive nitrofurantoin 100 mg capsule, BID, orally on Day 1 to Day 5. The total daily dose of nitrofurantoin received was 200 mg. Participants also received 2 tablets of placebo matched with gepotidacin BID, orally on Day 1 to Day 5. All doses were administered after food consumption and with water.
Overall Number of Participants Analyzed		781	777
Mean (Standard Deviation); Unit of Measure: gram per Liter (g/L)
Serum Albumin, Baseline	Number Analyzed	781 participants	777 participants
		45.2 (3.33)	45.2 (3.11)
Serum Albumin, On-Therapy	Number Analyzed	715 participants	725 participants
		-0.4 (2.38)	-0.8 (2.56)
Serum Albumin, Test of Cure	Number Analyzed	705 participants	720 participants
		-0.5 (2.65)	-0.6 (2.84)
Serum Protein, Baseline	Number Analyzed	778 participants	774 participants
		71.5 (5.12)	71.6 (4.72)
Serum Protein, On-Therapy	Number Analyzed	709 participants	719 participants
		-0.7 (3.71)	-1.2 (3.89)
Serum Protein, Test of Cure	Number Analyzed	700 participants	711 participants
		-1.0 (4.19)	-1.1 (4.32)

27. Secondary Outcome

Title	Change From Baseline in Clinical Chemistry Parameters: Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) and Alkaline Phosphatase (ALP) Levels
Description	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.
Time Frame	Baseline (on or before Day 1), On-Therapy (Days 2 to 5), and Test of cure (Days 9 to 16)

Outcome Measure Data

Analysis Population Description

Safety population. Only those participants with data available at the specified data points were analyzed.

Arm/Group Title		Gepotidacin	Nitrofurantoin
Arm/Group Description:		Participants with uncomplicated urinary tract infection (acute cystitis) randomized to receive gepotidacin 1500 milligram (mg) (2*750 mg, tablets), twice daily (BID), orally on Day 1 to Day 5. The total daily dose of gepotidacin received was 3000 mg. Participants also received 1 capsule of placebo matched with nitrofurantoin BID, orally on Day 1 to Day 5. All doses were administered after food consumption and with water.	Participants with uncomplicated urinary tract infection (acute cystitis) randomized to receive nitrofurantoin 100 mg capsule, BID, orally on Day 1 to Day 5. The total daily dose of nitrofurantoin received was 200 mg. Participants also received 2 tablets of placebo matched with gepotidacin BID, orally on Day 1 to Day 5. All doses were administered after food consumption and with water.
Overall Number of Participants Analyzed		777	774
Mean (Standard Deviation); Unit of Measure: Units per Liter (U/L)
Serum ALT, Baseline	Number Analyzed	776 participants	773 participants
		20.3 (20.34)	19.5 (14.66)
Serum ALT, On-Therapy	Number Analyzed	705 participants	716 participants
		0.2 (10.8)	-0.1 (7.9)
Serum ALT, Test of Cure	Number Analyzed	699 participants	710 participants
		0.4 (15.81)	-0.2 (9.93)
Serum AST, Baseline	Number Analyzed	777 participants	774 participants
		21.0 (13.72)	20.2 (10.48)
Serum AST, On-Therapy	Number Analyzed	706 participants	719 participants
		0.1 (9.83)	0.0 (7.90)
Serum AST, Test of Cure	Number Analyzed	700 participants	710 participants
		0.9 (9.89)	-0.5 (8.29)
Serum ALP, Baseline	Number Analyzed	776 participants	773 participants
		81.4 (29.96)	81.7 (28.99)
Serum ALP, On- Therapy	Number Analyzed	707 participants	717 participants
		-0.5 (9.61)	-0.1 (12.91)
Serum ALP, Test of Cure	Number Analyzed	698 participants	712 participants
		-1.0 (12.00)	-0.4 (15.38)

28. Secondary Outcome

Title	Number of Participants With Urinalysis Dipstick Results
Description	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.
Time Frame	Baseline (on or before Day 1), On-Therapy (Days 2 to 5), and Test of cure (Days 9 to 16)

Outcome Measure Data

Analysis Population Description

Safety population. Only those participants with data available at the specified data points were analyzed.

