Study Evaluating LAMICTAL Extended-Release Therapy Added To Current Seizure Treatments In Patients With Primary Generalized Tonic-Clonic Seizures (PGTC) Seizures

Condition(s) targeted: Seizures, Tonic-Clonic; Epilepsy

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

Phase: Phase 3

Status: Active, not recruiting

Sponsored by: GlaxoSmithKline

Official(s) and/or principal investigator(s):
GSK Clinical Trials, MD, Study Director, Affiliation: GlaxoSmithKline

This study is being conducted to compare the efficacy and safety of LAMICTAL (lamotrigine) extended-release with placebo in the treatment of 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.

Official title: A Multicenter, Double-Blind, Randomized, Parallel-Group Evaluation of LAMICTAL Extended-Release Adjunctive Therapy in Subjects With Primary Generalized Tonic-Clonic Seizures

Study design: Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome: Percentage change from baseline in PGTC seizure frequency during the double-blind treatment phase.

Secondary outcome:

Reduction in partial seizure frequency during portions of double-blind phase (=25%,=50%,=75%,100%).

Time to 50% reduction in PGTC seizure frequency.

Adverse events.

Weight change.

Health outcomes questionnaires.

Population Pharmacokinetics.

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.

Proportion of subjects with ≥25%, ≥50%, ≥75% or 100% reduction in PGTC seizure frequency during the entire Double-Blind Treatment Phase, the Escalation Phase, the Maintenance Phase, and the last 8 weeks of the Maintenance Phase.

Time to ≥50% reduction in seizure frequency.

Type and incidence of treatment-emergent adverse events.

Change from Baseline in body weight.

Proportion of subjects with improved clinical status on the Investigator assessment of subject's clinical status questionnaire and the subject's satisfaction with seizure control.

Serum concentrations and population pharmacokinetic parameters for lamotrigine.

For subjects ≥16 years of age if the questionnaire has been validated for the language of the country where the study is to be conducted:

Change from Baseline in Profile of Mood States (POMS) scores.

Change from Baseline in Center for Epidemiological Studies- Depression Scale (CES-D) score.

·Change from Baseline in the Neurological Disorders Depression Inventory-Epilepsy (NDDI-E, 46-item research version) score.

·Change from Baseline in the Quality of Life in Epilepsy (QOLIE-31-P) score.

·Change from Baseline in the Liverpool Adverse Experience Profile (AEP) score.

·Change from Baseline in the Seizure Severity Questionnaire (SSQ) score.

·Change from Baseline in the Epworth Sleepiness Scale (ESS) score.

Minimum age: 13 Years. Maximum age: N/A. Gender(s): Both.

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 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 (see Section 14. 2, Appendix 2: "Guidelines for Using a Historical Baseline Phase"):

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 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 (

"Use of Benzodiazepines").

- 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 ("Vagal Nerve Stimulators":

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 50mg estrogen for women

on EIAEDs, 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 in accordance with Section 14. 1.

- 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 as specified in Section 8. 1.2, "Use of Benzodiazepines".

- 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.

Exclusion criteria:

- Previous treatment with lamotrigine.

- Subjects receiving treatment with felbamate or currently following the ketogenic

diet.

- Subjects who are pregnant, breastfeeding, or planning to become pregnant.

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Last updated: February 27, 2008