Conversion To Monotherapy With Lamictal Extended Release Tablets For Treatment Of Partial Epilepsy

A Multicenter, Double-Blind, Randomized Conversion to Monotherapy Comparison of Two Doses of Lamotrigine for the Treatment of Partial Seizures

This study is being conducted to determine the effectiveness of a lower monotherapy dose of lamotrigine than that currently approved.

Study Overview

• Status: Completed
• Conditions: Epilepsy, Partial
• Intervention / Treatment: Drug: lamotrigine, 300 mg/day; Drug: lamotrigine, 250 mg/day

Detailed Description

The study consists of a Treatment phase, where efficacy is determined and a Continuation phase for extended safety information. The Continuation phase is open to all Treatment phase participants and those who did not qualify for treatment because of an insufficient number of seizures during the Baseline phase.

• Study Type: Interventional
• Enrollment (Actual): 226
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Ciudad Autonoma de Buenos Aires, Argentina
    • GSK Investigational Site
  • Ciudad Autónoma de Buenos Aires, Argentina, 1425
    • GSK Investigational Site
  • Buenos Aires
    • Capital Federal, Buenos Aires, Argentina, 1181
      • GSK Investigational Site
    • Capital Fefderal, Buenos Aires, Argentina
      • GSK Investigational Site
• Chile
  • Región Metro De Santiago
    • Providencia / Santiago, Región Metro De Santiago, Chile, 7500710
      • GSK Investigational Site
    • Santiago, Región Metro De Santiago, Chile
      • GSK Investigational Site
    • Santiago, Región Metro De Santiago, Chile, 7560356
      • GSK Investigational Site
• Costa Rica
  • San Jose, Costa Rica
    • GSK Investigational Site
• Korea, Republic of
  • Busan, Korea, Republic of, 614-735
    • GSK Investigational Site
  • Daegu, Korea, Republic of, 700-712
    • GSK Investigational Site
  • Daejeon, Korea, Republic of, 301-721
    • GSK Investigational Site
  • Seoul, Korea, Republic of, 120-752
    • GSK Investigational Site
  • Seoul, Korea, Republic of, 138-736
    • GSK Investigational Site
  • Seoul, Korea, Republic of, 110-744
    • GSK Investigational Site
  • Seoul, Korea, Republic of, 135-170
    • GSK Investigational Site
• Puerto Rico
  • San Juan, Puerto Rico, 00918
    • GSK Investigational Site
  • San Juan, Puerto Rico, 00936
    • GSK Investigational Site
• Russian Federation
  • Ekaterinburg, Russian Federation, 620102
    • GSK Investigational Site
  • Moscow, Russian Federation, 117049
    • GSK Investigational Site
  • Moscow, Russian Federation, 125412
    • GSK Investigational Site
  • Moscow, Russian Federation, 105066
    • GSK Investigational Site
  • Samara, Russian Federation, 443095
    • GSK Investigational Site
  • St.-Petersburg, Russian Federation, 194291
    • GSK Investigational Site
  • St.-Petersburg, Russian Federation, 193019
    • GSK Investigational Site
  • St.Petersburg, Russian Federation, 193167
    • GSK Investigational Site
• Ukraine
  • Dnepropetrovsk, Ukraine, 49005
    • GSK Investigational Site
  • Donetsk, Ukraine, 83037
    • GSK Investigational Site
  • Kharkiv, Ukraine, 61068
    • GSK Investigational Site
  • Kyiv, Ukraine
    • GSK Investigational Site
  • Kyiv, Ukraine, 02660
    • GSK Investigational Site
  • Lugansk, Ukraine, 91045
    • GSK Investigational Site
  • Lviv, Ukraine, 79021
    • GSK Investigational Site
  • Odesa, Ukraine, 65006
    • GSK Investigational Site
  • Poltava, Ukraine
    • GSK Investigational Site
  • Vinnitsa, Ukraine, 21005
    • GSK Investigational Site
  • Zaporizhzhya, Ukraine, 69057
    • GSK Investigational Site
• United States
  • Alabama
    • Alabaster, Alabama, United States, 35007
      • GSK Investigational Site
  • Arizona
    • Litchfield Park, Arizona, United States, 85340
      • GSK Investigational Site
    • Mesa, Arizona, United States, 85201
      • GSK Investigational Site
    • Phoenix, Arizona, United States, 85003
      • GSK Investigational Site
    • Phoenix, Arizona, United States, 85013
      • GSK Investigational Site
    • Tucson, Arizona, United States, 85724
      • GSK Investigational Site
    • Tucson, Arizona, United States, 85741
      • GSK Investigational Site
  • Arkansas
    • Fayetteville, Arkansas, United States, 72703
      • GSK Investigational Site
  • California
    • Los Angeles, California, United States, 90073
      • GSK Investigational Site
    • Pasadena, California, United States, 91105
      • GSK Investigational Site
    • Santa Ana, California, United States, 92705
      • GSK Investigational Site
    • Santa Monica, California, United States, 90404
      • GSK Investigational Site
  • Connecticut
    • Danbury, Connecticut, United States, 06810
      • GSK Investigational Site
    • Fairfield, Connecticut, United States, 06824
      • GSK Investigational Site
  • Delaware
    • Newark, Delaware, United States, 19713
      • GSK Investigational Site
  • Florida
    • Jacksonville, Florida, United States, 32224
      • GSK Investigational Site
