Trial Outcomes & Findings for Study Of The Safety And Efficacy Of Lyrica In The Treatment Of Newly Diagnosed Partial Epilepsy (NCT NCT00280059)

Last Updated: 2021-01-28

Results Overview

Responders = participants who achieved any 6 consecutive months (\>182 days) of seizure-freedom (absence of partial seizures, generalized seizures and unclassified epileptic seizures) during the 52 week efficacy assessment phase.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

660 participants

Primary outcome timeframe

Week 5 up to Week 56

Results posted on

2021-01-28

Participant Flow

Participant milestones

Participant milestones
Measure	Pregabalin Pregabalin 150, 300, 450 or 600 mg/day orally twice daily (BID); individual titration based on number of seizures experienced once Level 1 (150 mg/day) was maintained for at least 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.	Lamotrigine Lamotrigine 100, 200, 400, or 500 mg/day orally BID; individual titration based on number of seizures experienced once Level 1 (100 mg/day) was reached and maintained for 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.
Efficacy Assessment Phase STARTED	330	330
Efficacy Assessment Phase COMPLETED	236	250
Efficacy Assessment Phase NOT COMPLETED	94	80
Extension Phase STARTED	194	215
Extension Phase COMPLETED	145	177
Extension Phase NOT COMPLETED	49	38

Reasons for withdrawal

Reasons for withdrawal
Measure	Pregabalin Pregabalin 150, 300, 450 or 600 mg/day orally twice daily (BID); individual titration based on number of seizures experienced once Level 1 (150 mg/day) was maintained for at least 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.	Lamotrigine Lamotrigine 100, 200, 400, or 500 mg/day orally BID; individual titration based on number of seizures experienced once Level 1 (100 mg/day) was reached and maintained for 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.
Efficacy Assessment Phase Death	2	0
Efficacy Assessment Phase Adverse Event	33	31
Efficacy Assessment Phase Laboratory abnormaility	1	0
Efficacy Assessment Phase Lack of Efficacy	19	3
Efficacy Assessment Phase Lost to Follow-up	6	13
Efficacy Assessment Phase Other	7	8
Efficacy Assessment Phase Withdrawal by Subject	26	25

Baseline Characteristics

Study Of The Safety And Efficacy Of Lyrica In The Treatment Of Newly Diagnosed Partial Epilepsy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Pregabalin n=330 Participants Pregabalin 150, 300, 450 or 600 mg/day orally twice daily (BID); individual titration based on number of seizures experienced once Level 1 (150 mg/day) was maintained for at least 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.	Lamotrigine n=330 Participants Lamotrigine 100, 200, 400, or 500 mg/day orally BID; individual titration based on number of seizures experienced once Level 1 (100 mg/day) was reached and maintained for 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.	Total n=660 Participants Total of all reporting groups
Age, Customized < 18 years	9 participants n=5 Participants	9 participants n=7 Participants	18 participants n=5 Participants
Age, Customized Between 18 and 44 years	228 participants n=5 Participants	228 participants n=7 Participants	456 participants n=5 Participants
Age, Customized Between 45 and 64 years	79 participants n=5 Participants	74 participants n=7 Participants	153 participants n=5 Participants
Age, Customized >= 65 years	14 participants n=5 Participants	19 participants n=7 Participants	33 participants n=5 Participants
Sex: Female, Male Female	165 Participants n=5 Participants	146 Participants n=7 Participants	311 Participants n=5 Participants
Sex: Female, Male Male	165 Participants n=5 Participants	184 Participants n=7 Participants	349 Participants n=5 Participants

PRIMARY outcome

Timeframe: Week 5 up to Week 56

Population: Full analysis set (FAS) (intent to treat population): randomized participants who took at least 1 dose of study medication. N = number of participants who had at least 1 dose of study treatment and seizure efficacy data. Analysis excludes participants who did not enter maintenance phase of study.

Outcome measures

Outcome measures
Measure	Pregabalin n=314 Participants Pregabalin 150, 300, 450 or 600 mg/day orally twice daily (BID); individual titration based on number of seizures experienced once Level 1 (150 mg/day) was maintained for at least 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.	Lamotrigine n=308 Participants Lamotrigine 100, 200, 400, or 500 mg/day orally BID; individual titration based on number of seizures experienced once Level 1 (100 mg/day) was reached and maintained for 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.	Pregabalin 450 mg/Day Pregabalin 450 mg/day administered BID	Pregabalin 600 mg/Day Pregabalin 600 mg/day administered BID	Lamotrigine 100 mg/Day Lamotrigine 100 mg/day administered BID	Lamotrigine 200 mg/Day Lamotrigine 200 mg/day administered BID	Lamotrigine 400 mg/Day Lamotrigine 400 mg/day administered BID	Lamotrigine 500 mg/Day Lamotrigine 500 mg/day administered BID
Percentage of Seizure-free Participants (Responders) During Efficacy Assessment Phase	51.6 percentage of participants	67.9 percentage of participants	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Week 4 up to Week 56

Population: FAS. N = number of participants who entered maintenance phase of study and had seizure efficacy data.

Time in days, from first day of study medication to the first 6 months of seizure freedom after Day 28. Participants who did not achieve 6 months seizure freedom after Day 28 were censored from analysis.

Outcome measures

Outcome measures
Measure	Pregabalin n=314 Participants Pregabalin 150, 300, 450 or 600 mg/day orally twice daily (BID); individual titration based on number of seizures experienced once Level 1 (150 mg/day) was maintained for at least 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.	Lamotrigine n=308 Participants Lamotrigine 100, 200, 400, or 500 mg/day orally BID; individual titration based on number of seizures experienced once Level 1 (100 mg/day) was reached and maintained for 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.	Pregabalin 450 mg/Day Pregabalin 450 mg/day administered BID	Pregabalin 600 mg/Day Pregabalin 600 mg/day administered BID	Lamotrigine 100 mg/Day Lamotrigine 100 mg/day administered BID	Lamotrigine 200 mg/Day Lamotrigine 200 mg/day administered BID	Lamotrigine 400 mg/Day Lamotrigine 400 mg/day administered BID	Lamotrigine 500 mg/Day Lamotrigine 500 mg/day administered BID
Time to 6 Consecutive Months of Seizure-freedom After 4-week Dose Escalation Phase: All Seizures	254 days Interval 199.0 to 295.0	183 days Interval 183.0 to 209.0	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Week 0 to Week 56

Population: FAS. N = number of participants who entered maintenance phase of study and had seizure efficacy data. Time to exit due to adverse events was inestimable as survival estimate at end of maintenance phase was below 0.500.

Number of participants who exited the study due to adverse events during the double-blind treatment period. Time in days, from first day of study treatment to day of exit from the study due to an adverse event (ie, last day on study medication) during the double blind treatment period (including dose escalation phase) was inestimable. Observations with other reasons for exiting or participants who did not exit the study were right censored as of the last day on study medication.

