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

• 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: Achaogen, Inc.
• Information provided by (Responsible Party): Achaogen, Inc.

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).

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

Study Design

• 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

Arms and Interventions

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

Outcome Measures

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.

Eligibility Criteria

• 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

Contacts and Locations

Sponsors and Collaborators

Achaogen, Inc.

Investigators

• Study Director: Medical Director; Achaogen, Inc.

More Information

Publications:

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.

• Responsible Party: Achaogen, Inc.
• ClinicalTrials.gov Identifier: NCT01096849
• Other Study ID Numbers: ACHN-490-002
• First Posted: March 31, 2010
• 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:

Infections; Communicable Diseases; Urinary Tract Infections; Pyelonephritis; Disease Attributes; Pathologic Processes; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Nephritis, Interstitial; Nephritis; Kidney Diseases; Pyelitis; Levofloxacin; Anti-Infective Agents, Urinary; Anti-Infective 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