IV or IV/PO Omadacycline vs. IV/PO Levofloxacin for the Treatment of Acute Pyelonephritis
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| ClinicalTrials.gov Identifier: NCT03757234 |
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Recruitment Status :
Completed
First Posted : November 28, 2018
Results First Posted : July 7, 2020
Last Update Posted : July 7, 2020
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Sponsor:
Paratek Pharmaceuticals Inc
Information provided by (Responsible Party):
Paratek Pharmaceuticals Inc
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Acute Pyelonephritis | Drug: Omadacycline Drug: Levofloxacin | Phase 2 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 201 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Triple (Participant, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| Official Title: | A Randomized, Double-Blinded, Adaptive Phase 2 Study to Evaluate the Safety and Efficacy of iv or iv/po Omadacycline and iv/po Levofloxacin in the Treatment of Adults With Acute Pyelonephritis. |
| Actual Study Start Date : | November 19, 2018 |
| Actual Primary Completion Date : | June 26, 2019 |
| Actual Study Completion Date : | July 24, 2019 |
Resource links provided by the National Library of Medicine
| Arm | Intervention/treatment |
|---|---|
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Experimental: Omadacycline 200 iv/200 iv
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.
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Drug: Omadacycline
iv solution
Other Name: Nuzyra |
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Experimental: Omadacycline 200 iv/100 iv
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.
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Drug: Omadacycline
iv solution
Other Name: Nuzyra |
|
Experimental: Omadacycline 200 iv/300 po or 100 iv
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.
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Drug: Omadacycline
po tablets
Other Name: Nuzyra Drug: Omadacycline iv solution
Other Name: Nuzyra |
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Experimental: Omadacycline 200 iv/450 po or 100 iv
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.
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Drug: Omadacycline
po tablets
Other Name: Nuzyra Drug: Omadacycline iv solution
Other Name: Nuzyra |
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Active Comparator: Levofloxacin 750 iv/750 po or iv
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.
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Drug: Levofloxacin
iv solution/po tablets
Other Name: Levaquin |
Primary Outcome Measures :
- Number of Participants With an Investigator Assessment of Clinical Response at the Post Therapy Evaluation (PTE) Visit (ITT Population) [ Time Frame: Day 21 (A PTE occurred on Day 21 ± 2 days after the participant's first dose of study drug). ]Clinical response was determined by the investigator at the PTE visit by assessing whether or not the participant met the clinical outcome of Clinical Success, Clinical Failure, or Indeterminate. Clinical Success was defined as 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) [ Time Frame: Day 21 (A PTE occurred on Day 21 ± 2 days after the participant's first dose of study drug). ]Microbiological response was determined programmatically at the PTE visit by assessing whether or not the participant met the microbiological outcome of '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) [ Time Frame: Day 21 (A PTE occurred on Day 21 ± 2 days after the participant's first dose of study drug). ]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) [ Time Frame: Day 21 (A PTE occurred on Day 21 ± 2 days after the participant's first dose of study drug). ]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 [ Time Frame: up to approximately 28 days ]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.
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| Ages Eligible for Study: | 18 Years to 65 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | Female |
| Gender Based Eligibility: | Yes |
| Accepts Healthy Volunteers: | No |
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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03757234
Locations
Show 31 study locations
Sponsors and Collaborators
Paratek Pharmaceuticals Inc
Study Documents (Full-Text)
Documents provided by Paratek Pharmaceuticals Inc:
Documents provided by Paratek Pharmaceuticals Inc:
Study Protocol [PDF] March 26, 2018
Statistical Analysis Plan [PDF] June 4, 2019
| Responsible Party: | Paratek Pharmaceuticals Inc |
| ClinicalTrials.gov Identifier: | NCT03757234 |
| Other Study ID Numbers: |
PTK0796-AP-17202 |
| First Posted: | November 28, 2018 Key Record Dates |
| Results First Posted: | July 7, 2020 |
| Last Update Posted: | July 7, 2020 |
| Last Verified: | July 2020 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Additional relevant MeSH terms:
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Pyelonephritis Nephritis, Interstitial Nephritis Kidney Diseases Urologic Diseases Pyelitis Levofloxacin Ofloxacin Anti-Infective Agents, Urinary Anti-Infective Agents |
Renal Agents Anti-Bacterial Agents Topoisomerase II Inhibitors Topoisomerase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Cytochrome P-450 CYP1A2 Inhibitors Cytochrome P-450 Enzyme Inhibitors |