Oral Omadacycline vs. Oral Nitrofurantoin for the Treatment of Cystitis

• Sponsor: Paratek Pharmaceuticals Inc (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03425396
• Collaborator: (none)
• Enrollment: 225
• Locations: 23
• Arms: 5
• Actual Duration (Months): 17
• Patients Per Site: 9.8
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the safety and efficacy of oral omadacycline as compared to oral nitrofurantoin in the treatment of female adults with cystitis.

Condition or Disease	Intervention/Treatment	Phase
Uncomplicated Urinary Tract Infection; Cystitis	Drug: Omadacycline tablets; Drug: Nitrofurantoin capsules	Phase 2

Detailed Description

Participants were randomized to receive 7 days of treatment of either omadacycline or nitrofurantoin. The End of Treatment visit, Post Therapy Evaluation visit, and Final Follow-up visit was planned within 2 days following the last dose of study drug, on Day 14 (+/- 2 days) after the first dose of study drug, and within 30 to 37 days following the first dose of study drug, respectively. The study followed a double-dummy design. To maintain the study blinding, participants assigned to omadacycline received active omadacycline tablets and over-encapsulated nitrofurantoin placebo tablets. Participants assigned to the nitrofurantoin arm received omadacycline placebo tablets and over-encapsulated active nitrofurantoin capsules.

Study Design

• Study Type: Interventional
• Actual Enrollment: 225 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blinded, Adaptive Phase 2 Study to Evaluate the Safety and Efficacy of Oral Omadacycline and Oral Nitrofurantoin in the Treatment of Female Adults With Cystitis
• Actual Study Start Date: Jan 4, 2018
• Actual Primary Completion Date: May 15, 2019
• Actual Study Completion Date: Jun 5, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Omadacycline 300/300 once every 24 hours Participants received omadacycline 300 milligrams orally, once every 12 hours, fed on Day 1 and omadacycline 300 milligrams orally, once every 24 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.	Drug: Omadacycline tablets; Oral Omadacycline
Experimental: Omadacycline 450/300 once every 24 hours Participants received omadacycline 450 milligrams orally, once every 12 hours, fed on Day 1 and omadacycline 300 milligrams orally, once every 24 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.	Drug: Omadacycline tablets; Oral Omadacycline
Experimental: Omadacycline 450/450 once every 24 hours Participants received omadacycline 450 milligrams orally, once every 12 hours, fed on Day 1 and omadacycline 450 milligrams orally, once every 24 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.	Drug: Omadacycline tablets; Oral Omadacycline
Experimental: Omadacycline 450/450 once every 12 hours Participants received omadacycline 450 milligrams orally, once every 12 hours, fed on Day 1 and omadacycline 450 milligrams orally, once every 12 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.	Drug: Omadacycline tablets; Oral Omadacycline
Active Comparator: Nitrofurantoin 100/100 once every 12 hours Participants received nitrofurantoin 100 milligrams orally, once every 12 hours, fed on Day 1 and nitrofurantoin 100 milligrams orally, once every 12 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.	Drug: Nitrofurantoin capsules; Oral Nitrofurantoin

Outcome Measures

Primary Outcome Measures

1. Number of Participants With an Investigator Assessment of Clinical Response at the Post Therapy Evaluation (PTE) Visit (ITT Population) [Day 14 (A PTE occurred on Day 14 ± 2 days after the participant's first dose of study drug)]

   Clinical response was determined by the investigator at the PTE visit by assessing whether or not the participant met the clinical outcome of Clinical Success, Clinical Failure, or Indeterminate. Clinical Success was defined as sufficient resolution of cystitis signs and symptoms at the PTE visit such that no additional systemic antimicrobial therapy was required for the current infection. Clinical Failure was defined as no apparent response to therapy or persistence of signs and symptoms of infection or reappearance of signs and symptoms at or before the PTE visit such that use of additional systemic antimicrobial therapy for the current infection was required. The clinical outcome was deemed as Indeterminate when the PTE visit was not completed.

Secondary Outcome Measures

1. Number of Participants With an Investigator Assessment of Clinical Response at the End of Treatment (EOT) Visit (ITT Population) [EOT visit (within 1 to 2 days following the last dose of study drug i.e. up to approximately 9 days)]

   Clinical response was determined by the investigator at the EOT visit by assessing whether or not the participant met the clinical outcome of Clinical Success, Clinical Failure. Clinical Success was defined as sufficient resolution of cystitis signs and symptoms at the EOT visit such that no additional systemic antimicrobial therapy was required for the current infection. Clinical Failure was defined as no apparent response to therapy or persistence of signs and symptoms of infection at the EOT visit such that use of additional systemic antimicrobial therapy for the current infection was required. The clinical outcome was deemed as Indeterminate when the EOT visit was not completed.

2. Number of Participants With an Investigator Assessment of Clinical Response at the EOT Visit (Microbiological [Micro]-ITT Population) [EOT visit (within 1 to 2 days following the last dose of study drug i.e. up to approximately 9 days)]

   Clinical response was determined by the investigator at the EOT visit by assessing whether or not the participant met the clinical outcome of Clinical Success, Clinical Failure, or Indeterminate. Clinical Success was defined as sufficient resolution of cystitis signs and symptoms at the EOT visit such that no additional systemic antimicrobial therapy was required for the current infection. Clinical Failure was defined as no apparent response to therapy or persistence of signs and symptoms of infection at the EOT visit such that use of additional systemic antimicrobial therapy for the current infection was required. The clinical outcome was deemed as Indeterminate when the EOT visit was not completed.

3. Number of Participants With an Investigator Assessment of Clinical Response at the EOT Visit (CE-EOT Population) [EOT visit (within 1 to 2 days following the last dose of study drug i.e. up to approximately 9 days)]

   Clinical response was determined by the investigator at the EOT visit by assessing whether or not the participant met the clinical outcome of Clinical Success or Clinical Failure. Clinical Success was defined as sufficient resolution of cystitis signs and symptoms at the EOT visit such that no additional systemic antimicrobial therapy was required for the current infection. Clinical Failure was defined as no apparent response to therapy or persistence of signs and symptoms of infection at the EOT visit such that use of additional systemic antimicrobial therapy for the current infection was required. For the CE population, the clinical outcome was not deemed as indeterminate response.

4. Number of Participants With an Investigator Assessment of Clinical Response at the PTE Visit (CE-PTE Population) [Day 14 (A PTE occurred on Day 14 ± 2 days after the participant's first dose of study drug)]

   Clinical response was determined by the investigator at the PTE visit by assessing whether or not the participant met the clinical outcome of Clinical Success or Clinical Failure. Clinical Success was defined as sufficient resolution of cystitis signs and symptoms at the PTE visit such that no additional systemic antimicrobial therapy was required for the current infection. Clinical Failure was defined as no apparent response to therapy or persistence of signs and symptoms of infection or reappearance of signs and symptoms at or before the PTE visit such that use of additional systemic antimicrobial therapy for the current infection was required. For the CE population, the clinical outcome was not deemed as indeterminate response.

5. Number of Participants With an Investigator Assessment of Clinical Response at the PTE Visit (Micro-ITT Population) [Day 14 (A PTE occurred on Day 14 ± 2 days after the participant's first dose of study drug)]

   Clinical response was determined by the investigator at the PTE visit by assessing whether or not the participant met the clinical outcome of Clinical Success, Clinical Failure or indeterminate. Clinical Success was defined as sufficient resolution of cystitis signs and symptoms at the PTE visit such that no additional systemic antimicrobial therapy was required for the current infection. Clinical Failure was defined as no apparent response to therapy or persistence of signs and symptoms of infection or reappearance of signs and symptoms at or before the PTE visit such that use of additional systemic antimicrobial therapy for the current infection was required. The clinical outcome was deemed as Indeterminate when the PTE visit was not completed.

6. Number of Participants With an Investigator Assessment of Clinical Response at the Final Follow-up (FFU) Visit (ITT Population) [FFU visit (A FFU occurred 30 to 37 days following the first dose of study drug)]

   Clinical response was determined by the investigator at the FFU visit by assessing whether or not the participant met the clinical outcome of Clinical Success, Clinical Failure, or Indeterminate. Clinical Success was defined as sufficient resolution of cystitis signs and symptoms at the FFU visit such that no additional systemic antimicrobial therapy was required for the current infection. Clinical Failure was defined as no apparent response to therapy or persistence of signs and symptoms of infection at the FFU visit such that use of additional systemic antimicrobial therapy for the current infection was required. The clinical outcome was deemed as Indeterminate when the FFU visit was not completed

7. Number of Participants With an Investigator Assessment of Clinical Response at the FFU Visit (CE-FFU Population) [FFU visit (A FFU occurred 30 to 37 days following the first dose of study drug)]

   Clinical response was determined by the investigator at the FFU visit by assessing whether or not the participant met the clinical outcome of Clinical Success or Clinical Failure. Clinical Success was defined as sufficient resolution of cystitis signs and symptoms at the FFU visit such that no additional systemic antimicrobial therapy was required for the current infection. Clinical Failure was defined as no apparent response to therapy or persistence of signs and symptoms of infection at the FFU visit such that use of additional systemic antimicrobial therapy for the current infection was required. For the CE population, the clinical outcome was not deemed as indeterminate response.

