Complicated Urinary Tract Infection MedDRA version: 14.1 Level: PT Classification code 10054088 Term: Urinary tract infection bacterial System Organ Class: 10021881 - Infections and infestations
Conditions
Interventions
Product Name: Ceftaroline fosamil for injection
Pharmaceutical Form: Powder for solution for infusion
CAS Number: 229016-73-3
Current Sponsor code: ceftaroline fosamil
Other descriptive name: PPI-0903
Sponsors
Cerexa, Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female, at least 18 years of age. 2. Have pyuria, defined as = 10 white blood cells (WBCs) per mm3 in unspun urine or = 10 WBCs per high power field in spun urine. 3. A local urine Gram stain must demonstrate the presence of gram-negative bacilli. 4. Clinical signs and/or symptoms of cUTI defined as: a. Acute pyelonephritis, as indicated by BOTH of the following: i. Fever = 38.0ºC oral ii. Flank pain or costovertebral angle tenderness OR b. Complicated lower urinary tract infection, as indicated by at least one of the following symptoms AND at least one of the following complicating factors: i. Symptoms (at least one): • Dysuria • Frequency • Suprapubic pain • Urgency • Acute hematuria ii. Complicating factors (at least one): • Male gender • Current bladder instrumentation or indwelling urinary catheter (any tube, stent, or foreign body conduit that extends from the inside to the outside of the body) that is expected to be removed during the course of IV study drug administration • Obstructive uropathy (eg, nephrolithiasis, tumor, fibrosis) that is expected to be medically or surgically treated during the course of IV study drug administration • Urogenital surgery (eg, prostatectomy, transurethral resections) within 7 days prior to administration of the first dose of study drug • Functional or anatomical abnormality of the urogenital tract including anatomic malformations or neurogenic bladder, or with a postvoid residual urine volume of at least 100 mL 5. Have a pretreatment baseline urine culture specimen obtained within 48 hours before 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, but a local urine Gram stain must be performed and demonstrate the presence of gram-negative bacilli prior to start of study drug. 6. The subject’s infection would require initial treatment with IV antibiotics. 7. The subject must require initial hospitalization to manage the cUTI by the standard of care. 8. Female subjects of child-bearing potential, including those who are fewer than 2 years post-menopausal, must agree to, and comply with, using 2 highly effective methods of birth control (ie, condom plus spermicide, combined oral contraceptive, implant, injectable, indwelling intrauterine device, sexual abstinence, or a vasectomized partner) while participating in this study. In addition, all women of childbearing potential must agree to continue to use 2 forms of birth control throughout the study and for at least 30 days after administration of the last dose of study drug. 9. Signed informed consent, willingness, and ability to comply with all study procedures and restrictions. 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 143 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 72
Exclusion criteria
Exclusion criteria: 1. History of any hypersensitivity or allergic reaction to any ß-lactam (eg, cephalosporins, penicillins, carbapenems). 2. Requirement for concomitant systemic antibiotic or antifungal therapy for any reason. EXCEPTION: Topical antifungal or a single oral dose of any antifungal for treatment of vaginal candidiasis. 3. Known urinary tract infection or colonization with Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus, or any Enterococcus species. 4. The cUTI is known to be caused by a pathogen resistant to doripenem. 5. Confirmed fungal urinary tract infection with a colony count = 103 CFU/mL. 6. Receipt of any amount of potentially therapeutic antibiotic therapy after the collection of the pretreatment baseline urine culture and before administration of the first dose of study drug. 7. Receipt of more than 1 dose of a potentially therapeutic antibiotic agent for the treatment of the current cUTI within 96 hours before obtaining the study-qualifying pretreatment baseline urine culture. EXCEPTIONS: 1) Subjects who failed prior antibiotic treatment with a culture growing a pathogen resistant to the prior treatment; 2) Subjects receiving UTI prophylaxis are eligible to enroll if all other eligibility criteria are met, including obtaining a study-qualifying pretreatment baseline urine culture. These subjects must discontinue oral antibiotic prophylaxis from the time the pretreatment baseline urine culture is obtained until after TOC. 8. Intractable UTI anticipated to require more than 10 days of study drug therapy. 9. Complete, permanent obstruction of the urinary tract. 10. Permanent indwelling bladder catheter or instrumentation (including nephrostomy) or current urinary catheter that will not be removed during IV study drug administration. 11. Suspected or confirmed perinephric or intrarenal abscess. 12. Suspected or confirmed prostatitis. 13. Ileal loops or vesico-ureteral reflux. 14. Impairment of renal function including a calculated CrCl of 20 mg of prednisone (or equivalent systemic corticosteroid) per day 19. Probenecid administration within 3 day
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objectives of this study are to: • Determine the microbiological response in the Microbiologically Evaluable (ME) Population at Test-of-Cure (TOC). • Evaluate the safety of coadministered IV ceftaroline fosamil and NXL104 in subjects with cUTI.;Secondary Objective: Secondary objectives of this study include: • Determine the clinical response in the Clinically Evaluable (CE) Population at TOC. • Determine the microbiological and clinical responses in the microbiological Intent-to-Treat (mITT) Population at TOC. • Evaluate microbiological and clinical responses at End of Therapy (EOT) and at Late Follow-up (LFU). • Evaluate microbiological and clinical responses at TOC in subjects with complicated lower urinary tract infection (cLUTI) or acute pyelonephritis (AP). • Evaluate the pharmacokinetics of ceftaroline fosamil (prodrug), ceftaroline, ceftaroline M-1 (inactive metabolite), and NXL104 in subjects with cUTI.;Primary end point(s): Primary efficacy endpoint: Proportion of subjects with a favorable microbiological response in the ME Population at TOC.;Timepoint(s) of evaluation of this end point: The timing of the primary endpoint is TOC which occurs 5-11 days after the end of therapy. The study requires 7-10 days study drug administration. Therefore the timing of the primary endpoint is about 12-21 days after enrollment in the study. Note TOC could occur earlier if study drug is discontinued early. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Proportion of subjects with a clinical response of cure in the CE Population at TOC • Proportion of subjects with a favorable microbiological response in the mITT Population at TOC • Proportion of subjects with a clinical response of cure in the mITT Population at TOC • Proportion of subjects with a sustained favorable microbiological response in the ME Population at LFU • Proportion of subjects with a clinical response of sustained clinical cure in the CE Population at LFU • Proportion of subjects with a favorable microbiological response in the ME Population at TOC and the proportion of subjects with a clinical response of cure in the CE Population at TOC in subjects with cLUTI or AP • Per-pathogen outcome in the mITT and ME Populations at TOC • Proportion of subjects with a favorable microbiological response in the ME Population at EOT • Proportion of subjects with a clinical response of cure in the CE Population at EOT • Incidence of emergent infections;Timepoint(s) of evaluation of this end point: Secondary endpoints may occur at: End of Therapy (EOT) which occurs at the end of study drug administration and is 7-10 days after enrollment. Note, EOT could occur earlier if study drug is discontinued early. Test-of-cure (TOC) which is defined at E.5.1.1. Late Follow-up (LFU) which is 28-42 days after EOT therefore making this window 35-52 days after enrollment. Note LFU could occur earlier if study drug is discontinued early and EOT occurs earlier than 7-10 days after enrollment. | — |
Countries
Bulgaria, Germany, Lebanon, Poland, Russian Federation, Turkey, United States
Contacts
Public ContactDouglas Rank, MD
Cerexa, Inc.
Outcome results
None listed