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

NCT01096849 | Completed Phase 2 Results

• 1 other identifier: ACHN-490-002
• Study Type: interventional
• Target: 145
• Locations: 0 countries
• Sites: N/A

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).

Conditions

Complicated Urinary Tract Infection; Acute Pyelonephritis

Keywords

urinary tract infection; UTI; cUTI; pyelonephritis; AP; ACHN-490

Outcome Measures

Primary Outcomes (3)

• 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)

• 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)

• 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 Outcomes (13)

• 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)

• 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)

• 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)

• Percentage of Patients Who Attained MBE at the EOT Visit in the ME Population

  Day 1 to EOT (Day 5)

• Percentage of Patients Who Attained MBE at the EOT Visit in the MITT Population

  Day 1 to EOT (Day 5)

Study Arms (3)

plazomicin (10 mg/kg)

EXPERIMENTAL

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

plazomicin (15 mg/kg)

EXPERIMENTAL

Patients received two IV infusions daily for 5 consecutive days: 15 mg/kg plazomicin followed by placebo.

Drug: plazomicin; Drug: placebo

levofloxacin

ACTIVE COMPARATOR

Patients received two IV infusions daily for 5 consecutive days: placebo followed by 750 milligrams (mg) levofloxacin.

Drug: levofloxacin; Drug: placebo

Interventions

levofloxacin DRUG

levofloxacin

plazomicin DRUG

plazomicin (10 mg/kg); plazomicin (15 mg/kg)

placebo DRUG

levofloxacin; plazomicin (10 mg/kg); plazomicin (15 mg/kg)

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Achaogen, Inc.: lead

Related 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):e01989-17. doi: 10.1128/AAC.01989-17. Print 2018 Apr.

  PMID: 29378708 BACKGROUND

MeSH Terms

Conditions

Urinary Tract Infections; Pyelonephritis

Interventions

Levofloxacin; plazomicin

Condition Hierarchy (Ancestors)

Infections; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Nephritis, Interstitial; Nephritis; Kidney Diseases; Pyelitis

Intervention Hierarchy (Ancestors)

Ofloxacin; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Clinical Trials Posting Group
• Organization: Achaogen, Inc.

clinical-trials@achaogen.com

Study Officials

• Medical Director

  Achaogen, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 12, 2010
• First Posted: March 31, 2010
• Study Start: July 13, 2010
• Primary Completion: April 3, 2012
• Study Completion: April 3, 2012
• Last Updated: August 22, 2018
• Results First Posted: August 22, 2018

Record last verified: 2018-08