Lyrica (Pregabalin) Administered as an Add-on Therapy for Partial Seizures (LEADER). - Study Results

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized; Endpoint Classification: Safety/Efficacy Study; Intervention Model: Single Group Assignment; Masking: Open Label; Primary Purpose: Treatment
Condition:	Epilepsy
Intervention:	Drug: Pregabalin

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Planned to enroll approximately 100 subjects with partial seizures at up to 10 study centers in Greece.

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Single arm open label study without randomization. The study included the following 3 main phases with a total study treatment duration of up to 21 weeks: Treatment dose-optimization phase = 9 weeks. Treatment observation phase = 12 weeks.

	Description
Pregabalin	Pregabalin treatment, given as 2 divided doses, was initiated at a dose of 150 mg/day (75 mg BID). Then, based on individual subject response and tolerability, the dosage could have been increased to 300 mg/day after 1 week. The dosage could have been incrementally increased further to 600 mg/day after an additional week. After 9 weeks of treatment, the optimal dose of pregabalin was to be maintained for 3 months (12 week treatment observation period).

	Pregabalin
STARTED	98
COMPLETED	86
NOT COMPLETED	12
Adverse Event	5
Lack of Efficacy	4
Withdrawal by Subject	2
Unknown	1

	Description
Pregabalin	Pregabalin treatment, given as 2 divided doses, was initiated at a dose of 150 mg/day (75 mg BID). Then, based on individual subject response and tolerability, the dosage could have been increased to 300 mg/day after 1 week. The dosage could have been incrementally increased further to 600 mg/day after an additional week. After 9 weeks of treatment, the optimal dose of pregabalin was to be maintained for 3 months (12 week treatment observation period).

	Pregabalin
Number of Participants [units: participants]	98
Age, Customized [units: Participants]
18 to 44 years	69
45 to 64 years	25
>=65 years	4
Gender [units: participants]
Female	49
Male	49

Measure Type	Primary
Measure Title	Percentage Change in Partial Seizure Frequency (All Partial Seizure Types) Between Baseline and the 12 Week Observation Period
Measure Description	Percentage change from baseline=[(12 week treatment observation period seizure frequency rate minus 8 week baseline period seizure frequency rate)/ 8 week baseline period seizure frequency rate] x 100. Seizure frequencies per 28-day period: = (total # of partial seizures in period x 28 / (total # of days in period).
Time Frame	8 week baseline period & 12 week treatment observation period
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full analysis set (FAS)/intent-to-treat (ITT) population (all subjects who received at least 1 dose of study treatment & had a minimum of 2 partial seizures during baseline period). Seizure rate was calculated on last observation carried forward (LOCF) basis, whereby data from last 84 days prior to last dose was used to calculate seizure frequency.

Reporting Groups

	Description
Pregabalin	Pregabalin treatment, given as 2 divided doses, was initiated at a dose of 150 mg/day (75 mg BID). Then, based on individual subject response and tolerability, the dosage could have been increased to 300 mg/day after 1 week. The dosage could have been incrementally increased further to 600 mg/day after an additional week. After 9 weeks of treatment, the optimal dose of pregabalin was to be maintained for 3 months (12 week treatment observation period).

Description

Pregabalin

Pregabalin treatment, given as 2 divided doses, was initiated at a dose of 150 mg/day (75 mg BID). Then, based on individual subject response and tolerability, the dosage could have been increased to 300 mg/day after 1 week. The dosage could have been incrementally increased further to 600 mg/day after an additional week. After 9 weeks of treatment, the optimal dose of pregabalin was to be maintained for 3 months (12 week treatment observation period).

Measured Values

	Pregabalin
Number of Participants Analyzed [units: participants]	92
Percentage Change in Partial Seizure Frequency (All Partial Seizure Types) Between Baseline and the 12 Week Observation Period [units: percentage change in events] Median ( Full Range )	-33.33 ( -100.00 to 7566.67 )

Statistical Analysis 1 for Percentage Change in Partial Seizure Frequency (All Partial Seizure Types) Between Baseline and the 12 Week Observation Period

Groups ^[1]	Pregabalin
Mean Response Ratio ^[2]	-22.72
Standard Deviation	± 55.232
95% Confidence Interval	( -34.16 to -11.28 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Noncomparative study. Summary stats, 2 sided 95% CI to est. effect size. No adjustments made to alpha levels to acct for multiple 2o endpts. Sample size=83 patients (pts) sufficient to detect statistically significant difference in % change from baseline in 28-day seizure rate with 80% power, true change from baseline approximately 25%. Allowing for dropouts assume 85% pts analyzed.
[2]	Other relevant estimation information:
	Response ratio = 100 x [(t – b)/(t + b)] where t=treatment seizure frequency and b=baseline seizure frequency.

