Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
All participants (par.) that complete the Treatment Phase (TP) and all Baseline Failures (par. who did not meet randomization seizure criteria necessary to qualify for the TP) are eligible to enter the Continuation Phase (CP). The CP is for long-term safety exposure to lamotrigine (LTG) extended release (XR); it is not a cross-over phase.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
The number of par. starting the CP does not equal the number completing the TP, as 1) the CP was optional, 2) not everyone from the TP was eligible to enter the CP, and 3) Baseline Failures were allowed to enter the CP, however they were not included in the “started" count for the TP.

Reporting Groups

	Description
Double-Blind Phase: Placebo	Control - matching placebo once daily
Double-Blind Phase: LTG XR	Lamotrigine (LTG) extended release (XR) once daily
Continuation Phase: Placebo/LTG	Participants who received placebo in the Double-Blind Phase and then entered the CP, in which they received LTG
Continuation Phase: LTG/LTG	Participants who received LTG XR in the Double-Blind Phase and then entered the CP, in which they received LTG
Baseline Failures	Baseline failures who entered the CP without receiving treatment in the Double-Blind Phase. Baseline Failures were participants that successfully progressed through the Screening Phase and completed the Baseline Phase of the Double-blind Study, but ultimately did not meet the seizure frequency criteria for randomization into the Double-Blind Treatment Phase of the study. As a result, they were not counted as having started in the Double-Blind Study, but were eligible to enter the CP of the study.

Participant Flow for 2 periods

Period 1:   Double-Blind Phase

	Double-Blind Phase: Placebo	Double-Blind Phase: LTG XR	Continuation Phase: Placebo/LTG	Continuation Phase: LTG/LTG	Baseline Failures
STARTED	77	76	0	0	0
COMPLETED	69	66	0	0	0
NOT COMPLETED	8	10	0	0	0
Adverse Event	2	1	0	0	0
Lost to Follow-up	0	1	0	0	0
Protocol Violation	0	1	0	0	0
Withdrawal by Subject	2	3	0	0	0
Pregnancy	1	0	0	0	0
Participant Did Not Take Drug	3	4	0	0	0

Period 2:   Continuation Phase

	Double-Blind Phase: Placebo	Double-Blind Phase: LTG XR	Continuation Phase: Placebo/LTG	Continuation Phase: LTG/LTG	Baseline Failures
STARTED	0	0	69	67 [1]	32
COMPLETED	0	0	63	65	27
NOT COMPLETED	0	0	6	2	5
Adverse Event	0	0	2	0	2
Lost to Follow-up	0	0	1	0	1
Withdrawal by Subject	0	0	2	1	1
Pregnancy	0	0	1	1	0
Non-compliance	0	0	0	0	1

Reporting Groups

	Description
Double-Blind Phase: Placebo	Control - matching placebo once daily
Double-Blind Phase: LTG XR	LTG XR once daily

Baseline Measures

	Double-Blind Phase: Placebo	Double-Blind Phase: LTG XR	Total
Number of Participants   [units: participants]	73	70	143
Age [1] [units: years] Mean ± Standard Deviation	28.4  ± 11.48	29.4  ± 12.78	28.9  ± 12.10
Gender [1] [units: participants]
Female	38	32	70
Male	35	38	73
Race/Ethnicity, Customized [1] [units: participants]
African American/African Heritage	1	2	3
Asian	31	31	62
White	38	37	75
American Indian or Alaskan Native and White	2	0	2
Asian and White	1	0	1

1.  Primary:

Percent Change From Baseline in Weekly Primary Generalized Tonic-clonic (PGTC) Seizure Frequency During the Entire Double-Blind Treatment Phase   [ Time Frame: Baseline through end of Double-Blind Treatment Phase (up to Week 19) ]

2.  Secondary:

Number of Participants With >=25%, >=50%, >=75%, or 100% Reduction in PGTC Seizure Frequency During the Entire Double-Blind (DB)Treatment Phase (TP), the Escalation Phase, the Maintenance Phase, and the Last 8 Weeks of the Maintenance Phase   [ Time Frame: Entire DB Treatment Phase (Treatment Week 1 up to Week 19), Escalation Phase (Treatment Week 1 up to Week 7), Maintenance Phase (Treatment Week 8 up to Week 19), and the last 8 weeks of the Maintenance Phase (Treatment Week 12 up to Week 19) ]

3.  Secondary:

Percent Change From Baseline in PGTC Seizure Frequency During the Escalation Phase, the Maintenance Phase, and During the Last 8 Weeks of the Maintenance Phase of the Double-Blind Treatment Phase   [ Time Frame: Escalation Phase (Treatment Week 1 up to Week 7), Maintenance Phase (Treatment Week 8 up to Week 19), and the last 8 weeks of the Maintenance Phase (Week 12 up to Week 19) ]

4.  Secondary:

Number of Participants With the Indicated Time to >=50% Reduction in Seizure Frequency in the Double-Blind Treatment Phase   [ Time Frame: Baseline through end of Double-Blind Treatment Phase (up to Week 19) ]

5.  Secondary:

Change From Baseline in Body Weight at Week 19 of the Double-Blind Treatment Phase   [ Time Frame: Baseline and Week 19 (or last on-study measurement in Double-Blind Treatment Phase) ]

6.  Secondary:

Number of Participants With Improved Clinical Status on the Investigator’s Global Assessment in the Double-Blind Treatment Phase   [ Time Frame: Week 19 (or last on-study assessment in Double-Blind Treatment Phase) ]

7.  Secondary:

Number of Participants With Improved Satisfaction With Seizure Control on the Subject Satisfaction Questionnaire in the Double-Blind Treatment Phase   [ Time Frame: Week 19 (or last on-study assessment in Double-Blind Treatment Phase) ]

8.  Secondary:

Percent Change From Baseline in Weekly PGTC Seizure Frequency During the Entire Continuation Phase (CP), the Transition Phase, the Open-Label Phase, and the Last 8 Weeks of the Open-Label Phase   [ Time Frame: Entire CP (CP Week 1 up to Week 52), the Transition Phase (CP Week 1 up to Week 7), the Open-Label Phase (CP Week 8 up to Week 52), and the last 8 weeks of the Open-Label Phase (CP Week 45 up to Week 52) ]

9.  Secondary:

Number of Participants With >=25%, >=50%, >=75%, or 100% Reduction or >=50% Increase From Baseline in Weekly PGTC Seizure Frequency for the Entire Continuation Phase, the Transition Phase, the Open-Label (OL) Phase, and the Last 8 Weeks of the OL Phase.   [ Time Frame: Entire CP (CP Week 1 up to Week 52), the Transition Phase (CP Week 1 up to Week 7), the Open-Label Phase (CP Week 8 up to Week 52), and the last 8 weeks of the Open-Label Phase (CP Week 45 up to Week 52) ]

10.  Secondary:

Mean Change From Baseline in the Profile of Mood State (POMS) Mood Disturbance Total Score at Week 19 of the Double-Blind Treatment Phase   [ Time Frame: Baseline and Week 19 (or last on-study measurement in Double-Blind Treatment Phase) ]

11.  Secondary:

Mean Change From Baseline in the Center for Epidemiological Studies-Depression Scale (CES-D) Total Score at Week 19 of the Double-Blind Treatment Phase   [ Time Frame: Baseline and Week 19 (or last on-study measurement in Double-Blind Treatment Phase) ]

12.  Secondary:

Mean Change From Baseline in the Neurological Disorders Depression Inventory-Epilepsy (NDDI-E) 6-Item Total Score at Week 19 of the Double-Blind Treatment Phase   [ Time Frame: Baseline and Week 19 (or last on-study measurement in Double-Blind Treatment Phase) ]

13.  Secondary:

Mean Change From Baseline in the Quality of Life in Epilepsy-31-P (QOLIE-31P) Overall Score at Week 19 of the Double-Blind Treatment Phase   [ Time Frame: Baseline and Week 19 (or last on-study measurement in Double-Blind Treatment Phase) ]

14.  Secondary:

Mean Change From Baseline in the Adverse Experience Profile (AEP) Total Score at Week 19 of the Double-Blind Treatment Phase   [ Time Frame: Baseline and Week 19 (or last on-study measurement in Double-Blind Treatment Phase) ]

15.  Secondary:

Mean Change From Baseline in the Seizure Severity Questionnaire (SSQ) Global Bother Score at Week 19 Double-Blind Treatment Phase   [ Time Frame: Baseline and Week 19 (or last on-study measurement in Double-Blind Treatment Phase) ]

16.  Secondary:

Mean Change From Baseline in the Epworth Sleepiness Scale (ESS) 8-Item Total Score at Week 19 of the Double-Blind Treatment Phase   [ Time Frame: Baseline and Week 19 (or last on-study measurement in Double-Blind Treatment Phase) ]

17.  Secondary:

Serum Concentrations and Population (POP) Pharmacokinetic Parameters for Lamotrigine   [ Time Frame: Blood samples drawn at Treatment Weeks 11, 15, and 19 (or last on-study measurement in Double-Blind Treatment Phase) ]