8. Number of Participants With an Investigator Assessment of Clinical Response at the FFU Visit (Micro-ITT Population) [FFU visit (A FFU occurred 30 to 37 days following the first dose of study drug)]

   Clinical response was determined by the investigator at the FFU visit by assessing whether or not the participant met the clinical outcome of Clinical Success, Clinical Failure, or Indeterminate. Clinical Success was defined as sufficient resolution of cystitis signs and symptoms at the FFU visit such that no additional systemic antimicrobial therapy was required for the current infection. Clinical Failure was defined as no apparent response to therapy or persistence of signs and symptoms of infection at the FFU visit such that use of additional systemic antimicrobial therapy for the current infection was required. The clinical outcome was deemed as Indeterminate when the FFU visit was not completed.

9. Number of Participants With a Microbiological Response at the EOT Visit (Micro-ITT Population) [EOT visit (within 1 to 2 days following the last dose of study drug i.e. up to approximately 9 days)]

   Microbiological response was determined programmatically at the EOT visit by assessing whether or not the participant met the microbiological outcome of Favorable, Unfavorable, or Indeterminate. Favorable microbiological outcomes included eradication and presumed eradication i.e., urine specimen showed absence of the original baseline pathogen or the baseline pathogen grew at <10^4 CFU/mL at visit. Unfavorable microbiological outcome included persistence i.e. urine culture showed continued presence (defined as ≥10^4 CFU/mL) of the original baseline pathogen(s) at visit. The microbiological outcome was deemed as Indeterminate when the urine specimen was not available to culture or the culture result was not interpretable.

10. Number of Participants With a Microbiological Response at the EOT Visit (ME-EOT Population) [EOT visit (within 1 to 2 days following the last dose of study drug i.e. up to approximately 9 days)]

    Microbiological response was determined programmatically at the EOT visit by assessing whether or not the participant met the microbiological outcome of Favorable or Unfavorable. Favorable microbiological outcomes included eradication and presumed eradication i.e., urine specimen showed absence of the original baseline pathogen or the baseline pathogen grew at <10^4 CFU/mL at visit. Unfavorable microbiological outcome included persistence i.e. urine culture showed continued presence (defined as ≥10^4 CFU/mL) of the original baseline pathogen(s) at visit. For the ME population, the microbiological outcome was not deemed as indeterminate response.

11. Number of Participants With a Microbiological Response at the PTE Visit (Micro-ITT Population) [Day 14 (A PTE occurred on Day 14 ± 2 days after the participant's first dose of study drug)]

    Microbiological response was determined programmatically at the PTE visit by assessing whether or not the participant met the microbiological outcome of Favorable, Unfavorable, or Indeterminate. Favorable microbiological outcomes included eradication and presumed eradication i.e., urine specimen showed absence of the original baseline pathogen or the baseline pathogen grew at <10^4 CFU/mL at visit. Unfavorable microbiological outcome included persistence i.e. urine culture showed continued presence (defined as ≥10^4 CFU/mL) of the original baseline pathogen(s) at visit. The microbiological outcome was deemed as Indeterminate when the urine specimen was not available to culture or the culture result was not interpretable.

12. Number of Participants With a Microbiological Response at the PTE Visit (ME-PTE Population) [Day 14 (A PTE occurred on Day 14 ± 2 days after the participant's first dose of study drug)]

    Microbiological response was determined programmatically at the PTE visit by assessing whether or not the participant met the microbiological outcome of Favorable or Unfavorable. Favorable microbiological outcomes included eradication and presumed eradication i.e., urine specimen showed absence of the original baseline pathogen or the baseline pathogen grew at <10^4 CFU/mL at visit. Unfavorable microbiological outcome included persistence i.e. urine culture showed continued presence (defined as ≥10^4 CFU/mL) of the original baseline pathogen(s) at visit. For the ME population, the microbiological outcome was not deemed as indeterminate response.

Other Outcome Measures

1. Number of Participants With Resolution of All Urinary Tract Infection (UTI) Signs and Clinical Symptoms at PTE Visit (ITT Population) [Day 14 (A PTE occurred on Day 14 ± 2 days after the participant's first dose of study drug)]

   Participants recorded their assessments using the UTI Symptoms Assessment (UTISA) questionnaire, a 14-item questionnaire that assessed the levels of 'severity' and 'bothersomeness' for seven UTI signs and symptoms: Frequency, Urgency, Pain/burning on urination, Incomplete voiding, Pain in pelvic area, Low back pain, and Blood in urine. The sub-scale responses were recorded as 'did not have', 'mild', 'moderate', and 'severe' for 'severity'; and 'not at all', 'a little', 'moderately', and 'a lot' for 'bothersomeness', both scored 0-3. Total scores were calculated by summing the non-missing scores of the 7 items, divided by the number of non-missing items, and then multiplied by 7. For each sub-scale, the total score ranged from 0 (least Severe/ least bothersome) and 21 (worst severity/most bothersome). Number of participants with resolution of all symptoms, without occurrence of new symptoms is reported. Resolution was defined as absence of all baseline symptoms.

2. Number of Participants With No Worsening and Absence of New UTI Signs and Clinical Symptoms at PTE Visit (ITT Population) [Day 14 (A PTE occurred on Day 14 ± 2 days after the participant's first dose of study drug)]

   Participants recorded their assessments using the UTI Symptoms Assessment (UTISA) questionnaire, a 14-item questionnaire that assessed the levels of 'severity' and 'bothersomeness' for seven UTI signs and symptoms: Frequency, Urgency, Pain/burning on urination, Incomplete voiding, Pain in pelvic area, Low back pain, and Blood in urine. The sub-scale responses were recorded as 'did not have', 'mild', 'moderate', and 'severe' for 'severity'; and 'not at all', 'a little', 'moderately', and 'a lot' for 'bothersomeness', both scored 0-3. Total scores were calculated by summing the non-missing scores of the 7 items, divided by the number of non-missing items, and then multiplied by 7. For each sub-scale, the total score ranged from 0 (least Severe/ least bothersome) and 21 (worst severity/most bothersome). Number of participants with no worsening and absence of new UTI signs and clinical symptoms is reported. No worsening meant that each question score is same or better at post baseline.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Female participants, age 18 or older who have signed the informed consent form

• Must have a qualifying uncomplicated urinary tract infection

• Participants must not be pregnant at the time of enrollment

• Must agree to a reliable method of birth control during the study and for 30 days following the last dose of study drug

Exclusion Criteria:

• Males

• Evidence of complicated urinary tract infection (UTI), upper UTI, vaginitis, or sexually transmitted infection

• Evidence of significant immunological disease

• Has received an investigational drug within the past 30 days

• Participants who are pregnant or nursing

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Site 106	Chula Vista	California	United States	91911
2	Site 101	La Mesa	California	United States	91942
3	Site 109	Los Angeles	California	United States	90017
4	Site 114	Aventura	Florida	United States	33180
5	Site 102	DeLand	Florida	United States	32720
6	Site 103	Hialeah	Florida	United States	33015
7	Site 125	Jacksonville	Florida	United States	32256
8	Site 127	Miami Springs	Florida	United States	33166
9	Site 121	Miami	Florida	United States	33126
10	Site 130	Miami	Florida	United States	33126
11	Site 115	Miami	Florida	United States	33134
12	Site 126	Orlando	Florida	United States	82306
13	Site 113	Newton	Kansas	United States	67114
14	Site 110	Wichita	Kansas	United States	67207
15	Site 112	Omaha	Nebraska	United States	68144
16	Site 132	Las Vegas	Nevada	United States	89106
17	Site 108	Las Vegas	Nevada	United States	89109
18	Site 122	Berlin	New Jersey	United States	08009
19	Site 118	Raleigh	North Carolina	United States	27612
20	Site 104	Jackson	Tennessee	United States	38305
21	Site 105	Smyrna	Tennessee	United States	37167
22	Site 131	Houston	Texas	United States	77061
23	Site 120	San Antonio	Texas	United States	78229

Sponsors and Collaborators

• Paratek Pharmaceuticals Inc

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Feb 18, 2019
• Statistical Analysis Plan - May 22, 2019

More Information

Publications

None provided.