Measure Type	Secondary
Measure Title	Percentage Change in Partial Seizure Frequency (All Partial Seizure Types) Between Baseline and the Whole 21 Week Open-label Treatment Period.
Measure Description	Percentage change from baseline = ((21 weeks-8 weeks)/8 weeks)*100. Negative mean R-Ratios and associated 95% CIs that do not include zero indicate reduction in partial seizure frequency.
Time Frame	8 week baseline period and 21 week treatment period
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full analysis set (FAS)/intent-to-treat (ITT) population (all subjects who received at least 1 dose of study treatment & had a minimum of 2 partial seizures during baseline period). Seizure rate was calculated on last observation carried forward (LOCF) basis, whereby data from last 84 days prior to last dose was used to calculate seizure frequency.

Reporting Groups

	Description
Pregabalin	Pregabalin treatment, given as 2 divided doses, was initiated at a dose of 150 mg/day (75 mg BID). Then, based on individual subject response and tolerability, the dosage could have been increased to 300 mg/day after 1 week. The dosage could have been incrementally increased further to 600 mg/day after an additional week. After 9 weeks of treatment, the optimal dose of pregabalin was to be maintained for 3 months (12 week treatment observation period).

Description

Pregabalin

Pregabalin treatment, given as 2 divided doses, was initiated at a dose of 150 mg/day (75 mg BID). Then, based on individual subject response and tolerability, the dosage could have been increased to 300 mg/day after 1 week. The dosage could have been incrementally increased further to 600 mg/day after an additional week. After 9 weeks of treatment, the optimal dose of pregabalin was to be maintained for 3 months (12 week treatment observation period).

Measured Values

	Pregabalin
Number of Participants Analyzed [units: participants]	92
Percentage Change in Partial Seizure Frequency (All Partial Seizure Types) Between Baseline and the Whole 21 Week Open-label Treatment Period. [units: percentage change in events] Median ( Full Range )	-29.39 ( -100.00 to 7478.95 )

Statistical Analysis 1 for Percentage Change in Partial Seizure Frequency (All Partial Seizure Types) Between Baseline and the Whole 21 Week Open-label Treatment Period.

Groups ^[1]	Pregabalin
Mean Response Ratio ^[2]	-17.26
Standard Deviation	± 48.797
95% Confidence Interval	( -27.36 to -7.15 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Noncomparative study. Summary stats, 2 sided 95% CI to est. effect size. No adjustments made to alpha levels to acct for multiple 2o endpts. Sample size=83 patients (pts) sufficient to detect statistically significant difference in % change from baseline in 28-day seizure rate with 80% power, true change from baseline approximately 25%. Allowing for dropouts assume 85% pts analyzed.
[2]	Other relevant estimation information:
	Response ratio = 100 x [(t – b)/(t + b)] where t=treatment seizure frequency and b=baseline seizure frequency.

Measure Type	Secondary
Measure Title	Percentage Change in Partial Seizure Frequency (All Partial Seizure Types) Between the 8 Week Baseline Period and 4 Week Intervals During the 21 Week Open-label Treatment Period.
Measure Description	Percentage change from baseline = [(4 week seizure frequency minus 8 week baseline) / (8 week baseline seizure frequency)] x 100. Negative mean R-Ratios and associated 95% CIs that do not include zero indicate reduction in partial seizure frequency.
Time Frame	8 week baseline period and 21 week treatment period
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full analysis set (FAS)/intent-to-treat (ITT) population (all subjects who received at least 1 dose of study treatment & had a minimum of 2 partial seizures during baseline period). Seizure date from patients who discontinued during any of these 4 week intervals will not be included in the summary for that interval.

Reporting Groups

	Description
Pregabalin	Pregabalin treatment, given as 2 divided doses, was initiated at a dose of 150 mg/day (75 mg BID). Then, based on individual subject response and tolerability, the dosage could have been increased to 300 mg/day after 1 week. The dosage could have been incrementally increased further to 600 mg/day after an additional week. After 9 weeks of treatment, the optimal dose of pregabalin was to be maintained for 3 months (12 week treatment observation period).

Description

Pregabalin

Pregabalin treatment, given as 2 divided doses, was initiated at a dose of 150 mg/day (75 mg BID). Then, based on individual subject response and tolerability, the dosage could have been increased to 300 mg/day after 1 week. The dosage could have been incrementally increased further to 600 mg/day after an additional week. After 9 weeks of treatment, the optimal dose of pregabalin was to be maintained for 3 months (12 week treatment observation period).

