Fasting Bioavailability Study of Zonisamide Capsules

A Relative Bioavailability Study of 100 mg Zonisamide Capsules Under Fasting Conditions

The purpose of this study is to evaluate and compare the relative bioavailability of a test formulation of zonisamide capsules to an equivalent dose of a reference formulation, Zonegran® (zonisamide) capsules, after a single oral dose administered under fasting conditions.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Zonisamide 100 mg Capsule; Drug: Zonisamide (Zonegran®) 100 mg Capsule

Detailed Description

The purpose of this study is to evaluate and compare the relative bioavailability of a test formulation of zonisamide capsules to an equivalent dose of a reference formulation, Zonegran® (zonisamide) capsules, after a single oral dose administered under fasting conditions.

Thirty-four 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 zonisamide dosing regimens in sequence with a 28 day washout period between dosing periods. On the morning of Day 1, after an overnight fast, subjects will receive either a single oral dose of the test formulation, zonisamide (1 x 100 mg capsule) or a single oral dose of the reference formulation, Zonegran® (1 x 100 mg capsule). After a 28 day washout period, on the morning of Day 29 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 zonisamide. 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 drug and/or procedures. Blood pressure and heart rate will be obtained prior to dosing and as scheduled following dose administration. 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.

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Screening Demographics:
• All volunteers selected for this study will be healthy men and women 18 years of age or older at the time of dosing
• Weight range will not exceed ± 20% for height and body frame
• Screening Procedures:
• Each volunteer 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 observation, 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, Clinical Chemistry, HIV antibody, Hepatitis B-surface antigen, Hepatitis C antibody, Urinalysis, Urine Drug Screen, Serum Pregnancy Screen, Follicle Stimulating Hormone
• If female: postmenopausal for 1 year or surgically sterile.

Exclusion Criteria:

• Volunteers with a recent history of drug or alcohol addiction or abuse
• Volunteers with the presence of a clinically significant disorder involving the cardiovascular, respiratory, renal, gastrointestinal, immunologic, hematologic, endocrine, or neurologic system(s) or psychiatric disease
• Volunteers whose clinical laboratory test values are outside the accepted reference range and when confirmed on re-examination are deemed to be clinically significant
• Volunteers demonstrating a reactive screen for hepatitis B surface antigen, hepatitis C antibody or HIV antibody screen
• Volunteers demonstrating a positive drug abuse screen when screened for this study
• Female volunteers demonstrating a positive pregnancy screen
• Female volunteers who are currently breastfeeding
• Volunteers with a history of allergic response(s) to zonisamide or related drugs
• Volunteers with a history of clinically significant allergies including drug allergies
• Volunteers with a clinically significant illness during the 4 weeks prior to Period I dosing (as determined by the clinical investigator)
• Volunteers who currently use tobacco products
• Volunteers who have taken any drug known to induce or inhibit hepatic drug metabolism in the 28 days prior to Period I dosing
• Volunteers who report donating greater than 150mL 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
• Volunteers who report receiving any investigational drug within 14 days prior to Period I dosing.
• Volunteers 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
• Volunteers who report taking any systemic prescription medication in the 14 days prior to Period I dosing.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Zonisamide 100 mg Capsule; A single dose of zonisamide 100 mg administered after an overnight fast.	Drug: Zonisamide 100 mg Capsule; 100 mg capsule administered after an overnight fast.
Experimental: Zonisamide (Zonegran® ) 100 mg Capsule; A single dose of Zonegran® 100 mg administered after an overnight fast.	Drug: Zonisamide (Zonegran®) 100 mg Capsule; 100 mg capsule administered after an overnight fast.; Other Names: Zonegran®

What is the study measuring?

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 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 8, 10, 12, 16, 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 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 8, 10, 12, 16, 24, 36, 48, 60 and 72 hours after drug administration.

Collaborators and Investigators

• Sponsor: Mutual Pharmaceutical Company, Inc.

Publications and helpful links

Helpful Links

• Recalls, Market Withdrawals and Safety Alerts
• Daily Med - Posting of Recently Submitted Labeling to the FDA
• URL Pharma Generic Division

Study record dates

Study Major Dates

• Study Start: January 1, 2005
• Primary Completion (Actual): March 1, 2005
• Study Completion (Actual): March 1, 2005

Study Registration Dates

• First Submitted: May 24, 2008
• First Submitted That Met QC Criteria: May 24, 2008
• First Posted (Estimate): May 28, 2008

Study Record Updates

• Last Update Posted (Estimate): January 26, 2010
• Last Update Submitted That Met QC Criteria: January 11, 2010
• Last Verified: January 1, 2010

More Information

Terms related to this study

• Keywords: Therapeutic Equivalency
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Anticonvulsants; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Zonisamide
• Other Study ID Numbers: R04-1376

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No