• Responsible Party: Paratek Pharmaceuticals Inc
• ClinicalTrials.gov Identifier: NCT03425396
• Other Study ID Numbers: PTK0796-UUTI-17201
• First Posted: Feb 7, 2018
• Last Update Posted: Jun 9, 2020
• Last Verified: Jun 1, 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Urinary Tract Infections; Cystitis; Nitrofurantoin

Study Results

Participant Flow

Arm/Group Title	Omadacycline 300/300 Once Every 24 Hours	Omadacycline 450/300 Once Every 24 Hours	Omadacycline 450/450 Once Every 24 Hours	Omadacycline 450/450 Once Every 12 Hours	Nitrofurantoin 100/100 Once Every 12 Hours
Arm/Group Description	Participants received omadacycline 300 milligrams orally, once every 12 hours, fed on Day 1 and omadacycline 300 milligrams orally, once every 24 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.	Participants received omadacycline 450 milligrams orally, once every 12 hours, fed on Day 1 and omadacycline 300 milligrams orally, once every 24 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.	Participants received omadacycline 450 milligrams orally, once every 12 hours, fed on Day 1 and omadacycline 450 milligrams orally, once every 24 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.	Participants received omadacycline 450 milligrams orally, once every 12 hours, fed on Day 1 and omadacycline 450 milligrams orally, once every 12 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.	Participants received nitrofurantoin 100 milligrams orally, once every 12 hours, fed on Day 1 and nitrofurantoin 100 milligrams orally, once every 12 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.
Period Title: Overall Study
STARTED	55	54	54	8	54
Completed End of Treatment Visit	53	52	51	7	53
Completed Post-therapy Evaluation Visit	53	49	51	7	54
Completed Final Follow-up Visit	53	47	51	7	53
COMPLETED	53	47	51	7	53
NOT COMPLETED	2	7	3	1	1

Baseline Characteristics

Arm/Group Title	Omadacycline 300/300 Once Every 24 Hours	Omadacycline 450/300 Once Every 24 Hours	Omadacycline 450/450 Once Every 24 Hours	Omadacycline 450/450 Once Every 12 Hours	Nitrofurantoin 100/100 Once Every 12 Hours	Total
Arm/Group Description	Participants received omadacycline 300 milligrams orally, once every 12 hours, fed on Day 1 and omadacycline 300 milligrams orally, once every 24 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.	Participants received omadacycline 450 milligrams orally, once every 12 hours, fed on Day 1 and omadacycline 300 milligrams orally, once every 24 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.	Participants received omadacycline 450 milligrams orally, once every 12 hours, fed on Day 1 and omadacycline 450 milligrams orally, once every 24 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.	Participants received omadacycline 450 milligrams orally, once every 12 hours, fed on Day 1 and omadacycline 450 milligrams orally, once every 12 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.	Participants received nitrofurantoin 100 milligrams orally, once every 12 hours, fed on Day 1 and nitrofurantoin 100 milligrams orally, once every 12 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.	Total of all reporting groups
Overall Participants	55	54	54	8	54	225
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	45.3 (17.05)	47.4 (15.70)	45.0 (15.49)	37.5 (13.60)	45.5 (17.82)	45.5 (16.41)
Sex: Female, Male (Count of Participants)
Female	55 100%	54 100%	54 100%	8 100%	54 100%	225 100%
Male	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	47 85.5%	47 87%	43 79.6%	7 87.5%	47 87%	191 84.9%
Not Hispanic or Latino	8 14.5%	7 13%	11 20.4%	1 12.5%	7 13%	34 15.1%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	1 1.9%	1 0.4%
Asian	0 0%	1 1.9%	1 1.9%	0 0%	1 1.9%	3 1.3%
Native Hawaiian or Other Pacific Islander	1 1.8%	0 0%	0 0%	0 0%	1 1.9%	2 0.9%
Black or African American	2 3.6%	1 1.9%	4 7.4%	2 25%	4 7.4%	13 5.8%
White	52 94.5%	52 96.3%	48 88.9%	6 75%	47 87%	205 91.1%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	1 1.9%	0 0%	0 0%	1 0.4%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With an Investigator Assessment of Clinical Response at the Post Therapy Evaluation (PTE) Visit (ITT Population)
Description	Clinical response was determined by the investigator at the PTE visit by assessing whether or not the participant met the clinical outcome of Clinical Success, Clinical Failure, or Indeterminate. Clinical Success was defined as sufficient resolution of cystitis signs and symptoms at the PTE visit such that no additional systemic antimicrobial therapy was required for the current infection. Clinical Failure was defined as no apparent response to therapy or persistence of signs and symptoms of infection or reappearance of signs and symptoms at or before the PTE visit such that use of additional systemic antimicrobial therapy for the current infection was required. The clinical outcome was deemed as Indeterminate when the PTE visit was not completed.
Time Frame	Day 14 (A PTE occurred on Day 14 ± 2 days after the participant's first dose of study drug)

Outcome Measure Data

Analysis Population Description

The Intent-to-Treat (ITT) Population consisted of all randomized participants regardless of whether or not the participant received study drug.

Arm/Group Title	Omadacycline 300/300 Once Every 24 Hours	Omadacycline 450/300 Once Every 24 Hours	Omadacycline 450/450 Once Every 24 Hours	Omadacycline 450/450 Once Every 12 Hours	Nitrofurantoin 100/100 Once Every 12 Hours
Arm/Group Description	Participants received omadacycline 300 milligrams orally, once every 12 hours, fed on Day 1 and omadacycline 300 milligrams orally, once every 24 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.	Participants received omadacycline 450 milligrams orally, once every 12 hours, fed on Day 1 and omadacycline 300 milligrams orally, once every 24 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.	Participants received omadacycline 450 milligrams orally, once every 12 hours, fed on Day 1 and omadacycline 450 milligrams orally, once every 24 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.	Participants received omadacycline 450 milligrams orally, once every 12 hours, fed on Day 1 and omadacycline 450 milligrams orally, once every 12 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.	Participants received nitrofurantoin 100 milligrams orally, once every 12 hours, fed on Day 1 and nitrofurantoin 100 milligrams orally, once every 12 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.
Measure Participants	55	54	54	8	54
Clinical Success	48 87.3%	42 77.8%	46 85.2%	7 87.5%	49 90.7%
Clinical Failure	5 9.1%	6 11.1%	5 9.3%	0 0%	5 9.3%
Indeterminate	2 3.6%	6 11.1%	3 5.6%	1 12.5%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Omadacycline 300/300 Once Every 24 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority margin for comparison of the doses was set at 10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-3.5
	Confidence Interval	(2-Sided) 95%; -16.8 to 9.6
	Parameter Dispersion	Type: Value:
	Estimation Comments	Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Omadacycline 450/300 Once Every 24 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority margin for comparison of the doses was set at 10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-13.0
	Confidence Interval	(2-Sided) 95%; -27.4 to 1.2
	Parameter Dispersion	Type: Value:
	Estimation Comments	Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Omadacycline 450/450 Once Every 24 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority margin for comparison of the doses was set at 10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-5.6
	Confidence Interval	(2-Sided) 95%; -19.6 to 7.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Omadacycline 450/450 Once Every 12 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority margin for comparison of the doses was set at 10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-3.2
	Confidence Interval	(2-Sided) 95%; -44.1 to 14.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.

2. Secondary Outcome

Title	Number of Participants With an Investigator Assessment of Clinical Response at the End of Treatment (EOT) Visit (ITT Population)
Description	Clinical response was determined by the investigator at the EOT visit by assessing whether or not the participant met the clinical outcome of Clinical Success, Clinical Failure. Clinical Success was defined as sufficient resolution of cystitis signs and symptoms at the EOT visit such that no additional systemic antimicrobial therapy was required for the current infection. Clinical Failure was defined as no apparent response to therapy or persistence of signs and symptoms of infection at the EOT visit such that use of additional systemic antimicrobial therapy for the current infection was required. The clinical outcome was deemed as Indeterminate when the EOT visit was not completed.
Time Frame	EOT visit (within 1 to 2 days following the last dose of study drug i.e. up to approximately 9 days)

Outcome Measure Data

Analysis Population Description

The ITT Population consisted of all randomized participants regardless of whether or not the participant received study drug.

Arm/Group Title	Omadacycline 300/300 Once Every 24 Hours	Omadacycline 450/300 Once Every 24 Hours	Omadacycline 450/450 Once Every 24 Hours	Omadacycline 450/450 Once Every 12 Hours	Nitrofurantoin 100/100 Once Every 12 Hours
Arm/Group Description	Participants received omadacycline 300 milligrams orally, once every 12 hours, fed on Day 1 and omadacycline 300 milligrams orally, once every 24 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.	Participants received omadacycline 450 milligrams orally, once every 12 hours, fed on Day 1 and omadacycline 300 milligrams orally, once every 24 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.	Participants received omadacycline 450 milligrams orally, once every 12 hours, fed on Day 1 and omadacycline 450 milligrams orally, once every 24 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.	Participants received omadacycline 450 milligrams orally, once every 12 hours, fed on Day 1 and omadacycline 450 milligrams orally, once every 12 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.	Participants received nitrofurantoin 100 milligrams orally, once every 12 hours, fed on Day 1 and nitrofurantoin 100 milligrams orally, once every 12 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.
Measure Participants	55	54	54	8	54
Clinical Success	49 89.1%	47 87%	49 90.7%	7 87.5%	49 90.7%
Clinical Failure	4 7.3%	5 9.3%	2 3.7%	0 0%	4 7.4%
Indeterminate	2 3.6%	2 3.7%	3 5.6%	1 12.5%	1 1.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Omadacycline 300/300 Once Every 24 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority margin for comparison of the doses was set at 10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-1.6
	Confidence Interval	(2-Sided) 95%; -14.3 to 11.2
	Parameter Dispersion	Type: Value:
	Estimation Comments	Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Omadacycline 450/300 Once Every 24 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority margin for comparison of the doses was set at 10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-3.7
	Confidence Interval	(2-Sided) 95%; -16.8 to 9.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Omadacycline 450/450 Once Every 24 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority margin for comparison of the doses was set at 10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; -12.3 to 12.3
	Parameter Dispersion	Type: Value:
	Estimation Comments	Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Omadacycline 450/450 Once Every 12 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority margin for comparison of the doses was set at 10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-3.2
	Confidence Interval	(2-Sided) 95%; -44.1 to 14.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.