Measured Values

	Pregabalin
Number of Participants Analyzed [units: participants]	92
Percentage Change in Partial Seizure Frequency (All Partial Seizure Types) Between the 8 Week Baseline Period and 4 Week Intervals During the 21 Week Open-label Treatment Period. [units: percentage change of events] Median ( Full Range )
1-28 Days	-28.12 ( -100.00 to 4833.33 )
29-56 Days	-22.50 ( -100.00 to 9633.33 )
57-84 Days	-25.00 ( -100.00 to 3433.33 )
85-112 Days	-40.00 ( -100.00 to 5100.00 )
113-140 Days	-58.72 ( -100.00 to 9166.67 )
>140 Days	-85.42 ( -100.00 to 12344.44 )

Statistical Analysis 1 for Percentage Change in Partial Seizure Frequency (All Partial Seizure Types) Between the 8 Week Baseline Period and 4 Week Intervals During the 21 Week Open-label Treatment Period.

Groups ^[1]	Pregabalin
Mean Response Ratio ^[2]	-22.43
Standard Deviation	± 56.615
95% Confidence Interval	( -34.16 to -10.71 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Noncomparative study.Summary stats, 2 sided 95% CI to est. effect size. No adjustments made to alpha levels to acct for multiple 2o endpts.Sample size=83 patients (pts) sufficient to detect statistically significant difference in % change from baseline in 28-day seizure rate with 80% power, true change from baseline approximately 25%.Allowing for dropouts assume 85% pts analyzed.
[2]	Other relevant estimation information:
	1-28 Days. Response ratio = 100 x [(t – b)/(t + b)] where t= 4 wk interval seizure frequency and b=baseline seizure frequency.

Statistical Analysis 2 for Percentage Change in Partial Seizure Frequency (All Partial Seizure Types) Between the 8 Week Baseline Period and 4 Week Intervals During the 21 Week Open-label Treatment Period.

Groups ^[1]	Pregabalin
Mean Response Ratio ^[2]	-22.83
Standard Deviation	± 57.543
95% Confidence Interval	( -34.74 to -10.91 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Noncomparative study.Summary stats, 2 sided 95% CI to est. effect size. No adjustments made to alpha levels to acct for multiple 2o endpts. Sample size=83 patients (pts) sufficient to detect statistically significant difference in % change from baseline in 28-day seizure rate with 80% power,true change from baseline approximately 25%. Allowing for dropouts assume 85% pts analyzed.
[2]	Other relevant estimation information:
	29-56 Days. Response ratio = 100 x [(t – b)/(t + b)] where t= 4 wk interval seizure frequency and b=baseline seizure frequency.

Statistical Analysis 3 for Percentage Change in Partial Seizure Frequency (All Partial Seizure Types) Between the 8 Week Baseline Period and 4 Week Intervals During the 21 Week Open-label Treatment Period.

Groups ^[1]	Pregabalin
Mean Response Ratio ^[2]	-27.18
Standard Deviation	± 59.323
95% Confidence Interval	( -39.90 to -14.46 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Noncomparative study.Summary stats, 2 sided 95% CI to est. effect size. No adjustments made to alpha levels to acct for multiple 2o endpts. Sample size=83 patients (pts) sufficient to detect statistically significant difference in % change from baseline in 28-day seizure rate with 80% power, true change from baseline approximately 25%. Allowing for dropouts assume 85% pts analyzed.
[2]	Other relevant estimation information:
	57-84 Days. Response ratio = 100 x [(t – b)/(t + b)] where t= 4 wk interval seizure frequency and b=baseline seizure frequency. .

Statistical Analysis 4 for Percentage Change in Partial Seizure Frequency (All Partial Seizure Types) Between the 8 Week Baseline Period and 4 Week Intervals During the 21 Week Open-label Treatment Period.

Groups ^[1]	Pregabalin
Mean Response Ratio ^[2]	-30.75
Standard Deviation	± 58.110
95% Confidence Interval	( -43.44 to -18.06 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Noncomparative study.Summary stats, 2 sided 95% CI to est. effect size. No adjustments made to alpha levels to acct for multiple 2o endpts. Sample size=83 patients (pts) sufficient to detect statistically significant difference in % change from baseline in 28-day seizure rate with 80% power, true change from baseline approximately 25%.Allowing for dropouts assume 85% pts analyzed.
[2]	Other relevant estimation information:
	85-112 Days. Response ratio=100 x [(t – b)/(t + b)] where t= 4 wk interval seizure frequency and b=baseline seizure frequency.

Statistical Analysis 5 for Percentage Change in Partial Seizure Frequency (All Partial Seizure Types) Between the 8 Week Baseline Period and 4 Week Intervals During the 21 Week Open-label Treatment Period.

