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A Study of the Pharmacokinetics, Safety and Tolerability of Topiramate in Infants (Age 1-24 Months) With Refractory Partial-onset Seizures

Primary Purpose

Seizures

Status
Completed
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Topiramate
Sponsored by
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional trial for Seizures focused on measuring Refractory partial-onset seizures, Infants aged 1-24 months, Pharmacokinetics, Topiramate

Eligibility Criteria

1 Month - 24 Months (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Regular enteral feeding (solid food bottle- or cup-fed) with or without breastfeeding weigh >/=3.5 kilograms (kg) and <15.5 kg Length using an infant measuring table (heel to crown) must be = 49 cm clinical or electroencephalographic (EEG) evidence of POS (simple or complex) with or without secondary generalization of at least 1 month in duration in infants >6 months of age, or at least 2 weeks in duration in infants <6 months of age Multiple seizure types allowed as long as POS is present Taking 1 or 2 concurrent marketed antiepileptic drugs (AEDs) for >1 month for infants >6 months of age and for >2 weeks for infants <6 months of age the regimen of AEDs at entry must be considered inadequate in controlling seizures, after being optimized in the opinion of the investigator Have had a computerized tomography or magnetic resonance imaging scan to confirm the absence of a progressive lesion such as a tumor, with the exception of lesions of tuberous sclerosis and Sturge-Weber syndrome, which are allowed. Exclusion Criteria: Exclusively breast-fed and cannot take oral liquid medication Receives regular enteral feeding using gastrostomy, jejunostomy, or nasogastric tube have surgically implanted and functioning vagus nerve stimulator Have febrile seizures or seizures due to an acute medical illness Have infantile seizures as a result of a correctable medical condition such as metabolic disturbance, toxic exposure, neoplasm, or active infection History of nonepileptic seizures, either current or at any point in the past Any progressive neurologic disorder, including malignancy, brain tumor, active central nervous system infection, demyelinating disease, or degenerative or progressive central nervous system disease with the exception of tuberous sclerosis and Sturge Weber syndrome.

Sites / Locations

    Outcomes

    Primary Outcome Measures

    Individual (each patient) and mean (each treatment) topiramate plasma concentration-time profiles.

    Secondary Outcome Measures

    Incidence of adverse events throughout the study. Changes from pretreatment to the end of posttreatment phase in take-home records, clinical laboratory results, physical & neurologic examination results, ECGs, renal ultrasounds, vital sign measurements

    Full Information

    First Posted
    October 3, 2005
    Last Updated
    May 24, 2010
    Sponsor
    Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
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    1. Study Identification

    Unique Protocol Identification Number
    NCT00233012
    Brief Title
    A Study of the Pharmacokinetics, Safety and Tolerability of Topiramate in Infants (Age 1-24 Months) With Refractory Partial-onset Seizures
    Official Title
    A Randomized, Open-label (OL), Multicenter Study With OL Extension of the Pharmacokinetics and Safety of Topiramate Administered as Oral Liquid and Sprinkle Formulations as an Adjunct to Concurrent Anticonvulsant Therapy in Infants (Aged 1-24 Months, Inclusive) With Refractory Partial-onset Seizures
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    May 2010
    Overall Recruitment Status
    Completed
    Study Start Date
    June 2005 (undefined)
    Primary Completion Date
    undefined (undefined)
    Study Completion Date
    October 2007 (Actual)

