A Safety and Tolerability Study of Doripenem Compared With Meropenem in Children Hospitalized With Complicated Intra-abdominal Infections

This study has been terminated.
(Trial terminated early per business decision)
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT01110382
First received: April 15, 2010
Last updated: October 14, 2013
Last verified: October 2013
  Purpose

The purpose of the study is to evaluate the safety and tolerability of doripenem compared with meropenem in children hospitalized with complicated intra-abdominal infections.


Condition Intervention Phase
Abscess, Intra-Abdominal
Abdominal Abscess
Abdomen, Acute
Abdominal Pain
Appendicitis
Rupture
Infection
Intestinal Perforation
Peritonitis
Ileus
Drug: Doripenem
Drug: Meropenem placebo
Drug: Meropenem
Drug: Doripenem placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Prospective, Randomized, Double-Blind, Multicenter Study to Establish the Safety and Tolerability of Doripenem Compared With Meropenem in Hospitalized Children With Complicated Intra-Abdominal Infections

Resource links provided by NLM:


Further study details as provided by Janssen Research & Development, LLC:

Primary Outcome Measures:
  • The safety of doripenem compared with meropenem in children with cIAI will be evaluated by monitoring adverse events, changes in clinical laboratory tests, and findings from vital signs measurements and physical examinations. [ Time Frame: Safety will be assessed during the 5 to 14 day treatment period and at posttreatment visits scheduled 7 to 14 days and 28 to 42 days, respectively, after the last dose of study drug. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Clinical cure rate and favorable per-patient microbiological response rate of doripenem compared with meropenem at test of cure (TOC) visit [ Time Frame: 7 to 14 days after the last dose of study drug ] [ Designated as safety issue: No ]
  • Clinical improvement of doripenem compared with meropenem at end of treatment (EIV) for iv study drug therapy [ Time Frame: Within 24 hours after completion of the last dose of iv study drug ] [ Designated as safety issue: No ]
  • Clinical cure rate and favorable per-patient microbiological response rate of doripenem compared with meropenem at late follow Up (LFU) visit [ Time Frame: 28 to 42 days after the last dose of study drug ] [ Designated as safety issue: No ]
  • Characterize pharmacokinetics of doripenem in hospitalized children with cIAI on the basis of a sparse pharmacokinetic sampling scheme [ Time Frame: 1, 2, 4 and 6 hours after the 4th, 5th, 6th, or 7th dose administrations of doripenem/doripenem placebo ] [ Designated as safety issue: No ]

Enrollment: 41
Study Start Date: December 2010
Study Completion Date: September 2013
Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Meropenem placebo/Doripenem
Patients will receive at least 3 days of doripenem administered IV every 8 hours immediately after meropenem placebo for up to 14 days.
Drug: Doripenem
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 meropenem placebo for up to 14 days
Drug: Meropenem placebo
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.
Experimental: Meropenem/Doripenem placebo
Patients will receive at least 3 days of meropenem administered IV every 8 hours immediately before doripenem placebo for up to 14 days.
Drug: Meropenem
Type=once every 8 hours infused over 30 minutes, Unit=mg, Number=20 mg/kg to 1 gram per dose, Form=solution for infusion, Route=intravenous use. At least 3 days of iv meropenem administered every 8 hours immediately before doripenem placebo for up to 14 days
Drug: Doripenem placebo
Form=solution for infusion, Route=intravenous use, administered once every 8 hours infused over 60 minutes immediately after each iv infusion of meropenem for up to 14 days

Detailed Description:

This is a randomized (study drug assigned by chance), double-blind (neither physician nor patient knows the name of the assigned study drugs), double-dummy (all patients are given both a placebo [salt solution] and study drug in alternating periods of time during the study), active comparator-controlled (compare the "test" treatment to standard-of-care therapy), multinational, multicenter study to evaluate the safety of the study drugs (doripenem and meropenem) administered by intravenous (iv) infusion (slow injection of drug solution into the vein over a period of time) in children aged 3 months to less than 18 years who are hospitalized with complicated intra abdominal infections (cIAI). Complicated intra abdominal infections include but are not limited to appendicitis with rupture and/or abscess (local collection of pus), acute (severe or intense) gastric, duodenal (beginning section of the small intestine), or gall bladder perforation (a hole in the wall of the stomach, small intestine, or gallbladder), and secondary peritonitis. The study will include 3 periods: a pretreatment (screening) period that will occur within 2 days prior to randomization (assignment of study drug), a treatment period of 5 to 14 days where patients will receive iv study drug treatment only or IV study therapy and a switch to oral antibiotic therapy, and a posttreatment period consisting of 2 study visits. The max duration of study drug therapy is 14 days. The total duration of the study is approximately 7 to 8 weeks. Safety and tolerability will be evaluated by examining the incidence, severity, and type of adverse events, changes in clinical laboratory tests, vital signs measurements, and findings from physical examinations observed during treatment and at each posttreatment visit. An independent monitoring committee (IDMC) will be established for this study to ensure that the safety of patients is not compromised. The IDMC will consist of individuals who are not associated with the conduct of the study, and will include but will not be limited to individuals with expertise relevant to the care of pediatric patients, and including at least one infectious disease physician and at least one statistician. Patients will receive IV Doripenem (20 mg/kg to 500 mg/dose) and meropenem placebo OR meropenem (20 mg/kg to 1 gram/dose) and doripenem placebo once every 8 hours for up to 14 days. If the patient's cIAI symptoms improve after 72 hours of treatment with iv study drug, the investigator may choose to stop iv study drug and switch the patient to an orally administered antibiotic (amoxicillin/clavulanate postassium) to complete the 5- to 14 day course of antibiotic therapy.

