Epilepsy, Partial
Conditions
Keywords
Epilepsy, partial seizures, pregabalin monotherapy, lamotrigine comparator, double-blind and randomized trial
Brief summary
The purpose of this study is to assess whether Lyrica is a safe and effective treatment for partial epilepsy in comparison with an established treatment, Lamictal.
Interventions
DRUGPregabalin
dose 150-600 mg/day given BID
DRUGLamotrigine
dose 100-500 mg/day given BID
Sponsors
Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients must be diagnosed with partial epilepsy and have experienced at least 2 partial seizures (simple partial, complex partial or partial seizure with secondary generalization) in the past year with one in the past 6 months.
Exclusion criteria
* Treatable causes of seizures, for example identified etiologies including metabolic, neoplastic or active infectious origin. * Primary generalized seizures.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Seizure-free Participants (Responders) During Efficacy Assessment Phase | Week 5 up to Week 56 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Median Monthy Seizure Frequency: All Seizures | Baseline up to Week 60 | 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). |
| Exit Due to Adverse Events During the Double-blind Treatment Phase (Including Dose Escalation Phase) | Week 0 to Week 56 | 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. |
| Exit for Any Reason During the Double-blind Treatment Phase (Including Dose Escalation Phase) | Week 0 to Week 56 | 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. |
| Exit Due to Lack of Efficacy After 4-week Dose Escalation Phase | Week 4 up to Week 56 | 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. |
| Mean Monthy Seizure Frequency: All Seizures | Baseline up to Week 60 | 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). |
| Exit Due to Any Reason After 4-week Dose Escalation Phase | Week 4 up to Week 56 | 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. |
| Time to First Seizure After the 4-Week Dose Escalation Phase | Week 4 up to Week 56 | 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. |
| Median Monthy Seizure Frequency: All Partial Seizures | Baseline up to Week 60 | 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). |
| Time to 6 Consecutive Months of Seizure-freedom After 4-week Dose Escalation Phase: All Seizures | Week 4 up to Week 56 | 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. |
| Median Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Partial Seizures | Month 1 through Month 9 (after 6 months seizure freedom achieved) | 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. |
| Mean Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Partial Seizures | Month 1 through Month 9 (after 6 months seizure freedom achieved) | 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. |
| Median Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Seizures | Month 1 through Month 9 (after 6 months seizure freedom achieved) | 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. |
| Mean Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Seizures | Month 1 through Month 9 (after 6 months seizure freedom achieved) | 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. |
| Percentage of Participants Who Achieved at Least 6 Consecutive Months of Seizure Freedom (Responders) by Final Dosage Levels and Treatment Group | Week 5 up to Week 56 | 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. |
| Change From Baseline to Week 56 in Hospital Anxiety and Depression Scale (HADS) | Baseline to Week 56 | Participant rated questionnaire with 2 subscales. HADS-A assesses state of generalized anxiety (anxious mood, restlessness, anxious thoughts, panic attacks); HADS-D assesses state of lost interest and diminished pleasure response (lowering of hedonic tone). Each subscale comprised of 7 items; range: 0 (no presence of anxiety or depression) to 3 (severe feeling of anxiety or depression). Total score 0 to 21 for each subscale; higher score indicates greater severity of symptoms. Scores relative to start of randomized treatment. |
| Medical Outcomes Study Sleep Scale (MOS-SS): Optimal Sleep Subscale | Week 8, Week 32, and Week 56 | 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. |
| Mean Monthy Seizure Frequency: All Partial Seizures | Baseline up to Week 60 | 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). |
Countries
Belgium, Bulgaria, China, Colombia, Czechia, Estonia, Finland, France, Germany, Hong Kong, Hungary, India, Ireland, Italy, Latvia, Lithuania, Mexico, Netherlands, Norway, Portugal, Romania, Singapore, Slovakia, South Korea, Spain, Sweden, Taiwan, Thailand, United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 330 |
| 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. | 330 |
| Total | 660 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Efficacy Assessment Phase | Adverse Event | 33 | 31 |
| Efficacy Assessment Phase | Death | 2 | 0 |
| Efficacy Assessment Phase | Laboratory abnormaility | 1 | 0 |
| Efficacy Assessment Phase | Lack of Efficacy | 19 | 3 |
| Efficacy Assessment Phase | Lost to Follow-up | 6 | 13 |
| Efficacy Assessment Phase | Other | 7 | 8 |
| Efficacy Assessment Phase | Withdrawal by Subject | 26 | 25 |
Baseline characteristics
| Characteristic | Pregabalin | Lamotrigine | Total |
|---|---|---|---|
| Age, Customized < 18 years | 9 participants | 9 participants | 18 participants |
| Age, Customized >= 65 years | 14 participants | 19 participants | 33 participants |
| Age, Customized Between 18 and 44 years | 228 participants | 228 participants | 456 participants |
| Age, Customized Between 45 and 64 years | 79 participants | 74 participants | 153 participants |
| Sex: Female, Male Female | 165 Participants | 146 Participants | 311 Participants |
| Sex: Female, Male Male | 165 Participants | 184 Participants | 349 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 186 / 330 | 171 / 330 |
| serious Total, serious adverse events | 44 / 330 | 32 / 330 |
Outcome results
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.
