Back to resultsIV or IV/PO Omadacycline vs. IV/PO Levofloxacin for the Treatment of Acute Pyelonephritis
Primary Purpose
Acute Pyelonephritis
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Omadacycline
Levofloxacin
Omadacycline
Sponsored by
About this trial
This is an interventional treatment trial for Acute Pyelonephritis
Eligibility Criteria
Inclusion Criteria:
- Female participants, age 18-65 years who have signed the informed consent form
- Must have a qualifying acute pyelonephritis
- Participants must not be pregnant at the time of enrollment
- Must agree to a reliable method of birth control during the study and for 30 days following the last dose of study drug
- Must be able to comply with all of the requirements of the study
Exclusion Criteria:
- Males
- Symptoms of acute pyelonephritis present for longer 7 days prior to randomization
- Infections that require antibacterial treatment for greater than 14 days
- Evidence of suspected non-renal source of infections, vaginitis, or sexually transmitted infection
- Evidence of significant immunological disease
- Evidence of liver impairment or disease
- Evidence of unstable cardiac disease
- Severe renal disease or requirement for dialysis
- Evidence of septic shock
- Has a history of hypersensitivity or allergic reaction to any tetracycline or to levofloxacin
- Has received an investigational drug within the past 30 days
- Participants who are pregnant or nursing
- Unable or unwilling to comply with the protocol requirements
Sites / Locations
- Site 201
- Site 202
- Site 203
- Site 204
- Site 301
- Site 304
- Site 302
- Site 305
- Site 303
- Site 409
- Site 408
- Site 410
- Site 415
- Site 407
- Site 405
- Site 411
- Site 406
- Site 402
- Site 412
- Site 403
- Site 414
- Site 401
- Site 404
- Site 413
- Site 502
- Site 506
- Site 505
- Site 504
- Site 503
- Site 501
- Site 507
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm Type
Experimental
Experimental
Experimental
Experimental
Active Comparator
Arm Label
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
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.
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.
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.
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.
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.
Outcomes
Primary Outcome Measures
Number of Participants With an Investigator Assessment of Clinical Response at the Post Therapy Evaluation (PTE) Visit (ITT Population)
Clinical response was determined by the investigator at the PTE visit by assessing whether or not the participant met the clinical outcome of Clinical Success, Clinical Failure, or Indeterminate. Clinical Success was defined as 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.
Number of Participants With a Microbiological Response at the PTE Visit (Micro-ITT Population)
Microbiological response was determined programmatically at the PTE visit by assessing whether or not the participant met the microbiological outcome of '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.
Number of Participants With Resolution of All AP Signs and Clinical Symptoms at PTE Visit (ITT Population)
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.
Number of Participants With No Worsening and Absence of New AP Signs and Clinical Symptoms at PTE Visit (ITT Population)
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.
Secondary Outcome Measures
Number of Participants With Treatment Emergent Adverse Events and Serious Adverse Events
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.
Full Information
NCT ID
NCT03757234
First Posted
November 27, 2018
Last Updated
July 2, 2020
Sponsor
Paratek Pharmaceuticals Inc
1. Study Identification
Unique Protocol Identification Number
NCT03757234
Brief Title
IV or IV/PO Omadacycline vs. IV/PO Levofloxacin for the Treatment of Acute Pyelonephritis
Official Title
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.
Study Type
Interventional
2. Study Status
Record Verification Date
July 2020
Overall Recruitment Status
Completed
Study Start Date
November 19, 2018 (Actual)
Primary Completion Date
June 26, 2019 (Actual)
Study Completion Date
July 24, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Paratek Pharmaceuticals Inc
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
Detailed Description
This was a randomized (1:1:1:1:1), double-blind, double-dummy, adaptive designed, Phase 2 study. Based on review of the efficacy and microbiology data, the DMC modified the randomization algorithm, and no further participants were enrolled in the following treatment arms after May 2019: the omadacycline 200 iv/100 iv, omadacycline 200 iv/300 po or 100 iv, and omadacycline 200 iv/450 po or 100 iv arms. After this change, participants were randomized in a 1:1 ratio to either the omadacycline 200 iv/200 iv or levofloxacin arms.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Pyelonephritis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
201 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Omadacycline 200 iv/200 iv
Arm Type
Experimental
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 Title
Omadacycline 200 iv/100 iv
Arm Type
Experimental
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 Title
Omadacycline 200 iv/300 po or 100 iv
Arm Type
Experimental
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 Title
Omadacycline 200 iv/450 po or 100 iv
Arm Type
Experimental
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 Title
Levofloxacin 750 iv/750 po or iv
Arm Type
Active Comparator
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.
Intervention Type
Drug
Intervention Name(s)
Omadacycline
Other Intervention Name(s)
Nuzyra
Intervention Description
po tablets
Intervention Type
Drug
Intervention Name(s)
Levofloxacin
Other Intervention Name(s)
Levaquin
Intervention Description
iv solution/po tablets
Intervention Type
Drug
Intervention Name(s)
Omadacycline
Other Intervention Name(s)
Nuzyra
Intervention Description
iv solution
Primary Outcome Measure Information:
Title
Number of Participants With an Investigator Assessment of Clinical Response at the Post Therapy Evaluation (PTE) Visit (ITT Population)
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.
