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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00355082
First received: July 19, 2006
Last updated: October 30, 2014
Last verified: May 2013
  Purpose

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


Condition Intervention Phase
Epilepsy, Partial
Drug: lamotrigine, 300 mg/day
Drug: lamotrigine, 250 mg/day
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Multicenter, Double-Blind, Randomized Conversion to Monotherapy Comparison of Two Doses of Lamotrigine for the Treatment of Partial Seizures

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • 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) [ Time Frame: From Study Visit 5 through Visit 9 of the Treatment Phase (approximately Week 7 through Week 23) ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • 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) [ Time Frame: From Study Visit 5 through Visit 9 of the Treatment phase (approximately Week 7 through Week 23) ] [ Designated as safety issue: No ]
    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.

  • Time to Discontinuation in the Treatment Phase [ Time Frame: From Study Visit 5 through Visit 9 of the Treatment phase (approximately Week 7 through Week 23) ] [ Designated as safety issue: No ]
    Time (days) until the participant discontinued the study

  • Percentage of Participants Meeting Escape Criteria in the Treatment Phase [ Time Frame: Study Visit 5 through Visit 9 of the Treatment phase (approximately Week 7 through Week 23) ] [ Designated as safety issue: No ]
    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.

  • Percent Change From Baseline in Weekly Seizure Frequency Between Study Visits 3 (Start of Dosing) and 9 (End of the Treatment Phase) [ Time Frame: Baseline and Study Visit 3 through Visit 9 of the Treatment phase (Treatment Week 0 through Week 23) ] [ Designated as safety issue: No ]
    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.

  • Number of Seizure-free Participants During the Last 12 Weeks of Treatment of the Treatment Phase [ Time Frame: The last 12 weeks of treatment of the Treatment phase (Monotherapy phase - approximately Week 11 through Week 23) ] [ Designated as safety issue: No ]
    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

  • Percent Change From Baseline in the Average Seizure Frequency Measured at the End of Participation in the Continuation Phase [ Time Frame: Baseline and start of Continuation phase through Week 24 or end of participation in the Continuation phase ] [ Designated as safety issue: No ]
    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.

  • 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) [ Time Frame: Baseline and entire Continuation phase (24 Weeks) ] [ Designated as safety issue: No ]
    Change in seizure frequency was calculated as the average seizure frequency during the Continuation Phase minus the seizure frequency at Baseline.


Enrollment: 226
Study Start Date: May 2006
Study Completion Date: November 2008
Primary Completion Date: November 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: lamotrigine 300
300 mg/day treatment
Drug: lamotrigine, 300 mg/day
300 mg/day
Other Name: lamotrigine
Experimental: lamotrigine 250
250 mg/day treatment
Drug: lamotrigine, 250 mg/day
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.

  Eligibility

Ages Eligible for Study:   13 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00355082

