Acute Pyelonephritis, Complicated Urinary Tract Infection
Conditions
Keywords
urinary tract infection, UTI, cUTI, pyelonephritis, AP, ACHN-490
Brief summary
This was a multi-center, multi-national, double-blind, randomized, comparator-controlled study of plazomicin administered intravenously compared with levofloxacin, a standard approved intravenous therapy for complicated urinary tract infection (cUTI) and acute pyelonephritis (AP).
Interventions
Sponsors
Achaogen, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Documented or suspected cUTI/AP with clinical signs and symptoms * Normal kidney function defined as creatinine clearance (CLcr) of ≥60mL/min using Cockcroft-Gault formula Key
Exclusion criteria
* Acute bacterial prostatis, orchitis, epididymitis, or chronic bacterial prostatis * Gross heanaturia requiring intervention other than study drug * Urinary tract surgery within 7 days of randomization or during the study period * A known nonrenal source of infection diagnosed within 7 days of randomization * A corrected QT interval \> 440 msec * History of hearing loss with onset before the age of 40 years, sensorineural hearing loss, or family history of hearing loss * Pregnant or breastfeeding women
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients Who Attained Microbiological Eradication (MBE) at the Test of Cure (TOC) Visit in the Microbiological Intent to Treat (MITT) Population | Day 1 to TOC (Day 12) | MBE was defined as documented eradication of all isolated pathogens. This was based on a urine culture, taken at the TOC visit that showed that all pathogens isolated at baseline at ≥10\^5 colony forming unit(s) per milliliter (CFU/mL) were reduced to \<10\^4 CFU/mL. |
| Percentage of Patients Who Attained MBE at the TOC Visit in the Microbiologically Evaluable (ME) Population | Day 1 to TOC (Day 12) | MBE was defined as documented eradication of all isolated pathogens. This was based on a urine culture, taken at the TOC visit that showed that all pathogens isolated at baseline at ≥10\^5 CFU/mL were reduced to \<10\^4 CFU/mL. |
| Percentage of Patients With Treatment-Emergent Adverse Events (TEAE) | Day 1 to the end of study (Day 40) | An adverse event (AE) is any untoward medical occurrence associated with the use of a drug in humans, whether or not it is considered to be drug related. An AE (also referred to as an adverse experience) can be any unfavorable and unintended sign (eg, an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, and it does not imply any judgment about causality. Adverse events also include the exacerbation or worsening of a condition present at screening other than the index infection for which the patient was enrolled in the study. A TEAE is any AE that newly appeared, increased in frequency, or worsened in severity following initiation of study drug. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients Who Attained MBE at the EOT Visit in the ME Population | Day 1 to EOT (Day 5) | MBE was defined as documented eradication of all isolated pathogens. This was based on a urine culture, taken at the EOT visit that showed that all pathogens isolated at baseline at ≥10\^5 CFU/mL were reduced to \<10\^4 CFU/mL. |
| Percentage of Patients Who Attained MBE at the EOT Visit in the MITT Population | Day 1 to EOT (Day 5) | MBE was defined as documented eradication of all isolated pathogens. This was based on a urine culture, taken at the EOT visit that showed that all pathogens isolated at baseline at ≥10\^5 CFU/mL were reduced to \<10\^4 CFU/mL. |
| Percentage of Patients Who Attained MBE at the TOC Visit in the ME Population by Baseline Pathogen | Day 1 to TOC (Day 12) | MBE was defined as documented eradication of all isolated pathogens. This was based on a urine culture, taken at the TOC visit that showed that all pathogens isolated at baseline at ≥10\^5 CFU/mL were reduced to \<10\^4 CFU/mL. |
| Percentage of Patients Who Attained MBE at the TOC Visit in the ME Population Stratified by Infection Category | Day 1 to TOC (Day 12) | MBE was defined as documented eradication of all isolated pathogens. This was based on a urine culture, taken at the TOC visit that showed that all pathogens isolated at baseline at ≥10\^5 CFU/mL were reduced to \<10\^4 CFU/mL. |
| Percentage of Patients Who Attained MBE at the TOC Visit in the ME Population by Country/Region | Day 1 to TOC (Day 12) | MBE was defined as documented eradication of all isolated pathogens. This was based on a urine culture, taken at the TOC visit that showed that all pathogens isolated at baseline at ≥10\^5 CFU/mL were reduced to \<10\^4 CFU/mL. |
| Percentage of Patients Who Attained Clinical Cure Based on Investigator and Sponsor Assessments at TOC Visit in the Intent-to-treat (ITT) Population | Day 1 to TOC (Day 12) | Investigator's assessment criteria defined Clinical Cure as resolution of baseline clinical signs and symptoms of infection through the TOC visit. The sponsor's assessment criteria was programmatically based on the investigator's assessment of participant clinical outcome, the number of days and doses of drug received and whether an antibiotic was administered. |