Groups ^[1]	Pregabalin
Mean Response Ratio ^[2]	-38.75
Standard Deviation	± 59.368
95% Confidence Interval	( -51.79 to -25.70 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Noncomparative study.Summary stats, 2 sided 95% CI to est. effect size. No adjustments made to alpha levels to acct for multiple 2o endpts. Sample size=83 patients (pts) sufficient to detect statistically significant difference in % change from baseline in 28-day seizure rate with 80% power, true change from baseline approximately 25%.Allowing for dropouts assume 85% pts analyzed.
[2]	Other relevant estimation information:
	113-140 Days. Response ratio=100 x [(t – b)/(t + b)] where t= 4 wk interval seizure frequency and b=baseline seizure frequency.

Statistical Analysis 6 for Percentage Change in Partial Seizure Frequency (All Partial Seizure Types) Between the 8 Week Baseline Period and 4 Week Intervals During the 21 Week Open-label Treatment Period.

Groups ^[1]	Pregabalin
Mean Response Ratio ^[2]	-44.24
Standard Deviation	± 62.703
95% Confidence Interval	( -58.47 to -30.01 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Noncomparative study.Summary stats, 2 sided 95% CI to est. effect size. No adjustments made to alpha levels to acct for multiple 2o endpts. Sample size=83 patients (pts) sufficient to detect statistically significant difference in % change from baseline in 28-day seizure rate with 80% power,true change from baseline approximately 25%.Allowing for dropouts assume 85% pts analyzed.
[2]	Other relevant estimation information:
	>140 Days. Response ratio= 100 x [(t – b)/(t + b)] where t= 4 wk interval seizure frequency and b=baseline seizure frequency.

Measure Type	Secondary
Measure Title	Number of Subjects Seizure-free
Measure Description	Count of subjects seizure free during the period.
Time Frame	last 4 weeks & whole 12 week treatment observation period
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full analysis set(FAS)/intent-to-treat(ITT) all subjects who received >= 1 dose of study Tx & >= 2 partial seizures during baseline pd. LOCF if subjects withdrew then last 4 wks prior to last dose (but after visit 3). 12 wk subjects who withdrew were regarded as missing. n= # subjects evaluable for seizure freedom during defined observation pd.

Reporting Groups

	Description
Pregabalin	Pregabalin treatment, given as 2 divided doses, was initiated at a dose of 150 mg/day (75 mg BID). Then, based on individual subject response and tolerability, the dosage could have been increased to 300 mg/day after 1 week. The dosage could have been incrementally increased further to 600 mg/day after an additional week. After 9 weeks of treatment, the optimal dose of pregabalin was to be maintained for 3 months (12 week treatment observation period).

Description

Pregabalin

Pregabalin treatment, given as 2 divided doses, was initiated at a dose of 150 mg/day (75 mg BID). Then, based on individual subject response and tolerability, the dosage could have been increased to 300 mg/day after 1 week. The dosage could have been incrementally increased further to 600 mg/day after an additional week. After 9 weeks of treatment, the optimal dose of pregabalin was to be maintained for 3 months (12 week treatment observation period).

Measured Values

	Pregabalin
Number of Participants Analyzed [units: participants]	93
Number of Subjects Seizure-free [units: participants]
During 12 week Observation period (n=84)	18
During the last 4 weeks of Obs. period (n=86)	30

No statistical analysis provided for Number of Subjects Seizure-free

Measure Type	Secondary
Measure Title	Reduction in Partial Seizure Frequency Between Baseline and the Final 4 Weeks of the Observation Period.
Measure Description	Number of subjects with at least a 50% or 75% reduction in partial seizure frequency between baseline and treatment period.
Time Frame	8 week baseline observation period & last 4 weeks of observation period
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full analysis set (FAS)/intent-to-treat (ITT) population (all subjects who received at least 1 dose of study treatment & had a minimum of 2 partial seizures during baseline period). Patients who discontinued less than 4 weeks into the observation period (after Visit 3/week 9) will be regarded as missing. No data prior to week 9 will be used.

Reporting Groups

	Description
Pregabalin	Pregabalin treatment, given as 2 divided doses, was initiated at a dose of 150 mg/day (75 mg BID). Then, based on individual subject response and tolerability, the dosage could have been increased to 300 mg/day after 1 week. The dosage could have been incrementally increased further to 600 mg/day after an additional week. After 9 weeks of treatment, the optimal dose of pregabalin was to be maintained for 3 months (12 week treatment observation period).

Description

Pregabalin

Pregabalin treatment, given as 2 divided doses, was initiated at a dose of 150 mg/day (75 mg BID). Then, based on individual subject response and tolerability, the dosage could have been increased to 300 mg/day after 1 week. The dosage could have been incrementally increased further to 600 mg/day after an additional week. After 9 weeks of treatment, the optimal dose of pregabalin was to be maintained for 3 months (12 week treatment observation period).

Measured Values

	Pregabalin
Number of Participants Analyzed [units: participants]	93
Reduction in Partial Seizure Frequency Between Baseline and the Final 4 Weeks of the Observation Period. [units: participants]
>= 50% reduction	42
>= 75% reduction	33

No statistical analysis provided for Reduction in Partial Seizure Frequency Between Baseline and the Final 4 Weeks of the Observation Period.

