Divalproex Sodium Delayed-Release Tablets Under Fasting Conditions
Condition: Healthy
Intervention: divalproex sodium; Depakote®
Intervention description: delayed-release 500 mg tablet; delayed-release 500 mg tablet
Intervention MeSH terms: Valproic Acid
Phase: Phase 1
Study type: Interventional
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 24.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Bioequivalence; Healthy Subjects

Summary:

      This study will compare the relative bioavailability of 500 mg Divalproex Sodium
      Delayed-Release Tablets with that of 500 mg Depakote® Tablets following a single oral dose (1
      x 500 mg tablets)in healthy subjects under fasting conditions.
    

Eligibility criteria:

        Inclusion Criteria

          -  Screening Demographics: All subjects selected for this study will be healthy men or
             women 18-65 years of age, inclusive, at the time of dosing. The subject's body mass
             index (BMI) should be less than or equal to 30.

          -  Screening Procedures: Each subject will complete the screening process within 28 days
             prior to period I dosing. Consent documents for both the screening evaluation and HIV
             antibody determination will be reviewed, discussed and signed by each potential
             participant before full implementation of screening procedures.

        Screening will include general observations, physical examination, demographics, medical
        and medication history, an electrocardiogram, sitting blood pressure and heart rate,
        respiratory rate and temperature. The physical examination will include, but may not be
        limited to, an evaluation of the cardiovascular, gastrointestinal, respiratory and central
        nervous systems.

        The screening clinical laboratory procedures will include:

          -  HEMATOLOGY: hematocrit, hemoglobin, WBC count with differential, RBC count, platelet
             count

          -  CLINICAL CHEMISTRY: serum creatinine, BUN, glucose, AST(GOT), ALT(GPT), albumin, total
             bilirubin, total protein, and alkaline phosphatase

          -  HIV antibody, hepatitis B surface antigen, hepatitis C antibody screens

          -  URINALYSIS: by dipstick; full microscopic examination if dipstick positive

          -  URINE DRUG SCREEN: ethyl alcohol, amphetamines, barbiturates, benzodiazepines,
             cannabinoids, cocaine metabolites, opiates and phencyclidine

          -  SERUM PREGNANCY SCREEN (female subjects only)

          -  FOLLICLE STIMULATING HORMONE (FSH; female subjects only): verify postmenopausal status

        If female and:

          -  Is postmenopausal for at least 1 year with postmenopausal status defined as: > 60
             years of age and amenorrheic for at least one year; if 60 years of age or younger,
             must also have a serum FSH level > 30 IU/L; or

          -  Is surgically sterile for at least 6 months (bilateral tubal ligation, bilateral
             oophorectomy, or hysterectomy)

        Exclusion Criteria

          -  Subjects with a recent history of drug or alcohol addiction or abuse.

          -  Subjects with the presence of a clinically significant disorder involving the
             cardiovascular, respiratory, renal, gastrointestinal, immunologic, hematologic,
             endocrine, or neurologic system(s) or psychiatric disease (as determined by the
             clinical investigators).

          -  Subjects whose clinical laboratory test values are outside the accepted reference
             range and when confirmed on re-examination are deemed to be clinically significant.

          -  Subjects demonstrating a positive hepatitis B surface antigen screen, a positive
             hepatitis C antibody screen, or a reactive HIV antibody screen.

          -  Subjects demonstrating a positive drug abuse screen when screened for this study.

          -  Female subjects demonstrating a positive pregnancy screen.

          -  Female subjects who are currently breastfeeding.

          -  Subjects with a history of allergic response(s) to divalproex sodium or related drugs.

          -  Subjects with a history of clinically significant allergies including drug allergies.

          -  Subjects with a clinically significant illness during the 4 weeks prior to Period I
             dosing (as determined by the clinical investigators).

          -  Subjects who currently or report using tobacco products within 90 days of Period I
             dose administration.

          -  Subjects who have taken any drug known to induce or inhibit hepatic drug metabolism in
             the 28 days prior to Period I dosing.

          -  Subjects who report donating greater than 150 mL of blood within 28 days prior to
             Period I dosing. All subjects will be advised not to donate blood for four weeks after
             completing the study.

          -  Subjects who have donated plasma (e.g. plasmapheresis) within 14 days prior to Period
             I dosing. All subjects will be advised not to donate plasma for four weeks after
             completing the study.

          -  Subjects who report receiving any investigational drug within 28 days prior to Period
             I dosing.

          -  Subjects who report taking any systemic prescription medication in the 14 days prior
             to Period I dosing.

          -  Subjects who report an intolerance of direct venipuncture.

          -  Subjects who report consuming an abnormal diet during the 28 days prior to Period I
             dosing.