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Oral Omadacycline vs. Oral Nitrofurantoin for the Treatment of Cystitis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Uncomplicated Urinary Tract Infection
Cystitis
Interventions Drug: Omadacycline tablets
Drug: Nitrofurantoin capsules
Enrollment 225
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Omadacycline 300/300 Once Every 24 Hours Omadacycline 450/300 Once Every 24 Hours Omadacycline 450/450 Once Every 24 Hours Omadacycline 450/450 Once Every 12 Hours Nitrofurantoin 100/100 Once Every 12 Hours
Hide Arm/Group Description 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. 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. 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. 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. 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.
Period Title: Overall Study
Started 55 54 54 8 54
Completed End of Treatment Visit 53 52 51 7 53
Completed Post-therapy Evaluation Visit 53 49 51 7 54
Completed Final Follow-up Visit 53 47 51 7 53
Completed 53 47 51 7 53
Not Completed 2 7 3 1 1
Reason Not Completed
Lost to Follow-up             2             5             2             0             0
Withdrawal by Subject             0             1             0             1             0
Other             0             1             1             0             1
Arm/Group Title Omadacycline 300/300 Once Every 24 Hours Omadacycline 450/300 Once Every 24 Hours Omadacycline 450/450 Once Every 24 Hours Omadacycline 450/450 Once Every 12 Hours Nitrofurantoin 100/100 Once Every 12 Hours Total
Hide Arm/Group Description 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. 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. 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. 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. 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. Total of all reporting groups
Overall Number of Baseline Participants 55 54 54 8 54 225
Hide Baseline Analysis Population Description
The Intent-to-Treat (ITT) Population consisted of all randomized participants regardless of whether or not the participant received study drug.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 55 participants 54 participants 54 participants 8 participants 54 participants 225 participants
45.3  (17.05) 47.4  (15.70) 45.0  (15.49) 37.5  (13.60) 45.5  (17.82) 45.5  (16.41)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 55 participants 54 participants 54 participants 8 participants 54 participants 225 participants
Female
55
 100.0%
54
 100.0%
54
 100.0%
8
 100.0%
54
 100.0%
225
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 55 participants 54 participants 54 participants 8 participants 54 participants 225 participants
Hispanic or Latino
47
  85.5%
47
  87.0%
43
  79.6%
7
  87.5%
47
  87.0%
191
  84.9%
Not Hispanic or Latino
8
  14.5%
7
  13.0%
11
  20.4%
1
  12.5%
7
  13.0%
34
  15.1%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 55 participants 54 participants 54 participants 8 participants 54 participants 225 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   1.9%
1
   0.4%
Asian
0
   0.0%
1
   1.9%
1
   1.9%
0
   0.0%
1
   1.9%
3
   1.3%
Native Hawaiian or Other Pacific Islander
1
   1.8%
0
   0.0%
0
   0.0%
0
   0.0%
1
   1.9%
2
   0.9%
Black or African American
2
   3.6%
1
   1.9%
4
   7.4%
2
  25.0%
4
   7.4%
13
   5.8%
White
52
  94.5%
52
  96.3%
48
  88.9%
6
  75.0%
47
  87.0%
205
  91.1%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
1
   1.9%
0
   0.0%
0
   0.0%
1
   0.4%
1.Primary Outcome
Title Number of Participants With an Investigator Assessment of Clinical Response at the Post Therapy Evaluation (PTE) Visit (ITT Population)
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent-to-Treat (ITT) Population consisted of all randomized participants regardless of whether or not the participant received study drug.
Arm/Group Title Omadacycline 300/300 Once Every 24 Hours Omadacycline 450/300 Once Every 24 Hours Omadacycline 450/450 Once Every 24 Hours Omadacycline 450/450 Once Every 12 Hours Nitrofurantoin 100/100 Once Every 12 Hours
Hide Arm/Group Description:
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.
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.
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.
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.
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.
Overall Number of Participants Analyzed 55 54 54 8 54
Measure Type: Count of Participants
Unit of Measure: Participants
Clinical Success
48
  87.3%
42
  77.8%
46
  85.2%
7
  87.5%
49
  90.7%
Clinical Failure
5
   9.1%
6
  11.1%
5
   9.3%
0
   0.0%
5
   9.3%
Indeterminate
2
   3.6%
6
  11.1%
3
   5.6%
1
  12.5%
0
   0.0%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Omadacycline 300/300 Once Every 24 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Non-inferiority margin for comparison of the doses was set at 10%.
