IV or IV/PO Omadacycline vs. IV/PO Levofloxacin for the Treatment of Acute Pyelonephritis

Paratek Pharmaceuticals Inc201 enrolled

Overview

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.

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

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

201

Conditions

Acute Pyelonephritis

Interventions

OmadacyclineDRUG

po tablets

LevofloxacinDRUG

iv solution/po tablets

OmadacyclineDRUG

iv solution

Eligibility

Sex: FEMALEMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

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

Locations (31)

Site 201

Tbilisi, Georgia

Outcomes

Primary Outcomes

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.

Time frame: Day 21 (A PTE occurred on Day 21 ± 2 days after the participant's first dose of study drug).

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.

Time frame: Day 21 (A PTE occurred on Day 21 ± 2 days after the participant's first dose of study drug).

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.

Data from ClinicalTrials.gov

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