Tolerability and Efficacy of Depakote-extended Release in the Elderly

This study has been completed.
Sponsor:
Collaborator:
Abbott
Information provided by (Responsible Party):
Virginia Commonwealth University
ClinicalTrials.gov Identifier:
NCT00318929
First received: April 25, 2006
Last updated: February 21, 2012
Last verified: June 2010

April 25, 2006
February 21, 2012
April 2006
January 2008   (final data collection date for primary outcome measure)
Effectiveness of Medication as Measured by Participation Through the End of the Trial. [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
Number of participants completing the trial
To assess the effectiveness, i.e. the efficacy and tolerability, of Depakote-ER (controlled release sodium divalproex) in elderly patients with epilepsy. Effectiveness will be measured by survival in the study, i.e.
Complete list of historical versions of study NCT00318929 on ClinicalTrials.gov Archive Site
  • Patient's Compliance With Once a Day Dosing. [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    Subjects pill count for once a day dosing and compliance with medication as a percent of total doses prescribed.
  • Number of Seizures Per Month [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    Count of seizures per month determined by seizures recorded in diaries.
  • Change From Baseline as Measured by the Seizure Severity Questionnaire (SSQ) [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    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
  • Patient’s preference and adherence for once versus twice a day dosing
  • Change from baseline in quality of life as measured by the QUOLIE – 31
  • Change from baseline in depression as measured by the Beck’s Depression Inventory
Not Provided
Not Provided
 
Tolerability and Efficacy of Depakote-extended Release in the Elderly
Tolerability and Efficacy of Depakote-ER in the Elderly

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.

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.

Interventional
Not Provided
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Elderly
  • Epilepsy
  • Seizures
Drug: Divalproex Sodium Extended-Release Tablets
Once a day dosing
Not Provided
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
14
January 2008
January 2008   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Is > 60 years of age (male or female)
  • Has a confirmed diagnosis of epilepsy with partial seizures
  • Has one of the following

    1. newly diagnosed partial seizures
    2. has inadequately controlled partial seizures, i.e. continues to have seizure activity while on his/her medication regimen
    3. 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
Both
60 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00318929
VCUHM10204
No
Virginia Commonwealth University
Virginia Commonwealth University
Abbott
Principal Investigator: Alan R Towne, M.D. Virginia Commonwealth University
Virginia Commonwealth University
June 2010

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP