This registration study in China is a multi-centre, double-blind, placebo-controlled clinical
trial to evaluate the efficacy and safety of lamotrigine in the prevention of
recurrence/relapse of mood episodes in subjects with bipolar I disorder. Subjects are bipolar
I disorder patients with recent/current manic, hypomanic, mixed or depressive episode. The
study will include an open-label phase and a randomized phase. During the open-label phase,
subjects will have lamotrigine monotherapy or combination therapy escalation. The target dose
of lamotrigine is 200 milligram (mg)/day monotherapy. The duration of treatment in the
open-label phase will last 6-16 weeks, until subjects reach a stable dose of lamotrigine.
Beginning at week 7 of the open-label phase, subjects who have reached a stable dose of
lamotrigine and met response criteria, defined as maintaining a Clinical Global Impression of
Severity (CGI-S) score <= 3 for at least 4 continuous weeks and maintaining lamotrigine 200
mg/day monotherapy for at least 1 week, will be eligible to enroll in the double-blind phase
of the study. Subjects who have not met response criteria after 16 weeks of participation in
the open-label phase will be withdrawn from the study. Subjects will have lamotrigine 200
mg/day monotherapy for at least 1 week prior to randomization. Subjects who have met
randomization requirements will be randomized 1:1 to lamotrigine 200 mg/day or placebo for 36
weeks double-blind treatment. After randomization, subjects will be assessed at weekly
intervals for the first month, biweekly intervals for the second month, and then at monthly
intervals for up to 36 weeks of double-blind treatment. The primary endpoint will be TIME,
defined as the time to intervention (addition of pharmacotherapy or electroconvulsive therapy
[ECT]) for any mood episode (relapse or recurrence of a depressive, manic, hypomanic or mixed
episode) after randomization. The secondary endpoints will include time to intervention for
manic, hypomanic or mixed episode (TIMan) and time to intervention for depressive episode
(TIDep).The scores on the Hamilton Depression (HAMD), Young Mania Rating Scale (YMRS), CGI-I,
CGI-S and Global Assessment Scale (GAS) will be used as indicators for both intensity and
duration of mood symptoms during this phase. Subjects who withdraw early from the study prior
to week 36 or reach TIME will have a follow-up visit 14 days after the last dose of
investigational drug.