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -3.5
Confidence Interval (2-Sided) 95%
-16.8 to 9.6
Estimation Comments Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Omadacycline 450/300 Once Every 24 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Non-inferiority margin for comparison of the doses was set at 10%.
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -13.0
Confidence Interval (2-Sided) 95%
-27.4 to 1.2
Estimation Comments Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Omadacycline 450/450 Once Every 24 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Non-inferiority margin for comparison of the doses was set at 10%.
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -5.6
Confidence Interval (2-Sided) 95%
-19.6 to 7.4
Estimation Comments Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Omadacycline 450/450 Once Every 12 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Non-inferiority margin for comparison of the doses was set at 10%.
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -3.2
Confidence Interval (2-Sided) 95%
-44.1 to 14.7
Estimation Comments Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.
2.Secondary Outcome
Title Number of Participants With an Investigator Assessment of Clinical Response at the End of Treatment (EOT) Visit (ITT Population)
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT Population consisted of all randomized participants regardless of whether or not the participant received study drug.
Arm/Group Title Omadacycline 300/300 Once Every 24 Hours Omadacycline 450/300 Once Every 24 Hours Omadacycline 450/450 Once Every 24 Hours Omadacycline 450/450 Once Every 12 Hours Nitrofurantoin 100/100 Once Every 12 Hours
Hide Arm/Group Description:
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.
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.
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.
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.
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.
Overall Number of Participants Analyzed 55 54 54 8 54
Measure Type: Count of Participants
Unit of Measure: Participants
Clinical Success
49
  89.1%
47
  87.0%
49
  90.7%
7
  87.5%
49
  90.7%
Clinical Failure
4
   7.3%
5
   9.3%
2
   3.7%
0
   0.0%
4
   7.4%
Indeterminate
2
   3.6%
2
   3.7%
3
   5.6%
1
  12.5%
1
   1.9%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Omadacycline 300/300 Once Every 24 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Non-inferiority margin for comparison of the doses was set at 10%.
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -1.6
Confidence Interval (2-Sided) 95%
-14.3 to 11.2
Estimation Comments Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Omadacycline 450/300 Once Every 24 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Non-inferiority margin for comparison of the doses was set at 10%.
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -3.7
Confidence Interval (2-Sided) 95%
-16.8 to 9.0
Estimation Comments Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Omadacycline 450/450 Once Every 24 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Non-inferiority margin for comparison of the doses was set at 10%.
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
-12.3 to 12.3
Estimation Comments Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Omadacycline 450/450 Once Every 12 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Non-inferiority margin for comparison of the doses was set at 10%.
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -3.2
Confidence Interval (2-Sided) 95%
-44.1 to 14.7
Estimation Comments Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.
3.Secondary Outcome
Title Number of Participants With an Investigator Assessment of Clinical Response at the EOT Visit (Microbiological [Micro]-ITT Population)
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Omadacycline 300/300 Once Every 24 Hours Omadacycline 450/300 Once Every 24 Hours Omadacycline 450/450 Once Every 24 Hours Omadacycline 450/450 Once Every 12 Hours Nitrofurantoin 100/100 Once Every 12 Hours
Hide Arm/Group Description:
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.
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.
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.
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.
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.
Overall Number of Participants Analyzed 25 34 23 5 30
Measure Type: Count of Participants
Unit of Measure: Participants
Clinical Success
22
  88.0%
29
  85.3%
22
  95.7%
5
 100.0%
27
  90.0%
Clinical Failure
1
   4.0%
4
  11.8%
1
   4.3%
0
   0.0%
3
  10.0%
Indeterminate
2
   8.0%
1
   2.9%
0
   0.0%
0
   0.0%
0
   0.0%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Omadacycline 300/300 Once Every 24 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Non-inferiority margin for comparison of the doses was set at 10%.
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -2.0
Confidence Interval (2-Sided) 95%
-22.5 to 16.8
Estimation Comments Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Omadacycline 450/300 Once Every 24 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Non-inferiority margin for comparison of the doses was set at 10%.