| Time (Days) to Clinical Cure Based on Investigator's and Sponsor's Assessments in the MITT Population | Day 1 to End of Study (Day 40) | Investigator's assessment criteria defined Clinical Cure as a resolution of baseline clinical signs and symptoms of infection through the TOC visit. The Sponsor's assessment criteria was programmatically based on the investigator's assessment of participant clinical outcome, the number of days and doses of drug received and whether an antibiotic was administered. |
| Time (Days) to Defervescense in the MITT Population | Day 1 to End of Study (Day 40) | Defervescence is defined as the absence of fever \<37.7 degrees Celsius and is assessed in patients who were afebrile at baseline. |
| Percentage of Patients Experiencing a Clinical Relapse or Microbiological Recurrence in the ME Population | Day 1 to LTFU (Day 40) | Patients who had a clinical relapse (defined as the return of clinical signs and symptoms requiring antibiotic therapy) or microbiological recurrence (defined as eradication of the original pathogen\[s\] at the TOC visit but regrowth at the level \>10\^5 CFU/mL by the LTFU \[long term follow up\] visit). |
| Percentage of Patients With a Superinfection or New Infection in the ME Population | Day 1 to to End of Study (Day 40) | Superinfections are defined as a pathogen other than the one at baseline found in urine at ≥10\^5 CFU/mL any time after the first infusion through EOT. New infections are defined as a pathogen other than the one at baseline found in urine at ≥10\^5 CFU/mL any time after EOT. |
| Time (Days) to Resolution of Signs and Symptoms of cUTI and AP in the MITT Population | Day 1 to End of Study (Day 40) | Resolution of clinical signs and symptoms is defined as absence of all signs and symptoms present at baseline. |
| Percentage of Patients Who Attained Clinical Cure Based on Investigator and Sponsor Assessments at the TOC Visit in the CE Population | Day 1 to TOC (Day 12) | Investigator's assessment criteria defined Clinical Cure as a resolution of baseline clinical signs and symptoms of infection through the TOC visit. The sponsor's assessment criteria was programmatically based on the investigator's assessment of participant clinical outcome, the number of days and doses of drug received and whether an antibiotic was administered. |
| Percentage of Patients Who Attained Clinical Cure Based on Investigator and Sponsor Assessments at the End of Treatment (EOT) Visit in the CE Population | Day 1 to EOT (Day 5) | Investigator's assessment criteria defined Clinical Cure as a resolution of baseline clinical signs and symptoms of infection through the EOT visit. The Sponsor's assessment criteria was programmatically based on the investigator's assessment of participant clinical outcome, the number of days and doses of drug received and whether an antibiotic was administered. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Plazomicin (10 mg/kg) Patients received two IV infusions daily for 5 consecutive days: 10 mg/kg plazomicin followed by placebo. | 22 |
| Plazomicin (15 mg/kg) Patients received two IV infusions daily for 5 consecutive days: 15 mg/kg plazomicin followed by placebo. | 76 |
| Levofloxacin Patients received two IV infusions daily for 5 consecutive days: placebo followed by 750 mg levofloxacin. | 47 |
| Total | 145 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Administrative Reasons | 0 | 1 | 2 |
| Overall Study | Consent Withdrawn | 1 | 4 | 2 |
| Overall Study | Investigator or Medical Monitor Decision | 0 | 1 | 0 |
| Overall Study | Lack of Efficacy | 0 | 2 | 0 |
| Overall Study | Lost to Follow-up | 1 | 3 | 1 |
| Overall Study | Unacceptable/ Intolerable AE(s) | 0 | 1 | 1 |
Baseline characteristics
| Characteristic | Plazomicin (10 mg/kg) | Plazomicin (15 mg/kg) | Levofloxacin | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 5 Participants | 4 Participants | 5 Participants | 14 Participants |
| Age, Categorical Between 18 and 65 years | 17 Participants | 72 Participants | 42 Participants | 131 Participants |
| Age, Continuous | 46.5 years STANDARD_DEVIATION 18.12 | 40.00 years STANDARD_DEVIATION 15.02 | 44.8 years STANDARD_DEVIATION 14.61 | 42.6 years STANDARD_DEVIATION 15.53 |
| Sex: Female, Male Female | 18 Participants | 61 Participants | 37 Participants | 116 Participants |
| Sex: Female, Male Male | 4 Participants | 15 Participants | 10 Participants | 29 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 22 | 0 / 74 | 0 / 44 |
| other Total, other adverse events | 2 / 22 | 22 / 74 | 3 / 44 |
| serious Total, serious adverse events | 0 / 22 | 1 / 74 | 2 / 44 |
Outcome results
Primary
Percentage of Patients Who Attained MBE at the TOC Visit in the Microbiologically Evaluable (ME) Population
MBE was defined as documented eradication of all isolated pathogens. This was based on a urine culture, taken at the TOC visit that showed that all pathogens isolated at baseline at ≥10\^5 CFU/mL were reduced to \<10\^4 CFU/mL.