Outcome measures

Outcome measures
Measure	Pregabalin n=330 Participants Pregabalin 150, 300, 450 or 600 mg/day orally twice daily (BID); individual titration based on number of seizures experienced once Level 1 (150 mg/day) was maintained for at least 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.	Lamotrigine n=330 Participants Lamotrigine 100, 200, 400, or 500 mg/day orally BID; individual titration based on number of seizures experienced once Level 1 (100 mg/day) was reached and maintained for 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.	Pregabalin 450 mg/Day Pregabalin 450 mg/day administered BID	Pregabalin 600 mg/Day Pregabalin 600 mg/day administered BID	Lamotrigine 100 mg/Day Lamotrigine 100 mg/day administered BID	Lamotrigine 200 mg/Day Lamotrigine 200 mg/day administered BID	Lamotrigine 400 mg/Day Lamotrigine 400 mg/day administered BID	Lamotrigine 500 mg/Day Lamotrigine 500 mg/day administered BID
Exit Due to Adverse Events During the Double-blind Treatment Phase (Including Dose Escalation Phase)	33 participants	31 participants	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Week 0 to Week 56

Population: FAS. N = number of participants who had at least 1 dose of study treatment and seizure efficacy data Time to exit for any reason during the double-blind treatment phase was inestimable as the survival estimate at the end of the maintenance phase was below 0.500.

Number of participants who exited the study for any reason during the double blind treatment phase. Time in days, from first day of study treatment to day of exit from the study due to any reason (ie, last day on study medication) was inestimable. Participants who did not exit the study were right censored as of the last day on study medication.

Outcome measures

Outcome measures
Measure	Pregabalin n=330 Participants Pregabalin 150, 300, 450 or 600 mg/day orally twice daily (BID); individual titration based on number of seizures experienced once Level 1 (150 mg/day) was maintained for at least 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.	Lamotrigine n=330 Participants Lamotrigine 100, 200, 400, or 500 mg/day orally BID; individual titration based on number of seizures experienced once Level 1 (100 mg/day) was reached and maintained for 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.	Pregabalin 450 mg/Day Pregabalin 450 mg/day administered BID	Pregabalin 600 mg/Day Pregabalin 600 mg/day administered BID	Lamotrigine 100 mg/Day Lamotrigine 100 mg/day administered BID	Lamotrigine 200 mg/Day Lamotrigine 200 mg/day administered BID	Lamotrigine 400 mg/Day Lamotrigine 400 mg/day administered BID	Lamotrigine 500 mg/Day Lamotrigine 500 mg/day administered BID
Exit for Any Reason During the Double-blind Treatment Phase (Including Dose Escalation Phase)	94 participants	80 participants	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Week 4 up to Week 56

Population: FAS. N = number of participants who entered maintenance phase of study and had seizure efficacy data. Time to exit due to lack of efficacy after 4-week dose escalation phase was inestimable as survival estimate at end of maintenance phase was below 0.500.

Number of participants who exited the study due to lack of efficacy after the 4-week dose escalation phase. Time in days, from first day of study treatment to day of exit due to lack of efficacy after Day 28 of the escalation phase (ie, last day on study medication) was inestimable. Participants who did not exit or exited for a different reason were right censored as of the last day on study medication.

Outcome measures

Outcome measures
Measure	Pregabalin n=329 Participants Pregabalin 150, 300, 450 or 600 mg/day orally twice daily (BID); individual titration based on number of seizures experienced once Level 1 (150 mg/day) was maintained for at least 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.	Lamotrigine n=330 Participants Lamotrigine 100, 200, 400, or 500 mg/day orally BID; individual titration based on number of seizures experienced once Level 1 (100 mg/day) was reached and maintained for 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.	Pregabalin 450 mg/Day Pregabalin 450 mg/day administered BID	Pregabalin 600 mg/Day Pregabalin 600 mg/day administered BID	Lamotrigine 100 mg/Day Lamotrigine 100 mg/day administered BID	Lamotrigine 200 mg/Day Lamotrigine 200 mg/day administered BID	Lamotrigine 400 mg/Day Lamotrigine 400 mg/day administered BID	Lamotrigine 500 mg/Day Lamotrigine 500 mg/day administered BID
Exit Due to Lack of Efficacy After 4-week Dose Escalation Phase	78 participants	58 participants	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Week 4 up to Week 56

Population: FAS. N = number of participants who entered maintenance phase of study and had seizure efficacy data. Time to exit for any reason after the 4-week dose escalation phase was inestimable as the survival estimate at the end of the maintenance phase was below 0.500.

Number of participants who exited the study due to any reason after the 4-week dose escalation phase. Time in days, from first day of study treatment to day of exit after Day 28 of the study due to any reason (ie, last day on study medication) was inestimable. Participants who did not exit or did not reach this phase were right censored as of the last day on study medication.

Outcome measures

Outcome measures
Measure	Pregabalin n=329 Participants Pregabalin 150, 300, 450 or 600 mg/day orally twice daily (BID); individual titration based on number of seizures experienced once Level 1 (150 mg/day) was maintained for at least 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.	Lamotrigine n=300 Participants Lamotrigine 100, 200, 400, or 500 mg/day orally BID; individual titration based on number of seizures experienced once Level 1 (100 mg/day) was reached and maintained for 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.	Pregabalin 450 mg/Day Pregabalin 450 mg/day administered BID	Pregabalin 600 mg/Day Pregabalin 600 mg/day administered BID	Lamotrigine 100 mg/Day Lamotrigine 100 mg/day administered BID	Lamotrigine 200 mg/Day Lamotrigine 200 mg/day administered BID	Lamotrigine 400 mg/Day Lamotrigine 400 mg/day administered BID	Lamotrigine 500 mg/Day Lamotrigine 500 mg/day administered BID
Exit Due to Any Reason After 4-week Dose Escalation Phase	78 participants	58 participants	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Week 4 up to Week 56

Population: FAS. N = number of participants who entered maintenance phase of study and had seizure efficacy data.

Time in days, from first day of study treatment to the day of first seizure after Day 28 of the escalation phase (ie, last day on study medication). Participants who did not reach this phase or who did not have a seizure after Day 28 were right censored from the analysis as of the last day on study medication.

Outcome measures

Outcome measures
Measure	Pregabalin n=329 Participants Pregabalin 150, 300, 450 or 600 mg/day orally twice daily (BID); individual titration based on number of seizures experienced once Level 1 (150 mg/day) was maintained for at least 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.	Lamotrigine n=300 Participants Lamotrigine 100, 200, 400, or 500 mg/day orally BID; individual titration based on number of seizures experienced once Level 1 (100 mg/day) was reached and maintained for 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.	Pregabalin 450 mg/Day Pregabalin 450 mg/day administered BID	Pregabalin 600 mg/Day Pregabalin 600 mg/day administered BID	Lamotrigine 100 mg/Day Lamotrigine 100 mg/day administered BID	Lamotrigine 200 mg/Day Lamotrigine 200 mg/day administered BID	Lamotrigine 400 mg/Day Lamotrigine 400 mg/day administered BID	Lamotrigine 500 mg/Day Lamotrigine 500 mg/day administered BID
Time to First Seizure After the 4-Week Dose Escalation Phase	85 days Interval 59.0 to 120.0	211 days Interval 145.0 to 342.0	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline up to Week 60

Population: FAS. N = number of participants with analyzable data; n = number of participants with analyzable data at observation.