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -4.7
Confidence Interval (2-Sided) 95%
-23.3 to 14.2
Estimation Comments Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Omadacycline 450/450 Once Every 24 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Non-inferiority margin for comparison of the doses was set at 10%.
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 5.7
Confidence Interval (2-Sided) 95%
-13.0 to 22.6
Estimation Comments Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Omadacycline 450/450 Once Every 12 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Non-inferiority margin for comparison of the doses was set at 10%.
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 10.0
Confidence Interval (2-Sided) 95%
-40.4 to 28.9
Estimation Comments Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.
4.Secondary Outcome
Title Number of Participants With an Investigator Assessment of Clinical Response at the EOT Visit (CE-EOT Population)
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Omadacycline 300/300 Once Every 24 Hours Omadacycline 450/300 Once Every 24 Hours Omadacycline 450/450 Once Every 24 Hours Omadacycline 450/450 Once Every 12 Hours Nitrofurantoin 100/100 Once Every 12 Hours
Hide Arm/Group Description:
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.
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.
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.
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.
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.
Overall Number of Participants Analyzed 50 47 47 7 52
Measure Type: Count of Participants
Unit of Measure: Participants
Clinical Success
47
  94.0%
42
  89.4%
47
 100.0%
7
 100.0%
48
  92.3%
Clinical Failure
3
   6.0%
5
  10.6%
0
   0.0%
0
   0.0%
4
   7.7%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Omadacycline 300/300 Once Every 24 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Non-inferiority margin for comparison of the doses was set at 10%.
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 1.7
Confidence Interval (2-Sided) 95%
-10.0 to 13.4
Estimation Comments Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Omadacycline 450/300 Once Every 24 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Non-inferiority margin for comparison of the doses was set at 10%
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -2.9
Confidence Interval (2-Sided) 95%
-16.2 to 9.7
Estimation Comments Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Omadacycline 450/450 Once Every 24 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Non-inferiority margin for comparison of the doses was set at 10%
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value 7.7
Confidence Interval (2-Sided) 95%
-0.3 to 18.5
Estimation Comments Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Omadacycline 450/450 Once Every 12 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Non-inferiority margin for comparison of the doses was set at 10%.
Method of Estimation Estimation Parameter Treatm,ent difference
Estimated Value 7.7
Confidence Interval (2-Sided) 95%
-34.9 to 20.6
Estimation Comments Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.
5.Secondary Outcome
Title Number of Participants With an Investigator Assessment of Clinical Response at the PTE Visit (CE-PTE Population)
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Omadacycline 300/300 Once Every 24 Hours Omadacycline 450/300 Once Every 24 Hours Omadacycline 450/450 Once Every 24 Hours Omadacycline 450/450 Once Every 12 Hours Nitrofurantoin 100/100 Once Every 12 Hours
Hide Arm/Group Description:
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.
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.
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.
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.
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.
Overall Number of Participants Analyzed 49 46 47 7 49
Measure Type: Count of Participants
Unit of Measure: Participants
Clinical success
45
  91.8%
41
  89.1%
46
  97.9%
7
 100.0%
45
  91.8%
Clinical failure
4
   8.2%
5
  10.9%
1
   2.1%
0
   0.0%
4
   8.2%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Omadacycline 300/300 Once Every 24 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Non-inferiority margin for comparison of the doses was set at 10%
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
-12.6 to 12.6
Estimation Comments Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Omadacycline 450/300 Once Every 24 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Non-inferiority margin for comparison of the doses was set at 10%.
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -2.7
Confidence Interval (2-Sided) 95%
-16.3 to 10.2
Estimation Comments Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Omadacycline 450/450 Once Every 24 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Non-inferiority margin for comparison of the doses was set at 10%.
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 6.0
Confidence Interval (2-Sided) 95%
-4.5 to 17.7
Estimation Comments Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Omadacycline 450/450 Once Every 12 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Non-inferiority margin for comparison of the doses was set at 10%.
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 8.2
Confidence Interval (2-Sided) 95%
-35.3 to 20.7
Estimation Comments Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.