Time frame: Day 1 to TOC (Day 12)
Population: The ME population was defined as clinically evaluable (CE) patients who had a causative pathogen isolated at baseline (ie, patients in both the MITT and CE populations). To be included in the ME population, a patient must also have had results obtained from non-contaminated urine culture at TOC.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Plazomicin (10 mg/kg) | Percentage of Patients Who Attained MBE at the TOC Visit in the Microbiologically Evaluable (ME) Population | 85.7 percentage of patients |
| Plazomicin (15 mg/kg) | Percentage of Patients Who Attained MBE at the TOC Visit in the Microbiologically Evaluable (ME) Population | 88.6 percentage of patients |
| Levofloxacin | Percentage of Patients Who Attained MBE at the TOC Visit in the Microbiologically Evaluable (ME) Population | 81.0 percentage of patients |
Primary
Percentage of Patients Who Attained Microbiological Eradication (MBE) at the Test of Cure (TOC) Visit in the Microbiological Intent to Treat (MITT) Population
MBE was defined as documented eradication of all isolated pathogens. This was based on a urine culture, taken at the TOC visit that showed that all pathogens isolated at baseline at ≥10\^5 colony forming unit(s) per milliliter (CFU/mL) were reduced to \<10\^4 CFU/mL.
Time frame: Day 1 to TOC (Day 12)
Population: The MITT population was defined as a subset patients from the ITT population with at least one isolated causative pathogen from an acceptable pretreatment urine specimen.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Plazomicin (10 mg/kg) | Percentage of Patients Who Attained Microbiological Eradication (MBE) at the Test of Cure (TOC) Visit in the Microbiological Intent to Treat (MITT) Population | 50 percentage of patients |
| Plazomicin (15 mg/kg) | Percentage of Patients Who Attained Microbiological Eradication (MBE) at the Test of Cure (TOC) Visit in the Microbiological Intent to Treat (MITT) Population | 60.8 percentage of patients |
| Levofloxacin | Percentage of Patients Who Attained Microbiological Eradication (MBE) at the Test of Cure (TOC) Visit in the Microbiological Intent to Treat (MITT) Population | 58.6 percentage of patients |
Primary
Percentage of Patients With Treatment-Emergent Adverse Events (TEAE)
An adverse event (AE) is any untoward medical occurrence associated with the use of a drug in humans, whether or not it is considered to be drug related. An AE (also referred to as an adverse experience) can be any unfavorable and unintended sign (eg, an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, and it does not imply any judgment about causality. Adverse events also include the exacerbation or worsening of a condition present at screening other than the index infection for which the patient was enrolled in the study. A TEAE is any AE that newly appeared, increased in frequency, or worsened in severity following initiation of study drug.
Time frame: Day 1 to the end of study (Day 40)
Population: The Safety population was defined as all randomized patients who received any amount of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Plazomicin (10 mg/kg) | Percentage of Patients With Treatment-Emergent Adverse Events (TEAE) | 31.8 percentage of patients |
| Plazomicin (15 mg/kg) | Percentage of Patients With Treatment-Emergent Adverse Events (TEAE) | 35.1 percentage of patients |
| Levofloxacin | Percentage of Patients With Treatment-Emergent Adverse Events (TEAE) | 47.7 percentage of patients |
Secondary
Percentage of Patients Experiencing a Clinical Relapse or Microbiological Recurrence in the ME Population
Patients who had a clinical relapse (defined as the return of clinical signs and symptoms requiring antibiotic therapy) or microbiological recurrence (defined as eradication of the original pathogen\[s\] at the TOC visit but regrowth at the level \>10\^5 CFU/mL by the LTFU \[long term follow up\] visit).
