Recruitment

Recruitment Status
Completed
Estimated Enrollment
30

Inclusion Criteria

Tonic-clonic seizures with or without myoclonus but without other generalized seizure type(s)
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)
Partial seizures (with or without secondary generalization)
...
Tonic-clonic seizures with or without myoclonus but without other generalized seizure type(s)
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)
Partial seizures (with or without secondary generalization)
Subjects having a confident diagnosis of epilepsy that is uncomplicated by pseudoseizures such as psychogenic nonepileptic seizures
(Age and gender)

Exclusion Criteria

Subjects with a history of rash associated with other AED treatments.
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
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
...
Subjects with a history of rash associated with other AED treatments.
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
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
Subjects with a family history of infant death of unknown cause or urea cycle disorder
Subjects with an acute or progressive neurological disorder or an organic disease
Subjects with a severe psychiatric disorder that affects the procedures of the study or drug assessment
Subjects who are pregnant or lactating, who may be pregnant, or who plan for pregnancy during the study
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.
Subjects with status epilepticus during the 6 months prior to start of the investigational product
Subjects with a history of hypersensitivity to LTG
Subjects with a history of encephalopathy or coma of unknown cause
Subjects who have received another AED besides VPA during the 12 weeks prior to start of the investigational product
Subjects whom the investigator or subinvestigator considers ineligible for the study
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.
Subjects taking inducers of LTG glucuronidation (i.e., rifampicinor lopinavir/ritonavir), atazanavir/ritonavir, risperidone, or oral contraceptives or hormone drugs containing estrogen
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
Subjects who have participated in other clinical studies within 3 months prior to start of the investigational product
Subjects taking carbapenem antibiotic (i.e., panipenem/betamipron, meropenem hydrate, imipenem hydrate/cilastatin sodium, biapenem, doripenem hydrate, or tebipenem pivoxil)

Summary

Conditions
Epilepsy
Type
Interventional
Phase
Phase 4
Design
  • Allocation: N/A
  • Intervention Model: Single Group Assignment
  • Masking: None (Open Label)
  • Primary Purpose: Treatment

Participation Requirements

Age
Between 15 years and 125 years
Gender
Only females

Description

RATIONALE In several studies that investigated the effects of in utero exposure to AEDs (antiepileptic drugs) on fetal malformations and intellectual development in children after birth, it has been reported that VPA causes neonatal malformations and decreases intelligence of children in a dose depe...

RATIONALE In several studies that investigated the effects of in utero exposure to AEDs (antiepileptic drugs) on fetal malformations and intellectual development in children after birth, it has been reported that VPA causes neonatal malformations and decreases intelligence of children in a dose dependent manner, whereas such a risk is low in LTG (Hernandez-Díaz et al., 2012; Meador et al., 2013). It has also been reported that LTG as adjunctive therapy with VPA is effective in inhibiting seizures in patients with poorly controlled seizures, and adverse events under VPA monotherapy can be relieved by subsequently reducing VPA dose after LTG is combined (Sale et al., 2005; Jozwiak et al., 2000; Morris et al, 2004; Buchanan, 1996). Thus, by considering the benefits of replacing VPA by LTG in childbearing women, we will examine whether VPA dose can be reduced by introducing LTG in Japanese female epilepsy patients under VPA monotherapy (aged ≥ 15 years, pre-menopausal). STUDY DESIGN Single arm, multicenter, and open-label study TIME FRAME Screening(Retrospective review of medical records for 12 weeks) LTG escalation phase (8-18 weeks) VPA reduction phase (3-16 weeks) LTG & VPA maintenance phase (12 weeks) Follow up (1-4 weeks) PRIMARY OBJECTIVE To examine whether the VPA dose can be reduced by additional administration of LTG (up to 200 mg/d if there are no safety concerns) in Japanese pre-menopausal female epilepsy patients aged 15 years or older, whose seizures are well controlled by VPA monotherapy (fixed maintenance dose of 400-1200 mg/d). SECONDARY OBJECTIVES To investigate the steady state concentration of LTG immediately before VPA dose reduction, at the time of VPA dose reduction, and during the LTG&VPA maintenance phase. To investigate the safety and tolerability associated with additional administration of LTG followed by dose reduction of VPA.

Inclusion Criteria

Tonic-clonic seizures with or without myoclonus but without other generalized seizure type(s)
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)
Partial seizures (with or without secondary generalization)
...
Tonic-clonic seizures with or without myoclonus but without other generalized seizure type(s)
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)
Partial seizures (with or without secondary generalization)
Subjects having a confident diagnosis of epilepsy that is uncomplicated by pseudoseizures such as psychogenic nonepileptic seizures
(Age and gender)

Exclusion Criteria

Subjects with a history of rash associated with other AED treatments.
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
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
...
Subjects with a history of rash associated with other AED treatments.
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
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
Subjects with a family history of infant death of unknown cause or urea cycle disorder
Subjects with an acute or progressive neurological disorder or an organic disease
Subjects with a severe psychiatric disorder that affects the procedures of the study or drug assessment
Subjects who are pregnant or lactating, who may be pregnant, or who plan for pregnancy during the study
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.
Subjects with status epilepticus during the 6 months prior to start of the investigational product
Subjects with a history of hypersensitivity to LTG
Subjects with a history of encephalopathy or coma of unknown cause
Subjects who have received another AED besides VPA during the 12 weeks prior to start of the investigational product
Subjects whom the investigator or subinvestigator considers ineligible for the study
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.
Subjects taking inducers of LTG glucuronidation (i.e., rifampicinor lopinavir/ritonavir), atazanavir/ritonavir, risperidone, or oral contraceptives or hormone drugs containing estrogen
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
Subjects who have participated in other clinical studies within 3 months prior to start of the investigational product
Subjects taking carbapenem antibiotic (i.e., panipenem/betamipron, meropenem hydrate, imipenem hydrate/cilastatin sodium, biapenem, doripenem hydrate, or tebipenem pivoxil)

Tracking Information

NCT #
NCT02100644
Collaborators
Not Provided
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
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