Complicated Urinary tract Infection including Pyelonephritis MedDRA version: 9.1 Level: LLT Classification code 10037596 Term: Pyelonephritis MedDRA version: 9.1 Level: LLT Classification code 10046571 Term: Urinary tract infection MedDRA version: 9.1 Level: LLT Classification code 10054088 Term: Urinary tract infection bacterial MedDRA version: 9.1 Level: LLT Classification code 10062279 Term: Urinary tract infection pseudomonal
Conditions
Interventions
Product Name: CXA-101
Product Code: CXA-101
Pharmaceutical Form: Powder for infusion*
CAS Number: 936111-69-2
Current Sponsor code: CXA-101
Other descriptive name: FR264205
Concentration unit: mg mill
Sponsors
Calixa Therapeutics Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects are each required to meet the following inclusion criteria: 1. Males and females 18 to 90 years of age, inclusive. Females of childbearing potential must have a documented negative serum pregnancy test and be using a highly effective method of birth control. 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. 4. Have a pretreatment baseline urine culture specimen obtained within two calendar days before the start of administration of the first dose of study drug NOTE: Subjects may be enrolled in this study and start IV study drug therapy before the Investigator knows the results of the baseline urine culture. 5. Require IV antibacterial therapy for the treatment of the presumed cUTI 6. Provide written informed consent. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Subjects must each NOT meet any of the following exclusion criteria: 1. Documented history of any hypersensitivity or allergic reaction to any ß-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. Receipt of any amount of potentially therapeutic antibacterial therapy after collection of the pretreatment baseline urine culture and before administration of the first dose of study drug 4. Receipt of more than one dose of a potentially therapeutic antibacterial agent for the treatment of the current UTI within 96 hours before obtaining the study- qualifying pretreatment baseline urine NOTE: Subjects receiving UTI prophylaxis are eligible to enroll if all other eligibility criteria are met, including obtaining a study-qualifying pretreatment baseline urine culture (see Section 7.3) 5. Intractable infection anticipated to require more than 10 days of study drug therapy 6. Complete, permanent obstruction of the urinary tract 7. Confirmed (at time of randomization) fungal urinary tract infection (with = 103 fungal CFU/mL) 8. Permanent indwelling bladder catheter or instrumentation including nephrostomy 9. Suspected or confirmed perinephric or intrarenal abscess 10. Suspected or confirmed prostatitis 11. Known ileal loop or vesico-ureteral reflux 12. Moderate or severe impairment of renal function including a estimated CrCl < 50 mL/min, requirement for peritoneal dialysis, hemodialysis or hemofiltration, or oliguria (< 20 mL/h urine output over 24 hours) 13. Current urinary catheter that will not be removed (Intermittent straight catheterization during the IV study drug administration period is acceptable) 14. Any condition or circumstance that, in the opinion of the Investigator, would compromise the safety of the subject or the quality of study data 15. Any rapidly progressing disease or immediately life-threatening illness including acute hepatic failure, respiratory failure, and septic shock 16. Immunocompromising condition, including known infection with human immunodeficiency virus (HIV), AIDS, hematological malignancy, or bone marrow transplantation, or immunosuppressive therapy including cancer chemotherapy, medications for prevention of organ transplantation rejection, or the administration of corticosteroids equivalent to or greater than 40 mg of prednisone per day administered for more than 14 days preceding randomization 17. One or more of the following laboratory abnormalities in baseline specimens: AST, ALT, or alkaline phosphatase level greater than 3 times the upper limit of normal (ULN), total bilirubin greater than 2 times ULN, absolute neutrophil count less than 1000/µL, platelet count less than 50,000/µL, or hematocrit less than 25% 18. Clinically significant abnormality in baseline ECG 19. Participation within the last 30 days in any clinical study of an investigational product 20. Previous participation in any study of CXA 101 21. Women who are pregnant or nursing
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Determine the microbiological response at 6 to 9 days after treatment in subjects with complicated Urinary Tract Infection (cUTI) including pyelonephritis following a 7- to 10-day treatment regimen.;Secondary Objective: - Evaluate the safety of CXA 101 in subjects with cUTI including pyelonephritis; - Determine the clinical response at 6 to 9 days after treatment in subjects with cUTI including pyelonephritis following a 7- to 10-day treatment regimen; - Evaluate the population plasma PK profile in subjects with cUTI. ;Primary end point(s): The primary outcome measure is the per-subject microbiological response at the Test of Cure (TOC) visit in the microbiologically evaluable (ME) and microbiological modified intent-to-treat (mMITT) populations. The Intent-to-Treat (ITT) Population will consist of all randomized subjects The Modified Intent-to-Treat Population (MITT) Population is the same as the ITT Population and consists of all randomized subjects who receive any amount of study drug. The Microbiological Modified Intent-to-treat (mMITT) Population will be a subset of the MITT Population and include subjects who have at least one acceptable causative pathogen from a study-qualifying pretreatment baseline urine specimen or a blood culture. The ME Population will be a subset of the mMITT Population and will include subjects who meet all the following conditions: • Met the minimal disease criteria (defined by inclusion criterion 2); • Had no protocol deviation likely to impact the microbiological outcome, including receiving a confounding non-study antibacterial agent. A confounding nonstudy antibacterial agent is one, with potential activity against the subject’s baseline uropathogen and that was given systemically at any time from the time of the study-qualifying baseline culture through the TOC visit. • Received an appropriate duration of study drug therapy or was classified as an evaluable microbiologic failure after completing at least 3 | — |
Countries
Belgium, Czech Republic, Germany, Poland
Outcome results
None listed