Time frame: Day 1 to LTFU (Day 40)
Population: The ME population was defined as CE patients who had a causative pathogen isolated at baseline (ie, patients in both the MITT and CE populations). To be included in the ME population, a patient must also have had results obtained from non-contaminated urine culture at TOC.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Plazomicin (10 mg/kg) | Percentage of Patients Experiencing a Clinical Relapse or Microbiological Recurrence in the ME Population | Clinical Relapse | 0 percentage of patients |
| Plazomicin (10 mg/kg) | Percentage of Patients Experiencing a Clinical Relapse or Microbiological Recurrence in the ME Population | Microbiological Recurrence | 0 percentage of patients |
| Plazomicin (15 mg/kg) | Percentage of Patients Experiencing a Clinical Relapse or Microbiological Recurrence in the ME Population | Clinical Relapse | 14.3 percentage of patients |
| Plazomicin (15 mg/kg) | Percentage of Patients Experiencing a Clinical Relapse or Microbiological Recurrence in the ME Population | Microbiological Recurrence | 6.5 percentage of patients |
| Levofloxacin | Percentage of Patients Experiencing a Clinical Relapse or Microbiological Recurrence in the ME Population | Clinical Relapse | 6.3 percentage of patients |
| Levofloxacin | Percentage of Patients Experiencing a Clinical Relapse or Microbiological Recurrence in the ME Population | Microbiological Recurrence | 23.5 percentage of patients |
Secondary
Percentage of Patients Who Attained Clinical Cure Based on Investigator and Sponsor Assessments at the End of Treatment (EOT) Visit in the CE Population
Investigator's assessment criteria defined Clinical Cure as a resolution of baseline clinical signs and symptoms of infection through the EOT visit. The Sponsor's assessment criteria was programmatically based on the investigator's assessment of participant clinical outcome, the number of days and doses of drug received and whether an antibiotic was administered.
Time frame: Day 1 to EOT (Day 5)
Population: The CE population was defined as patients who received at least 80% of study drug for clinical successes or 40% for clinical failures and must not have had indeterminate clinical response at TOC.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Plazomicin (10 mg/kg) | Percentage of Patients Who Attained Clinical Cure Based on Investigator and Sponsor Assessments at the End of Treatment (EOT) Visit in the CE Population | Sponsor's Assessment: Cured | 94.4 percentage of patients |
| Plazomicin (10 mg/kg) | Percentage of Patients Who Attained Clinical Cure Based on Investigator and Sponsor Assessments at the End of Treatment (EOT) Visit in the CE Population | Investigator's Assessment: Cured | 94.4 percentage of patients |
| Plazomicin (15 mg/kg) | Percentage of Patients Who Attained Clinical Cure Based on Investigator and Sponsor Assessments at the End of Treatment (EOT) Visit in the CE Population | Investigator's Assessment: Cured | 82.8 percentage of patients |
| Plazomicin (15 mg/kg) | Percentage of Patients Who Attained Clinical Cure Based on Investigator and Sponsor Assessments at the End of Treatment (EOT) Visit in the CE Population | Sponsor's Assessment: Cured | 82.8 percentage of patients |
| Levofloxacin | Percentage of Patients Who Attained Clinical Cure Based on Investigator and Sponsor Assessments at the End of Treatment (EOT) Visit in the CE Population | Investigator's Assessment: Cured | 88.1 percentage of patients |
| Levofloxacin | Percentage of Patients Who Attained Clinical Cure Based on Investigator and Sponsor Assessments at the End of Treatment (EOT) Visit in the CE Population | Sponsor's Assessment: Cured | 85.7 percentage of patients |
Secondary
Percentage of Patients Who Attained Clinical Cure Based on Investigator and Sponsor Assessments at the TOC Visit in the CE Population
Investigator's assessment criteria defined Clinical Cure as a resolution of baseline clinical signs and symptoms of infection through the TOC visit. The sponsor's assessment criteria was programmatically based on the investigator's assessment of participant clinical outcome, the number of days and doses of drug received and whether an antibiotic was administered.