Arm/Group Title		Gepotidacin	Nitrofurantoin
Arm/Group Description:		Participants with uncomplicated urinary tract infection (acute cystitis) randomized to receive gepotidacin 1500 milligram (mg) (2*750 mg, tablets), twice daily (BID), orally on Day 1 to Day 5. The total daily dose of gepotidacin received was 3000 mg. Participants also received 1 capsule of placebo matched with nitrofurantoin BID, orally on Day 1 to Day 5. All doses were administered after food consumption and with water.	Participants with uncomplicated urinary tract infection (acute cystitis) randomized to receive nitrofurantoin 100 mg capsule, BID, orally on Day 1 to Day 5. The total daily dose of nitrofurantoin received was 200 mg. Participants also received 2 tablets of placebo matched with gepotidacin BID, orally on Day 1 to Day 5. All doses were administered after food consumption and with water.
Overall Number of Participants Analyzed		789	783
Measure Type: Count of Participants; Unit of Measure: Participants
GLU, Baseline, Negative	Number Analyzed	779 participants	773 participants
		751 96.4%	738 95.5%
GLU, Baseline, 50 mg/dL	Number Analyzed	779 participants	773 participants
		4 0.5%	5 0.6%
GLU, Baseline, 150 mg/dL	Number Analyzed	779 participants	773 participants
		3 0.4%	4 0.5%
GLU, Baseline, >= 500 mg/dL	Number Analyzed	779 participants	773 participants
		21 2.7%	26 3.4%
GLU, On-Therapy, Negative	Number Analyzed	731 participants	737 participants
		700 95.8%	697 94.6%
GLU, On-Therapy, 50 mg/dL	Number Analyzed	731 participants	737 participants
		7 1.0%	7 0.9%
GLU, On-Therapy, 150 mg/dL	Number Analyzed	731 participants	737 participants
		1 0.1%	5 0.7%
GLU, On-Therapy, >= 500 mg/dL	Number Analyzed	731 participants	737 participants
		23 3.1%	28 3.8%
GLU, Test of Cure, Negative	Number Analyzed	719 participants	727 participants
		686 95.4%	693 95.3%
GLU, Test of Cure, 50 mg/dL	Number Analyzed	719 participants	727 participants
		9 1.3%	10 1.4%
GLU, Test of Cure, 150 mg/dL	Number Analyzed	719 participants	727 participants
		12 1.7%	4 0.6%
GLU, Test of Cure, >= 500 mg/dL	Number Analyzed	719 participants	727 participants
		12 1.7%	20 2.8%
PRO, Baseline, Negative	Number Analyzed	778 participants	769 participants
		524 67.4%	529 68.8%
PRO, Baseline, 30 mg/dL	Number Analyzed	778 participants	769 participants
		171 22.0%	149 19.4%
PRO, Baseline, 100 mg/dL	Number Analyzed	778 participants	769 participants
		78 10.0%	85 11.1%
PRO, Baseline, >=500 mg/dL	Number Analyzed	778 participants	769 participants
		5 0.6%	6 0.8%
PRO, On-Therapy, Negative	Number Analyzed	731 participants	737 participants
		575 78.7%	631 85.6%
PRO, On-Therapy, 30 mg/dL	Number Analyzed	731 participants	737 participants
		110 15.0%	83 11.3%
PRO, On-Therapy, 100 mg/dL	Number Analyzed	719 participants	727 participants
		43 6.0%	19 2.6%
PRO, On-Therapy, >=500 mg/dL	Number Analyzed	731 participants	737 participants
		3 0.4%	4 0.5%
PRO, Test of Cure, Negative	Number Analyzed	719 participants	727 participants
		605 84.1%	605 83.2%
PRO, Test of Cure, 30 mg/dL	Number Analyzed	719 participants	727 participants
		88 12.2%	88 12.1%
PRO, Test of Cure, 100 mg/dL	Number Analyzed	731 participants	737 participants
		25 3.4%	34 4.6%
PRO, Test of Cure, >=500 mg/dL	Number Analyzed	719 participants	727 participants
		1 0.1%	0 0.0%
BLO, Baseline, Positive	Number Analyzed	784 participants	777 participants
		0 0.0%	2 0.3%
BLO, Baseline, Negative	Number Analyzed	784 participants	777 participants
		345 44.0%	348 44.8%
BLO, Baseline, Trace	Number Analyzed	784 participants	777 participants
		2 0.3%	0 0.0%
BLO, Baseline, Small	Number Analyzed	784 participants	777 participants
		229 29.2%	217 27.9%
BLO, Baseline, Moderate	Number Analyzed	784 participants	777 participants
		128 16.3%	129 16.6%
BLO, Baseline, Large	Number Analyzed	784 participants	777 participants
