A Dose Ranging Pilot Study for Intracerebroventricular (ICV) Delivery of Valproate in Subjects With Temporal Seizures
Condition: Epilepsy
MeSH terms: Epilepsy; Seizures
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      Patients with medically refractory epilepsy will be treated by intracerebroventricular (ICV)
      delivery of valproate using an implantable drug pump system. The dose of valproate will be
      escalated weekly during a blinded-evaluation period through Day 64 to determine the maximum
      tolerated dose (MTD). After Day 64, patients can continue for 52 weeks in the open-label
      evaluation period (non-blinded). .
    

Detailed description: 
      Epilepsy patients that are refractory to oral anti-epileptic drug (AED) treatment have
      significantly higher mortality, higher morbidity, higher economic costs and diminished
      quality of life compared to those who suffer from epilepsy that can be adequately controlled
      with medical management. Current options for refractory patients include neurosurgical brain
      resection, responsive neurostimulation, and vagal nerve stimulation. None of these options is
      satisfactory due to the low applicability of surgery for patients with poorly localized or
      multifocal seizures and the limited success of currently available alternative treatment
      options.

      In this study, patients with medically refractory focal epilepsy will be treated with
      intracerebroventricular (ICV) administration of valproate using an implantable drug pump
      system. This is a dose ranging study, with a randomized, double-blind dose escalation
      component, to establish the dose range of ICV valproate delivery. Clinical assessments,
      adverse events (AEs), seizure diaries, concomitant medications, blood samples and
      cerebrospinal fluid (CSF) will be collected and reviewed at designated time points. Magnetic
      resonance imaging (MRI) and electroencephalography (EEG) will also be performed. Subjects
      will have their surgery, dose changes and pharmacokinetics performed in an inpatient setting.

      The ICV Valproate dose will be escalated stepwise from 3 mg/day to 60 mg/day through Day 64
      if tolerated, or stopped earlier upon establishment of a subject's maximum tolerated dose
      (MTD). The MTD for each subject will be determined based on the highest dose tolerated
      without experiencing a dose-limiting adverse event (AE). After establishing a subject's MTD,
      delivery of ICV Valproate will continue at the MTD through Day 64 of the blinded evaluation
      period. Subjects and assessing physicians will remain blinded to the treatment dose during
      the blinded evaluation period. Subjects can continue in the open-label evaluation period
      (non-blinded) for 52 weeks following the blinded evaluation period.
    

Intervention name(s): Valproate
Intervention type(s): Drug
Intervention description(s): ICV Valproate is a dilution of the commercially available Epilim product, which is a sterile intravenous (IV) formulation of Sodium Valproate.
Other intervention name(s): Valproic acid; Depacon; Epilim
Intervention MeSH terms: Valproic Acid
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Epilepsy