Fasted Bioequivalence Study of Primidone Tablets and Mysoline Tablets

Official Title: “A Randomized, Two-Way, Single-Dose, Open-Label Study to Evaluate the Bioequivalence of a Test Tablet Formulation of Primidone 50 mg, Compared to an Equivalent Dose of Primidone (Mysoline®) in Healthy Adult Subjects”

The purpose of this study is to compare the bioequivalence of a test formulation of primidone tablets to an equivalent oral dose of the commercially available Mysoline®(primidone tablets) in adult subjects under fasting conditions.

The purpose of this study is to compare the bioequivalence of a test formulation of primidone tablets to an equivalent oral dose of the commercially available Mysoline® (primidone tablets) in adult subjects under fasting conditions.

Twenty-two healthy, non-smoking, non-obese male and female volunteers at least 18 years of age will be randomly assigned in a crossover fashion to receive each of two primidone dosing regimens in sequence with a 14 day washout period between dosing periods. On the morning of Day 1, after an overnight fast of at least 10 hours, subjects will receive either a single oral dose of the test formulation, primidone (1 x 50 mg tablet) or a single oral dose of the reference formulation, Mysoline® (1 x 50 mg tablet). After a 14 day washout period, on the morning of Day 15 after an overnight fast, subjects will receive the alternate regimen.

Blood samples will be drawn from all participants before dosing and for 72 hours post dose at times sufficient to adequately define the pharmacokinetics of primidone. A further goal of this study is to evaluate the safety and tolerability of this regimen in healthy volunteers. Subjects will be monitored throughout the confinement portion of the study for adverse reactions to the study drugs and/or procedures. Blood pressure and heart rate will be obtained prior to dosing and at 3, 4, 6, 24 and 72 hours post-dose. All adverse events whether elicited by query, spontaneously reported or observed by clinic staff will be evaluated by the investigator and reported in the subject's case report form.

Intervention(s) in this Clinical Trial

• Drug: Primidone 50 mg Tablet
  • 50 mg tablet administered after an overnight fast of at least 10 hours.
• Drug: Primidone (Mysoline®) 50 mg Tablet
  • 50 mg tablet administered after an overnight fast of at least 10 hours.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Primidone 50 mg Tablets
  • A single dose of primidone 50 mg administered after an overnight fast of at least 10 hours.
• Experimental: Primidone (Mysoline®) 50 mg Tablets
  • A single dose of Mysoline® 50 mg administered after an overnight fast of at least 10 hours.

Primary Measures

• Maximum Plasma Concentration (Cmax)
  • Time Frame: serial pharmacokinetic plasma concentrations were drawn prior to dose administration (0 hour) and at 0.33, 0.67, 1, 1.33, 1.67, 2, 2.33, 2.67, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 18, 24, 36, 48, 60 and 72 hours after drug administration.
    Safety Issue?: No
• Area Under the Concentration Versus Time Curve From Time 0 to Time t [AUC(0-t)]
  • Time Frame: serial pharmacokinetic plasma concentrations were drawn prior to dose administration (0 hour) and at 0.33, 0.67, 1, 1.33, 1.67, 2, 2.33, 2.67, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 18, 24, 36, 48, 60 and 72 hours after drug administration.
    Safety Issue?: No
• Area Under the Concentration Versus Time Curve From Time 0 Extrapolated to Infinity [AUC(0-∞)]
  • Time Frame: serial pharmacokinetic plasma concentrations were drawn prior to dose administration (0 hour) and at 0.33, 0.67, 1, 1.33, 1.67, 2, 2.33, 2.67, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 18, 24, 36, 48, 60 and 72 hours after drug administration.
    Safety Issue?: No

Inclusion Criteria:

• male or female
• at least 18 years of age
• weight must be 15% of ideal weight for height and frame
• subjects must be in good health and physical condition as determined by medical history
• subjects must read and sign consent form

Exclusion Criteria:

• history of treatment for alcoholism, substance abuse, or drug abuse within the last 24 months
• history of malignancy, stroke, diabetes, cardiac, renal or liver disease
• history of gastroesophageal reflux disease (GERD), malabsorption syndrome, colon cancer, chronic colitis, including Crohn's disease
• history of porphyria, hyperkinesia, respiratory diseases (eg. asthma, emphysema, difficulty breathing, pulmonary obstruction)
• females who pregnant or lactating
• history of hypersensitivity to primidone, barbiturates, and anticonvulsants
• sitting systolic blood pressure below 90mm Hg, or diastolic pressure below 50mm Hg (conditions upon screening which might contraindicate or require that caution be used in the administration of primidone)
• heart rate less than 50 beats per minute after a 5 minute rest
• treatment with any other investigational drug during the four weeks prior to initial dosing
• subjects who have donated blood within four weeks prior to the initial dosing
• subjects who smoke or use tobacco products or nicotine products. Three months abstinence is required.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Investigator: Mutual Pharmaceutical Company, Inc. Industry

Information obtained from ClinicalTrials.gov on February 09, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00685165

Study ID Number: 04090

ClinicalTrials.gov Identifier: NCT00685165

Health Authority: United States: Institutional Review Board

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