		80 10.2%	81 10.4%
BLO, On-Therapy, Negative	Number Analyzed	731 participants	737 participants
		560 76.6%	520 70.6%
BLO, On-Therapy, Small	Number Analyzed	731 participants	737 participants
		116 15.9%	161 21.8%
BLO, On-Therapy, Moderate	Number Analyzed	731 participants	737 participants
		23 3.1%	30 4.1%
BLO, On-Therapy, Large	Number Analyzed	731 participants	737 participants
		32 4.4%	26 3.5%
BLO, Test of Cure, Negative	Number Analyzed	719 participants	727 participants
		517 71.9%	511 70.3%
BLO, Test of Cure, Small	Number Analyzed	719 participants	727 participants
		128 17.8%	139 19.1%
BLO, Test of Cure, Moderate	Number Analyzed	719 participants	727 participants
		49 6.8%	45 6.2%
BLO, Test of Cure, Large	Number Analyzed	719 participants	727 participants
		25 3.5%	32 4.4%
KET, Baseline, Negative	Number Analyzed	779 participants	773 participants
		754 96.8%	748 96.8%
KET, Baseline, 5 mg/dL	Number Analyzed	779 participants	773 participants
		14 1.8%	18 2.3%
KET, Baseline, 20 mg/dL	Number Analyzed	779 participants	773 participants
		11 1.4%	7 0.9%
KET, On-Therapy, Negative	Number Analyzed	731 participants	737 participants
		712 97.4%	699 94.8%
KET, On-Therapy, 5 mg/dL	Number Analyzed	731 participants	737 participants
		14 1.9%	22 3.0%
KET, On-Therapy, 20 mg/dL	Number Analyzed	731 participants	737 participants
		5 0.7%	15 2.0%
KET, On-Therapy, >=80 mg/dL	Number Analyzed	731 participants	737 participants
		0 0.0%	1 0.1%
KET, Test of Cure, Negative	Number Analyzed	719 participants	727 participants
		706 98.2%	700 96.3%
KET, Test of Cure, 5 mg/dL	Number Analyzed	719 participants	727 participants
		7 1.0%	20 2.8%
KET, Test of Cure, 20 mg/dL	Number Analyzed	719 participants	727 participants
		6 0.8%	7 1.0%
NIT, Baseline, Negative	Number Analyzed	789 participants	783 participants
		552 70.0%	531 67.8%
NIT, Baseline, Positive	Number Analyzed	789 participants	783 participants
		237 30.0%	252 32.2%
NIT, On-Therapy, Negative	Number Analyzed	731 participants	737 participants
		694 94.9%	697 94.6%
NIT, On-Therapy, Positive	Number Analyzed	731 participants	737 participants
		37 5.1%	40 5.4%
NIT, Test of Cure, Negative	Number Analyzed	719 participants	727 participants
		697 96.9%	669 92.0%
NIT, Test of Cure, Positive	Number Analyzed	719 participants	727 participants
		22 3.1%	58 8.0%
LEU, Baseline, Negative	Number Analyzed	789 participants	782 participants
		245 31.1%	232 29.7%
LEU, Baseline, Trace	Number Analyzed	789 participants	782 participants
		96 12.2%	91 11.6%
LEU, Baseline, Small	Number Analyzed	789 participants	782 participants
		75 9.5%	80 10.2%
LEU, Baseline, Moderate	Number Analyzed	789 participants	782 participants
		120 15.2%	116 14.8%
LEU, Baseline, Large	Number Analyzed	789 participants	782 participants
		251 31.8%	262 33.5%
LEU, Baseline, Missing	Number Analyzed	789 participants	782 participants
		2 0.3%	1 0.1%
LEU, On-Therapy, Negative	Number Analyzed	731 participants	737 participants
		510 69.8%	475 64.5%
LEU, On-Therapy, Trace	Number Analyzed	731 participants	737 participants
		79 10.8%	82 11.1%
LEU, On-Therapy, Small	Number Analyzed	731 participants	737 participants
		50 6.8%	49 6.6%
LEU, On-Therapy, Moderate	Number Analyzed	731 participants	737 participants
		34 4.7%	57 7.7%
LEU, On-Therapy, Large	Number Analyzed	731 participants	737 participants
		58 7.9%	74 10.0%
LEU, Test of Cure, Negative	Number Analyzed	719 participants	727 participants
		526 73.2%	494 68.0%
LEU, Test of Cure, Trace	Number Analyzed	719 participants	727 participants
		61 8.5%	49 6.7%
LEU, Test of Cure, Small	Number Analyzed	719 participants	727 participants
		43 6.0%	48 6.6%
LEU, Test of Cure, Moderate	Number Analyzed	719 participants	727 participants
		35 4.9%	59 8.1%
LEU, Test of Cure, Large	Number Analyzed	719 participants	727 participants
		54 7.5%	77 10.6%