6.Secondary Outcome
Title Number of Participants With an Investigator Assessment of Clinical Response at the PTE Visit (Micro-ITT Population)
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Omadacycline 300/300 Once Every 24 Hours Omadacycline 450/300 Once Every 24 Hours Omadacycline 450/450 Once Every 24 Hours Omadacycline 450/450 Once Every 12 Hours Nitrofurantoin 100/100 Once Every 12 Hours
Hide Arm/Group Description:
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.
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.
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.
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.
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.
Overall Number of Participants Analyzed 25 34 23 5 30
Measure Type: Count of Participants
Unit of Measure: Participants
Clinical success
21
  84.0%
27
  79.4%
21
  91.3%
5
 100.0%
27
  90.0%
Clinical failure
2
   8.0%
5
  14.7%
2
   8.7%
0
   0.0%
3
  10.0%
Indeterminate
2
   8.0%
2
   5.9%
0
   0.0%
0
   0.0%
0
   0.0%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Omadacycline 300/300 Once Every 24 Hours
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Non-inferiority margin for comparison of the doses was set at 10%
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -6.0
Confidence Interval (2-Sided) 95%
-27.3 to 13.3
Estimation Comments Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Omadacycline 450/300 Once Every 24 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Non-inferiority margin for comparison of the doses was set at 10%.
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -10.6
Confidence Interval (2-Sided) 95%
-29.2 to 8.6
Estimation Comments Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Omadacycline 450/450 Once Every 24 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Non-inferiority margin for comparison of the doses was set at 10%.
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value 1.3
Confidence Interval (2-Sided) 95%
-19.0 to 19.2
Estimation Comments Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Omadacycline 450/450 Once Every 12 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Non-inferiority margin for comparison of the doses was set at 10%.
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 10.0
Confidence Interval (2-Sided) 95%
-40.4 to 28.9
Estimation Comments Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.
7.Secondary Outcome
Title Number of Participants With an Investigator Assessment of Clinical Response at the Final Follow-up (FFU) Visit (ITT Population)
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT Population consisted of all randomized participants regardless of whether or not the participant received study drug.
Arm/Group Title Omadacycline 300/300 Once Every 24 Hours Omadacycline 450/300 Once Every 24 Hours Omadacycline 450/450 Once Every 24 Hours Omadacycline 450/450 Once Every 12 Hours Nitrofurantoin 100/100 Once Every 12 Hours
Hide Arm/Group Description:
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.
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.
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.
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.
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.
Overall Number of Participants Analyzed 55 54 54 8 54
Measure Type: Count of Participants
Unit of Measure: Participants
Clinical success
47
  85.5%
41
  75.9%
44
  81.5%
7
  87.5%
49
  90.7%
Clinical failure
6
  10.9%
7
  13.0%
7
  13.0%
0
   0.0%
5
   9.3%
Indeterminate
2
   3.6%
6
  11.1%
3
   5.6%
1
  12.5%
0
   0.0%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Omadacycline 300/300 Once Every 24 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Non-inferiority margin for comparison of the doses was set at 10%.
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -5.3
Confidence Interval (2-Sided) 95%
-18.6 to 7.8
Estimation Comments Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Omadacycline 450/300 Once Every 24 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Non-inferiority margin for comparison of the doses was set at 10%.
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -14.8
Confidence Interval (2-Sided) 95%
-29.6 to -0.6
Estimation Comments Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Omadacycline 450/450 Once Every 24 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Non-inferiority margin for comparison of the doses was set at 10%.
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -9.3
Confidence Interval (2-Sided) 95%
-23.2 to 4.4
Estimation Comments Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Omadacycline 450/450 Once Every 12 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Non-inferiority margin for comparison of the doses was set at 10%.
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -3.2
Confidence Interval (2-Sided) 95%
-44.1 to 14.7
Estimation Comments Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.
8.Secondary Outcome
Title Number of Participants With an Investigator Assessment of Clinical Response at the FFU Visit (CE-FFU Population)
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Omadacycline 300/300 Once Every 24 Hours Omadacycline 450/300 Once Every 24 Hours Omadacycline 450/450 Once Every 24 Hours Omadacycline 450/450 Once Every 12 Hours Nitrofurantoin 100/100 Once Every 12 Hours
Hide Arm/Group Description:
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.
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.
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.
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.
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.