Measure Type	Secondary
Measure Title	Subjects Achieving Seizure Freedom During Observation Period
Measure Description	Number of subjects achieving seizure freedom (no seizures) during last 4 weeks or duration of 12 week observation period.
Time Frame	Day 147 from the first dose of study drug
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full analysis set (FAS)/intent-to-treat (ITT) population (all subjects who received at least 1 dose of study treatment & had a minimum of 2 partial seizures during baseline period).

Reporting Groups

Description

Pregabalin

Pregabalin treatment, given as 2 divided doses, was initiated at a dose of 150 mg/day (75 mg BID). Then, based on individual subject response and tolerability, the dosage could have been increased to 300 mg/day after 1 week. The dosage could have been incrementally increased further to 600 mg/day after an additional week. After 9 weeks of treatment, the optimal dose of pregabalin was to be maintained for 3 months (12 week treatment observation period).

Measured Values

	Pregabalin
Number of Participants Analyzed [units: participants]	93
Subjects Achieving Seizure Freedom During Observation Period [units: participants]
seizure-free during last 4 weeks	30
seizure-free during 12 weeks	18

No statistical analysis provided for Subjects Achieving Seizure Freedom During Observation Period

Measure Type	Secondary
Measure Title	Change in Partial Seizure Frequency (All Partial Seizure Types) Between Baseline and the 12 Week Observation Period Categorized by Baseline Seizure Frequency
Measure Description	Percentage change from baseline = ((12 weeks - 8 weeks)/8 weeks)*100. Negative mean R-Ratios and associated 95% CIs that do not include zero indicate reduction in partial seizure frequency.
Time Frame	8 week baseline observation period & 12 week treatment observation period
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full analysis set (FAS)/intent-to-treat (ITT) (all subjects who received at least 1 dose of study treatment & minimum 2 partial seizures during baseline pd). Seizure rate was calculated on last observation carried forward (LOCF) basis, whereby data from last 84 days prior to last dose was used to calculate seizure frequency.

Reporting Groups

Description

Pregabalin

Pregabalin treatment, given as 2 divided doses, was initiated at a dose of 150 mg/day (75 mg BID). Then, based on individual subject response and tolerability, the dosage could have been increased to 300 mg/day after 1 week. The dosage could have been incrementally increased further to 600 mg/day after an additional week. After 9 weeks of treatment, the optimal dose of pregabalin was to be maintained for 3 months (12 week treatment observation period).

Measured Values

	Pregabalin
Number of Participants Analyzed [units: participants]	92
Change in Partial Seizure Frequency (All Partial Seizure Types) Between Baseline and the 12 Week Observation Period Categorized by Baseline Seizure Frequency [units: percentage change in events] Median ( Full Range )
Baseline seizure frequency ≤3 per 28 days (n=43)	-33.33 ( -100.00 to 7566.67 )
Baseline seizure frequency >3 per 28 days (n=49)	-21.99 ( -100.00 to 516.09 )

Statistical Analysis 1 for Change in Partial Seizure Frequency (All Partial Seizure Types) Between Baseline and the 12 Week Observation Period Categorized by Baseline Seizure Frequency

Groups ^[1]	Pregabalin
Mean Response Ratio ^[2]	-24.93
Standard Deviation	± 60.867
95% Confidence Interval	( -43.66 to -6.20 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Noncomparative study. Summary stats, 2 sided 95% CI to est. effect size. No adjustments made to alpha levels to acct for multiple 2o endpts. Sample size=83 patients (pts) sufficient to detect statistically significant difference in % change from baseline in 28-day seizure rate with 80% power, true change from baseline approximately 25%. Allowing for dropouts assume 85% pts analyzed.
[2]	Other relevant estimation information:
	Seizure freq. ≤3 / 28 d. Resp. ratio = 100 x [(t – b)/(t + b)] where t=treatment seizure frequency and b=baseline seizure frequency.

Statistical Analysis 2 for Change in Partial Seizure Frequency (All Partial Seizure Types) Between Baseline and the 12 Week Observation Period Categorized by Baseline Seizure Frequency

Groups ^[1]	Pregabalin
Mean Response Ratio ^[2]	-20.78
Standard Deviation	± 50.334
95% Confidence Interval	( -35.24 to -6.33 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Noncomparative study. Summary stats, 2 sided 95% CI to est. effect size. No adjustments made to alpha levels to acct for multiple 2o endpts. Sample size=83 patients (pts) sufficient to detect statistically significant difference in % change from baseline in 28-day seizure rate with 80% power, true change from baseline approximately 25%. Allowing for dropouts assume 85% pts analyzed.
[2]	Other relevant estimation information:
	Seizure freq. >3 / 28 d. Resp. ratio = 100 x [(t – b)/(t + b)] where t=treatment seizure frequency and b=baseline seizure frequency.

