Clinical trial NCT00104416: Study Evaluating LAMICTAL Extended-Release Therapy Added To Current Seizure Treatments In Patients With Primary Generalized Tonic-Clonic Seizures (PGTC) Seizures
Official title: A Multicenter, Double-blind, Randomized, Parallel-group Evaluation of LAMICTAL Extended-Release Adjunctive Therapy in Patients With Primary Generalized Tonic-Clonic Seizures
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Epilepsy, Tonic-Clonic
Keywords: antiepileptic drugs
seizures
primary generalized tonic-clonic seizures
Epilepsy
lamotrigine
anticonvulsants
LAMICTAL
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2005-03-01
Enrollment: 153
Sex: ALL
Minimum age (years): 13
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is being conducted to compare the efficacy and safety of LAMICTAL (lamotrigine) extended-release with placebo in the treatment of Primary Generalized Tonic-Clonic (PGTC) seizures. LAMICTAL extended-release is an investigational drug. Placebo tablets look like LAMICTAL extended-release tablets but do not contain active medication. In this study, LAMICTAL extended-release or placebo tablets will be added to current seizure treatments.


Eligibility criteria: Inclusion Criteria:

* Is ≥13 years of age (male or female).
* Has a confident diagnosis of epilepsy with PGTC seizures for more than 24 weeks prior to the Baseline Phase.
* Has electroencephalogram (EEG) evidence of either spike-and-wave discharges consistent with PGTC, or at least 2 EEGs with no indication of focal abnormalities. The EEG may be historical or prospective. Investigators may use a historical EEG as long as there is appropriate documentation.
* Has a documented history of PGTC seizures with or without other generalized seizure type(s) with no focal onset, and at least 1 PGTC seizure during the eight consecutive weeks (i.e., 56 consecutive days) prior to starting the 8-week Baseline Phase.
* Has at least 3 PGTC seizures occurring anytime during an 8-week (i.e., 56 days) prospective Baseline Phase.

  * NOTE: When a historical baseline is used, the same time period cannot count for documentation of inclusion criteria 4 and 5. Additionally, innumerable seizure activity will not count towards the number of seizures required for randomization.
  * NOTE: With authorization from GSK, a maximum of four weeks (i.e., 28 days) of historical seizure data may replace up to four weeks (i.e., 28 days) of the prospective Baseline Phase for subjects providing reliable documentation of the following:

    1. complete daily seizure diary that includes the number of seizures experienced each day along with the exact classification of each seizure type for consecutive days prior to the prospective Baseline Phase
    2. stability of prescribed dosages of background antiepileptic drugs (AEDs)
    3. compliance with background AEDs.
  * All subjects permitted to use historical seizure data must complete a minimum of four weeks (i.e., 28 days) of the prospective Baseline Phase. The historical Baseline Phase and the prospective Baseline Phase must equal 56 consecutive days.
* Is currently treated with a stable regimen of one or two AED(s) for at least four weeks prior to starting the Baseline Phase (historical or prospective).

  * NOTE: Benzodiazepines used chronically will be considered to be concurrent AEDs.
  * NOTE: Subjects with surgically implanted vagal nerve stimulators (VNS) will be allowed to enter the study provided that all of the following conditions are met:

    1. VNS has been in place for at least 24 weeks prior to the Baseline Phase.
    2. The settings must remain the same for at least 28 days prior to the Baseline Phase.
    3. The settings must remain the same during the Baseline, Escalation, Maintenance and Transition Phases.
    4. The battery is expected to last for the duration of the study.
    5. VNS is counted as a "concurrent AED."
* Is able and willing to maintain an accurate and complete daily written seizure diary, or has a parent/caregiver who is able and willing to maintain an accurate and complete daily written seizure diary for the entire duration of the study.
* Is able to comply with dosing of study drugs, background AEDs and all study procedures.
* Has given written informed consent, or has a parent/legally authorized representative who has given written informed consent, prior to the performance of any study assessments.
* If female, and of childbearing potential, must 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 3 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
     * Implants of levonorgestrel
     * Injectable progestogen
     * Oral contraceptive (either combined, with at least 50mcg estrogen for women on enzyme-induced AEDs, or progestogen only)
     * 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.

