A Multicenter, Phase 3 Study to Confirm the Safety and Efficacy of Intravenous Doripenem in Complicated Lower Urinary Tract Infection or Pyelonephritis

• Conditions: Complicated Lower Urinary Tract Infection or PyelonephritisMedDRA: Lower urinary tract infection or pyelonephritis (10024981 and/or 10059517); MedDRA version: 7.0Level: LLTClassification code 10024981

• Registration Number: EUCTR2004-004573-29-AT
• Lead Sponsor: Peninsula Pharmaceuticals, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2004-12-17
• Last Update Posted: 22 April 2013

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 220

Inclusion Criteria

Be males or females >18 years of age
Demonstrate clinical signs and/or symptoms of cUTI, either of:
a. Pyelonephritis, as indicated by all three of the following:
i.Fever (oral temperature =37.8°C)
ii.Flank pain or costovertebral angle tenderness
iii.Pyuria (>10 white blood cells [WBC] per µL in unspun urine or >10 WBC per high power field in spun urine)
OR
b. Complicated lower UTI, as indicated by all three of the following:
i.At least one of the following symptoms:
•Dysuria
•Frequency
•Suprapubic pain
•Urgency
ii.Pyuria (>10 WBC per µL in unspun urine or >10 WBC per high power field in spun urine)
iii.At least one of the following complicating factors:
•Male gender
•Current bladder instrumentation or indwelling urinary catheter that is anticipated to be removed during the course of IV study drug administration
•Obstructive uropathy that is anticipated to be medically or surgically treated during the course of IV study drug administration
•Urogenital surgery 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 with voiding disturbance of at least 100 mL residual urine
Have a study-qualifying pretreatment baseline urine culture specimen obtained within 48 hours prior to the start of administration of the first dose of study drug from which a bacterial uropathogen is isolated with a growth of =105 CFU/mL.
NOTE: Patients may be enrolled in this study and start IV study drug therapy prior to the investigator knowing the results of the baseline urine culture. However, if the final results of the baseline urine culture do not meet the definition of a study-qualifying pretreatment baseline urine culture, then the patient must be withdrawn from study drug therapy.
Require antibacterial therapy for the treatment of the presumed cUTI
Provide written informed consent. If the patient is unable to provide written informed consent, the patient’s legally accepted representative may provide written consent as approved by institution-specific guidelines.

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

1.Women who are pregnant, nursing or of child-bearing potential and not using a medically accepted, effective method of birth control (e.g., condom, hormonal contraceptive, indwelling intrauterine device, sexual abstinence)
2.History of moderate or severe hypersensitivity reactions to carbapenems, penicillins, other beta-lactam antibiotics or any quinolone (mild rash is not a contraindication to enrollment)
3.Complete, permanent obstruction of the urinary tract
4.Confirmed fungal urinary tract infection with a colony count =103 CFU/mL
5.Permanent indwelling bladder catheter or instrumentation including nephrostomy
6.Suspected or confirmed perinephric or intrarenal abscess
7.Suspected or confirmed prostatitis
8.Any rapidly progressing disease or immediately life-threatening illness including acute hepatic failure, respiratory failure and septic shock
9.Immunocompromising illness including known infection with human immunodeficiency virus (HIV), AIDS, hematological malignancy and bone marrow transplantation, or immunosuppressive therapy including cancer chemotherapy, medications for prevention of organ transplantation rejection, imuran and the administration of corticosteroids equivalent to or greater than 40 mg of prednisone per day administered for more than 14 days.
10.Severe impairment of renal function including a calculated creatinine clearance of <10 mL/min, requirement for peritoneal dialysis, hemodialysis or hemofiltration or oliguria (<20 cc urine output per hour over 24 hours)
11.One or more of the following laboratory abnormalities: aspartate aminotransferase, alanine aminotransferase, bilirubin or alkaline phosphatase levels >3 times the upper limit of normal (ULN), absolute neutrophil count of <500 per µL, platelet count of <40,000 per µL or hematocrit of <20%
12.Known ileal loops or vesico-ureteral reflux
13.Concomitant infection requiring systemic antibiotic or antifungal therapy in addition to IV study drug therapy at the time of assignment of a patient number. (Clarification: possible bacteremia with the presumed same urinary pathogen is acceptable)
14. Receipt of any amount of potentially therapeutic antimicrobial therapy after collection of the pretreatment baseline urine culture and before administration of the first dose of study drug
15. Receipt of any amount of potentially therapeutic antibiotic for the treatment of the current UTI within 96 hours prior to obtaining the study-qualifying pretreatment baseline urine. (Exception: patients 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 6.3])
16. Intractable infection anticipated to require more than 10 days of study drug therapy
17. Current urinary catheter that will not be removed or anticipation of urinary catheter placement that will not be removed during the course of IV study drug administration. (Clarification: Intermittent straight catheterization after the IV study drug administration period is acceptable.)
18. Known or suspected CNS disorder that may predispose to seizures or lower the seizure threshold (e.g. severe cerebral arteriosclerosis, epilepsy) or the presence of other risk factors that may predispose to seizures or lower the seizure threshold (e.g. certain drug therapy, renal dysfunction)
19.Participation in any study of an investigational drug or device within

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective of this study is to determine the microbiological response at 6-9 days post-therapy in patients with cUTI following a 10-day treatment regimen.<br><br>;Secondary Objective: Secondary objectives of this study are to:<br>• Determine the clinical response at 6-9 days post-therapy in patients with cUTI following a 10-day treatment regimen <br>• Evaluate the safety of doripenem in patients with cUTI;Primary end point(s): Primary:<br>• Microbiological response at the TOC visit in the microbiologically evaluable at TOC population<br>Secondary:<br>• Clinical response at the TOC visit in the clinically evaluable at TOC population