Time frame: Week 5 up to Week 56
Population: Full analysis set (FAS) (intent to treat population): randomized participants who took at least 1 dose of study medication. N = number of participants who had at least 1 dose of study treatment and seizure efficacy data. Analysis excludes participants who did not enter maintenance phase of study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pregabalin | Percentage of Seizure-free Participants (Responders) During Efficacy Assessment Phase | 51.6 percentage of participants |
| Lamotrigine | Percentage of Seizure-free Participants (Responders) During Efficacy Assessment Phase | 67.9 percentage of participants |
Comparison: 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 100.95% CI: [-0.24, -0.09]Gart and Nam: correction of skewness
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.
Time frame: Baseline to Week 56
Population: FAS; N = number of participants with a HADS measurement at baseline and Week 56.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin | Change From Baseline to Week 56 in Hospital Anxiety and Depression Scale (HADS) | Anxiety | -0.3 scores on scale | Standard Error 0.25 |
| Pregabalin | Change From Baseline to Week 56 in Hospital Anxiety and Depression Scale (HADS) | Depression | -0.1 scores on scale | Standard Error 0.23 |
| Lamotrigine | Change From Baseline to Week 56 in Hospital Anxiety and Depression Scale (HADS) | Anxiety | -1.1 scores on scale | Standard Error 0.25 |
| Lamotrigine | Change From Baseline to Week 56 in Hospital Anxiety and Depression Scale (HADS) | Depression | -0.7 scores on scale | Standard Error 0.23 |
Comparison: Anxiety; model includes treatment and geographical cluster as fixed effects and respective baseline scores as a continuous covariate.p-value: 0.002595% CI: [0.3, 1.4]ANCOVA
Comparison: Depression; model includes treatment and geographical cluster as fixed effects and respective baseline scores as a continuous covariate.p-value: 0.018695% CI: [0.1, 1.1]ANCOVA
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.
Time frame: Week 0 to Week 56
Population: FAS. N = number of participants who entered maintenance phase of study and had seizure efficacy data. Time to exit due to adverse events was inestimable as survival estimate at end of maintenance phase was below 0.500.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pregabalin | Exit Due to Adverse Events During the Double-blind Treatment Phase (Including Dose Escalation Phase) | 33 participants |
| Lamotrigine | Exit Due to Adverse Events During the Double-blind Treatment Phase (Including Dose Escalation Phase) | 31 participants |
Comparison: 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.p-value: 0.804795% CI: [0.65, 1.74]Cox proportional hazards model
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.
Time frame: Week 4 up to Week 56
Population: FAS. N = number of participants who entered maintenance phase of study and had seizure efficacy data. Time to exit for any reason after the 4-week dose escalation phase was inestimable as the survival estimate at the end of the maintenance phase was below 0.500.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pregabalin | Exit Due to Any Reason After 4-week Dose Escalation Phase | 78 participants |
| Lamotrigine | Exit Due to Any Reason After 4-week Dose Escalation Phase | 58 participants |
Comparison: 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.p-value: 0.074495% CI: [0.97, 1.91]Cox proportional hazards model
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.
Time frame: Week 4 up to Week 56
Population: FAS. N = number of participants who entered maintenance phase of study and had seizure efficacy data. Time to exit due to lack of efficacy after 4-week dose escalation phase was inestimable as survival estimate at end of maintenance phase was below 0.500.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pregabalin | Exit Due to Lack of Efficacy After 4-week Dose Escalation Phase | 78 participants |
| Lamotrigine | Exit Due to Lack of Efficacy After 4-week Dose Escalation Phase | 58 participants |
Comparison: 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.p-value: 0.002595% CI: [1.93, 22.04]Cox proportional hazards model
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.
Time frame: Week 0 to Week 56
Population: FAS. N = number of participants who had at least 1 dose of study treatment and seizure efficacy data Time to exit for any reason during the double-blind treatment phase was inestimable as the survival estimate at the end of the maintenance phase was below 0.500.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pregabalin | Exit for Any Reason During the Double-blind Treatment Phase (Including Dose Escalation Phase) | 94 participants |
| Lamotrigine | Exit for Any Reason During the Double-blind Treatment Phase (Including Dose Escalation Phase) | 80 participants |
Comparison: 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.p-value: 0.253795% CI: [0.88, 1.6]Cox proportional hazards model
Secondary
Mean 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).