Measure Type	Secondary
Measure Title	Impression of Change in Overall Status Using the Patient Global Impression of Change (PGIC)
Measure Description	The PGIC is a patient-rated instrument that measures change in patient’s overall status on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse).
Time Frame	End of 21-week treatment
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full analysis set (FAS)/intent-to-treat (ITT) population (all subjects who received at least 1 dose of study treatment and had a minimum of 2 partial seizures during the baseline period).

Reporting Groups

Description

Pregabalin

Pregabalin treatment, given as 2 divided doses, was initiated at a dose of 150 mg/day (75 mg BID). Then, based on individual subject response and tolerability, the dosage could have been increased to 300 mg/day after 1 week. The dosage could have been incrementally increased further to 600 mg/day after an additional week. After 9 weeks of treatment, the optimal dose of pregabalin was to be maintained for 3 months (12 week treatment observation period).

Measured Values

	Pregabalin
Number of Participants Analyzed [units: participants]	93
Impression of Change in Overall Status Using the Patient Global Impression of Change (PGIC) [units: participants]
Very Much Improved	14
Much Improved	36
Minimally Improved	17
No Change	9
Minimally Worse	3
Much Worse	1
Very Much Worse	0
Missing / Not Done	13

No statistical analysis provided for Impression of Change in Overall Status Using the Patient Global Impression of Change (PGIC)

Measure Type	Secondary
Measure Title	Subjects With Categorical Impression of Change in Overall Status Using the Clinical Global Impression of Change (CGIC)
Measure Description	The CGIC is a clinician’s judgment of the overall change in the patient’s condition over a defined period on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse).
Time Frame	End of 21-week treatment
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full analysis set (FAS)/intent-to-treat (ITT) population (all subjects who received at least 1 dose of study treatment and had a minimum of 2 partial seizures during the baseline period).

Reporting Groups

Description

Pregabalin

Pregabalin treatment, given as 2 divided doses, was initiated at a dose of 150 mg/day (75 mg BID). Then, based on individual subject response and tolerability, the dosage could have been increased to 300 mg/day after 1 week. The dosage could have been incrementally increased further to 600 mg/day after an additional week. After 9 weeks of treatment, the optimal dose of pregabalin was to be maintained for 3 months (12 week treatment observation period).

Measured Values

	Pregabalin
Number of Participants Analyzed [units: participants]	93
Subjects With Categorical Impression of Change in Overall Status Using the Clinical Global Impression of Change (CGIC) [units: partcipants]
Very Much Improved	15
Much Improved	35
Minimally Improved	24
No Change	11
Minimally Worse	4
Much Worse	2
Very Much Worse	0
Missing / Not Done	2

No statistical analysis provided for Subjects With Categorical Impression of Change in Overall Status Using the Clinical Global Impression of Change (CGIC)

Measure Type	Secondary
Measure Title	Changes From Baseline in Medical Outcomes Study (MOS) Sleep Scale Scores
Measure Description	Subjects recall sleep related activities over the previous 4 weeks. Low scores reflect greater impairment (except sleep adequacy, optimal sleep, &quantity). Range = 0 - 100 for Sleep Disturbance, Snoring, Awaken Short of Breath, Sleep Adequacy, Somnolence, & Sleep Problems Index. Quantity of Sleep Range = 0 - 24. Optimal Sleep Range 0 – 1.
Time Frame	Baseline, end of 21-week treatment
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full analysis set (FAS)/intent-to-treat (ITT) population (all subjects who received at least 1 dose of study treatment & had a minimum of 2 partial seizures during baseline period). "n" is the number of subjects contributing to the mean at the specified time point.

Reporting Groups

Description

Pregabalin

Pregabalin treatment, given as 2 divided doses, was initiated at a dose of 150 mg/day (75 mg BID). Then, based on individual subject response and tolerability, the dosage could have been increased to 300 mg/day after 1 week. The dosage could have been incrementally increased further to 600 mg/day after an additional week. After 9 weeks of treatment, the optimal dose of pregabalin was to be maintained for 3 months (12 week treatment observation period).

