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

This study has been completed.
Sponsor:
Information provided by:
Pfizer
ClinicalTrials.gov Identifier:
NCT00288639
First received: February 7, 2006
Last updated: August 28, 2009
Last verified: August 2009
Results First Received: December 16, 2008  
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

  Participant Flow
  Hide Participant Flow

Recruitment Details
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.

Pre-Assignment Details
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.

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).

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



  Baseline Characteristics
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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.
No text entered.

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).

Baseline Measures
    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  



  Outcome Measures
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1.  Primary:   Percentage Change in Partial Seizure Frequency (All Partial Seizure Types) Between Baseline and the 12 Week Observation Period   [ Time Frame: 8 week baseline period & 12 week treatment observation period ]

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).

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.



2.  Secondary:   Percentage Change in Partial Seizure Frequency (All Partial Seizure Types) Between Baseline and the Whole 21 Week Open-label Treatment Period.   [ Time Frame: 8 week baseline period and 21 week treatment period ]

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).

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.



3.  Secondary:   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.   [ Time Frame: 8 week baseline period and 21 week treatment period ]

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).

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.



4.  Secondary:   Number of Subjects Seizure-free   [ Time Frame: last 4 weeks & whole 12 week treatment observation period ]

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).

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



5.  Secondary:   Reduction in Partial Seizure Frequency Between Baseline and the Final 4 Weeks of the Observation Period.   [ Time Frame: 8 week baseline observation period & last 4 weeks of observation period ]

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).

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.



6.  Secondary:   Subjects Achieving Seizure Freedom During Observation Period   [ Time Frame: Day 147 from the first dose of study drug ]

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



7.  Secondary:   Change in Partial Seizure Frequency (All Partial Seizure Types) Between Baseline and the 12 Week Observation Period Categorized by Baseline Seizure Frequency   [ Time Frame: 8 week baseline observation period & 12 week treatment 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.



8.  Secondary:   Impression of Change in Overall Status Using the Patient Global Impression of Change (PGIC)   [ Time Frame: End of 21-week treatment ]

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)



9.  Secondary:   Subjects With Categorical Impression of Change in Overall Status Using the Clinical Global Impression of Change (CGIC)   [ Time Frame: End of 21-week treatment ]

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)



10.  Secondary:   Changes From Baseline in Medical Outcomes Study (MOS) Sleep Scale Scores   [ Time Frame: Baseline, end of 21-week treatment ]

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



11.  Secondary:   Change From Baseline in Hospital Anxiety and Depression Scale(HADS) Depression and Anxiety Symptoms Subscales Between Baseline and Week 21.   [ Time Frame: Baseline, End of 21-week treatment ]

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.



12.  Secondary:   Number of Subjects With a Weight Gain at End of Treatment of at Least 7% Relative to Baseline   [ Time Frame: Baseline, End of 21-week treatment ]

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



13.  Secondary:   Subjects Assessment of Optimal Sleep   [ Time Frame: Baseline, End of 21-week treatment ]

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



14.  Post-Hoc:   Change in Partial Seizure Frequency by Type Between the 8 Week Baseline Period and During the 12 Week Observation Period.   [ Time Frame: 8 week baseline period & 12 week treatment observation period ]

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.




  Serious Adverse Events


  Other Adverse Events


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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Limitations and Caveats
Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.  


Results Point of Contact:  
Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
phone: 1-800-718-1021
e-mail: ClinicalTrials.govCallCenter@pfizer.com


No publications provided


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