Time frame: Baseline up to Week 60
Population: FAS. N = number of participants with analyzable data; n = number of participants with analyzable data at observation.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin | Mean Monthy Seizure Frequency: All Partial Seizures | Month 4 (n=279, 278) | 0.89 seizures/28 days | Standard Deviation 2.313 |
| Pregabalin | Mean Monthy Seizure Frequency: All Partial Seizures | Month 8 (n=256, 266) | 0.77 seizures/28 days | Standard Deviation 3.247 |
| Pregabalin | Mean Monthy Seizure Frequency: All Partial Seizures | Month 1 (n=314, 308) | 2.23 seizures/28 days | Standard Deviation 6.139 |
| Pregabalin | Mean Monthy Seizure Frequency: All Partial Seizures | Month 9 (n=253, 262) | 0.71 seizures/28 days | Standard Deviation 2.538 |
| Pregabalin | Mean Monthy Seizure Frequency: All Partial Seizures | Month 5 (n=274, 276) | 0.78 seizures/28 days | Standard Deviation 2.27 |
| Pregabalin | Mean Monthy Seizure Frequency: All Partial Seizures | Month 10 (n=250, 257) | 1.05 seizures/28 days | Standard Deviation 4.935 |
| Pregabalin | Mean Monthy Seizure Frequency: All Partial Seizures | Month 3 (n=287, 288) | 0.94 seizures/28 days | Standard Deviation 2.568 |
| Pregabalin | Mean Monthy Seizure Frequency: All Partial Seizures | Month 11 (n=242, 254) | 0.79 seizures/28 days | Standard Deviation 3.082 |
| Pregabalin | Mean Monthy Seizure Frequency: All Partial Seizures | Month 6 (n=266, 272) | 0.82 seizures/28 days | Standard Deviation 2.702 |
| Pregabalin | Mean Monthy Seizure Frequency: All Partial Seizures | Month 12 (n=238, 252) | 0.94 seizures/28 days | Standard Deviation 7.018 |
| Pregabalin | Mean Monthy Seizure Frequency: All Partial Seizures | Month 2 (n=300, 295) | 1.18 seizures/28 days | Standard Deviation 3.382 |
| Pregabalin | Mean Monthy Seizure Frequency: All Partial Seizures | Month 13 (n=210, 227) | 0.65 seizures/28 days | Standard Deviation 3.247 |
| Pregabalin | Mean Monthy Seizure Frequency: All Partial Seizures | Month 7 (n=260, 270) | 0.78 seizures/28 days | Standard Deviation 2.839 |
| Pregabalin | Mean Monthy Seizure Frequency: All Partial Seizures | Taper (n=71, 45) | 2.13 seizures/28 days | Standard Deviation 6.418 |
| Pregabalin | Mean Monthy Seizure Frequency: All Partial Seizures | Dose escalation phase (n=329, 330) | 2.56 seizures/28 days | Standard Deviation 9.348 |
| Lamotrigine | Mean Monthy Seizure Frequency: All Partial Seizures | Taper (n=71, 45) | 19.97 seizures/28 days | Standard Deviation 97.196 |
| Lamotrigine | Mean Monthy Seizure Frequency: All Partial Seizures | Dose escalation phase (n=329, 330) | 5.08 seizures/28 days | Standard Deviation 27.118 |
| Lamotrigine | Mean Monthy Seizure Frequency: All Partial Seizures | Month 1 (n=314, 308) | 4.21 seizures/28 days | Standard Deviation 31.453 |
| Lamotrigine | Mean Monthy Seizure Frequency: All Partial Seizures | Month 2 (n=300, 295) | 3.21 seizures/28 days | Standard Deviation 28.839 |
| Lamotrigine | Mean Monthy Seizure Frequency: All Partial Seizures | Month 3 (n=287, 288) | 3.54 seizures/28 days | Standard Deviation 32.783 |
| Lamotrigine | Mean Monthy Seizure Frequency: All Partial Seizures | Month 4 (n=279, 278) | 1.67 seizures/28 days | Standard Deviation 16.046 |
| Lamotrigine | Mean Monthy Seizure Frequency: All Partial Seizures | Month 5 (n=274, 276) | 1.58 seizures/28 days | Standard Deviation 15.254 |
| Lamotrigine | Mean Monthy Seizure Frequency: All Partial Seizures | Month 6 (n=266, 272) | 1.41 seizures/28 days | Standard Deviation 15.126 |
| Lamotrigine | Mean Monthy Seizure Frequency: All Partial Seizures | Month 7 (n=260, 270) | 1.50 seizures/28 days | Standard Deviation 16.855 |
| Lamotrigine | Mean Monthy Seizure Frequency: All Partial Seizures | Month 8 (n=256, 266) | 1.36 seizures/28 days | Standard Deviation 19.111 |
| Lamotrigine | Mean Monthy Seizure Frequency: All Partial Seizures | Month 9 (n=253, 262) | 1.38 seizures/28 days | Standard Deviation 17.204 |
| Lamotrigine | Mean Monthy Seizure Frequency: All Partial Seizures | Month 10 (n=250, 257) | 1.33 seizures/28 days | Standard Deviation 16.905 |
| Lamotrigine | Mean Monthy Seizure Frequency: All Partial Seizures | Month 11 (n=242, 254) | 1.41 seizures/28 days | Standard Deviation 19.268 |
| Lamotrigine | Mean Monthy Seizure Frequency: All Partial Seizures | Month 12 (n=238, 252) | 1.67 seizures/28 days | Standard Deviation 19.59 |
| Lamotrigine | Mean Monthy Seizure Frequency: All Partial Seizures | Month 13 (n=210, 227) | 2.11 seizures/28 days | Standard Deviation 19.462 |
Secondary
Mean 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).
