Tolerability and Efficacy of Depakote-extended Release in the Elderly

Study Overview
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Brief Summary
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There is a bimodal distribution to the new onset seizures with one peak occurring in the very young and the second peak occurring in persons over age 65 years. The presentation of seizures in the elderly may vary from that of younger patients and the diagnosis may be confused with other conditions such as transient ischemic attacks. However, the consequences of epilepsy in the elderly can be severe leading to impaired cognition, increased falls, and a decreased quality of life. The treatment of epilepsy may be complicated by pharmacokinetic and pharmacodynamic changes occurring in the elderly.

Detailed Description
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There is a bimodal distribution to the new onset seizures with one peak occurring in the very young and the second peak occurring in persons over age 65 years. The presentation of seizures in the elderly may vary from that of younger patients and the diagnosis may be confused with other conditions such as transient ischemic attacks. However, the consequences of epilepsy in the elderly can be severe leading to impaired cognition, increased falls, and a decreased quality of life. The treatment of epilepsy may be complicated by pharmacokinetic and pharmacodynamic changes occurring in the elderly. Three Veterans Cooperative trials evaluating antiepileptic drug (AED) therapy in the elderly demonstrated that the ability to tolerate the AED is a more determining factor for long term success than the ability to suppress seizure activity. In general, elderly patients appear more intolerable to medications. This may stem from co-morbid conditions, concurrent medications, pharmacokinetic changes, and/or pharmacodynamic changes. Therefore, it is important to study the efficacy and tolerability of AEDs in the elderly. Valproic acid has been available for the treatment of partial and generalized seizures since 1978. Sodium divalproex is metabolized in the gut to valproic acid. Depakote and Depakote-ER (extended release)are among the dosage forms of sodium divalproex. Depakote is an enteric coated tablet that is designed to dissolve in the more alkaline milieu of the small intestine rather than the more acidic milieu of the stomach. This helps the drug to bypass the stomach and reduces gastrointestinal distress. Once the enteric coating dissolves, the sodium divalproex is metabolized to valproic acid and rapidly absorbed. Depakote is administered twice a day. Depakote-ER is a controlled release drug delivery system designed to release drug over a 22 hour period which allows for once a day dosing. The efficacy and tolerability of Depakote-ER has not been described in elderly patients with epilepsy.

Official Title
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Tolerability and Efficacy of Depakote-ER in the Elderly

Conditions
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Elderly, Epilepsy, Seizures

Intervention / Treatment
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* Drug: Divalproex Sodium Extended-Release Tablets


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Is > 60 years of age (male or female) Has a confirmed diagnosis of epilepsy with partial seizures Has one of the following newly diagnosed partial seizures has inadequately controlled partial seizures, i.e. continues to have seizure activity while on his/her medication regimen is taking Depakote twice a day for partial seizures but is having side effects or problems with adherence and may benefit from once a day dosing Is able and willing to maintain an accurate, complete, written daily seizure diary Is able and willing to complete the QOLIE, the Beck Depression Inventory, and the SSQ Is able to given written informed consent Is compliant with clinic visits Is able to swallow Depakote-ER Exclusion Criteria: Has had status epilepticus in the 24 weeks prior to the Baseline Phase of the Study Is taking three or more AEDs chronically Is currently abusing alcohol and/or any other substance Has taken an investigational drug within the previous 30 days or plans to take an investigational drug anytime during the study Is receiving any medication that could influence seizure control Is currently following the ketogenic diet Is planning surgery or the insertion of the vagal nerve stimulator for seizure control during the course of the study. Is suffering from acute or progressive neurologic disease, severe psychiatric disease, or severe mental abnormality that are likely to interfere with the objectives of the study Has any clinically significant cardiac, renal, hepatic condition, or a condition that affects the absorption, distribution, metabolism or excretion of drugs. Baseline elevations of LFTs more than 3 times normal, clinically elevated amylase, and clinically significant thrombocytopenia

Ages Eligible for Study
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Minimum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Divalproex Sodium Extended-Release Tablets|Once a day dosing|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effectiveness of Medication as Measured by Participation Through the End of the Trial. | Number of participants completing the trial | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient's Compliance With Once a Day Dosing. | Subjects pill count for once a day dosing and compliance with medication as a percent of total doses prescribed. | 24 weeks | 
| Number of Seizures Per Month | Count of seizures per month determined by seizures recorded in diaries. | 24 weeks | 
| Change From Baseline as Measured by the Seizure Severity Questionnaire (SSQ) | Seizure Severity Questionnaire summary score, on a scale of 1 to 7 with one being the least severe and 7 being the most severe, components of seizures include; warning, activity and recovery | 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Treatment Efficacy, pharmacokinetics