All partial seizures include complex partial seizures, simple partial seizures, and partial seizures evolving to secondarily generalized seizures. Seizure frequency based on 28-day seizure rate: number (#) of seizures in period (month) divided by # days in period minus # of missing diary days in period \* 28. Month of time = number of months after Week 4 (Dose Escalation).

Outcome measures

Outcome measures
Measure	Pregabalin n=329 Participants Pregabalin 150, 300, 450 or 600 mg/day orally twice daily (BID); individual titration based on number of seizures experienced once Level 1 (150 mg/day) was maintained for at least 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.	Lamotrigine n=330 Participants Lamotrigine 100, 200, 400, or 500 mg/day orally BID; individual titration based on number of seizures experienced once Level 1 (100 mg/day) was reached and maintained for 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.	Pregabalin 450 mg/Day Pregabalin 450 mg/day administered BID	Pregabalin 600 mg/Day Pregabalin 600 mg/day administered BID	Lamotrigine 100 mg/Day Lamotrigine 100 mg/day administered BID	Lamotrigine 200 mg/Day Lamotrigine 200 mg/day administered BID	Lamotrigine 400 mg/Day Lamotrigine 400 mg/day administered BID	Lamotrigine 500 mg/Day Lamotrigine 500 mg/day administered BID
Median Monthy Seizure Frequency: All Partial Seizures Dose-escalation phase (Weeks 1 - 4) (n=329, 330)	0.0 seizures/28 days Standard Deviation 9.348	0.0 seizures/28 days Standard Deviation 27.118	—	—	—	—	—	—
Median Monthy Seizure Frequency: All Partial Seizures Month 1 (n=314, 308)	0.0 seizures/28 days Standard Deviation 6.139	0.0 seizures/28 days Standard Deviation 31.453	—	—	—	—	—	—
Median Monthy Seizure Frequency: All Partial Seizures Month 2 (n=300, 295)	0.0 seizures/28 days Standard Deviation 3.382	0.0 seizures/28 days Standard Deviation 28.839	—	—	—	—	—	—
Median Monthy Seizure Frequency: All Partial Seizures Month 3 (n=287, 288)	0.0 seizures/28 days Standard Deviation 2.568	0.0 seizures/28 days Standard Deviation 32.783	—	—	—	—	—	—
Median Monthy Seizure Frequency: All Partial Seizures Month 4 (n=279, 278)	0.0 seizures/28 days Standard Deviation 2.313	0.0 seizures/28 days Standard Deviation 16.046	—	—	—	—	—	—
Median Monthy Seizure Frequency: All Partial Seizures Month 5 (n=274, 276)	0.0 seizures/28 days Standard Deviation 2.270	0.0 seizures/28 days Standard Deviation 15.254	—	—	—	—	—	—
Median Monthy Seizure Frequency: All Partial Seizures Month 6 (n=266, 272)	0.0 seizures/28 days Standard Deviation 2.702	0.0 seizures/28 days Standard Deviation 15.126	—	—	—	—	—	—
Median Monthy Seizure Frequency: All Partial Seizures Month 7 (n=260, 270)	0.0 seizures/28 days Standard Deviation 2.839	0.0 seizures/28 days Standard Deviation 16.855	—	—	—	—	—	—
Median Monthy Seizure Frequency: All Partial Seizures Month 8 (n=256, 266)	0.0 seizures/28 days Standard Deviation 3.247	0.0 seizures/28 days Standard Deviation 19.111	—	—	—	—	—	—
Median Monthy Seizure Frequency: All Partial Seizures Month 9 (n=253, 262)	0.0 seizures/28 days Standard Deviation 2.538	0.0 seizures/28 days Standard Deviation 17.204	—	—	—	—	—	—
Median Monthy Seizure Frequency: All Partial Seizures Month 10 (n=250, 257)	0.0 seizures/28 days Standard Deviation 4.935	0.0 seizures/28 days Standard Deviation 16.905	—	—	—	—	—	—
Median Monthy Seizure Frequency: All Partial Seizures Month 11 (n=242, 254)	0.0 seizures/28 days Standard Deviation 3.082	0.0 seizures/28 days Standard Deviation 19.268	—	—	—	—	—	—
Median Monthy Seizure Frequency: All Partial Seizures Month 12 (n=238, 252)	0.0 seizures/28 days Standard Deviation 7.018	0.0 seizures/28 days Standard Deviation 19.590	—	—	—	—	—	—
Median Monthy Seizure Frequency: All Partial Seizures Month 13 (n=210, 227)	0.0 seizures/28 days Standard Deviation 3.247	0.0 seizures/28 days Standard Deviation 19.462	—	—	—	—	—	—
Median Monthy Seizure Frequency: All Partial Seizures Taper (Week 57 to Week 60) (n=71, 45)	0.0 seizures/28 days Standard Deviation 6.418	0.0 seizures/28 days Standard Deviation 97.196	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline up to Week 60

Population: FAS. N = number of participants with analyzable data; n = number of participants with analyzable data at observation.

Outcome measures

Outcome measures
Measure	Pregabalin n=329 Participants Pregabalin 150, 300, 450 or 600 mg/day orally twice daily (BID); individual titration based on number of seizures experienced once Level 1 (150 mg/day) was maintained for at least 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.	Lamotrigine n=330 Participants Lamotrigine 100, 200, 400, or 500 mg/day orally BID; individual titration based on number of seizures experienced once Level 1 (100 mg/day) was reached and maintained for 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.	Pregabalin 450 mg/Day Pregabalin 450 mg/day administered BID	Pregabalin 600 mg/Day Pregabalin 600 mg/day administered BID	Lamotrigine 100 mg/Day Lamotrigine 100 mg/day administered BID	Lamotrigine 200 mg/Day Lamotrigine 200 mg/day administered BID	Lamotrigine 400 mg/Day Lamotrigine 400 mg/day administered BID	Lamotrigine 500 mg/Day Lamotrigine 500 mg/day administered BID
Mean Monthy Seizure Frequency: All Partial Seizures Dose escalation phase (n=329, 330)	2.56 seizures/28 days Standard Deviation 9.348	5.08 seizures/28 days Standard Deviation 27.118	—	—	—	—	—	—
Mean Monthy Seizure Frequency: All Partial Seizures Month 1 (n=314, 308)	2.23 seizures/28 days Standard Deviation 6.139	4.21 seizures/28 days Standard Deviation 31.453	—	—	—	—	—	—
Mean Monthy Seizure Frequency: All Partial Seizures Month 2 (n=300, 295)	1.18 seizures/28 days Standard Deviation 3.382	3.21 seizures/28 days Standard Deviation 28.839	—	—	—	—	—	—
Mean Monthy Seizure Frequency: All Partial Seizures Month 3 (n=287, 288)	0.94 seizures/28 days Standard Deviation 2.568	3.54 seizures/28 days Standard Deviation 32.783	—	—	—	—	—	—
Mean Monthy Seizure Frequency: All Partial Seizures Month 4 (n=279, 278)	0.89 seizures/28 days Standard Deviation 2.313	1.67 seizures/28 days Standard Deviation 16.046	—	—	—	—	—	—
Mean Monthy Seizure Frequency: All Partial Seizures Month 5 (n=274, 276)	0.78 seizures/28 days Standard Deviation 2.270	1.58 seizures/28 days Standard Deviation 15.254	—	—	—	—	—	—
Mean Monthy Seizure Frequency: All Partial Seizures Month 6 (n=266, 272)	0.82 seizures/28 days Standard Deviation 2.702	1.41 seizures/28 days Standard Deviation 15.126	—	—	—	—	—	—
Mean Monthy Seizure Frequency: All Partial Seizures Month 7 (n=260, 270)	0.78 seizures/28 days Standard Deviation 2.839	1.50 seizures/28 days Standard Deviation 16.855	—	—	—	—	—	—
Mean Monthy Seizure Frequency: All Partial Seizures Month 8 (n=256, 266)	0.77 seizures/28 days Standard Deviation 3.247	1.36 seizures/28 days Standard Deviation 19.111	—	—	—	—	—	—
Mean Monthy Seizure Frequency: All Partial Seizures Month 9 (n=253, 262)	0.71 seizures/28 days Standard Deviation 2.538	1.38 seizures/28 days Standard Deviation 17.204	—	—	—	—	—	—
Mean Monthy Seizure Frequency: All Partial Seizures Month 10 (n=250, 257)	1.05 seizures/28 days Standard Deviation 4.935	1.33 seizures/28 days Standard Deviation 16.905	—	—	—	—	—	—
Mean Monthy Seizure Frequency: All Partial Seizures Month 11 (n=242, 254)	0.79 seizures/28 days Standard Deviation 3.082	1.41 seizures/28 days Standard Deviation 19.268	—	—	—	—	—	—
Mean Monthy Seizure Frequency: All Partial Seizures Month 12 (n=238, 252)	0.94 seizures/28 days Standard Deviation 7.018	1.67 seizures/28 days Standard Deviation 19.590	—	—	—	—	—	—
Mean Monthy Seizure Frequency: All Partial Seizures Month 13 (n=210, 227)	0.65 seizures/28 days Standard Deviation 3.247	2.11 seizures/28 days Standard Deviation 19.462	—	—	—	—	—	—
Mean Monthy Seizure Frequency: All Partial Seizures Taper (n=71, 45)	2.13 seizures/28 days Standard Deviation 6.418	19.97 seizures/28 days Standard Deviation 97.196	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline up to Week 60

