A Study of Plazomicin Compared With Levofloxacin for the Treatment of Complicated Urinary Tract Infection (cUTI) and Acute Pyelonephritis (AP)

Acute Pyelonephritis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01096849
• Other study ID #: ACHN-490-002
• Status: Completed
• Phase: Phase 2
• Start date: July 13, 2010
• Est. completion date: April 3, 2012

Study information

• Verified date: August 2018
• Source: Achaogen, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 145
• Est. completion date: April 3, 2012
• Est. primary completion date: April 3, 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute Pyelonephritis
• Communicable Diseases
• Complicated Urinary Tract Infection
• Infection
• Pyelonephritis
• Urinary Tract Infections

Intervention

Drug:
• levofloxacin

• plazomicin

• placebo

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Achaogen, Inc.

References & Publications (1)

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). pii: e01989-17. doi: 10.1128/AAC.01989-17. Print 2018 Apr. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	Day 1 to TOC (Day 12)
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.	Day 1 to TOC (Day 12)
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.	Day 1 to the end of study (Day 40)
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.	Day 1 to TOC (Day 12)
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.	Day 1 to TOC (Day 12)
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.	Day 1 to EOT (Day 5)
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.	Day 1 to EOT (Day 5)
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.	Day 1 to EOT (Day 5)
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.	Day 1 to TOC (Day 12)
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.	Day 1 to TOC (Day 12)
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.	Day 1 to TOC (Day 12)
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.	Day 1 to End of Study (Day 40)
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.	Day 1 to End of Study (Day 40)
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.	Day 1 to End of Study (Day 40)
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).	Day 1 to LTFU (Day 40)
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.	Day 1 to to End of Study (Day 40)