Bioequivalence Study of 200 mg Lamotrigine Tablet Under Non-Fasting Conditions

Randomized, 2-Way, Crossover, Bioequivalence Study of Lamotrigine 200 mg Tablets and Lamictal® 200 mg Tablets Administered as 1 x 200 mg Tablet in Healthy Subjects Under Fed Conditions

The objective of this study is to compare the rate and extent of absorption of lamotrigine 200 mg tablets (test) versus Lamictal® (reference) administered as 1 x 200 mg tablet under fed conditions.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Lamotrigine; Drug: Lamictal®

Detailed Description

Criteria for Evaluation: FDA Bioequivalence Criteria

Statistical Methods: FDA bioequivalence statistical methods

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Sainte-Foy, Quebec, Canada, G1V 2K8
      • Anapharm Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria

• Subjects will be females and/or males, non-smokers, 18 years of age and older.
• Female Subjects will be post-menopausal or surgically sterilized.
• Post-menopausal status is defined as absence of menses for the past 12 months,
• Sterile status is defined as hysterectomy, bilateral oophorectomy or tubal ligation at least 6 months ago.

Exclusion Criteria

Subjects to whom any of the following applies will be excluded from the study:

• Clinically significant illnesses within 4 weeks of the administration of study medication.
• Clinically significant surgery within 4 weeks prior to the administration of the study medication.
• Any clinically significant abnormality found during medical screening.
• Subjects with a history of renal, hepatic or cardiovascular disease, tuberculosis, epilepsy, asthma, diabetes, psychosis or glaucoma will not be eligible for this study.
• Any reason which, in the opinion of the medical subinvestigator, would prevent the subject from participating in the study.
• Abnormal laboratory tests judged clinically significant.
• Positive urine drug screen at screening.
• Positive testing for hepatitis B, hepatitis C or HIV at screening.
• ECG abnormalities (clinically significant) or vital sign abnormalities (systolic blood pressure lower than 90 or over 140 mmHg, or diastolic blood pressure lower than 50 or over 90; or heart rate less than 50 bpm) at screening.
• Subjects with BMI ≥30.0.
• History of significant alcohol abuse within six months of the screening visit or any indication of the regular use of more than two units of alcohol per day (1 Unit = 150 mL of wine or 360 mL of beer or 45 mL of alcohol 40%).
• History of drug abuse or use of illegal drugs: use of soft drugs (such as marijuana) within 3 months of the screening visit or hard drugs (such as cocaine, phencyclidine (PCP) and crack) within 1 year of the screening visit.
• Any food allergy, intolerance, restriction or special diet that, in the opinion of the medical subinvestigator, contraindicates the subject's participation in this study.
• History of allergic reactions to lamotrigine.
• Use of any drugs known to induce or inhibit hepatic drug metabolism (examples of inducers: barbiturates, carbamazepine, phenytoin, glucocorticoids, rifampin/rifabutin; examples of inhibitors: antidepressants, cimetidine, diltiazem, erythromycin, ketoconazole, MAO inhibitors, neuroleptics, verapamil, quinidine, valproic acid, use of an investigational drug or participation on an investigation study within 30 days prior to the administration of the study medication.
• Use of prescription medication within 14 days prior to administration of study medication or over-the-counter products )including natural products, vitamins, garlic as a supplement) within 7 days prior to administration of study medication, except for topical products without systemic absorption.
• Subjects who have had a depot injection or an implant of any drug 3 months prior to administration of study medication.
• Donation of plasma (500 mL) within 7 days. Donation or loss of whole blood prior to administration of the study medication as follows:
• Less than 300 mL of whole blood within 30 days or
• 300 mL to 500 mL of whole blood within 45 days or
• more than 500 mL of whole blood within 56 days.
• Positive alcohol breath test at screening.
• Subjects who have used tobacco in any form within the 90 days preceding study drug administration.

Additional exclusion criteria for female subjects only:

• Breast feeding subjects.
• Positive urine pregnancy test at screening (performed on all females).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lamotrigine; Lamotrigine 200 mg Tablet (test) dosed in first period followed by Lamictal® 200 mg Tablet (reference) dosed in second period	Drug: Lamotrigine; 200 mg Tablet
Active Comparator: Lamictal®; Lamictal® 200 mg Tablet (reference) dosed in first period followed by Lamotrigine 200 mg Tablet (test) dosed in second period	Drug: Lamictal®; 200 mg Tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC0-inf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated)	Bioequivalence based on AUC0-inf	Blood samples collected over 120 hour period
AUC0-t - Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant)	Bioequivalence based on AUC0-t	Blood samples collected over 120 hour period
Cmax - Maximum Observed Concentration	Bioequivalence based on Cmax	Blood samples collected over 120 hour period

Collaborators and Investigators

• Sponsor: Teva Pharmaceuticals USA
• Investigators: Principal Investigator: Benoit Girard, MD, Anapharm

Study record dates

Study Major Dates

• Study Start: January 1, 2002
• Primary Completion (Actual): February 1, 2002
• Study Completion (Actual): February 1, 2002

Study Registration Dates

• First Submitted: January 30, 2009
• First Submitted That Met QC Criteria: January 30, 2009
• First Posted (Estimated): February 3, 2009

Study Record Updates

• Last Update Posted (Actual): August 19, 2024
• Last Update Submitted That Met QC Criteria: August 15, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: Bioequivalence; Healthy Subjects
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Membrane Transport Modulators; Anticonvulsants; Sodium Channel Blockers; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Lamotrigine
• Other Study ID Numbers: 01306