Study Of The Safety And Efficacy Of Lyrica In The Treatme... | NCT00280059

Study Of The Safety And Efficacy Of Lyrica In The Treatme... | NCT00280059 | Trialant

Arms/Interventions Module

Label	Type	Description	Intervention Names
1	Experimental		Drug: Pregabalin
2	Active Comparator		Drug: Lamotrigine

Name	Type	Description	Arm Group Labels	Other Names
Pregabalin	Drug	dose 150-600 mg/day given BID	1
Lamotrigine

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Percentage of Seizure-free Participants (Responders) During Efficacy Assessment Phase	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.	Week 5 up to Week 56

Secondary Outcomes

Measure	Description	Time Frame
Time to 6 Consecutive Months of Seizure-freedom After 4-week Dose Escalation Phase: All Seizures	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.	Week 4 up to Week 56

Contacts/Locations Module

Name	Affiliation	Role
Pfizer CT.gov Call Center	Pfizer	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Pfizer Investigational Site		Bruges		8000	Belgium
Pfizer Investigational Site

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
21889410	Derived	Kwan P, Brodie MJ, Kalviainen R, Yurkewicz L, Weaver J, Knapp LE. Efficacy and safety of pregabalin versus lamotrigine in patients with newly diagnosed partial seizures: a phase 3, double-blind, randomised, parallel-group trial. Lancet Neurol. 2011 Oct;10(10):881-90. doi: 10.1016/S1474-4422(11)70154-5. Epub 2011 Aug 31.

Label	URL
To obtain contact information for a study center near you, click here.	View source

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	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.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Comment	Reasons
Death		FG0002 subjects FG0010 subjects
Adverse Event		FG00033 subjects FG00131 subjects
Laboratory abnormaility		FG0001 subjects FG0010 subjects
Lack of Efficacy		FG00019 subjects FG0013 subjects
Lost to Follow-up		FG0006 subjects FG00113 subjects
Other		FG0007 subjects FG0018 subjects
Withdrawal by Subject		FG00026 subjects FG00125 subjects

Extension Phase

Type	Comment	Milestone Data
STARTED		FG000194 subjectsOptional phase; number entered was less than the number who completed the efficacy assessment phase. FG001215 subjectsOptional phase; number entered was less than the number who completed the efficacy assessment phase.
COMPLETED		FG000145 subjects FG001177 subjects
NOT COMPLETED		FG00049 subjects FG00138 subjects

Arm/Group Information

ID	Title	Description
BG000	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.
BG001	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.
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Customized

Number

participants

Title

Denominators

Categories

< 18 years

Title	Measurements
	BG0009 BG0019 BG00218

Between 18 and 44 years

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG000165 BG001146 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Percentage of Seizure-free Participants (Responders) During Efficacy Assessment Phase

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.

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.

Posted

Number

percentage of participants

Week 5 up to Week 56

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants	OG000314 OG001308

Title

Denominators

Categories

Title	Measurements
	OG00051.6 OG00167.9

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Analysis of the binary response variable for 6 consecutive months seizure freedom analyzed by comparing the proportions of favorable responders between the two treatment groups after stratifying by clusters and correcting for skewness (Gart and Nam, 1990). Percentage can be obtained by multiplying proportion by 100.	Gart and Nam: correction of skewness				Mean Difference (Final Values)	-0.16			2-Sided	95	-0.24	-0.09			95% confidence interval for the true difference in proportions, as well as a one-sided test at α=0.025; confidence interval adjusted for centers clustered within a geographical region, with upper and lower confidence limits.

Secondary

Time to 6 Consecutive Months of Seizure-freedom After 4-week Dose Escalation Phase: All Seizures

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.

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

Posted

Median

95% Confidence Interval

days

Week 4 up to Week 56

ID	Title	Description
OG000	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.
OG001	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.

Secondary

Exit Due to Adverse Events During the Double-blind Treatment Phase (Including Dose Escalation Phase)

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.

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.

Posted

Number

participants

Week 0 to Week 56

ID	Title	Description
OG000	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.
OG001	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.

Secondary

Exit for Any Reason During the Double-blind Treatment Phase (Including Dose Escalation Phase)

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.

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.

Posted

Number

participants

Week 0 to Week 56

ID	Title	Description
OG000	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.
OG001	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.

Secondary

Exit Due to Lack of Efficacy After 4-week Dose Escalation Phase

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.

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.

Posted

Number

participants

Week 4 up to Week 56

ID	Title	Description
OG000	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.
OG001	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.

Secondary

Exit Due to Any Reason After 4-week Dose Escalation Phase

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.

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.

Posted

Number

participants

Week 4 up to Week 56

ID	Title	Description
OG000	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.
OG001	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.

Secondary

Time to First Seizure After the 4-Week Dose Escalation Phase

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.

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

Posted

Median

95% Confidence Interval

days

Week 4 up to Week 56

ID	Title	Description
OG000	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.
OG001	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.

Secondary

Median Monthy Seizure Frequency: All Partial Seizures

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).

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

Posted

Median

Standard Deviation

seizures/28 days

Baseline up to Week 60

ID	Title	Description
OG000	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.
OG001	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.

Secondary

Mean Monthy Seizure Frequency: All Partial Seizures

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

Posted

Mean

Standard Deviation

seizures/28 days

Baseline up to Week 60

ID	Title	Description
OG000	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.
OG001	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.

Secondary

Median Monthy Seizure Frequency: All 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).

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

Posted

Median

Standard Deviation

seizures/28 days

Baseline up to Week 60

ID	Title	Description
OG000	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.
OG001	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.

Secondary

Mean Monthy Seizure Frequency: All Seizures

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

Posted

Mean

Standard Deviation

seizures/28 days

Baseline up to Week 60

ID	Title	Description
OG000	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.
OG001	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.

Secondary

Median Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Partial Seizures

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.

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

Posted

Median

Standard Deviation

seizures/28 days

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

ID	Title	Description
OG000	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.
OG001	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.

Secondary

Mean Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Partial Seizures

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.

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

Posted

Mean

Standard Deviation

28-day seizure rate

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

ID	Title	Description
OG000	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.
OG001	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.

Secondary

Median Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All 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.

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

Posted

Median

Standard Deviation

seizures/28 days

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

ID	Title	Description
OG000	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.
OG001	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.

Secondary

Mean Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Seizures

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

Posted

Mean

Standard Deviation

28-day seizure rate

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

ID	Title	Description
OG000	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.
OG001	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.

Secondary

Percentage of Participants Who Achieved at Least 6 Consecutive Months of Seizure Freedom (Responders) by Final Dosage Levels and Treatment Group

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.

FAS; N = number of participants with analyzable data.

Posted

Number

percentage of participants

Week 5 up to Week 56

ID	Title	Description
OG000	Pregabalin 150 mg/Day	Pregabalin 150 mg/day administered twice daily (BID)
OG001	Pregabalin 300 mg/Day	Pregabalin 300 mg/day administered BID
OG002	Pregabalin 450 mg/Day	Pregabalin 450 mg/day administered BID
OG003	Pregabalin 600 mg/Day	Pregabalin 600 mg/day administered BID
OG004

Secondary

Change From Baseline to Week 56 in Hospital Anxiety and Depression Scale (HADS)

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.

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

Posted

Least Squares Mean

Standard Error

scores on scale

Baseline to Week 56

ID	Title	Description
OG000	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.
OG001	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.

Secondary

Medical Outcomes Study Sleep Scale (MOS-SS): Optimal Sleep Subscale

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.

FAS

Posted

Number

participants

Week 8, Week 32, and Week 56

ID	Title	Description
OG000	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.
OG001	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.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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.			44	330	186	330
EG001	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.			32	330	171	330

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Pancytopenia	Blood and lymphatic system disorders	MedDRA 12.1	Systematic Assessment	EG0001 affected330 at risk EG0010 affected330 at risk
Splenomegaly	Blood and lymphatic system disorders	MedDRA 12.1	Systematic Assessment	EG0000 affected330 at risk EG0011 affected330 at risk
Myocardial ischaemia	Cardiac disorders	MedDRA 12.1	Systematic Assessment	EG0001 affected330 at risk EG0010 affected330 at risk
Multiple endocrine adenomatosis Type II	Congenital, familial and genetic disorders	MedDRA 12.1	Systematic Assessment	EG0001 affected330 at risk EG0010 affected330 at risk
Parathyroid gland enlargement	Endocrine disorders	MedDRA 12.1	Systematic Assessment	EG0001 affected330 at risk EG0010 affected330 at risk
Entropion	Eye disorders	MedDRA 12.1	Systematic Assessment	EG0000 affected330 at risk EG0011 affected330 at risk
Trichiasis	Eye disorders	MedDRA 12.1	Systematic Assessment	EG0000 affected330 at risk EG0011 affected330 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 12.1	Systematic Assessment	EG0001 affected330 at risk EG0010 affected330 at risk
Gastritis	Gastrointestinal disorders	MedDRA 12.1	Systematic Assessment	EG0000 affected330 at risk EG0011 affected330 at risk
Vomiting	Gastrointestinal disorders	MedDRA 12.1	Systematic Assessment	EG0002 affected330 at risk EG0010 affected330 at risk
Chest pain	General disorders	MedDRA 12.1	Systematic Assessment	EG0000 affected330 at risk EG0011 affected330 at risk
Drowning	General disorders	MedDRA 12.1	Systematic Assessment	EG0001 affected330 at risk EG0010 affected330 at risk
General physical health deterioration	General disorders	MedDRA 12.1	Systematic Assessment	EG0000 affected330 at risk EG0011 affected330 at risk
Pyrexia	General disorders	MedDRA 12.1	Systematic Assessment	EG0001 affected330 at risk EG0010 affected330 at risk
Sudden unexplained death in epilepsy	General disorders	MedDRA 12.1	Systematic Assessment	EG0001 affected330 at risk EG0010 affected330 at risk
Cholecystitis acute	Hepatobiliary disorders	MedDRA 12.1	Systematic Assessment	EG0001 affected330 at risk EG0010 affected330 at risk
Hepatic function abnormal	Hepatobiliary disorders	MedDRA 12.1	Systematic Assessment	EG0001 affected330 at risk EG0010 affected330 at risk
Diverticulitis	Infections and infestations	MedDRA 12.1	Systematic Assessment	EG0000 affected330 at risk EG0011 affected330 at risk
Hepatitis B	Infections and infestations	MedDRA 12.1	Systematic Assessment	EG0001 affected330 at risk EG0010 affected330 at risk
Pneumonia	Infections and infestations	MedDRA 12.1	Systematic Assessment	EG0001 affected330 at risk EG0010 affected330 at risk
Sinusitis	Infections and infestations	MedDRA 12.1	Systematic Assessment	EG0001 affected330 at risk EG0010 affected330 at risk
Tuberculosis	Infections and infestations	MedDRA 12.1	Systematic Assessment	EG0000 affected330 at risk EG0011 affected330 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 12.1	Systematic Assessment	EG0001 affected330 at risk EG0010 affected330 at risk
Vulvovaginitis	Infections and infestations	MedDRA 12.1	Systematic Assessment	EG0000 affected330 at risk EG0011 affected330 at risk
Cartilage injury	Injury, poisoning and procedural complications	MedDRA 12.1	Systematic Assessment	EG0001 affected330 at risk EG0010 affected330 at risk
Concussion	Injury, poisoning and procedural complications	MedDRA 12.1	Systematic Assessment	EG0001 affected330 at risk EG0010 affected330 at risk
Excoriation	Injury, poisoning and procedural complications	MedDRA 12.1	Systematic Assessment	EG0001 affected330 at risk EG0010 affected330 at risk
Fall	Injury, poisoning and procedural complications	MedDRA 12.1	Systematic Assessment	EG0000 affected330 at risk EG0014 affected330 at risk
Foot fracture	Injury, poisoning and procedural complications	MedDRA 12.1	Systematic Assessment	EG0000 affected330 at risk EG0013 affected330 at risk
Hand fracture	Injury, poisoning and procedural complications	MedDRA 12.1	Systematic Assessment	EG0000 affected330 at risk EG0011 affected330 at risk
Head injury	Injury, poisoning and procedural complications	MedDRA 12.1	Systematic Assessment	EG0000 affected330 at risk EG0012 affected330 at risk
Joint dislocation	Injury, poisoning and procedural complications	MedDRA 12.1	Systematic Assessment	EG0000 affected330 at risk EG0011 affected330 at risk
Joint sprain	Injury, poisoning and procedural complications	MedDRA 12.1	Systematic Assessment	EG0001 affected330 at risk EG0010 affected330 at risk
Ligament rupture	Injury, poisoning and procedural complications	MedDRA 12.1	Systematic Assessment	EG0001 affected330 at risk EG0010 affected330 at risk
Limb injury	Injury, poisoning and procedural complications	MedDRA 12.1	Systematic Assessment	EG0001 affected330 at risk EG0010 affected330 at risk
Meniscus lesion	Injury, poisoning and procedural complications	MedDRA 12.1	Systematic Assessment	EG0000 affected330 at risk EG0011 affected330 at risk
Pelvic fracture	Injury, poisoning and procedural complications	MedDRA 12.1	Systematic Assessment	EG0000 affected330 at risk EG0011 affected330 at risk
Road traffic accident	Injury, poisoning and procedural complications	MedDRA 12.1	Systematic Assessment	EG0002 affected330 at risk EG0010 affected330 at risk
Thermal burn	Injury, poisoning and procedural complications	MedDRA 12.1	Systematic Assessment	EG0001 affected330 at risk EG0010 affected330 at risk
Arthropathy	Musculoskeletal and connective tissue disorders	MedDRA 12.1	Systematic Assessment	EG0001 affected330 at risk EG0010 affected330 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 12.1	Systematic Assessment	EG0001 affected330 at risk EG0010 affected330 at risk
Muscle haemorrhage	Musculoskeletal and connective tissue disorders	MedDRA 12.1	Systematic Assessment	EG0000 affected330 at risk EG0011 affected330 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA 12.1	Systematic Assessment	EG0000 affected330 at risk EG0011 affected330 at risk
Trigger finger	Musculoskeletal and connective tissue disorders	MedDRA 12.1	Systematic Assessment	EG0001 affected330 at risk EG0010 affected330 at risk
Abdominal neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 12.1	Systematic Assessment	EG0000 affected330 at risk EG0011 affected330 at risk
Brain neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 12.1	Systematic Assessment	EG0000 affected330 at risk EG0011 affected330 at risk
Metastases to lymph nodes	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 12.1	Systematic Assessment	EG0001 affected330 at risk EG0010 affected330 at risk
T-cell lymphoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 12.1	Systematic Assessment	EG0000 affected330 at risk EG0011 affected330 at risk
Thyroid cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 12.1	Systematic Assessment	EG0001 affected330 at risk EG0011 affected330 at risk
Uterine leiomyoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 12.1	Systematic Assessment	EG0001 affected330 at risk EG0011 affected330 at risk
Waldenstrom's macroglobulinaemia	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 12.1	Systematic Assessment	EG0000 affected330 at risk EG0011 affected330 at risk
Brain oedema	Nervous system disorders	MedDRA 12.1	Systematic Assessment	EG0001 affected330 at risk EG0010 affected330 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA 12.1	Systematic Assessment	EG0000 affected330 at risk EG0011 affected330 at risk
Convulsion	Nervous system disorders	MedDRA 12.1	Systematic Assessment	EG00010 affected330 at risk EG0011 affected330 at risk
Dementia	Nervous system disorders	MedDRA 12.1	Systematic Assessment	EG0001 affected330 at risk EG0010 affected330 at risk
Dizziness	Nervous system disorders	MedDRA 12.1	Systematic Assessment	EG0001 affected330 at risk EG0010 affected330 at risk
Drug withdrawal convulsions	Nervous system disorders	MedDRA 12.1	Systematic Assessment	EG0001 affected330 at risk EG0010 affected330 at risk
Epilepsy	Nervous system disorders	MedDRA 12.1	Systematic Assessment	EG0005 affected330 at risk EG0014 affected330 at risk
Grand mal convulsion	Nervous system disorders	MedDRA 12.1	Systematic Assessment	EG0002 affected330 at risk EG0010 affected330 at risk
Headache	Nervous system disorders	MedDRA 12.1	Systematic Assessment	EG0001 affected330 at risk EG0010 affected330 at risk
Hemiparesis	Nervous system disorders	MedDRA 12.1	Systematic Assessment	EG0000 affected330 at risk EG0011 affected330 at risk
Partial seizures	Nervous system disorders	MedDRA 12.1	Systematic Assessment	EG0002 affected330 at risk EG0010 affected330 at risk
Partial seizures with secondary generalisation	Nervous system disorders	MedDRA 12.1	Systematic Assessment	EG0002 affected330 at risk EG0010 affected330 at risk
Postictal headache	Nervous system disorders	MedDRA 12.1	Systematic Assessment	EG0000 affected330 at risk EG0011 affected330 at risk
Spinal cord disorder	Nervous system disorders	MedDRA 12.1	Systematic Assessment	EG0001 affected330 at risk EG0010 affected330 at risk
Status epilepticus	Nervous system disorders	MedDRA 12.1	Systematic Assessment	EG0004 affected330 at risk EG0011 affected330 at risk
Transient ischaemic attack	Nervous system disorders	MedDRA 12.1	Systematic Assessment	EG0001 affected330 at risk EG0010 affected330 at risk
Wernicke's encephalopathy	Nervous system disorders	MedDRA 12.1	Systematic Assessment	EG0000 affected330 at risk EG0011 affected330 at risk
Anxiety	Psychiatric disorders	MedDRA 12.1	Systematic Assessment	EG0001 affected330 at risk EG0010 affected330 at risk
Conversion disorder	Psychiatric disorders	MedDRA 12.1	Systematic Assessment	EG0001 affected330 at risk EG0011 affected330 at risk
Delirium tremens	Psychiatric disorders	MedDRA 12.1	Systematic Assessment	EG0000 affected330 at risk EG0011 affected330 at risk
Depression	Psychiatric disorders	MedDRA 12.1	Systematic Assessment	EG0000 affected330 at risk EG0011 affected330 at risk
Psychotic disorder	Psychiatric disorders	MedDRA 12.1	Systematic Assessment	EG0000 affected330 at risk EG0011 affected330 at risk
Calculus ureteric	Renal and urinary disorders	MedDRA 12.1	Systematic Assessment	EG0000 affected330 at risk EG0011 affected330 at risk
Urinary retention	Renal and urinary disorders	MedDRA 12.1	Systematic Assessment	EG0001 affected330 at risk EG0010 affected330 at risk
Vulval oedema	Reproductive system and breast disorders	MedDRA 12.1	Systematic Assessment	EG0000 affected330 at risk EG0011 affected330 at risk
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA 12.1	Systematic Assessment	EG0000 affected330 at risk EG0011 affected330 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 12.1	Systematic Assessment	EG0001 affected330 at risk EG0011 affected330 at risk
Vocal cord cyst	Respiratory, thoracic and mediastinal disorders	MedDRA 12.1	Systematic Assessment	EG0000 affected330 at risk EG0011 affected330 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 12.1	Systematic Assessment	EG0001 affected330 at risk EG0010 affected330 at risk
Stevens-Johnson syndrome	Skin and subcutaneous tissue disorders	MedDRA 12.1	Systematic Assessment	EG0001 affected330 at risk EG0010 affected330 at risk
Toxic epidermal necrolysis	Skin and subcutaneous tissue disorders	MedDRA 12.1	Systematic Assessment	EG0000 affected330 at risk EG0011 affected330 at risk
Carpal tunnel decompression	Surgical and medical procedures	MedDRA 12.1	Systematic Assessment	EG0001 affected330 at risk EG0010 affected330 at risk
Hip arthroplasty	Surgical and medical procedures	MedDRA 12.1	Systematic Assessment	EG0001 affected330 at risk EG0010 affected330 at risk
Ostectomy	Surgical and medical procedures	MedDRA 12.1	Systematic Assessment	EG0001 affected330 at risk EG0010 affected330 at risk
Splenectomy	Surgical and medical procedures	MedDRA 12.1	Systematic Assessment	EG0000 affected330 at risk EG0011 affected330 at risk
Haematoma	Vascular disorders	MedDRA 12.1	Systematic Assessment	EG0000 affected330 at risk EG0011 affected330 at risk
Vasculitis	Vascular disorders	MedDRA 12.1	Systematic Assessment	EG0000 affected330 at risk EG0011 affected330 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Vision blurred	Eye disorders	MedDRA 12.1	Systematic Assessment	EG0007 affected330 at risk EG0012 affected330 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 12.1	Systematic Assessment	EG0004 affected330 at risk EG0019 affected330 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 12.1	Systematic Assessment	EG00012 affected330 at risk EG00117 affected330 at risk
Constipation	Gastrointestinal disorders	MedDRA 12.1	Systematic Assessment	EG0009 affected330 at risk EG0015 affected330 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 12.1	Systematic Assessment	EG00012 affected330 at risk EG00113 affected330 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 12.1	Systematic Assessment	EG0008 affected330 at risk EG00112 affected330 at risk
Nausea	Gastrointestinal disorders	MedDRA 12.1	Systematic Assessment	EG00014 affected330 at risk EG00111 affected330 at risk
Toothache	Gastrointestinal disorders	MedDRA 12.1	Systematic Assessment	EG0009 affected330 at risk EG0014 affected330 at risk
Vomiting	Gastrointestinal disorders	MedDRA 12.1	Systematic Assessment	EG0007 affected330 at risk EG0018 affected330 at risk
Fatigue	General disorders	MedDRA 12.1	Systematic Assessment	EG00030 affected330 at risk EG00119 affected330 at risk
Pyrexia	General disorders	MedDRA 12.1	Systematic Assessment	EG0006 affected330 at risk EG00114 affected330 at risk
Influenza	Infections and infestations	MedDRA 12.1	Systematic Assessment	EG00014 affected330 at risk EG00112 affected330 at risk
Nasopharyngitis	Infections and infestations	MedDRA 12.1	Systematic Assessment	EG00015 affected330 at risk EG00121 affected330 at risk
Pharyngitis	Infections and infestations	MedDRA 12.1	Systematic Assessment	EG0007 affected330 at risk EG0014 affected330 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 12.1	Systematic Assessment	EG00020 affected330 at risk EG00123 affected330 at risk
Weight increased	Investigations	MedDRA 12.1	Systematic Assessment	EG00022 affected330 at risk EG0017 affected330 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 12.1	Systematic Assessment	EG0002 affected330 at risk EG0017 affected330 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 12.1	Systematic Assessment	EG0009 affected330 at risk EG00110 affected330 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 12.1	Systematic Assessment	EG0007 affected330 at risk EG0016 affected330 at risk
Disturbance in attention	Nervous system disorders	MedDRA 12.1	Systematic Assessment	EG0007 affected330 at risk EG0016 affected330 at risk
Dizziness	Nervous system disorders	MedDRA 12.1	Systematic Assessment	EG00057 affected330 at risk EG00147 affected330 at risk
Headache	Nervous system disorders	MedDRA 12.1	Systematic Assessment	EG00075 affected330 at risk EG00173 affected330 at risk
Memory impairment	Nervous system disorders	MedDRA 12.1	Systematic Assessment	EG0008 affected330 at risk EG00113 affected330 at risk
Somnolence	Nervous system disorders	MedDRA 12.1	Systematic Assessment	EG00029 affected330 at risk EG00116 affected330 at risk
Anxiety	Psychiatric disorders	MedDRA 12.1	Systematic Assessment	EG0005 affected330 at risk EG00110 affected330 at risk
Depression	Psychiatric disorders	MedDRA 12.1	Systematic Assessment	EG00010 affected330 at risk EG00114 affected330 at risk
Insomnia	Psychiatric disorders	MedDRA 12.1	Systematic Assessment	EG00015 affected330 at risk EG00119 affected330 at risk
Sleep disorder	Psychiatric disorders	MedDRA 12.1	Systematic Assessment	EG0002 affected330 at risk EG0017 affected330 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 12.1	Systematic Assessment	EG0002 affected330 at risk EG0019 affected330 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 12.1	Systematic Assessment	EG0002 affected330 at risk EG00110 affected330 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 12.1	Systematic Assessment	EG0004 affected330 at risk EG0018 affected330 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 12.1	Systematic Assessment	EG00012 affected330 at risk EG00118 affected330 at risk
Hypertension	Vascular disorders	MedDRA 12.1	Systematic Assessment	EG0004 affected330 at risk EG0017 affected330 at risk

Ancestor Terms

ID	Term
D001927	Brain Diseases
D002493	Central Nervous System Diseases
D009422	Nervous System Diseases
D009461	Neurologic Manifestations
D012816	Signs and Symptoms
D013568	Pathological Conditions, Signs and Symptoms

Ancestor Terms

ID	Term
D005680	gamma-Aminobutyric Acid
D000613	Aminobutyrates
D002087	Butyrates
D000144	Acids, Acyclic
D002264	Carboxylic Acids
D009930	Organic Chemicals
D000596	Amino Acids
D000602	Amino Acids, Peptides, and Proteins
D014227	Triazines
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Risk ratio=hazard ratio estimated from the Cox proportional hazards model for assessing a treatment difference, risk ratio > 1 is in favor of pregabalin. The 95% confidence interval is for the true risk ratio.	Regression, Cox		0.0034	Nominal value for 2-sided test calculated using Cox proportional hazards model, adjusted for geographic regions.	Risk Ratio (RR)	0.74			2-Sided	95	0.60	0.90					Superiority or Other (legacy)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Risk ratio=hazard ratio estimated from the Cox proportional hazards model for assessing a treatment difference, risk ratio < 1 is in favor of pregabalin. The 95% confidence interval is for the true risk ratio.	Cox proportional hazards model		0.8047	Nominal value for 2-sided test calculated using Cox proportional hazards model adjusted for geographical cluster.	Risk Ratio (RR)	1.06			2-Sided	95	0.65	1.74					Superiority or Other (legacy)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Risk ratio=hazard ratio estimated from the Cox proportional hazards model for assessing a treatment difference, risk ratio < 1 is in favor of pregabalin. The 95% confidence interval is for the true risk ratio.	Cox proportional hazards model		0.2537	Nominal value for 2-sided test calculated using Cox proportional hazards model adjusted for geographical cluster.	Risk Ratio (RR)	1.19			2-Sided	95	0.88	1.60					Superiority or Other (legacy)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Risk ratio=hazard ratio estimated from the Cox proportional hazards model for assessing a treatment difference, risk ratio < 1 is in favor of pregabalin. The 95% confidence interval is for the true risk ratio.	Cox proportional hazards model		0.0025	Nominal value for 2-sided test calculated using Cox proportional hazards model adjusted for geographical cluster.	Risk Ratio (RR)	6.52			2-Sided	95	1.93	22.04					Superiority or Other (legacy)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Risk ratio=hazard ratio estimated from the Cox proportional hazards model for assessing a treatment difference, risk ratio < 1 is in favor of pregabalin. The 95% confidence interval is for the true risk ratio.	Cox proportional hazards model		0.0744	Nominal value for 2-sided test calculated using Cox proportional hazards model adjusted for geographical cluster.	Risk Ratio (RR)	1.36			2-Sided	95	0.97	1.91					Superiority or Other (legacy)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Risk ratio=hazard ratio estimated from the Cox proportional hazards model for assessing a treatment difference, risk ratio < 1 is in favor of pregabalin. The 95% confidence interval is for the true risk ratio.	Cox proportional hazards model		0.0003	Nominal value for 2-sided test calculated using Cox proportional hazards model adjusted for geographical cluster.	Risk Ratio (RR)	1.47			2-Sided	95	1.19	1.80					Superiority or Other (legacy)

Title

Denominators

Categories

Dose-escalation phase (Weeks 1 - 4) (n=329, 330)

Title	Measurements
	OG0000.0± 9.348 OG0010.0± 27.118

Month 1 (n=314, 308)

Title	Measurements
	OG0000.0± 6.139 OG0010.0± 31.453

Month 2 (n=300, 295)

Title	Measurements
	OG0000.0± 3.382 OG0010.0± 28.839

Month 3 (n=287, 288)

Title	Measurements
	OG0000.0± 2.568 OG0010.0± 32.783

Month 4 (n=279, 278)

Title	Measurements
	OG0000.0± 2.313 OG0010.0± 16.046

Month 5 (n=274, 276)

Title	Measurements
	OG0000.0± 2.270 OG0010.0± 15.254

Month 6 (n=266, 272)

Title	Measurements
	OG0000.0± 2.702 OG0010.0± 15.126

Month 7 (n=260, 270)

Title	Measurements
	OG0000.0± 2.839 OG0010.0± 16.855

Month 8 (n=256, 266)

Title	Measurements
	OG0000.0± 3.247 OG0010.0± 19.111

Month 9 (n=253, 262)

Title	Measurements
	OG0000.0± 2.538 OG0010.0± 17.204

Month 10 (n=250, 257)

Title	Measurements
	OG0000.0± 4.935 OG0010.0± 16.905

Month 11 (n=242, 254)

Title	Measurements
	OG0000.0± 3.082 OG0010.0± 19.268

Month 12 (n=238, 252)

Title	Measurements
	OG0000.0± 7.018 OG0010.0± 19.590

Month 13 (n=210, 227)

Title	Measurements
	OG0000.0± 3.247 OG0010.0± 19.462

Taper (Week 57 to Week 60) (n=71, 45)

Title	Measurements
	OG0000.0± 6.418 OG0010.0± 97.196

Title

Denominators

Categories

Dose escalation phase (n=329, 330)

Title	Measurements
	OG0002.56± 9.348 OG0015.08± 27.118

Month 1 (n=314, 308)

Title	Measurements
	OG0002.23± 6.139 OG0014.21± 31.453

Month 2 (n=300, 295)

Title	Measurements
	OG0001.18± 3.382 OG0013.21± 28.839

Month 3 (n=287, 288)

Title	Measurements
	OG0000.94± 2.568 OG0013.54± 32.783

Month 4 (n=279, 278)

Title	Measurements
	OG0000.89± 2.313 OG0011.67± 16.046

Month 5 (n=274, 276)

Title	Measurements
	OG0000.78± 2.270 OG0011.58± 15.254

Month 6 (n=266, 272)

Title	Measurements
	OG0000.82± 2.702 OG0011.41± 15.126

Month 7 (n=260, 270)

Title	Measurements
	OG0000.78± 2.839 OG0011.50± 16.855

Month 8 (n=256, 266)

Title	Measurements
	OG0000.77± 3.247 OG0011.36± 19.111

Month 9 (n=253, 262)

Title	Measurements
	OG0000.71± 2.538 OG0011.38± 17.204

Month 10 (n=250, 257)

Title	Measurements
	OG0001.05± 4.935 OG0011.33± 16.905

Month 11 (n=242, 254)

Title	Measurements
	OG0000.79± 3.082 OG0011.41± 19.268

Month 12 (n=238, 252)

Title	Measurements
	OG0000.94± 7.018 OG0011.67± 19.590

Month 13 (n=210, 227)

Title	Measurements
	OG0000.65± 3.247 OG0012.11± 19.462

Taper (n=71, 45)

Title	Measurements
	OG0002.13± 6.418 OG00119.97± 97.196

Title

Denominators

Categories

Dose-escalation phase (Weeks 1 - 4)(n=329, 330)

Title	Measurements
	OG0000.0± 9.819 OG0010.0± 27.128

Month 1 (n=314, 308)

