Partial Onset Epilepsy and other Seizures
Conditions
Interventions
Product Name: Topiramate Oral Solution
Product Code: F017
Pharmaceutical Form: Oral solution
INN or Proposed INN: Topiramate
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equa
Sponsors
Janssen-Cilag International N.V.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Subjects must be male or female infants between 1 and 23 months of age, inclusive, at screening. • Subjects must be at least 41 weeks of gestational age at screening. • Subjects must be receiving regular enteral feeding (solid food; bottle- or cup-fed; or using gastrostomy, jejunostomy, or nasogastric tube), with or without breast-feeding. • Subjects must weigh > or =3.5 kg and or =49 cm. There must be evidence of continued weight and height gain prior to the first day of screening. • Parents (or their legally acceptable representatives) of subjects must have signed 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 must have clinical or EEG evidence of POS (simple or complex), with or without secondary generalization, at least 1 month prior to the first day of screening in subjects >6 months of age, or at least 2 weeks prior to the first day of screening in subjects or =1 month for subjects >6 months of age and for >2 weeks for subjects < or =6 months of age; this regimen must remain unchanged throughout the screening and double-blind treatment phases. • As documented on the worksheet for inadequacy of treatment, the regimen of AEDs at entry: - Must be considered to be optimized (including, if clinically appropriate, recent demonstration of adequate blood levels) in the opinion of the investigator - Must be considered 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 4 weeks prior to the first day of screening - Must have been unchanged for at least 5 half-lives prior to the first day of screening, as described in Section 8.1 and Attachment 2 • Caregivers (parents or their legally acceptable representatives) of the subjects must be able to accurately maintain the subject take-home record, including items of general health. • Subjects must 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. • Subjects must have an ECG at screening with no abnormal, clinically significant interpretations by the central reader. Subjects who meet all previous inclusion criteria, and meet the following additional inclusion criterion, will be eligible for the baseline 48-hour vEEG: • Subjects must have a retrospective history of at least 7 seizures in the 2 weeks before the first day of scree
Exclusion criteria
Exclusion criteria: Potential subjects who meet any of the following criteria will be excluded from participating in the study: • Infants who are exclusively breast-fed and cannot take oral liquid medication • Subjects with a surgically implanted and functioning vagus nerve stimulator • Subjects with a history of febrile seizures or seizures due to an acute medical illness within 2 weeks prior to the first day of screening • Subjects with a history of infantile 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 • Subjects with a history of nonepileptic seizures within 2 weeks prior to the first day of screening • Subjects who have had epilepsy surgery within 3 months prior to the first day of screening • Subjects with 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 • Subjects with any clinically significant uncontrolled medical illness, including hepatic or renal failure, ischemic cardiac disease, malignancy, or any disorder that, in the opinion of the investigator, places the subject at risk through participation in a clinical study • Subjects with nephrocalcinosis, renal stones of any type, or hydronephrosis, as evidenced by medical history or screening examination • Subjects with congenital glaucoma, abnormal slit-lamp examination (if previously performed), or known ocular deficits, or subjects receiving any ocular medications except lubricating eye drops or topical antibiotics • Subjects with a known history of central hyperthermia, dysautonomia, or other disturbances of autonomic function • Subjects with a known history of inborn errors of metabolism, mitochondrial dysfunction, or prior evidence of hyperammonemia • Subjects with any clinically significant abnormality in laboratory tests at screening, including but not limited to: - White blood cell (WBC) count 6 months of age or at any time for those or =2 times the ULN - Total bilirubin > or =1.5 mg/dL or conjugated bilirubin > or =20% of total - Venous ammonia > or =2 times the ULN - Creatinine clearance or =1 month to or =6 months to <2 years of age; creatinine clearance at screening should be estimated using the Schwartz formula as follows: • Subjects who are receiving 3 or more concurrent AEDs (including phenobarbital or benzodiazepines, regardless of the reason for prescription) • Subjects being treated with furosemide, hydrochlorothiazide, vigabatrin, vitamin B6 therapy for epilepsy, monoamine oxidase (A or B) inhibitors, felbamate, zonisamide, or any other medication that is a potent carbonic anhydrase inhibitor (e.g., acetazolamide). Past treatment with furosemide for more than 2 weeks must be discussed with the sponsor. • Subjects who have been treated with an investigational drug within 2 weeks prior to the first day of screening • Subjects who have previously used topiramate or who have participated in a topiramate clinical study within 1 month prior to the first day of screening • Subjects with a known allergy or hyp
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is: • To compare the effectiveness of topiramate 5, 15, or 25 mg/kg/day (administered as either sprinkle capsules or oral liquid formulation) with that of placebo as an adjunct to concurrent anticonvulsant therapy in reducing POS seizure rates in infants (1 to 23 months of age, inclusive) with POS after 20 days of double-blind treatment ;Secondary Objective: • To evaluate the safety and tolerability of topiramate oral liquid and sprinkle formulations in infants with epilepsy at dosages up to 5, 15, and 25 mg/kg/day (in 20 days of double-blind treatment) and up to 60 mg/kg/day (in up to 1 year of open-label treatment) Pharmacokinetic assessments will be conducted to supplement data from other studies, for further characterization of the pharmacokinetics of topiramate and to evaluate the effects of covariates on the pharmacokinetics of topiramate in infants with epilepsy. ;Primary end point(s): The primary efficacy variable will be the percentage reduction in POS seizure rate from baseline to end point in the double-blind treatment phase as recorded on 48-hour vEEG and read by the central reader. | — |
Countries
Belgium, Czech Republic, Finland, Hungary, Italy, Norway, Spain, United Kingdom
Outcome results
None listed