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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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ClinicalTrials.gov Identifier: NCT01096849
Recruitment Status : Completed
First Posted : March 31, 2010
Results First Posted : August 22, 2018
Last Update Posted : August 22, 2018
Sponsor:
Information provided by (Responsible Party):
Achaogen, Inc.

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).

Condition or disease Intervention/treatment Phase
Complicated Urinary Tract Infection Acute Pyelonephritis Drug: levofloxacin Drug: plazomicin Drug: placebo Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 145 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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
Actual Study Start Date : July 13, 2010
Actual Primary Completion Date : April 3, 2012
Actual Study Completion Date : April 3, 2012

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: plazomicin (10 mg/kg)
Patients received two intravenous (IV) infusions daily for 5 consecutive days: 10 milligrams per kilogram (mg/kg) plazomicin followed by placebo.
Drug: plazomicin
Drug: placebo
Experimental: plazomicin (15 mg/kg)
Patients received two IV infusions daily for 5 consecutive days: 15 mg/kg plazomicin followed by placebo.
Drug: plazomicin
Drug: placebo
Active Comparator: levofloxacin
Patients received two IV infusions daily for 5 consecutive days: placebo followed by 750 milligrams (mg) levofloxacin.
Drug: levofloxacin
Drug: placebo



Primary Outcome Measures :
  1. Percentage of Patients Who Attained Microbiological Eradication (MBE) at the Test of Cure (TOC) Visit in the Microbiological Intent to Treat (MITT) Population [ Time Frame: 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.

  2. Percentage of Patients Who Attained MBE at the TOC Visit in the Microbiologically Evaluable (ME) Population [ Time Frame: 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.

  3. Percentage of Patients With Treatment-Emergent Adverse Events (TEAE) [ Time Frame: 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 Outcome Measures :
  1. Percentage of Patients Who Attained Clinical Cure Based on Investigator and Sponsor Assessments at TOC Visit in the Intent-to-treat (ITT) Population [ Time Frame: 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.


  2. Percentage of Patients Who Attained Clinical Cure Based on Investigator and Sponsor Assessments at the TOC Visit in the CE Population [ Time Frame: 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.


  3. Percentage of Patients Who Attained Clinical Cure Based on Investigator and Sponsor Assessments at the End of Treatment (EOT) Visit in the CE Population [ Time Frame: 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.


  4. Percentage of Patients Who Attained MBE at the EOT Visit in the ME Population [ Time Frame: 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.

  5. Percentage of Patients Who Attained MBE at the EOT Visit in the MITT Population [ Time Frame: 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.

  6. Percentage of Patients Who Attained MBE at the TOC Visit in the ME Population by Baseline Pathogen [ Time Frame: 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.

  7. Percentage of Patients Who Attained MBE at the TOC Visit in the ME Population Stratified by Infection Category [ Time Frame: 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.

  8. Percentage of Patients Who Attained MBE at the TOC Visit in the ME Population by Country/Region [ Time Frame: 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.

  9. Time (Days) to Resolution of Signs and Symptoms of cUTI and AP in the MITT Population [ Time Frame: 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.

  10. Time (Days) to Clinical Cure Based on Investigator's and Sponsor's Assessments in the MITT Population [ Time Frame: 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.


  11. Time (Days) to Defervescense in the MITT Population [ Time Frame: 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.

  12. Percentage of Patients Experiencing a Clinical Relapse or Microbiological Recurrence in the ME Population [ Time Frame: 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).

  13. Percentage of Patients With a Superinfection or New Infection in the ME Population [ Time Frame: 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.



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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

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): NCT01096849


Sponsors and Collaborators
Achaogen, Inc.
Investigators
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Study Director: Medical Director Achaogen, Inc.

Publications:
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Responsible Party: Achaogen, Inc.
ClinicalTrials.gov Identifier: NCT01096849     History of Changes
Other Study ID Numbers: ACHN-490-002
First Posted: March 31, 2010    Key Record Dates
Results First Posted: August 22, 2018
Last Update Posted: August 22, 2018
Last Verified: August 2018

Keywords provided by Achaogen, Inc.:
urinary tract infection
UTI
cUTI
pyelonephritis
AP
ACHN-490

Additional relevant MeSH terms:
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Infection
Communicable Diseases
Urinary Tract Infections
Pyelonephritis
Urologic Diseases
Nephritis, Interstitial
Nephritis
Kidney 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