- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01345929
Study Comparing the Safety and Efficacy of Intravenous CXA-201 and Intravenous Levofloxacin in Complicated Urinary Tract Infection, Including Pyelonephritis
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
Study Overview
Status
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
-
-
-
Rio de Janeiro, Brazil
-
Sao Paulo, Brazil
-
-
Minas Gerais
-
Belo Horizonte, Minas Gerais, Brazil
-
-
Rio Grande De Sul
-
Porto Alegre, Rio Grande De Sul, Brazil
-
-
Santa Catarina
-
Joinville, Santa Catarina, Brazil
-
-
Sao Paulo
-
Campinas, Sao Paulo, Brazil
-
Sao Jose De Rio Preto, Sao Paulo, Brazil
-
-
-
-
-
Armenia, Colombia
-
Barranquilla, Colombia
-
Bogota, Colombia
-
-
Valle Del Cauca
-
Cali, Valle Del Cauca, Colombia
-
-
-
-
-
Kohtla-Jarve, Estonia
-
Tallinn, Estonia
-
Tartu, Estonia
-
-
-
-
-
Tbilsi, Georgia
-
-
-
-
Hessen
-
Giessen, Hessen, Germany
-
-
Schleswig-Holstein
-
Lubeck, Schleswig-Holstein, Germany
-
-
-
-
-
Budapest, Hungary
-
Tatabánya, Hungary
-
-
Borsod-Abauj-Zemplen
-
Miskolc, Borsod-Abauj-Zemplen, Hungary
-
-
Budapest
-
Gyor, Budapest, Hungary
-
-
Csongrad
-
Szentes, Csongrad, Hungary
-
-
Gyor-moson-sopron
-
Sopron, Gyor-moson-sopron, Hungary
-
-
Nograd
-
Salgotarjan, Nograd, Hungary
-
-
Szabolcs-Szatmar-Bereg
-
Nyiregyhaza, Szabolcs-Szatmar-Bereg, Hungary
-
-
Zala
-
Zalaegerszeg, Zala, Hungary
-
-
-
-
-
Haifa, Israel
-
Jerusalem, Israel
-
Safed, Israel
-
-
Sharon
-
Kfar Saba, Sharon, Israel
-
-
Teah Tiqwa
-
Petach Tikva, Teah Tiqwa, Israel
-
-
Tel Aviv
-
Tel Hashomer, Tel Aviv, Israel
-
-
-
-
-
Daugavpils, Latvia
-
Liepaja, Latvia
-
Riga, Latvia
-
Valmiera, Latvia
-
Ventspills, Latvia
-
-
-
-
-
Chihuahua, Mexico
-
San Luis Potosi, Mexico
-
Veracruz, Mexico
-
-
Jalisco
-
Guadalajara, Jalisco, Mexico
-
-
-
-
-
Chisinau, Moldova, Republic of
-
-
-
-
-
Brasov, Romania
-
Bucuresti, Romania
-
Iasi, Romania
-
Sibiu, Romania
-
-
Bihor
-
Oradea, Bihor, Romania
-
-
Bucuresti
-
Bucharest, Bucuresti, Romania
-
-
Timis
-
Timisoara, Timis, Romania
-
-
-
-
-
Kemerovo, Russian Federation
-
Moscow, Russian Federation
-
Nizhniy Novgorod, Russian Federation
-
Novosibirsk, Russian Federation
-
Penza, Russian Federation
-
Saratov, Russian Federation
-
St. Petersburg, Russian Federation
-
-
-
-
-
Belgrade, Serbia
-
-
-
-
-
Banska Bystrica, Slovakia
-
Levice, Slovakia
-
Martin, Slovakia
-
Presov, Slovakia
-
Skalica, Slovakia
-
-
-
-
Free State
-
Bloemfontein, Free State, South Africa
-
-
Gauteng
-
Pretoria, Gauteng, South Africa
-
Soweto, Gauteng, South Africa
-
-
Mpumalanga
-
Middleburg, Mpumalanga, South Africa
-
-
Western Cape
-
Bellville, Western Cape, South Africa
-
-
-
-
-
Chiang Mai, Thailand
-
Lop Buri, Thailand
-
Prachuap Khiri Khan, Thailand
-
-
Nakhon Ratchasima
-
Nakorn Ratchasima, Nakhon Ratchasima, Thailand
-
-
-
-
California
-
San Diego, California, United States
-
-
Colorado
-
Wheat Ridge, Colorado, United States
-
-
Florida
-
Hialeah, Florida, United States
-
-
New Jersey
-
Teaneck, New Jersey, United States
-
-
South Carolina
-
Charleston, South Carolina, United States
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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).