  Hide Study Locations
Locations
United States, Alabama
GSK Investigational Site
Alabaster, Alabama, United States, 35007
United States, Arizona
GSK Investigational Site
Litchfield Park, Arizona, United States, 85340
GSK Investigational Site
Mesa, Arizona, United States, 85201
GSK Investigational Site
Phoenix, Arizona, United States, 85013
GSK Investigational Site
Phoenix, Arizona, United States, 85003
GSK Investigational Site
Tucson, Arizona, United States, 85724
GSK Investigational Site
Tucson, Arizona, United States, 85741
United States, Arkansas
GSK Investigational Site
Fayetteville, Arkansas, United States, 72703
United States, California
GSK Investigational Site
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
United States, Connecticut
GSK Investigational Site
Danbury, Connecticut, United States, 06810
GSK Investigational Site
Fairfield, Connecticut, United States, 06824
United States, Delaware
GSK Investigational Site
Newark, Delaware, United States, 19713
United States, Florida
GSK Investigational Site
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
United States, Georgia
GSK Investigational Site
Atlanta, Georgia, United States, 30338
GSK Investigational Site
Atlanta, Georgia, United States, 30342
GSK Investigational Site
Decatur, Georgia, United States, 30033
United States, Idaho
GSK Investigational Site
Boise, Idaho, United States, 83702
United States, Illinois
GSK Investigational Site
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
United States, Iowa
GSK Investigational Site
Des Moines, Iowa, United States, 50309
United States, Kentucky
GSK Investigational Site
Lexington, Kentucky, United States, 40536
GSK Investigational Site
Lexington, Kentucky, United States, 40513
GSK Investigational Site
Louisville, Kentucky, United States, 40202
United States, Louisiana
GSK Investigational Site
New Orleans, Louisiana, United States, 70115
United States, Maryland
GSK Investigational Site
Bethesda, Maryland, United States, 20817
GSK Investigational Site
Glen Burnie, Maryland, United States, 21061
GSK Investigational Site
Pikesville, Maryland, United States, 21208
United States, Massachusetts
GSK Investigational Site
Springfield, Massachusetts, United States, 01104
United States, Michigan
GSK Investigational Site
Detroit, Michigan, United States, 48202
United States, Minnesota
GSK Investigational Site
Minneapolis, Minnesota, United States, 55455
GSK Investigational Site
St. Cloud, Minnesota, United States, 56303
United States, Mississippi
GSK Investigational Site
Hattiesburg, Mississippi, United States, 39401
United States, Missouri
GSK Investigational Site
Kansas City, Missouri, United States, 64111
GSK Investigational Site
St. Louis, Missouri, United States, 63104
GSK Investigational Site
St. Louis, Missouri, United States, 63110
United States, Nevada
GSK Investigational Site
Henderson, Nevada, United States, 89014
GSK Investigational Site
Las Vegas, Nevada, United States, 81902
GSK Investigational Site
Las Vegas, Nevada, United States, 89106
United States, New Jersey
GSK Investigational Site
Edison, New Jersey, United States, 08818
GSK Investigational Site
Vorhees, New Jersey, United States, 08043
United States, New York
GSK Investigational Site
Lawrence, New York, United States, 11559
GSK Investigational Site
Plainview, New York, United States, 11803
GSK Investigational Site
Syracuse, New York, United States, 13210
United States, North Carolina
GSK Investigational Site
Asheville, North Carolina, United States, 28803
United States, Ohio
GSK Investigational Site
Columbus, Ohio, United States, 43210-1296
United States, Oklahoma
GSK Investigational Site
Oklahoma City, Oklahoma, United States, 73112
United States, Pennsylvania
GSK Investigational Site
Philadelphia, Pennsylvania, United States, 19107
GSK Investigational Site
Sellersville, Pennsylvania, United States, 18960
United States, Texas
GSK Investigational Site
Dallas, Texas, United States, 75230
GSK Investigational Site
Houston, Texas, United States, 77025
GSK Investigational Site
San Antonio, Texas, United States, 78258
GSK Investigational Site
San Antonio, Texas, United States, 78229
GSK Investigational Site
Temple, Texas, United States, 76502
United States, Utah
GSK Investigational Site
Midvale, Utah, United States, 84047
United States, Washington
GSK Investigational Site
Renton, Washington, United States, 98055
United States, West Virginia
GSK Investigational Site
Charleston, West Virginia, United States, 25301
GSK Investigational Site
Morgantown, West Virginia, United States, 26506
United States, Wisconsin
GSK Investigational Site
Madison, Wisconsin, United States, 53715
GSK Investigational Site
Milwaukee, Wisconsin, United States, 53215
Argentina
GSK Investigational Site
Capital Federal, Buenos Aires, Argentina, 1181
GSK Investigational Site
Capital Fefderal, Buenos Aires, Argentina
GSK Investigational Site
Ciudad Autonoma de Buenos Aires, Argentina
GSK Investigational Site
Ciudad Autónoma de Buenos Aires, Argentina, 1425
Chile
GSK Investigational Site
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
Costa Rica
GSK Investigational Site
San Jose, Costa Rica
Korea, Republic of
GSK Investigational Site
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, 110-744
GSK Investigational Site
Seoul, Korea, Republic of, 138-736
GSK Investigational Site
Seoul, Korea, Republic of, 120-752
GSK Investigational Site
Seoul, Korea, Republic of, 135-170
Puerto Rico
GSK Investigational Site
San Juan, Puerto Rico, 00918
GSK Investigational Site
San Juan, Puerto Rico, 00936
Russian Federation
GSK Investigational Site
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, 193019
GSK Investigational Site
St.-Petersburg, Russian Federation, 194291
GSK Investigational Site
St.Petersburg, Russian Federation, 193167
Ukraine
GSK Investigational Site
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
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

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;101:141-147.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00355082     History of Changes
Other Study ID Numbers: LAM30055
Study First Received: July 19, 2006
Results First Received: September 8, 2009
Last Updated: October 30, 2014
Health Authority: Russia: Ministry of Health of the Russian Federation
United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
epilepsy
monotherapy
Lamictal
lamotrigine

Additional relevant MeSH terms:
Epilepsies, Partial
Epilepsy
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Anticonvulsants
Lamotrigine
Calcium Channel Blockers
Cardiovascular Agents
Central Nervous System Agents
Excitatory Amino Acid Agents
Excitatory Amino Acid Antagonists
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs
Sodium Channel Blockers
Therapeutic Uses
Voltage-Gated Sodium Channel Blockers

ClinicalTrials.gov processed this record on November 27, 2014