Time frame: Baseline up to Week 60
Population: FAS. N = number of participants with analyzable data; n = number of participants with analyzable data at observation.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin | Mean Monthy Seizure Frequency: All Seizures | Month 7 (n=260, 270) | 0.83 seizures/28 days | Standard Deviation 2.898 |
| Pregabalin | Mean Monthy Seizure Frequency: All Seizures | Dose-escalation phase (n=329, 330) | 2.74 seizures/28 days | Standard Deviation 9.819 |
| Pregabalin | Mean Monthy Seizure Frequency: All Seizures | Month 8 (n=256, 266) | 0.82 seizures/28 days | Standard Deviation 3.304 |
| Pregabalin | Mean Monthy Seizure Frequency: All Seizures | Month 4 (n=279, 278) | 1.06 seizures/28 days | Standard Deviation 3.223 |
| Pregabalin | Mean Monthy Seizure Frequency: All Seizures | Month 9 (n=253, 262) | 0.78 seizures/28 days | Standard Deviation 2.636 |
| Pregabalin | Mean Monthy Seizure Frequency: All Seizures | Month 2 (n=300, 295) | 1.53 seizures/28 days | Standard Deviation 5.498 |
| Pregabalin | Mean Monthy Seizure Frequency: All Seizures | Month 10 (n=250, 257) | 1.06 seizures/28 days | Standard Deviation 4.934 |
| Pregabalin | Mean Monthy Seizure Frequency: All Seizures | Month 5 (n=274, 276) | 0.87 seizures/28 days | Standard Deviation 2.458 |
| Pregabalin | Mean Monthy Seizure Frequency: All Seizures | Month 11 (n=242, 254) | 0.81 seizures/28 days | Standard Deviation 3.224 |
| Pregabalin | Mean Monthy Seizure Frequency: All Seizures | Month 1 (n=314, 308) | 2.31 seizures/28 days | Standard Deviation 6.164 |
| Pregabalin | Mean Monthy Seizure Frequency: All Seizures | Month 12 (n=238, 252) | 0.96 seizures/28 days | Standard Deviation 7.019 |
| Pregabalin | Mean Monthy Seizure Frequency: All Seizures | Month 6 (n=266, 272) | 0.89 seizures/28 days | Standard Deviation 2.853 |
| Pregabalin | Mean Monthy Seizure Frequency: All Seizures | Month 13 (n=210, 227) | 0.65 seizures/28 days | Standard Deviation 3.247 |
| Pregabalin | Mean Monthy Seizure Frequency: All Seizures | Taper (n=71, 45) | 2.13 seizures/28 days | Standard Deviation 6.418 |
| Pregabalin | Mean Monthy Seizure Frequency: All Seizures | Month 3 (n=287, 288) | 1.02 seizures/28 days | Standard Deviation 2.702 |
| Lamotrigine | Mean Monthy Seizure Frequency: All Seizures | Taper (n=71, 45) | 19.97 seizures/28 days | Standard Deviation 97.196 |
| Lamotrigine | Mean Monthy Seizure Frequency: All Seizures | Dose-escalation phase (n=329, 330) | 5.10 seizures/28 days | Standard Deviation 27.128 |
| Lamotrigine | Mean Monthy Seizure Frequency: All Seizures | Month 1 (n=314, 308) | 4.24 seizures/28 days | Standard Deviation 31.452 |
| Lamotrigine | Mean Monthy Seizure Frequency: All Seizures | Month 2 (n=300, 295) | 3.22 seizures/28 days | Standard Deviation 28.838 |
| Lamotrigine | Mean Monthy Seizure Frequency: All Seizures | Month 3 (n=287, 288) | 3.57 seizures/28 days | Standard Deviation 32.782 |
| Lamotrigine | Mean Monthy Seizure Frequency: All Seizures | Month 4 (n=279, 278) | 1.68 seizures/28 days | Standard Deviation 16.046 |
| Lamotrigine | Mean Monthy Seizure Frequency: All Seizures | Month 5 (n=274, 276) | 1.59 seizures/28 days | Standard Deviation 15.254 |
| Lamotrigine | Mean Monthy Seizure Frequency: All Seizures | Month 6 (n=266, 272) | 1.41 seizures/28 days | Standard Deviation 15.126 |
| Lamotrigine | Mean Monthy Seizure Frequency: All Seizures | Month 7 (n=260, 270) | 1.50 seizures/28 days | Standard Deviation 16.855 |
| Lamotrigine | Mean Monthy Seizure Frequency: All Seizures | Month 8 (n=256, 266) | 1.37 seizures/28 days | Standard Deviation 19.11 |
| Lamotrigine | Mean Monthy Seizure Frequency: All Seizures | Month 9 (n=253, 262) | 1.38 seizures/28 days | Standard Deviation 17.204 |
| Lamotrigine | Mean Monthy Seizure Frequency: All Seizures | Month 10 (n=250, 257) | 1.33 seizures/28 days | Standard Deviation 16.905 |
| Lamotrigine | Mean Monthy Seizure Frequency: All Seizures | Month 11 (n=242, 254) | 1.41 seizures/28 days | Standard Deviation 19.268 |
| Lamotrigine | Mean Monthy Seizure Frequency: All Seizures | Month 12 (n=238, 252) | 1.67 seizures/28 days | Standard Deviation 19.59 |
| Lamotrigine | Mean Monthy Seizure Frequency: All Seizures | Month 13 (n=210, 227) | 2.12 seizures/28 days | Standard Deviation 19.462 |
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.