3. Secondary Outcome

Title	Number of Participants With an Investigator Assessment of Clinical Response at the EOT Visit (Microbiological [Micro]-ITT Population)
Description	Clinical response was determined by the investigator at the EOT visit by assessing whether or not the participant met the clinical outcome of Clinical Success, Clinical Failure, or Indeterminate. Clinical Success was defined as sufficient resolution of cystitis signs and symptoms at the EOT visit such that no additional systemic antimicrobial therapy was required for the current infection. Clinical Failure was defined as no apparent response to therapy or persistence of signs and symptoms of infection at the EOT visit such that use of additional systemic antimicrobial therapy for the current infection was required. The clinical outcome was deemed as Indeterminate when the EOT visit was not completed.
Time Frame	EOT visit (within 1 to 2 days following the last dose of study drug i.e. up to approximately 9 days)

Outcome Measure Data

Analysis Population Description

The micro-ITT population consisted of all randomized participants who had a study-qualifying pre-treatment Baseline urine culture. A study-qualifying pretreatment Baseline culture was defined as a culture from a clean-catch urine sample which grew at least 1 and no more than 2 bacterial isolates at ≥ 10^5 colony forming unit (CFU)/mL each.

Arm/Group Title	Omadacycline 300/300 Once Every 24 Hours	Omadacycline 450/300 Once Every 24 Hours	Omadacycline 450/450 Once Every 24 Hours	Omadacycline 450/450 Once Every 12 Hours	Nitrofurantoin 100/100 Once Every 12 Hours
Arm/Group Description	Participants received omadacycline 300 milligrams orally, once every 12 hours, fed on Day 1 and omadacycline 300 milligrams orally, once every 24 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.	Participants received omadacycline 450 milligrams orally, once every 12 hours, fed on Day 1 and omadacycline 300 milligrams orally, once every 24 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.	Participants received omadacycline 450 milligrams orally, once every 12 hours, fed on Day 1 and omadacycline 450 milligrams orally, once every 24 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.	Participants received omadacycline 450 milligrams orally, once every 12 hours, fed on Day 1 and omadacycline 450 milligrams orally, once every 12 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.	Participants received nitrofurantoin 100 milligrams orally, once every 12 hours, fed on Day 1 and nitrofurantoin 100 milligrams orally, once every 12 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.
Measure Participants	25	34	23	5	30
Clinical Success	22 40%	29 53.7%	22 40.7%	5 62.5%	27 50%
Clinical Failure	1 1.8%	4 7.4%	1 1.9%	0 0%	3 5.6%
Indeterminate	2 3.6%	1 1.9%	0 0%	0 0%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Omadacycline 300/300 Once Every 24 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority margin for comparison of the doses was set at 10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-2.0
	Confidence Interval	(2-Sided) 95%; -22.5 to 16.8
	Parameter Dispersion	Type: Value:
	Estimation Comments	Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Omadacycline 450/300 Once Every 24 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority margin for comparison of the doses was set at 10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-4.7
	Confidence Interval	(2-Sided) 95%; -23.3 to 14.2
	Parameter Dispersion	Type: Value:
	Estimation Comments	Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Omadacycline 450/450 Once Every 24 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority margin for comparison of the doses was set at 10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	5.7
	Confidence Interval	(2-Sided) 95%; -13.0 to 22.6
	Parameter Dispersion	Type: Value:
	Estimation Comments	Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Omadacycline 450/450 Once Every 12 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority margin for comparison of the doses was set at 10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	10.0
	Confidence Interval	(2-Sided) 95%; -40.4 to 28.9
	Parameter Dispersion	Type: Value:
	Estimation Comments	Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.

4. Secondary Outcome

Title	Number of Participants With an Investigator Assessment of Clinical Response at the EOT Visit (CE-EOT Population)
Description	Clinical response was determined by the investigator at the EOT visit by assessing whether or not the participant met the clinical outcome of Clinical Success or Clinical Failure. Clinical Success was defined as sufficient resolution of cystitis signs and symptoms at the EOT visit such that no additional systemic antimicrobial therapy was required for the current infection. Clinical Failure was defined as no apparent response to therapy or persistence of signs and symptoms of infection at the EOT visit such that use of additional systemic antimicrobial therapy for the current infection was required. For the CE population, the clinical outcome was not deemed as indeterminate response.
Time Frame	EOT visit (within 1 to 2 days following the last dose of study drug i.e. up to approximately 9 days)

Outcome Measure Data

Analysis Population Description

The clinically evaluable (CE)-EOT population consisted of all ITT participants who completed the EOT visit, received test article, had a qualifying infection, an assessment of outcome, and met all other evaluability criterias.

Arm/Group Title	Omadacycline 300/300 Once Every 24 Hours	Omadacycline 450/300 Once Every 24 Hours	Omadacycline 450/450 Once Every 24 Hours	Omadacycline 450/450 Once Every 12 Hours	Nitrofurantoin 100/100 Once Every 12 Hours
Arm/Group Description	Participants received omadacycline 300 milligrams orally, once every 12 hours, fed on Day 1 and omadacycline 300 milligrams orally, once every 24 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.	Participants received omadacycline 450 milligrams orally, once every 12 hours, fed on Day 1 and omadacycline 300 milligrams orally, once every 24 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.	Participants received omadacycline 450 milligrams orally, once every 12 hours, fed on Day 1 and omadacycline 450 milligrams orally, once every 24 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.	Participants received omadacycline 450 milligrams orally, once every 12 hours, fed on Day 1 and omadacycline 450 milligrams orally, once every 12 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.	Participants received nitrofurantoin 100 milligrams orally, once every 12 hours, fed on Day 1 and nitrofurantoin 100 milligrams orally, once every 12 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.
Measure Participants	50	47	47	7	52
Clinical Success	47 85.5%	42 77.8%	47 87%	7 87.5%	48 88.9%
Clinical Failure	3 5.5%	5 9.3%	0 0%	0 0%	4 7.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Omadacycline 300/300 Once Every 24 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority margin for comparison of the doses was set at 10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	1.7
	Confidence Interval	(2-Sided) 95%; -10.0 to 13.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Omadacycline 450/300 Once Every 24 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority margin for comparison of the doses was set at 10%
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-2.9
	Confidence Interval	(2-Sided) 95%; -16.2 to 9.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Omadacycline 450/450 Once Every 24 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority margin for comparison of the doses was set at 10%
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment Difference
	Estimated Value	7.7
	Confidence Interval	(2-Sided) 95%; -0.3 to 18.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Omadacycline 450/450 Once Every 12 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority margin for comparison of the doses was set at 10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatm,ent difference
	Estimated Value	7.7
	Confidence Interval	(2-Sided) 95%; -34.9 to 20.6
	Parameter Dispersion	Type: Value:
	Estimation Comments	Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.

5. Secondary Outcome

Title	Number of Participants With an Investigator Assessment of Clinical Response at the PTE Visit (CE-PTE Population)
Description	Clinical response was determined by the investigator at the PTE visit by assessing whether or not the participant met the clinical outcome of Clinical Success or Clinical Failure. Clinical Success was defined as sufficient resolution of cystitis signs and symptoms at the PTE visit such that no additional systemic antimicrobial therapy was required for the current infection. Clinical Failure was defined as no apparent response to therapy or persistence of signs and symptoms of infection or reappearance of signs and symptoms at or before the PTE visit such that use of additional systemic antimicrobial therapy for the current infection was required. For the CE population, the clinical outcome was not deemed as indeterminate response.
Time Frame	Day 14 (A PTE occurred on Day 14 ± 2 days after the participant's first dose of study drug)

Outcome Measure Data

Analysis Population Description

The clinically evaluable (CE)-PTE population consisted of all ITT participants who completed the PTE visit, received test article, had a qualifying infection, an assessment of outcome, and met all other evaluability criterias.

Arm/Group Title	Omadacycline 300/300 Once Every 24 Hours	Omadacycline 450/300 Once Every 24 Hours	Omadacycline 450/450 Once Every 24 Hours	Omadacycline 450/450 Once Every 12 Hours	Nitrofurantoin 100/100 Once Every 12 Hours
Arm/Group Description	Participants received omadacycline 300 milligrams orally, once every 12 hours, fed on Day 1 and omadacycline 300 milligrams orally, once every 24 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.	Participants received omadacycline 450 milligrams orally, once every 12 hours, fed on Day 1 and omadacycline 300 milligrams orally, once every 24 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.	Participants received omadacycline 450 milligrams orally, once every 12 hours, fed on Day 1 and omadacycline 450 milligrams orally, once every 24 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.	Participants received omadacycline 450 milligrams orally, once every 12 hours, fed on Day 1 and omadacycline 450 milligrams orally, once every 12 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.	Participants received nitrofurantoin 100 milligrams orally, once every 12 hours, fed on Day 1 and nitrofurantoin 100 milligrams orally, once every 12 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.
Measure Participants	49	46	47	7	49
Clinical success	45 81.8%	41 75.9%	46 85.2%	7 87.5%	45 83.3%
Clinical failure	4 7.3%	5 9.3%	1 1.9%	0 0%	4 7.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Omadacycline 300/300 Once Every 24 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority margin for comparison of the doses was set at 10%
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; -12.6 to 12.6
	Parameter Dispersion	Type: Value:
	Estimation Comments	Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Omadacycline 450/300 Once Every 24 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority margin for comparison of the doses was set at 10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-2.7
	Confidence Interval	(2-Sided) 95%; -16.3 to 10.2
	Parameter Dispersion	Type: Value:
	Estimation Comments	Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Omadacycline 450/450 Once Every 24 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority margin for comparison of the doses was set at 10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	6.0
	Confidence Interval	(2-Sided) 95%; -4.5 to 17.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Omadacycline 450/450 Once Every 12 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority margin for comparison of the doses was set at 10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	8.2
	Confidence Interval	(2-Sided) 95%; -35.3 to 20.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.

