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    Clinical Trial Results:
    A Randomized, Double-Blinded, Adaptive Phase 2 Study to Evaluate the Safety and Efficacy of IV or IV/PO Omadacycline and IV/PO Levofloxacin in the Treatment of Adults with Acute Pyelonephritis.

    Summary
    EudraCT number
    		 2018-000037-13
    Trial protocol
    		 LV  
    Global end of trial date
    24 Jul 2019

    Results information
    Results version number
    		 v1(current)
    This version publication date
    10 Jun 2021
    First version publication date
    10 Jun 2021
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    PTK0796-AP-17202
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03757234
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Paratek Pharmaceuticals Inc
    Sponsor organisation address
    75 Park Plaza, 4th Floor, Boston, Massachusetts, United States, 02116
    Public contact
    Paratek Medical Information, Paratek Pharmaceuticals Inc, 1 833-727-2835, medinfo@paratekpharma.com
    Scientific contact
    Paratek Medical Information, Paratek Pharmaceuticals Inc, 1 833-727-2835, medinfo@paratekpharma.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    23 Mar 2020
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    26 Jun 2019
    Global end of trial reached?
    Yes
    Global end of trial date
    24 Jul 2019
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The purpose of this study was to evaluate the safety and efficacy of intravenous (iv) or iv/per oral (po) omadacycline as compared to iv or iv/po levofloxacin in the treatment of female adults with acute pyelonephritis.
    Protection of trial subjects
    The study was designed, implemented, and reported in accordance with the International Council for Harmonisation Harmonized Tripartite Guideline for Good Clinical Practice, with applicable local regulations (including European Directive 2001/20/EC, United States Code of Federal Regulations Title 21, and Japanese Ministry of Health, Labor, and Welfare), and with the ethical principles laid down in the Declaration of Helsinki.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    19 Nov 2018
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Georgia: 51
    Country: Number of subjects enrolled
    Russian Federation: 73
    Country: Number of subjects enrolled
    Ukraine: 54
    Country: Number of subjects enrolled
    Latvia: 23
    Worldwide total number of subjects
    201
    EEA total number of subjects
    23
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    201
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 A total of 207 subjects were screened for entry into the study. Of these, 6 subjects failed screening, and 201 subjects were enrolled and randomized in the study.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Omadacycline 200 iv/200 iv
    Arm description
    		 On Day 1, participants received omadacycline 200 milligrams intravenously (iv). On Days 2 through 7, participants continued to receive omadacycline 200 milligrams iv. All doses were administered once-per-day and iv doses were administered in 150 milliliters of normal saline as continuous infusions over 90 minutes.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Omadacycline
    Investigational medicinal product code
    PTK 0796
    Other name
    Nuzyra
    Pharmaceutical forms
    Powder for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    200 iv: 200 milligrams omadacycline reconstituted in 150 milliliters normal saline

    Arm title
    		 Omadacycline 200 iv/100 iv
    Arm description
    		 On Day 1, participants received omadacycline 200 milligrams iv. On Days 2 through 7, participants received omadacycline 100 milligrams iv. All doses were administered once-per-day and iv doses were administered in 150 milliliters of normal saline as continuous infusions over 90 minutes.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Omadacycline
    Investigational medicinal product code
    PTK 0796
    Other name
    Nuzyra
    Pharmaceutical forms
    Powder for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    100 iv: 100 milligrams omadacycline reconstituted in 150 milliliters normal saline; 200 iv: 200 milligrams omadacycline reconstituted in 150 milliliters normal saline

    Arm title
    		 Omadacycline 200 iv/300 po or 100 iv
    Arm description
    		 On Day 1, participants received omadacycline 200 milligrams iv. On Days 2 through 7, participants received omadacycline 100 milligrams iv or omadacycline 300 milligrams per oral (po). All doses were administered once-per-day and iv doses were administered in 150 milliliters of normal saline as continuous infusions over 90 minutes. All oral doses were taken in a fasted state.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Omadacycline
    Investigational medicinal product code
    PTK 0796
    Other name
    Nuzyra
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    300 po: 2 tablets of 150 milligrams omadacycline were taken with water in fasted state