    3. Sponsor/Collaborators

    Name of the Sponsor
    Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

    4. Oversight

    5. Study Description

    Brief Summary
    The purpose of this study is to evaluate the pharmacokinetics safety and tolerability of topiramate in infants aged 1-24 months with refractory partial-onset seizures. Topiramate is an antiepileptic drug approved for use in adult and pediatric patients (aged 2 to 16 years) with refractory partial onset seizures (POS) with or without secondarily generalized seizures, primary generalized tonic clonic seizures, or Lennox-Gastaut syndrome (LGS).
    Detailed Description
    This is a open-label, randomized (patients are assigned different treatments based on chance), dose comparison, multicenter study of topiramate in infants of age 1-24 months with refractory partial-onset seizures (POS). The trial will evaluate the pharmacokinetics, safety, and tolerability of topiramate used as additional treatment in infants with refractory POS. Topiramate is administered as liquid and sprinkles as adjunct (additional treatment) to concurrent anticonvulsant therapy. The study will consist of 4 phases: a pretreatment phase that includes screening (up to 7 days) and baseline (1 day), an open-label treatment phase (up to 6 weeks), an open-label extension phase (54 weeks), and a posttreatment phase (up to 4 weeks). Seizure diaries will be maintained throughout the study by the patients' parents, legally acceptable representatives, or caregivers. In the open-label treatment phase, patients will be randomly assigned to 1 of 4 treatments: topiramate 3, 5, 15, or 25 mg/kg per day. Venous blood samples (four 1 milliliter [mL] samples) will be collected on 2 days during the study to determine plasma concentration of topiramate. Safety will be evaluated throughout the study by monitoring adverse events and by results from clinical laboratory tests (serum chemistry, venous ammonia, hematology, and urinalysis), electrocardiograms (ECGs), vital sign measurements (pulse and blood pressure), physical examination, neurologic examination, Vineland Scales of Adaptive Behavior, renal ultrasound, assessments for adequate food and liquid intake, hyperthermia, oligohydrosis, and rash, and take-home records. Liquid or sprinkles form of topiramate, 3,5,15,or 25mg/kg per day for 54 weeks.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Seizures
    Keywords
    Refractory partial-onset seizures, Infants aged 1-24 months, Pharmacokinetics, Topiramate

    7. Study Design

    Study Phase
    Phase 1
    Enrollment
    16 (Actual)

    8. Arms, Groups, and Interventions

    Intervention Type
    Drug
    Intervention Name(s)
    Topiramate
    Primary Outcome Measure Information:
    Title
    Individual (each patient) and mean (each treatment) topiramate plasma concentration-time profiles.
    Secondary Outcome Measure Information:
    Title
    Incidence of adverse events throughout the study. Changes from pretreatment to the end of posttreatment phase in take-home records, clinical laboratory results, physical & neurologic examination results, ECGs, renal ultrasounds, vital sign measurements

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    1 Month
    Maximum Age & Unit of Time
    24 Months
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Regular enteral feeding (solid food bottle- or cup-fed) with or without breastfeeding weigh >/=3.5 kilograms (kg) and <15.5 kg Length using an infant measuring table (heel to crown) must be = 49 cm clinical or electroencephalographic (EEG) evidence of POS (simple or complex) with or without secondary generalization of at least 1 month in duration in infants >6 months of age, or at least 2 weeks in duration in infants <6 months of age Multiple seizure types allowed as long as POS is present Taking 1 or 2 concurrent marketed antiepileptic drugs (AEDs) for >1 month for infants >6 months of age and for >2 weeks for infants <6 months of age the regimen of AEDs at entry must be considered inadequate in controlling seizures, after being optimized in the opinion of the investigator Have had a computerized tomography or magnetic resonance imaging scan to confirm the absence of a progressive lesion such as a tumor, with the exception of lesions of tuberous sclerosis and Sturge-Weber syndrome, which are allowed. Exclusion Criteria: Exclusively breast-fed and cannot take oral liquid medication Receives regular enteral feeding using gastrostomy, jejunostomy, or nasogastric tube have surgically implanted and functioning vagus nerve stimulator Have febrile seizures or seizures due to an acute medical illness Have infantile seizures as a result of a correctable medical condition such as metabolic disturbance, toxic exposure, neoplasm, or active infection History of nonepileptic seizures, either current or at any point in the past Any progressive neurologic disorder, including malignancy, brain tumor, active central nervous system infection, demyelinating disease, or degenerative or progressive central nervous system disease with the exception of tuberous sclerosis and Sturge Weber syndrome.
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial
    Organizational Affiliation
    Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Citations:
    PubMed Identifier
    22633629
    Citation
    Ness S, Todd MJ, Wang S, Eerdekens M, Nye JS, Ford L. Adaptive behavior outcomes in infants treated with adjunctive topiramate. Pediatr Neurol. 2012 Jun;46(6):350-8. doi: 10.1016/j.pediatrneurol.2012.02.028.
    Results Reference
    derived
    PubMed Identifier
    21673279
    Citation
    Puri V, Ness S, Sattaluri SJ, Wang S, Todd M, Yuen E, Eerdekens M, Nye JS, Manitpisitkul P, Shalayda K, Ford L. Long-term open-label study of adjunctive topiramate in infants with refractory partial-onset seizures. J Child Neurol. 2011 Oct;26(10):1271-83. doi: 10.1177/0883073811406982. Epub 2011 Jun 14.
    Results Reference
    derived

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    A Study of the Pharmacokinetics, Safety and Tolerability of Topiramate in Infants (Age 1-24 Months) With Refractory Partial-onset Seizures

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