Exclusion Criteria:

* Has a history of partial seizures or interictal expression of partial seizures as evidenced by EEG NOTE: EEG may be historical or prospective.
* Has had status epilepticus within the 24 weeks prior to, or during, the Baseline Phase.
* Is taking three or more background AEDs chronically.
* Has Lennox-Gastaut syndrome.
* Is currently using or has previously used lamotrigine.
* Is currently taking felbamate.
* Is abusing alcohol and/or other substance(s).
* 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.
* Is currently following the ketogenic diet.
* Is planning surgery to control seizures during the study.
* Is suffering from acute or progressive neurological disease, severe psychiatric disease, or severe mental abnormality that are 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.
* Is pregnant, breastfeeding, or planning to become pregnant during the study or within the three weeks after the last dose of study drug.

Primary outcomes:
measure: Percent Change From Baseline in Weekly Primary Generalized Tonic-clonic (PGTC) Seizure Frequency During the Entire Double-Blind Treatment Phase
timeFrame: Baseline through end of Double-Blind Treatment Phase (up to Week 19)
Secondary outcomes:
measure: Number of Participants With >=25%, >=50%, >=75%, or 100% Reduction in PGTC Seizure Frequency During the Entire Double-Blind (DB)Treatment Phase (TP), the Escalation Phase, the Maintenance Phase, and the Last 8 Weeks of the Maintenance Phase
timeFrame: Entire DB Treatment Phase (Treatment Week 1 up to Week 19), Escalation Phase (Treatment Week 1 up to Week 7), Maintenance Phase (Treatment Week 8 up to Week 19), and the last 8 weeks of the Maintenance Phase (Treatment Week 12 up to Week 19)
measure: Percent Change From Baseline in PGTC Seizure Frequency During the Escalation Phase, the Maintenance Phase, and During the Last 8 Weeks of the Maintenance Phase of the Double-Blind Treatment Phase
timeFrame: Escalation Phase (Treatment Week 1 up to Week 7), Maintenance Phase (Treatment Week 8 up to Week 19), and the last 8 weeks of the Maintenance Phase (Week 12 up to Week 19)
measure: Number of Participants With the Indicated Time to >=50% Reduction in Seizure Frequency in the Double-Blind Treatment Phase
timeFrame: Baseline through end of Double-Blind Treatment Phase (up to Week 19)
measure: Change From Baseline in Body Weight at Week 19 of the Double-Blind Treatment Phase
timeFrame: Baseline and Week 19 (or last on-study measurement in Double-Blind Treatment Phase)
measure: Number of Participants With Improved Clinical Status on the Investigator's Global Assessment in the Double-Blind Treatment Phase
timeFrame: Week 19 (or last on-study assessment in Double-Blind Treatment Phase)
measure: Number of Participants With Improved Satisfaction With Seizure Control on the Subject Satisfaction Questionnaire in the Double-Blind Treatment Phase
timeFrame: Week 19 (or last on-study assessment in Double-Blind Treatment Phase)
measure: Percent Change From Baseline in Weekly PGTC Seizure Frequency During the Entire Continuation Phase (CP), the Transition Phase, the Open-Label Phase, and the Last 8 Weeks of the Open-Label Phase
timeFrame: Entire CP (CP Week 1 up to Week 52), the Transition Phase (CP Week 1 up to Week 7), the Open-Label Phase (CP Week 8 up to Week 52), and the last 8 weeks of the Open-Label Phase (CP Week 45 up to Week 52)
measure: Number of Participants With >=25%, >=50%, >=75%, or 100% Reduction or >=50% Increase From Baseline in Weekly PGTC Seizure Frequency for the Entire Continuation Phase, the Transition Phase, the Open-Label (OL) Phase, and the Last 8 Weeks of the OL Phase.
timeFrame: Entire CP (CP Week 1 up to Week 52), the Transition Phase (CP Week 1 up to Week 7), the Open-Label Phase (CP Week 8 up to Week 52), and the last 8 weeks of the Open-Label Phase (CP Week 45 up to Week 52)
measure: Mean Change From Baseline in the Profile of Mood State (POMS) Mood Disturbance Total Score at Week 19 of the Double-Blind Treatment Phase
timeFrame: Baseline and Week 19 (or last on-study measurement in Double-Blind Treatment Phase)
measure: Mean Change From Baseline in the Center for Epidemiological Studies-Depression Scale (CES-D) Total Score at Week 19 of the Double-Blind Treatment Phase
timeFrame: Baseline and Week 19 (or last on-study measurement in Double-Blind Treatment Phase)
measure: Mean Change From Baseline in the Neurological Disorders Depression Inventory-Epilepsy (NDDI-E) 6-Item Total Score at Week 19 of the Double-Blind Treatment Phase
timeFrame: Baseline and Week 19 (or last on-study measurement in Double-Blind Treatment Phase)
measure: Mean Change From Baseline in the Quality of Life in Epilepsy-31-P (QOLIE-31P) Overall Score at Week 19 of the Double-Blind Treatment Phase
timeFrame: Baseline and Week 19 (or last on-study measurement in Double-Blind Treatment Phase)
measure: Mean Change From Baseline in the Adverse Experience Profile (AEP) Total Score at Week 19 of the Double-Blind Treatment Phase
timeFrame: Baseline and Week 19 (or last on-study measurement in Double-Blind Treatment Phase)
measure: Mean Change From Baseline in the Seizure Severity Questionnaire (SSQ) Global Bother Score at Week 19 Double-Blind Treatment Phase
timeFrame: Baseline and Week 19 (or last on-study measurement in Double-Blind Treatment Phase)