  Eligibility

Ages Eligible for Study:   3 Months to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients who are eligible for the study must have clinical evidence of cIAI
  • Require surgical intervention (eg, laparotomy, laparoscopic surgery, or percutaneous drainage) to manage the cIAI
  • Require antibacterial therapy for 5 to 14 days in addition to the surgical intervention
  • Must, based on the judgment of the investigator, require hospitalization initially and antibacterial therapy for 5 to 14 days in addition to surgical intervention for the treatment of the current cIAI. (Note that the patient must require at least 3 days of IV antibiotic therapy initially)
  • 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 and older)

Exclusion Criteria:

  • 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 nonstudy systemic antibiotic therapy for cIAI for more than 24 hours immediately preceding the start of the infusion of the first dose of iv study drug therapy
  • Have a diagnosis of abdominal wall abscess confined to musculature of the abdominal wall, small bowel obstruction or ischemic bowel disease without perforation, traumatic bowel perforation requiring surgery within 12 hours of perforation, or perforation of gastroduodenal ulcers requiring surgery within 24 hours of perforation (these are considered situations of peritoneal soiling before the infection has become established)
  • Have simple (noncomplicated), nonperforated appendicitis or gangrenous appendicitis without rupture into the peritoneal cavity identified during a surgical procedure OR presence of spontaneous bacterial peritonitis or peritonitis associated with cirrhosis or chronic ascites
  • Known at the time of randomization to have a cIAI caused by at least one pathogen that is nonsusceptible to doripenem or meropenem
  • Presence of any of the following clinically significant laboratory abnormalities: Hematocrit of less than 20%, absolute neutrophil count (ANC) <500 cells/µL, platelet count <40,000 cells/µL, serum alanine aminotransferase or aspartate aminotransferase (AST) or total bilirubin 5 times or greater the age-specific upper limit of normal (ULN) or acute/chronic renal insufficiency with a baseline creatinine clearance <50 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01110382

Locations
United States, California
San Diego, California, United States
United States, District of Columbia
Washington, District of Columbia, United States
United States, Ohio
Cleveland, Ohio, United States
Toledo, Ohio, United States
Argentina
Buenos Aires, Argentina
Buenos Aires N/A, Argentina
Córdoba, Argentina
Loma Hermosa N/A, Argentina
Paraná, Entre Ríos, Argentina
Santa Fe, Argentina
Brazil
Passo Fundo, Brazil
São Paulo, Brazil
Chile
Santiago, Chile
Valdivia X Región, Chile
Colombia
Bogota, Colombia
Floridablanca, Colombia
Latvia
Riga, Latvia
Lithuania
Kaunas, Lithuania
Vilnius, Lithuania
Panama
Zona, Panama
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
Study Director: Janssen Research & Development, LLC C. Clinical Trial Janssen Research & Development, LLC
  More Information

No publications provided

Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT01110382     History of Changes
Other Study ID Numbers: CR016789, DORIPED3001, 2009-015864-32
Study First Received: April 15, 2010
Last Updated: October 14, 2013
Health Authority: United States: Food and Drug Administration
Argentina: Ministry of Health
Latvia: State Agency of Medicines

Keywords provided by Janssen Research & Development, LLC:
Anti-Infective Agents
Doripenem
Meropenem
Child, Hospitalized
Complicated Intra-Abdominal Infections

Additional relevant MeSH terms:
Abdomen, Acute
Abdominal Pain
Abscess
Appendicitis
Intestinal Perforation
Peritonitis
Abdominal Abscess
Ileus
Rupture
Pain
Signs and Symptoms
Signs and Symptoms, Digestive
Suppuration
Infection
Inflammation
Pathologic Processes
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Cecal Diseases
Intestinal Diseases
Peritoneal Diseases
Intestinal Obstruction
Wounds and Injuries
Meropenem
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Anti-Bacterial Agents

ClinicalTrials.gov processed this record on April 17, 2014