Time Frame
Day 21 (A PTE occurred on Day 21 ± 2 days after the participant's first dose of study drug).
Title
Number of Participants With a Microbiological Response at the PTE Visit (Micro-ITT Population)
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.
Time Frame
Day 21 (A PTE occurred on Day 21 ± 2 days after the participant's first dose of study drug).
Title
Number of Participants With Resolution of All AP Signs and Clinical Symptoms at PTE Visit (ITT Population)
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.
Time Frame
Day 21 (A PTE occurred on Day 21 ± 2 days after the participant's first dose of study drug).
Title
Number of Participants With No Worsening and Absence of New AP Signs and Clinical Symptoms at PTE Visit (ITT Population)
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.
Time Frame
Day 21 (A PTE occurred on Day 21 ± 2 days after the participant's first dose of study drug).
Secondary Outcome Measure Information:
Title
Number of Participants With Treatment Emergent Adverse Events and Serious Adverse Events
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.
Time Frame
up to approximately 28 days
10. Eligibility
Sex
Female
Gender Based
Yes
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Female participants, age 18-65 years who have signed the informed consent form
Must have a qualifying acute pyelonephritis
Participants must not be pregnant at the time of enrollment
Must agree to a reliable method of birth control during the study and for 30 days following the last dose of study drug
Must be able to comply with all of the requirements of the study
Exclusion Criteria:
Males
Symptoms of acute pyelonephritis present for longer 7 days prior to randomization
Infections that require antibacterial treatment for greater than 14 days
Evidence of suspected non-renal source of infections, vaginitis, or sexually transmitted infection
Evidence of significant immunological disease
Evidence of liver impairment or disease
Evidence of unstable cardiac disease
Severe renal disease or requirement for dialysis
Evidence of septic shock
Has a history of hypersensitivity or allergic reaction to any tetracycline or to levofloxacin
Has received an investigational drug within the past 30 days
Participants who are pregnant or nursing
Unable or unwilling to comply with the protocol requirements
Facility Information:
Facility Name
Site 201
City
Tbilisi
Country
Georgia
Facility Name
Site 202
City
Tbilisi
Country
Georgia
Facility Name
Site 203
City
Tbilisi
Country
Georgia
Facility Name
Site 204
City
Tbilisi
Country
Georgia
Facility Name
Site 301
City
Daugavpils
Country
Latvia
Facility Name
Site 304
City
Liepāja
ZIP/Postal Code
LV-3414
Country
Latvia
Facility Name
Site 302
City
Riga
Country
Latvia
Facility Name
Site 305
City
Rēzekne
Country
Latvia
Facility Name
Site 303
City
Valmiera
Country
Latvia
Facility Name
Site 409
City
Krasnoyarsk
ZIP/Postal Code
660062
Country
Russian Federation
Facility Name
Site 408
City
Moscow
ZIP/Postal Code
141435
Country
Russian Federation
Facility Name
Site 410
City
Moscow
ZIP/Postal Code
Moscow
Country
Russian Federation
Facility Name
Site 415
City
Penza
ZIP/Postal Code
440026
Country
Russian Federation
Facility Name
Site 407
City
Rostov-on-Don
ZIP/Postal Code
344022
Country
Russian Federation
Facility Name
Site 405
City
Rostov-on-Don
ZIP/Postal Code
344037
Country
Russian Federation
Facility Name
Site 411
City
Saint Petersburg
ZIP/Postal Code
194291
Country
Russian Federation
Facility Name
Site 406
City
Saint Petersburg
ZIP/Postal Code
195067
Country
Russian Federation
Facility Name
Site 402
City
Saint Petersburg
ZIP/Postal Code
196247
Country
Russian Federation
Facility Name
Site 412
City
Saint Petersburg
ZIP/Postal Code
197022
Country
Russian Federation
Facility Name
Site 403
City
Saint Petersburg
ZIP/Postal Code
197374
Country
Russian Federation
Facility Name
Site 414
City
Saint Petersburg
ZIP/Postal Code
198205
Country
Russian Federation
Facility Name
Site 401
City
Saint Petersburg
ZIP/Postal Code
198412
Country
Russian Federation
Facility Name
Site 404
City
Saint Petersburg
ZIP/Postal Code
199106
Country
Russian Federation
Facility Name
Site 413
City
Smolensk
ZIP/Postal Code
214018
Country
Russian Federation
Facility Name
Site 502
City
Chernivtsi
ZIP/Postal Code
58001
Country
Ukraine
Facility Name
Site 506
City
Dnipro
ZIP/Postal Code
49005
Country
Ukraine
Facility Name
Site 505
City
Kharkiv
ZIP/Postal Code
61037
Country
Ukraine
Facility Name
Site 504
City
Kyiv
ZIP/Postal Code
2660
Country
Ukraine
Facility Name
Site 503
City
Kyiv
ZIP/Postal Code
4053
Country
Ukraine
Facility Name
Site 501
City
Lviv
ZIP/Postal Code
79059
Country
Ukraine
Facility Name
Site 507
City
Zaporizhzhia
ZIP/Postal Code
69600
Country
Ukraine
12. IPD Sharing Statement
Learn more about this trial
IV or IV/PO Omadacycline vs. IV/PO Levofloxacin for the Treatment of Acute Pyelonephritis
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