Time frame: Day 1 to TOC (Day 12)
Population: The CE population was defined as patients who received at least 80% of study drug for clinical successes or 40% for clinical failures and must not have had indeterminate clinical response at TOC.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Plazomicin (10 mg/kg) | Percentage of Patients Who Attained Clinical Cure Based on Investigator and Sponsor Assessments at the TOC Visit in the CE Population | Investigator's Assessment: Cured | 66.7 percentage of patients |
| Plazomicin (10 mg/kg) | Percentage of Patients Who Attained Clinical Cure Based on Investigator and Sponsor Assessments at the TOC Visit in the CE Population | Sponsor's Assessment: Cured | 66.7 percentage of patients |
| Plazomicin (15 mg/kg) | Percentage of Patients Who Attained Clinical Cure Based on Investigator and Sponsor Assessments at the TOC Visit in the CE Population | Investigator's Assessment: Cured | 76.6 percentage of patients |
| Plazomicin (15 mg/kg) | Percentage of Patients Who Attained Clinical Cure Based on Investigator and Sponsor Assessments at the TOC Visit in the CE Population | Sponsor's Assessment: Cured | 76.6 percentage of patients |
| Levofloxacin | Percentage of Patients Who Attained Clinical Cure Based on Investigator and Sponsor Assessments at the TOC Visit in the CE Population | Sponsor's Assessment: Cured | 76.2 percentage of patients |
| Levofloxacin | Percentage of Patients Who Attained Clinical Cure Based on Investigator and Sponsor Assessments at the TOC Visit in the CE Population | Investigator's Assessment: Cured | 78.6 percentage of patients |
Secondary
Percentage of Patients Who Attained Clinical Cure Based on Investigator and Sponsor Assessments at TOC Visit in the Intent-to-treat (ITT) Population
Investigator's assessment criteria defined Clinical Cure as resolution of baseline clinical signs and symptoms of infection through the TOC visit. The sponsor's assessment criteria was programmatically based on the investigator's assessment of participant clinical outcome, the number of days and doses of drug received and whether an antibiotic was administered.
Time frame: Day 1 to TOC (Day 12)
Population: The intent-to-treat (ITT) population was defined as all randomized patients.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Plazomicin (10 mg/kg) | Percentage of Patients Who Attained Clinical Cure Based on Investigator and Sponsor Assessments at TOC Visit in the Intent-to-treat (ITT) Population | Investigator's Assessment: Cured | 63.6 percentage of patients |
| Plazomicin (10 mg/kg) | Percentage of Patients Who Attained Clinical Cure Based on Investigator and Sponsor Assessments at TOC Visit in the Intent-to-treat (ITT) Population | Sponsor's Assessment: Cured | 59.1 percentage of patients |
| Plazomicin (15 mg/kg) | Percentage of Patients Who Attained Clinical Cure Based on Investigator and Sponsor Assessments at TOC Visit in the Intent-to-treat (ITT) Population | Sponsor's Assessment: Cured | 69.7 percentage of patients |
| Plazomicin (15 mg/kg) | Percentage of Patients Who Attained Clinical Cure Based on Investigator and Sponsor Assessments at TOC Visit in the Intent-to-treat (ITT) Population | Investigator's Assessment: Cured | 69.7 percentage of patients |
| Levofloxacin | Percentage of Patients Who Attained Clinical Cure Based on Investigator and Sponsor Assessments at TOC Visit in the Intent-to-treat (ITT) Population | Investigator's Assessment: Cured | 70.2 percentage of patients |
| Levofloxacin | Percentage of Patients Who Attained Clinical Cure Based on Investigator and Sponsor Assessments at TOC Visit in the Intent-to-treat (ITT) Population | Sponsor's Assessment: Cured | 68.1 percentage of patients |
Secondary
Percentage of Patients Who Attained MBE at the EOT Visit in the ME Population
MBE was defined as documented eradication of all isolated pathogens. This was based on a urine culture, taken at the EOT visit that showed that all pathogens isolated at baseline at ≥10\^5 CFU/mL were reduced to \<10\^4 CFU/mL.