Overall Number of Participants Analyzed 47 43 43 7 49
Measure Type: Count of Participants
Unit of Measure: Participants
Clinical success
43
  91.5%
37
  86.0%
39
  90.7%
7
 100.0%
45
  91.8%
Clinical failure
4
   8.5%
6
  14.0%
4
   9.3%
0
   0.0%
4
   8.2%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Omadacycline 300/300 Once Every 24 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Non-inferiority margin for comparison of the doses was set at 10%.
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -0.3
Confidence Interval (2-Sided) 95%
-13.1 to 12.7
Estimation Comments Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Omadacycline 450/300 Once Every 24 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Non-inferiority margin for comparison of the doses was set at 10%.
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -5.8
Confidence Interval (2-Sided) 95%
-20.7 to 7.8
Estimation Comments Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Omadacycline 450/450 Once Every 24 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Non-inferiority margin for comparison of the doses was set at 10%.
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -1.1
Confidence Interval (2-Sided) 95%
-15.1 to 11.6
Estimation Comments Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Nitrofurantoin 100/100 Once Every 12 Hours
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Non-inferiority margin for comparison of the doses was set at 10%.
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 8.2
Confidence Interval (2-Sided) 95%
-35.3 to 20.7
Estimation Comments Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.
9.Secondary Outcome
Title Number of Participants With an Investigator Assessment of Clinical Response at the FFU Visit (Micro-ITT Population)
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Omadacycline 300/300 Once Every 24 Hours Omadacycline 450/300 Once Every 24 Hours Omadacycline 450/450 Once Every 24 Hours Omadacycline 450/450 Once Every 12 Hours Nitrofurantoin 100/100 Once Every 12 Hours
Hide Arm/Group Description:
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.
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.
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.
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.
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.
Overall Number of Participants Analyzed 25 34 23 5 30
Measure Type: Count of Participants
Unit of Measure: Participants
Clinical success
21
  84.0%
26
  76.5%
20
  87.0%
5
 100.0%
27
  90.0%
Clinical failure
2
   8.0%
6
  17.6%
3
  13.0%
0
   0.0%
3
  10.0%
Indeterminate
2
   8.0%
2
   5.9%
0
   0.0%
0
   0.0%
0
   0.0%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Omadacycline 300/300 Once Every 24 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Non-inferiority margin for comparison of the doses was set at 10%.
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -6.0
Confidence Interval (2-Sided) 95%
-27.3 to 13.3
Estimation Comments Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Omadacycline 450/300 Once Every 24 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Non-inferiority margin for comparison of the doses was set at 10%.
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -13.5
Confidence Interval (2-Sided) 95%
-32.4 to 5.9
Estimation Comments Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Omadacycline 450/450 Once Every 24 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Non-inferiority margin for comparison of the doses was set at 10%.
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -3.0
Confidence Interval (2-Sided) 95%
-25.7 to 15.6
Estimation Comments Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Omadacycline 450/450 Once Every 12 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Non-inferiority margin for comparison of the doses was set at 10%.
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 10.0
Confidence Interval (2-Sided) 95%
-40.4 to 28.9
Estimation Comments Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated
10.Secondary Outcome
Title Number of Participants With a Microbiological Response at the EOT Visit (Micro-ITT Population)
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Omadacycline 300/300 Once Every 24 Hours Omadacycline 450/300 Once Every 24 Hours Omadacycline 450/450 Once Every 24 Hours Omadacycline 450/450 Once Every 12 Hours Nitrofurantoin 100/100 Once Every 12 Hours
Hide Arm/Group Description:
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.
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.
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.
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.
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.
Overall Number of Participants Analyzed 25 34 23 5 30
Measure Type: Count of Participants
Unit of Measure: Participants
Favorable
18
  72.0%
27
  79.4%
17
  73.9%
5
 100.0%
28
  93.3%
Unfavorable
5
  20.0%
6
  17.6%
6
  26.1%
0
   0.0%
1
   3.3%
Indeterminate
2
   8.0%
1
   2.9%
0
   0.0%
0
   0.0%
1
   3.3%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Omadacycline 300/300 Once Every 24 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Non-inferiority margin for comparison of the doses was set at 10%.
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -21.3
Confidence Interval (2-Sided) 95%
-44.1 to -1.0
Estimation Comments Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Omadacycline 450/300 Once Every 24 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Non-inferiority margin for comparison of the doses was set at 10%.
