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Clinical Trials/NCT00104416
NCT00104416CompletedPhase 3

A Multicenter, Double-blind, Randomized, Parallel-group Evaluation of LAMICTAL Extended-Release Adjunctive Therapy in Patients With Primary Generalized Tonic-Clonic Seizures

GlaxoSmithKline1 site in 1 country153 target enrollmentStarted: December 2004Last updated:
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Conditions
Interventions
Drugs

Trial Snapshot

Phase
Phase 3
Status
Completed
Enrollment
153
Locations
1
Primary Endpoint
Percent Change From Baseline in Weekly Primary Generalized Tonic-clonic (PGTC) Seizure Frequency During the Entire Double-Blind Treatment Phase
Study OverviewStudy DesignEligibility CriteriaArms & InterventionsOutcomesInvestigatorsSitesRecords & IdentifiersSimilar Trials

Study Overview

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.

Study Design

Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel
Primary Purpose
Treatment
Masking
Double (Participant, Investigator)

Eligibility Criteria

Ages
13 Years to — (Child, Adult, Older Adult)
Sex
All
Accepts Healthy Volunteers
No

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
  • •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:
  • •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
  • •stability of prescribed dosages of background antiepileptic drugs (AEDs)
  • •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:
  • •VNS has been in place for at least 24 weeks prior to the Baseline Phase.
  • •The settings must remain the same for at least 28 days prior to the Baseline Phase.
  • •The settings must remain the same during the Baseline, Escalation, Maintenance and Transition Phases.
  • •The battery is expected to last for the duration of the study.
  • •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:
  • •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).
  • •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.

Arms & Interventions

Placebo

Placebo Comparator

Intervention: Placebo (Drug)

lamotrigine (LAMICTAL) extended-relesase

Experimental

Intervention: lamotrigine (LAMICTAL) extended-release (Drug)

Outcomes

Primary Outcomes

Percent Change From Baseline in Weekly Primary Generalized Tonic-clonic (PGTC) Seizure Frequency During the Entire Double-Blind Treatment Phase

Time Frame: Baseline through end of Double-Blind Treatment Phase (up to Week 19)

Percent change from baseline is calculated as the number of seizures by week during the Double-Blind Treatment Phase (Treatment Week 1 up to Week 19) compared to the number of seizures per week during the Baseline Phase (Baseline Week 1 up to Week 8). A positive number equals a reduction in seizure frequency. PGTC seizures are more commonly known as gran mal seizures.

Secondary Outcomes

  • 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(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))
  • Number of Participants With the Indicated Time to >=50% Reduction in Seizure Frequency in the Double-Blind Treatment Phase(Baseline through end of Double-Blind Treatment Phase (up to Week 19))
  • 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(Baseline and Week 19 (or last on-study measurement in Double-Blind Treatment Phase))
  • Mean Change From Baseline in the Seizure Severity Questionnaire (SSQ) Global Bother Score at Week 19 Double-Blind Treatment Phase(Baseline and Week 19 (or last on-study measurement in Double-Blind Treatment Phase))
  • Number of Participants With Improved Clinical Status on the Investigator's Global Assessment in the Double-Blind Treatment Phase(Week 19 (or last on-study assessment in Double-Blind Treatment Phase))
  • Number of Participants With Improved Satisfaction With Seizure Control on the Subject Satisfaction Questionnaire in the Double-Blind Treatment Phase(Week 19 (or last on-study assessment in Double-Blind Treatment Phase))
  • Mean Change From Baseline in the Adverse Experience Profile (AEP) Total Score at Week 19 of the Double-Blind Treatment Phase(Baseline and Week 19 (or last on-study measurement in Double-Blind Treatment Phase))
  • Mean Change From Baseline in the Epworth Sleepiness Scale (ESS) 8-Item Total Score at Week 19 of the Double-Blind Treatment Phase(Baseline and Week 19 (or last on-study measurement in Double-Blind Treatment Phase))
  • 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(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))
  • Change From Baseline in Body Weight at Week 19 of the Double-Blind Treatment Phase(Baseline and Week 19 (or last on-study measurement in Double-Blind Treatment Phase))
  • 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(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))
  • Serum Concentrations and Population (POP) Pharmacokinetic Parameters for Lamotrigine(Blood samples drawn at Treatment Weeks 11, 15, and 19 (or last on-study measurement in Double-Blind Treatment Phase))
  • 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.(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))
  • Mean Change From Baseline in the Profile of Mood State (POMS) Mood Disturbance Total Score at Week 19 of the Double-Blind Treatment Phase(Baseline and Week 19 (or last on-study measurement in Double-Blind Treatment Phase))
  • 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(Baseline and Week 19 (or last on-study measurement in Double-Blind Treatment Phase))
  • 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(Baseline and Week 19 (or last on-study measurement in Double-Blind Treatment Phase))

Investigators

Sponsor Class
Industry
Responsible Party
Sponsor

Study Sites (1)

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