Safety and Efficacy of IV CXA-101 and IV Ceftazidime in Patients With Complicated Urinary Tract Infections

A Multicenter, Double-blind, Randomized, Phase 2 Study to Compare the Safety and Efficacy of Intravenous CXA-101 and Intravenous Ceftazidime in Complicated Urinary Tract Infection, Including Pyelonephritis

The purpose of this study is to evaluate the safety and efficacy of intravenous CXA 101 and comparator in complicated urinary tract infection

Study Overview

• Status: Completed
• Conditions: Complicated Urinary Tract Infection
• Intervention / Treatment: Drug: CXA-101; Drug: Ceftazidime

Detailed Description

This is a Phase 2, multicenter, prospective, randomized, double-blind, comparative efficacy and safety study of IV CXA 101 versus IV ceftazidime for 7 to 10 days.

Subjects are followed up 6 to 9 days after the last dose of study drug to assess clinical signs and symptoms of infection. A Late Follow Up evaluation (21 to 28 days after the last dose of study drug) occurs for those subjects who respond to therapy. The primary assessment of effectiveness is the microbiological response (the eradication at post-therapy of the infectious organism identified at the start of study). An additional assessment of efficacy includes the overall clinical response, which is described as cured, improved, or failed. Safety assessments include the incidence of adverse events throughout the study, clinical laboratory tests (hematology, serum chemistry, and urinalysis) and physical examinations at the start of the study and post-therapy.

• Study Type: Interventional
• Enrollment (Actual): 129
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Backnang, Germany, 71522
    • Kreiskrankenhaus Backnang
  • Berlin, Germany, 10115
    • URO Forschungs GmbH
  • Giessen, Germany, 35392
    • Uniklinikum Giessen
  • Giessen, Germany, 35398
    • Evangelisches Krankenhaus Giessen Urologie
  • Lübeck, Germany, 23538
    • Universitatsklinikum Schleswig Holstein Campus Lubeck
  • Paderborn, Germany, 33098
    • Brüderkrankenhaus St. Josef Paderborn
  • Planegg, Germany, 82152
    • Urologische Klinik Dr. Castringius München-Planegg
• Poland
  • Lublin, Poland, 20-954
    • Samodzielny Publiczny Szpital Kliniczny nr 4 Katedra i Klinika Nefrologii
  • Tychy, Poland, 43-100
    • Wojewódźki Szpital Specjalistyczny nr 1 Oddział Chorób Wewnętrznych
  • Warszawa, Poland, 01-809
    • Szpital Bielański im.Ks. Jerzego Popiełuszki Samodzielny Publiczny Zakład Opieki Zdrowotnej IV Kliniczny Oddzial Chorób Wewnętrznych
  • Warszawa, Poland, 02-005
    • Szpital Kliniczny Dzieciątka Jezus-Centrum Leczenia Obrażeń Klinika Urologii Ogólnej, Onkologicznej Czynnościowej
  • Warszawa, Poland, 03-401
    • Szpital Praski p.w. Przemienienia Pańskiego Samodzielny Publiczny Zakład Opieki Zdrowotnej ll Oddział Wewnętrznych
  • Wrocław, Poland, 51-124
    • Wojewódźki Szpital Specjalistyczny Oddział Nefrologiczny
  • Zamość, Poland, 22-400
    • Samodzielny Publiczny Szpital Wojewódźki im. Papieża Jana Pawła ll Oddział Wewnętrznych Nefrologiczno-Endokrynologiczny ze Stacją Dializ
• United States
  • California
    • Los Angeles, California, United States, 90015
      • HealthCare Partners Medical Group
  • Florida
    • Orlando, Florida, United States, 32806
      • Compass Research, LLC
  • Georgia
    • Decatur, Georgia, United States, 30030
      • Atlanta Institute for Medical Research, Inc.
  • Indiana
    • Indianapolis, Indiana, United States, 46280
      • Infectious Disease Of Indiana, Psc
  • Mississippi
    • Picayune, Mississippi, United States, 39466
      • Mississippi Medical Research, LLC
  • Montana
    • Butte, Montana, United States, 59701
      • Great Falls Clinic, LLP
  • Ohio
    • Columbus, Ohio, United States, 43215
      • Remington-Davis, Inc. Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Males and females 18 to 90 years of age, inclusive.
2. Pyuria (white blood cell [WBC] count > 10/µL in unspun urine or ≥ 10 per high power field in spun urine)