measure: Mean Change From Baseline in the Epworth Sleepiness Scale (ESS) 8-Item Total Score at Week 19 of the Double-Blind Treatment Phase
timeFrame: Baseline and Week 19 (or last on-study measurement in Double-Blind Treatment Phase)
measure: Serum Concentrations and Population (POP) Pharmacokinetic Parameters for Lamotrigine
timeFrame: Blood samples drawn at Treatment Weeks 11, 15, and 19 (or last on-study measurement in Double-Blind Treatment Phase)
Other outcomes:
Locations:
city: Anniston
country: United States
facility: GSK Investigational Site
state: Alabama
city: Birmingham
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facility: GSK Investigational Site
state: Alabama
city: Northport
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city: Little Rock
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city: Newport Beach
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city: Santa Monica
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facility: GSK Investigational Site
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city: Sepuldeva
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facility: GSK Investigational Site
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city: Washington
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state: District of Columbia
city: Hollywood
country: United States
facility: GSK Investigational Site
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city: Maitland
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city: Ocala
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state: Florida
city: Atlanta
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state: Georgia
city: Augusta
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state: Georgia
city: Marietta
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city: Savannah
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state: Georgia
city: Suwanee
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facility: GSK Investigational Site
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city: Chicago
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state: Illinois
city: Flossmoor
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state: Illinois
city: Springfield
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city: Des Moines
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state: Iowa
city: Wichita
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state: Kansas
city: Crestview Hills
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state: Kentucky
city: Louisville
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state: New Jersey
city: West Orange
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city: Amherst
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state: New York
city: New York
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state: New York
city: Asheville
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state: North Carolina
city: Greenville
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state: North Carolina
city: Raleigh
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state: North Carolina
city: Columbus
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state: Ohio
city: Oklahoma City
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state: Oklahoma
city: Oklahoma City
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state: Oklahoma
city: Philadelphia
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state: Pennsylvania
city: Philadelphia
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state: Pennsylvania
city: Pittsburgh
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state: Tennessee
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state: Texas
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state: Texas
city: Houston
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state: Texas
city: San Antonio
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state: Texas
city: Wichita Falls
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state: Texas
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country: United States
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state: Utah
city: Burlington
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state: Vermont
city: Richmond
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state: Virginia
city: Madison
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state: Wisconsin
city: Milwaukee
country: United States
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state: Wisconsin
city: Capital Federal
country: Argentina
facility: GSK Investigational Site
state: Buenos Aires
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: Ciudad Autónoma de Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: Curitiba
country: Brazil
facility: GSK Investigational Site
state: Paraná
city: Campinas
country: Brazil
facility: GSK Investigational Site
state: São Paulo
city: São Paulo
country: Brazil
facility: GSK Investigational Site
city: Santiago
country: Chile
facility: GSK Investigational Site
state: Región Metro De Santiago
city: Santiago
country: Chile
facility: GSK Investigational Site
state: Región Metro De Santiago
city: Singen
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Ulm
