Bioequivalence Study of Torrent Pharmaceutical Ltd.'s Topiramate Tablets Under Fasted Conditions

Study Overview
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Brief Summary
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Objective: Compare the bioequivalence of a test topiramate formulation (Torrent Pharmaceuticals Limited) to an equivalent oral dose of the commercially available topiramate (Topamax®, Ortho-McNeil Neurologics, Inc.) in a test population of 26 adult subjects under fasted conditions. Clinical Design: Studies were Randomized, Two-Way Crossover, Single-Dose,Open-Label in healthy human adult subjects.

Official Title
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Study to Evaluate the Bioequivalence of a Test Tablet Formulation of Topiramate (2 x 25 mg), Compared to an Equivalent Dose of a Commercially Available Reference Drug Product (Topamax®, Ortho-McNeil Neurologics, Inc.)in Fasted, Healthy, Adult Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: Topiramate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Sex: Male or Female; similar proportions of each preferred. Age: At least 18 - 55 years (inclusive). Weight: BMI (Body Mass Index) 19 kg/m2 - 30 kg/m2 (inclusive). Qualifying subjects must be in good health and physical condition as determined by medical history, complete physical examination, and laboratory tests, all obtained within four (4) weeks prior to study start. The subject may not have a history of significant past illness expected to affect the investigation. The normal status of subjects will be confirmed by the following procedures: Laboratory Tests: Serum pregnancy test (female subjects only), hemoglobin, hematocrit, RBC, WBC, platelet count, differential count, serum electrolytes (Na, K, Cl), fasting blood glucose, BUN, bilirubin, creatinine, AST, ALT, LD, alkaline phosphatase, urinalysis, drugs of abuse, HIV, Hepatitis B, and Hepatitis C will be done for screening purposes. Laboratory values which are greater than 20% of the normal range will not qualify unless specifically accepted by a physician who is an investigator or sub-investigator for the clinical trial. Results of a serum pregnancy test (female subjects only), HIV, Hepatitis B, Hepatitis C, and drugs of abuse must be negative or non-reactive for the subject to qualify for the study. Electrocardiogram: A 12-lead electrocardiogram (ECG) will be obtained for all subjects. The original tracings, plus interpretation, will be included in the case report form packet. Subjects must read and sign the Consent Form. Exclusion Criteria: Subjects not complying with the above inclusion criteria must be excluded from the study. In addition, any one (1) of the conditions listed below will exclude a subject from the study: History of treatment for alcoholism, substance abuse, or drug abuse within the past 24 months. History of malignancy, stroke, diabetes, cardiac, renal or liver disease, or other serious illness. History of GERD (gastroesophageal reflux disease), malabsorption syndrome, colon cancer, or chronic colitis, including Crohn's disease. History of treatment for asthma within the past five (5) years. History of predisposition to renal calculi. History of surgery within the past eight (8) weeks. History of application of tattoo(s) within the past 30 days. History of body piercing(s) within the past 30 days. Females who are pregnant or lactating. History of hypersensitivity to topiramate or any anticonvulsant medication. Conditions upon screening which might contraindicate or require that caution be used in the administration of topiramate, including: Sitting systolic blood pressure below 90 mm Hg, or diastolic pressure below 50 mm Hg. Heart rate less than 50 beats per minute after a 5-minute rest in a seated position. Inability to read and/or sign the consent form. Treatment with any other investigational drug during the 30 days prior to the initial dosing for this study. Subjects who have donated blood within 30 days prior to the initial dosing for this study. Subjects who smoke more than 10 cigarettes per day. Subjects who do not tolerate venipuncture. Subjects who have difficulty fasting or consuming standardized meals.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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: Screening
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Torrent Topiramate<br>tablet containing 25 mg of topiramate (Torrent Pharmaceuticals) | Drug: Topiramate<br>* Topiramate (brand name Topamax) is an anticonvulsant (antiepilepsy) drug. IUPAC name 2,3:4,5-Bis-O-(1-methylethylidene)-beta-D-fructopyranose sulfamate<br>|
| Active Comparator: Topamax<br>tablet containing 25 mg of topiramate (Topamax®, Ortho-McNeil Neurologics, Inc.) | Drug: Topiramate<br>* Topiramate (brand name Topamax) is an anticonvulsant (antiepilepsy) drug. IUPAC name 2,3:4,5-Bis-O-(1-methylethylidene)-beta-D-fructopyranose sulfamate<br>|

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 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48 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) | serial pharmacokinetic plasma concentrations were drawn prior to dose administration (0 hour) and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours after drug administration. | 
| The Area Under the Plasma Concentration Versus Time Curve From Time 0 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 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours after drug administration. |