Back to resultsA Study of Plazomicin Compared With Levofloxacin for the Treatment of Complicated Urinary Tract Infection (cUTI) and Acute Pyelonephritis (AP)
Primary Purpose
Complicated Urinary Tract Infection, Acute Pyelonephritis
Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
levofloxacin
plazomicin
placebo
Sponsored by
About this trial
This is an interventional treatment trial for Complicated Urinary Tract Infection focused on measuring urinary tract infection, UTI, cUTI, pyelonephritis, AP, ACHN-490
Eligibility 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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Active Comparator
Arm Label
plazomicin (10 mg/kg)
plazomicin (15 mg/kg)
levofloxacin
Arm Description
Patients received two intravenous (IV) infusions daily for 5 consecutive days: 10 milligrams per kilogram (mg/kg) plazomicin followed by placebo.
Patients received two IV infusions daily for 5 consecutive days: 15 mg/kg plazomicin followed by placebo.
Patients received two IV infusions daily for 5 consecutive days: placebo followed by 750 milligrams (mg) levofloxacin.
Outcomes
Primary Outcome Measures
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.
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.
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.
Secondary Outcome Measures
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.
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.
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.
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.
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.
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.
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.
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 (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 (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 (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.
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).
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01096849
Brief Title
A Study of Plazomicin Compared With Levofloxacin for the Treatment of Complicated Urinary Tract Infection (cUTI) and Acute Pyelonephritis (AP)
Official Title
A Double-blind, Randomized, Comparator-controlled Study to Assess the Safety, Efficacy, and Pharmacokinetics of ACHN-490 Injection Administered IV in Patients With Complicated Urinary Tract Infections or Acute Pyelonephritis
Study Type
Interventional
2. Study Status
Record Verification Date
August 2018
Overall Recruitment Status
Completed
Study Start Date
July 13, 2010 (Actual)
Primary Completion Date
April 3, 2012 (Actual)
Study Completion Date
April 3, 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Achaogen, Inc.
4. Oversight
Data Monitoring Committee
No
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Complicated Urinary Tract Infection, Acute Pyelonephritis
Keywords
urinary tract infection, UTI, cUTI, pyelonephritis, AP, ACHN-490
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
145 (Actual)
8. Arms, Groups, and Interventions
Arm Title
plazomicin (10 mg/kg)
Arm Type
Experimental
Arm Description
Patients received two intravenous (IV) infusions daily for 5 consecutive days: 10 milligrams per kilogram (mg/kg) plazomicin followed by placebo.
Arm Title
plazomicin (15 mg/kg)
Arm Type
Experimental
Arm Description
Patients received two IV infusions daily for 5 consecutive days: 15 mg/kg plazomicin followed by placebo.
Arm Title
levofloxacin
Arm Type
Active Comparator
Arm Description
Patients received two IV infusions daily for 5 consecutive days: placebo followed by 750 milligrams (mg) levofloxacin.
Intervention Type
Drug
Intervention Name(s)
levofloxacin
Intervention Type
Drug
Intervention Name(s)
plazomicin
Intervention Type
Drug
Intervention Name(s)
placebo
Primary Outcome Measure Information:
Title
Percentage of Patients Who Attained Microbiological Eradication (MBE) at the Test of Cure (TOC) Visit in the Microbiological Intent to Treat (MITT) Population
Description
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)
Title
Percentage of Patients Who Attained MBE at the TOC Visit in the Microbiologically Evaluable (ME) Population
Description
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)
Title
Percentage of Patients With Treatment-Emergent Adverse Events (TEAE)
Description
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)
Secondary Outcome Measure Information:
Title
Percentage of Patients Who Attained Clinical Cure Based on Investigator and Sponsor Assessments at TOC Visit in the Intent-to-treat (ITT) Population
Description
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)
Title
Percentage of Patients Who Attained Clinical Cure Based on Investigator and Sponsor Assessments at the TOC Visit in the CE Population
Description
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)
Title
Percentage of Patients Who Attained Clinical Cure Based on Investigator and Sponsor Assessments at the End of Treatment (EOT) Visit in the CE Population
Description
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)
Title
Percentage of Patients Who Attained MBE at the EOT Visit in the ME Population
Description
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)
Title
Percentage of Patients Who Attained MBE at the EOT Visit in the MITT Population
Description
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)
Title
Percentage of Patients Who Attained MBE at the TOC Visit in the ME Population by Baseline Pathogen
Description
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)
Title
Percentage of Patients Who Attained MBE at the TOC Visit in the ME Population Stratified by Infection Category
Description
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)
Title
Percentage of Patients Who Attained MBE at the TOC Visit in the ME Population by Country/Region
Description
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)
Title
Time (Days) to Resolution of Signs and Symptoms of cUTI and AP in the MITT Population
Description
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)
Title
Time (Days) to Clinical Cure Based on Investigator's and Sponsor's Assessments in the MITT Population
Description
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)
Title
Time (Days) to Defervescense in the MITT Population
Description
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)
Title
Percentage of Patients Experiencing a Clinical Relapse or Microbiological Recurrence in the ME Population
Description
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)
Title
Percentage of Patients With a Superinfection or New Infection in the ME Population
Description
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)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Achaogen, Inc.
Official's Role
Study Director
12. IPD Sharing Statement
Citations:
PubMed Identifier
29378708
Citation
Connolly LE, Riddle V, Cebrik D, Armstrong ES, Miller LG. A Multicenter, Randomized, Double-Blind, Phase 2 Study of the Efficacy and Safety of Plazomicin Compared with Levofloxacin in the Treatment of Complicated Urinary Tract Infection and Acute Pyelonephritis. Antimicrob Agents Chemother. 2018 Mar 27;62(4):e01989-17. doi: 10.1128/AAC.01989-17. Print 2018 Apr.
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A Study of Plazomicin Compared With Levofloxacin for the Treatment of Complicated Urinary Tract Infection (cUTI) and Acute Pyelonephritis (AP)
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