A Dose Ranging Pilot Study for Intracerebroventricular (ICV) Delivery of Valproate in Subjects With Temporal Seizures
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02899611|
Recruitment Status : Recruiting
First Posted : September 14, 2016
Last Update Posted : January 25, 2018
|Condition or disease||Intervention/treatment||Phase|
|Epilepsy||Drug: Valproate||Phase 1 Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||12 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Dose Ranging Pilot Study to Assess Intracerebroventricular (ICV) Delivery of Valproate in Subjects With Focal Seizures, With Temporal Lobe Onset With or Without Secondary Generalization|
|Study Start Date :||August 2016|
|Estimated Primary Completion Date :||February 2020|
|Estimated Study Completion Date :||February 2021|
Experimental: ICV Valproate
Patients receive a daily dose of ICV Valproate that increases from 3 mg to 60 mg (or MTD) over 8 weeks. A placebo week is randomly inserted in the dose escalation. During the placebo week, the patient receives normal saline.
ICV Valproate is a dilution of the commercially available Epilim product, which is a sterile intravenous (IV) formulation of Sodium Valproate.
- Maximum Tolerated Dose (MTD) [ Time Frame: 2 months ]The ICV Valproate dose will be escalated stepwise through Day 64, if tolerated, or stopped earlier upon establishment of a subject's MTD. The MTD for each subject will be determined based on the highest dose tolerated without experiencing a dose-limiting AE.
- Safety: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [ Time Frame: 14 months ]Safety will be evaluated by monitoring for adverse events (AEs) and serious adverse events (SAEs). This will be monitored using various metrics including: clinical assessments, seizure diaries, concomitant medications, blood and CSF sampling. MRI Scan, EEG and ECG will also be performed and monitored to evaluate safety.
- Changes in the Number of Seizures [ Time Frame: 14 months ]Seizure diaries will be collected, monitored and reviewed at designated time points.
- Pharmacokinetic Parameters [ Time Frame: 20 months ]Peak Plasma Concentration (Cmax) will be measured for plasma and cerebrospinal fluid levels of valproate for each subject.
- Pharmacokinetic Parameters 2 [ Time Frame: 20 months ]Area Under Curve will be measured for plasma and cerebrospinal fluid levels of valproate for each subject.
- Pharmacokinetic Parameters 3 [ Time Frame: 20 months ]Half Life will be measured for plasma and cerebrospinal fluid levels of valproate for each subject.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02899611
|Contact: Rebecca Gibsonfirstname.lastname@example.org|
|St. Vincent Hospital||Recruiting|
|Melbourne, Victoria, Australia, 3010|
|Contact: Emma Priest email@example.com|