6. Secondary Outcome

Title	Number of Participants With an Investigator Assessment of Clinical Response at the PTE Visit (Micro-ITT Population)
Description	Clinical response was determined by the investigator at the PTE visit by assessing whether or not the participant met the clinical outcome of Clinical Success, Clinical Failure or indeterminate. Clinical Success was defined as sufficient resolution of cystitis signs and symptoms at the PTE visit such that no additional systemic antimicrobial therapy was required for the current infection. Clinical Failure was defined as no apparent response to therapy or persistence of signs and symptoms of infection or reappearance of signs and symptoms at or before the PTE visit such that use of additional systemic antimicrobial therapy for the current infection was required. The clinical outcome was deemed as Indeterminate when the PTE visit was not completed.
Time Frame	Day 14 (A PTE occurred on Day 14 ± 2 days after the participant's first dose of study drug)

Outcome Measure Data

Analysis Population Description

The micro-ITT population consisted of consisted of all randomized participants who had a study-qualifying pre-treatment baseline urine culture. A study-qualifying pretreatment Baseline culture was defined as a culture from a clean-catch urine sample which grew at least 1 and no more than 2 bacterial isolates at ≥ 10^5 CFU/mL each.

Arm/Group Title	Omadacycline 300/300 Once Every 24 Hours	Omadacycline 450/300 Once Every 24 Hours	Omadacycline 450/450 Once Every 24 Hours	Omadacycline 450/450 Once Every 12 Hours	Nitrofurantoin 100/100 Once Every 12 Hours
Arm/Group Description	Participants received omadacycline 300 milligrams orally, once every 12 hours, fed on Day 1 and omadacycline 300 milligrams orally, once every 24 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.	Participants received omadacycline 450 milligrams orally, once every 12 hours, fed on Day 1 and omadacycline 300 milligrams orally, once every 24 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.	Participants received omadacycline 450 milligrams orally, once every 12 hours, fed on Day 1 and omadacycline 450 milligrams orally, once every 24 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.	Participants received omadacycline 450 milligrams orally, once every 12 hours, fed on Day 1 and omadacycline 450 milligrams orally, once every 12 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.	Participants received nitrofurantoin 100 milligrams orally, once every 12 hours, fed on Day 1 and nitrofurantoin 100 milligrams orally, once every 12 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.
Measure Participants	25	34	23	5	30
Clinical success	21 38.2%	27 50%	21 38.9%	5 62.5%	27 50%
Clinical failure	2 3.6%	5 9.3%	2 3.7%	0 0%	3 5.6%
Indeterminate	2 3.6%	2 3.7%	0 0%	0 0%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Omadacycline 300/300 Once Every 24 Hours
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority margin for comparison of the doses was set at 10%
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-6.0
	Confidence Interval	(2-Sided) 95%; -27.3 to 13.3
	Parameter Dispersion	Type: Value:
	Estimation Comments	Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Omadacycline 450/300 Once Every 24 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority margin for comparison of the doses was set at 10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-10.6
	Confidence Interval	(2-Sided) 95%; -29.2 to 8.6
	Parameter Dispersion	Type: Value:
	Estimation Comments	Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Omadacycline 450/450 Once Every 24 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority margin for comparison of the doses was set at 10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment Difference
	Estimated Value	1.3
	Confidence Interval	(2-Sided) 95%; -19.0 to 19.2
	Parameter Dispersion	Type: Value:
	Estimation Comments	Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Omadacycline 450/450 Once Every 12 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority margin for comparison of the doses was set at 10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	10.0
	Confidence Interval	(2-Sided) 95%; -40.4 to 28.9
	Parameter Dispersion	Type: Value:
	Estimation Comments	Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.

7. Secondary Outcome

Title	Number of Participants With an Investigator Assessment of Clinical Response at the Final Follow-up (FFU) Visit (ITT Population)
Description	Clinical response was determined by the investigator at the FFU visit by assessing whether or not the participant met the clinical outcome of Clinical Success, Clinical Failure, or Indeterminate. Clinical Success was defined as sufficient resolution of cystitis signs and symptoms at the FFU visit such that no additional systemic antimicrobial therapy was required for the current infection. Clinical Failure was defined as no apparent response to therapy or persistence of signs and symptoms of infection at the FFU visit such that use of additional systemic antimicrobial therapy for the current infection was required. The clinical outcome was deemed as Indeterminate when the FFU visit was not completed
Time Frame	FFU visit (A FFU occurred 30 to 37 days following the first dose of study drug)

Outcome Measure Data

Analysis Population Description

The ITT Population consisted of all randomized participants regardless of whether or not the participant received study drug.

Arm/Group Title	Omadacycline 300/300 Once Every 24 Hours	Omadacycline 450/300 Once Every 24 Hours	Omadacycline 450/450 Once Every 24 Hours	Omadacycline 450/450 Once Every 12 Hours	Nitrofurantoin 100/100 Once Every 12 Hours
Arm/Group Description	Participants received omadacycline 300 milligrams orally, once every 12 hours, fed on Day 1 and omadacycline 300 milligrams orally, once every 24 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.	Participants received omadacycline 450 milligrams orally, once every 12 hours, fed on Day 1 and omadacycline 300 milligrams orally, once every 24 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.	Participants received omadacycline 450 milligrams orally, once every 12 hours, fed on Day 1 and omadacycline 450 milligrams orally, once every 24 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.	Participants received omadacycline 450 milligrams orally, once every 12 hours, fed on Day 1 and omadacycline 450 milligrams orally, once every 12 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.	Participants received nitrofurantoin 100 milligrams orally, once every 12 hours, fed on Day 1 and nitrofurantoin 100 milligrams orally, once every 12 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.
Measure Participants	55	54	54	8	54
Clinical success	47 85.5%	41 75.9%	44 81.5%	7 87.5%	49 90.7%
Clinical failure	6 10.9%	7 13%	7 13%	0 0%	5 9.3%
Indeterminate	2 3.6%	6 11.1%	3 5.6%	1 12.5%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Omadacycline 300/300 Once Every 24 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority margin for comparison of the doses was set at 10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-5.3
	Confidence Interval	(2-Sided) 95%; -18.6 to 7.8
	Parameter Dispersion	Type: Value:
	Estimation Comments	Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Omadacycline 450/300 Once Every 24 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority margin for comparison of the doses was set at 10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-14.8
	Confidence Interval	(2-Sided) 95%; -29.6 to -0.6
	Parameter Dispersion	Type: Value:
	Estimation Comments	Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Omadacycline 450/450 Once Every 24 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority margin for comparison of the doses was set at 10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-9.3
	Confidence Interval	(2-Sided) 95%; -23.2 to 4.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Omadacycline 450/450 Once Every 12 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority margin for comparison of the doses was set at 10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-3.2
	Confidence Interval	(2-Sided) 95%; -44.1 to 14.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.

8. Secondary Outcome

Title	Number of Participants With an Investigator Assessment of Clinical Response at the FFU Visit (CE-FFU Population)
Description	Clinical response was determined by the investigator at the FFU visit by assessing whether or not the participant met the clinical outcome of Clinical Success or Clinical Failure. Clinical Success was defined as sufficient resolution of cystitis signs and symptoms at the FFU visit such that no additional systemic antimicrobial therapy was required for the current infection. Clinical Failure was defined as no apparent response to therapy or persistence of signs and symptoms of infection at the FFU visit such that use of additional systemic antimicrobial therapy for the current infection was required. For the CE population, the clinical outcome was not deemed as indeterminate response.
Time Frame	FFU visit (A FFU occurred 30 to 37 days following the first dose of study drug)

Outcome Measure Data

Analysis Population Description

The clinically evaluable (CE)-FFU Population consisted of all ITT participants who completed the FFU visit, received test article, had a qualifying infection, an assessment of outcome, and met all other evaluability criteria.

Arm/Group Title	Omadacycline 300/300 Once Every 24 Hours	Omadacycline 450/300 Once Every 24 Hours	Omadacycline 450/450 Once Every 24 Hours	Omadacycline 450/450 Once Every 12 Hours	Nitrofurantoin 100/100 Once Every 12 Hours
Arm/Group Description	Participants received omadacycline 300 milligrams orally, once every 12 hours, fed on Day 1 and omadacycline 300 milligrams orally, once every 24 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.	Participants received omadacycline 450 milligrams orally, once every 12 hours, fed on Day 1 and omadacycline 300 milligrams orally, once every 24 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.	Participants received omadacycline 450 milligrams orally, once every 12 hours, fed on Day 1 and omadacycline 450 milligrams orally, once every 24 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.	Participants received omadacycline 450 milligrams orally, once every 12 hours, fed on Day 1 and omadacycline 450 milligrams orally, once every 12 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.	Participants received nitrofurantoin 100 milligrams orally, once every 12 hours, fed on Day 1 and nitrofurantoin 100 milligrams orally, once every 12 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.
Measure Participants	47	43	43	7	49
Clinical success	43 78.2%	37 68.5%	39 72.2%	7 87.5%	45 83.3%
Clinical failure	4 7.3%	6 11.1%	4 7.4%	0 0%	4 7.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Omadacycline 300/300 Once Every 24 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority margin for comparison of the doses was set at 10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-0.3
	Confidence Interval	(2-Sided) 95%; -13.1 to 12.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Omadacycline 450/300 Once Every 24 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority margin for comparison of the doses was set at 10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-5.8
	Confidence Interval	(2-Sided) 95%; -20.7 to 7.8
	Parameter Dispersion	Type: Value:
	Estimation Comments	Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Omadacycline 450/450 Once Every 24 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority margin for comparison of the doses was set at 10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-1.1
	Confidence Interval	(2-Sided) 95%; -15.1 to 11.6
	Parameter Dispersion	Type: Value:
	Estimation Comments	Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Nitrofurantoin 100/100 Once Every 12 Hours
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority margin for comparison of the doses was set at 10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	8.2
	Confidence Interval	(2-Sided) 95%; -35.3 to 20.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.

9. Secondary Outcome

Title	Number of Participants With an Investigator Assessment of Clinical Response at the FFU Visit (Micro-ITT Population)
Description	Clinical response was determined by the investigator at the FFU visit by assessing whether or not the participant met the clinical outcome of Clinical Success, Clinical Failure, or Indeterminate. Clinical Success was defined as sufficient resolution of cystitis signs and symptoms at the FFU visit such that no additional systemic antimicrobial therapy was required for the current infection. Clinical Failure was defined as no apparent response to therapy or persistence of signs and symptoms of infection at the FFU visit such that use of additional systemic antimicrobial therapy for the current infection was required. The clinical outcome was deemed as Indeterminate when the FFU visit was not completed.
Time Frame	FFU visit (A FFU occurred 30 to 37 days following the first dose of study drug)

Outcome Measure Data

Analysis Population Description

The micro-ITT population consisted of all randomized participants who had a study-qualifying pre-treatment baseline urine culture. A study-qualifying pretreatment Baseline culture was defined as a culture from a clean-catch urine sample which grew at least 1 and no more than 2 bacterial isolates at ≥ 10^5 CFU/mL each.

Arm/Group Title	Omadacycline 300/300 Once Every 24 Hours	Omadacycline 450/300 Once Every 24 Hours	Omadacycline 450/450 Once Every 24 Hours	Omadacycline 450/450 Once Every 12 Hours	Nitrofurantoin 100/100 Once Every 12 Hours
Arm/Group Description	Participants received omadacycline 300 milligrams orally, once every 12 hours, fed on Day 1 and omadacycline 300 milligrams orally, once every 24 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.	Participants received omadacycline 450 milligrams orally, once every 12 hours, fed on Day 1 and omadacycline 300 milligrams orally, once every 24 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.	Participants received omadacycline 450 milligrams orally, once every 12 hours, fed on Day 1 and omadacycline 450 milligrams orally, once every 24 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.	Participants received omadacycline 450 milligrams orally, once every 12 hours, fed on Day 1 and omadacycline 450 milligrams orally, once every 12 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.	Participants received nitrofurantoin 100 milligrams orally, once every 12 hours, fed on Day 1 and nitrofurantoin 100 milligrams orally, once every 12 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.
Measure Participants	25	34	23	5	30
Clinical success	21 38.2%	26 48.1%	20 37%	5 62.5%	27 50%
Clinical failure	2 3.6%	6 11.1%	3 5.6%	0 0%	3 5.6%
Indeterminate	2 3.6%	2 3.7%	0 0%	0 0%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Omadacycline 300/300 Once Every 24 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority margin for comparison of the doses was set at 10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-6.0
	Confidence Interval	(2-Sided) 95%; -27.3 to 13.3
	Parameter Dispersion	Type: Value:
	Estimation Comments	Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Omadacycline 450/300 Once Every 24 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority margin for comparison of the doses was set at 10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-13.5
	Confidence Interval	(2-Sided) 95%; -32.4 to 5.9
	Parameter Dispersion	Type: Value:
	Estimation Comments	Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Omadacycline 450/450 Once Every 24 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority margin for comparison of the doses was set at 10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-3.0
	Confidence Interval	(2-Sided) 95%; -25.7 to 15.6
	Parameter Dispersion	Type: Value:
	Estimation Comments	Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Omadacycline 450/450 Once Every 12 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority margin for comparison of the doses was set at 10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	10.0
	Confidence Interval	(2-Sided) 95%; -40.4 to 28.9
	Parameter Dispersion	Type: Value:
	Estimation Comments	Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated

10. Secondary Outcome

Title	Number of Participants With a Microbiological Response at the EOT Visit (Micro-ITT Population)
Description	Microbiological response was determined programmatically at the EOT visit by assessing whether or not the participant met the microbiological outcome of Favorable, Unfavorable, or Indeterminate. Favorable microbiological outcomes included eradication and presumed eradication i.e., urine specimen showed absence of the original baseline pathogen or the baseline pathogen grew at <10^4 CFU/mL at visit. Unfavorable microbiological outcome included persistence i.e. urine culture showed continued presence (defined as ≥10^4 CFU/mL) of the original baseline pathogen(s) at visit. The microbiological outcome was deemed as Indeterminate when the urine specimen was not available to culture or the culture result was not interpretable.
Time Frame	EOT visit (within 1 to 2 days following the last dose of study drug i.e. up to approximately 9 days)

Outcome Measure Data

Analysis Population Description

The micro-ITT population consisted of all randomized participants who had a study-qualifying pre-treatment baseline urine culture. A study-qualifying pretreatment Baseline culture was defined as a culture from a clean-catch urine sample which grew at least 1 and no more than 2 bacterial isolates at ≥ 10^5 CFU/mL each.

Arm/Group Title	Omadacycline 300/300 Once Every 24 Hours	Omadacycline 450/300 Once Every 24 Hours	Omadacycline 450/450 Once Every 24 Hours	Omadacycline 450/450 Once Every 12 Hours	Nitrofurantoin 100/100 Once Every 12 Hours
Arm/Group Description	Participants received omadacycline 300 milligrams orally, once every 12 hours, fed on Day 1 and omadacycline 300 milligrams orally, once every 24 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.	Participants received omadacycline 450 milligrams orally, once every 12 hours, fed on Day 1 and omadacycline 300 milligrams orally, once every 24 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.	Participants received omadacycline 450 milligrams orally, once every 12 hours, fed on Day 1 and omadacycline 450 milligrams orally, once every 24 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.	Participants received omadacycline 450 milligrams orally, once every 12 hours, fed on Day 1 and omadacycline 450 milligrams orally, once every 12 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.	Participants received nitrofurantoin 100 milligrams orally, once every 12 hours, fed on Day 1 and nitrofurantoin 100 milligrams orally, once every 12 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.
Measure Participants	25	34	23	5	30
Favorable	18 32.7%	27 50%	17 31.5%	5 62.5%	28 51.9%
Unfavorable	5 9.1%	6 11.1%	6 11.1%	0 0%	1 1.9%
Indeterminate	2 3.6%	1 1.9%	0 0%	0 0%	1 1.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Omadacycline 300/300 Once Every 24 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority margin for comparison of the doses was set at 10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-21.3
	Confidence Interval	(2-Sided) 95%; -44.1 to -1.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Omadacycline 450/300 Once Every 24 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority margin for comparison of the doses was set at 10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-13.9
	Confidence Interval	(2-Sided) 95%; -32.2 to 4.9
	Parameter Dispersion	Type: Value:
	Estimation Comments	Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Omadacycline 450/450 Once Every 24 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority margin for comparison of the doses was set at 10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-19.4
	Confidence Interval	(2-Sided) 95%; -43.1 to 1.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Omadacycline 450/450 Once Every 12 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority margin for comparison of the doses was set at 10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	6.7
	Confidence Interval	(2-Sided) 95%; -43.8 to 23.2
	Parameter Dispersion	Type: Value:
	Estimation Comments	Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.

11. Secondary Outcome

Title	Number of Participants With a Microbiological Response at the EOT Visit (ME-EOT Population)
Description	Microbiological response was determined programmatically at the EOT visit by assessing whether or not the participant met the microbiological outcome of Favorable or Unfavorable. Favorable microbiological outcomes included eradication and presumed eradication i.e., urine specimen showed absence of the original baseline pathogen or the baseline pathogen grew at <10^4 CFU/mL at visit. Unfavorable microbiological outcome included persistence i.e. urine culture showed continued presence (defined as ≥10^4 CFU/mL) of the original baseline pathogen(s) at visit. For the ME population, the microbiological outcome was not deemed as indeterminate response.
Time Frame	EOT visit (within 1 to 2 days following the last dose of study drug i.e. up to approximately 9 days)

Outcome Measure Data

Analysis Population Description

The microbiologically evaluable (ME)-EOT population consisted of participants in the micro-ITT and CE-EOT populations who had a study-qualifying pre-treatment baseline urine culture with 1 or 2 uropathogens at ≥ 10^5 CFU/mL.

