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

Sponsor:	Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Information provided by:	Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
ClinicalTrials.gov Identifier:	NCT00233012

Purpose

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).

Condition	Intervention	Phase
Seizures	Drug: Topiramate	Phase I

Study Type:	Interventional
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

Resource links provided by NLM:

Genetics Home Reference related topics: pyridoxal 5'-phosphate-dependent epilepsy pyridoxine-dependent epilepsy

MedlinePlus related topics: Seizures

Drug Information available for: Topiramate

U.S. FDA Resources

Further study details as provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.:

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

Enrollment:	16
Study Start Date:	June 2005
Study Completion Date:	October 2007

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.

Eligibility

Ages Eligible for Study:	1 Month to 24 Months
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00233012

Sponsors and Collaborators

Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Investigators

Study Director:

Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial

Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

More Information

No publications provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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. Epub 2011 Jun 14.

ClinicalTrials.gov Identifier:	NCT00233012 History of Changes
Other Study ID Numbers:	CR002236
Study First Received:	October 3, 2005
Last Updated:	May 24, 2010
Health Authority:	United States: Food and Drug Administration

Keywords provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.:

Refractory partial-onset seizures
Infants aged 1-24 months
Pharmacokinetics
Topiramate

Additional relevant MeSH terms:

Seizures
Epilepsy
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurologic Manifestations
Signs and Symptoms
Topiramate

Anticonvulsants
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Neuroprotective Agents
Protective Agents
Physiological Effects of Drugs
Anti-Obesity Agents

ClinicalTrials.gov processed this record on February 12, 2012