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Alzenau
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Bamberg
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Fuerth
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Muenchen
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Neuoetting
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Straubing
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Unterhaching
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Wuerzburg
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Bernau
country: Germany
facility: GSK Investigational Site
state: Brandenburg
city: Ludwigsfelde
country: Germany
facility: GSK Investigational Site
state: Brandenburg
city: Bad Homburg
country: Germany
facility: GSK Investigational Site
state: Hessen
city: Frankfurt
country: Germany
facility: GSK Investigational Site
state: Hessen
city: Wismar
country: Germany
facility: GSK Investigational Site
state: Mecklenburg-Vorpommern
city: Wismar
country: Germany
facility: GSK Investigational Site
state: Mecklenburg-Vorpommern
city: Bueckeburg
country: Germany
facility: GSK Investigational Site
state: Niedersachsen
city: Goettingen
country: Germany
facility: GSK Investigational Site
state: Niedersachsen
city: Osnabrueck
country: Germany
facility: GSK Investigational Site
state: Niedersachsen
city: Baesweiler
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Bochum
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Bochum
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Essen
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Essen
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Hattingen
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Koeln
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Moenchengladbach
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Muenster
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Limburgerhof
country: Germany
facility: GSK Investigational Site
state: Rheinland-Pfalz
city: Bernburg
country: Germany
facility: GSK Investigational Site
state: Sachsen-Anhalt
city: Halle
country: Germany
facility: GSK Investigational Site
state: Sachsen-Anhalt
city: Koethen
country: Germany
facility: GSK Investigational Site
state: Sachsen-Anhalt
city: Magdeburg
country: Germany
facility: GSK Investigational Site
state: Sachsen-Anhalt
city: Magdeburg
country: Germany
facility: GSK Investigational Site
state: Sachsen-Anhalt
city: Naumburg
country: Germany
facility: GSK Investigational Site
state: Sachsen-Anhalt
city: Floeha
country: Germany
facility: GSK Investigational Site
state: Sachsen
city: Leipzig
country: Germany
facility: GSK Investigational Site
state: Sachsen
city: Leipzig
country: Germany
facility: GSK Investigational Site
state: Sachsen
city: Kiel
country: Germany
facility: GSK Investigational Site
state: Schleswig-Holstein
city: Jena
country: Germany
facility: GSK Investigational Site
state: Thueringen
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Hamburg
country: Germany
facility: GSK Investigational Site
city: Hamburg
country: Germany
facility: GSK Investigational Site
city: Hamburg
country: Germany
facility: GSK Investigational Site
city: Hamburg
country: Germany
facility: GSK Investigational Site
city: Hamburg
country: Germany
facility: GSK Investigational Site
city: Hyderabad, Andhra Pradesh
country: India
facility: GSK Investigational Site
city: Lucknow
country: India
facility: GSK Investigational Site
city: New Delhi
country: India
facility: GSK Investigational Site
city: Daejeon
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Kubang Kerian
country: Malaysia
facility: GSK Investigational Site
city: San German
country: Puerto Rico
facility: GSK Investigational Site
city: San Juan
country: Puerto Rico
facility: GSK Investigational Site
city: San Juan
country: Puerto Rico
facility: GSK Investigational Site
city: Ekaterinburg
country: Russian Federation
facility: GSK Investigational Site
city: Moscow
country: Russian Federation
facility: GSK Investigational Site
city: Moscow
country: Russian Federation
facility: GSK Investigational Site
city: Moscow
country: Russian Federation
facility: GSK Investigational Site
city: Moscow
country: Russian Federation
facility: GSK Investigational Site
city: Moscow
country: Russian Federation
facility: GSK Investigational Site
city: Moscow
country: Russian Federation
facility: GSK Investigational Site
city: Samara
country: Russian Federation
facility: GSK Investigational Site
city: St'Petersburg
country: Russian Federation
facility: GSK Investigational Site
city: St.-Petersburg
country: Russian Federation
facility: GSK Investigational Site
city: St.-Petersburg
country: Russian Federation
facility: GSK Investigational Site
city: Kharkiv
country: Ukraine
facility: GSK Investigational Site
city: Kyiv
country: Ukraine
facility: GSK Investigational Site
city: Lviv
country: Ukraine
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Biton V, Di Memmo J, Shukla R, Lee YY, Poverennova I, Demchenko V, Saiers J, Adams B, Hammer A, Vuong A, Messenheimer J. Adjunctive lamotrigine XR for primary generalized tonic-clonic seizures in a randomized, placebo-controlled study. Epilepsy Behav. 2010 Nov;19(3):352-8. doi: 10.1016/j.yebeh.2010.07.022. Epub 2010 Oct 30.