Time frame: Month 1 through Month 9 (after 6 months seizure freedom achieved)
Population: FAS. N = number of responders; n = number of responders with analyzable data at observation.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin | Mean Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Partial Seizures | Month 2 (n=155, 194) | 0.28 28-day seizure rate | Standard Deviation 1.783 |
| Pregabalin | Mean Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Partial Seizures | Month 6 (n=122, 152) | 0.02 28-day seizure rate | Standard Deviation 0.156 |
| Pregabalin | Mean Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Partial Seizures | Month 4 (n=139, 173) | 0.09 28-day seizure rate | Standard Deviation 0.329 |
| Pregabalin | Mean Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Partial Seizures | Month 7 (n=105, 136) | 0.00 28-day seizure rate | Standard Deviation 0 |
| Pregabalin | Mean Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Partial Seizures | Month 3 (n=147, 184) | 0.05 28-day seizure rate | Standard Deviation 0.384 |
| Pregabalin | Mean Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Partial Seizures | Month 8 (n=1, 5) | 0.00 28-day seizure rate | — |
| Pregabalin | Mean Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Partial Seizures | Month 5 (n=127, 158) | 0.15 28-day seizure rate | Standard Deviation 0.926 |
| Pregabalin | Mean Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Partial Seizures | Month 9 (n=0, 1) | NA 28-day seizure rate | — |
| Pregabalin | Mean Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Partial Seizures | Month 1 (n=162, 208) | 0.19 28-day seizure rate | Standard Deviation 1 |
| Lamotrigine | Mean Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Partial Seizures | Month 9 (n=0, 1) | 6.00 28-day seizure rate | — |
| Lamotrigine | Mean Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Partial Seizures | Month 1 (n=162, 208) | 0.04 28-day seizure rate | Standard Deviation 0.226 |
| Lamotrigine | Mean Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Partial Seizures | Month 2 (n=155, 194) | 0.03 28-day seizure rate | Standard Deviation 0.226 |
| Lamotrigine | Mean Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Partial Seizures | Month 3 (n=147, 184) | 0.07 28-day seizure rate | Standard Deviation 0.439 |
| Lamotrigine | Mean Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Partial Seizures | Month 4 (n=139, 173) | 0.05 28-day seizure rate | Standard Deviation 0.211 |
| Lamotrigine | Mean Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Partial Seizures | Month 5 (n=127, 158) | 0.10 28-day seizure rate | Standard Deviation 0.823 |
| Lamotrigine | Mean Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Partial Seizures | Month 6 (n=122, 152) | 0.03 28-day seizure rate | Standard Deviation 0.213 |
| Lamotrigine | Mean Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Partial Seizures | Month 7 (n=105, 136) | 0.28 28-day seizure rate | Standard Deviation 2.843 |
| Lamotrigine | Mean Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Partial Seizures | Month 8 (n=1, 5) | 0.00 28-day seizure rate | Standard Deviation 0 |
Secondary
Mean 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.
Time frame: Month 1 through Month 9 (after 6 months seizure freedom achieved)
Population: FAS. N = number of responders; n = number of responders with analyzable data at observation.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin | Mean Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Seizures | Month 2 (n=155, 194) | 0.28 28-day seizure rate | Standard Deviation 1.783 |
| Pregabalin | Mean Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Seizures | Month 6 (n=122, 152) | 0.02 28-day seizure rate | Standard Deviation 0.156 |
| Pregabalin | Mean Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Seizures | Month 4 (n=139, 173) | 0.09 28-day seizure rate | Standard Deviation 0.359 |
| Pregabalin | Mean Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Seizures | Month 7 (n=105, 136) | 0.00 28-day seizure rate | Standard Deviation 0 |
| Pregabalin | Mean Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Seizures | Month 3 (n=147, 184) | 0.07 28-day seizure rate | Standard Deviation 0.4 |
| Pregabalin | Mean Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Seizures | Month 8 (n=1, 5) | 0.00 28-day seizure rate | — |
| Pregabalin | Mean Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Seizures | Month 5 (n=127, 158) | 0.18 28-day seizure rate | Standard Deviation 0.971 |
| Pregabalin | Mean Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Seizures | Month 9 (n=0, 1) | NA 28-day seizure rate | — |
| Pregabalin | Mean Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Seizures | Month 1 (n=162, 208) | 0.19 28-day seizure rate | Standard Deviation 1 |
| Lamotrigine | Mean Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Seizures | Month 9 (n=0, 1) | 6.00 28-day seizure rate | — |
| Lamotrigine | Mean Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Seizures | Month 1 (n=162, 208) | 0.05 28-day seizure rate | Standard Deviation 0.236 |
| Lamotrigine | Mean Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Seizures | Month 2 (n=155, 194) | 0.03 28-day seizure rate | Standard Deviation 0.226 |
| Lamotrigine | Mean Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Seizures | Month 3 (n=147, 184) | 0.07 28-day seizure rate | Standard Deviation 0.439 |
| Lamotrigine | Mean Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Seizures | Month 4 (n=139, 173) | 0.05 28-day seizure rate | Standard Deviation 0.211 |
| Lamotrigine | Mean Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Seizures | Month 5 (n=127, 158) | 0.10 28-day seizure rate | Standard Deviation 0.823 |
| Lamotrigine | Mean Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Seizures | Month 6 (n=122, 152) | 0.03 28-day seizure rate | Standard Deviation 0.213 |
| Lamotrigine | Mean Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Seizures | Month 7 (n=105, 136) | 0.29 28-day seizure rate | Standard Deviation 2.844 |
| Lamotrigine | Mean Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Seizures | Month 8 (n=1, 5) | 0.00 28-day seizure rate | Standard Deviation 0 |
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).
Time frame: Baseline up to Week 60
Population: FAS. N = number of participants with analyzable data; n = number of participants with analyzable data at observation.
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin | Median Monthy Seizure Frequency: All Partial Seizures | Month 4 (n=279, 278) | 0.0 seizures/28 days | Standard Deviation 2.313 |
| Pregabalin | Median Monthy Seizure Frequency: All Partial Seizures | Month 8 (n=256, 266) | 0.0 seizures/28 days | Standard Deviation 3.247 |
| Pregabalin | Median Monthy Seizure Frequency: All Partial Seizures | Month 1 (n=314, 308) | 0.0 seizures/28 days | Standard Deviation 6.139 |
| Pregabalin | Median Monthy Seizure Frequency: All Partial Seizures | Month 9 (n=253, 262) | 0.0 seizures/28 days | Standard Deviation 2.538 |
| Pregabalin | Median Monthy Seizure Frequency: All Partial Seizures | Month 5 (n=274, 276) | 0.0 seizures/28 days | Standard Deviation 2.27 |
| Pregabalin | Median Monthy Seizure Frequency: All Partial Seizures | Month 10 (n=250, 257) | 0.0 seizures/28 days | Standard Deviation 4.935 |
| Pregabalin | Median Monthy Seizure Frequency: All Partial Seizures | Month 3 (n=287, 288) | 0.0 seizures/28 days | Standard Deviation 2.568 |
| Pregabalin | Median Monthy Seizure Frequency: All Partial Seizures | Month 11 (n=242, 254) | 0.0 seizures/28 days | Standard Deviation 3.082 |
| Pregabalin | Median Monthy Seizure Frequency: All Partial Seizures | Month 6 (n=266, 272) | 0.0 seizures/28 days | Standard Deviation 2.702 |
| Pregabalin | Median Monthy Seizure Frequency: All Partial Seizures | Month 12 (n=238, 252) | 0.0 seizures/28 days | Standard Deviation 7.018 |
| Pregabalin | Median Monthy Seizure Frequency: All Partial Seizures | Month 2 (n=300, 295) | 0.0 seizures/28 days | Standard Deviation 3.382 |
| Pregabalin | Median Monthy Seizure Frequency: All Partial Seizures | Month 13 (n=210, 227) | 0.0 seizures/28 days | Standard Deviation 3.247 |
| Pregabalin | Median Monthy Seizure Frequency: All Partial Seizures | Month 7 (n=260, 270) | 0.0 seizures/28 days | Standard Deviation 2.839 |
| Pregabalin | Median Monthy Seizure Frequency: All Partial Seizures | Taper (Week 57 to Week 60) (n=71, 45) | 0.0 seizures/28 days | Standard Deviation 6.418 |
| Pregabalin | Median Monthy Seizure Frequency: All Partial Seizures | Dose-escalation phase (Weeks 1 - 4) (n=329, 330) | 0.0 seizures/28 days | Standard Deviation 9.348 |
| Lamotrigine | Median Monthy Seizure Frequency: All Partial Seizures | Taper (Week 57 to Week 60) (n=71, 45) | 0.0 seizures/28 days | Standard Deviation 97.196 |
| Lamotrigine | Median Monthy Seizure Frequency: All Partial Seizures | Dose-escalation phase (Weeks 1 - 4) (n=329, 330) | 0.0 seizures/28 days | Standard Deviation 27.118 |
| Lamotrigine | Median Monthy Seizure Frequency: All Partial Seizures | Month 1 (n=314, 308) | 0.0 seizures/28 days | Standard Deviation 31.453 |
| Lamotrigine | Median Monthy Seizure Frequency: All Partial Seizures | Month 2 (n=300, 295) | 0.0 seizures/28 days | Standard Deviation 28.839 |
| Lamotrigine | Median Monthy Seizure Frequency: All Partial Seizures | Month 3 (n=287, 288) | 0.0 seizures/28 days | Standard Deviation 32.783 |
| Lamotrigine | Median Monthy Seizure Frequency: All Partial Seizures | Month 4 (n=279, 278) | 0.0 seizures/28 days | Standard Deviation 16.046 |
| Lamotrigine | Median Monthy Seizure Frequency: All Partial Seizures | Month 5 (n=274, 276) | 0.0 seizures/28 days | Standard Deviation 15.254 |
| Lamotrigine | Median Monthy Seizure Frequency: All Partial Seizures | Month 6 (n=266, 272) | 0.0 seizures/28 days | Standard Deviation 15.126 |
| Lamotrigine | Median Monthy Seizure Frequency: All Partial Seizures | Month 7 (n=260, 270) | 0.0 seizures/28 days | Standard Deviation 16.855 |
| Lamotrigine | Median Monthy Seizure Frequency: All Partial Seizures | Month 8 (n=256, 266) | 0.0 seizures/28 days | Standard Deviation 19.111 |
| Lamotrigine | Median Monthy Seizure Frequency: All Partial Seizures | Month 9 (n=253, 262) | 0.0 seizures/28 days | Standard Deviation 17.204 |
| Lamotrigine | Median Monthy Seizure Frequency: All Partial Seizures | Month 10 (n=250, 257) | 0.0 seizures/28 days | Standard Deviation 16.905 |
| Lamotrigine | Median Monthy Seizure Frequency: All Partial Seizures | Month 11 (n=242, 254) | 0.0 seizures/28 days | Standard Deviation 19.268 |
| Lamotrigine | Median Monthy Seizure Frequency: All Partial Seizures | Month 12 (n=238, 252) | 0.0 seizures/28 days | Standard Deviation 19.59 |
| Lamotrigine | Median Monthy Seizure Frequency: All Partial Seizures | Month 13 (n=210, 227) | 0.0 seizures/28 days | Standard Deviation 19.462 |
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).