29. Secondary Outcome

Title	Absolute Mean Values of Urine Specific Gravity
Description	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.
Time Frame	Baseline (on or before Day 1), On-Therapy (Days 2 to 5), and Test of cure (Days 9 to 16)

Outcome Measure Data

Analysis Population Description

Safety population. Only those participants with data available at the specified data points were analyzed.

Arm/Group Title		Gepotidacin	Nitrofurantoin
Arm/Group Description:		Participants with uncomplicated urinary tract infection (acute cystitis) randomized to receive gepotidacin 1500 milligram (mg) (2*750 mg, tablets), twice daily (BID), orally on Day 1 to Day 5. The total daily dose of gepotidacin received was 3000 mg. Participants also received 1 capsule of placebo matched with nitrofurantoin BID, orally on Day 1 to Day 5. All doses were administered after food consumption and with water.	Participants with uncomplicated urinary tract infection (acute cystitis) randomized to receive nitrofurantoin 100 mg capsule, BID, orally on Day 1 to Day 5. The total daily dose of nitrofurantoin received was 200 mg. Participants also received 2 tablets of placebo matched with gepotidacin BID, orally on Day 1 to Day 5. All doses were administered after food consumption and with water.
Overall Number of Participants Analyzed		779	773
Mean (Standard Deviation); Unit of Measure: Ratio
Baseline	Number Analyzed	779 participants	773 participants
		1.0172 (0.00693)	1.0174 (0.00686)
On-Therapy	Number Analyzed	731 participants	737 participants
		1.0176 (0.00716)	1.0167 (0.00696)
Test of Cure	Number Analyzed	719 participants	727 participants
		1.0179 (0.00712)	1.0179 (0.00719)

30. Secondary Outcome

Title	Absolute Mean Values of Urine Potential of Hydrogen (pH)
Description	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.
Time Frame	Baseline (on or before Day 1), On-Therapy (Days 2 to 5), and Test of cure (Days 9 to 16)

Outcome Measure Data

Analysis Population Description

Safety population. Only those participants with data available at the specified data points were analyzed.

Arm/Group Title		Gepotidacin	Nitrofurantoin
Arm/Group Description:		Participants with uncomplicated urinary tract infection (acute cystitis) randomized to receive gepotidacin 1500 milligram (mg) (2*750 mg, tablets), twice daily (BID), orally on Day 1 to Day 5. The total daily dose of gepotidacin received was 3000 mg. Participants also received 1 capsule of placebo matched with nitrofurantoin BID, orally on Day 1 to Day 5. All doses were administered after food consumption and with water.	Participants with uncomplicated urinary tract infection (acute cystitis) randomized to receive nitrofurantoin 100 mg capsule, BID, orally on Day 1 to Day 5. The total daily dose of nitrofurantoin received was 200 mg. Participants also received 2 tablets of placebo matched with gepotidacin BID, orally on Day 1 to Day 5. All doses were administered after food consumption and with water.
Overall Number of Participants Analyzed		763	764
Mean (Standard Deviation); Unit of Measure: pH
pH, Baseline	Number Analyzed	763 participants	764 participants
		5.7 (0.8)	5.7 (0.79)
pH, On-Therapy	Number Analyzed	726 participants	733 participants
		5.6 (0.66)	5.6 (0.69)
pH, Test of Cure	Number Analyzed	716 participants	726 participants
		5.6 (0.69)	5.7 (0.71)

31. Secondary Outcome

Title	Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at On-Therapy and Test of Cure Visit
Description	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.
Time Frame	Baseline (on or before Day 1), On-Therapy (Days 2 to 5), and Test of cure (Days 9 to 16)

Outcome Measure Data

Analysis Population Description

Safety population. Only those participants with data available at the specified data points were analyzed.