    • Loxahatchee, Florida, United States, 33470
      • GSK Investigational Site
    • Sunrise, Florida, United States, 33351
      • GSK Investigational Site
    • Tampa, Florida, United States, 33613
      • GSK Investigational Site
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • GSK Investigational Site
    • Atlanta, Georgia, United States, 30338
      • GSK Investigational Site
    • Decatur, Georgia, United States, 30033
      • GSK Investigational Site
  • Idaho
    • Boise, Idaho, United States, 83702
      • GSK Investigational Site
  • Illinois
    • Chicago, Illinois, United States, 60637
      • GSK Investigational Site
    • Chicago, Illinois, United States, 60611
      • GSK Investigational Site
    • Flossmoor, Illinois, United States, 60422
      • GSK Investigational Site
    • Urbana, Illinois, United States, 61801
      • GSK Investigational Site
  • Iowa
    • Des Moines, Iowa, United States, 50309
      • GSK Investigational Site
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • GSK Investigational Site
    • Lexington, Kentucky, United States, 40513
      • GSK Investigational Site
    • Louisville, Kentucky, United States, 40202
      • GSK Investigational Site
  • Louisiana
    • New Orleans, Louisiana, United States, 70115
      • GSK Investigational Site
  • Maryland
    • Bethesda, Maryland, United States, 20817
      • GSK Investigational Site
    • Glen Burnie, Maryland, United States, 21061
      • GSK Investigational Site
    • Pikesville, Maryland, United States, 21208
      • GSK Investigational Site
  • Massachusetts
    • Springfield, Massachusetts, United States, 01104
      • GSK Investigational Site
  • Michigan
    • Detroit, Michigan, United States, 48202
      • GSK Investigational Site
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • GSK Investigational Site
    • St. Cloud, Minnesota, United States, 56303
      • GSK Investigational Site
  • Mississippi
    • Hattiesburg, Mississippi, United States, 39401
      • GSK Investigational Site
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • GSK Investigational Site
    • St. Louis, Missouri, United States, 63110
      • GSK Investigational Site
    • St. Louis, Missouri, United States, 63104
      • GSK Investigational Site
  • Nevada
    • Henderson, Nevada, United States, 89014
      • GSK Investigational Site
    • Las Vegas, Nevada, United States, 89106
      • GSK Investigational Site
    • Las Vegas, Nevada, United States, 81902
      • GSK Investigational Site
  • New Jersey
    • Edison, New Jersey, United States, 08818
      • GSK Investigational Site
    • Vorhees, New Jersey, United States, 08043
      • GSK Investigational Site
  • New York
    • Lawrence, New York, United States, 11559
      • GSK Investigational Site
    • Plainview, New York, United States, 11803
      • GSK Investigational Site
    • Syracuse, New York, United States, 13210
      • GSK Investigational Site
  • North Carolina
    • Asheville, North Carolina, United States, 28803
      • GSK Investigational Site
  • Ohio
    • Columbus, Ohio, United States, 43210-1296
      • GSK Investigational Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • GSK Investigational Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • GSK Investigational Site
    • Sellersville, Pennsylvania, United States, 18960
      • GSK Investigational Site
  • Texas
    • Dallas, Texas, United States, 75230
      • GSK Investigational Site
    • Houston, Texas, United States, 77025
      • GSK Investigational Site
    • San Antonio, Texas, United States, 78229
      • GSK Investigational Site
    • San Antonio, Texas, United States, 78258
      • GSK Investigational Site
    • Temple, Texas, United States, 76502
      • GSK Investigational Site
  • Utah
    • Midvale, Utah, United States, 84047
      • GSK Investigational Site
  • Washington
    • Renton, Washington, United States, 98055
      • GSK Investigational Site
  • West Virginia
    • Charleston, West Virginia, United States, 25301
      • GSK Investigational Site
    • Morgantown, West Virginia, United States, 26506
      • GSK Investigational Site
  • Wisconsin
    • Madison, Wisconsin, United States, 53715
      • GSK Investigational Site
    • Milwaukee, Wisconsin, United States, 53215
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 13 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

• Male or Female ≥13 years of age
• Have a confident diagnosis of epilepsy with partial seizures for at least 24 weeks prior to the Baseline Phase
• Have a documented history of partial seizures such that the investigator must judge that the subject is likely to have at least 4 partial seizures during the 8-week Baseline Phase.
• Have experienced at least 4 partial seizures (i.e., simple or complex partial seizures with or without secondary generalization) during an 8-week (i.e., 56 days) prospective Baseline Phase with at least one partial seizure occurring during each 4-week (i.e., 28-day) period.

