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

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

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 Infec

Brief Summary: 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.

Detailed Summary: 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
Sponsor: Janssen Research & Development, LLC

Current Primary Outcome: The Number of Participants With Clinical Cure Rate at Test Of Cure (TOC) Visit [ Time Frame: TOC (7 to 14 days after the last dose of study medication therapy) ]

Original Primary Outcome: 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: Baseline up to 42 days after the last dose of study drug ]

Current Secondary Outcome:

• The Number of Participants With Clinical Improvement Rate at End of IV (EIV) Visit [ Time Frame: EIV (within 24 hours after completion of the last dose of IV study medication therapy) ]
  The participants were considered as clinical improved if they had clinical improvement in signs and symptoms of the intra-abdominal infection, no fever, decrease in WBC, and not received any nonstudy antibiotics for the treatment of intra-abdominal infection after IV study drug therapy had begun.
• The Number of Participants With Clinical Cure Rate at Late Follow-Up (LFU) Visit [ Time Frame: LFU (28 to 42 days after the last dose of study medication therapy) ]
  The participants were considered as clinical cure if they had clinical improvement in signs and symptoms of the intra-abdominal infection such that no additional antibacterial therapy or surgical or percutaneous intervention is/was required for the treatment of the index infection, no fever, and a favorable response at End of IV visit.
• The Number of Participants With Favorable Per-participant Microbiological Response [ Time Frame: 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) ]
  Favorable per-participant microbiological response rate was evaluated at the at End of IV (EIV) visit, Test Of Cure (TOC) visit, and Late Follow-Up (LFU) visit. The favorable per-participant microbiological response was considered when all baseline pathogens were eradicated (absence) or presumed eradicated (absence of material to culture in a participant who has a positive clinical response to treatment).
• Number of Participants With Favorable Per-pathogen Microbiological Outcome Rate at End of IV (EIV) Visit [ Time Frame: EIV (within 24 hours after completion of the last dose of IV study medication therapy) ]
  A total of 24 pathogens in the doripenem group and 6 pathogens in the meropenem group were isolated at baseline from the intra-abdominal culture and were susceptible to the study drug received. The most common pathogens isolated from the intra-abdominal culture are listed in the table below; the numbers in parenthesis next to each pathogen represent the number of participants with the pathogen isolated at baseline in the doripenem and meropenem treatment groups, respectively. The favorable per-pathogen microbiological outcome was considered when all baseline pathogens were eradicated (absence) or presumed eradicated (absence of material to culture in a participant who has a positive clinical response to treatment).
• Number of Participants With Favorable Per-pathogen Microbiological Outcome Rate at Test Of Cure (TOC) Visit [ Time Frame: TOC (7 to 14 days after the last dose of study medication therapy) ]
  A total of 24 pathogens in the doripenem group and 6 pathogens in the meropenem group were isolated at baseline from the intra-abdominal culture and were susceptible to the study drug received. The most common pathogens isolated from the intra-abdominal culture are listed in the table below; the numbers in parenthesis next to each pathogen represent the number of participants with the pathogen isolated at baseline in the doripenem and meropenem treatment groups, respectively. The favorable per-pathogen microbiological outcome was considered when all baseline pathogens were eradicated (absence) or presumed eradicated (absence of material to culture in a participant who has a positive clinical response to treatment).
• Number of Participants With Favorable Per-pathogen Microbiological Outcome Rate at Late Follow-Up (LFU) Visit [ Time Frame: LFU (28 to 42 days after the last dose of study medication therapy) ]
  A total of 24 pathogens in the doripenem group and 6 pathogens in the meropenem group were isolated at baseline from the intra-abdominal culture and were susceptible to the study drug received. The most common pathogens isolated at baseline from the intra-abdominal culture are listed in the table below; the numbers in parenthesis next to each pathogen represent the number of participants with the pathogen isolated in the doripenem and meropenem treatment groups, respectively. The favorable per-pathogen microbiological outcome was considered when all baseline pathogens were eradicated (absence) or presumed eradicated (absence of material to culture in a participant who has a positive clinical response to treatment).

Original Secondary Outcome:

• 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 iv study drug ]
• 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 ]
• 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 iv study drug ]
• 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 ]

Dates:
Date Received: April 15, 2010
Date Started: December 2010
Date Completion:
Last Updated: July 2, 2014
Last Verified: July 2014