    Investigational medicinal product name
    Omadacycline
    Investigational medicinal product code
    PTK 0796
    Other name
    Nuzyra
    Pharmaceutical forms
    Powder for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    100 iv: 100 milligrams omadacycline reconstituted in 150 milliliters normal saline; 200 iv: 200 milligrams omadacycline reconstituted in 150 milliliters normal saline

    Arm title
    		 Omadacycline 200 iv/450 po or 100 iv
    Arm description
    		 On Day 1, participants received omadacycline 200 milligrams iv. On Days 2 through 7, participants received omadacycline 100 milligrams iv or omadacycline 450 milligrams po. All doses were administered once-per-day and iv doses were administered in 150 milliliters of normal saline as continuous infusions over 90 minutes. All oral doses were taken in a fasted state.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Omadacycline
    Investigational medicinal product code
    PTK 0796
    Other name
    Nuzyra
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    450 po: 3 tablets of 150 milligrams omadacycline were taken with water in fasted state

    Investigational medicinal product name
    Omadacycline
    Investigational medicinal product code
    PTK 0796
    Other name
    Nuzyra
    Pharmaceutical forms
    Powder for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    100 iv: 100 milligrams omadacycline reconstituted in 150 milliliters normal saline; 200 iv: 200 milligrams omadacycline reconstituted in 150 milliliters normal saline

    Arm title
    		 Levofloxacin 750 iv/750 po or iv
    Arm description
    		 On Day 1, participants received levofloxacin 750 milligrams iv. On Days 2 through 7, participants received levofloxacin 750 milligrams iv or levofloxacin 750 milligrams po. All doses were administered once-per-day and iv doses were administered in 150 milliliters of normal saline as continuous infusions over 90 minutes. All oral doses were taken in a fasted state.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Levofloxacin
    Investigational medicinal product code
    Other name
    Levaquin
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    750 iv: 750 milligrams levofloxacin reconstituted in 150 milliliters normal saline

    Investigational medicinal product name
    Levofloxacin
    Investigational medicinal product code
    Other name
    Levaquin
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    750 po: 3 tablets of 250 milligrams levofloxacin were taken with water in fasted state

    Number of subjects in period 1
    		Omadacycline 200 iv/200 iv Omadacycline 200 iv/100 iv Omadacycline 200 iv/300 po or 100 iv Omadacycline 200 iv/450 po or 100 iv Levofloxacin 750 iv/750 po or iv
    Started
    75
    18
    17
    17
    74
    Completed PTE visit
    72
    16
    17
    16
    71
    Completed
    72
    16
    17
    16
    70
    Not completed
    3
    2
    0
    1
    4
         Consent withdrawn by subject
    1
    1
    -
    1
    2
         Adverse event, non-fatal
    -
    -
    -
    -
    1
         Other
    1
    1
    -
    -
    -
         Lost to follow-up
    1
    -
    -
    -
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Omadacycline 200 iv/200 iv
    Reporting group description
    		 On Day 1, participants received omadacycline 200 milligrams intravenously (iv). On Days 2 through 7, participants continued to receive omadacycline 200 milligrams iv. All doses were administered once-per-day and iv doses were administered in 150 milliliters of normal saline as continuous infusions over 90 minutes.

    Reporting group title
    Omadacycline 200 iv/100 iv
    Reporting group description
    		 On Day 1, participants received omadacycline 200 milligrams iv. On Days 2 through 7, participants received omadacycline 100 milligrams iv. All doses were administered once-per-day and iv doses were administered in 150 milliliters of normal saline as continuous infusions over 90 minutes.

    Reporting group title
    Omadacycline 200 iv/300 po or 100 iv
    Reporting group description
    		 On Day 1, participants received omadacycline 200 milligrams iv. On Days 2 through 7, participants received omadacycline 100 milligrams iv or omadacycline 300 milligrams per oral (po). All doses were administered once-per-day and iv doses were administered in 150 milliliters of normal saline as continuous infusions over 90 minutes. All oral doses were taken in a fasted state.

    Reporting group title
    Omadacycline 200 iv/450 po or 100 iv
    Reporting group description
    		 On Day 1, participants received omadacycline 200 milligrams iv. On Days 2 through 7, participants received omadacycline 100 milligrams iv or omadacycline 450 milligrams po. All doses were administered once-per-day and iv doses were administered in 150 milliliters of normal saline as continuous infusions over 90 minutes. All oral doses were taken in a fasted state.

