Oral Omadacycline vs. Oral Nitrofurantoin for the Treatment of Cystitis

Cystitis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03425396
• Other study ID #: PTK0796-UUTI-17201
• Status: Completed
• Phase: Phase 2
• Start date: January 4, 2018
• Est. completion date: June 5, 2019

Study information

• Verified date: June 2020
• Source: Paratek Pharmaceuticals Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 225
• Est. completion date: June 5, 2019
• Est. primary completion date: May 15, 2019
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cystitis
• Uncomplicated Urinary Tract Infection
• Urinary Tract Infections

Intervention

Drug:
• Omadacycline tablets
Oral Omadacycline
• Nitrofurantoin capsules
Oral Nitrofurantoin

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Paratek Pharmaceuticals Inc

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of Participants With Resolution of All Urinary Tract Infection (UTI) Signs and Clinical Symptoms at PTE Visit (ITT Population)	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.	Day 14 (A PTE occurred on Day 14 ± 2 days after the participant's first dose of study drug)
Other	Number of Participants With No Worsening and Absence of New UTI Signs and Clinical Symptoms at PTE Visit (ITT Population)	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.	Day 14 (A PTE occurred on Day 14 ± 2 days after the participant's first dose of study drug)
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)