Population: FAS. N = number of participants with analyzable data; n = number of participants with analyzable data at observation.

Seizure frequency based on 28-day seizure rate: number (#) of seizures in period (month) divided by # days in period minus # of missing diary days in period \* 28. Month of time = number of months after Week 4 (Dose Escalation).

Outcome measures

Outcome measures
Measure	Pregabalin n=329 Participants Pregabalin 150, 300, 450 or 600 mg/day orally twice daily (BID); individual titration based on number of seizures experienced once Level 1 (150 mg/day) was maintained for at least 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.	Lamotrigine n=330 Participants Lamotrigine 100, 200, 400, or 500 mg/day orally BID; individual titration based on number of seizures experienced once Level 1 (100 mg/day) was reached and maintained for 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.	Pregabalin 450 mg/Day Pregabalin 450 mg/day administered BID	Pregabalin 600 mg/Day Pregabalin 600 mg/day administered BID	Lamotrigine 100 mg/Day Lamotrigine 100 mg/day administered BID	Lamotrigine 200 mg/Day Lamotrigine 200 mg/day administered BID	Lamotrigine 400 mg/Day Lamotrigine 400 mg/day administered BID	Lamotrigine 500 mg/Day Lamotrigine 500 mg/day administered BID
Median Monthy Seizure Frequency: All Seizures Dose-escalation phase (Weeks 1 - 4)(n=329, 330)	0.0 seizures/28 days Standard Deviation 9.819	0.0 seizures/28 days Standard Deviation 27.128	—	—	—	—	—	—
Median Monthy Seizure Frequency: All Seizures Month 1 (n=314, 308)	0.0 seizures/28 days Standard Deviation 6.164	0.0 seizures/28 days Standard Deviation 31.452	—	—	—	—	—	—
Median Monthy Seizure Frequency: All Seizures Month 2 (n=300, 295)	0.0 seizures/28 days Standard Deviation 5.498	0.0 seizures/28 days Standard Deviation 28.838	—	—	—	—	—	—
Median Monthy Seizure Frequency: All Seizures Month 3 (n=287, 288)	0.0 seizures/28 days Standard Deviation 2.702	0.0 seizures/28 days Standard Deviation 32.782	—	—	—	—	—	—
Median Monthy Seizure Frequency: All Seizures Month 4 (n=279, 278)	0.0 seizures/28 days Standard Deviation 3.223	0.0 seizures/28 days Standard Deviation 16.046	—	—	—	—	—	—
Median Monthy Seizure Frequency: All Seizures Month 5 (n=274, 276)	0.0 seizures/28 days Standard Deviation 2.458	0.0 seizures/28 days Standard Deviation 15.254	—	—	—	—	—	—
Median Monthy Seizure Frequency: All Seizures Month 6 (n=266, 272)	0.0 seizures/28 days Standard Deviation 2.853	0.0 seizures/28 days Standard Deviation 15.126	—	—	—	—	—	—
Median Monthy Seizure Frequency: All Seizures Month 7 (n=260, 270)	0.0 seizures/28 days Standard Deviation 2.898	0.0 seizures/28 days Standard Deviation 16.855	—	—	—	—	—	—
Median Monthy Seizure Frequency: All Seizures Month 8 (n=256, 266)	0.0 seizures/28 days Standard Deviation 3.304	0.0 seizures/28 days Standard Deviation 19.110	—	—	—	—	—	—
Median Monthy Seizure Frequency: All Seizures Month 9 (n=253, 262)	0.0 seizures/28 days Standard Deviation 2.636	0.0 seizures/28 days Standard Deviation 17.204	—	—	—	—	—	—
Median Monthy Seizure Frequency: All Seizures Month 10 (n=250, 257)	0.0 seizures/28 days Standard Deviation 4.934	0.0 seizures/28 days Standard Deviation 16.905	—	—	—	—	—	—
Median Monthy Seizure Frequency: All Seizures Month 11 (n=242, 254)	0.0 seizures/28 days Standard Deviation 3.224	0.0 seizures/28 days Standard Deviation 19.268	—	—	—	—	—	—
Median Monthy Seizure Frequency: All Seizures Month 12 (n=238, 252)	0.0 seizures/28 days Standard Deviation 7.019	0.0 seizures/28 days Standard Deviation 19.590	—	—	—	—	—	—
Median Monthy Seizure Frequency: All Seizures Month 13 (n=210, 227)	0.0 seizures/28 days Standard Deviation 3.247	0.0 seizures/28 days Standard Deviation 19.462	—	—	—	—	—	—
Median Monthy Seizure Frequency: All Seizures Taper (Week 57 to Week 60) (n=71, 45)	0.0 seizures/28 days Standard Deviation 6.418	0.0 seizures/28 days Standard Deviation 97.196	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline up to Week 60

Population: FAS. N = number of participants with analyzable data; n = number of participants with analyzable data at observation.

