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: May 9, 2013
Last verified: March 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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00355082

Locations
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
Samara, Russian Federation, 443095
GSK Investigational Site
St.Petersburg, Russian Federation, 193167
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: May 9, 2013
Health Authority: Russia: Ministry of Health of the Russian Federation
United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
epilepsy
lamotrigine
Lamictal
monotherapy

Additional relevant MeSH terms:
Epilepsy
Epilepsies, Partial
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Lamotrigine
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Cardiovascular Agents
Therapeutic Uses
Anticonvulsants
Central Nervous System Agents

ClinicalTrials.gov processed this record on April 15, 2014