Efficacy and Safety Study of Eravacycline Compared With Levofloxacin in Complicated Urinary Tract Infections

Conditions: Complicated urinary tract Infections
MedDRA version: 16.1Level: LLTClassification code 10046576Term: Urinary tract infection, site not specifiedSystem Organ Class: 100000004862
Therapeutic area: Diseases [C] - Bacterial Infections and Mycoses [C01]

Registration Number: EUCTR2013-004556-38-IT

Lead Sponsor: Tetraphase Pharmaceuticals, Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 840

Inclusion Criteria

1. Male and female subjects with either:
a. Pyelonephritis and normal urinary tract anatomy (no more than 30% of the total population), OR
b. cUTI with at least one of the following conditions associated with a risk for developing cUTI:
i. Indwelling urinary catheter
ii. Urinary retention (approximately 100 mL of residual urine after voiding)
iii. Neurogenic bladder
iv. Partial obstructive uropathy (eg, nephrolithiasis, bladder stones, and ureteral strictures)
v. Azotemia of renal origin (not CHF or volume related) such that the serum BUN is elevated (> 20 mg/dL) AND the serum BUN:creatinine ratio is < 15
vi. Surgically modified or abnormal urinary tract anatomy (eg, bladder diverticula, redundant urine collection system, etc.) EXCEPT surgery within the last month
2. At least 18 years of age (and not over 65 years of age for subjects in India)
3. Able to provide informed consent
4. At least two of the following signs or symptoms:
a. Chills, rigors, or warmth associated with fever (oral, rectal, tympanic, or by temporal artery temperature > 38°C) or hypothermia (oral, rectal, tympanic, or by temporal artery temperature < 35°C)
b. Flank pain (pyelonephritis) or pelvic pain (cUTI)
c. Nausea or vomiting
d. Dysuria, urinary frequency, or urinary urgency
e. Costo-vertebral angle tenderness on physical examination
5. Urine specimen with evidence of pyuria
a. Dipstick analysis positive for leukocyte esterase, OR
b. At least 10 white blood cells per cubic millimeter, OR
> 10 white blood cells cells per high power field AND = 2 epithelial cells per high power field
6. The following subjects who have received previous/ongoing antibiotics will be eligible for enrollment:
a. Subjects with cUTI and a known baseline pathogen who have received prior antibiotic therapy for a minimum of 72 hours, but who are deemed clinical and microbiological failures (> 10,000 CFU/mL)
b. Subjects with suspected acute cUTI who have received a single dose of effective non-study antibiotics for the acute cUTI in the previous 24 hours
7. Subjects must agree to use a highly reliable method of birth control
a. Male subjects must agree to use an effective barrier method of contraception during the study and for 30 days following the last dose if sexually active with a female of childbearing potential
b. Female subjects must not be pregnant or nursing. For females of childbearing potential, subjects must commit to either:
i. Use at least two medically accepted, effective methods of birth control (eg, condom, oral contraceptive, indwelling intrauterine device, hormonal implant /patch, injections, approved cervical ring, etc.) during study drug dosing and for 30 days following last study drug dose, OR
ii. Sexual abstinence
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 756
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 84

Exclusion Criteria

1. Concurrent use of non-study antibacterial drug therapy that would have a potential effect on outcome evaluations in subjects with cUTI, including:
a. Subjects with a history of a levofloxacin-resistant urinary tract infection
b. Likely to receive ongoing antibacterial drug prophylaxis prior to the LPT visit (eg, subjects with vesiculo-ureteral reflux)
2. Likelihood that the subject will not survive at least through the duration of the study (approximately 4 weeks)
3. Hypotension, systolic blood pressure = 90 mmHg
4. Complicated pyelonephritis with complete obstruction or known or suspected renal or perinephric abscess, emphysematous pyelonephritis, OR
Any condition likely to require surgery to achieve cure (this does NOT include procedure to place cathertors or obtain diagnosis)
5. Known or suspected urinary fungal infection
6. Uncomplicated lower urinary tract infections
7. Suspected or confirmed active prostatitis, or currently under treatment for prostatitis
8. Subjects with high risk for cUTI due to Pseudomonas sp. (eg, history of prior cUTIs due to Pseudomonas, = 20mg QD prednisone or equivalent steroid, and other risk factors as perceived by the investigator)
9. History of renal transplantation
10. Presence of an ileal loop
11. Any recent history of trauma to the pelvis or urinary tract
12. Indwelling urethral catheters present at screening expected to remain in place after therapy has been completed
13. Known concomitant HIV infection with CD4 counts below 200 cells/µL within the last six months, or an AIDS defining diagnosis within the last six months
14. Neutropenia (ANC < 1,000 PMNs/µL)
15. Creatinine clearance of < 50 mL/min as estimated by the Cockcroft-Gault equation (eCCr):
eCCr [mL/min]=((140-Age [yrs] ) × Body Weight [kg] × [0.85 if Female])/(72 × Serum Creatinine [mg/dL])
16. Presence or possible signs of significant hepatic disease:
a. Alanine aminotransferase or aspartate aminotransferase > 3 x ULN; > 5 x ULN for patients with hepatic abscess, OR
b. Total bilirubin > 3 x ULN, unless isolated hyperbilirubinemia is directly related to the acute process, OR
c. Alkaline phosphatase > 3 x ULN, OR
d. Subjects with diagnosis of hepatic failure
17. Participation in a study with an experimental drug within 30 days
18. Known or suspected hypersensitivity to tetracyclines or fluoroquinolones
19. Any other unstable or clinically significant concurrent medical condition (ie, immunosuppressive therapy, chemotherapy, or class IV heart or lung disease) that would, in the opinion of the investigator, jeopardize the safety of a subject and/or their compliance with the protocol

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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