Time frame: Day 1 to EOT (Day 5)
Population: The ME population was defined as CE patients who had a causative pathogen isolated at baseline (ie, patients in both the MITT and CE populations). To be included in the ME population, a patient must also have had results obtained from non-contaminated urine culture at TOC.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Plazomicin (10 mg/kg) | Percentage of Patients Who Attained MBE at the EOT Visit in the ME Population | 85.7 percentage of patients |
| Plazomicin (15 mg/kg) | Percentage of Patients Who Attained MBE at the EOT Visit in the ME Population | 82.9 percentage of patients |
| Levofloxacin | Percentage of Patients Who Attained MBE at the EOT Visit in the ME Population | 76.2 percentage of patients |
Secondary
Percentage of Patients Who Attained MBE at the EOT Visit in the MITT Population
MBE was defined as documented eradication of all isolated pathogens. This was based on a urine culture, taken at the EOT visit that showed that all pathogens isolated at baseline at ≥10\^5 CFU/mL were reduced to \<10\^4 CFU/mL.
Time frame: Day 1 to EOT (Day 5)
Population: The MITT population was defined as a subset patients from the ITT population with at least one isolated causative pathogen from an acceptable pretreatment urine specimen.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Plazomicin (10 mg/kg) | Percentage of Patients Who Attained MBE at the EOT Visit in the MITT Population | 83.3 percentage of patients |
| Plazomicin (15 mg/kg) | Percentage of Patients Who Attained MBE at the EOT Visit in the MITT Population | 74.5 percentage of patients |
| Levofloxacin | Percentage of Patients Who Attained MBE at the EOT Visit in the MITT Population | 72.4 percentage of patients |
Secondary
Percentage of Patients Who Attained MBE at the TOC Visit in the ME Population by Baseline Pathogen
MBE was defined as documented eradication of all isolated pathogens. This was based on a urine culture, taken at the TOC visit that showed that all pathogens isolated at baseline at ≥10\^5 CFU/mL were reduced to \<10\^4 CFU/mL.
Time frame: Day 1 to TOC (Day 12)
Population: The ME population was defined as CE patients who had a causative pathogen isolated at baseline (ie, patients in both the MITT and CE populations). To be included in the ME population, a patient must also have had results obtained from non-contaminated urine culture at TOC.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Plazomicin (10 mg/kg) | Percentage of Patients Who Attained MBE at the TOC Visit in the ME Population by Baseline Pathogen | Gram-positive bacteria (aerobes), eradication | 100 percentage of patients |
| Plazomicin (10 mg/kg) | Percentage of Patients Who Attained MBE at the TOC Visit in the ME Population by Baseline Pathogen | Gram-negative bacteria (aerobes), eradication | 83.3 percentage of patients |
| Plazomicin (15 mg/kg) | Percentage of Patients Who Attained MBE at the TOC Visit in the ME Population by Baseline Pathogen | Gram-positive bacteria (aerobes), eradication | 100 percentage of patients |
| Plazomicin (15 mg/kg) | Percentage of Patients Who Attained MBE at the TOC Visit in the ME Population by Baseline Pathogen | Gram-negative bacteria (aerobes), eradication | 87.5 percentage of patients |
| Levofloxacin | Percentage of Patients Who Attained MBE at the TOC Visit in the ME Population by Baseline Pathogen | Gram-positive bacteria (aerobes), eradication | 100 percentage of patients |
| Levofloxacin | Percentage of Patients Who Attained MBE at the TOC Visit in the ME Population by Baseline Pathogen | Gram-negative bacteria (aerobes), eradication | 80.0 percentage of patients |
Secondary
Percentage of Patients Who Attained MBE at the TOC Visit in the ME Population by Country/Region
MBE was defined as documented eradication of all isolated pathogens. This was based on a urine culture, taken at the TOC visit that showed that all pathogens isolated at baseline at ≥10\^5 CFU/mL were reduced to \<10\^4 CFU/mL.
