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

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.

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