Fasted Bioequivalence Study of Primidone Tablets and Mysoline Tablets

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Therapeutic Equivalency

Intervention / Treatment
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* Drug: Primidone 50 mg Tablet
* Drug: Primidone (Mysoline®) 50 mg Tablet


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Primidone 50 mg Tablets<br>A single dose of primidone 50 mg administered after an overnight fast of at least 10 hours. | Drug: Primidone 50 mg Tablet<br>* 50 mg tablet administered after an overnight fast of at least 10 hours.<br>|
| Experimental: Primidone (Mysoline®) 50 mg Tablets<br>A single dose of Mysoline® 50 mg administered after an overnight fast of at least 10 hours. | Drug: Primidone (Mysoline®) 50 mg Tablet<br>* 50 mg tablet administered after an overnight fast of at least 10 hours.<br>* Other names: Mysoline®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Plasma Concentration (Cmax) | The maximum or peak concentration that the drug reaches in the plasma. | 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. | 
| Area Under the Concentration Versus Time Curve From Time 0 to Time t [AUC(0-t)] | The area under the plasma concentration versus time curve, from time 0 to the time of the last measurable concentration (t), as calculated by the linear trapezoidal rule. | 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. | 
| Area Under the Concentration Versus Time Curve From Time 0 Extrapolated to Infinity [AUC(0-∞)] | The area under the plasma concentration versus time curve from time 0 to infinity. AUC(0-∞) was calculated as the sum of AUC(0-t) plus the ratio of the last measurable plasma concentration to the elimination rate constant. | 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. |