Study Evaluating LAMICTAL Extended-Release Therapy Added To Current Seizure Treatments In Patients With Primary Generalized Tonic-Clonic Seizures (PGTC) Seizures
Condition: Epilepsy, Tonic-Clonic
MeSH terms: Epilepsy; Seizures; Epilepsy, Generalized; Epilepsy, Tonic-Clonic
Intervention: lamotrigine (LAMICTAL) extended-release; Placebo
Intervention description: Primary experimental dosage form; Placebo control
Intervention MeSH terms: Lamotrigine
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 153.0
Sex: All
Minimum age: 13 Years
Healthy volunteers: No
Keywords: antiepileptic drugs; seizures; primary generalized tonic-clonic seizures; Epilepsy; lamotrigine; anticonvulsants; LAMICTAL

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.