Complicated Urinary Tract Infection
Conditions
Keywords
Complicated Urinary Tract Infection, Pyelonephritis, Antimicrobial, Cephalosporin, Intravenous
Brief summary
The purpose of this study is to evaluate the safety and efficacy of intravenous CXA 101 and comparator in complicated urinary tract infection
Detailed description
This is a Phase 2, multicenter, prospective, randomized, double-blind, comparative efficacy and safety study of IV CXA 101 versus IV ceftazidime for 7 to 10 days. Subjects are followed up 6 to 9 days after the last dose of study drug to assess clinical signs and symptoms of infection. A Late Follow Up evaluation (21 to 28 days after the last dose of study drug) occurs for those subjects who respond to therapy. The primary assessment of effectiveness is the microbiological response (the eradication at post-therapy of the infectious organism identified at the start of study). An additional assessment of efficacy includes the overall clinical response, which is described as cured, improved, or failed. Safety assessments include the incidence of adverse events throughout the study, clinical laboratory tests (hematology, serum chemistry, and urinalysis) and physical examinations at the start of the study and post-therapy.
Interventions
DRUGCXA-101
intravenous
DRUGCeftazidime
intravenous
Sponsors
Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
1. Males and females 18 to 90 years of age, inclusive. 2. Pyuria (white blood cell \[WBC\] count \> 10/µL in unspun urine or ≥ 10 per high power field in spun urine) 3. Clinical signs and/or symptoms of cUTI, either of: a. Pyelonephritis, as indicated by both of the following: i. Fever (oral temperature ≥ 37.8°C); ii. Flank pain or costovertebral angle tenderness; OR b. Complicated lower UTI, as indicated by both of the following: i. At least one of the following new or worsening symptoms: * Dysuria; * Frequency; * Suprapubic pain; * Urgency ii. At least one of the following complicating factors: * Male gender; * Current bladder instrumentation or indwelling urinary catheter that is expected to be removed during the course of IV study drug administration; * Obstructive uropathy that is expected to be medically or surgically treated during the course of IV study drug administration; * Urogenital surgery within 7 days preceding administration of the first dose of study drug; * Functional or anatomical abnormality of the urogenital tract including anatomic malformations or neurogenic bladder with voiding disturbance of at least 100 mL residual urine.
Exclusion criteria
1. Documented history of any hypersensitivity or allergic reaction to any β-lactam antibacterial 2. Concomitant infection requiring systemic antibacterial therapy in addition to IV study drug therapy at the time of randomization. Drugs with only gram-positive activity (e.g. vancomycin, linezolid) are allowed 3. Complete, permanent obstruction of the urinary tract 4. Confirmed (at time of randomization) fungal urinary tract infection (with ≥ 103 fungal CFU/mL) 5. Suspected or confirmed perinephric or intrarenal abscess 6. Suspected or confirmed prostatitis 7. Known ileal loop or vesico-ureteral reflux 8. Women who are pregnant or nursing
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Microbiological Response at the Test of Cure (TOC) Visit in the Microbiological Modified Intent-to-Treat (mMITT) Population | TOC; 6-9 days after last study drug administration | Microbiological response is eradication for each baseline pathogen |
| Microbiological Response at the TOC Visit in the Microbiologically Evaluable (ME) Population. | TOC; 6-9 days after last study drug administration | Microbiological response is eradication for each baseline pathogen |
Countries
Germany, Poland, United States
Participant flow
Pre-assignment details
Two subjects, one in each arm, did not receive treatment.
Participants by arm
| Arm | Count |
|---|---|
| CXA-101 CXA-101: intravenous 1000 mg every 8 hours | 85 |
| Ceftazidime Ceftazidime: intravenous 1000 mg every 8 hours | 42 |
| Total | 127 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 2 | 0 |
| Overall Study | Received concomittant therapy | 2 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 3 |
Baseline characteristics
| Characteristic | CXA-101 | Ceftazidime | Total |
|---|---|---|---|
| Age, Continuous | 56.8 years STANDARD_DEVIATION 19.78 | 62.7 years STANDARD_DEVIATION 19.74 | 58.8 years STANDARD_DEVIATION 19.88 |
| Sex: Female, Male Female | 42 Participants | 16 Participants | 58 Participants |
| Sex: Female, Male Male | 43 Participants | 26 Participants | 69 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 33 / 85 | 16 / 42 |
| serious Total, serious adverse events | 1 / 85 | 0 / 42 |
Outcome results
Primary
Microbiological Response at the Test of Cure (TOC) Visit in the Microbiological Modified Intent-to-Treat (mMITT) Population
Microbiological response is eradication for each baseline pathogen
Time frame: TOC; 6-9 days after last study drug administration
Population: mMITT: Treated patients, with baseline pathogen.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CXA-101 | Microbiological Response at the Test of Cure (TOC) Visit in the Microbiological Modified Intent-to-Treat (mMITT) Population | 83.1 percentage of patients |
| Ceftazidime | Microbiological Response at the Test of Cure (TOC) Visit in the Microbiological Modified Intent-to-Treat (mMITT) Population | 76.3 percentage of patients |
Primary
Microbiological Response at the TOC Visit in the Microbiologically Evaluable (ME) Population.
Microbiological response is eradication for each baseline pathogen
Time frame: TOC; 6-9 days after last study drug administration
Population: ME: Treated patients, with baseline pathogen, complied with protocol.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CXA-101 | Microbiological Response at the TOC Visit in the Microbiologically Evaluable (ME) Population. | 85.5 percentage of patients |
| Ceftazidime | Microbiological Response at the TOC Visit in the Microbiologically Evaluable (ME) Population. | 92.6 percentage of patients |