Bioequivalence and Food Effect of 250mg of Lamotrigine XR

A Pivotal, Single-Dose, Randomised, Parallel-Group, Open-Label Study to Demonstrate Bioequivalence of 250mg Lamotrigine XR Relative to 200mg + 50mg Lamotrigine XR and to Demonstrate Lack of Food Effect on 250mg Lamotrigine XR in Healthy Male and Female Volunteers

This study intends to demonstrate bioequivalence and lack of food effect on 250mg lamotrigine XR in healthy male and female volunteers

Study Overview

• Status: Completed
• Conditions: Epilepsy
• Intervention / Treatment: Drug: Lamotrigine tablet; Drug: Lamotrigine caplet

• Study Type: Interventional
• Enrollment (Actual): 209
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Washington
    • Tacoma, Washington, United States, 98418
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female subjects aged from 19 to 55 years, inclusive.
• Body weight >50 kg (males) or >45 kg (females) and BMI within the range 19 - 32 kg/m2 inclusive.
• Healthy as determined by a responsible physician, based on a medical evaluation including history, physical examination, laboratory tests, vital signs and ECG. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator considers that the finding will not introduce additional risk factors and will not interfere with the study procedures

• Female subjects of non-child bearing potential will be eligible to participate if they meet the following criteria:

  • Post-menopausal females defined as being amenorrhoeic for greater than 2 years with an appropriate clinical profile, e.g. age appropriate, history of vasomotor symptoms. However if indicated this should be confirmed by oestradiol and FSH levels consistent with menopause (according to local laboratory ranges).
  • Pre-menopausal females with a documented (medical report verification) hysterectomy and/or bilateral oophorectomy, the latter only when the reproductive status of the woman has been confirmed by follow up hormone level assessment.
  • Female subjects of child bearing potential will be eligible to participate if they comply with the contraception requirements.
• A negative pre-study Hepatitis B surface antigen (HBsAg), Hepatitis C antibody, and HIV antibody result at screening.
• A negative pre-study urine drug screen.
• A negative screen for alcohol (urine, blood or breath test).
• Signed and dated written informed consent prior to admission to the study.

Exclusion Criteria:

• Female subjects of childbearing potential will not be eligible to participate who are unwilling or unable to use an appropriate method of contraception as outlined in the inclusion criteria from at least the commencement of their last normal period prior to the first dose of study medication; and to continue until the first normal period (defined as normal for the woman, both in terms of duration and quantity of menses) after treatment or 5 half lives of the study medication, whichever is the longest .
• Female subject is pregnant (positive serum human chorionic gonadotrophin (hCG) test at screening) or lactating.
• Female subjects using hormonal contraceptive precautions including progesterone-coated IUD.
• Female subjects using oestrogen-containing hormone replacement therapy.
• Subjects who have received lamotrigine previously (subjects who received placebo in a previous study will be allowed)
• History or evidence of drug or alcohol abuse within 12 months of study start.
• QTc >450msec for women and QTc >430 msec for men on the screening 12-lead ECG.
• Current smokers of 10 or more cigarettes per day.
• History of regular alcohol consumption averaging >7 drinks/week for women or >14 drinks/week for men within 6 months of screening. One drink is equivalent to 12 g alcohol = 5 ounces (150 ml) of wine or 12 ounces (360 ml) of beer or 1.5 ounces (45 ml) of 80 proof distilled spirits.
• Has received prescribed or non-prescribed medication (including vitamins and herbal remedies) within 14 days prior to the dosing day, which in the opinion of the Principal/Co-Investigator, may interfere with the study procedures or compromise safety.
• History of gastro-intestinal, hepatic, or renal disease or other condition known to interfere with the absorption, distribution, metabolism or excretion of drugs.
• History of clinically relevant skin rashes that, in the opinion of the investigator, might interfere with the conduct of the study.
• Treatment with an investigational drug within 30 days or 5 half-lives (whichever is longer) preceding the first dose of study medication.
• History of allergic, anaphylactic, hypersensitivity or idiosyncratic reaction(s) to lamotrigine or drugs of a similar type.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Subjects receiving regimen A; Eligible subjects will receive regimen A containing lamotrigine extended release tablet of 200 milligrams plus 50 milligrams in fasted state	Drug: Lamotrigine tablet; Lamotrigine extended release single dose tablet will be available with dosing strengths of 200 milligrams and 50 milligrams intended to be administered orally in fasted state. It will be a round standard convex shape tablet.
Experimental: Subjects receiving regimen B; Eligible subjects will receive regimen B containing lamotrigine extended release caplet of 250 milligrams in fasted state.	Drug: Lamotrigine caplet; Lamotrigine extended release single dose caplet will be available with dosing strength of 200 milligrams and 50 milligrams intended to be administered orally in fasted and fed state.
Experimental: Subjects receiving regimen C; Eligible subjects will receive regimen C containing lamotrigine extended release caplet of 250 milligrams in fed state.	Drug: Lamotrigine caplet; Lamotrigine extended release single dose caplet will be available with dosing strength of 200 milligrams and 50 milligrams intended to be administered orally in fasted and fed state.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetics ie Serum lamotrigine Cmax and AUC(0-inf)	Pre-dose and 0.25, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 22, 24, 26, 36, 48, 72, 96, 120 and 144 hours Post-dose

Secondary Outcome Measures

Outcome Measure	Time Frame
PK (AUC (0-t), tmax and t1/2 )	Pre-dose and 0.25, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 22, 24, 26, 36, 48, 72, 96, 120 and 144 hours Post-dose
Adverse events, changes in biochemistry, haematology, urinalysis parameters, electrocardiogram parameters, blood pressure and heart rate	Up to day 21
Serum lamotrigine AUC (0-t), tmax and t1/2	Pre-dose and 0.25, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 22, 24, 26, 36, 48, 72, 96, 120 and 144 hours Post-dose

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• This study has not been published in the scientific literature.

Helpful Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Study record dates

Study Major Dates

• Study Start (Actual): January 15, 2008
• Primary Completion (Actual): March 6, 2008
• Study Completion (Actual): March 6, 2008

Study Registration Dates

• First Submitted: January 18, 2008
• First Submitted That Met QC Criteria: January 18, 2008
• First Posted (Estimate): January 31, 2008

Study Record Updates

• Last Update Posted (Actual): September 11, 2017
• Last Update Submitted That Met QC Criteria: September 8, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: Healthy volunteers; Bioequivalence; Food Effects
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Membrane Transport Modulators; Sodium Channel Blockers; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Lamotrigine; Anticonvulsants
• Other Study ID Numbers: LEP111102

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Study Data/Documents

1. Informed Consent Form
   Information identifier: LEP111102
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Clinical Study Report
   Information identifier: LEP111102
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Annotated Case Report Form
   Information identifier: LEP111102
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Dataset Specification
   Information identifier: LEP111102
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Study Protocol
   Information identifier: LEP111102
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Individual Participant Data Set
   Information identifier: LEP111102
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Statistical Analysis Plan
   Information identifier: LEP111102
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register

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