Arm/Group Title	Omadacycline 300/300 Once Every 24 Hours	Omadacycline 450/300 Once Every 24 Hours	Omadacycline 450/450 Once Every 24 Hours	Omadacycline 450/450 Once Every 12 Hours	Nitrofurantoin 100/100 Once Every 12 Hours
Arm/Group Description	Participants received omadacycline 300 milligrams orally, once every 12 hours, fed on Day 1 and omadacycline 300 milligrams orally, once every 24 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.	Participants received omadacycline 450 milligrams orally, once every 12 hours, fed on Day 1 and omadacycline 300 milligrams orally, once every 24 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.	Participants received omadacycline 450 milligrams orally, once every 12 hours, fed on Day 1 and omadacycline 450 milligrams orally, once every 24 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.	Participants received omadacycline 450 milligrams orally, once every 12 hours, fed on Day 1 and omadacycline 450 milligrams orally, once every 12 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.	Participants received nitrofurantoin 100 milligrams orally, once every 12 hours, fed on Day 1 and nitrofurantoin 100 milligrams orally, once every 12 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.
Measure Participants	22	31	22	5	29
Favorable	18 32.7%	25 46.3%	16 29.6%	5 62.5%	28 51.9%
Unfavorable	4 7.3%	6 11.1%	6 11.1%	0 0%	1 1.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Omadacycline 300/300 Once Every 24 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority margin for comparison of the doses was set at 10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-14.7
	Confidence Interval	(2-Sided) 95%; -37.2 to 3.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Omadacycline 450/300 Once Every 24 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority margin for comparison of the doses was set at 10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-15.9
	Confidence Interval	(2-Sided) 95%; -34.3 to 1.2
	Parameter Dispersion	Type: Value:
	Estimation Comments	Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Omadacycline 450/450 Once Every 24 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority margin for comparison of the doses was set at 10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-23.8
	Confidence Interval	(2-Sided) 95%; -46.9 to -4.3
	Parameter Dispersion	Type: Value:
	Estimation Comments	Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Omadacycline 450/450 Once Every 12 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority margin for comparison of the doses was set at 10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	3.4
	Confidence Interval	(2-Sided) 95%; -48.5 to 19.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.

12. Secondary Outcome

Title	Number of Participants With a Microbiological Response at the PTE Visit (Micro-ITT Population)
Description	Microbiological response was determined programmatically at the PTE visit by assessing whether or not the participant met the microbiological outcome of Favorable, Unfavorable, or Indeterminate. Favorable microbiological outcomes included eradication and presumed eradication i.e., urine specimen showed absence of the original baseline pathogen or the baseline pathogen grew at <10^4 CFU/mL at visit. Unfavorable microbiological outcome included persistence i.e. urine culture showed continued presence (defined as ≥10^4 CFU/mL) of the original baseline pathogen(s) at visit. The microbiological outcome was deemed as Indeterminate when the urine specimen was not available to culture or the culture result was not interpretable.
Time Frame	Day 14 (A PTE occurred on Day 14 ± 2 days after the participant's first dose of study drug)

Outcome Measure Data

Analysis Population Description

The micro-ITT population consisted of all randomized participants who had a study-qualifying pre-treatment baseline urine culture. A study-qualifying pretreatment Baseline culture was defined as a culture from a clean-catch urine sample which grew at least 1 and no more than 2 bacterial isolates at ≥ 10^5 colony forming unit (CFU)/mL each.

Arm/Group Title	Omadacycline 300/300 Once Every 24 Hours	Omadacycline 450/300 Once Every 24 Hours	Omadacycline 450/450 Once Every 24 Hours	Omadacycline 450/450 Once Every 12 Hours	Nitrofurantoin 100/100 Once Every 12 Hours
Arm/Group Description	Participants received omadacycline 300 milligrams orally, once every 12 hours, fed on Day 1 and omadacycline 300 milligrams orally, once every 24 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.	Participants received omadacycline 450 milligrams orally, once every 12 hours, fed on Day 1 and omadacycline 300 milligrams orally, once every 24 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.	Participants received omadacycline 450 milligrams orally, once every 12 hours, fed on Day 1 and omadacycline 450 milligrams orally, once every 24 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.	Participants received omadacycline 450 milligrams orally, once every 12 hours, fed on Day 1 and omadacycline 450 milligrams orally, once every 12 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.	Participants received nitrofurantoin 100 milligrams orally, once every 12 hours, fed on Day 1 and nitrofurantoin 100 milligrams orally, once every 12 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.
Measure Participants	25	34	23	5	30
Favorable	14 25.5%	20 37%	15 27.8%	4 50%	23 42.6%
Unfavorable	8 14.5%	11 20.4%	8 14.8%	1 12.5%	6 11.1%
Indeterminate	3 5.5%	3 5.6%	0 0%	0 0%	1 1.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Omadacycline 300/300 Once Every 24 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority margin for comparison of the doses was set at 10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-20.7
	Confidence Interval	(2-Sided) 95%; -45.1 to 6.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Omadacycline 450/300 Once Every 24 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority margin for comparison of the doses was set at 10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-17.8
	Confidence Interval	(2-Sided) 95%; -40.2 to 5.9
	Parameter Dispersion	Type: Value:
	Estimation Comments	Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Omadacycline 450/450 Once Every 24 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority margin for comparison of the doses was set at 10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-11.4
	Confidence Interval	(2-Sided) 95%; -36.8 to 14.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Omadacycline 450/450 Once Every 12 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority margin for comparison of the doses was set at 10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	3.3
	Confidence Interval	(2-Sided) 95%; -47.0 to 33.2
	Parameter Dispersion	Type: Value:
	Estimation Comments	Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.

13. Secondary Outcome

Title	Number of Participants With a Microbiological Response at the PTE Visit (ME-PTE Population)
Description	Microbiological response was determined programmatically at the PTE visit by assessing whether or not the participant met the microbiological outcome of Favorable or Unfavorable. Favorable microbiological outcomes included eradication and presumed eradication i.e., urine specimen showed absence of the original baseline pathogen or the baseline pathogen grew at <10^4 CFU/mL at visit. Unfavorable microbiological outcome included persistence i.e. urine culture showed continued presence (defined as ≥10^4 CFU/mL) of the original baseline pathogen(s) at visit. For the ME population, the microbiological outcome was not deemed as indeterminate response.
Time Frame	Day 14 (A PTE occurred on Day 14 ± 2 days after the participant's first dose of study drug)

Outcome Measure Data

Analysis Population Description

The ME-PTE population consisted of participants in the micro-ITT and CE-PTE populations who had a study-qualifying pre-treatment baseline urine culture with 1 or 2 uropathogens at ≥ 10^5 CFU/mL.

Arm/Group Title	Omadacycline 300/300 Once Every 24 Hours	Omadacycline 450/300 Once Every 24 Hours	Omadacycline 450/450 Once Every 24 Hours	Omadacycline 450/450 Once Every 12 Hours	Nitrofurantoin 100/100 Once Every 12 Hours
Arm/Group Description	Participants received omadacycline 300 milligrams orally, once every 12 hours, fed on Day 1 and omadacycline 300 milligrams orally, once every 24 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.	Participants received omadacycline 450 milligrams orally, once every 12 hours, fed on Day 1 and omadacycline 300 milligrams orally, once every 24 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.	Participants received omadacycline 450 milligrams orally, once every 12 hours, fed on Day 1 and omadacycline 450 milligrams orally, once every 24 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.	Participants received omadacycline 450 milligrams orally, once every 12 hours, fed on Day 1 and omadacycline 450 milligrams orally, once every 12 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.	Participants received nitrofurantoin 100 milligrams orally, once every 12 hours, fed on Day 1 and nitrofurantoin 100 milligrams orally, once every 12 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.
Measure Participants	20	29	21	5	28
Favorable	13 23.6%	20 37%	14 25.9%	4 50%	22 40.7%
Unfavorable	7 12.7%	9 16.7%	7 13%	1 12.5%	6 11.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Omadacycline 300/300 Once Every 24 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority margin for comparison of the doses was set at 10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-13.6
	Confidence Interval	(2-Sided) 95%; -40.4 to 13.2
	Parameter Dispersion	Type: Value:
	Estimation Comments	Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Omadacycline 450/300 Once Every 24 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority margin for comparison of the doses was set at 10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-9.6
	Confidence Interval	(2-Sided) 95%; -32.7 to 14.6
	Parameter Dispersion	Type: Value:
	Estimation Comments	Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Omadacycline 450/450 Once Every 24 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority margin for comparison of the doses was set at 10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-11.9
	Confidence Interval	(2-Sided) 95%; -38.2 to 14.9
	Parameter Dispersion	Type: Value:
	Estimation Comments	Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Omadacycline 450/450 Once Every 12 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority margin for comparison of the doses was set at 10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	1.4
	Confidence Interval	(2-Sided) 95%; -50.3 to 30.9
	Parameter Dispersion	Type: Value:
	Estimation Comments	Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.

14. Other Pre-specified Outcome

Title	Number of Participants With Resolution of All Urinary Tract Infection (UTI) Signs and Clinical Symptoms at PTE Visit (ITT Population)
Description	Participants recorded their assessments using the UTI Symptoms Assessment (UTISA) questionnaire, a 14-item questionnaire that assessed the levels of 'severity' and 'bothersomeness' for seven UTI signs and symptoms: Frequency, Urgency, Pain/burning on urination, Incomplete voiding, Pain in pelvic area, Low back pain, and Blood in urine. The sub-scale responses were recorded as 'did not have', 'mild', 'moderate', and 'severe' for 'severity'; and 'not at all', 'a little', 'moderately', and 'a lot' for 'bothersomeness', both scored 0-3. Total scores were calculated by summing the non-missing scores of the 7 items, divided by the number of non-missing items, and then multiplied by 7. For each sub-scale, the total score ranged from 0 (least Severe/ least bothersome) and 21 (worst severity/most bothersome). Number of participants with resolution of all symptoms, without occurrence of new symptoms is reported. Resolution was defined as absence of all baseline symptoms.
Time Frame	Day 14 (A PTE occurred on Day 14 ± 2 days after the participant's first dose of study drug)

Outcome Measure Data

Analysis Population Description

The ITT population consisted of all randomized participants regardless of whether or not the participant received study drug. Participants who completed the PTE visit were analyzed for this end point.