    Reporting group title
    Levofloxacin 750 iv/750 po or iv
    Reporting group description
    		 On Day 1, participants received levofloxacin 750 milligrams iv. On Days 2 through 7, participants received levofloxacin 750 milligrams iv or levofloxacin 750 milligrams po. All doses were administered once-per-day and iv doses were administered in 150 milliliters of normal saline as continuous infusions over 90 minutes. All oral doses were taken in a fasted state.

    Reporting group values
    		 Omadacycline 200 iv/200 iv Omadacycline 200 iv/100 iv Omadacycline 200 iv/300 po or 100 iv Omadacycline 200 iv/450 po or 100 iv Levofloxacin 750 iv/750 po or iv Total
    Number of subjects
    		 75 18 17 17 74 201
    Age categorical
    Units:
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 38.2 ± 14.97 33.9 ± 14.48 37.1 ± 15.97 38.2 ± 17.66 38.8 ± 14.74 -
    Gender categorical
    Units: Subjects
        Female
    		 75 18 17 17 74 201
        Male
    		 0 0 0 0 0 0
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 0 0 0 0 0 0
        Asian
    		 1 0 0 0 0 1
        Native Hawaiian or Other Pacific Islander
    		 0 0 0 0 0 0
        Black or African American
    		 0 0 0 0 0 0
        White
    		 74 18 17 17 74 200
        More than one race
    		 0 0 0 0 0 0
        Unknown or Not Reported
    		 0 0 0 0 0 0
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 1 0 0 0 0 1
        Not Hispanic or Latino
    		 74 18 17 17 74 200
        Unknown or Not Reported
    		 0 0 0 0 0 0

    End points

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    End points reporting groups
    Reporting group title
    Omadacycline 200 iv/200 iv
    Reporting group description
    		 On Day 1, participants received omadacycline 200 milligrams intravenously (iv). On Days 2 through 7, participants continued to receive omadacycline 200 milligrams iv. All doses were administered once-per-day and iv doses were administered in 150 milliliters of normal saline as continuous infusions over 90 minutes.

    Reporting group title
    Omadacycline 200 iv/100 iv
    Reporting group description
    		 On Day 1, participants received omadacycline 200 milligrams iv. On Days 2 through 7, participants received omadacycline 100 milligrams iv. All doses were administered once-per-day and iv doses were administered in 150 milliliters of normal saline as continuous infusions over 90 minutes.

    Reporting group title
    Omadacycline 200 iv/300 po or 100 iv
    Reporting group description
    		 On Day 1, participants received omadacycline 200 milligrams iv. On Days 2 through 7, participants received omadacycline 100 milligrams iv or omadacycline 300 milligrams per oral (po). All doses were administered once-per-day and iv doses were administered in 150 milliliters of normal saline as continuous infusions over 90 minutes. All oral doses were taken in a fasted state.

    Reporting group title
    Omadacycline 200 iv/450 po or 100 iv
    Reporting group description
    		 On Day 1, participants received omadacycline 200 milligrams iv. On Days 2 through 7, participants received omadacycline 100 milligrams iv or omadacycline 450 milligrams po. All doses were administered once-per-day and iv doses were administered in 150 milliliters of normal saline as continuous infusions over 90 minutes. All oral doses were taken in a fasted state.

    Reporting group title
    Levofloxacin 750 iv/750 po or iv
    Reporting group description
    		 On Day 1, participants received levofloxacin 750 milligrams iv. On Days 2 through 7, participants received levofloxacin 750 milligrams iv or levofloxacin 750 milligrams po. All doses were administered once-per-day and iv doses were administered in 150 milliliters of normal saline as continuous infusions over 90 minutes. All oral doses were taken in a fasted state.