• NOTE: With prior authorization from GlaxoSmithKline (GSK), retrospective data may take the place of up to the first 4 weeks (i.e., first 28 days) of the Baseline Phase for subjects providing reliable documentation of the following:

  1. A complete daily seizure diary that includes the number, and type (i.e., simple or complex partial seizures with or without secondary generalization), of seizures experienced each day for up to 28 consecutive days immediately prior to the prospective Baseline Phase
  2. Stability of prescribed dosages of background antiepileptic drug (AED)
  3. Compliance with background AED

All subjects permitted to use retrospective baseline data must complete a minimum of four weeks (i.e., 28 days) of the prospective Baseline Phase. The retrospective plus the prospective Baseline Phases must equal the 56 consecutive days prior to the start of dosing with study drug.

• be currently receiving AED monotherapy treatment with a stable regimen of a non-enzyme inducing AED for at least four weeks prior to starting the Baseline Phase.
• be able and willing to maintain an accurate, complete, written daily seizure diary, or has a parent/caregiver who is able and willing to maintain and accurate, complete, written daily seizure diary for the entire duration of the study.
• be able to comply with the dosing of study drugs, background AED, and all study procedures.
• understand and sign written informed consent, or will have a parent or a legally authorized representative who has done so, prior to the performance of any study assessments

• if female, and of childbearing potential be using an acceptable form of birth control, to include one of the following:

  1. Complete abstinence from intercourse for two weeks before exposure to the study drug, throughout the clinical trial, and for a period after the trial to account for elimination of the drug (a minimum of 2 weeks).
  2. Consistent and correct use of one of the following methods of birth control:

Male partner who is sterile prior to the female subject's entry into the study and is the sole sexual partner for that female subject.

Any intrauterine device (IUD) with a documented failure rate of less than 1% per year

Double barrier method consisting of spermicide plus a mechanical barrier (e.g., spermicide plus a male condom or a female diaphragm).

NOTE: Women who have had a hysterectomy, tubal ligation, or are post-menopausal are considered to be of non-childbearing potential.

NOTE: A pharmacokinetic interaction has been observed between lamotrigine (LTG) and estrogen-based oral contraceptives. Therefore, the use of hormonal therapy (e.g., for contraception or hormone replacement therapy) is not allowed.

Exclusion criteria:

