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

NCT01345929 | Completed Phase 3 Results

• 3 other identifiers: 7625A-005CXA-cUTI-10-04CXA-cUTI-10-05
• Study Type: interventional
• Target: 558
• Locations: 17 countries
• Sites: 76

Brief Summary

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).

Conditions

Complicated Urinary Tract Infection; Pyelonephritis

Keywords

cUTI

Outcome Measures

Primary Outcomes (1)

• 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

  Test of Cure Visit (7 Days [± 2 days] after completion of study drug administration)

Secondary Outcomes (1)

• 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.

  Test of Cure Visit (7 Days [± 2 days] after completion of study drug administration)

Study Arms (2)

CXA-201 as treatment for cUTI

EXPERIMENTAL

CXA-201 IV infusion (1500mg q8) for 7 days

Drug: CXA-201

Levofloxacin as treatment for cUTI

ACTIVE COMPARATOR

Levofloxacin IV infusion (750mg qd) for 7 days

Drug: Levofloxacin

Interventions

CXA-201 DRUG

CXA-201 IV infusion (1500mg q8) for 7 days

CXA-201 as treatment for cUTI

Levofloxacin DRUG

Levofloxacin IV infusion (750mg qd) for 7 days

Levofloxacin as treatment for cUTI

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:

You may not qualify if:

• 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.

Sponsors & Collaborators

• Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA): lead

Study Sites (76)

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San Diego, California, United States

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Wheat Ridge, Colorado, United States

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Hialeah, Florida, United States

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Teaneck, New Jersey, United States

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Charleston, South Carolina, United States

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Belo Horizonte, Minas Gerais, Brazil

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Porto Alegre, Rio Grande de Sul, Brazil

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Joinville, Santa Catarina, Brazil

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Campinas, São Paulo, Brazil

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Sao Jose de Rio Preto, São Paulo, Brazil

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Rio de Janeiro, Brazil

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São Paulo, Brazil

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Cali, Valle del Cauca Department, Colombia

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Armenia, Colombia

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Barranquilla, Colombia

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Bogotá, Colombia

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Kohtla-Järve, Estonia

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Tallinn, Estonia

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Tartu, Estonia

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Tbilisi, Georgia

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Giessen, Hesse, Germany

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Lübeck, Schleswig-Holstein, Germany

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Miskolc, Borsod-Abauj Zemplen county, Hungary

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Gyor, Budapest, Hungary

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Szentes, Csongrád megye, Hungary

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Sopron, Győr-Moson-Sopron, Hungary

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Salgótarján, Nógrád megye, Hungary

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Nyíregyháza, Szabolcs-Szatmár-Bereg, Hungary

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Zalaegerszeg, Zala County, Hungary

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Budapest, Hungary

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Tatabánya, Hungary

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Kfar Saba, Sharon, Israel

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Petah Tikva, Teah Tiqwa, Israel

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Tel Litwinsky, Tel Aviv, Israel

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Haifa, Israel

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Jerusalem, Israel

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Safed, Israel

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Daugavpils, Latvia

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Liepāja, Latvia

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Riga, Latvia

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Valmiera, Latvia

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Ventspills, Latvia

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Guadalajara, Jalisco, Mexico

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Chihuahua City, Mexico

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San Luis Potosí City, Mexico

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Veracruz, Mexico

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Chisinau, Moldova

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Oradea, Bihor County, Romania

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Bucharest, București, Romania

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Timișoara, Timiș County, Romania

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Brasov, Romania

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Bucharest, Romania

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Iași, Romania

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Sibiu, Romania

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Kemerovo, Russia

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Moscow, Russia

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Nizhny Novgorod, Russia

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Novosibirsk, Russia

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Penza, Russia

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Saint Petersburg, Russia

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Saratov, Russia

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Belgrade, Serbia

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Banská Bystrica, Slovakia

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Levice, Slovakia

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Martin, Slovakia

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Prešov, Slovakia

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Skalica, Slovakia

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Bloemfontein, Free State, South Africa

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Pretoria, Gauteng, South Africa

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Soweto, Gauteng, South Africa

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Middleburg, Mpumalanga, South Africa

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Bellville, Western Cape, South Africa

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Nakorn Ratchasima, Changwat Nakhon Ratchasima, Thailand

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Chiang Mai, Thailand

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Lopburi, Thailand

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Prachuap Khiri Khan, Thailand

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Related Publications (6)

• 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.

  PMID: 28464828 DERIVED

• 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.

  PMID: 28446129 DERIVED

• 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.

  PMID: 27999024 DERIVED

• 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.

  PMID: 27887579 DERIVED

• 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.

  PMID: 26994090 DERIVED

• 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.

  PMID: 25931244 DERIVED

MeSH Terms

Conditions

Pyelonephritis

Interventions

Levofloxacin

Condition Hierarchy (Ancestors)

Nephritis, Interstitial; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Pyelitis; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Ofloxacin; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and Caveats

Two identical P3 protocols were initiated (NCT01345929 and NCT01345955) subsequently, Cubist and FDA agreed that integrated data from the 2 protocols could be analyzed and reported in a single Clinical Study Report. These analyses are presented here.

Results Point of Contact

• Title: Dr. Obi Umeh, Vice President Global Medical Sciences
• Organization: Cubist Pharmaceuticals, Inc.

obiamiwe.umeh@cubist.com

781-860-8415

Study Officials

• Obiamiwe Umeh, M.D., MSc.

  Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 28, 2011
• First Posted: May 2, 2011
• Study Start: June 20, 2011
• Primary Completion: August 11, 2013
• Study Completion: September 4, 2013
• Last Updated: October 25, 2018
• Results First Posted: January 15, 2015

Record last verified: 2018-09

Data Sharing

• IPD Sharing: Will share

Locations

BR (7); SL (5); ME (4); RO (7); ES (3); CO (4); SE (1); GE (1); HU (9); IL (6); DE (2); ZA (5); US (5); RU (7); LA (5); MO (1); TH (4)