- Be males or females ≥ 18 years of age
If female, subject is non-lactating, and is either:
- 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
- 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.
- 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.
- Pyuria (white blood cell [WBC] count > 10/μL in unspun urine or ≥ 10 per high power field in spun urine).
Clinical signs and/or symptoms of cUTI, either of:
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
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.
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.
- Require IV antibacterial therapy for the treatment of the presumed cUTI.
Exclusion Criteria:
- 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)
- 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.)
- 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.
- 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).
- Intractable urinary infection at baseline that the Investigator anticipates would require more than 7 days of study drug therapy.
- Complete, permanent obstruction of the urinary tract.
- Confirmed fungal urinary tract infection at time of randomization (with ≥ 103 fungal CFU/mL).
- Permanent indwelling bladder catheter or urinary stent including nephrostomy.
- Suspected or confirmed perinephric or intrarenal abscess.
- Suspected or confirmed prostatitis.
- Ileal loop or known vesico-ureteral reflux.
- 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).
- 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).
- Any condition or circumstance that, in the opinion of the Investigator, would compromise the safety of the subject or the quality of study data.
- Any rapidly progressing disease or immediately life-threatening illness including acute hepatic failure, respiratory failure, and septic shock.
- 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.
- 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%.
- Participation in any clinical study of an investigational product within 30 days prior to the proposed first day of study drug.
- Previous participation in any study of CXA-101 or CXA-201.
- Women who are pregnant or nursing.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: QUADRUPLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: CXA-201 as treatment for cUTI
CXA-201 IV infusion (1500mg q8) for 7 days
|
CXA-201 IV infusion (1500mg q8) for 7 days
|
ACTIVE_COMPARATOR: Levofloxacin as treatment for cUTI
Levofloxacin IV infusion (750mg qd) for 7 days
|
Levofloxacin IV infusion (750mg qd) for 7 days
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
The Percentage of Subjects Who Have Both a Per-subject Microbiological Outcome of Eradication and a Clinical Outcome of Cure at the Test of Cure (TOC) Visit in the Microbiological Modified ITT (mMITT) Population
Time Frame: Test of Cure Visit (7 Days [± 2 days] after completion of study drug administration)
|
Test of Cure Visit (7 Days [± 2 days] after completion of study drug administration)
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
The Percentage of Subjects Who Have Both a Per-subject Microbiological Outcome of Eradication and a Clinical Outcome of Cure at the TOC Visit in the Microbiologically Evaluable (ME) Population.
Time Frame: Test of Cure Visit (7 Days [± 2 days] after completion of study drug administration)
|
Test of Cure Visit (7 Days [± 2 days] after completion of study drug administration)
|
Collaborators and Investigators
Sponsor
Investigators
- Study Director: Obiamiwe Umeh, M.D., MSc., Cubist Pharmaceuticals LLC
Publications and helpful links
General Publications
- Popejoy MW, Long J, Huntington JA. Analysis of patients with diabetes and complicated intra-abdominal infection or complicated urinary tract infection in phase 3 trials of ceftolozane/tazobactam. BMC Infect Dis. 2017 May 2;17(1):316. doi: 10.1186/s12879-017-2414-9.
- Xiao Y, Tong ML, Liu LL, Lin LR, Chen MJ, Zhang HL, Zheng WH, Li SL, Lin HL, Lin ZF, Xing HQ, Niu JJ, Yang TC. Novel predictors of neurosyphilis among HIV-negative syphilis patients with neurological symptoms: an observational study. BMC Infect Dis. 2017 Apr 26;17(1):310. doi: 10.1186/s12879-017-2339-3. Erratum In: BMC Infect Dis. 2017 May 22;17 (1):357.
- Armstrong ES, Mikulca JA, Cloutier DJ, Bliss CA, Steenbergen JN. Outcomes of high-dose levofloxacin therapy remain bound to the levofloxacin minimum inhibitory concentration in complicated urinary tract infections. BMC Infect Dis. 2016 Nov 25;16(1):710. doi: 10.1186/s12879-016-2057-2.
- Wagenlehner FM, Umeh O, Steenbergen J, Yuan G, Darouiche RO. Ceftolozane-tazobactam compared with levofloxacin in the treatment of complicated urinary-tract infections, including pyelonephritis: a randomised, double-blind, phase 3 trial (ASPECT-cUTI). Lancet. 2015 May 16;385(9981):1949-56. doi: 10.1016/S0140-6736(14)62220-0. Epub 2015 Apr 27.