Measured Values

	Pregabalin
Number of Participants Analyzed [units: participants]	93
Changes From Baseline in Medical Outcomes Study (MOS) Sleep Scale Scores [units: score on scale] Mean ( 95% Confidence Interval )
Sleep Disturbance (n=72)	-3.95 ( -8.83 to 0.94 )
Snoring (n=76)	7.89 ( 1.97 to 13.82 )
Awaken Short of Breath (n=77)	-1.82 ( -5.93 to 2.29 )
Quantity of Sleep (n=66)	0.05 ( -0.33 to 0.42 )
Sleep Adequacy (n=77)	4.29 ( -2.20 to 10.77 )
Somnolence (n=77)	0.52 ( -4.61 to 5.65 )
Sleep Problems Index (n=72)	-2.81 ( -6.50 to 0.88 )

No statistical analysis provided for Changes From Baseline in Medical Outcomes Study (MOS) Sleep Scale Scores

Measure Type	Secondary
Measure Title	Change From Baseline in Hospital Anxiety and Depression Scale(HADS) Depression and Anxiety Symptoms Subscales Between Baseline and Week 21.
Measure Description	Change in total HADS score between Baseline and Week 21. Each of the 14 items is scored 0, 1, 2 or 3 where a score of 3 corresponds to the most anxious/depressed. 7-item depression and 7-item anxiety subscales are summed; each resulting in a total score of 0-21.
Time Frame	Baseline, End of 21-week treatment
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full analysis set (FAS)/intent-to-treat (ITT) population (all subjects who received at least 1 dose of study treatment & had a minimum of 2 partial seizures during baseline period). "n" is the number of subjects contributing to the mean at the specified time point.

Reporting Groups

Description

Pregabalin

Pregabalin treatment, given as 2 divided doses, was initiated at a dose of 150 mg/day (75 mg BID). Then, based on individual subject response and tolerability, the dosage could have been increased to 300 mg/day after 1 week. The dosage could have been incrementally increased further to 600 mg/day after an additional week. After 9 weeks of treatment, the optimal dose of pregabalin was to be maintained for 3 months (12 week treatment observation period).

Measured Values

	Pregabalin
Number of Participants Analyzed [units: participants]	93
Change From Baseline in Hospital Anxiety and Depression Scale(HADS) Depression and Anxiety Symptoms Subscales Between Baseline and Week 21. [units: score on scale] Mean ( 95% Confidence Interval )
HADS Depression Subscale (n=76)	-0.59 ( -1.38 to 0.19 )
HADS Anxiety Subscale (n=76)	-1.68 ( -2.60 to -0.76 )

No statistical analysis provided for Change From Baseline in Hospital Anxiety and Depression Scale(HADS) Depression and Anxiety Symptoms Subscales Between Baseline and Week 21.

Measure Type	Secondary
Measure Title	Number of Subjects With a Weight Gain at End of Treatment of at Least 7% Relative to Baseline
Measure Description	Count of subjects with a weight gain of at least 7 percent relative to baseline.
Time Frame	Baseline, End of 21-week treatment
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Safety population (all subjects who had taken at least

1 dose of study drug).

Reporting Groups

Description

Pregabalin

Pregabalin treatment, given as 2 divided doses, was initiated at a dose of 150 mg/day (75 mg BID). Then, based on individual subject response and tolerability, the dosage could have been increased to 300 mg/day after 1 week. The dosage could have been incrementally increased further to 600 mg/day after an additional week. After 9 weeks of treatment, the optimal dose of pregabalin was to be maintained for 3 months (12 week treatment observation period).

Measured Values

	Pregabalin
Number of Participants Analyzed [units: participants]	98
Number of Subjects With a Weight Gain at End of Treatment of at Least 7% Relative to Baseline [units: participants]
Weight gain ≥7% to <10%	8
Weight gain ≥10% to <15%	2
Weight gain ≥15% to <20%	2
Weight gain ≥20%	1

No statistical analysis provided for Number of Subjects With a Weight Gain at End of Treatment of at Least 7% Relative to Baseline

Measure Type	Secondary
Measure Title	Subjects Assessment of Optimal Sleep
Measure Description	Number of subjects that responded optimal or non-optimal sleep in Optimal Sleep subscale of Medical Outcomes Study (MOS) Sleep scale.
Time Frame	Baseline, End of 21-week treatment
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full analysis set (FAS)/intent-to-treat (ITT) population (all subjects who received at least 1 dose of study treatment & had a minimum of 2 partial seizures during baseline period).

Reporting Groups

Description

Pregabalin

Pregabalin treatment, given as 2 divided doses, was initiated at a dose of 150 mg/day (75 mg BID). Then, based on individual subject response and tolerability, the dosage could have been increased to 300 mg/day after 1 week. The dosage could have been incrementally increased further to 600 mg/day after an additional week. After 9 weeks of treatment, the optimal dose of pregabalin was to be maintained for 3 months (12 week treatment observation period).

