A Safety and Tolerability Study of Doripenem Compared With Cefepime in Children Hospitalized With Complicated Urinary Tract Infections

NCT01110408 | Terminated Phase 3 Results DMC

• 3 other identifiers: CR016792DORIPED30022009-015953-18
• Study Type: interventional
• Target: 41
• Locations: 12 countries
• Sites: 38

Brief Summary

The purpose of this study is to evaluate the safety and tolerability of doripenem compared to cefepime in children hospitalized with complicated urinary tract infections.

Conditions

Complicated Urinary Tract Infections or Pyelonephritis

Keywords

Antibiotic; Child, Hospitalized; Complicated Urinary Tract Infection; Pyelonephritis; Doripenem; Cefepime

Outcome Measures

Primary Outcomes (1)

• The Number of Participants With Clinical Cure Rate at Test Of Cure (TOC) Visit

  The participants were classified as cure if they had resolution or clinical improvement in signs and symptoms of complicated urinary tract infection; had no fever; no additional antimicrobial therapy was required for the treatment of the infection; and a clinical response assessment of improvement at End of IV visit.

  TOC (7 to 14 days after the last dose of study medication therapy)

Secondary Outcomes (6)

• The Number of Participants With Clinical Improvement Rate at End of IV (EIV) Visit

  EIV (within 24 hours after completion of the last dose of IV study medication therapy)

• The Number of Participants With Clinical Cure Rate at Late Follow-Up (LFU) Visit

  LFU (28 to 42 days after the last dose of study medication therapy)

• The Number of Participants With Favorable Per-participant Microbiological Response

  EIV (within 24 hours after completion of the last dose of IV study medication therapy), TOC (7 to 14 days after the last dose of study medication therapy), and LFU (28 to 42 days after the last dose of study medication therapy)

• Number of Participants With Favorable Per-pathogen Microbiological Outcome Rate at End of IV (EIV) Visit

  EIV (within 24 hours after completion of the last dose of IV study medication therapy)

• Number of Participants With Favorable Per-pathogen Microbiological Outcome Rate at Test Of Cure (TOC) Visit

  TOC (7 to 14 days after the last dose of study medication therapy)

Study Arms (2)

Doripenem

EXPERIMENTAL

Doripenem 20 mg/kg per dose (up to 500 mg/dose) will be administered every 8 hours as 60-minutes IV (at least 3 days of IV doripenem only or IV doripenem followed by oral amoxicillin/clavulanate potassium or ciprofloxacin). Total duration of treatment 10 to 14 days.

Drug: Doripenem; Drug: Cefepime placebo; Drug: Amoxicillin/clavulanate potassium

Cefepime

EXPERIMENTAL

Cefepime 50 mg/kg per dose (up to 2 g/dose) will be dministered every 8 hours as 30-minutes IV (at least 3 days of IV cefepime only or IV cefepime followed by oral amoxicillin/clavulanate potassium or ciprofloxacin). Total duration of treatment 10 to 14 days.

Drug: Doripenem placebo; Drug: Cefepime; Drug: Amoxicillin/clavulanate potassium

Interventions

Doripenem DRUG

Type=once every 8 hours infused over 60 minutes, Unit=mg,Number=20mg/kg up to 500mg/dose, Form=solution for infusion,Route=intravenous use. At least 3 days of iv doripenem administered every 8 hours immediately after each iv infusion of cefepime placebo for up to 14 days

Doripenem

Doripenem placebo DRUG

Form=solution for infusion, Route=intravenous use, administered once every 8 hours infused over 60 minutes immediately following each iv infusion of cefepime for up to 14 days

Cefepime

Cefepime DRUG

Type=once every 8 hours, Unit=mg, Number=50 mg/kg up to 2g/dose, Form=solution for infusion, Route=intravenous use. At least 3 days of iv cefepime administered every 8 hours infused over 30 minutes immediately before each iv infusion of doripenem placebo for up to 14 days

Cefepime

Cefepime placebo DRUG

Form=solution for infusion, Route=intravenous use, administered once every 8 hours infused over 30 minutes immediately before each iv infusion of doripenem for up to 14 days

Doripenem

Amoxicillin/clavulanate potassium DRUG

Form=suspension or tablets, Route=oral (by mouth), may be administered at the discretion of the investigator once every 12 hours for up to 14 days following IV therapy with doripenem or cefepime.

Cefepime; Doripenem

Eligibility Criteria

• Age: 3 Months - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Patients who are eligible for the study must have a current episode of cUTI or pyelonephritis
• Have evidence of pyuria that meets criteria specified in the study protocol
• Have a study-qualifying pretreatment "baseline" urine culture specimen obtained by an acceptable method within 48 hours before the start of the administration of the first dose of iv study drug from which a bacterial pathogen is isolated with a growth of \>= 100000 colony forming units (CFU)/mL
• Require hospitalization initially and 10 to 14 days of antibacterial therapy \[of which at least 72 hours should be iv therapy\] for the treatment of the presumed UTI
• Have a signed informed consent form completed by the patient's parent or legal representative (and a signed assent form obtained from patients who are capable of providing assent, typically, children 7 years of age or older)

You may not qualify if:

• Have a history of hypersensitivity reactions to carbapenems, cephalosporins, penicillins, or other beta-lactam antibiotics
• concomitant infection including but not limited to suspected or confirmed meningitis or central nervous system infection requiring systemic antibiotic or antifungal therapy in addition to the iv study drug therapy at the time of randomization
• Receipt of any amount of systemic antibiotic within 96 hours before obtaining the study-qualifying pretreatment baseline urine or systemic antibiotic therapy for more than 24 hours after obtaining the study-qualifying pretreatment baseline urine specimen
• Have a diagnosis of intractable UTI/pyelonephritis infection anticipated to require more than 14 days of study drug therapy, a permanent indwelling bladder catheter or instrumentation including nephrostomy or current urinary catheter that will not be removed or anticipation of urinary catheter placement that will not be removed during the course of iv study drug therapy administration, complete and permanent obstruction of the urinary tract, confirmed fungal UTI, suspected or confirmed perinephric or intrarenal abscess, suspected or confirmed prostatitis, known ileal loops, or any of the following clinically significant laboratory abnormalities: absolute neutrophil count (ANC) \<500 cells/µL, platelet count \<40,000 cells/µL, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), or total bilirubin \>5x the age-specific upper limit of normal (ULN), acute or chronic renal insufficiency with a baseline creatinine clearance \<60 mL per minute or requires dialysis therapy for any reason
• Have a history of uncontrolled epilepsy defined as at least 1 seizure within the 6 months before randomization

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (38)

Unknown Facility

Little Rock, Arkansas, United States

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Oakland, California, United States

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Orange, California, United States

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San Diego, California, United States

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Washington D.C., District of Columbia, United States

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New Brunswick, New Jersey, United States

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Albany, New York, United States

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The Bronx, New York, United States

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Cleveland, Ohio, United States

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Toledo, Ohio, United States

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Pittsburgh, Pennsylvania, United States

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Buenos Aires, Argentina

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Córdoba, Argentina

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Loma Hermosa, Argentina

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Santa Fe, Argentina

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Belo Horizonte, Brazil

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Caxias do Sul, Brazil

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Passo Fundo, Brazil

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São Paulo, Brazil

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Santiago, Chile

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Valdivia X Región, Chile

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Bogotá, Colombia

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Cali, Colombia

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Floridablanca, Colombia

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Medellín, Colombia

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Hradec Králové, Czechia

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Prague, Czechia

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Riga, Latvia

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Kaunas, Lithuania

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Vilnius, Lithuania

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Guadajalara, Mexico

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Monterrey, Mexico

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Zapopan, Mexico

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Zona, Panama

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Lublin, Poland

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Szczecin, Poland

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Kharkiv, Ukraine

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Poltava, Ukraine

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Related Links

• Related Info

MeSH Terms

Conditions

Pyelonephritis

Interventions

Doripenem; Cefepime; Amoxicillin-Potassium Clavulanate Combination

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)

Carbapenems; beta-Lactams; Lactams; Amides; Organic Chemicals; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Cephalosporins; Thiazines; Sulfur Compounds; Clavulanic Acid; Clavulanic Acids; Amoxicillin; Ampicillin; Penicillin G; Penicillins; Drug Combinations; Pharmaceutical Preparations

Limitations and Caveats

This study was terminated early due to business reasons and not related to safety concerns or issues. As such, the limited enrollment precludes a meaningful conclusion about the efficacy and safety of doripenem compared with cefepime.

Results Point of Contact

• Title: Therapeutic Areas Director
• Organization: Janssen R&D US

ClinicalTrialDisclosure@its.jnj.com

Study Officials

• Janssen Research & Development, LLC C. Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• 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 15, 2010
• First Posted: April 26, 2010
• Study Start: December 1, 2010
• Primary Completion: June 1, 2013
• Study Completion: June 1, 2013
• Last Updated: July 15, 2014
• Results First Posted: July 2, 2014

Record last verified: 2014-07

Locations

ME (3); PA (1); PL (2); CZ (2); US (11); UA (2); CL (2); AR (4); LI (2); LA (1); BR (4); CO (4)