Arm/Group Title		Gepotidacin	Nitrofurantoin
Arm/Group Description:		Participants with uncomplicated urinary tract infection (acute cystitis) randomized to receive gepotidacin 1500 milligram (mg) (2*750 mg, tablets), twice daily (BID), orally on Day 1 to Day 5. The total daily dose of gepotidacin received was 3000 mg. Participants also received 1 capsule of placebo matched with nitrofurantoin BID, orally on Day 1 to Day 5. All doses were administered after food consumption and with water.	Participants with uncomplicated urinary tract infection (acute cystitis) randomized to receive nitrofurantoin 100 mg capsule, BID, orally on Day 1 to Day 5. The total daily dose of nitrofurantoin received was 200 mg. Participants also received 2 tablets of placebo matched with gepotidacin BID, orally on Day 1 to Day 5. All doses were administered after food consumption and with water.
Overall Number of Participants Analyzed		804	798
Mean (Standard Deviation); Unit of Measure: Millimeters of mercury (mmHg)
SBP, Baseline	Number Analyzed	804 participants	798 participants
		122 (13.33)	122.7 (13.98)
SBP, On-Therapy	Number Analyzed	745 participants	751 participants
		-1.1 (10.14)	-1.1 (10.72)
SBP, Test of Cure	Number Analyzed	732 participants	752 participants
		-0.4 (11.67)	-1.8 (12.19)
DBP, Baseline	Number Analyzed	804 participants	798 participants
		76.9 (8.17)	77 (9)
DBP, On-Therapy	Number Analyzed	745 participants	751 participants
		-0.5 (7.30)	-0.6 (7.73)
DBP, Test of Cure	Number Analyzed	732 participants	752 participants
		-0.1 (7.98)	-1.3 (8.37)

32. Secondary Outcome

Title	Change From Baseline in Pulse Rate at On Therapy and Test of Cure Visit
Description	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.
Time Frame	Baseline (on or before Day 1), On-Therapy (Days 2 to 5), and Test of cure (Days 9 to 16)

Outcome Measure Data

Analysis Population Description

Safety population. Only those participants with data available at the specified data points were analyzed.

Arm/Group Title		Gepotidacin	Nitrofurantoin
Arm/Group Description:		Participants with uncomplicated urinary tract infection (acute cystitis) randomized to receive gepotidacin 1500 milligram (mg) (2*750 mg, tablets), twice daily (BID), orally on Day 1 to Day 5. The total daily dose of gepotidacin received was 3000 mg. Participants also received 1 capsule of placebo matched with nitrofurantoin BID, orally on Day 1 to Day 5. All doses were administered after food consumption and with water.	Participants with uncomplicated urinary tract infection (acute cystitis) randomized to receive nitrofurantoin 100 mg capsule, BID, orally on Day 1 to Day 5. The total daily dose of nitrofurantoin received was 200 mg. Participants also received 2 tablets of placebo matched with gepotidacin BID, orally on Day 1 to Day 5. All doses were administered after food consumption and with water.
Overall Number of Participants Analyzed		804	798
Mean (Standard Deviation); Unit of Measure: beats per minute (bpm)
Pulse rate, Baseline	Number Analyzed	804 participants	798 participants
		73.2 (9.64)	73.7 (10.32)
Pulse rate, On-Therapy	Number Analyzed	745 participants	751 participants
		0.9 (8.24)	1.3 (8.66)
Pulse rate, Test of Cure	Number Analyzed	732 participants	752 participants
		1.8 (9.74)	1.7 (9.95)

33. Secondary Outcome

Title	Change From Baseline in Body Temperature
Description	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.
Time Frame	Baseline (on or before Day 1), On-Therapy (Days 2 to 5), and Test of cure (Days 9 to 16)

Outcome Measure Data

Analysis Population Description

Safety population. Only those participants with data available at the specified data points were analyzed.