Time frame: Day 1 to TOC (Day 12)
Population: The ME population was defined as CE patients who had a causative pathogen isolated at baseline (ie, patients in both the MITT and CE populations). To be included in the ME population, a patient must also have had results obtained from non-contaminated urine culture at TOC.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Plazomicin (10 mg/kg) | Percentage of Patients Who Attained MBE at the TOC Visit in the ME Population by Country/Region | North America, eradication | 100 percentage of patients |
| Plazomicin (10 mg/kg) | Percentage of Patients Who Attained MBE at the TOC Visit in the ME Population by Country/Region | India, eradicaton | 66.7 percentage of patients |
| Plazomicin (10 mg/kg) | Percentage of Patients Who Attained MBE at the TOC Visit in the ME Population by Country/Region | Latin America, eradication | 100 percentage of patients |
| Plazomicin (15 mg/kg) | Percentage of Patients Who Attained MBE at the TOC Visit in the ME Population by Country/Region | North America, eradication | 88.9 percentage of patients |
| Plazomicin (15 mg/kg) | Percentage of Patients Who Attained MBE at the TOC Visit in the ME Population by Country/Region | Latin America, eradication | 100 percentage of patients |
| Plazomicin (15 mg/kg) | Percentage of Patients Who Attained MBE at the TOC Visit in the ME Population by Country/Region | India, eradicaton | 66.7 percentage of patients |
| Levofloxacin | Percentage of Patients Who Attained MBE at the TOC Visit in the ME Population by Country/Region | Latin America, eradication | 100 percentage of patients |
| Levofloxacin | Percentage of Patients Who Attained MBE at the TOC Visit in the ME Population by Country/Region | North America, eradication | 90 percentage of patients |
| Levofloxacin | Percentage of Patients Who Attained MBE at the TOC Visit in the ME Population by Country/Region | India, eradicaton | 0 percentage of patients |
Secondary
Percentage of Patients Who Attained MBE at the TOC Visit in the ME Population Stratified by Infection Category
MBE was defined as documented eradication of all isolated pathogens. This was based on a urine culture, taken at the TOC visit that showed that all pathogens isolated at baseline at ≥10\^5 CFU/mL were reduced to \<10\^4 CFU/mL.
Time frame: Day 1 to TOC (Day 12)
Population: The ME population was defined as CE patients who had a causative pathogen isolated at baseline (ie, patients in both the MITT and CE populations). To be included in the ME population, a patient must also have had results obtained from non-contaminated urine culture at TOC.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Plazomicin (10 mg/kg) | Percentage of Patients Who Attained MBE at the TOC Visit in the ME Population Stratified by Infection Category | Acute pyelonephritis, eradication | 100 percentage of patients |
| Plazomicin (10 mg/kg) | Percentage of Patients Who Attained MBE at the TOC Visit in the ME Population Stratified by Infection Category | cUTI with indwelling catheter, eradication | 0 percentage of patients |
| Plazomicin (10 mg/kg) | Percentage of Patients Who Attained MBE at the TOC Visit in the ME Population Stratified by Infection Category | Complicated Lower UTI, eradication | 80.0 percentage of patients |
| Plazomicin (10 mg/kg) | Percentage of Patients Who Attained MBE at the TOC Visit in the ME Population Stratified by Infection Category | cUTI without indwelling catheter, eradication | 100 percentage of patients |
| Plazomicin (15 mg/kg) | Percentage of Patients Who Attained MBE at the TOC Visit in the ME Population Stratified by Infection Category | Complicated Lower UTI, eradication | 88.2 percentage of patients |
| Plazomicin (15 mg/kg) | Percentage of Patients Who Attained MBE at the TOC Visit in the ME Population Stratified by Infection Category | cUTI without indwelling catheter, eradication | 92.3 percentage of patients |
| Plazomicin (15 mg/kg) | Percentage of Patients Who Attained MBE at the TOC Visit in the ME Population Stratified by Infection Category | Acute pyelonephritis, eradication | 88.9 percentage of patients |
| Plazomicin (15 mg/kg) | Percentage of Patients Who Attained MBE at the TOC Visit in the ME Population Stratified by Infection Category | cUTI with indwelling catheter, eradication | 75 percentage of patients |
| Levofloxacin | Percentage of Patients Who Attained MBE at the TOC Visit in the ME Population Stratified by Infection Category | cUTI without indwelling catheter, eradication | 83.3 percentage of patients |
| Levofloxacin | Percentage of Patients Who Attained MBE at the TOC Visit in the ME Population Stratified by Infection Category | Complicated Lower UTI, eradication | 83.3 percentage of patients |
| Levofloxacin | Percentage of Patients Who Attained MBE at the TOC Visit in the ME Population Stratified by Infection Category | Acute pyelonephritis, eradication | 80 percentage of patients |
Secondary
Percentage of Patients With a Superinfection or New Infection in the ME Population
Superinfections are defined as a pathogen other than the one at baseline found in urine at ≥10\^5 CFU/mL any time after the first infusion through EOT. New infections are defined as a pathogen other than the one at baseline found in urine at ≥10\^5 CFU/mL any time after EOT.