Outcome measures

Outcome measures
Measure	Pregabalin n=329 Participants Pregabalin 150, 300, 450 or 600 mg/day orally twice daily (BID); individual titration based on number of seizures experienced once Level 1 (150 mg/day) was maintained for at least 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.	Lamotrigine n=330 Participants Lamotrigine 100, 200, 400, or 500 mg/day orally BID; individual titration based on number of seizures experienced once Level 1 (100 mg/day) was reached and maintained for 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.	Pregabalin 450 mg/Day Pregabalin 450 mg/day administered BID	Pregabalin 600 mg/Day Pregabalin 600 mg/day administered BID	Lamotrigine 100 mg/Day Lamotrigine 100 mg/day administered BID	Lamotrigine 200 mg/Day Lamotrigine 200 mg/day administered BID	Lamotrigine 400 mg/Day Lamotrigine 400 mg/day administered BID	Lamotrigine 500 mg/Day Lamotrigine 500 mg/day administered BID
Mean Monthy Seizure Frequency: All Seizures Month 9 (n=253, 262)	0.78 seizures/28 days Standard Deviation 2.636	1.38 seizures/28 days Standard Deviation 17.204	—	—	—	—	—	—
Mean Monthy Seizure Frequency: All Seizures Month 10 (n=250, 257)	1.06 seizures/28 days Standard Deviation 4.934	1.33 seizures/28 days Standard Deviation 16.905	—	—	—	—	—	—
Mean Monthy Seizure Frequency: All Seizures Month 11 (n=242, 254)	0.81 seizures/28 days Standard Deviation 3.224	1.41 seizures/28 days Standard Deviation 19.268	—	—	—	—	—	—
Mean Monthy Seizure Frequency: All Seizures Month 12 (n=238, 252)	0.96 seizures/28 days Standard Deviation 7.019	1.67 seizures/28 days Standard Deviation 19.590	—	—	—	—	—	—
Mean Monthy Seizure Frequency: All Seizures Month 13 (n=210, 227)	0.65 seizures/28 days Standard Deviation 3.247	2.12 seizures/28 days Standard Deviation 19.462	—	—	—	—	—	—
Mean Monthy Seizure Frequency: All Seizures Taper (n=71, 45)	2.13 seizures/28 days Standard Deviation 6.418	19.97 seizures/28 days Standard Deviation 97.196	—	—	—	—	—	—
Mean Monthy Seizure Frequency: All Seizures Dose-escalation phase (n=329, 330)	2.74 seizures/28 days Standard Deviation 9.819	5.10 seizures/28 days Standard Deviation 27.128	—	—	—	—	—	—
Mean Monthy Seizure Frequency: All Seizures Month 1 (n=314, 308)	2.31 seizures/28 days Standard Deviation 6.164	4.24 seizures/28 days Standard Deviation 31.452	—	—	—	—	—	—
Mean Monthy Seizure Frequency: All Seizures Month 2 (n=300, 295)	1.53 seizures/28 days Standard Deviation 5.498	3.22 seizures/28 days Standard Deviation 28.838	—	—	—	—	—	—
Mean Monthy Seizure Frequency: All Seizures Month 3 (n=287, 288)	1.02 seizures/28 days Standard Deviation 2.702	3.57 seizures/28 days Standard Deviation 32.782	—	—	—	—	—	—
Mean Monthy Seizure Frequency: All Seizures Month 4 (n=279, 278)	1.06 seizures/28 days Standard Deviation 3.223	1.68 seizures/28 days Standard Deviation 16.046	—	—	—	—	—	—
Mean Monthy Seizure Frequency: All Seizures Month 5 (n=274, 276)	0.87 seizures/28 days Standard Deviation 2.458	1.59 seizures/28 days Standard Deviation 15.254	—	—	—	—	—	—
Mean Monthy Seizure Frequency: All Seizures Month 6 (n=266, 272)	0.89 seizures/28 days Standard Deviation 2.853	1.41 seizures/28 days Standard Deviation 15.126	—	—	—	—	—	—
Mean Monthy Seizure Frequency: All Seizures Month 7 (n=260, 270)	0.83 seizures/28 days Standard Deviation 2.898	1.50 seizures/28 days Standard Deviation 16.855	—	—	—	—	—	—
Mean Monthy Seizure Frequency: All Seizures Month 8 (n=256, 266)	0.82 seizures/28 days Standard Deviation 3.304	1.37 seizures/28 days Standard Deviation 19.110	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Month 1 through Month 9 (after 6 months seizure freedom achieved)

Population: FAS. N = number of responders; n = number of responders with analyzable data at observation.

All partial seizures include complex partial seizures, simple partial seizures, and partial seizures evolving to secondarily generalized seizures. Seizure frequency based on 28-day seizure rate: number (#) of seizures in period (month) divided by # days in period minus # of missing diary days in period \* 28. Responder = participant who achieved at least 6 months of seizure freedom after Week 4 and up to Week 56. Monthly seizure frequency measured from day of achievement of 6 months of seizure freedom.

Outcome measures

Outcome measures
Measure	Pregabalin n=162 Participants Pregabalin 150, 300, 450 or 600 mg/day orally twice daily (BID); individual titration based on number of seizures experienced once Level 1 (150 mg/day) was maintained for at least 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.	Lamotrigine n=208 Participants Lamotrigine 100, 200, 400, or 500 mg/day orally BID; individual titration based on number of seizures experienced once Level 1 (100 mg/day) was reached and maintained for 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.	Pregabalin 450 mg/Day Pregabalin 450 mg/day administered BID	Pregabalin 600 mg/Day Pregabalin 600 mg/day administered BID	Lamotrigine 100 mg/Day Lamotrigine 100 mg/day administered BID	Lamotrigine 200 mg/Day Lamotrigine 200 mg/day administered BID	Lamotrigine 400 mg/Day Lamotrigine 400 mg/day administered BID	Lamotrigine 500 mg/Day Lamotrigine 500 mg/day administered BID
Median Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Partial Seizures Month 4 (n=139, 173)	0.0 seizures/28 days Standard Deviation 0.329	0.0 seizures/28 days Standard Deviation 0.211	—	—	—	—	—	—
Median Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Partial Seizures Month 1 (n=162, 208)	0.0 seizures/28 days Standard Deviation 1.000	0.0 seizures/28 days Standard Deviation 0.226	—	—	—	—	—	—
Median Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Partial Seizures Month 2 (n=155, 194)	0.0 seizures/28 days Standard Deviation 1.783	0.0 seizures/28 days Standard Deviation 0.226	—	—	—	—	—	—
Median Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Partial Seizures Month 3 (n=147, 184)	0.0 seizures/28 days Standard Deviation 0.384	0.0 seizures/28 days Standard Deviation 0.439	—	—	—	—	—	—
Median Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Partial Seizures Month 5 (n=127, 158)	0.0 seizures/28 days Standard Deviation 0.926	0.0 seizures/28 days Standard Deviation 0.823	—	—	—	—	—	—
Median Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Partial Seizures Month 6 (n=122, 152)	0.0 seizures/28 days Standard Deviation 0.156	0.0 seizures/28 days Standard Deviation 0.213	—	—	—	—	—	—
Median Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Partial Seizures Month 7 (n=105, 136)	0.0 seizures/28 days Standard Deviation 0.000	0.0 seizures/28 days Standard Deviation 2.843	—	—	—	—	—	—
Median Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Partial Seizures Month 8 (n=1, 5)	0.0 seizures/28 days Standard Deviation NA n = 1.	0.0 seizures/28 days Standard Deviation 0.000	—	—	—	—	—	—
Median Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Partial Seizures Month 9 (n=0, 1)	NA seizures/28 days Standard Deviation NA No responders with analyzable data at Month 9.	6.0 seizures/28 days Standard Deviation NA n = 1.	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Month 1 through Month 9 (after 6 months seizure freedom achieved)

Population: FAS. N = number of responders; n = number of responders with analyzable data at observation.