3. Clinical signs and/or symptoms of cUTI, either of:

   a. Pyelonephritis, as indicated by both of the following: i. Fever (oral temperature ≥ 37.8°C); ii. Flank pain or costovertebral angle tenderness;

OR

b. Complicated lower UTI, as indicated by both of the following: i. At least one of the following new or worsening symptoms:

• Dysuria;
• Frequency;
• Suprapubic pain;
• Urgency

ii. At least one of the following complicating factors:

• Male gender;
• Current bladder instrumentation or indwelling urinary catheter that is expected to be removed during the course of IV study drug administration;
• Obstructive uropathy that is expected to be medically or surgically treated during the course of IV study drug administration;
• Urogenital surgery within 7 days preceding administration of the first dose of study drug;
• Functional or anatomical abnormality of the urogenital tract including anatomic malformations or neurogenic bladder with voiding disturbance of at least 100 mL residual urine.

Exclusion Criteria

1. Documented history of any hypersensitivity or allergic reaction to any β-lactam antibacterial
2. Concomitant infection requiring systemic antibacterial therapy in addition to IV study drug therapy at the time of randomization. Drugs with only gram-positive activity (e.g. vancomycin, linezolid) are allowed
3. Complete, permanent obstruction of the urinary tract
4. Confirmed (at time of randomization) fungal urinary tract infection (with ≥ 103 fungal CFU/mL)
5. Suspected or confirmed perinephric or intrarenal abscess
6. Suspected or confirmed prostatitis
7. Known ileal loop or vesico-ureteral reflux
8. Women who are pregnant or nursing

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 1; CXA-101	Drug: CXA-101; intravenous
ACTIVE_COMPARATOR: 2; Ceftazidime	Drug: Ceftazidime; intravenous

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Microbiological Response at the Test of Cure (TOC) Visit in the Microbiological Modified Intent-to-Treat (mMITT) Population	Microbiological response is eradication for each baseline pathogen	TOC; 6-9 days after last study drug administration
Microbiological Response at the TOC Visit in the Microbiologically Evaluable (ME) Population.	Microbiological response is eradication for each baseline pathogen	TOC; 6-9 days after last study drug administration

Collaborators and Investigators

• Sponsor: Cubist Pharmaceuticals LLC
• Investigators: Principal Investigator: Ahmad Haidar, MD, Mississippi Medical Research, LLC; Principal Investigator: Ryszard Gellert, MD, Szpital Bielański im.Ks. Jerzego Popiełuszki Samodzielny Publiczny Zakład Opieki Zdrowotnej IV Kliniczny Oddzial Chorób Wewnętrznych i Pododdział Nefrologiczny; Principal Investigator: Florian Wagenlehner, MD, Uniklinikum Giessen

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 30, 2009
• Primary Completion (ACTUAL): February 25, 2010
• Study Completion (ACTUAL): March 11, 2010

Study Registration Dates

• First Submitted: June 12, 2009
• First Submitted That Met QC Criteria: June 12, 2009
• First Posted (ESTIMATE): June 16, 2009

Study Record Updates

• Last Update Posted (ACTUAL): October 18, 2018
• Last Update Submitted That Met QC Criteria: September 21, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Keywords: Cephalosporin; Intravenous; Complicated Urinary Tract Infection; Pyelonephritis; Antimicrobial
• Additional Relevant MeSH Terms: Pathologic Processes; Kidney Diseases; Urologic Diseases; Disease Attributes; Nephritis; Nephritis, Interstitial; Pyelitis; Infections; Communicable Diseases; Urinary Tract Infections; Pyelonephritis; Anti-Infective Agents; Anti-Bacterial Agents; Ceftazidime; Ceftolozane
• Other Study ID Numbers: 7625-001; CXA 101-03 (OTHER: Cubist Study Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf