Complicated Urinary Tract Infection
Conditions
Brief summary
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.
Interventions
DRUGNXL104/ceftazidime
125mg/500mg TID
4 x daily
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Microbiological Outcome at the Test of Cure (TOC) Visit | 5 to 9 days post-therapy | Eradication: a uropathogen found at entry at \>10\^5 CFU/mL was reduced to \<10\^4 CFU/mL |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Outcome in CE Patients at the TOC Visit | 5 to 9 days post-therapy | Cure: all or most pre-therapy signs and symptoms of the index infection had resolved and no additional antibiotic was required |
| Clinical Outcome in CE Patients at the Late Follow-up (LFU) Visit | 4 to 6 weeks post-therapy | Cure: all or most pre-therapy signs and symptoms of the index infection showed no evidence of resurgence and no additional antibiotic was required |
| Microbiological Outcome in ME Patients at the End of IV Therapy Visit | End of IV therapy (4 to 14 days) | Eradication: a uropathogen found at entry at \>10\^5 CFU/mL was reduced to \<10\^4 CFU/mL |
| Microbiological Outcome in ME Patients at the LFU Visit | 4 to 6 weeks post-therapy | Sustained eradication: a uropathogen found at entry at \>10\^5 CFU/mL remained \<10\^4 CFU/mL |
| Microbiological Outcome for the Urine Pathogen C. Koseri in ME Patients at the End of IV Therapy Visit | End of IV therapy (4 to 14 days) | Eradication: a uropathogen found at entry at \>10\^5 CFU/mL was reduced to \<10\^4 CFU/mL |
| Microbiological Outcome for the Urine Pathogen E. Cloacae in ME Patients at the End of IV Therapy Visit | End of IV therapy (4 to 14 days) | Eradication: a uropathogen found at entry at \>10\^5 CFU/mL was reduced to \<10\^4 CFU/mL |
| Microbiological Outcome for the Urine Pathogen E. Coli in ME Patients at the End of IV Therapy Visit | End of IV therapy (4 to 14 days) | Eradication: a uropathogen found at entry at \>10\^5 CFU/mL was reduced to \<10\^4 CFU/mL |
| Microbiological Outcome for the Urine Pathogen P. Mirabilis in ME Patients at the End of IV Therapy Visit | End of IV therapy (4 to 14 days) | Eradication: a uropathogen found at entry at \>10\^5 CFU/mL was reduced to \<10\^4 CFU/mL |
| Microbiological Outcome for the Urine Pathogen P. Aeruginosa in ME Patients at the End of IV Therapy Visit | End of IV therapy (4 to 14 days) | Eradication: a uropathogen found at entry at \>10\^5 CFU/mL was reduced to \<10\^4 CFU/mL |
| Clinical Outcome in Clinically Evaluable (CE) Patients at the End of Intravenous (IV) Therapy Visit | End of IV therapy (4 to 14 days) | Cure: all or most pre-therapy signs and symptoms of the index infection had resolved and no additional antibiotic was required |
| Microbiological Outcome for the Urine Pathogen E. Cloacae in ME Patients at the TOC Visit | 5 to 9 days post-therapy | Eradication: a uropathogen found at entry at \>10\^5 CFU/mL was reduced to \<10\^4 CFU/mL |
| Microbiological Outcome for the Urine Pathogen E. Coli in ME Patients at the TOC Visit | 5 to 9 days post-therapy | Eradication: a uropathogen found at entry at \>10\^5 CFU/mL was reduced to \<10\^4 CFU/mL |
| Microbiological Outcome for the Urine Pathogen P. Mirabilis in ME Patients at the TOC Visit | 5 to 9 days post-therapy | Eradication: a uropathogen found at entry at \>10\^5 CFU/mL was reduced to \<10\^4 CFU/mL |
| Microbiological Outcome for the Urine Pathogen P. Aeruginosa in ME Patients at the TOC Visit | 5 to 9 days post-therapy | Eradication: a uropathogen found at entry at \>10\^5 CFU/mL was reduced to \<10\^4 CFU/mL |
| Microbiological Outcome for the Urine Pathogen C. Koseri in ME Patients at the LFU Visit | 4 to 6 weeks post-therapy | Sustained eradication: a uropathogen found at entry at \>10\^5 CFU/mL remained \<10\^4 CFU/mL |
| Microbiological Outcome for the Urine Pathogen E. Coli in ME Patients at the LFU Visit | 4 to 6 weeks post-therapy | Sustained eradication: a uropathogen found at entry at \>10\^5 CFU/mL remained \<10\^4 CFU/mL |
| Microbiological Outcome for the Urine Pathogen P. Mirabilis in ME Patients at the LFU Visit | 4 to 6 weeks post-therapy | Sustained eradication: a uropathogen found at entry at \>10\^5 CFU/mL remained \<10\^4 CFU/mL |
| Microbiological Outcome for the Urine Pathogen P. Aeruginosa in ME Patients at the LFU Visit | 4 to 6 weeks post-therapy | Sustained eradication: a uropathogen found at entry at \>10\^5 CFU/mL remained \<10\^4 CFU/mL |
| Microbiological Outcome for the Urine Pathogen C. Koseri in ME Patients at the TOC Visit | 5 to 9 days post-therapy | Eradication: a uropathogen found at entry at \>10\^5 CFU/mL was reduced to \<10\^4 CFU/mL |
