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

Browse trials for

• Pyelonephritis 83

Study arms

• 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.

  Drug: Omadacycline

• 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.

  Drug: Omadacycline

• 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.

  Drug: Omadacycline

• 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.

  Drug: Omadacycline

• 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.

  Drug: Levofloxacin

Interventions

• DrugOmadacycline

  po tablets

  Also known as: Nuzyra

• DrugLevofloxacin

  iv solution/po tablets

  Also known as: Levaquin

• DrugOmadacycline

  iv solution

  Also known as: Nuzyra

Primary outcomes

1. 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).

2. 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).

3. 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.

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

4. 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.

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

Secondary outcomes

1. 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.

   Time frame: up to approximately 28 days

Baseline characteristics

Study documents

• Study protocol · Mar 26, 2018
• Statistical analysis plan · Jun 4, 2019

Documents are hosted by the registry — open the source record to download them.