Arm/Group Title		Gepotidacin	Nitrofurantoin
Arm/Group Description:		Participants with uncomplicated urinary tract infection (acute cystitis) randomized to receive gepotidacin 1500 milligram (mg) (2*750 mg, tablets), twice daily (BID), orally on Day 1 to Day 5. The total daily dose of gepotidacin received was 3000 mg. Participants also received 1 capsule of placebo matched with nitrofurantoin BID, orally on Day 1 to Day 5. All doses were administered after food consumption and with water.	Participants with uncomplicated urinary tract infection (acute cystitis) randomized to receive nitrofurantoin 100 mg capsule, BID, orally on Day 1 to Day 5. The total daily dose of nitrofurantoin received was 200 mg. Participants also received 2 tablets of placebo matched with gepotidacin BID, orally on Day 1 to Day 5. All doses were administered after food consumption and with water.
Overall Number of Participants Analyzed		804	798
Mean (Standard Deviation); Unit of Measure: Celsius
Temperature, Baseline	Number Analyzed	804 participants	798 participants
		36.61 (0.346)	36.63 (0.317)
Temperature, On-Therapy	Number Analyzed	744 participants	751 participants
		-0.01 (0.334)	-0.01 (0.372)
Temperature, Test of Cure	Number Analyzed	732 participants	752 participants
		-0.01 (0.349)	-0.04 (0.351)

34. Secondary Outcome

Title	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
Description	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.
Time Frame	Up to Day 31

Outcome Measure Data

Analysis Population Description

Safety population. Only those participants with data available at the specified data points were analyzed.

Arm/Group Title		Gepotidacin	Nitrofurantoin
Arm/Group Description:		Participants with uncomplicated urinary tract infection (acute cystitis) randomized to receive gepotidacin 1500 milligram (mg) (2*750 mg, tablets), twice daily (BID), orally on Day 1 to Day 5. The total daily dose of gepotidacin received was 3000 mg. Participants also received 1 capsule of placebo matched with nitrofurantoin BID, orally on Day 1 to Day 5. All doses were administered after food consumption and with water.	Participants with uncomplicated urinary tract infection (acute cystitis) randomized to receive nitrofurantoin 100 mg capsule, BID, orally on Day 1 to Day 5. The total daily dose of nitrofurantoin received was 200 mg. Participants also received 2 tablets of placebo matched with gepotidacin BID, orally on Day 1 to Day 5. All doses were administered after food consumption and with water.
Overall Number of Participants Analyzed		791	784
Measure Type: Count of Participants; Unit of Measure: Participants
<= 450 msec	Number Analyzed	746 participants	743 participants
	<=30 msec	675 90.5%	700 94.2%
	31-60 msec	23 3.1%	12 1.6%
	>60 msec	1 0.1%	0 0.0%
	Missing	47 6.3%	31 4.2%
>450 to <=480 msec	Number Analyzed	45 participants	40 participants
	<=30 msec	40 88.9%	37 92.5%
	31-60 msec	2 4.4%	0 0.0%
	>60 msec	0 0.0%	0 0.0%
	Missing	3 6.7%	3 7.5%
>480 to <=500 msec	Number Analyzed	0 participants	1 participants
	<=30 msec		1 100.0%
	31-60 msec		0 0.0%
	>60 msec		0 0.0%
	Missing		0 0.0%

35. Secondary Outcome

Title	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
Description	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.
Time Frame	Up to Day 31

Outcome Measure Data

Analysis Population Description

Safety population. Only those participants with data available at the specified data points were analyzed.

Arm/Group Title		Gepotidacin	Nitrofurantoin
Arm/Group Description:		Participants with uncomplicated urinary tract infection (acute cystitis) randomized to receive gepotidacin 1500 milligram (mg) (2*750 mg, tablets), twice daily (BID), orally on Day 1 to Day 5. The total daily dose of gepotidacin received was 3000 mg. Participants also received 1 capsule of placebo matched with nitrofurantoin BID, orally on Day 1 to Day 5. All doses were administered after food consumption and with water.	Participants with uncomplicated urinary tract infection (acute cystitis) randomized to receive nitrofurantoin 100 mg capsule, BID, orally on Day 1 to Day 5. The total daily dose of nitrofurantoin received was 200 mg. Participants also received 2 tablets of placebo matched with gepotidacin BID, orally on Day 1 to Day 5. All doses were administered after food consumption and with water.
Overall Number of Participants Analyzed		791	784
Measure Type: Count of Participants; Unit of Measure: Participants
<= 450 msec	Number Analyzed	783 participants	779 participants
	<=30 msec	721 92.1%	742 95.3%
	31-60 msec	12 1.5%	4 0.5%
	>60 msec	0 0.0%	0 0.0%
	Missing	50 6.4%	33 4.2%
>450 to <=480 msec	Number Analyzed	8 participants	5 participants
	<=30 msec	8 100.0%	4 80.0%
	31-60 msec	0 0.0%	0 0.0%
	>60 msec	0 0.0%	0 0.0%
	Missing	0 0.0%	1 20.0%