    Primary: Number of Participants With an Investigator Assessment of Clinical Response at the Post Therapy Evaluation (PTE) Visit (ITT Population)

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    End point title
    		 Number of Participants With an Investigator Assessment of Clinical Response at the Post Therapy Evaluation (PTE) Visit (ITT Population)
    End point 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 the complete resolution or significant improvement of the baseline AP signs and symptoms at the PTE visit such that no additional antimicrobial therapy is 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 or death at or before the PTE visit. The clinical outcome was deemed as Indeterminate when the PTE visit was not completed.
    End point type
    Primary
    End point timeframe
    Day 21 (A PTE occurred on Day 21 ± 2 days after the participant's first dose of study drug).
    End point values
    		 Omadacycline 200 iv/200 iv Omadacycline 200 iv/100 iv Omadacycline 200 iv/300 po or 100 iv Omadacycline 200 iv/450 po or 100 iv Levofloxacin 750 iv/750 po or iv
    Number of subjects analysed
    75
    18
    17
    17
    74
    Units: participants
    number (not applicable)
        Clinical Success
    68
    15
    15
    16
    69
        Clinical Failure
    5
    1
    2
    0
    1
        Indeterminate
    2
    2
    0
    1
    4
    Statistical analysis title
    		 Clinical Response
    Comparison groups
    Omadacycline 200 iv/200 iv v Levofloxacin 750 iv/750 po or iv
    Number of subjects included in analysis
    149
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [1]
    Method
    Parameter type
    		 Treatment difference
    Point estimate
    -2.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -12.4
         upper limit
    		 6.9
    Notes
    [1] - Non-inferiority margin for comparison of the doses was set at 10%.
    Statistical analysis title
    		 Clinical Response
    Comparison groups
    Omadacycline 200 iv/100 iv v Levofloxacin 750 iv/750 po or iv
    Number of subjects included in analysis
    92
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [2]
    Method
    Parameter type
    		 Treatment difference
    Point estimate
    -9.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -34.8
         upper limit
    		 5.3
    Notes
    [2] - Non-inferiority margin for comparison of the doses was set at 10%.
    Statistical analysis title
    		 Clinical Response
    Comparison groups
    Omadacycline 200 iv/300 po or 100 iv v Levofloxacin 750 iv/750 po or iv
    Number of subjects included in analysis
    91
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [3]
    Method
    Parameter type
    		 Treatment difference
    Point estimate
    -5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -30.6
         upper limit
    		 8.2
    Notes
    [3] - Non-inferiority margin for comparison of the doses was set at 10%.
    Statistical analysis title
    		 Clinical Response
    Comparison groups
    Omadacycline 200 iv/450 po or 100 iv v Levofloxacin 750 iv/750 po or iv
    Number of subjects included in analysis
    91
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [4]
    Method
    Parameter type
    		 Treatment Difference
    Point estimate
    0.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -22.4
         upper limit
    		 11.8
    Notes
    [4] - Non-inferiority margin for comparison of the doses was set at 10%.

    Primary: Number of Participants With a Microbiological Response at the PTE Visit (Micro-ITT Population)

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    End point title
    		 Number of Participants With a Microbiological Response at the PTE Visit (Micro-ITT Population)
    End point description
    Microbiological response was determined programmatically at the PTE visit by assessing whether or not the participant met the microbiological outcome of ‘Success’, ‘Failure’, or ‘Indeterminate’. Participants were considered to have a microbiological response of ‘Success’ if the outcomes of each baseline pathogens were eradication at the PTE visit. Participants were considered to have a microbiological response of ‘Failure’ if the outcome for any pathogen was persistence. Participants were considered to have a microbiological response of ‘Indeterminate’, if the outcome of at least 1 baseline pathogen was indeterminate and there was no outcome of persistence for any baseline pathogen.
    End point type
    Primary
    End point timeframe
    Day 21 (A PTE occurred on Day 21 ± 2 days after the participant's first dose of study drug).
    End point values
    		 Omadacycline 200 iv/200 iv Omadacycline 200 iv/100 iv Omadacycline 200 iv/300 po or 100 iv Omadacycline 200 iv/450 po or 100 iv Levofloxacin 750 iv/750 po or iv
    Number of subjects analysed
    46
    11
    14
    13
    52
    Units: participants
    number (not applicable)
        Clinical Success
    32
    3
    9
    5
    39
        Clinical Failure
    13
    7
    5
    7
    11
        Indeterminate
    1
    1
    0
    1
    2
    Statistical analysis title
    		 Clinical Response
    Comparison groups
    Omadacycline 200 iv/200 iv v Levofloxacin 750 iv/750 po or iv
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [5]
    Method
    Parameter type
    		 Treatment difference
    Point estimate
    -5.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -23.6
         upper limit
    		 12.7
    Notes
    [5] - Non-inferiority margin for comparison of the doses was set at 10%.
    Statistical analysis title
    		 Clinical Response
    Comparison groups
    Omadacycline 200 iv/100 iv v Levofloxacin 750 iv/750 po or iv
    Number of subjects included in analysis
    63
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [6]
    Method
    Parameter type
    		 Treatment difference
    Point estimate
    -47.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -71.3
         upper limit
    		 -6
    Notes
    [6] - Non-inferiority margin for comparison of the doses was set at 10%.
    Statistical analysis title
    		 Clinical Response
    Comparison groups
    Omadacycline 200 iv/300 po or 100 iv v Levofloxacin 750 iv/750 po or iv
    Number of subjects included in analysis
    66
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [7]
    Method
    Parameter type
    		 Treatment difference
    Point estimate
    -10.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -40.8
         upper limit
    		 15.1
    Notes
    [7] - Non-inferiority margin for comparison of the doses was set at 10%.
    Statistical analysis title
    		 Clinical Response
    Comparison groups
    Omadacycline 200 iv/450 po or 100 iv v Levofloxacin 750 iv/750 po or iv
    Number of subjects included in analysis
    65
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [8]
    Method
    Parameter type
    		 Treatment difference
    Point estimate
    -36.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -62.6
         upper limit
    		 -1.1
    Notes
    [8] - Non-inferiority margin for comparison of the doses was set at 10%.

