Comparative Study of NXL104/Ceftazidime Versus Comparator in Adults With Complicated Urinary Tract Infections

Study Overview
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Brief Summary
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The purpose of this study is to determine whether NXL104 plus ceftazidime is effective in the treatment of complicated urinary tract infections as compared to a comparator group.

Official Title
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Prospective, Multicenter, Investigator-blinded, Randomized, Comparative Study Estimate Safety, Tolerability, Efficacy of NXL104/Ceftazidime vs. Comparator Followed Appropriate Oral Therapy Treatment Complicated UTI Hosp Adults

Conditions
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Complicated Urinary Tract Infection

Intervention / Treatment
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* Drug: NXL104/ceftazidime
* Drug: Imipenem/Cilastatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Acute pyelonephritis or other complicated urinary tract infection due to gram negative pathogens Exclusion Criteria: ileal loops or vesicoureteral reflux complete obstruction of any portion of urinary tract, perinephric or intrarenal abscess. fungal urinary tract infection permanent indirect catheter or nephrostomy unless removed within 48 hours of study entry history hypersensitivity to study medication

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>NXL/104 ceftazidime | Drug: NXL104/ceftazidime<br>* 125mg/500mg TID<br>|
| Active Comparator: 2<br>comparator 4 x daily | Drug: Imipenem/Cilastatin<br>* 4 x daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Microbiological Outcome at the Test of Cure (TOC) Visit | Eradication: a uropathogen found at entry at >10^5 CFU/mL was reduced to <10^4 CFU/mL | 5 to 9 days post-therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Outcome in Clinically Evaluable (CE) Patients at the End of Intravenous (IV) Therapy Visit | Cure: all or most pre-therapy signs and symptoms of the index infection had resolved and no additional antibiotic was required | End of IV therapy (4 to 14 days) | 
| Clinical Outcome in CE Patients at the TOC Visit | Cure: all or most pre-therapy signs and symptoms of the index infection had resolved and no additional antibiotic was required | 5 to 9 days post-therapy | 
| Clinical Outcome in CE Patients at the Late Follow-up (LFU) Visit | Cure: all or most pre-therapy signs and symptoms of the index infection showed no evidence of resurgence and no additional antibiotic was required | 4 to 6 weeks post-therapy | 
| Microbiological Outcome in ME Patients at the End of IV Therapy Visit | Eradication: a uropathogen found at entry at >10^5 CFU/mL was reduced to <10^4 CFU/mL | End of IV therapy (4 to 14 days) | 
| Microbiological Outcome in ME Patients at the LFU Visit | Sustained eradication: a uropathogen found at entry at >10^5 CFU/mL remained <10^4 CFU/mL | 4 to 6 weeks post-therapy | 
| Microbiological Outcome for the Urine Pathogen C. Koseri in ME Patients at the End of IV Therapy Visit | Eradication: a uropathogen found at entry at >10^5 CFU/mL was reduced to <10^4 CFU/mL | End of IV therapy (4 to 14 days) | 
| Microbiological Outcome for the Urine Pathogen E. Cloacae in ME Patients at the End of IV Therapy Visit | Eradication: a uropathogen found at entry at >10^5 CFU/mL was reduced to <10^4 CFU/mL | End of IV therapy (4 to 14 days) | 
| Microbiological Outcome for the Urine Pathogen E. Coli in ME Patients at the End of IV Therapy Visit | Eradication: a uropathogen found at entry at >10^5 CFU/mL was reduced to <10^4 CFU/mL | End of IV therapy (4 to 14 days) | 
| Microbiological Outcome for the Urine Pathogen P. Mirabilis in ME Patients at the End of IV Therapy Visit | Eradication: a uropathogen found at entry at >10^5 CFU/mL was reduced to <10^4 CFU/mL | End of IV therapy (4 to 14 days) | 
| Microbiological Outcome for the Urine Pathogen P. Aeruginosa in ME Patients at the End of IV Therapy Visit | Eradication: a uropathogen found at entry at >10^5 CFU/mL was reduced to <10^4 CFU/mL | End of IV therapy (4 to 14 days) | 
| Microbiological Outcome for the Urine Pathogen C. Koseri in ME Patients at the TOC Visit | Eradication: a uropathogen found at entry at >10^5 CFU/mL was reduced to <10^4 CFU/mL | 5 to 9 days post-therapy | 
| Microbiological Outcome for the Urine Pathogen E. Cloacae in ME Patients at the TOC Visit | Eradication: a uropathogen found at entry at >10^5 CFU/mL was reduced to <10^4 CFU/mL | 5 to 9 days post-therapy | 
| Microbiological Outcome for the Urine Pathogen E. Coli in ME Patients at the TOC Visit | Eradication: a uropathogen found at entry at >10^5 CFU/mL was reduced to <10^4 CFU/mL | 5 to 9 days post-therapy | 
| Microbiological Outcome for the Urine Pathogen P. Mirabilis in ME Patients at the TOC Visit | Eradication: a uropathogen found at entry at >10^5 CFU/mL was reduced to <10^4 CFU/mL | 5 to 9 days post-therapy | 
| Microbiological Outcome for the Urine Pathogen P. Aeruginosa in ME Patients at the TOC Visit | Eradication: a uropathogen found at entry at >10^5 CFU/mL was reduced to <10^4 CFU/mL | 5 to 9 days post-therapy | 
| Microbiological Outcome for the Urine Pathogen C. Koseri in ME Patients at the LFU Visit | Sustained eradication: a uropathogen found at entry at >10^5 CFU/mL remained <10^4 CFU/mL | 4 to 6 weeks post-therapy | 
| Microbiological Outcome for the Urine Pathogen E. Coli in ME Patients at the LFU Visit | Sustained eradication: a uropathogen found at entry at >10^5 CFU/mL remained <10^4 CFU/mL | 4 to 6 weeks post-therapy | 
| Microbiological Outcome for the Urine Pathogen P. Mirabilis in ME Patients at the LFU Visit | Sustained eradication: a uropathogen found at entry at >10^5 CFU/mL remained <10^4 CFU/mL | 4 to 6 weeks post-therapy | 
| Microbiological Outcome for the Urine Pathogen P. Aeruginosa in ME Patients at the LFU Visit | Sustained eradication: a uropathogen found at entry at >10^5 CFU/mL remained <10^4 CFU/mL | 4 to 6 weeks post-therapy |