Comparative Study of Coadministered Ceftaroline Fosamil and NXL104 vs. Intravenous Doripenem in Adult Subjects With Complicated Urinary Tract Infections

• Microbiological response of Microbiologically Evaluable (ME) at Test of Cure (TOC) [ Time Frame: 5 to 11 days after last dose of study drug ] [ Designated as safety issue: No ]
  The number and percentage of subjects in each treatment group recorded as having a favorable microbiological response in the ME Population at Test-of-Cure (TOC)
• Evaluate safety [ Time Frame: from administration of first dose of study drug to the Late -Follow -Up (LFU) visit (28 to 42 days after administration of the last dose of study drug) ] [ Designated as safety issue: No ]
  Evaluate the safety of coadministered IV ceftaroline fosamil and NXL104 in subjects with cUTI. Summaries of AEs, SAEs, deaths, laboratory evaluations (hematology and coagulation studies, comprehensive metabolic panel, and urinalysis), vital signs, ECGs, and physical examinations will be provided for each treatment group.

This is a study in adult subjects with complicated urinary tract infection (cUTI) comparing treatment with intravenous (IV) coadministered ceftaroline fosamil and NXL104 versus treatment with IV doripenem.

• Drug: Ceftaroline fosamil and NXL104
  600 mg ceftaroline fosamil/600 mg NXL104 IV coadministered every 8 hours (q8h);
  Other Name: Ceftaroline fosamil and NXL104
• Drug: Ceftaroline fosamil and NXL104
  600 mg ceftaroline fosamil/600 mg NXL104 IV coadministered every 12 hours (q12h);
  Other Name: Ceftaroline fosamil and NXL104 (q12h)
• Drug: Doripenem
  500 mg doripenem IV q8h;
  Other Name: Doripenem
• Drug: Placebo
  IV Placebo (saline) is administered to maintain the study blind
  Other Name: placebo

• Experimental: Ceftaroline fosamil and NXL104 (q8h)
  Interventions:

  • Drug: Ceftaroline fosamil and NXL104
  • Drug: Placebo
• Experimental: Ceftaroline fosamil and NXL104 (q12h)
  Interventions:

  • Drug: Ceftaroline fosamil and NXL104
  • Drug: Placebo
• Active Comparator: Doripenem
  Interventions:

  • Drug: Doripenem
  • Drug: Placebo

Inclusion Criteria:

Subjects must meet the following inclusion criteria:

• Have pyuria (white blood cells in the urine)
• Clinical signs and/or symptoms of cUTI (including acute pyelonephritis)
• Have a pretreatment baseline urine culture specimen
• The subject's infection would require initial treatment with IV antibiotics
• The subject must require initial hospitalization to manage the cUTI by the standard of care.

Exclusion Criteria:

Subjects must NOT meet any of the following exclusion criteria:

• History of any hypersensitivity or allergic reaction to any β-lactam (eg, cephalosporins, penicillins, carbapenems)
• Confirmed fungal urinary tract infection
• Intractable UTI anticipated to require more than 10 days of study drug therapy
• Complete, permanent obstruction of the urinary tract\
• Permanent indwelling bladder catheter or instrumentation (including nephrostomy) or current urinary catheter that will not be removed during IV study drug administration
• Suspected or confirmed perinephric or intrarenal abscess
• Suspected or confirmed prostatitis
• Ileal loops or vesico-ureteral reflux
• Impairment of renal function including a calculated CrCl of < 30 mL/min, requirement for peritoneal dialysis, hemodialysis or hemofiltration, or oliguria
• Renal transplantation
• Life expectancy less than 3 months
• Evidence of significant hepatic, hematological, or immunologic disease or dysfunction
• Past or current history of epilepsy or seizure disorder
• Women who are pregnant or nursing