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Oral Omadacycline vs. Oral Nitrofurantoin for the Treatment of Cystitis

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ClinicalTrials.gov Identifier: NCT03425396
Recruitment Status : Completed
First Posted : February 7, 2018
Results First Posted : June 4, 2020
Last Update Posted : June 9, 2020
Sponsor:
Information provided by (Responsible Party):
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.

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.

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Study Type : Interventional  (Clinical Trial)
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 : January 4, 2018
Actual Primary Completion Date : May 15, 2019
Actual Study Completion Date : June 5, 2019

Resource links provided by the National Library of Medicine


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




Primary Outcome Measures :
  1. Number of Participants With an Investigator Assessment of Clinical Response at the Post Therapy Evaluation (PTE) Visit (ITT Population) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03425396


Locations
Show Show 23 study locations
Sponsors and Collaborators
Paratek Pharmaceuticals Inc
  Study Documents (Full-Text)

Documents provided by Paratek Pharmaceuticals Inc:
Study Protocol  [PDF] February 18, 2019
Statistical Analysis Plan  [PDF] May 22, 2019

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Responsible Party: Paratek Pharmaceuticals Inc
ClinicalTrials.gov Identifier: NCT03425396    
Other Study ID Numbers: PTK0796-UUTI-17201
First Posted: February 7, 2018    Key Record Dates
Results First Posted: June 4, 2020
Last Update Posted: June 9, 2020
Last Verified: June 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Urinary Tract Infections
Cystitis
Infection
Urologic Diseases
Urinary Bladder Diseases
Nitrofurantoin
Anti-Infective Agents, Urinary
Anti-Infective Agents
Renal Agents
Anti-Bacterial Agents