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This is a prospective, randomized, double-blind, placebo-controlled cross over study designed to evaluate the efficacy and safety of everolimus (trough 5-15 ng/mL) given as adjunctive therapy in patients with focal cortical dysplasia type II who already failed more than two antiepileptic drugs and surgery.
This study will assess the impact of everolimus to placebo on seizure frequency in focal cortical dysplasia type II. The number of patients who experience seizure reduction of 50% or more will be counted during last 4 weeks of each core phase.
This is a prospective, randomized, double-blind, placebo-controlled cross over study to evaluate the efficacy and safety of everolimus (trough 5-15 ng/mL) given as adjunctive therapy in patients with FCDII who already failed more than 2 antiepileptic drugs and surgery.
1. Baseline phase (4 weeks, week -4~-1): From Screening Visit (Week -4, V1) to starting titration visit at Week -1 (V2). For baseline seizure frequency calculations, the 4-week prospective period seizure counts will be totaled. Antiepileptic drug use will be assessed, and patients are required to be on a stable dose of AEDs. All patients who meet eligibility criteria will be randomized in a 1:1 ratio to treatment first arm and placebo first arm.
2. Core phase I (12 weeks, week 0~11) 2.1.Titration I period (4 weeks, week 0~3): Everolimus doses will be 4.5mg/m2 po daily given at first time and then during the 4-week titration period everolimus dose may get adjusted to reach trough concentration of 5 - 15 ng/mL. At week 2 (V3), 3 (V4) pre-dose PK blood samples will be taken for potential dose adjustments.
2.2. Maintenance I period (8 weeks, week 4~11): After the completion of the titration period, the vast majority of patients are expected to continue at their current dose level during the entire 8 week maintenance period. However, the possibility of further titration does still exist, based on the planned pre-dose PK blood samples that will be collected every 4 weeks [week 4(V5) and 8(V6)].
3. Core phase II (12 weeks, week 12~23): After the completion of the core phase I, the everolimus first group will be changed to the placebo and the placebo first group will take everolimus. Dose titration method is same with core phase I.
4. Unblinded extension phase (29 weeks, week 24-52): After approval, all enrolled patients will be offered the opportunity to enter the unblinded extension phase of the study at the end of week 23 and continue everolimus. Everolimus will be provided to every study patient during the extension phase of 29 weeks. During the extension phase Everolimus doses will be titrated based on pre-dose PK blood samples at week 24 (V12), 28 (V13), 40 (V14), seizure frequency and everolimus tolerability. At week 52 (V15), the final analysis which include serum and CSF PK studies will be performed.
Epilepsy and Focal Cortical Dysplasia II
Not yet recruiting
Published on BioPortfolio: 2017-06-27T05:08:22-0400
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A disorder characterized by recurrent partial seizures marked by impairment of cognition. During the seizure the individual may experience a wide variety of psychic phenomenon including formed hallucinations, illusions, deja vu, intense emotional feelings, confusion, and spatial disorientation. Focal motor activity, sensory alterations and AUTOMATISM may also occur. Complex partial seizures often originate from foci in one or both temporal lobes. The etiology may be idiopathic (cryptogenic partial complex epilepsy) or occur as a secondary manifestation of a focal cortical lesion (symptomatic partial complex epilepsy). (From Adams et al., Principles of Neurology, 6th ed, pp317-8)
Cortical malformations secondary to abnormal cortical maturation after CELL MIGRATION in NEUROGENESIS. This group includes injury to the cortex during later stages of cortical development such as POLYMICROGYRIA and focal cortical dysplasias.
Heterogeneous disorders of cortical malformation characterized by excessive and small fused gyri and shallow sulci of the CORTEX with abnormal cortical lamination. It is considered a malformation secondary to abnormal post-migrational development of the neurons during cerebral cortical development and is associated with EPILEPSY and learning difficulties.
A neurosurgical procedure that removes or disconnects the epileptogenic CEREBRAL CORTEX of a hemisphere. Hemispherectomy is usually performed for patients with intractable unilateral EPILEPSY due to malformations of cortical development or brain lesions. Depending on the epileptogenic area in the hemisphere, cortical removal can be total or partial.
A disorder characterized by recurrent focal onset seizures which have sensory (i.e., olfactory, visual, tactile, gustatory, or auditory) manifestations. Partial seizures that feature alterations of consciousness are referred to as complex partial seizures (EPILEPSY, COMPLEX PARTIAL).
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