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

Study Overview
=================
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.

Official Title
-----------------
A Phase 2, Multicenter, Randomized, Double-blind, Comparative Study to Evaluate the Efficacy and Safety of Intravenous Coadministered Ceftaroline Fosamil and NXL104 Versus Intravenous Doripenem in Adult Subjects With Complicated Urinary Tract Infection

Conditions
-----------------
Urinary Tract Infections

Intervention / Treatment
-----------------
* Drug: Ceftaroline fosamil and NXL104 (q8h)
* Drug: Ceftaroline fosamil and NXL104 (q12h)
* Drug: Doripenem
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ceftaroline fosamil and NXL104 (q8h)<br> | Drug: Ceftaroline fosamil and NXL104 (q8h)<br>* 600 mg ceftaroline fosamil/600 mg NXL104 IV coadministered every 8 hours (q8h);<br>* Other names: Ceftaroline fosamil and Avibactam(NXL104) (q8h);Drug: Placebo<br>* On CXL-MD-02, there were (3) treatment arms (meaning a subject could be randomized to 1 of 3 possible treatment regimens). Each treatment arm contained 1 or 2 placebo doses of IV saline in order to preserve the blind.<br>* Other names: placebo (saline);|
| Experimental: Ceftaroline fosamil and NXL104 (q12h)<br> | Drug: Ceftaroline fosamil and NXL104 (q12h)<br>* 600 mg ceftaroline fosamil/600 mg NXL104 IV coadministered every 12 hours (q12h);<br>* Other names: Ceftaroline fosamil and Avibactam(NXL104) (q12h);Drug: Placebo<br>* On CXL-MD-02, there were (3) treatment arms (meaning a subject could be randomized to 1 of 3 possible treatment regimens). Each treatment arm contained 1 or 2 placebo doses of IV saline in order to preserve the blind.<br>* Other names: placebo (saline);|
| Active Comparator: Doripenem<br> | Drug: Doripenem<br>* 500 mg doripenem IV q8h;<br>Drug: Placebo<br>* On CXL-MD-02, there were (3) treatment arms (meaning a subject could be randomized to 1 of 3 possible treatment regimens). Each treatment arm contained 1 or 2 placebo doses of IV saline in order to preserve the blind.<br>* Other names: placebo (saline);|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Microbiological response of Microbiologically Evaluable (ME) at Test of Cure (TOC) | 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) | 5 to 11 days after last dose of study drug | 
| Evaluate safety | 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. | 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) | 

Secondary Outcome Measures

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

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
complicated Urinary Tract Infection, Acute Pyelonephritis