Adverse Events

Time Frame	All cause mortality, non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected from the time of first dose (Day 1) through the final follow-up visit (Day 21-31)
Adverse Event Reporting Description	Safety population included all randomized participants who receive at least 1 dose of study treatment.
Arm/Group Title	Gepotidacin		Nitrofurantoin
Arm/Group Description	Participants with uncomplicated urinary tract infection (acute cystitis) randomized to receive gepotidacin 1500 milligram (mg) (2*750 mg, tablets), twice daily (BID), orally on Day 1 to Day 5. The total daily dose of gepotidacin received was 3000 mg. Participants also received 1 capsule of placebo matched with nitrofurantoin BID, orally on Day 1 to Day 5. All doses were administered after food consumption and with water.		Participants with uncomplicated urinary tract infection (acute cystitis) randomized to receive nitrofurantoin 100 mg capsule, BID, orally on Day 1 to Day 5. The total daily dose of nitrofurantoin received was 200 mg. Participants also received 2 tablets of placebo matched with gepotidacin BID, orally on Day 1 to Day 5. All doses were administered after food consumption and with water.
All-Cause Mortality
	Gepotidacin		Nitrofurantoin
	Affected / at Risk (%)		Affected / at Risk (%)
Total	0/804 (0.00%)		0/798 (0.00%)
Serious Adverse Events
	Gepotidacin		Nitrofurantoin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/804 (0.62%)		5/798 (0.63%)
Cardiac disorders
Atrial fribrillation † 1	1/804 (0.12%)	1	0/798 (0.00%)	0
Gastrointestinal disorders
Abdominal pain † 1	1/804 (0.12%)	1	0/798 (0.00%)	0
Gastroesophageal reflux disease † 1	1/804 (0.12%)	1	0/798 (0.00%)	0
Pancreatitis † 1	0/804 (0.00%)	0	1/798 (0.13%)	1
Infections and infestations
COVID-19 † 1	2/804 (0.25%)	2	0/798 (0.00%)	0
Pyelonephritis acute † 1	0/804 (0.00%)	0	2/798 (0.25%)	2
Urosepsis † 1	0/804 (0.00%)	0	1/798 (0.13%)	1
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous † 1	0/804 (0.00%)	0	1/798 (0.13%)	1
1 Term from vocabulary, 25.1; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	1%
	Gepotidacin		Nitrofurantoin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	235/804 (29.23%)		119/798 (14.91%)
Gastrointestinal disorders
Diarrhoea † 1	147/804 (18.28%)	166	24/798 (3.01%)	25
Nausea † 1	65/804 (8.08%)	66	35/798 (4.39%)	36
Flatulence † 1	28/804 (3.48%)	29	4/798 (0.50%)	4
Faeces soft † 1	23/804 (2.86%)	30	4/798 (0.50%)	4
Vomiting † 1	18/804 (2.24%)	18	7/798 (0.88%)	7
Abdominal pain † 1	12/804 (1.49%)	12	7/798 (0.88%)	8
Abdominal discomfort † 1	9/804 (1.12%)	9	4/798 (0.50%)	5
General disorders
Fatigue † 1	3/804 (0.37%)	3	8/798 (1.00%)	8
Infections and infestations
Urinary tract infection † 1	11/804 (1.37%)	11	15/798 (1.88%)	15
Fungal infection † 1	9/804 (1.12%)	9	10/798 (1.25%)	10
COVID-19 † 1	9/804 (1.12%)	9	5/798 (0.63%)	6
Nervous system disorders
Headache † 1	21/804 (2.61%)	23	22/798 (2.76%)	27
Dizziness † 1	18/804 (2.24%)	18	11/798 (1.38%)	12
1 Term from vocabulary, 25.1; † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single site data not precede the primary publication of the entire clinical trial.

Results Point of Contact

• Name/Title: GSK Response Center
• Organization: GlaxoSmithKline
• Phone: 866-435-7343
• EMail: GSKClinicalSupportHD@gsk.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT04187144
• Other Study ID Numbers: 212390; 2020-000553-27 ( EudraCT Number )
• First Submitted: December 3, 2019
• First Posted: December 5, 2019
• Results First Submitted: May 29, 2023
• Results First Posted: July 18, 2023
• Last Update Posted: July 18, 2023