Time frame: Day 1 to to End of Study (Day 40)
Population: The ME population was defined as CE patients who had a causative pathogen isolated at baseline (ie, patients in both the MITT and CE populations). To be included in the ME population, a patient must also have had results obtained from non-contaminated urine culture at TOC.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Plazomicin (10 mg/kg) | Percentage of Patients With a Superinfection or New Infection in the ME Population | Superinfection | 28.6 percentage of patients |
| Plazomicin (10 mg/kg) | Percentage of Patients With a Superinfection or New Infection in the ME Population | New infection | 0 percentage of patients |
| Plazomicin (15 mg/kg) | Percentage of Patients With a Superinfection or New Infection in the ME Population | Superinfection | 8.6 percentage of patients |
| Plazomicin (15 mg/kg) | Percentage of Patients With a Superinfection or New Infection in the ME Population | New infection | 2.9 percentage of patients |
| Levofloxacin | Percentage of Patients With a Superinfection or New Infection in the ME Population | New infection | 4.8 percentage of patients |
| Levofloxacin | Percentage of Patients With a Superinfection or New Infection in the ME Population | Superinfection | 0 percentage of patients |
Secondary
Time (Days) to Clinical Cure Based on Investigator's and Sponsor's Assessments in the MITT Population
Investigator's assessment criteria defined Clinical Cure as a resolution of baseline clinical signs and symptoms of infection through the TOC visit. The Sponsor's assessment criteria was programmatically based on the investigator's assessment of participant clinical outcome, the number of days and doses of drug received and whether an antibiotic was administered.
Time frame: Day 1 to End of Study (Day 40)
Population: The MITT population was defined as a subset patients from the ITT population with at least one isolated causative pathogen from an acceptable pretreatment urine specimen.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Plazomicin (10 mg/kg) | Time (Days) to Clinical Cure Based on Investigator's and Sponsor's Assessments in the MITT Population | Investigator's Assessment | 9.5 days | Standard Error 2.43 |
| Plazomicin (10 mg/kg) | Time (Days) to Clinical Cure Based on Investigator's and Sponsor's Assessments in the MITT Population | Sponsor's Assessment | 9.5 days | Standard Error 2.43 |
| Plazomicin (15 mg/kg) | Time (Days) to Clinical Cure Based on Investigator's and Sponsor's Assessments in the MITT Population | Investigator's Assessment | 7.0 days | Standard Error 0.71 |
| Plazomicin (15 mg/kg) | Time (Days) to Clinical Cure Based on Investigator's and Sponsor's Assessments in the MITT Population | Sponsor's Assessment | 7.0 days | Standard Error 0.71 |
| Levofloxacin | Time (Days) to Clinical Cure Based on Investigator's and Sponsor's Assessments in the MITT Population | Investigator's Assessment | 7.6 days | Standard Error 0.82 |
| Levofloxacin | Time (Days) to Clinical Cure Based on Investigator's and Sponsor's Assessments in the MITT Population | Sponsor's Assessment | 7.4 days | Standard Error 0.83 |
Secondary
Time (Days) to Defervescense in the MITT Population
Defervescence is defined as the absence of fever \<37.7 degrees Celsius and is assessed in patients who were afebrile at baseline.
Time frame: Day 1 to End of Study (Day 40)
Population: The MITT population was defined as a subset patients from the ITT population with at least one isolated causative pathogen from an acceptable pretreatment urine specimen.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Plazomicin (10 mg/kg) | Time (Days) to Defervescense in the MITT Population | 1.0 days | — |
| Plazomicin (15 mg/kg) | Time (Days) to Defervescense in the MITT Population | 2.1 days | Standard Error 0.26 |
| Levofloxacin | Time (Days) to Defervescense in the MITT Population | 2.0 days | Standard Error 0.58 |
Secondary
Time (Days) to Resolution of Signs and Symptoms of cUTI and AP in the MITT Population
Resolution of clinical signs and symptoms is defined as absence of all signs and symptoms present at baseline.
Time frame: Day 1 to End of Study (Day 40)
Population: The MITT population was defined as a subset patients from the ITT population with at least one isolated causative pathogen from an acceptable pretreatment urine specimen.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Plazomicin (10 mg/kg) | Time (Days) to Resolution of Signs and Symptoms of cUTI and AP in the MITT Population | 11.8 days | Standard Error 2.67 |
| Plazomicin (15 mg/kg) | Time (Days) to Resolution of Signs and Symptoms of cUTI and AP in the MITT Population | 10.7 days | Standard Error 1.93 |
| Levofloxacin | Time (Days) to Resolution of Signs and Symptoms of cUTI and AP in the MITT Population | 13.3 days | Standard Error 3.16 |