    Primary: Number of Participants With Resolution of All AP Signs and Clinical Symptoms at PTE Visit (ITT Population)

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    End point title
    		 Number of Participants With Resolution of All AP Signs and Clinical Symptoms at PTE Visit (ITT Population) [9]
    End point description
    Participants recorded their assessments using the Modified Patient Symptom Assessment Questionnaire (mPSAQ), a 6-item questionnaire that assessed the levels of ‘severity’ and ‘bothersomeness’ for six pyelonephritis signs and symptoms. 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 6 items, divided by the number of non-missing items, and then multiplied by 6. For each sub-scale, the total score ranged from 0 (least Severe/ least bothersome) and 18 (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.
    End point type
    Primary
    End point timeframe
    Day 21 (A PTE occurred on Day 21 ± 2 days after the participant's first dose of study drug).
    Notes
    [9] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Descriptive statistics were summarized for this primary endpoint.
    End point values
    		 Omadacycline 200 iv/200 iv Omadacycline 200 iv/100 iv Omadacycline 200 iv/300 po or 100 iv Omadacycline 200 iv/450 po or 100 iv Levofloxacin 750 iv/750 po or iv
    Number of subjects analysed
    64
    16
    16
    16
    66
    Units: participants
        number (not applicable)
    51
    15
    14
    13
    54
    No statistical analyses for this end point

    Primary: Number of Participants With No Worsening and Absence of New AP Signs and Clinical Symptoms at PTE Visit (ITT Population)

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    End point title
    		 Number of Participants With No Worsening and Absence of New AP Signs and Clinical Symptoms at PTE Visit (ITT Population) [10]
    End point description
    Participants recorded their assessments using the mPSAQ, a 6-item questionnaire that assessed the levels of ‘severity’ and ‘bothersomeness’ for six pyelonephritis signs and symptoms. 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 6 items, divided by the number of non-missing items, and then multiplied by 6. For each sub-scale, the total score ranged from 0 (least Severe/ least bothersome) and 18 (worst severity/most bothersome). Number of participants with no worsening and absence of AP signs and clinical symptoms is reported. No worsening meant that each question score is same or better at post baseline.
    End point type
    Primary
    End point timeframe
    Day 21 (A PTE occurred on Day 21 ± 2 days after the participant's first dose of study drug).
    Notes
    [10] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Descriptive statistics were summarized for this primary endpoint.
    End point values
    		 Omadacycline 200 iv/200 iv Omadacycline 200 iv/100 iv Omadacycline 200 iv/300 po or 100 iv Omadacycline 200 iv/450 po or 100 iv Levofloxacin 750 iv/750 po or iv
    Number of subjects analysed
    64
    16
    16
    16
    66
    Units: participants
        number (not applicable)
    62
    16
    16
    15
    65
    No statistical analyses for this end point

    Secondary: Number of Participants With Treatment Emergent Adverse Events and Serious Adverse Events