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -13.9
Confidence Interval (2-Sided) 95%
-32.2 to 4.9
Estimation Comments Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Omadacycline 450/450 Once Every 24 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Non-inferiority margin for comparison of the doses was set at 10%.
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -19.4
Confidence Interval (2-Sided) 95%
-43.1 to 1.1
Estimation Comments Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Omadacycline 450/450 Once Every 12 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Non-inferiority margin for comparison of the doses was set at 10%.
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 6.7
Confidence Interval (2-Sided) 95%
-43.8 to 23.2
Estimation Comments Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.
11.Secondary Outcome
Title Number of Participants With a Microbiological Response at the EOT Visit (ME-EOT Population)
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Omadacycline 300/300 Once Every 24 Hours Omadacycline 450/300 Once Every 24 Hours Omadacycline 450/450 Once Every 24 Hours Omadacycline 450/450 Once Every 12 Hours Nitrofurantoin 100/100 Once Every 12 Hours
Hide Arm/Group Description:
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.
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.
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.
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.
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.
Overall Number of Participants Analyzed 22 31 22 5 29
Measure Type: Count of Participants
Unit of Measure: Participants
Favorable
18
  81.8%
25
  80.6%
16
  72.7%
5
 100.0%
28
  96.6%
Unfavorable
4
  18.2%
6
  19.4%
6
  27.3%
0
   0.0%
1
   3.4%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Omadacycline 300/300 Once Every 24 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Non-inferiority margin for comparison of the doses was set at 10%.
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -14.7
Confidence Interval (2-Sided) 95%
-37.2 to 3.1
Estimation Comments Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Omadacycline 450/300 Once Every 24 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Non-inferiority margin for comparison of the doses was set at 10%.
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -15.9
Confidence Interval (2-Sided) 95%
-34.3 to 1.2
Estimation Comments Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Omadacycline 450/450 Once Every 24 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Non-inferiority margin for comparison of the doses was set at 10%.
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -23.8
Confidence Interval (2-Sided) 95%
-46.9 to -4.3
Estimation Comments Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Omadacycline 450/450 Once Every 12 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Non-inferiority margin for comparison of the doses was set at 10%.
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 3.4
Confidence Interval (2-Sided) 95%
-48.5 to 19.7
Estimation Comments Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.
12.Secondary Outcome
Title Number of Participants With a Microbiological Response at the PTE Visit (Micro-ITT Population)
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Omadacycline 300/300 Once Every 24 Hours Omadacycline 450/300 Once Every 24 Hours Omadacycline 450/450 Once Every 24 Hours Omadacycline 450/450 Once Every 12 Hours Nitrofurantoin 100/100 Once Every 12 Hours
Hide Arm/Group Description:
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.
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.
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.
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.
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.
Overall Number of Participants Analyzed 25 34 23 5 30
Measure Type: Count of Participants
Unit of Measure: Participants
Favorable
14
  56.0%
20
  58.8%
15
  65.2%
4
  80.0%
23
  76.7%
Unfavorable
8
  32.0%
11
  32.4%
8
  34.8%
1
  20.0%
6
  20.0%
Indeterminate
3
  12.0%
3
   8.8%
0
   0.0%
0
   0.0%
1
   3.3%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Omadacycline 300/300 Once Every 24 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Non-inferiority margin for comparison of the doses was set at 10%.
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -20.7
Confidence Interval (2-Sided) 95%
-45.1 to 6.0
Estimation Comments Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Omadacycline 450/300 Once Every 24 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Non-inferiority margin for comparison of the doses was set at 10%.
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -17.8
Confidence Interval (2-Sided) 95%
-40.2 to 5.9
Estimation Comments Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Omadacycline 450/450 Once Every 24 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Non-inferiority margin for comparison of the doses was set at 10%.
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -11.4
Confidence Interval (2-Sided) 95%
-36.8 to 14.7
Estimation Comments Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Omadacycline 450/450 Once Every 12 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Non-inferiority margin for comparison of the doses was set at 10%.
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 3.3
Confidence Interval (2-Sided) 95%
-47.0 to 33.2
Estimation Comments Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.
