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

Phase 2

Completed

Interventions: Drug: Ceftaroline fosamil and NXL104 (q8h)
Drug: Ceftaroline fosamil and NXL104 (q12h)
Drug: Doripenem
Drug: Placebo

Brief Summary: 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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Ceftaroline fosamil and NXL104 (q8h)	Ceftaroline fosamil and NXL104 (q8h)	-
Ceftaroline fosamil and NXL104 (q8h)	Placebo	-
Ceftaroline fosamil and NXL104 (q12h)	Ceftaroline fosamil and NXL104 (q12h)	-
Ceftaroline fosamil and NXL104 (q12h)	Placebo	-
Doripenem	Placebo	-
Doripenem	Doripenem	-

Primary Outcome Measures

Name	Time	Method
Microbiological response of Microbiologically Evaluable (ME) at Test of Cure (TOC)	5 to 11 days after last dose of study drug	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	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)	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.

Secondary Outcome Measures

Name	Time	Method
Clinical response in CE at Test of Cure	5 to 11 days after last dose of study drug	The number and percentage of subjects in each treatment group classified as clinical cure Clinically Evaluable (CE) Population at TOC