All partial seizures include complex partial seizures, simple partial seizures, and partial seizures evolving to secondarily generalized seizures. Seizure frequency based on 28-day seizure rate: number (#) of seizures in period (month) divided by # days in period minus # of missing diary days in period \* 28. Responder = participant who achieved at least 6 months of seizure freedom after Week 4 and up to Week 56. Monthly seizure frequency measured from day of achievement of 6 months of seizure freedom.

Outcome measures

Outcome measures
Measure	Pregabalin n=162 Participants Pregabalin 150, 300, 450 or 600 mg/day orally twice daily (BID); individual titration based on number of seizures experienced once Level 1 (150 mg/day) was maintained for at least 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.	Lamotrigine n=208 Participants Lamotrigine 100, 200, 400, or 500 mg/day orally BID; individual titration based on number of seizures experienced once Level 1 (100 mg/day) was reached and maintained for 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.	Pregabalin 450 mg/Day Pregabalin 450 mg/day administered BID	Pregabalin 600 mg/Day Pregabalin 600 mg/day administered BID	Lamotrigine 100 mg/Day Lamotrigine 100 mg/day administered BID	Lamotrigine 200 mg/Day Lamotrigine 200 mg/day administered BID	Lamotrigine 400 mg/Day Lamotrigine 400 mg/day administered BID	Lamotrigine 500 mg/Day Lamotrigine 500 mg/day administered BID
Mean Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Partial Seizures Month 2 (n=155, 194)	0.28 28-day seizure rate Standard Deviation 1.783	0.03 28-day seizure rate Standard Deviation 0.226	—	—	—	—	—	—
Mean Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Partial Seizures Month 1 (n=162, 208)	0.19 28-day seizure rate Standard Deviation 1.000	0.04 28-day seizure rate Standard Deviation 0.226	—	—	—	—	—	—
Mean Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Partial Seizures Month 3 (n=147, 184)	0.05 28-day seizure rate Standard Deviation 0.384	0.07 28-day seizure rate Standard Deviation 0.439	—	—	—	—	—	—
Mean Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Partial Seizures Month 4 (n=139, 173)	0.09 28-day seizure rate Standard Deviation 0.329	0.05 28-day seizure rate Standard Deviation 0.211	—	—	—	—	—	—
Mean Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Partial Seizures Month 5 (n=127, 158)	0.15 28-day seizure rate Standard Deviation 0.926	0.10 28-day seizure rate Standard Deviation 0.823	—	—	—	—	—	—
Mean Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Partial Seizures Month 6 (n=122, 152)	0.02 28-day seizure rate Standard Deviation 0.156	0.03 28-day seizure rate Standard Deviation 0.213	—	—	—	—	—	—
Mean Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Partial Seizures Month 7 (n=105, 136)	0.00 28-day seizure rate Standard Deviation 0.000	0.28 28-day seizure rate Standard Deviation 2.843	—	—	—	—	—	—
Mean Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Partial Seizures Month 8 (n=1, 5)	0.00 28-day seizure rate Standard Deviation NA Measure of dispersion cannot be calculated with a sample size of 1.	0.00 28-day seizure rate Standard Deviation 0.000	—	—	—	—	—	—
Mean Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Partial Seizures Month 9 (n=0, 1)	NA 28-day seizure rate Standard Deviation NA No responders with analyzable data at Month 9.	6.00 28-day seizure rate Standard Deviation NA Measure of dispersion cannot be calculated with a sample size of 1.	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Month 1 through Month 9 (after 6 months seizure freedom achieved)

Population: FAS. N = number of responders; n = number of responders with analyzable data at observation.

Seizure frequency based on 28-day seizure rate: number (#) of seizures in period (month) divided by # days in period minus # of missing diary days in period \* 28. Responder = participant who achieved at least 6 months of seizure freedom after Week 4 and up to Week 56. Monthly seizure frequency measured from day of achievement of 6 months of seizure freedom.

Outcome measures

Outcome measures
Measure	Pregabalin n=162 Participants Pregabalin 150, 300, 450 or 600 mg/day orally twice daily (BID); individual titration based on number of seizures experienced once Level 1 (150 mg/day) was maintained for at least 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.	Lamotrigine n=208 Participants Lamotrigine 100, 200, 400, or 500 mg/day orally BID; individual titration based on number of seizures experienced once Level 1 (100 mg/day) was reached and maintained for 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.	Pregabalin 450 mg/Day Pregabalin 450 mg/day administered BID	Pregabalin 600 mg/Day Pregabalin 600 mg/day administered BID	Lamotrigine 100 mg/Day Lamotrigine 100 mg/day administered BID	Lamotrigine 200 mg/Day Lamotrigine 200 mg/day administered BID	Lamotrigine 400 mg/Day Lamotrigine 400 mg/day administered BID	Lamotrigine 500 mg/Day Lamotrigine 500 mg/day administered BID
Median Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Seizures Month 3 (n=147, 184)	0.0 seizures/28 days Standard Deviation 0.400	0.0 seizures/28 days Standard Deviation 0.439	—	—	—	—	—	—
Median Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Seizures Month 1 (n=162, 208)	0.0 seizures/28 days Standard Deviation 1.000	0.0 seizures/28 days Standard Deviation 0.236	—	—	—	—	—	—
Median Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Seizures Month 2 (n=155, 194)	0.0 seizures/28 days Standard Deviation 1.783	0.0 seizures/28 days Standard Deviation 0.226	—	—	—	—	—	—
Median Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Seizures Month 4 (n=139, 173)	0.0 seizures/28 days Standard Deviation 0.359	0.0 seizures/28 days Standard Deviation 0.211	—	—	—	—	—	—
Median Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Seizures Month 5 (n=127, 158)	0.0 seizures/28 days Standard Deviation 0.971	0.0 seizures/28 days Standard Deviation 0.823	—	—	—	—	—	—
Median Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Seizures Month 6 (n=122, 152)	0.0 seizures/28 days Standard Deviation 0.156	0.0 seizures/28 days Standard Deviation 0.213	—	—	—	—	—	—
Median Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Seizures Month 7 (n=105, 136)	0.0 seizures/28 days Standard Deviation 0.000	0.0 seizures/28 days Standard Deviation 2.844	—	—	—	—	—	—
Median Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Seizures Month 8 (n=1, 5)	0.0 seizures/28 days Standard Deviation NA n=1.	0.0 seizures/28 days Standard Deviation 0.000	—	—	—	—	—	—
Median Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Seizures Month 9 (n=0, 1)	NA seizures/28 days Standard Deviation NA No responders with analyzable data at Month 9.	6.0 seizures/28 days Standard Deviation NA n=1.	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Month 1 through Month 9 (after 6 months seizure freedom achieved)

Population: FAS. N = number of responders; n = number of responders with analyzable data at observation.

Outcome measures

Outcome measures
Measure	Pregabalin n=162 Participants Pregabalin 150, 300, 450 or 600 mg/day orally twice daily (BID); individual titration based on number of seizures experienced once Level 1 (150 mg/day) was maintained for at least 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.	Lamotrigine n=208 Participants Lamotrigine 100, 200, 400, or 500 mg/day orally BID; individual titration based on number of seizures experienced once Level 1 (100 mg/day) was reached and maintained for 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.	Pregabalin 450 mg/Day Pregabalin 450 mg/day administered BID	Pregabalin 600 mg/Day Pregabalin 600 mg/day administered BID	Lamotrigine 100 mg/Day Lamotrigine 100 mg/day administered BID	Lamotrigine 200 mg/Day Lamotrigine 200 mg/day administered BID	Lamotrigine 400 mg/Day Lamotrigine 400 mg/day administered BID	Lamotrigine 500 mg/Day Lamotrigine 500 mg/day administered BID
Mean Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Seizures Month 5 (n=127, 158)	0.18 28-day seizure rate Standard Deviation 0.971	0.10 28-day seizure rate Standard Deviation 0.823	—	—	—	—	—	—
Mean Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Seizures Month 1 (n=162, 208)	0.19 28-day seizure rate Standard Deviation 1.000	0.05 28-day seizure rate Standard Deviation 0.236	—	—	—	—	—	—
Mean Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Seizures Month 2 (n=155, 194)	0.28 28-day seizure rate Standard Deviation 1.783	0.03 28-day seizure rate Standard Deviation 0.226	—	—	—	—	—	—
Mean Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Seizures Month 3 (n=147, 184)	0.07 28-day seizure rate Standard Deviation 0.400	0.07 28-day seizure rate Standard Deviation 0.439	—	—	—	—	—	—
Mean Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Seizures Month 4 (n=139, 173)	0.09 28-day seizure rate Standard Deviation 0.359	0.05 28-day seizure rate Standard Deviation 0.211	—	—	—	—	—	—
Mean Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Seizures Month 6 (n=122, 152)	0.02 28-day seizure rate Standard Deviation 0.156	0.03 28-day seizure rate Standard Deviation 0.213	—	—	—	—	—	—
Mean Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Seizures Month 7 (n=105, 136)	0.00 28-day seizure rate Standard Deviation 0.000	0.29 28-day seizure rate Standard Deviation 2.844	—	—	—	—	—	—
Mean Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Seizures Month 8 (n=1, 5)	0.00 28-day seizure rate Standard Deviation NA Measure of dispersion cannot be calculated with a sample size of 1.	0.00 28-day seizure rate Standard Deviation 0.000	—	—	—	—	—	—
Mean Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Seizures Month 9 (n=0, 1)	NA 28-day seizure rate Standard Deviation NA No responders with analyzable data at Month 9.	6.00 28-day seizure rate Standard Deviation NA Measure of dispersion cannot be calculated with a sample size of 1.	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Week 5 up to Week 56

Population: FAS; N = number of participants with analyzable data.

Responder = participant who achieved at least 6-months of seizure freedom (all seizures) after Week 4, and up to Week 56. Dose Level defined as last total-daily-dose received after Week 4, and up to Week 56.

Outcome measures

Outcome measures
Measure	Pregabalin n=149 Participants Pregabalin 150, 300, 450 or 600 mg/day orally twice daily (BID); individual titration based on number of seizures experienced once Level 1 (150 mg/day) was maintained for at least 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.	Lamotrigine n=67 Participants Lamotrigine 100, 200, 400, or 500 mg/day orally BID; individual titration based on number of seizures experienced once Level 1 (100 mg/day) was reached and maintained for 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.	Pregabalin 450 mg/Day n=49 Participants Pregabalin 450 mg/day administered BID	Pregabalin 600 mg/Day n=46 Participants Pregabalin 600 mg/day administered BID	Lamotrigine 100 mg/Day n=164 Participants Lamotrigine 100 mg/day administered BID	Lamotrigine 200 mg/Day n=84 Participants Lamotrigine 200 mg/day administered BID	Lamotrigine 400 mg/Day n=34 Participants Lamotrigine 400 mg/day administered BID	Lamotrigine 500 mg/Day n=18 Participants Lamotrigine 500 mg/day administered BID
Percentage of Participants Who Achieved at Least 6 Consecutive Months of Seizure Freedom (Responders) by Final Dosage Levels and Treatment Group	70.5 percentage of participants	59.7 percentage of participants	20.4 percentage of participants	13.0 percentage of participants	80.5 percentage of participants	67.9 percentage of participants	38.2 percentage of participants	16.7 percentage of participants

SECONDARY outcome

Timeframe: Baseline to Week 56

Population: FAS; N = number of participants with a HADS measurement at baseline and Week 56.

Participant rated questionnaire with 2 subscales. HADS-A assesses state of generalized anxiety (anxious mood, restlessness, anxious thoughts, panic attacks); HADS-D assesses state of lost interest and diminished pleasure response (lowering of hedonic tone). Each subscale comprised of 7 items; range: 0 (no presence of anxiety or depression) to 3 (severe feeling of anxiety or depression). Total score 0 to 21 for each subscale; higher score indicates greater severity of symptoms. Scores relative to start of randomized treatment.

Outcome measures

Outcome measures
Measure	Pregabalin n=237 Participants Pregabalin 150, 300, 450 or 600 mg/day orally twice daily (BID); individual titration based on number of seizures experienced once Level 1 (150 mg/day) was maintained for at least 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.	Lamotrigine n=238 Participants Lamotrigine 100, 200, 400, or 500 mg/day orally BID; individual titration based on number of seizures experienced once Level 1 (100 mg/day) was reached and maintained for 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.	Pregabalin 450 mg/Day Pregabalin 450 mg/day administered BID	Pregabalin 600 mg/Day Pregabalin 600 mg/day administered BID	Lamotrigine 100 mg/Day Lamotrigine 100 mg/day administered BID	Lamotrigine 200 mg/Day Lamotrigine 200 mg/day administered BID	Lamotrigine 400 mg/Day Lamotrigine 400 mg/day administered BID	Lamotrigine 500 mg/Day Lamotrigine 500 mg/day administered BID
Change From Baseline to Week 56 in Hospital Anxiety and Depression Scale (HADS) Anxiety	-0.3 scores on scale Standard Error 0.25	-1.1 scores on scale Standard Error 0.25	—	—	—	—	—	—
Change From Baseline to Week 56 in Hospital Anxiety and Depression Scale (HADS) Depression	-0.1 scores on scale Standard Error 0.23	-0.7 scores on scale Standard Error 0.23	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Week 8, Week 32, and Week 56

Population: FAS

MOS-SS: subject-rated instrument used to assess the key constructs of sleep over the past week; assesses sleep quantity and quality and is comprised 12 items yielding 7 subscale scores and 2 composite index scores. Optimal Sleep subscale is derived from sleep quantity average hours of sleep each night during the past week. Number of subjects with response Optimal if sleep quantity was 7 or 8 hours of sleep per night, and Non-optimal if average sleep was less than or greater than 7 to 8 hours per night. Analysis assesses the MOS-Sleep scale relative to the start of randomized treatment.