13.Secondary Outcome
Title Number of Participants With a Microbiological Response at the PTE Visit (ME-PTE Population)
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Omadacycline 300/300 Once Every 24 Hours Omadacycline 450/300 Once Every 24 Hours Omadacycline 450/450 Once Every 24 Hours Omadacycline 450/450 Once Every 12 Hours Nitrofurantoin 100/100 Once Every 12 Hours
Hide Arm/Group Description:
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.
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.
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.
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.
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.
Overall Number of Participants Analyzed 20 29 21 5 28
Measure Type: Count of Participants
Unit of Measure: Participants
Favorable
13
  65.0%
20
  69.0%
14
  66.7%
4
  80.0%
22
  78.6%
Unfavorable
7
  35.0%
9
  31.0%
7
  33.3%
1
  20.0%
6
  21.4%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Omadacycline 300/300 Once Every 24 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Non-inferiority margin for comparison of the doses was set at 10%.
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -13.6
Confidence Interval (2-Sided) 95%
-40.4 to 13.2
Estimation Comments Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Omadacycline 450/300 Once Every 24 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Non-inferiority margin for comparison of the doses was set at 10%.
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -9.6
Confidence Interval (2-Sided) 95%
-32.7 to 14.6
Estimation Comments Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Omadacycline 450/450 Once Every 24 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Non-inferiority margin for comparison of the doses was set at 10%.
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -11.9
Confidence Interval (2-Sided) 95%
-38.2 to 14.9
Estimation Comments Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Omadacycline 450/450 Once Every 12 Hours, Nitrofurantoin 100/100 Once Every 12 Hours
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Non-inferiority margin for comparison of the doses was set at 10%.
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 1.4
Confidence Interval (2-Sided) 95%
-50.3 to 30.9
Estimation Comments Point estimate and exact 95% confidence intervals for difference from nitrofurantoin (omadacycline minus nitrofurantoin) in clinical success rate was estimated.
14.Other Pre-specified Outcome
Title Number of Participants With Resolution of All Urinary Tract Infection (UTI) Signs and Clinical Symptoms at PTE Visit (ITT Population)
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Omadacycline 300/300 Once Every 24 Hours Omadacycline 450/300 Once Every 24 Hours Omadacycline 450/450 Once Every 24 Hours Omadacycline 450/450 Once Every 12 Hours Nitrofurantoin 100/100 Once Every 12 Hours
Hide Arm/Group Description:
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.
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.
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.
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.
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.
Overall Number of Participants Analyzed 51 47 49 7 51
Measure Type: Count of Participants
Unit of Measure: Participants
33
  64.7%
30
  63.8%
32
  65.3%
6
  85.7%
34
  66.7%
15.Other Pre-specified Outcome
Title Number of Participants With No Worsening and Absence of New UTI Signs and Clinical Symptoms at PTE Visit (ITT Population)
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Omadacycline 300/300 Once Every 24 Hours Omadacycline 450/300 Once Every 24 Hours Omadacycline 450/450 Once Every 24 Hours Omadacycline 450/450 Once Every 12 Hours Nitrofurantoin 100/100 Once Every 12 Hours
Hide Arm/Group Description:
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.
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.
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.
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.
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.
Overall Number of Participants Analyzed 51 47 49 7 51
Measure Type: Count of Participants
Unit of Measure: Participants
50
  98.0%
45
  95.7%
45
  91.8%
7
 100.0%
50
  98.0%
Time Frame Up to approximately 37 days
Adverse Event Reporting Description A treatment-emergent adverse event was defined as any adverse event that newly appeared, increased in frequency, or worsened in severity on or after the initiation of the study drug.
 
Arm/Group Title Omadacycline 300/300 Once Every 24 Hours Omadacycline 450/300 Once Every 24 Hours Omadacycline 450/450 Once Every 24 Hours Omadacycline 450/450 Once Every 12 Hours Nitrofurantoin 100/100 Once Every 12 Hours
Hide Arm/Group Description 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. 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. 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. 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. 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.
