LAMICTAL (Lamotrigine) For The Treatment Of Absence Seizures

Evaluation of Lamotrigine in Subjects With Absence Seizures

This is an open-label study evaluating the efficacy and safety of lamotrigine (LTG) for the treatment of newly-diagnosed typical absence seizures. Subjects will be children and adolescents < 13 years of age. It will be conducted at multiple sites in the US. The study will consist of 4 phases: Screen Phase (up to 1 week), Baseline Phase (24 hours), Escalation Phase (up to 20 weeks) and Maintenance Phase (12 weeks). Subjects will receive increasing doses of LTG according to the dosing schedule until attaining seizure freedom as confirmed by hyperventilation (HV) for clinical signs and a 1-hr EEG at 2 consecutive weekly visits. At that point, subjects will move into the 12-week Maintenance Phase. Subjects who do not achieve seizure freedom upon reaching the maximum dose (10.2mg/kg/day) with the specified dose escalation will be discontinued from the study. During the Maintenance Phase, the investigators will use their best effort to maintain the subjects at the efficacious dose reached. If the subjects have unacceptable side effects or inadequate seizure control, the doses of study drug can be increased or decreased as specified in the dosing schedule. Safety will be assessed by monitoring adverse events, laboratory assessments, and serum lamotrigine levels. Health outcomes assessments will also be conducted.

Study Overview

• Status: Completed
• Conditions: Seizure, Absence
• Intervention / Treatment: Drug: Lamotrigine

• Study Type: Interventional
• Enrollment (Actual): 54
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • San Jose, California, United States, 95128
      • GSK Investigational Site
  • Florida
    • Loxahatchee Groves, Florida, United States, 33470
      • GSK Investigational Site
    • Melbourne, Florida, United States, 32901
      • GSK Investigational Site
    • Panama City, Florida, United States, 32405
      • GSK Investigational Site
    • Tallahassee, Florida, United States, 32308
      • GSK Investigational Site
    • Tampa, Florida, United States, 33607-6350
      • GSK Investigational Site
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • GSK Investigational Site
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • GSK Investigational Site
  • Missouri
    • Springfield, Missouri, United States, 65804
      • GSK Investigational Site
  • New Jersey
    • Newark, New Jersey, United States, 07103
      • GSK Investigational Site
  • New York
    • Buffalo, New York, United States, 14222
      • GSK Investigational Site
    • Rochester, New York, United States, 14642
      • GSK Investigational Site
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599-7600
      • GSK Investigational Site
    • Greenville, North Carolina, United States, 27834
      • GSK Investigational Site
    • Raleigh, North Carolina, United States, 27607
      • GSK Investigational Site
  • Oregon
    • Portland, Oregon, United States, 97239
      • GSK Investigational Site
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • GSK Investigational Site
    • Nashville, Tennessee, United States, 37212
      • GSK Investigational Site
  • Texas
    • Fort Worth, Texas, United States, 76104
      • GSK Investigational Site
  • Washington
    • Seattle, Washington, United States, 98105
      • GSK Investigational Site
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • GSK Investigational Site
    • Milwaukee, Wisconsin, United States, 53226
      • GSK Investigational Site
    • Milwaukee, Wisconsin, United States, 53215
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 12 years (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

• Newly-diagnosed with absence epilepsy and never been treated with Anti-epileptic drugs (AEDs).
• Diagnosis demonstrated on one of two 5-minute hyperventilation tests.
• Investigator must judge that the subject and parent/guardian are likely to comply with all study procedures.
• Parent/guardian must given written informed consent. Subjects who are intellectually able to understand the concepts and procedures of the protocol must give assent by also signing the consent or by signing a separate assent form.
• Results of all screen assessments are judged to be clinically acceptable to the investigator and do not indicate any reasons why entry into the study would be contraindicated.

Exclusion criteria:

• Seizures are the result of a currently active, known, and identifiable intracerebral lesion.
• Has partial or generalized tonic-clonic seizures.
• Has a progressive neurological disorder defined as being unstable for at least 12 weeks prior to the Screen Phase.
• Has a psychiatric disorder requiring medication, or has had a past psychiatric condition that was both judged to be severe and required hospitalization.
• Has any clinically significant chronic cardiac, renal, or hepatic medical condition.
• Has a condition that affects the absorption, distribution, metabolism, or excretion of drugs.
• Is currently taking any psychoactive drugs to treat hyperactivity disorder or attention deficit disorder.
• Has taken any investigational drug within 12 weeks prior to the Screen Phase.
• Is sexually active.
• Is either pregnant (i.e., confirmed by pregnancy test at Screen) or breastfeeding.
• Has a clinically significant chronic medical disorder which the investigator and/or GSK medical monitor determine warrants exclusion.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Subjects receiving lamotrigine; Eligible subjects will receive chewable dispersible tablets of lamotrigine with a starting dose of 0.3 milligrams per kilogram administered orally.	Drug: Lamotrigine; Lamotrigine will be given as chewable dispersible tablets with dosing strengths of 2, 5, 25, and 100 milligrams.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The proportion of subjects with no typical absence seizures for two consecutive weeks as confirmed by hyperventilation (HV) for clinical signs and 1-hour electroencephalogram (EEG)	Up to 8 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Freq of seizures pre/post-treatment with lamotrigine, proportion of subjects with >=25, 50 and 75% decrease in seizure frequency, proportion of subjects with >=25, 50 and 75% decrease in clinical signs.	Up to 8 months

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Holmes GL, Frank LM, Sheth RD, Philbrook B, Wooten JD, Vuong A, Kerls S, Hammer AE, Messenheimer J. Lamotrigine monotherapy for newly diagnosed typical absence seizures in children. Epilepsy Res. 2008 Dec;82(2-3):124-32. doi: 10.1016/j.eplepsyres.2008.07.016. Epub 2008 Sep 7.

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): November 1, 2004
• Primary Completion (ACTUAL): April 22, 2006
• Study Completion (ACTUAL): April 22, 2006

Study Registration Dates

• First Submitted: September 1, 2005
• First Submitted That Met QC Criteria: September 1, 2005
• First Posted (ESTIMATE): September 5, 2005

Study Record Updates

• Last Update Posted (ACTUAL): September 29, 2017
• Last Update Submitted That Met QC Criteria: September 27, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: Epilepsy; EEG; Absence Seizures; LAMICTAL; LTG; Typical Absence Epilepsy
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy, Generalized; Epileptic Syndromes; Neurologic Manifestations; Epilepsy; Seizures; Epilepsy, Absence; 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: LAM100118

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. Dataset Specification
   Information identifier: LAM100118
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Clinical Study Report
   Information identifier: LAM100118
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Informed Consent Form
   Information identifier: LAM100118
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Statistical Analysis Plan
   Information identifier: LAM100118
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Individual Participant Data Set
   Information identifier: LAM100118
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Annotated Case Report Form
   Information identifier: LAM100118
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Study Protocol
   Information identifier: LAM100118
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register