Time frame: Baseline up to Week 60
Population: FAS. N = number of participants with analyzable data; n = number of participants with analyzable data at observation.
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin | Median Monthy Seizure Frequency: All Seizures | Month 4 (n=279, 278) | 0.0 seizures/28 days | Standard Deviation 3.223 |
| Pregabalin | Median Monthy Seizure Frequency: All Seizures | Month 8 (n=256, 266) | 0.0 seizures/28 days | Standard Deviation 3.304 |
| Pregabalin | Median Monthy Seizure Frequency: All Seizures | Month 1 (n=314, 308) | 0.0 seizures/28 days | Standard Deviation 6.164 |
| Pregabalin | Median Monthy Seizure Frequency: All Seizures | Month 9 (n=253, 262) | 0.0 seizures/28 days | Standard Deviation 2.636 |
| Pregabalin | Median Monthy Seizure Frequency: All Seizures | Month 5 (n=274, 276) | 0.0 seizures/28 days | Standard Deviation 2.458 |
| Pregabalin | Median Monthy Seizure Frequency: All Seizures | Month 10 (n=250, 257) | 0.0 seizures/28 days | Standard Deviation 4.934 |
| Pregabalin | Median Monthy Seizure Frequency: All Seizures | Month 3 (n=287, 288) | 0.0 seizures/28 days | Standard Deviation 2.702 |
| Pregabalin | Median Monthy Seizure Frequency: All Seizures | Month 11 (n=242, 254) | 0.0 seizures/28 days | Standard Deviation 3.224 |
| Pregabalin | Median Monthy Seizure Frequency: All Seizures | Month 6 (n=266, 272) | 0.0 seizures/28 days | Standard Deviation 2.853 |
| Pregabalin | Median Monthy Seizure Frequency: All Seizures | Month 12 (n=238, 252) | 0.0 seizures/28 days | Standard Deviation 7.019 |
| Pregabalin | Median Monthy Seizure Frequency: All Seizures | Month 2 (n=300, 295) | 0.0 seizures/28 days | Standard Deviation 5.498 |
| Pregabalin | Median Monthy Seizure Frequency: All Seizures | Month 13 (n=210, 227) | 0.0 seizures/28 days | Standard Deviation 3.247 |
| Pregabalin | Median Monthy Seizure Frequency: All Seizures | Month 7 (n=260, 270) | 0.0 seizures/28 days | Standard Deviation 2.898 |
| Pregabalin | Median Monthy Seizure Frequency: All Seizures | Taper (Week 57 to Week 60) (n=71, 45) | 0.0 seizures/28 days | Standard Deviation 6.418 |
| Pregabalin | Median Monthy Seizure Frequency: All Seizures | Dose-escalation phase (Weeks 1 - 4)(n=329, 330) | 0.0 seizures/28 days | Standard Deviation 9.819 |
| Lamotrigine | Median Monthy Seizure Frequency: All Seizures | Taper (Week 57 to Week 60) (n=71, 45) | 0.0 seizures/28 days | Standard Deviation 97.196 |
| Lamotrigine | Median Monthy Seizure Frequency: All Seizures | Dose-escalation phase (Weeks 1 - 4)(n=329, 330) | 0.0 seizures/28 days | Standard Deviation 27.128 |
| Lamotrigine | Median Monthy Seizure Frequency: All Seizures | Month 1 (n=314, 308) | 0.0 seizures/28 days | Standard Deviation 31.452 |
| Lamotrigine | Median Monthy Seizure Frequency: All Seizures | Month 2 (n=300, 295) | 0.0 seizures/28 days | Standard Deviation 28.838 |
| Lamotrigine | Median Monthy Seizure Frequency: All Seizures | Month 3 (n=287, 288) | 0.0 seizures/28 days | Standard Deviation 32.782 |
| Lamotrigine | Median Monthy Seizure Frequency: All Seizures | Month 4 (n=279, 278) | 0.0 seizures/28 days | Standard Deviation 16.046 |
| Lamotrigine | Median Monthy Seizure Frequency: All Seizures | Month 5 (n=274, 276) | 0.0 seizures/28 days | Standard Deviation 15.254 |
| Lamotrigine | Median Monthy Seizure Frequency: All Seizures | Month 6 (n=266, 272) | 0.0 seizures/28 days | Standard Deviation 15.126 |
| Lamotrigine | Median Monthy Seizure Frequency: All Seizures | Month 7 (n=260, 270) | 0.0 seizures/28 days | Standard Deviation 16.855 |
| Lamotrigine | Median Monthy Seizure Frequency: All Seizures | Month 8 (n=256, 266) | 0.0 seizures/28 days | Standard Deviation 19.11 |
| Lamotrigine | Median Monthy Seizure Frequency: All Seizures | Month 9 (n=253, 262) | 0.0 seizures/28 days | Standard Deviation 17.204 |
| Lamotrigine | Median Monthy Seizure Frequency: All Seizures | Month 10 (n=250, 257) | 0.0 seizures/28 days | Standard Deviation 16.905 |
| Lamotrigine | Median Monthy Seizure Frequency: All Seizures | Month 11 (n=242, 254) | 0.0 seizures/28 days | Standard Deviation 19.268 |
| Lamotrigine | Median Monthy Seizure Frequency: All Seizures | Month 12 (n=238, 252) | 0.0 seizures/28 days | Standard Deviation 19.59 |
| Lamotrigine | Median Monthy Seizure Frequency: All Seizures | Month 13 (n=210, 227) | 0.0 seizures/28 days | Standard Deviation 19.462 |
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.
