A Randomized, Active-Controlled, Open-Label, Flexible-Dose Study to Assess the Safety and Tolerability of Topiramate as Monotherapy Compared With Levetiracetam as Monotherapy in Pediatric Subjects With New or Recent-Onset Epilepsy - Long term Safety TOPAMAX monotherapy in pediatric patients
- Conditions
- ew-onset or recent-onset epilepsy.MedDRA version: 17.0Level: PTClassification code 10015037Term: EpilepsySystem Organ Class: 10029205 - Nervous system disordersTherapeutic area: Diseases [C] - Nervous System Diseases [C10]
- Registration Number
- EUCTR2012-001552-19-IT
- Lead Sponsor
- Janssen-Cilag International N.V.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 63
1 Subject must be a child or adolescent (male or female) 2 to 15 years of age with a clinical diagnosis of new-onset or recent-onset epilepsy characterized by POS (with or without secondary generalization) or PGTCS in accordance with criteria of the International League Against Epilepsy. The epilepsy diagnosis must be within the previous 2 years before screening.2 Subject must have clinical or electroencephalogram (EEG) evidence of POS (simple or complex), with or without secondary generalization, or PGTCS at least 3 months prior to the first day of screening. Subjects should have at least 1, but no more than 2, unprovoked seizures during the 3 months prior to screening. Acceptable evidence of POS includes 1 of the following:
•Documented recurrent clinical seizures with asymmetric motor features or characteristic behavioral alterations. The interictal EEGs may be negative or inconclusive, provided that the clinical criterion for POS is met.
•A routine EEG or video EEG showing focal or asymmetric EEG findings (epileptiform discharges, focal slowing, focal attenuation, or a combination), with or without secondary generalization. Clinical seizures with symmetric or behavioral features are acceptable in the presence of EEG evidence of an asymmetric origin.
Acceptable evidence of PGTCS includes 1 of the following:
•Documented recurrent clinical seizures with seizures that are initially generalized, associated with tonic contractions and clonic movements
•EEG expression that is a generalized, synchronous, symmetrical discharge
•Interictal EEGs may be normal or show generalized discharges such as spikes, polyspike, spike-wave, and polyspike wave.
3 At screening, subject must have weight and height values within the 5th to 95th percentile for chronological age (based on standard Child Height and Weight Charts from the CDC). 4 Subject must never have been treated for epilepsy (treatment-naïve) or have been treated with no more than 1 standard AED if temporary or urgent AED use was necessary. Previous AED exposure must not exceed either of the following:
•Thirty-one days immediately preceding enrollment, or
•A total of 6 months of previous AED exposure in the past if the AED has been discontinued for at least 1 year prior to enrollment
5 If subject is currently treated with an AED, inadequacy of current epilepsy treatment must be documented on a worksheet provided to the investigator. Criteria for inadequacy include:
•AED dosage is considered optimized (including, if clinically appropriate, recent demonstration of adequate blood levels) in the opinion of the investigator and unchanged for at least 5 half-lives prior to the first day of screening and found to be:
-Inadequate in controlling seizures in the opinion of the investigator, as shown in part by a retrospective history of at least 1 seizure in the 3 months prior to screening, or
-Not well tolerated
6 Parents (or legally acceptable representatives) of the subject must sign an informed consent/permission document, indicating that they understand the purpose of and procedures required for the study and are willing to give permission for their child to participate in the study. Subjects 7 years of age and older, capable of understanding the nature of the study, must provide assent for their participation. 7 Caregivers (parents or legally acceptable representatives) of the subject must be able to accurately maintain the subject take-home record and seizure diary. 8 Subject m
1 Subject has a surgically implanted and functioning vagus nerve stimulator. 2 Subject has a history of seizures as a result of a correctable medical condition, such as metabolic disturbance, toxic exposure, neoplasm, or active infection within 2 weeks prior to the first day of screening. 3 Subject has had uncontrolled seizures while previously taking either topiramate or levetiracetam. 4 Subject has a history of nonepileptic seizures within 2 weeks prior to the first day of screening. 5 Subject has myoclonic or absence seizures. 6 Subject has a history of status epilepticus within 2 weeks prior to first day of screening. Status epilepticus is defined as 30 minutes of continuous motor seizures. 7 Subject has had epilepsy surgery within 3 months prior to the first day of screening. 8 Subject has 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. 9 Subject has any clinically significant uncontrolled medical illness, including hepatic or renal failure, ischemic cardiac disease, bone disorders, growth and maturation disorders of any type, malignancy, physical impairments that prevent normal ambulation, or any disorder that, in the opinion of the investigator, places the subject at risk through participation in a clinical study. 10 Subject has nephrocalcinosis, renal stones of any type, or hydronephrosis, as evidenced by medical history or screening examination. 11 Subject has a history of =2 long bone fractures if the subject is =10 years old; =3 long bone fractures if the subject is >10 years old, where at least 1 of the fractures was a low-impact fracture, defined as slight trauma that may include:
•Falling to the ground from <0.5 m (standing height)
•Falling to a resilient surface (rubber or sand) from 0.5 to 3 m
•Falling from a bed or cot
•Playing injuries, including playground scuffles
12 Subject has indwelling hardware, or has an abnormality of the skeleton or spine, such as scoliosis of 20 degrees or more, kyphosis, or skeletal dysplasia. 13 Subject has clinically relevant abnormalities noted on renal ultrasound or DEXA scans. Subjects with baseline BMD Z-scores =-2, for either posterior-anterior lumbar spine (L1 L4) or total body less head, will not be enrolled. 14 Subject has congenital glaucoma or known ocular deficits, or is receiving any ocular medications except lubricating eye drops or topical antibiotics. 15 Subject has a known history of central hyperthermia, dysautonomia, or other disturbances of autonomic function. 16 Subject has a known history of inborn errors of metabolism, mitochondrial dysfunction, or prior evidence of hyperammonemia. 17 Subject has any clinically significant abnormality in laboratory tests at screening, including but not limited to:
•WBC count <3,000/mL or absolute neutrophil count <1,000 /mL in the last 6 months
•Aspartate aminotransferase (AST), alanine aminotransferase (ALT), or gamma-glutamyltransferase (GGT) 3 times the ULN
•Total bilirubin 1.5 mg/dL or conjugated bilirubin 20% of total
•Venous ammonia 2 times the ULN
•25-hydroxy-vitamin D (normal reference range is =20.0 ng/mL)
•Parathyroid hormone (normal reference range is 14.0 to 72.0 pg/mL)
•1,25-dihydroxy-vitamin D, as determined by the age-dependent reference ranges (see lab manual)
•Insulin-like growth factor
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method