Oral Omadacycline vs. Oral Nitrofurantoin for the Treatment of Cystitis

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)

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

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)

Population: 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.

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)

Population: 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.

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)

Population: 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.

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)

Population: 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.

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)

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

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)

Population: 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.

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)

Population: 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.

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)

Population: 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.

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)

Population: 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.

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)

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

Time frame: Day 14 (A PTE occurred on Day 14 ± 2 days after the participant's first dose of study drug)

Population: 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.

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)

Population: 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.

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)

Population: 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.

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)

Population: 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.