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    End point title
    		 Number of Participants With Treatment Emergent Adverse Events and Serious Adverse Events
    End point description
    An adverse event is any untoward, undesired, or unplanned event in the form of signs, symptoms, disease, or laboratory or physiologic observations occurring in a person given a study drug or in a clinical study. 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.
    End point type
    Secondary
    End point timeframe
    Up to approximately 28 days
    End point values
    		 Omadacycline 200 iv/200 iv Omadacycline 200 iv/100 iv Omadacycline 200 iv/300 po or 100 iv Omadacycline 200 iv/450 po or 100 iv Levofloxacin 750 iv/750 po or iv
    Number of subjects analysed
    75
    18
    17
    17
    74
    Units: participants
    number (not applicable)
        Treatment Emergent Adverse Events
    23
    6
    9
    8
    24
        Treatment Emergent Serious Adverse Events
    0
    0
    2
    2
    2
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Up to approximately 28 days
    Adverse event reporting additional description
    The Safety Population consisted of all randomized participants who received at least one dose of study drug.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    20.1
    Reporting groups
    Reporting group title
    Omadacycline 200 iv/100 iv
    Reporting group description
    		 On Day 1, participants received omadacycline 200 milligrams iv. On Days 2 through 7, participants received omadacycline 100 milligrams iv. All doses were administered once-per-day and iv doses were administered in 150 milliliters of normal saline as continuous infusions over 90 minutes.

    Reporting group title
    Omadacycline 200 iv/450 po or 100 iv
    Reporting group description
    		 On Day 1, participants received omadacycline 200 milligrams iv. On Days 2 through 7, participants received omadacycline 100 milligrams iv or omadacycline 450 milligrams po. All doses were administered once-per-day and iv doses were administered in 150 milliliters of normal saline as continuous infusions over 90 minutes. All oral doses were taken in a fasted state.

    Reporting group title
    Omadacycline 200 iv/200 iv
    Reporting group description
    		 On Day 1, participants received omadacycline 200 milligrams intravenously (iv). On Days 2 through 7, participants continued to receive omadacycline 200 milligrams iv. All doses were administered once-per-day and iv doses were administered in 150 milliliters of normal saline as continuous infusions over 90 minutes.

    Reporting group title
    Levofloxacin 750 iv/750 po or iv
    Reporting group description
    		 On Day 1, participants received levofloxacin 750 milligrams iv. On Days 2 through 7, participants received levofloxacin 750 milligrams iv or levofloxacin 750 milligrams po. All doses were administered once-per-day and iv doses were administered in 150 milliliters of normal saline as continuous infusions over 90 minutes. All oral doses were taken in a fasted state.

    Reporting group title
    Omadacycline 200 iv/300 po or 100 iv
    Reporting group description
    		 On Day 1, participants received omadacycline 200 milligrams iv. On Days 2 through 7, participants received omadacycline 100 milligrams iv or omadacycline 300 milligrams po. All doses were administered once-per-day and iv doses were administered in 150 milliliters of normal saline. All oral doses were taken in a fasted state.

