Study Comparing the Safety and Efficacy of Intravenous CXA-201 and Intravenous Levofloxacin in Complicated Urinary Tract Infection, Including Pyelonephritis

• Register: ClinicalTrials.gov
• Last refreshed on: 28 January 2013
• Main ID: NCT01345955
• Date of registration: 28/04/2011
• Primary sponsor: Cubist Pharmaceuticals
• Public title: Study Comparing the Safety and Efficacy of Intravenous CXA-201 and Intravenous Levofloxacin in Complicated Urinary Tract Infection, Including Pyelonephritis
• Scientific title: A Multicenter, Double-Blind, Randomized, Phase 3 Study to Compare the Safety and Efficacy of Intravenous CXA-201 and Intravenous Levofloxacin in Complicated Urinary Tract Infection, Including Pyelonephritis
• Date of first enrolment: June 2011
• Target sample size: 776
• Recruitment status: Recruiting
• URL: http://clinicaltrials.gov/show/NCT01345955
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Countries of recruitment

Bulgaria, Chile, Croatia, India, Korea, Republic of, Peru, Poland, Russian Federation, Slovenia, Spain, Ukraine, United States

Contacts

• Name: Thomas Feinberg

• Name: Obiamiwe Umeh, M.D., MSc.
• Affiliation: Cubist Pharmaceuticals

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Provide written informed consent prior to any study-related procedure not part of
normal medical care (a legally acceptable representative may provide consent if the
subject is unable to do so, provided this is approved by local country and
institution specific guidelines).

2. Be males or females = 18 years of age

3. If female, subject is non-lactating, and is either:

1. Not of childbearing potential, defined as postmenopausal for at least 1 year or
surgically sterile due to bilateral tubal ligation, bilateral oophorectomy, or
hysterectomy; or

2. Of childbearing potential and is practicing a barrier method of birth control
(e.g., a diaphragm or contraceptive sponge) along with 1 of the following
methods: oral or parenteral contraceptives (for 3 months prior to study drug
administration), or a vasectomized partner. Or, subject is practicing abstinence
from sexual intercourse. Subjects must be willing to practice these methods for
the duration of the trial and for at least 35 days after last dose of study
medication.

4. Males are required to practice reliable birth control methods (condom or other
barrier device) during the conduct of the study and for at least 35 days after last
dose of study medication.

5. Pyuria (white blood cell [WBC] count > 10/µL in unspun urine or = 10 per high power
field in spun urine).

6. Clinical signs and/or symptoms of cUTI, either of:

1. Pyelonephritis, as indicated by at least 2 of the following:

- Documented fever (oral temperature > 38°C) accompanied by patient symptoms
of rigors, chills, or "warmth";

- Flank pain;

- Costovertebral angle tenderness or suprapubic tenderness on physical exam;
or

- nausea or vomiting; OR

2. Complicated lower UTI, as indicated by at least 2 of the following:

- At least 2 of the following new or worsening symptoms of cUTI:

- Dysuria; urinary frequency or urinary urgency;

- Documented fever (oral temperature > 38°C) accompanied by patient
symptoms of rigors, chills, or "warmth";

- Suprapubic pain or flank pain;

- Costovertebral angle tenderness or suprapubic tenderness on physical
exam; or

- Nausea or vomiting; plus,

- At least 1 of the following complicating factors:

- Males with documented history of urinary retention;

- Indwelling urinary catheter that is scheduled to be removed during IV
study therapy and before the EOT;

- Current obstructive uropathy that is scheduled to be medically or
surgically relieved during IV study therapy and before the EOT; or

- Any functional or anatomical abnormality of the urogenital tract
(including anatomic malformations or neurogenic bladder) with voiding
disturbance resulting in at least 100 mL residual urine.

7. Have a pretreatment baseline urine culture specimen obtained within 24 hours 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.

8. Require IV antibacterial therapy for the treatment of the presumed cUTI.

Exclusion Criteria:

1. Have a documented history of any moderate or severe hypersensitivity or allergic
reaction to any ß-lactam or quinilone antibacterial (Note: for ß-lactams, a history
of a mild rash followed by uneventful re-exposure is not a contraindication to
enrollment)

2. Have a concomitant infection at the time of randomization, which requires non-study
systemic antibacterial therapy in addition to IV study drug therapy. (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 any dose of a potentially therapeutic antibacterial agent for the
treatment of the current UTI within 48 hours before the study-qualifying pretreatment
baseline urine is obtained (exceptions: subjects with an active cUTI who have
received prior antibiotics may be enrolled provided a minimum of 48 hours have
elapsed between the last dose of the prior antibiotic and the time of obtaining the
baseline urine specimen. Subjects receiving current antibiotic prophylaxis for cUTI
who present with signs and symptoms consistent with an active new cUTI may be
enrolled provided all other eligibility criteria are met including obtaining a
pre-treatment qualifying baseline urine culture).

5. Intractable urinary infection at baseline that the Investigator anticipates would
require more than 7 days of study drug therapy.

6. Complete, permanent obstruction of the urinary tract.

7. Confirmed fungal urinary tract infection at time of randomization (with = 103 fungal
CFU/mL).

8. Permanent indwelling bladder catheter or urinary stent including nephrostomy.

9. Suspected or confirmed perinephric or intrarenal abscess.

10. Suspected or confirmed prostatitis.

11. Ileal loop or known vesico-ureteral reflux.

12. Severe impairment of renal function including an estimated CrCl < 30 mL/min,
requirement for peritoneal dialysis, hemodialysis or hemofiltration, or oliguria (<
20 mL/h urine output over 24 hours).

13. Current urinary catheter that is not scheduled to be removed before the EOT
(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 established 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 continuously for mo


Age minimum: 18 Years
Age maximum: N/A
Gender: Both

Health Condition(s) or Problem(s) studied

Complicated Urinary Tract Infection

Pyelonephritis

Intervention(s)

Drug: CXA-201

Drug: Levofloxacin

Primary Outcome(s)

The proportion of subjects who have both a per-subject microbiological outcome of eradication and a clinical outcome of cure. [Time Frame: Test of Cure Visit (7 Days [± 2 days] after completion of study drug administration)]

Secondary Outcome(s)

For each unique pathogen, the number and percentage of subjects in each treatment group recorded as a microbiologic eradication or persistence for that particular pathogen. [Time Frame: Late Follow Up (28-35 Days after completion of study drug administration)]

Safety will be evaluated in the safety population by presenting summaries of AEs, laboratory evaluations, vital signs, and physical examinations in the 2 treatment groups. [Time Frame: All study visits through the Late Follow Up (28-35 Days after completion of study drug administration)]

The number and percentage of subjects in each treatment group recorded as a clinical cure or failure or indeterminate. [Time Frame: Multiple visits up until the Late Follow Up (28-35 Days after completion of study drug administration)]

The number and percentage of subjects in each treatment group recorded as a microbiological eradication or persistence or indeterminate. [Time Frame: Multiple visits up until the Late Follow Up (28-35 Days after completion of study drug administration)]

Secondary ID(s)

CXA-cUTI-10-05

Source(s) of Monetary Support

Please refer to primary and secondary sponsors