All-Cause Mortality
Omadacycline 300/300 Once Every 24 Hours Omadacycline 450/300 Once Every 24 Hours Omadacycline 450/450 Once Every 24 Hours Omadacycline 450/450 Once Every 12 Hours Nitrofurantoin 100/100 Once Every 12 Hours
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/55 (0.00%)   0/54 (0.00%)   0/54 (0.00%)   0/8 (0.00%)   0/54 (0.00%) 
Hide Serious Adverse Events
Omadacycline 300/300 Once Every 24 Hours Omadacycline 450/300 Once Every 24 Hours Omadacycline 450/450 Once Every 24 Hours Omadacycline 450/450 Once Every 12 Hours Nitrofurantoin 100/100 Once Every 12 Hours
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/55 (0.00%)   0/54 (0.00%)   1/54 (1.85%)   0/8 (0.00%)   0/54 (0.00%) 
Infections and infestations           
Pyelonephritis Acute † 1  0/55 (0.00%)  0/54 (0.00%)  1/54 (1.85%)  0/8 (0.00%)  0/54 (0.00%) 
1
Term from vocabulary, MedDra 20.1
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2%
Omadacycline 300/300 Once Every 24 Hours Omadacycline 450/300 Once Every 24 Hours Omadacycline 450/450 Once Every 24 Hours Omadacycline 450/450 Once Every 12 Hours Nitrofurantoin 100/100 Once Every 12 Hours
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   16/55 (29.09%)   13/54 (24.07%)   15/54 (27.78%)   4/8 (50.00%)   9/54 (16.67%) 
Gastrointestinal disorders           
Abdominal discomfort † 1  0/55 (0.00%)  0/54 (0.00%)  0/54 (0.00%)  1/8 (12.50%)  0/54 (0.00%) 
Diarrhoea † 1  2/55 (3.64%)  1/54 (1.85%)  3/54 (5.56%)  0/8 (0.00%)  2/54 (3.70%) 
Nausea † 1  12/55 (21.82%)  8/54 (14.81%)  10/54 (18.52%)  4/8 (50.00%)  5/54 (9.26%) 
Vomiting † 1  3/55 (5.45%)  3/54 (5.56%)  3/54 (5.56%)  1/8 (12.50%)  0/54 (0.00%) 
Infections and infestations           
Asymptomatic bacteriuria † 1  1/55 (1.82%)  2/54 (3.70%)  1/54 (1.85%)  0/8 (0.00%)  0/54 (0.00%) 
Bronchitis † 1  0/55 (0.00%)  0/54 (0.00%)  0/54 (0.00%)  0/8 (0.00%)  2/54 (3.70%) 
Hordeolum † 1  0/55 (0.00%)  0/54 (0.00%)  0/54 (0.00%)  1/8 (12.50%)  0/54 (0.00%) 
Urinary tract infection † 1  1/55 (1.82%)  1/54 (1.85%)  2/54 (3.70%)  0/8 (0.00%)  0/54 (0.00%) 
Nervous system disorders           
Dysgeusia † 1  0/55 (0.00%)  0/54 (0.00%)  0/54 (0.00%)  1/8 (12.50%)  0/54 (0.00%) 
Headache † 1  3/55 (5.45%)  2/54 (3.70%)  4/54 (7.41%)  2/8 (25.00%)  1/54 (1.85%) 
Renal and urinary disorders           
Dysuria † 1  2/55 (3.64%)  0/54 (0.00%)  1/54 (1.85%)  0/8 (0.00%)  0/54 (0.00%) 
1
Term from vocabulary, MedDra 20.1
†
Indicates events were collected by systematic assessment
An additional treatment group (omadacycline 450/450 once every 12 hours) was added with Protocol Amendment 2. However, the majority of enrollment was completed by this time, and therefore, fewer participants were enrolled in this group.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The only disclosure restriction on the Principal Investigator is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days from the time submitted to the sponsor for review. The sponsor can request changes to the communication and require the removal of confidential information.
Results Point of Contact
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Name/Title: Paratek Medical Information
Organization: Paratek Pharmaceuticals, Inc.
Phone: 1-833-727-2835
EMail: medinfo@paratekpharma.com
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Responsible Party: Paratek Pharmaceuticals Inc
ClinicalTrials.gov Identifier: NCT03425396    
Other Study ID Numbers: PTK0796-UUTI-17201
First Submitted: December 28, 2017
First Posted: February 7, 2018
Results First Submitted: May 15, 2020
Results First Posted: June 4, 2020
Last Update Posted: June 9, 2020