    Serious adverse events
    		 Omadacycline 200 iv/100 iv Omadacycline 200 iv/450 po or 100 iv Omadacycline 200 iv/200 iv Levofloxacin 750 iv/750 po or iv Omadacycline 200 iv/300 po or 100 iv
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 18 (0.00%)
    2 / 17 (11.76%)
    0 / 75 (0.00%)
    2 / 74 (2.70%)
    2 / 17 (11.76%)
         number of deaths (all causes)
    0
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 17 (0.00%)
    0 / 75 (0.00%)
    1 / 74 (1.35%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Duodenal ulcer haemorrhage
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 17 (5.88%)
    0 / 75 (0.00%)
    0 / 74 (0.00%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Renal abscess
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 17 (0.00%)
    0 / 75 (0.00%)
    0 / 74 (0.00%)
    1 / 17 (5.88%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis acute
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 17 (0.00%)
    0 / 75 (0.00%)
    0 / 74 (0.00%)
    1 / 17 (5.88%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 17 (5.88%)
    0 / 75 (0.00%)
    1 / 74 (1.35%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Escherichia bacteraemia
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 17 (5.88%)
    0 / 75 (0.00%)
    0 / 74 (0.00%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 2%
    Non-serious adverse events
    		 Omadacycline 200 iv/100 iv Omadacycline 200 iv/450 po or 100 iv Omadacycline 200 iv/200 iv Levofloxacin 750 iv/750 po or iv Omadacycline 200 iv/300 po or 100 iv
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    6 / 18 (33.33%)
    8 / 17 (47.06%)
    21 / 75 (28.00%)
    16 / 74 (21.62%)
    7 / 17 (41.18%)
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 17 (0.00%)
    1 / 75 (1.33%)
    0 / 74 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    Aspartate aminotransferase increased
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 17 (0.00%)
    0 / 75 (0.00%)
    0 / 74 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Body temperature increased
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 17 (5.88%)
    0 / 75 (0.00%)
    1 / 74 (1.35%)
    0 / 17 (0.00%)
         occurrences all number
    0
    1
    0
    1
    0
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 17 (5.88%)
    0 / 75 (0.00%)
    0 / 74 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Vascular disorders
    Hypertension
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 17 (5.88%)
    0 / 75 (0.00%)
    1 / 74 (1.35%)
    0 / 17 (0.00%)
         occurrences all number
    0
    1
    0
    1
    0
    Cardiac disorders
    Tachycardia
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 17 (5.88%)
    0 / 75 (0.00%)
    0 / 74 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 17 (0.00%)
    3 / 75 (4.00%)
    0 / 74 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    3
    0
    0
    Dysgeusia
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 17 (0.00%)
    0 / 75 (0.00%)
    0 / 74 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    1
    Headache
         subjects affected / exposed
    0 / 18 (0.00%)
    3 / 17 (17.65%)
    8 / 75 (10.67%)
    5 / 74 (6.76%)
    2 / 17 (11.76%)
         occurrences all number
    0
    3
    9
    5
    2
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 17 (0.00%)
    2 / 75 (2.67%)
    1 / 74 (1.35%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    2
    1
    0
    Hyperthermia
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 17 (0.00%)
    0 / 75 (0.00%)
    0 / 74 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    1 / 18 (5.56%)
    1 / 17 (5.88%)
    1 / 75 (1.33%)
    5 / 74 (6.76%)
    0 / 17 (0.00%)
         occurrences all number
    1
    1
    1
    5
    0
    Nausea
         subjects affected / exposed
    0 / 18 (0.00%)
    4 / 17 (23.53%)
    3 / 75 (4.00%)
    5 / 74 (6.76%)
    0 / 17 (0.00%)
         occurrences all number
    0
    4
    4
    6
    0
    Vomiting
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 17 (5.88%)
    0 / 75 (0.00%)
    1 / 74 (1.35%)
    0 / 17 (0.00%)
         occurrences all number
    0
    1
    0
    1
    0
    Respiratory, thoracic and mediastinal disorders
    Epistaxis
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 17 (0.00%)
    0 / 75 (0.00%)
    0 / 74 (0.00%)
    2 / 17 (11.76%)
         occurrences all number
    0
    0
    0
    0
    2
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 17 (0.00%)
    2 / 75 (2.67%)
    0 / 74 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    Rash erythematous
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 17 (0.00%)
    3 / 75 (4.00%)
    0 / 74 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    6
    0
    0
    Urticaria
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 17 (0.00%)
    2 / 75 (2.67%)
    0 / 74 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    3
    0
    0
    Infections and infestations
    Asymptomatic bacteriuria
         subjects affected / exposed
    2 / 18 (11.11%)
    1 / 17 (5.88%)
    3 / 75 (4.00%)
    1 / 74 (1.35%)
    2 / 17 (11.76%)
         occurrences all number
    2
    1
    3
    1
    2
    Oral herpes
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 17 (0.00%)
    0 / 75 (0.00%)
    0 / 74 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    1
    Pharyngitis
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 17 (0.00%)
    0 / 75 (0.00%)
    0 / 74 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Viral rhinitis
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 17 (0.00%)
    0 / 75 (0.00%)
    0 / 74 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    1
    Vulvovaginal candidiasis
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 17 (0.00%)
    0 / 75 (0.00%)
    0 / 74 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    1

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? No

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    In May 2019, the DMC modified the randomization algorithm based on their review of the data. After this change, participants were randomized in a 1:1 ratio to either the omadacycline 200 iv/200 iv or levofloxacin arms.
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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