Clinical trial NCT02100644
Conditions: Epilepsy
Sponsor: GlaxoSmithKline
Start date: 2014-04-12; Completion date: 2015-05-11
Enrollment: 33 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief 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.

Detailed 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 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.

Arms: arm 1: The study objective is to examine whether the VPA dose can be reduced by additional administration of LTG in Japanese pre-menopausal female epilepsy patients, whose seizures are well controlled by VPA monotherapy. Then VPA is the standard product in this stuudy, not the investigational product.
Interventions: intervention 1: Lamotrigine tablets 25/100 mg
Intervention descriptions: intervention 1: 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.

Protocol documents: