Oral Omadacycline vs. Oral Nitrofurantoin for the Treatment of Cystitis

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Uncomplicated Urinary Tract Infection, Cystitis

Intervention / Treatment
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* Drug: Omadacycline tablets
* Drug: Nitrofurantoin capsules


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Omadacycline 300/300 once every 24 hours<br>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<br>* Oral Omadacycline<br>|
| Experimental: Omadacycline 450/300 once every 24 hours<br>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<br>* Oral Omadacycline<br>|
| Experimental: Omadacycline 450/450 once every 24 hours<br>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<br>* Oral Omadacycline<br>|
| Experimental: Omadacycline 450/450 once every 12 hours<br>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<br>* Oral Omadacycline<br>|
| Active Comparator: Nitrofurantoin 100/100 once every 12 hours<br>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<br>* Oral Nitrofurantoin<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With an Investigator Assessment of Clinical Response at the Post Therapy Evaluation (PTE) Visit (ITT Population) | 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. | Day 14 (A PTE occurred on Day 14 ± 2 days after the participant's first dose of study drug) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With an Investigator Assessment of Clinical Response at the End of Treatment (EOT) Visit (ITT Population) | 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. | EOT visit (within 1 to 2 days following the last dose of study drug i.e. up to approximately 9 days) | 
| Number of Participants With an Investigator Assessment of Clinical Response at the EOT Visit (Microbiological [Micro]-ITT Population) | 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. | EOT visit (within 1 to 2 days following the last dose of study drug i.e. up to approximately 9 days) | 
| Number of Participants With an Investigator Assessment of Clinical Response at the EOT Visit (CE-EOT Population) | 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. | EOT visit (within 1 to 2 days following the last dose of study drug i.e. up to approximately 9 days) | 
| Number of Participants With an Investigator Assessment of Clinical Response at the PTE Visit (CE-PTE Population) | 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. | Day 14 (A PTE occurred on Day 14 ± 2 days after the participant's first dose of study drug) | 
| Number of Participants With an Investigator Assessment of Clinical Response at the PTE Visit (Micro-ITT Population) | 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. | Day 14 (A PTE occurred on Day 14 ± 2 days after the participant's first dose of study drug) | 
| Number of Participants With an Investigator Assessment of Clinical Response at the Final Follow-up (FFU) Visit (ITT Population) | 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 | FFU visit (A FFU occurred 30 to 37 days following the first dose of study drug) | 
| Number of Participants With an Investigator Assessment of Clinical Response at the FFU Visit (CE-FFU Population) | 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. | FFU visit (A FFU occurred 30 to 37 days following the first dose of study drug) | 
| Number of Participants With an Investigator Assessment of Clinical Response at the FFU Visit (Micro-ITT Population) | 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. | FFU visit (A FFU occurred 30 to 37 days following the first dose of study drug) | 
| Number of Participants With a Microbiological Response at the EOT Visit (Micro-ITT Population) | 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. | EOT visit (within 1 to 2 days following the last dose of study drug i.e. up to approximately 9 days) | 
| Number of Participants With a Microbiological Response at the EOT Visit (ME-EOT Population) | 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. | EOT visit (within 1 to 2 days following the last dose of study drug i.e. up to approximately 9 days) | 
| Number of Participants With a Microbiological Response at the PTE Visit (Micro-ITT Population) | 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. | Day 14 (A PTE occurred on Day 14 ± 2 days after the participant's first dose of study drug) | 
| Number of Participants With a Microbiological Response at the PTE Visit (ME-PTE Population) | 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. | Day 14 (A PTE occurred on Day 14 ± 2 days after the participant's first dose of study drug) |