Bioequivalence Study of Divalproex Sodium Delayed-Release Tablets, 500 mg

• Register: ClinicalTrials.gov
• Last refreshed on: 17 October 2012
• Main ID: NCT01184391
• Date of registration: 24/09/2009
• Primary sponsor: Mylan Pharmaceuticals
• Public title: Bioequivalence Study of Divalproex Sodium Delayed-Release Tablets, 500 mg
• Scientific title: Single-Dose Fasting Bioequivalence Study of Divalproex Sodium Delayed-Release Tablets (500 mg; Mylan) and Depakote Tablets (500 mg; Abbott) in Healthy Adult Male And Female (Not of Childbearing Potential) Volunteers
• Date of first enrolment: July 2007
• Target sample size: 17
• Recruitment status: Completed
• URL: http://clinicaltrials.gov/show/NCT01184391
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Bio-equivalence Study, Intervention Model: Crossover Assignment, Masking: Open Label

Countries of recruitment

United States

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Age: 18 years and older.

2. Sex: Females not of child bearing potential and males.

- No hormonal contraceptives or hormonal replacement therapies are permitted in
this study.

- Women will not be considered of childbearing potential if one of the following
is reported and documented on the medical history:

- postmenopausal with spontaneous amenorrhea for at least one (1) year, or
spontaneous amenorrhea for less than one (1) year with serum FSH levels >
40 mIU/ml, or

- bilateral oophorectomy with or without a hysterectomy and an absence of
bleeding for at least 6 months, or

- total hysterectomy and an absence of bleeding for at least 3 months.

- During the course of the study, from study screen until study exit - including
the washout period, all men must use a spermicide containing barrier method of
contraception in addition to their current contraceptive method. These
instructions should be documented in the informed consent form.

3. Weight Restrictions:

- At least 60 kg (132 lbs) for men and

- At least 48 kg (106 lbs) for women

- All subjects will have a Body Mass Index (BMI) less than or equal to 30 but
greater than or equal to 19 (see Part II, Administrative Aspects of
Bioequivalence Protocols). BMI values should be rounded to the nearest integer
(ex. 30.4 rounds down to 30, while 18.5 rounds up to 19)

4. All subjects should be judged by the principal or sub-investigator physician listed
on the Form FDA 1572 as normal and healthy during a pre-study medical evaluation
performed within 21 days of the initial dose of study medication which will include:

5. Normal or non-clinically significant physical examination including vital signs,

6. Within normal limits or non-clinically significant laboratory evaluation results for
the following tests:

- Serum Chemistries: sodium, potassium, chloride, BUN, iron, albumin, total
protein AST, Alk. Phos., Calcium, Creatinine, ALT, Total bilirubin, Total
Cholesterol, Phosphate, Uric Acid, Non-fasting Glucose Triglycerides

- Hematology: Platelet Count, Hemoglobin, Leukocyte Differential, Hematocrit, Red
Blood Cells

- Urinalysis: Appearance, Specific Gravity, Protein pH, Microscopic Examination

7. Negative Hepatitis B and Hepatitis C tests,

8. Negative HIV test,

9. Normal or non-clinically significant 12-lead ECG

10. Negative urine drug screen for all of the following compounds: amphetamines,
barbiturates, benzodiazepines, cannabinoid, cocaine, methadone, opiates, and
phencyclidine

Exclusion Criteria:

1. Institutionalized subjects will not be used.

2. Social Habits:

- Use of any tobacco-containing products within 1 year of the start of the study.

- Ingestion of any alcoholic, caffeine- or xanthine-containing food or beverage
within the 48 hours prior to the initial dose of study medication.

- Ingestion of any vitamins or herbal products within 7 days prior to the initial
dose of the study medication.

- Any recent, significant change in dietary or exercise habits.

- Individual has a history of drug and/or alcohol abuse.

3. Medications:

- Use of any prescription or over-the-counter (OTC) medications within fourteen
(14) days prior to the initial dose of study medication.

- Use of any hormone replacement therapy within 3 months prior to study medication
dosing.

- Use of any medication known to induce or inhibit hepatic enzyme activity within
28 days prior to the initial dose of study medication (see Part II,
Administrative Aspects of Bioequivalence Protocols for list).

4. Diseases:

- History of any significant cardiovascular, hepatic, renal, pulmonary,
hematologic, gastrointestinal, endocrine, immunologic, dermatologic, congenital
metabolic disorders or neurologic disease.

- Acute illness at the time of either the pre-study medical evaluation or dosing.

- All laboratory values reflecting hepatic function must be with in 10% of the
upper range of normal in order to be considered not clinically significant.

5. Subjects who have known urea cycle disorders which are a group of uncommon genetic
abnormalities (e.g. ornithine transcarbamylase deficiency).

6. Donation or loss of a significant volume of blood or plasma (> 450 mL) within 28 days
prior to the initial dose of study medication.

7. Subjects who have received an investigational drug within 30 days prior to the
initial dose of study medication.

8. Allergy or hypersensitivity to Divalproex Sodium or any related products.

9. History of difficulties in swallowing, or any gastrointestinal disease which could
affect the drug absorption.

10. Consumption of grapefruit or grapefruit containing products within 7 days of drug
administration



Age minimum: 18 Years
Age maximum: N/A
Gender: Both

Health Condition(s) or Problem(s) studied

Healthy

Intervention(s)

Drug: DEPAKOTE® Tablets, 500 MG

Drug: DIVALPROEX SODIUM DELAYED-RELEASE TABLETS, USP, 500 MG

Primary Outcome(s)

AUCI [Time Frame: 30 days]

AUCL [Time Frame: 30 days]

Cmax [Time Frame: 30 days]

Secondary ID(s)

DIVA-0771

Source(s) of Monetary Support

Please refer to primary and secondary sponsors