• Exhibits any primary generalized seizures (e.g., absence, myoclonic primary generalized tonic-clonic seizures).
• Has had status epilepticus within the 24 weeks prior to, or during, the Baseline Phase.
• Is taking an enzyme-inducing AED (EIAED - e.g. carbamazepine, phenytoin, phenobarbital, primidone) or is taking more than 1 background AED.
• Is currently taking lamotrigine (LTG) or has previously had an adequate trial of LTG.
• Is currently taking felbamate
• Is using hormone therapy
• Is abusing alcohol and/or other substances
• Has taken an investigational drug within the previous 30 days or plans to take an investigational drug anytime during the study.
• Is receiving chronic treatment with any medication that could influence seizure control
• NOTE: Use of benzodiazepines is allowed as specified in Section 8.1.2
• Is currently following the ketogenic diet.
• Is using vagal nerve stimulation
• Is planning surgery to control seizures during the study.
• Is pregnant, breastfeeding, or planning to become pregnant during the study or within the three weeks after the last dose of study drug.
• Is suffering from acute or progressive neurological disease, severe psychiatric disease or severe mental abnormality that is likely to interfere with the objectives of the study.
• Has any clinically significant cardiac, renal, hepatic condition, or a condition that affects the absorption, distribution, metabolism or excretion of drugs.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: lamotrigine 300; 300 mg/day treatment	Drug: lamotrigine, 300 mg/day; 300 mg/day; Other Names: lamotrigine
Experimental: lamotrigine 250; 250 mg/day treatment	Drug: lamotrigine, 250 mg/day; 250 mg/day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Percentage of Participants in the 300 mg/Day Dose Group Who Prematurely Discontinued the Study Between Study Visit 5 (Approximately Week 7) and Visit 9 (End of the Treatment Phase)	The percentage of participants prematurely discontinuing the study was calculated as the number of participants who discontinued the study divided by the number who reached Visit 5 minus major protocol violators. The Control group is composed of data from other similar studies and is not part of this study.	From Study Visit 5 through Visit 9 of the Treatment Phase (approximately Week 7 through Week 23)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Percentage of Participants in the 250 mg/Day Dose Group Who Prematurely Discontinued the Study Between Study Visit 5 (Approximately Week 7) and Visit 9 (End of the Treatment Phase)	The percentage of participants prematurely discontinuing the study was calculated as the number of participants who discontinued the study divided by the number who had reached Visit 5 minus major protocol violators. The Control group was composed of data from other similar studies and is not part of this study.	From Study Visit 5 through Visit 9 of the Treatment phase (approximately Week 7 through Week 23)
Time to Discontinuation in the Treatment Phase	Time (days) until the participant discontinued the study	From Study Visit 5 through Visit 9 of the Treatment phase (approximately Week 7 through Week 23)
Percentage of Participants Meeting Escape Criteria in the Treatment Phase	The percentage of participants meeting Escape Criteria was calculated as the number of participants who met an Escape Criterion divided by the number who had reached Visit 5 minus major protocol violators. Escape Criteria are: (1) doubling of average monthly seizure frequency; (2) doubling of the highest consecutive 2-day seizure total; (3) occurrence of a new, more severe seizure type; or (4) worsening of generalized tonic-clonic seizures.	Study Visit 5 through Visit 9 of the Treatment phase (approximately Week 7 through Week 23)
Percent Change From Baseline in Weekly Seizure Frequency Between Study Visits 3 (Start of Dosing) and 9 (End of the Treatment Phase)	Change from Baseline was measured as the number of seizures at Visits 3 through 9 minus the number of seizures at Baseline. The number of partial seizures during treatment divided by the number of weeks of treatment was compared to the weekly seizure frequency during Baseline. A positive number equals a reduction in seizure frequency.	Baseline and Study Visit 3 through Visit 9 of the Treatment phase (Treatment Week 0 through Week 23)
Number of Seizure-free Participants During the Last 12 Weeks of Treatment of the Treatment Phase	The number of participants who had no seizures during the treatment period was calculated. The last 12 weeks of treatment were either Weeks 11-22 or 12-23 depending on which background AED was being withdrawn	The last 12 weeks of treatment of the Treatment phase (Monotherapy phase - approximately Week 11 through Week 23)
Percent Change From Baseline in the Average Seizure Frequency Measured at the End of Participation in the Continuation Phase	Change from baseline was calculated as the average seizure frequency at the end of the Continuation Phase minus the average seizure frequency at Baseline. The number of seizures during the Continuation phase divided by the number of weeks was compared to the number of seizures at Baseline. A positive number indicates a reduction in seizure frequency.	Baseline and start of Continuation phase through Week 24 or end of participation in the Continuation phase
The Number of Participants With at Least the Specified Change in Seizure Frequency, Compared to Baseline, at the End of Participation in the Continuation Phase (Maximum of 24 Weeks)	Change in seizure frequency was calculated as the average seizure frequency during the Continuation Phase minus the seizure frequency at Baseline.	Baseline and entire Continuation phase (24 Weeks)

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• French JA, Hammer AE, Vuong A, Messenheimer JA. Analysis of three lamotrigine extended-release clinical trials: comparison of pragmatic ITT and LOCF methodologies. Epilepsy Res. 2012 Aug;101(1-2):141-7. doi: 10.1016/j.eplepsyres.2012.03.015. Epub 2012 Apr 10.
• French JA, Temkin NR, Shneker BF, Hammer AE, Caldwell PT, Messenheimer JA. Lamotrigine XR conversion to monotherapy: first study using a historical control group. Neurotherapeutics. 2012 Jan;9(1):176-84. doi: 10.1007/s13311-011-0088-3.

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: May 1, 2006
• Primary Completion (Actual): November 1, 2008
• Study Completion (Actual): November 1, 2008

Study Registration Dates

• First Submitted: July 19, 2006
• First Submitted That Met QC Criteria: July 19, 2006
• First Posted (Estimate): July 21, 2006

Study Record Updates

• Last Update Posted (Estimate): January 2, 2017
• Last Update Submitted That Met QC Criteria: November 15, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: epilepsy; monotherapy; lamotrigine; Lamictal
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy; Epilepsies, Partial; 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: LAM30055

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. Study Protocol
   Information identifier: LAM30055
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Dataset Specification
   Information identifier: LAM30055
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Annotated Case Report Form
   Information identifier: LAM30055
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Clinical Study Report
   Information identifier: LAM30055
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Individual Participant Data Set
   Information identifier: LAM30055
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Informed Consent Form
   Information identifier: LAM30055
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Statistical Analysis Plan
   Information identifier: LAM30055
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register