Study Designed to Evaluate the Safety of Prophylactic Depakote ER in the Treatment of Adolescents With Migraine

Divalproex Sodium Extended-Release Tablets for Migraine Prophylaxis in Adolescents: An Open-Label, Long-Term Safety Study

The purpose of this study is to determine if long-term treatment, up to 1 year, with Depakote ER is safe in the reduction of occurrence of migraine headaches in adolescents.

Inclusion Criteria:

• Subject and subject's legal representative have voluntarily signed and dated an IRB-approved informed assent form and an IRB-approved informed consent form, respectively, before any study-specific procedures or tests are performed;
• Subject is male, or a non-pregnant, non-lactating female;
• Subject is between 12 and 17 years of age, inclusive, at the Screening Visit;
• Subject weighs at least 77 lbs. (i.e., 35 kg);
• Subject currently has diagnosis of migraine headaches consistent with International Headache Society (IHS) criteria;
• Subject is judged to be in generally good health based on the results of a medical history, physical examination, 12-lead electrocardiogram (ECG), and laboratory profile; and
• In the investigator's opinion, the subject will benefit from Depakote ER for migraine prophylaxis.

Exclusion Criteria:

• History of allergic reaction or significant sensitivity to valproate or similar drugs;

• History of noncompliance with medication or medical instructions;

• Recent (previous 6 months) history of drug and/or alcohol abuse or has a positive urine drug screen, at the Screening Visit, for drugs of abuse (e.g., amphetamines, barbiturates, benzodiazepines, cocaine, opiates, and phencyclidine [PCP]);

• Female, of childbearing potential, and not using an effective method of birth control (e.g., total sexual abstinence or contraceptives) as judged by the investigator.

• Use of the following medication classes or any specific drug listed below:

  • anti-depressants, other antiepileptic drugs (AEDs)
  • aspirin and/or aspirin-containing products
  • chronic use of systemic corticosteroids, clonazepam,diazepam, erythromycin, ethosuximide, pemoline, phenobarbital,rifampin,tolbutamide, zidovudine
  • anticoagulant drug therapy;

• Any serious medical or psychiatric disorder(s), including epilepsy and obesity, that may confound the interpretation of the results from this study;

• Central nervous system (CNS) neoplasm, CNS infection, demyelinating disease, degenerative neurological disease, or any progressive CNS disease;

• History of encephalopathy, hepatitis, pancreatitis, or urea-cycle disorder or any underlying condition/disease, which might interfere with study drug absorption or completion of study drug therapy evaluation throughout the duration of the trial;

• Screening laboratory results indicate the presence of Hepatitis B surface antigen (HBsAg), or Hepatitis C antibody or known history of any positive test result for HIV;

• Screening laboratory results indicate:

  1. Platelet count =/< 100,000/uL
  2. ALT or AST =/> 2 times Upper Limit of Normal (ULN);

• Receipt of an investigational drug within 30 days prior to study drug administration or scheduled to receive any other investigational drug anytime during the study;

• Participation in a prior Depakote ER migraine study (M02-488 or M02-554); or if for any reason, subject is considered by the investigator to be an unsuitable candidate to receive Depakote or to participate in this study.