Title	Measurements
	OG0000.0± 6.164 OG0010.0± 31.452

Month 2 (n=300, 295)

Title	Measurements
	OG0000.0± 5.498 OG0010.0± 28.838

Month 3 (n=287, 288)

Title	Measurements
	OG0000.0± 2.702 OG0010.0± 32.782

Month 4 (n=279, 278)

Title	Measurements
	OG0000.0± 3.223 OG0010.0± 16.046

Month 5 (n=274, 276)

Title	Measurements
	OG0000.0± 2.458 OG0010.0± 15.254

Month 6 (n=266, 272)

Title	Measurements
	OG0000.0± 2.853 OG0010.0± 15.126

Month 7 (n=260, 270)

Title	Measurements
	OG0000.0± 2.898 OG0010.0± 16.855

Month 8 (n=256, 266)

Title	Measurements
	OG0000.0± 3.304 OG0010.0± 19.110

Month 9 (n=253, 262)

Title	Measurements
	OG0000.0± 2.636 OG0010.0± 17.204

Month 10 (n=250, 257)

Title	Measurements
	OG0000.0± 4.934 OG0010.0± 16.905

Month 11 (n=242, 254)

Title	Measurements
	OG0000.0± 3.224 OG0010.0± 19.268

Month 12 (n=238, 252)

Title	Measurements
	OG0000.0± 7.019 OG0010.0± 19.590

Month 13 (n=210, 227)

Title	Measurements
	OG0000.0± 3.247 OG0010.0± 19.462

Taper (Week 57 to Week 60) (n=71, 45)

Title	Measurements
	OG0000.0± 6.418 OG0010.0± 97.196

Title

Denominators

Categories

Dose-escalation phase (n=329, 330)

Title	Measurements
	OG0002.74± 9.819 OG0015.10± 27.128

Month 1 (n=314, 308)

Title	Measurements
	OG0002.31± 6.164 OG0014.24± 31.452

Month 2 (n=300, 295)

Title	Measurements
	OG0001.53± 5.498 OG0013.22± 28.838

Month 3 (n=287, 288)

Title	Measurements
	OG0001.02± 2.702 OG0013.57± 32.782

Month 4 (n=279, 278)

Title	Measurements
	OG0001.06± 3.223 OG0011.68± 16.046

Month 5 (n=274, 276)

Title	Measurements
	OG0000.87± 2.458 OG0011.59± 15.254

Month 6 (n=266, 272)

Title	Measurements
	OG0000.89± 2.853 OG0011.41± 15.126

Month 7 (n=260, 270)

Title	Measurements
	OG0000.83± 2.898 OG0011.50± 16.855

Month 8 (n=256, 266)

Title	Measurements
	OG0000.82± 3.304 OG0011.37± 19.110

Month 9 (n=253, 262)

Title	Measurements
	OG0000.78± 2.636 OG0011.38± 17.204

Month 10 (n=250, 257)

Title	Measurements
	OG0001.06± 4.934 OG0011.33± 16.905

Month 11 (n=242, 254)

Title	Measurements
	OG0000.81± 3.224 OG0011.41± 19.268

Month 12 (n=238, 252)

Title	Measurements
	OG0000.96± 7.019 OG0011.67± 19.590

Month 13 (n=210, 227)

Title	Measurements
	OG0000.65± 3.247 OG0012.12± 19.462

Taper (n=71, 45)

Title	Measurements
	OG0002.13± 6.418 OG00119.97± 97.196

Title

Denominators

Categories

Month 1 (n=162, 208)

Title	Measurements
	OG0000.0± 1.000 OG0010.0± 0.226

Month 2 (n=155, 194)

Title	Measurements
	OG0000.0± 1.783 OG0010.0± 0.226

Month 3 (n=147, 184)

Title	Measurements
	OG0000.0± 0.384 OG0010.0± 0.439

Month 4 (n=139, 173)

Title	Measurements
	OG0000.0± 0.329 OG0010.0± 0.211

Month 5 (n=127, 158)

Title	Measurements
	OG0000.0± 0.926 OG0010.0± 0.823

Month 6 (n=122, 152)

Title	Measurements
	OG0000.0± 0.156 OG0010.0± 0.213

Month 7 (n=105, 136)

Title	Measurements
	OG0000.0± 0.000 OG0010.0± 2.843

Month 8 (n=1, 5)

Title	Measurements
	OG0000.0± NAn = 1. OG0010.0± 0.000

Month 9 (n=0, 1)

Title	Measurements
	OG000NA± NANo responders with analyzable data at Month 9. OG0016.0± NAn = 1.

Title

Denominators

Categories

Month 1 (n=162, 208)

Title	Measurements
	OG0000.19± 1.000 OG0010.04± 0.226

Month 2 (n=155, 194)

Title	Measurements
	OG0000.28± 1.783 OG0010.03± 0.226

Month 3 (n=147, 184)

Title	Measurements
	OG0000.05± 0.384 OG0010.07± 0.439

Month 4 (n=139, 173)

Title	Measurements
	OG0000.09± 0.329 OG0010.05± 0.211

Month 5 (n=127, 158)

Title	Measurements
	OG0000.15± 0.926 OG0010.10± 0.823

Month 6 (n=122, 152)

Title	Measurements
	OG0000.02± 0.156 OG0010.03± 0.213

Month 7 (n=105, 136)

Title	Measurements
	OG0000.00± 0.000 OG0010.28± 2.843

Month 8 (n=1, 5)

Title	Measurements
	OG0000.00± NAMeasure of dispersion cannot be calculated with a sample size of 1. OG0010.00± 0.000

Month 9 (n=0, 1)

Title	Measurements
	OG000NA± NANo responders with analyzable data at Month 9. OG0016.00± NAMeasure of dispersion cannot be calculated with a sample size of 1.

Title

Denominators

Categories

Month 1 (n=162, 208)

Title	Measurements
	OG0000.0± 1.000 OG0010.0± 0.236

Month 2 (n=155, 194)

Title	Measurements
	OG0000.0± 1.783 OG0010.0± 0.226

Month 3 (n=147, 184)

Title	Measurements
	OG0000.0± 0.400 OG0010.0± 0.439

Month 4 (n=139, 173)

Title	Measurements
	OG0000.0± 0.359 OG0010.0± 0.211

Month 5 (n=127, 158)

Title	Measurements
	OG0000.0± 0.971 OG0010.0± 0.823

Month 6 (n=122, 152)

Title	Measurements
	OG0000.0± 0.156 OG0010.0± 0.213

Month 7 (n=105, 136)

Title	Measurements
	OG0000.0± 0.000 OG0010.0± 2.844

Month 8 (n=1, 5)

Title	Measurements
	OG0000.0± NAn=1. OG0010.0± 0.000

Month 9 (n=0, 1)

Title	Measurements
	OG000NA± NANo responders with analyzable data at Month 9. OG0016.0± NAn=1.

Title

Denominators

Categories

Month 1 (n=162, 208)

Title	Measurements
	OG0000.19± 1.000 OG0010.05± 0.236

Month 2 (n=155, 194)

Title	Measurements
	OG0000.28± 1.783 OG0010.03± 0.226

Month 3 (n=147, 184)

Title	Measurements
	OG0000.07± 0.400 OG0010.07± 0.439

Month 4 (n=139, 173)

Title	Measurements
	OG0000.09± 0.359 OG0010.05± 0.211

Month 5 (n=127, 158)

Title	Measurements
	OG0000.18± 0.971 OG0010.10± 0.823

Month 6 (n=122, 152)

Title	Measurements
	OG0000.02± 0.156 OG0010.03± 0.213

Month 7 (n=105, 136)

Title	Measurements
	OG0000.00± 0.000 OG0010.29± 2.844

Month 8 (n=1, 5)

Title	Measurements
	OG0000.00± NAMeasure of dispersion cannot be calculated with a sample size of 1. OG0010.00± 0.000

Month 9 (n=0, 1)

Title	Measurements
	OG000NA± NANo responders with analyzable data at Month 9. OG0016.00± NAMeasure of dispersion cannot be calculated with a sample size of 1.

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Anxiety; model includes treatment and geographical cluster as fixed effects and respective baseline scores as a continuous covariate.	ANCOVA		0.0025		Mean Difference (Final Values)	0.8			2-Sided	95	0.3	1.4					Superiority or Other (legacy)
OG000 OG001	Depression; model includes treatment and geographical cluster as fixed effects and respective baseline scores as a continuous covariate.	ANCOVA		0.0186		Mean Difference (Final Values)	0.6			2-Sided	95	0.1	1.1					Superiority or Other (legacy)

Title

Denominators

Categories

Week 8: Optimal sleep

Title	Measurements
	OG000195 OG001173

Week 8: Non-optimal sleep

Title	Measurements
	OG000103 OG001126

Week 32: Optimal sleep

Title	Measurements
	OG000167 OG001155

Week 32: Non-optimal sleep

Title	Measurements
	OG00097 OG001103

Week 56: Optimal sleep

Title	Measurements
	OG000152 OG001145

Week 56: Non-optimal sleep

Title	Measurements
	OG00082 OG00190

Group IDs	Group Description	Statistical Method	P-Value	Parameter Type	Parameter Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	Non-Inferiority Type
OG000 OG001	Week 8: dichotomized sleep assessment analyzed using a logistic regression model for repeated measures with fixed effects for treatment, geographical region, the average hours per night of sleep at baseline as a continuous covariate, time, and treatment-by-time interaction. The within subject covariance structure assumes an auto-regressive of order one covariance structure.	Regression, Logistic	0.0683	Odds Ratio (OR)	1.37	2-Sided	95	0.98	1.93	Superiority or Other (legacy)
OG000 OG001	Week 32: dichotomized sleep assessment analyzed using a logistic regression model for repeated measures with fixed effects for treatment, geographical region, the average hours per night of sleep at baseline as a continuous covariate, time, and treatment-by-time interaction. The within subject covariance structure assumes an auto-regressive of order one covariance structure.	Regression, Logistic	0.5096	Odds Ratio (OR)	1.14	2-Sided	95	0.78	1.66	Superiority or Other (legacy)
OG000 OG001	Week 56 (termination): dichotomized sleep assessment analyzed using a logistic regression model for repeated measures with fixed effects for treatment, geographical region, the average hours per night of sleep at baseline as a continuous covariate, time, and treatment-by-time interaction. The within subject covariance structure assumes an auto-regressive of order one covariance structure.	Regression, Logistic	0.6804	Odds Ratio (OR)	1.09	2-Sided	95	0.73	1.63	Superiority or Other (legacy)