Arm/Group Title	Omadacycline 300/300 Once Every 24 Hours	Omadacycline 450/300 Once Every 24 Hours	Omadacycline 450/450 Once Every 24 Hours	Omadacycline 450/450 Once Every 12 Hours	Nitrofurantoin 100/100 Once Every 12 Hours
Arm/Group Description	Participants received omadacycline 300 milligrams orally, once every 12 hours, fed on Day 1 and omadacycline 300 milligrams orally, once every 24 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.	Participants received omadacycline 450 milligrams orally, once every 12 hours, fed on Day 1 and omadacycline 300 milligrams orally, once every 24 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.	Participants received omadacycline 450 milligrams orally, once every 12 hours, fed on Day 1 and omadacycline 450 milligrams orally, once every 24 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.	Participants received omadacycline 450 milligrams orally, once every 12 hours, fed on Day 1 and omadacycline 450 milligrams orally, once every 12 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.	Participants received nitrofurantoin 100 milligrams orally, once every 12 hours, fed on Day 1 and nitrofurantoin 100 milligrams orally, once every 12 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.
Measure Participants	51	47	49	7	51
Count of Participants [Participants]	33 60%	30 55.6%	32 59.3%	6 75%	34 63%

15. Other Pre-specified Outcome

Title	Number of Participants With No Worsening and Absence of New UTI Signs and Clinical Symptoms at PTE Visit (ITT Population)
Description	Participants recorded their assessments using the UTI Symptoms Assessment (UTISA) questionnaire, a 14-item questionnaire that assessed the levels of 'severity' and 'bothersomeness' for seven UTI signs and symptoms: Frequency, Urgency, Pain/burning on urination, Incomplete voiding, Pain in pelvic area, Low back pain, and Blood in urine. The sub-scale responses were recorded as 'did not have', 'mild', 'moderate', and 'severe' for 'severity'; and 'not at all', 'a little', 'moderately', and 'a lot' for 'bothersomeness', both scored 0-3. Total scores were calculated by summing the non-missing scores of the 7 items, divided by the number of non-missing items, and then multiplied by 7. For each sub-scale, the total score ranged from 0 (least Severe/ least bothersome) and 21 (worst severity/most bothersome). Number of participants with no worsening and absence of new UTI signs and clinical symptoms is reported. No worsening meant that each question score is same or better at post baseline.
Time Frame	Day 14 (A PTE occurred on Day 14 ± 2 days after the participant's first dose of study drug)

Outcome Measure Data

Analysis Population Description

The ITT population consisted of all randomized participants regardless of whether or not the participant received study drug. Participants who completed the PTE visit were analyzed for this end point.

Arm/Group Title	Omadacycline 300/300 Once Every 24 Hours	Omadacycline 450/300 Once Every 24 Hours	Omadacycline 450/450 Once Every 24 Hours	Omadacycline 450/450 Once Every 12 Hours	Nitrofurantoin 100/100 Once Every 12 Hours
Arm/Group Description	Participants received omadacycline 300 milligrams orally, once every 12 hours, fed on Day 1 and omadacycline 300 milligrams orally, once every 24 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.	Participants received omadacycline 450 milligrams orally, once every 12 hours, fed on Day 1 and omadacycline 300 milligrams orally, once every 24 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.	Participants received omadacycline 450 milligrams orally, once every 12 hours, fed on Day 1 and omadacycline 450 milligrams orally, once every 24 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.	Participants received omadacycline 450 milligrams orally, once every 12 hours, fed on Day 1 and omadacycline 450 milligrams orally, once every 12 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.	Participants received nitrofurantoin 100 milligrams orally, once every 12 hours, fed on Day 1 and nitrofurantoin 100 milligrams orally, once every 12 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.
Measure Participants	51	47	49	7	51
Count of Participants [Participants]	50 90.9%	45 83.3%	45 83.3%	7 87.5%	50 92.6%

Adverse Events

Time Frame	Up to approximately 37 days
Adverse Event Reporting Description	A treatment-emergent adverse event was defined as any adverse event that newly appeared, increased in frequency, or worsened in severity on or after the initiation of the study drug.
Arm/Group Title	Omadacycline 300/300 Once Every 24 Hours		Omadacycline 450/300 Once Every 24 Hours		Omadacycline 450/450 Once Every 24 Hours		Omadacycline 450/450 Once Every 12 Hours		Nitrofurantoin 100/100 Once Every 12 Hours
Arm/Group Description	Participants received omadacycline 300 milligrams orally, once every 12 hours, fed on Day 1 and omadacycline 300 milligrams orally, once every 24 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.		Participants received omadacycline 450 milligrams orally, once every 12 hours, fed on Day 1 and omadacycline 300 milligrams orally, once every 24 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.		Participants received omadacycline 450 milligrams orally, once every 12 hours, fed on Day 1 and omadacycline 450 milligrams orally, once every 24 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.		Participants received omadacycline 450 milligrams orally, once every 12 hours, fed on Day 1 and omadacycline 450 milligrams orally, once every 12 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.		Participants received nitrofurantoin 100 milligrams orally, once every 12 hours, fed on Day 1 and nitrofurantoin 100 milligrams orally, once every 12 hours on Days 2 through 7. Odd doses on Days 2 to 7 were administered in a fasted state. Even doses on Days 2 to 7 were administered approximately 2 hours following a light meal.
All Cause Mortality
	Omadacycline 300/300 Once Every 24 Hours		Omadacycline 450/300 Once Every 24 Hours		Omadacycline 450/450 Once Every 24 Hours		Omadacycline 450/450 Once Every 12 Hours		Nitrofurantoin 100/100 Once Every 12 Hours
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/55 (0%)		0/54 (0%)		0/54 (0%)		0/8 (0%)		0/54 (0%)
Serious Adverse Events
	Omadacycline 300/300 Once Every 24 Hours		Omadacycline 450/300 Once Every 24 Hours		Omadacycline 450/450 Once Every 24 Hours		Omadacycline 450/450 Once Every 12 Hours		Nitrofurantoin 100/100 Once Every 12 Hours
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/55 (0%)		0/54 (0%)		1/54 (1.9%)		0/8 (0%)		0/54 (0%)
Infections and infestations
Pyelonephritis Acute	0/55 (0%)		0/54 (0%)		1/54 (1.9%)		0/8 (0%)		0/54 (0%)
Other (Not Including Serious) Adverse Events
	Omadacycline 300/300 Once Every 24 Hours		Omadacycline 450/300 Once Every 24 Hours		Omadacycline 450/450 Once Every 24 Hours		Omadacycline 450/450 Once Every 12 Hours		Nitrofurantoin 100/100 Once Every 12 Hours
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/55 (29.1%)		13/54 (24.1%)		15/54 (27.8%)		4/8 (50%)		9/54 (16.7%)
Gastrointestinal disorders
Abdominal discomfort	0/55 (0%)		0/54 (0%)		0/54 (0%)		1/8 (12.5%)		0/54 (0%)
Diarrhoea	2/55 (3.6%)		1/54 (1.9%)		3/54 (5.6%)		0/8 (0%)		2/54 (3.7%)
Nausea	12/55 (21.8%)		8/54 (14.8%)		10/54 (18.5%)		4/8 (50%)		5/54 (9.3%)
Vomiting	3/55 (5.5%)		3/54 (5.6%)		3/54 (5.6%)		1/8 (12.5%)		0/54 (0%)
Infections and infestations
Asymptomatic bacteriuria	1/55 (1.8%)		2/54 (3.7%)		1/54 (1.9%)		0/8 (0%)		0/54 (0%)
Bronchitis	0/55 (0%)		0/54 (0%)		0/54 (0%)		0/8 (0%)		2/54 (3.7%)
Hordeolum	0/55 (0%)		0/54 (0%)		0/54 (0%)		1/8 (12.5%)		0/54 (0%)
Urinary tract infection	1/55 (1.8%)		1/54 (1.9%)		2/54 (3.7%)		0/8 (0%)		0/54 (0%)
Nervous system disorders
Dysgeusia	0/55 (0%)		0/54 (0%)		0/54 (0%)		1/8 (12.5%)		0/54 (0%)
Headache	3/55 (5.5%)		2/54 (3.7%)		4/54 (7.4%)		2/8 (25%)		1/54 (1.9%)
Renal and urinary disorders
Dysuria	2/55 (3.6%)		0/54 (0%)		1/54 (1.9%)		0/8 (0%)		0/54 (0%)

Limitations/Caveats

An additional treatment group (omadacycline 450/450 once every 12 hours) was added with Protocol Amendment 2. However, the majority of enrollment was completed by this time, and therefore, fewer participants were enrolled in this group.

More Information

Certain Agreements

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

The only disclosure restriction on the Principal Investigator is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days from the time submitted to the sponsor for review. The sponsor can request changes to the communication and require the removal of confidential information.