Countries
Jordan, Lebanon, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| NXL104/CAZ NXL104 125mg/Ceftazidime 500mg TID | 68 |
| Imipenem Cilastatin Imipenem cilastatin 500mg 4xdaily | 67 |
| Total | 135 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Did not meet inc/exc criteria | 13 | 11 |
| Overall Study | Lost to Follow-up | 2 | 3 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Social problem | 1 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | NXL104/CAZ | Imipenem Cilastatin | Total |
|---|---|---|---|
| Age, Continuous | 46.4 Years STANDARD_DEVIATION 18.24 | 49.9 Years STANDARD_DEVIATION 18.44 | 48.15 Years STANDARD_DEVIATION 18.34 |
| Sex: Female, Male Female | 51 Participants | 49 Participants | 100 Participants |
| Sex: Female, Male Male | 17 Participants | 18 Participants | 35 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 30 / 68 | 33 / 67 |
| serious Total, serious adverse events | 6 / 68 | 2 / 67 |
Outcome results
Primary
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
Time frame: 5 to 9 days post-therapy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NXL104/CAZ | Number of Participants With Microbiological Outcome at the Test of Cure (TOC) Visit | 19 Participants |
| Imipenem Cilastatin | Number of Participants With Microbiological Outcome at the Test of Cure (TOC) Visit | 25 Participants |
Secondary
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
Time frame: 4 to 6 weeks post-therapy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NXL104/CAZ | Clinical Outcome in CE Patients at the Late Follow-up (LFU) Visit | 20 Participants |
| Imipenem Cilastatin | Clinical Outcome in CE Patients at the Late Follow-up (LFU) Visit | 24 Participants |
Secondary
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
Time frame: 5 to 9 days post-therapy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NXL104/CAZ | Clinical Outcome in CE Patients at the TOC Visit | 24 Participants |
| Imipenem Cilastatin | Clinical Outcome in CE Patients at the TOC Visit | 29 Participants |
Secondary
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
Time frame: End of IV therapy (4 to 14 days)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NXL104/CAZ | Clinical Outcome in Clinically Evaluable (CE) Patients at the End of Intravenous (IV) Therapy Visit | 28 Participants |
| Imipenem Cilastatin | Clinical Outcome in Clinically Evaluable (CE) Patients at the End of Intravenous (IV) Therapy Visit | 36 Participants |
Secondary
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
Time frame: End of IV therapy (4 to 14 days)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NXL104/CAZ | Microbiological Outcome for the Urine Pathogen C. Koseri in ME Patients at the End of IV Therapy Visit | 1 Participants |
| Imipenem Cilastatin | Microbiological Outcome for the Urine Pathogen C. Koseri in ME Patients at the End of IV Therapy Visit | 0 Participants |
Secondary
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
Time frame: 4 to 6 weeks post-therapy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NXL104/CAZ | Microbiological Outcome for the Urine Pathogen C. Koseri in ME Patients at the LFU Visit | 1 Participants |
| Imipenem Cilastatin | Microbiological Outcome for the Urine Pathogen C. Koseri in ME Patients at the LFU Visit | 0 Participants |
Secondary
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
Time frame: 5 to 9 days post-therapy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NXL104/CAZ | Microbiological Outcome for the Urine Pathogen C. Koseri in ME Patients at the TOC Visit | 1 Participants |
| Imipenem Cilastatin | Microbiological Outcome for the Urine Pathogen C. Koseri in ME Patients at the TOC Visit | 0 Participants |
Secondary
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
Time frame: End of IV therapy (4 to 14 days)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NXL104/CAZ | Microbiological Outcome for the Urine Pathogen E. Cloacae in ME Patients at the End of IV Therapy Visit | 0 Participants |
| Imipenem Cilastatin | Microbiological Outcome for the Urine Pathogen E. Cloacae in ME Patients at the End of IV Therapy Visit | 1 Participants |
Secondary
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
Time frame: 5 to 9 days post-therapy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NXL104/CAZ | Microbiological Outcome for the Urine Pathogen E. Cloacae in ME Patients at the TOC Visit | 0 Participants |
