Clinical Study of Lamotrigine to Treat Newly Diagnosed Epilepsy

Study Overview
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Brief Summary
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This is a multi-center, uncontrolled, open-label study conducted in Japan and South Korea to evaluate the efficacy and safety of lamotrigine monotherapy in subjects with newly diagnosed epilepsy and those with recurrent epilepsy (currently untreated). The study is composed of baseline, escalation phase, maintenance phase, taper phase and post study examination. During the escalation phase, the investigational product is administered orally at 25 mg/day for 2 weeks, then 50 mg/day for 2 weeks and finally 100 mg/day for 2 weeks. During the maintenance phase, 200 mg/day is administered orally for 24 weeks. However, the dose can be decreased to 100 mg/day if there are safety concerns. Also, if it is confirmed that the seizures cannot be controlled at the dose of 200 mg/day, the dose can be gradually increased up to 400 mg/day by 50-100 mg/day at intervals of at least 1 week. As a rule, lamotrigine should be administered once daily (in the evening), but the dose exceeding 200 mg/day can be administered in two divided doses (in the morning and evening). After the completion of maintenance phase, Japanese subjects who have responded to lamotrigine without tolerability issues are eligible to enter an extension phase of the study if indicated, until either approval of this indication (monotherapy in epilepsy) or after 24 months after LSLV (Last Subject's Last Visit) of the maintenance phase, whichever is sooner.

Official Title
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A Multi-center, Uncontrolled, Open-label, Evaluation of Lamotrigine Monotherapy in Newly Diagnosed Epilepsy or Recurrent Epilepsy (Currently Untreated)

Conditions
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Epilepsy

Intervention / Treatment
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* Drug: Lamictal


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Target disease: Subjects with newly diagnosed epilepsy or recurrent epilepsy which is untreated, having the following seizure types as classified by the International Classification of Seizures. Partial seizures (with or without secondarily generalisation) Generalized tonic-clonic seizures without focal onset, with or without myoclonus but without other generalized seizure type(s). Subjects have a confident diagnosis of epilepsy uncomplicated by pseudoseizures (psychogenic nonepileptic seizures). Subjects have had at least 2 seizures in the previous 6 months with at least 1 seizure in the previous 3 months. Age: ≥16 years (at the time of obtaining consent) Outpatients Subjects are able to write a seizure diary. Subjects understand and sign written informed consent. If a subject is under 20 years at the time of obtaining consent, a subject and a legally acceptable representative (e.g., a parent or a custodian) sign written consent to participate in this study. Gender: Male or female If female, and of childbearing potential, be using an acceptable form of birth control. 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. Subjects are able to comply with dosing of investigational products and all study procedures. Exclusion Criteria: Subjects having seizure types other than partial seizure or generalized tonic clonic seizures with or without myoclonus. Subjects having status epilepticus within the 6 months prior to the start of study treatment. Subjects with a history of treatment with AEDs (≥2 weeks) during 6 months before the start of treatment with the investigational product. Subjects with a history of treatment with lamotrigine. Subjects with a history of rash associated with other AED treatment. Subjects with a history of substance (including alcohol and drugs) dependence within 12 months before the start of investigational product or abuse within 1 month before the start of investigational product according to DSM-IV-TR. 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. Subjects with a severe psychiatric disorder which affects the procedure of study or drug assessment. Subjects with an acute or progressive neurological disorder or an organic disease. Subjects with any clinically significant chronic cardiac, renal, or hepatic medical condition. Any patient with these conditions are excluded from the study even if these conditions are being controlled with chronic therapy. 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). Female subjects who are pregnant or lactating, who may be pregnant, or who plan for pregnancy during the study. Subjects taking inducers of lamotrigine glucuronidation (i.e., rifampicin, lopinavir/ritonavir), atazanavir/ritonavir, risperidone, oral contraceptives or hormone drug which includes estrogen. Subjects having participated in other clinical study within 3 months before the start of investigational product. 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. Subjects whom the investigator or subinvestigator considers ineligible for the study.

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lamotrigine<br>No comparison. | Drug: Lamictal<br>* No comparison.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Were Seizure Free in the Maintenance Phase (Across Seizure Types and by Seizure Type Within 6 Months Prior to the Start of the Study) | Participants were considered to be seizure free if they did not report any seizures during the Maintenance Phase. Seizure types are defined as: ALL=any type of seizure; A: simple partial seizures, B: complex partial seizures; C: partial seizures evolving to secondary generation seizures; D5: tonic-clonic seizures. Simple partial seizures are seizures that affect only a small region of the brain, often the temporal lobes or hippocampi. Complex partial seizures are epileptic seizures that are associated with bilateral cerebral hemisphere involvement and cause impairment of awareness or responsiveness. Partial seizures evolving to secondary generation seizures are seizures that start as partial seizures, then spread to include the entire brain. Tonic-clonic seizures are a type of generalized seizure that affects the entire brain. | Weeks 7 to 30 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Withdrawal/Dropout From the Study (Across Seizure Types and by Seizure Type in Past 6 Months in the Escalation and Maintenance Phases) | Time to withdrawal is defined as the time from the start of treatment until withdrawal from the study. Seizure types are defined as: ALL=any type of seizure; A: simple partial seizures, B: complex partial seizures; C: partial seizures evolving to secondary generation seizures; D5: tonic-clonic seizures. Simple partial seizures are seizures which affect only a small region of the brain, often the temporal lobes or hippocampi. Simple partial seizures are seizures that affect only a small region of the brain, often the temporal lobes or hippocampi. Complex partial seizures are epileptic seizures that are associated with bilateral cerebral hemisphere involvement and cause impairment of awareness or responsiveness. Partial seizures evolving to secondary generation seizures are seizures that start as partial seizures, then spread to include the entire brain. Tonic-clonic seizures are a type of generalized seizure that affects the entire brain. | up to Week 30 | 
| Time to the First Seizure in the Maintenance Phase (Across Seizure Types and by Seizure Type) | The time to the first seizure in the Maintenance Phase is measured at the time the first seizure occurred in the Maintenance Phase. Seizure types are defined as: ALL=any type of seizure; A: simple partial seizures, B: complex partial seizures; C: partial seizures evolving to secondary generation seizures; D5: tonic-clonic seizures. Simple partial seizures are seizures that affect only a small region of the brain, often the temporal lobes or hippocampi. Complex partial seizures are epileptic seizures that are associated with bilateral cerebral hemisphere involvement and cause impairment of awareness or responsiveness. Partial seizures evolving to secondary generation seizures are seizures that start as partial seizures, then spread to include the entire brain. Tonic-clonic seizures are a type of generalized seizure that affects the entire brain. | Weeks 7 to 30 |