Partial seizures (including secondary generalized seizures) or tonic-clonic seizures with or without myoclonus but without other generalized seizure type(s) MedDRA version: 20.0 Level: LLT Classification code 10043999 Term: Tonic-clonic epilepsy System Organ Class: 100000038485 MedDRA version: 20.0 Level: LLT Classification code 10065336 Term: Partial epilepsy System Organ Class: 100000014703
Conditions
Interventions
Trade Name: Lamictal XR,Lamictal,LAMICTIN
Product Name: lamotrigine
Product Code: GI267119
Pharmaceutical Form: Tablet
INN or Proposed INN: LAMOTRIGINE
Other descriptive name: LAMOTRIGINE
Concentratio
Sponsors
GlaxoSmithKline K.K.
Eligibility
Sex/Gender
All
Inclusion 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 =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: •To examine plasma LTG concentrations immediately before VPA dose reduction, and during the VPA reduction phase and LTG/VPA maintenance phase. •To investigate the safety and tolerability of VPA dose reduction with additional administration of LTG. ;Primary end point(s): -Proportion of subjects who achieved a reduction in the daily VPA dose during the LTG/VPA maintenance phase and percent reduction in the daily VPA dose as compared to that at baseline ;Main Objective: To evaluate whether the sodium valproate (VPA) dose can be reduced by additional treatment with lamotrigine (LTG) (up to 200 mg/day if there were no safety concerns) in Japanese premenopausal female patients with epilepsy aged 15 years or older whose seizures were well controlled by VPA monotherapy (fixed maintenance dose of 400 to 1200 mg/day).;Timepoint(s) of evaluation of this end point: Endpoint assessed through out the study period i.e (Between weeks 8 and 42) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): .Change from screening in the number of day(s) that epileptic seizures occurred during the LTG/VPA maintenance phase ·Change from baseline in QOLIE-31-P (subjects aged 18 years or older) or QOLIE-AD-48 (subjects aged 15 to 17 years) at the end of the LTG/VPA maintenance phase ·Ratios of subjects who completed and were withdrawn from the study ;Timepoint(s) of evaluation of this end point: Endpoints assessed through out the study period i.e (Between weeks 8 and 42) | — |
Countries
Japan
Contacts
Public ContactToshio Maeda
GlaxoSmithKline K.K.
Outcome results
None listed