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A Study of Doripenem in CerebrospinalFluid After Doripenem Administration in Pediatric Patients Less Than 1 Year of Age

Phase 1
Terminated
Conditions
Meningitis
Interventions
Registration Number
NCT01366651
Lead Sponsor
Janssen Research & Development, LLC
Brief Summary

The purpose of this study is to characterize the penetration of doripenem in the cerebral spinal fluid in pediatric patients \<1 year of age who are hospitalized and have a documented or suspected infection and are planning to, or undergoing treatment with intravenous (IV) antibiotics.

Detailed Description

This is a multicenter, open-label (identity of treatment is known to patient's parent/legal guardian/caregiver and to all study staff) study to characterize the penetration of doripenem in the cerebral spinal fluid (CSF) in pediatric patients \<1 year of age who are hospitalized but medically stable, and who have a documented or suspected infection and are planning to, or undergoing treatment with antibiotics administered intravenously (in a vein, abbreviated as "IV"). Doripenem will not replace the patients' prescribed antibiotic(s). The study includes 3 phases: a pretreatment phase consisting of an up to 24-hour screening period; a 2-day open-label treatment period when doripenem will be administered, and CSF and blood samples will be collected, and a follow-up visit approximately 1 week after administration of the last dose of doripenem. The total duration of the study is approximately 10 days. During the study, patients \<12 weeks of age will receive a 10 mg/kg doripenem 1-hour IV infusion via a central or peripheral venous line (a catheter inserted in a large vein) every 8 hours; patients 12 weeks to \<1 year of age will receive a 30 mg/kg doripenem 1-hour IV infusion every 8 hours. A total of 5 doses of doripenem will be administered over a 2-day period while the patient is in the hospital.

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
1
Inclusion Criteria
  • Patient is expected to require hospitalization for the entire open-label phase of the study.
  • Patient must be scheduled to have cerebral spinal fluid obtained via a lumbar puncture (referred to as a "spinal tap") or ventriculoperitoneal (VP) shunt tap within 3 days of enrollment into this study.
  • Patient must have documented or suspected infection and is planning to, or undergoing treatment with IV antibiotics.
  • Parent or the patient's legally acceptable representative must have signed an informed consent document indicating they understand the purpose of and procedures required for the study and are willing to allow the infant to participate in the study.
Exclusion Criteria
  • Clinically significant abnormal values for hematology or clinical chemistry at screening that, at the option of the investigator, are not consistent with the patient's underlying disease(s) or therapies.
  • Any condition at screening that, in the opinion of the investigator, may interfere with the assessments of this study.
  • Patients with substantially compromised renal (kidney) function: e.g., urine output is <0.25cc/kg/hr within the 24 hours before screening.
  • History of clinically significant allergies to medications, especially known hypersensitivity or intolerance to carbapenems, penicillins, or other Beta-lactam antibiotics.
  • Known allergy to heparin or history of heparin-induced thrombocytopenia, if an in-dwelling cannula (e.g., heparin lock) or central line is used.
  • Patients concomitantly treated with or having received imipenem/cilastin within 48 hours before study drug administration.
  • Patients concomitantly treated with probenecid or valproic acid (VPA).

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
DoripenemDoripenemDoripenem Type=exact number unit=mg/kg number=10 form=solution for injection route=intravenous use every 8 hours for 2 days (total of 5 doses) for patients \<12 weeks of age.Doripenem 500-mg sterile powder will be supplied for the study in single use glass vials.,Doripenem Type=exact number unit=mg/kg number=30 form=solution for injection route=intravenous use every 8 hours for 2 days (total of 5 doses) for patients 12 weeks to \<1 year of age. Doripenem 500-mg sterile powder will be supplied for the study in single use glass vials.
Primary Outcome Measures
NameTimeMethod
Doripenem concentrations in CSF and plasmaFor up to 2 days
Secondary Outcome Measures
NameTimeMethod
The number of patients who receive concomitant therapyFrom Day -1 to Day 9
Number of patients with adverse eventsUp to Day 9
Changes in clinical laboratory test resultsFrom Day -1 to Day 9
Changes in physical examination results reported as adverse eventsFrom Day -1 to Day 9
Changes in vital signs measurementsFrom Day -1 to Day 9
The number of patients with changes from baseline in clinical laboratory test resultsFrom Day -1 to Day 9
Changes in concomitant therapyFrom Day -1 to Day 9
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