Oral Omadacycline vs. Oral Nitrofurantoin for the Treatment of Cystitis

Phase 2

Completed

Conditions: Cystitis
Uncomplicated Urinary Tract Infection

Interventions: Drug: Omadacycline tablets
Drug: Nitrofurantoin capsules

Registration Number: NCT03425396

Lead Sponsor: Paratek Pharmaceuticals Inc

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.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 225

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Omadacycline 450/300 once every 24 hours	Omadacycline tablets	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.
Omadacycline 450/450 once every 24 hours	Omadacycline tablets	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.
Omadacycline 450/450 once every 12 hours	Omadacycline tablets	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.
Nitrofurantoin 100/100 once every 12 hours	Nitrofurantoin capsules	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.
Omadacycline 300/300 once every 24 hours	Omadacycline tablets	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.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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.
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
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.

Trial Locations

Locations (23): Site 101
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La Mesa, California, United States
Site 102
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DeLand, Florida, United States
Site 114
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Aventura, Florida, United States
Site 106
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Chula Vista, California, United States
Site 125
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Jacksonville, Florida, United States
Site 103
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Hialeah, Florida, United States
Site 127
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Miami Springs, Florida, United States
Site 118
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Raleigh, North Carolina, United States
Site 131
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Houston, Texas, United States
Site 110
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Wichita, Kansas, United States
Site 113
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Newton, Kansas, United States
Site 104
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Jackson, Tennessee, United States
Site 105
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Smyrna, Tennessee, United States
Site 122
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Berlin, New Jersey, United States
Site 121
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Miami, Florida, United States
Site 109
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Los Angeles, California, United States
Site 130
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Miami, Florida, United States
Site 115
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Miami, Florida, United States
Site 126
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Orlando, Florida, United States
Site 112
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Omaha, Nebraska, United States
Site 132
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Las Vegas, Nevada, United States
Site 108
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Las Vegas, Nevada, United States
Site 120
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San Antonio, Texas, United States