Clinical Study of Lamotrigine to Treat Newly Diagnosed Typical Absence Seizure in Children and Adolescents
Condition: Epilepsy
MeSH terms: Seizures; Epilepsy, Absence
Intervention: Lamictal
Intervention description: No comparison
Intervention MeSH terms: Lamotrigine
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 20.0
Sex: All
Minimum age: 2 Years
Maximum age: 15 Years
Healthy volunteers: No

Summary:

      This is a multi-center, uncontrolled, open-label study to evaluate the efficacy and safety of
      lamotrigine monotherapy on newly diagnosed typical absence seizure in children and
      adolescents in Japan and South Korea.

      The study period is composed the baseline, fixed escalation phase, escalation phase,
      maintenance phase, taper phase, and post study examination. During the fixed escalation
      phase, the investigational product is administered at 0.3 mg/kg/day for 2 weeks (Week 1 to
      2), followed by 0.6 mg/kg/day for 2 weeks (Week 3 to 4). Subjects thereafter visit the clinic
      once every 1 to 2 weeks during the escalation phase to increase the dose by 0.6 mg/kg/day up
      to a maximum of 10.2 mg/kg/day or 400 mg/day (whichever was less) until patients are
      confirmed to be seizure-free by HV tests for clinical signs. After seizure free is confirmed
      by HV-clinical signs, the dose is increased by one level and HV-EEG (electroencephalography)
      test (first test) is assessed at the next visit. If seizure free is observed by HV-EEG, the
      same dose is administered. Thereafter, HV-EEG (second test) is assessed at the next visit and
      if seizure free is confirmed again, the subjects enter the 12-week maintenance phase. During
      the maintenance phase, patients visit the clinic once every 4 weeks. The dose can be adjusted
      as necessary within the range of 1.2 to 10.2 mg/kg/day or 400 mg/day (whichever was less)
      taking into account the status of seizures and the safety. The investigational product is
      administered once daily (in the evening). However, if the number of tablets is large,
      twice-daily administration (in the morning and evening) is also allowed. After the completion
      of maintenance phase, subjects who have responded to lamotrigine without tolerability issues
      are eligible to enter the extension phase of the study if clinically indicated.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Target disease: Subjects with newly diagnosed and untreated typical absence seizure
             which is classifiable by the International Classification of Seizures.

          2. Diagnosis of typical absence seizures is established by at least one of two 4-minute
             hyperventilation tests as supported by clinical signs and EEG findings.

             The following criteria will be used to define a typical absence seizure on the EEG: a
             discharge of generalized spike-and-wave or multiple spike-and-wave activity lasting ≥3
             seconds during the awake state. The frequency of the spike-and-wave should be between
             2.5-4.5 Hz.

          3. Age (at the time of obtaining consent):

               -  2 to 15 years of age in Japan

               -  2 to 12 years of age in South Korea

          4. Subjects must weigh at least 7 kg

          5. Outpatients

          6. Parent/guardian must have given written informed consent. Subjects who are
             intellectually able to understand the concepts and procedures of the protocol must
             give assent by also signing the consent.

          7. Gender: Male or female

          8. QTc<450 millisecond (msec) or <480msec for subjects with Bundle Branch Block - values
             based on either single ECG values or triplicate ECG averaged QTc values obtained over
             a brief recording period.

        Exclusion Criteria:

          1. Subjects with partial seizure or generalized seizures other than typical absence.

          2. Subjects with a history of rash associated with other treatment.

          3. Subjects with any clinically significant chronic cardiac, renal, or hepatic medical
             condition. Any patient with these conditions will be excluded from the study even if
             these conditions are being controlled with chronic therapy.

          4. Subjects with an acute or chronic illness likely to impair drug absorption,
             distribution, metabolism or excretion or with any unstable physical symptoms likely to
             require hospitalization during participation in the study.

          5. Subjects with a psychiatric disorder requiring medication, or who had psychiatric
             conditions in the past that was both judged to be severe and required hospitalization.

          6. Subjects with an acute or progressive neurological disorder or an organic disease.

          7. Subjects with currently taking any psychoactive drugs to treat hyperactivity disorder
             or attention deficit disorder.

          8. Subjects with an unstable liver disease (as defined by the presence of ascites,
             encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or gastric varices or
             persistent jaundice), cirrhosis, known biliary abnormalities (with the exception of
             Gilbert's syndrome or asymptomatic gallstones).

          9. Female subjects who are pregnant or lactating, who may be pregnant, or who plan for
             pregnancy during the study.

         10. Children in foster care: A child who has been placed under the control or protection
             of an agency, organisation, institution or entity by the courts, the government or a
             government body, acting in accordance with powers conferred on them by law or
             regulation. This can include a child cared for by foster parents or living in a care
             home or institution, provided that the arrangement falls within the definition above.
             The definition of a child in care does not include a child who is adopted or who has
             an appointed legal guardian.

         11. Subjects taking inducers of lamotrigine glucuronidation (i.e., rifampicin,
             lopinavir/ritonavir), atazanavir/ritonavir, risperidone, oral contraceptives or
             hormone drug which includes estrogen.

         12. Subjects having participated in other clinical study in the past 3 months before the
             start of investigational product.

         13. Subjects who have active suicidal plan/intent or have had active suicidal thoughts in
             the past 3 months before the start of investigational product or who have history of
             suicide attempt in the last 1 year before the start of investigational product or more
             than 1 lifetime suicide attempt.

         14. Subjects whom the investigator (or subinvestigator) considers ineligible for the
             study.