- Kullar R, Wagenlehner FM, Popejoy MW, Long J, Yu B, Goldstein EJ. Does moderate renal impairment affect clinical outcomes in complicated intra-abdominal and complicated urinary tract infections? Analysis of two randomized controlled trials with ceftolozane/tazobactam. J Antimicrob Chemother. 2017 Mar 1;72(3):900-905. doi: 10.1093/jac/dkw486.
- Huntington JA, Sakoulas G, Umeh O, Cloutier DJ, Steenbergen JN, Bliss C, Goldstein EJ. Efficacy of ceftolozane/tazobactam versus levofloxacin in the treatment of complicated urinary tract infections (cUTIs) caused by levofloxacin-resistant pathogens: results from the ASPECT-cUTI trial. J Antimicrob Chemother. 2016 Jul;71(7):2014-21. doi: 10.1093/jac/dkw053. Epub 2016 Mar 18.
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Pathologic Processes
- Kidney Diseases
- Urologic Diseases
- Disease Attributes
- Nephritis
- Nephritis, Interstitial
- Pyelitis
- Infections
- Communicable Diseases
- Urinary Tract Infections
- Pyelonephritis
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Enzyme Inhibitors
- Antineoplastic Agents
- Topoisomerase II Inhibitors
- Topoisomerase Inhibitors
- Anti-Bacterial Agents
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 CYP1A2 Inhibitors
- Anti-Infective Agents, Urinary
- Renal Agents
- Levofloxacin
- Ofloxacin
Other Study ID Numbers
- 7625A-005
- CXA-cUTI-10-04 (OTHER: Cubist Study Number)
- CXA-cUTI-10-05 (OTHER: Cubist Study # for Study 7625A-006)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Pyelonephritis
-
Hospital Universitario Dr. Jose E. GonzalezUnknownEmphysematous PyelonephritisMexico
-
Paratek Pharmaceuticals IncCompletedAcute PyelonephritisGeorgia, Latvia, Russian Federation, Ukraine
-
University Hospital, Clermont-FerrandCompletedAcute Uncomplicated PyelonephritisFrance
-
University of Southern DenmarkCompletedAcute PyelonephritisDenmark
-
University of Southern DenmarkCompletedAcute PyelonephritisDenmark
-
Shahid Beheshti UniversityUnknownAcute Pyelonephritis(APN)Iran, Islamic Republic of
-
University of ManitobaJanssen-Ortho Inc., Canada; PriCara, Unit of Ortho-McNeil, Inc.; Ortho-McNeil...TerminatedAcute Uncomplicated PyelonephritisCanada
-
MerLion Pharmaceuticals GmbHCompletedUrinary Tract Infections | Acute PyelonephritisGermany
-
Shahid Beheshti UniversityUnknownAcute Pyelonephritis(APN)Iran, Islamic Republic of
-
University of Southern DenmarkCompleted
Clinical Trials on CXA-201
-
Cubist Pharmaceuticals LLCCompletedComplicated Intra-abdominal InfectionUnited States, Argentina, Israel, Bulgaria, Serbia, Korea, Republic of, Estonia, Chile, Hungary, Lithuania, Latvia, Croatia, Moldova, Republic of, Poland, Germany
-
Complexa, Inc.Philips Healthcare; Medpace, Inc.; Allegheny Singer Research Institute (also... and other collaboratorsTerminatedPAHUnited States, United Kingdom
-
Complexa, Inc.Completed
-
Complexa, Inc.CompletedAcute Kidney InjuryUnited States
-
Complexa, Inc.Completed
-
QurAlis CorporationRecruitingAmyotrophic Lateral SclerosisCanada, Germany, Netherlands, Ireland, United Kingdom, Belgium
-
Modulation Therapeutics, Inc.H. Lee Moffitt Cancer Center and Research InstituteRecruitingUveal Melanoma | MetastaticUnited States
-
Royal Prince Alfred Hospital, Sydney, AustraliaCompleted
-
Complexa, Inc.Medpace, Inc.; MicroConstants; Kidney Research Network, formerly NephCure Accelerating... and other collaboratorsCompletedPrimary Focal Segmental GlomerulosclerosisUnited States
-
TWi Biotechnology, Inc.CompletedType 2 Diabetes MellitusUnited States, Taiwan