Valproate Dose Reduction and Its Clinical Evaluation by Introducing Lamotrigine in Japanese Women With Epilepsy - Single Arm, Multicenter, and Open-label Study
Condition: Epilepsy
MeSH terms: Epilepsy
Intervention: Lamotrigine tablets 25/100 mg
Intervention description: Lamotrigine (LTG) is administered according to the package insert: that is, 25 mg of LTG will be orally administered once every other day for the first 2 weeks and then once daily for the next 2 weeks. Thereafter, the dose will be gradually escalated by 25-50 mg every 1-2 week for once or twice daily administration. During the VPA reduction phase and LTG&amp;VPA maintenance phase, as specified in the information of package insert, maintenance dose of LTG will be administered twice daily.
Intervention MeSH terms: Lamotrigine
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 33.0
Sex: Female
Minimum age: 15 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to examine whether the VPA (Valproate) dose can be reduced by
      additional administration of LTG (Lamotrigine) in Japanese pre-menopausal female epilepsy
      patients aged 15 years or older, whose seizures are well controlled by VPA monotherapy.
    

Eligibility criteria:

        Inclusion Criteria:

          1. (Target disease) Epilepsy patients having the following seizure types as classified by
             the International Classification of Epileptic Seizures

               -  Partial seizures (with or without secondary generalization)

               -  Tonic-clonic seizures with or without myoclonus but without other generalized
                  seizure type(s)

          2. Subjects having a confident diagnosis of epilepsy that is uncomplicated by
             pseudoseizures such as psychogenic nonepileptic seizures

          3. Subjects whose seizures have been controlled for 12 weeks prior to start of the
             investigational product with a stable maintenance dose of VPA monotherapy (400-1200
             mg/d)

          4. (Age and gender)

        Japanese pre-menopausal women who are at least 15 years old at the time of consent, not
        lactating, and can agree to use any of the following types of contraception in a reliable
        fashion:

          1. Complete abstinence during the study as well as for a period after the study to
             account for elimination of the investigational product (a minimum of 2 weeks)

          2. Consistent and correct use of any of the following contraceptive methods

               -  Surgical sterilization of male partner (i.e., male partner is the sole sexual
                  partner for the female subject and is sterilized prior to the subject's entry
                  into the study)

               -  Intrauterine device with a failure rate of less than 1% per year

               -  Double barrier method (e.g., spermicide plus a condom or a diaphragm) Note: Women
                  who have had a hysterectomy or tubal ligation are considered to be of
                  non-childbearing potential. Since a pharmacokinetic interaction has been observed
                  between LTG and estrogen-based oral contraceptives, the use of hormonal therapy
                  such as for contraception or hormone replacement therapy is not allowed.

                  5.Outpatients 6.Subjects who can keep a seizure diary 7.Subjects who can
                  understand and sign the informed consent. If the subject is under 20 years old at
                  the time of consent, both the subject and subject's legally acceptable
                  representative have to sign the consent to participate in the study.

                  8.QTc <480 msec for subjects with bundle branch block or QTc <450 msec for other
                  subjects, in which QTc is measured by either single or triplicate-averaged ECG
                  9.Subjects who can comply with dosing of the investigational and standard
                  products and all study procedures

        Exclusion Criteria:

          1. Subjects with a history of hypersensitivity to LTG

          2. Subjects with a history of rash associated with other AED treatments.

          3. Subjects who have received another AED besides VPA during the 12 weeks prior to start
             of the investigational product

          4. Subjects with status epilepticus during the 6 months prior to start of the
             investigational product

          5. Subjects with a history of substance (including alcohol and drug) dependence or
             substance abuse as defined by the DSM-IV-TR within 12 months or 1 month, respectively,
             prior to start of the investigational product

          6. Subjects with a severe acute or chronic illness likely to impair drug absorption,
             distribution, metabolism, or excretion; or subjects with any unstable physical symptom
             likely to require hospitalization during the study

          7. Subjects with a severe psychiatric disorder that affects the procedures of the study
             or drug assessment

          8. Subjects with an acute or progressive neurological disorder or an organic disease

          9. Subjects with any clinically significant 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 a chronic therapy.

         10. Subjects with an unstable liver disease (as defined by the presence of ascites,
             encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or gastric varices, or
             persistent jaundice), cirrhosis, or known biliary abnormalities (with the exception of
             Gilbert's syndrome or asymptomatic gallstones) Note: Chronic stable hepatitis B and C
             are acceptable if the subjects otherwise meet the inclusion criteria. However, the
             subjects with chronic stable hepatitis B will be excluded if significant
             immunosuppressive agents are being administered due to a risk of hepatitis B
             reactivation.

         11. Subjects who are pregnant or lactating, who may be pregnant, or who plan for pregnancy
             during the study

         12. Subjects who are suspected to have an urea cycle disorder as below:

               -  Subjects with a history of encephalopathy or coma of unknown cause

               -  Subjects with a family history of infant death of unknown cause or urea cycle
                  disorder

         13. Subjects taking inducers of LTG glucuronidation (i.e., rifampicinor
             lopinavir/ritonavir), atazanavir/ritonavir, risperidone, or oral contraceptives or
             hormone drugs containing estrogen

         14. Subjects taking carbapenem antibiotic (i.e., panipenem/betamipron, meropenem hydrate,
             imipenem hydrate/cilastatin sodium, biapenem, doripenem hydrate, or tebipenem pivoxil)

         15. Subjects who have participated in other clinical studies within 3 months prior to
             start of the investigational product

         16. Subjects who have had active suicidal plans/intent or suicidal thoughts in the past 3
             months prior to start of the investigational product; or subjects who have history of
             suicide attempts in the last 1 year prior to start of the investigational product or
             of multiple suicide attempts in their lifetime

         17. Subjects whom the investigator or subinvestigator considers ineligible for the study