| Imipenem Cilastatin | Microbiological Outcome for the Urine Pathogen E. Cloacae in ME Patients at the TOC Visit | 1 Participants |
Secondary
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
Time frame: End of IV therapy (4 to 14 days)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NXL104/CAZ | Microbiological Outcome for the Urine Pathogen E. Coli in ME Patients at the End of IV Therapy Visit | 24 Participants |
| Imipenem Cilastatin | Microbiological Outcome for the Urine Pathogen E. Coli in ME Patients at the End of IV Therapy Visit | 32 Participants |
Secondary
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
Time frame: 4 to 6 weeks post-therapy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NXL104/CAZ | Microbiological Outcome for the Urine Pathogen E. Coli in ME Patients at the LFU Visit | 15 Participants |
| Imipenem Cilastatin | Microbiological Outcome for the Urine Pathogen E. Coli in ME Patients at the LFU Visit | 17 Participants |
Secondary
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
Time frame: 5 to 9 days post-therapy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NXL104/CAZ | Microbiological Outcome for the Urine Pathogen E. Coli in ME Patients at the TOC Visit | 19 Participants |
| Imipenem Cilastatin | Microbiological Outcome for the Urine Pathogen E. Coli in ME Patients at the TOC Visit | 23 Participants |
Secondary
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
Time frame: End of IV therapy (4 to 14 days)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NXL104/CAZ | Microbiological Outcome for the Urine Pathogen P. Aeruginosa in ME Patients at the End of IV Therapy Visit | 1 Participants |
| Imipenem Cilastatin | Microbiological Outcome for the Urine Pathogen P. Aeruginosa in ME Patients at the End of IV Therapy Visit | 0 Participants |
Secondary
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
Time frame: 4 to 6 weeks post-therapy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NXL104/CAZ | Microbiological Outcome for the Urine Pathogen P. Aeruginosa in ME Patients at the LFU Visit | 0 Participants |
| Imipenem Cilastatin | Microbiological Outcome for the Urine Pathogen P. Aeruginosa in ME Patients at the LFU Visit | 0 Participants |
Secondary
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
Time frame: 5 to 9 days post-therapy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NXL104/CAZ | Microbiological Outcome for the Urine Pathogen P. Aeruginosa in ME Patients at the TOC Visit | 0 Participants |
| Imipenem Cilastatin | Microbiological Outcome for the Urine Pathogen P. Aeruginosa in ME Patients at the TOC Visit | 0 Participants |
Secondary
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
Time frame: End of IV therapy (4 to 14 days)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NXL104/CAZ | Microbiological Outcome for the Urine Pathogen P. Mirabilis in ME Patients at the End of IV Therapy Visit | 0 Participants |
| Imipenem Cilastatin | Microbiological Outcome for the Urine Pathogen P. Mirabilis in ME Patients at the End of IV Therapy Visit | 1 Participants |
Secondary
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
Time frame: 4 to 6 weeks post-therapy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NXL104/CAZ | Microbiological Outcome for the Urine Pathogen P. Mirabilis in ME Patients at the LFU Visit | 0 Participants |
| Imipenem Cilastatin | Microbiological Outcome for the Urine Pathogen P. Mirabilis in ME Patients at the LFU Visit | 1 Participants |
Secondary
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
Time frame: 5 to 9 days post-therapy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NXL104/CAZ | Microbiological Outcome for the Urine Pathogen P. Mirabilis in ME Patients at the TOC Visit | 0 Participants |
| Imipenem Cilastatin | Microbiological Outcome for the Urine Pathogen P. Mirabilis in ME Patients at the TOC Visit | 1 Participants |
Secondary
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
Time frame: End of IV therapy (4 to 14 days)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NXL104/CAZ | Microbiological Outcome in ME Patients at the End of IV Therapy Visit | 25 Participants |
| Imipenem Cilastatin | Microbiological Outcome in ME Patients at the End of IV Therapy Visit | 34 Participants |
Secondary
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
Time frame: 4 to 6 weeks post-therapy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NXL104/CAZ | Microbiological Outcome in ME Patients at the LFU Visit | 15 Participants |
| Imipenem Cilastatin | Microbiological Outcome in ME Patients at the LFU Visit | 18 Participants |