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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Cubist Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01345955
First received: April 28, 2011
Last updated: July 10, 2013
Last verified: July 2013
  Purpose

This is a Phase 3, multicenter, prospective, randomized, double-blind, double dummy study of CXA 201 IV infusions (1500 mg q8h) versus levofloxacin IV infusions (750 mg qd) for the treatment of adults with a cUTI (including pyelonephritis).


Condition Intervention Phase
Complicated Urinary Tract Infection
Pyelonephritis
Drug: CXA-201
Drug: Levofloxacin
Phase 3

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
Official 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

Resource links provided by NLM:


Further study details as provided by Cubist Pharmaceuticals:

Primary Outcome Measures:
  • 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) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: Yes ]

Enrollment: 525
Study Start Date: June 2011
Study Completion Date: May 2013
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: CXA-201 as treatment for cUTI
CXA-201 IV infusion (1500mg q8) for 7 days
Drug: CXA-201
CXA-201 IV infusion (1500mg q8) for 7 days
Active Comparator: Levofloxacin as treatment for cUTI
Levofloxacin IV infusion (750mg qd) for 7 days
Drug: Levofloxacin
Levofloxacin IV infusion (750mg qd) for 7 days

Detailed Description:

Approximately 500 subjects will be enrolled into this study and randomized 1:1 to receive CXA-201 or comparator (levofloxacin) resulting in 250 subjects per treatment arm. Subject participation will require a minimum commitment of 35 days and a maximum of 42 days. Subjects will be hospitalized for the administration of all doses of IV study therapy. A test of cure visit will occur at 7 days after the last dose of study drug and a late follow-up evaluation or contact will occur a minimum of 28 days and a maximum of 35 days after the last dose of study drug.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 β-lactam or quinilone antibacterial (Note: for β-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 more than 14 days preceding randomization.
  17. One or more of the following laboratory abnormalities in baseline specimens: aspartate aminotransferase (AST [SGOT]), alanine aminotransferase (ALT [SGPT]), alkaline phosphatase, or total bilirubin level greater than 3 times the upper limit of normal (ULN), absolute neutrophil count less than 500/μL, platelet count less than 40,000/μL, or hematocrit less than 20%.
  18. Participation in any clinical study of an investigational product within 30 days prior to the proposed first day of study drug.
  19. Previous participation in any study of CXA-101 or CXA-201.
  20. Women who are pregnant or nursing.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01345955

  Show 62 Study Locations
Sponsors and Collaborators
Cubist Pharmaceuticals
Investigators
Study Director: Obiamiwe Umeh, M.D., MSc. Cubist Pharmaceuticals
  More Information

No publications provided

Responsible Party: Cubist Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01345955     History of Changes
Other Study ID Numbers: CXA-cUTI-10-05
Study First Received: April 28, 2011
Last Updated: July 10, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Cubist Pharmaceuticals:
cUTI

Additional relevant MeSH terms:
Communicable Diseases
Infection
Pyelonephritis
Urinary Tract Infections
Kidney Diseases
Nephritis
Nephritis, Interstitial
Pyelitis
Urologic Diseases
Levofloxacin
Ofloxacin
Anti-Bacterial Agents
Anti-Infective Agents
Anti-Infective Agents, Urinary
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Renal Agents
Therapeutic Uses
Topoisomerase II Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on November 27, 2014