Outcome measures

Outcome measures
Measure	Pregabalin n=330 Participants Pregabalin 150, 300, 450 or 600 mg/day orally twice daily (BID); individual titration based on number of seizures experienced once Level 1 (150 mg/day) was maintained for at least 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.	Lamotrigine n=330 Participants Lamotrigine 100, 200, 400, or 500 mg/day orally BID; individual titration based on number of seizures experienced once Level 1 (100 mg/day) was reached and maintained for 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.	Pregabalin 450 mg/Day Pregabalin 450 mg/day administered BID	Pregabalin 600 mg/Day Pregabalin 600 mg/day administered BID	Lamotrigine 100 mg/Day Lamotrigine 100 mg/day administered BID	Lamotrigine 200 mg/Day Lamotrigine 200 mg/day administered BID	Lamotrigine 400 mg/Day Lamotrigine 400 mg/day administered BID	Lamotrigine 500 mg/Day Lamotrigine 500 mg/day administered BID
Medical Outcomes Study Sleep Scale (MOS-SS): Optimal Sleep Subscale Week 8: Optimal sleep	195 participants	173 participants	—	—	—	—	—	—
Medical Outcomes Study Sleep Scale (MOS-SS): Optimal Sleep Subscale Week 8: Non-optimal sleep	103 participants	126 participants	—	—	—	—	—	—
Medical Outcomes Study Sleep Scale (MOS-SS): Optimal Sleep Subscale Week 32: Optimal sleep	167 participants	155 participants	—	—	—	—	—	—
Medical Outcomes Study Sleep Scale (MOS-SS): Optimal Sleep Subscale Week 32: Non-optimal sleep	97 participants	103 participants	—	—	—	—	—	—
Medical Outcomes Study Sleep Scale (MOS-SS): Optimal Sleep Subscale Week 56: Optimal sleep	152 participants	145 participants	—	—	—	—	—	—
Medical Outcomes Study Sleep Scale (MOS-SS): Optimal Sleep Subscale Week 56: Non-optimal sleep	82 participants	90 participants	—	—	—	—	—	—

Adverse Events

Pregabalin

Serious events: 44 serious events

Other events: 186 other events

Deaths: 0 deaths

Lamotrigine

Serious events: 32 serious events

Other events: 171 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer, Inc.

Phone: 1-800-718-1021

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	Pregabalin n=330 participants at risk Pregabalin 150, 300, 450 or 600 mg/day orally twice daily (BID); individual titration based on number of seizures experienced once Level 1 (150 mg/day) was maintained for at least 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.	Lamotrigine n=330 participants at risk Lamotrigine 100, 200, 400, or 500 mg/day orally BID; individual titration based on number of seizures experienced once Level 1 (100 mg/day) was reached and maintained for 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.
Blood and lymphatic system disorders Pancytopenia	0.30% 1/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders Splenomegaly	0.00% 0/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.30% 1/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Myocardial ischaemia	0.30% 1/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Congenital, familial and genetic disorders Multiple endocrine adenomatosis Type II	0.30% 1/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Endocrine disorders Parathyroid gland enlargement	0.30% 1/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Eye disorders Entropion	0.00% 0/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.30% 1/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Eye disorders Trichiasis	0.00% 0/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.30% 1/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Dyspepsia	0.30% 1/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Gastritis	0.00% 0/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.30% 1/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Vomiting	0.61% 2/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Chest pain	0.00% 0/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.30% 1/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Drowning	0.30% 1/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders General physical health deterioration	0.00% 0/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.30% 1/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Pyrexia	0.30% 1/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Sudden unexplained death in epilepsy	0.30% 1/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Hepatobiliary disorders Cholecystitis acute	0.30% 1/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Hepatobiliary disorders Hepatic function abnormal	0.30% 1/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Diverticulitis	0.00% 0/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.30% 1/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Hepatitis B	0.30% 1/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Pneumonia	0.30% 1/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Sinusitis	0.30% 1/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Tuberculosis	0.00% 0/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.30% 1/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Upper respiratory tract infection	0.30% 1/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Vulvovaginitis	0.00% 0/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.30% 1/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Cartilage injury	0.30% 1/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Concussion	0.30% 1/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Excoriation	0.30% 1/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Fall	0.00% 0/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	1.2% 4/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Foot fracture	0.00% 0/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.91% 3/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Hand fracture	0.00% 0/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.30% 1/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Head injury	0.00% 0/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.61% 2/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Joint dislocation	0.00% 0/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.30% 1/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Joint sprain	0.30% 1/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Ligament rupture	0.30% 1/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Limb injury	0.30% 1/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Meniscus lesion	0.00% 0/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.30% 1/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Pelvic fracture	0.00% 0/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.30% 1/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Road traffic accident	0.61% 2/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Thermal burn	0.30% 1/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Arthropathy	0.30% 1/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.

Other adverse events
Measure	Pregabalin n=330 participants at risk Pregabalin 150, 300, 450 or 600 mg/day orally twice daily (BID); individual titration based on number of seizures experienced once Level 1 (150 mg/day) was maintained for at least 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.	Lamotrigine n=330 participants at risk Lamotrigine 100, 200, 400, or 500 mg/day orally BID; individual titration based on number of seizures experienced once Level 1 (100 mg/day) was reached and maintained for 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.
Eye disorders Vision blurred	2.1% 7/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.61% 2/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Abdominal pain	1.2% 4/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.7% 9/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Abdominal pain upper	3.6% 12/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	5.2% 17/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Constipation	2.7% 9/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	1.5% 5/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Diarrhoea	3.6% 12/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	3.9% 13/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Dyspepsia	2.4% 8/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	3.6% 12/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Nausea	4.2% 14/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	3.3% 11/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Toothache	2.7% 9/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	1.2% 4/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Vomiting	2.1% 7/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.4% 8/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Fatigue	9.1% 30/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	5.8% 19/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Pyrexia	1.8% 6/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	4.2% 14/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Influenza	4.2% 14/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	3.6% 12/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Nasopharyngitis	4.5% 15/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	6.4% 21/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Pharyngitis	2.1% 7/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	1.2% 4/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Upper respiratory tract infection	6.1% 20/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	7.0% 23/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Investigations Weight increased	6.7% 22/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.1% 7/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Decreased appetite	0.61% 2/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.1% 7/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Back pain	2.7% 9/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	3.0% 10/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Myalgia	2.1% 7/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	1.8% 6/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Disturbance in attention	2.1% 7/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	1.8% 6/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Dizziness	17.3% 57/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	14.2% 47/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Headache	22.7% 75/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	22.1% 73/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Memory impairment	2.4% 8/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	3.9% 13/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Somnolence	8.8% 29/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	4.8% 16/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Anxiety	1.5% 5/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	3.0% 10/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Depression	3.0% 10/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	4.2% 14/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Insomnia	4.5% 15/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	5.8% 19/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Sleep disorder	0.61% 2/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.1% 7/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Cough	0.61% 2/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.7% 9/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.61% 2/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	3.0% 10/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Skin and subcutaneous tissue disorders Pruritus	1.2% 4/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.4% 8/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Skin and subcutaneous tissue disorders Rash	3.6% 12/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	5.5% 18/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Vascular disorders Hypertension	1.2% 4/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.1% 7/330 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.