Measured Values

	Pregabalin
Number of Participants Analyzed [units: participants]	93
Subjects Assessment of Optimal Sleep [units: participants]
Optimal Sleep Baseline, Optimal Sleep Wk21	21
Optimal Sleep Baseline, Non-Optimal Sleep Wk21	8
Non-Optimal Sleep Baseline, Optimal Sleep Wk21	12
Non-Optimal Sleep Baseline, Non-Optimal Sleep Wk21	25

No statistical analysis provided for Subjects Assessment of Optimal Sleep

Measure Type	Post-Hoc
Measure Title	Change in Partial Seizure Frequency by Type Between the 8 Week Baseline Period and During the 12 Week Observation Period.
Measure Description	Change from baseline = 12 week treatment observation period seizure frequency rate minus 8 week baseline period seizure frequency rate.
Time Frame	8 week baseline period & 12 week treatment observation period
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full analysis set (FAS)/intent-to-treat (ITT) population (all subjects who received at least 1 dose of study treatment & had a minimum of 2 partial seizures during baseline period). Seizure rate was calculated on last observation carried forward (LOCF) basis, whereby data from last 84 days prior to last dose was used to calculate seizure frequency.

Reporting Groups

Description

Pregabalin

Pregabalin treatment, given as 2 divided doses, was initiated at a dose of 150 mg/day (75 mg BID). Then, based on individual subject response and tolerability, the dosage could have been increased to 300 mg/day after 1 week. The dosage could have been incrementally increased further to 600 mg/day after an additional week. After 9 weeks of treatment, the optimal dose of pregabalin was to be maintained for 3 months (12 week treatment observation period).

Measured Values

	Pregabalin
Number of Participants Analyzed [units: participants]	92
Change in Partial Seizure Frequency by Type Between the 8 Week Baseline Period and During the 12 Week Observation Period. [units: change in median partial seizures] Median ( Full Range )
Simple Partial Seizures (n=47)	0.00 ( -15.50 to 149.67 )
Complex Partial Seizures (n=76)	0.00 ( -16.33 to 114.67 )
Evolve to Secondary Generalized (n=30)	0.00 ( -2.67 to 9.04 )

Statistical Analysis 1 for Change in Partial Seizure Frequency by Type Between the 8 Week Baseline Period and During the 12 Week Observation Period.

Groups ^[1]	Pregabalin
Mean Response Ratio ^[2]	7.19
Standard Deviation	± 84.425
95% Confidence Interval	( -17.60 to 31.98 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Noncomparative study. Summary stats, 2 sided 95% CI to est. effect size. No adjustments made to alpha levels to acct for multiple 2o endpts. Sample size=83 patients (pts) sufficient to detect statistically significant difference in % change from baseline in 28-day seizure rate with 80% power, true change from baseline approximately 25%. Allowing for dropouts assume 85% pts analyzed.
[2]	Other relevant estimation information:
	Simple Partial Seizures. Response ratio = 100 x [(t – b)/(t + b)] where t=treatment seizure frequency and b=baseline seizure frequency.

Statistical Analysis 2 for Change in Partial Seizure Frequency by Type Between the 8 Week Baseline Period and During the 12 Week Observation Period.

Groups ^[1]	Pregabalin
Mean Response Ratio ^[2]	-22.24
Standard Deviation	± 68.058
95% Confidence Interval	( -37.80 to -6.69 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Noncomparative study. Summary stats, 2 sided 95% CI to est. effect size. No adjustments made to alpha levels to acct for multiple 2o endpts. Sample size=83 patients (pts) sufficient to detect statistically significant difference in % change from baseline in 28-day seizure rate with 80% power, true change from baseline approximately 25%. Allowing for dropouts assume 85% pts analyzed.
[2]	Other relevant estimation information:
	Complex Partial Seizures. Response ratio = 100 x [(t – b)/(t + b)] where t=treatment seizure frequency and b=baseline seizure frequency.

Statistical Analysis 3 for Change in Partial Seizure Frequency by Type Between the 8 Week Baseline Period and During the 12 Week Observation Period.

Groups ^[1]	Pregabalin
Mean Response Ratio ^[2]	-23.85
Standard Deviation	± 84.313
95% Confidence Interval	( -55.33 to 7.64 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Noncomparative study. Summary stats, 2 sided 95% CI to est. effect size. No adjustments made to alpha levels to acct for multiple 2o endpts. Sample size=83 patients (pts) sufficient to detect statistically significant difference in % change from baseline in 28-day seizure rate with 80% power, true change from baseline approximately 25%. Allowing for dropouts assume 85% pts analyzed.
[2]	Other relevant estimation information:
	Evolved to Generalized. Response ratio = 100 x [(t – b)/(t + b)] where t=treatment seizure frequency and b=baseline seizure frequency.

Responsible Party:	Clinical Trials Disclosure Group, Pfizer, Inc.
ClinicalTrials.gov Identifier:	NCT00288639 History of Changes
Other Study ID Numbers:	A0081088
Study First Received:	February 7, 2006
Results First Received:	December 16, 2008
Last Updated:	August 28, 2009
Health Authority:	Greece: National Organization of Medicines