Time frame: Month 1 through Month 9 (after 6 months seizure freedom achieved)
Population: FAS. N = number of responders; n = number of responders with analyzable data at observation.
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin | Median Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Partial Seizures | Month 2 (n=155, 194) | 0.0 seizures/28 days | Standard Deviation 1.783 |
| Pregabalin | Median Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Partial Seizures | Month 6 (n=122, 152) | 0.0 seizures/28 days | Standard Deviation 0.156 |
| Pregabalin | Median Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Partial Seizures | Month 4 (n=139, 173) | 0.0 seizures/28 days | Standard Deviation 0.329 |
| Pregabalin | Median Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Partial Seizures | Month 7 (n=105, 136) | 0.0 seizures/28 days | Standard Deviation 0 |
| Pregabalin | Median Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Partial Seizures | Month 3 (n=147, 184) | 0.0 seizures/28 days | Standard Deviation 0.384 |
| Pregabalin | Median Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Partial Seizures | Month 8 (n=1, 5) | 0.0 seizures/28 days | — |
| Pregabalin | Median Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Partial Seizures | Month 5 (n=127, 158) | 0.0 seizures/28 days | Standard Deviation 0.926 |
| Pregabalin | Median Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Partial Seizures | Month 9 (n=0, 1) | NA seizures/28 days | — |
| Pregabalin | Median Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Partial Seizures | Month 1 (n=162, 208) | 0.0 seizures/28 days | Standard Deviation 1 |
| Lamotrigine | Median Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Partial Seizures | Month 9 (n=0, 1) | 6.0 seizures/28 days | — |
| Lamotrigine | Median Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Partial Seizures | Month 1 (n=162, 208) | 0.0 seizures/28 days | Standard Deviation 0.226 |
| Lamotrigine | Median Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Partial Seizures | Month 2 (n=155, 194) | 0.0 seizures/28 days | Standard Deviation 0.226 |
| Lamotrigine | Median Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Partial Seizures | Month 3 (n=147, 184) | 0.0 seizures/28 days | Standard Deviation 0.439 |
| Lamotrigine | Median Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Partial Seizures | Month 4 (n=139, 173) | 0.0 seizures/28 days | Standard Deviation 0.211 |
| Lamotrigine | Median Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Partial Seizures | Month 5 (n=127, 158) | 0.0 seizures/28 days | Standard Deviation 0.823 |
| Lamotrigine | Median Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Partial Seizures | Month 6 (n=122, 152) | 0.0 seizures/28 days | Standard Deviation 0.213 |
| Lamotrigine | Median Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Partial Seizures | Month 7 (n=105, 136) | 0.0 seizures/28 days | Standard Deviation 2.843 |
| Lamotrigine | Median Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Partial Seizures | Month 8 (n=1, 5) | 0.0 seizures/28 days | Standard Deviation 0 |
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.
Time frame: Month 1 through Month 9 (after 6 months seizure freedom achieved)
Population: FAS. N = number of responders; n = number of responders with analyzable data at observation.
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin | Median Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Seizures | Month 2 (n=155, 194) | 0.0 seizures/28 days | Standard Deviation 1.783 |
| Pregabalin | Median Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Seizures | Month 6 (n=122, 152) | 0.0 seizures/28 days | Standard Deviation 0.156 |
| Pregabalin | Median Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Seizures | Month 4 (n=139, 173) | 0.0 seizures/28 days | Standard Deviation 0.359 |
| Pregabalin | Median Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Seizures | Month 7 (n=105, 136) | 0.0 seizures/28 days | Standard Deviation 0 |
| Pregabalin | Median Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Seizures | Month 3 (n=147, 184) | 0.0 seizures/28 days | Standard Deviation 0.4 |
| Pregabalin | Median Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Seizures | Month 8 (n=1, 5) | 0.0 seizures/28 days | — |
| Pregabalin | Median Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Seizures | Month 5 (n=127, 158) | 0.0 seizures/28 days | Standard Deviation 0.971 |
| Pregabalin | Median Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Seizures | Month 9 (n=0, 1) | NA seizures/28 days | — |
| Pregabalin | Median Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Seizures | Month 1 (n=162, 208) | 0.0 seizures/28 days | Standard Deviation 1 |
| Lamotrigine | Median Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Seizures | Month 9 (n=0, 1) | 6.0 seizures/28 days | — |
| Lamotrigine | Median Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Seizures | Month 1 (n=162, 208) | 0.0 seizures/28 days | Standard Deviation 0.236 |
| Lamotrigine | Median Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Seizures | Month 2 (n=155, 194) | 0.0 seizures/28 days | Standard Deviation 0.226 |
| Lamotrigine | Median Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Seizures | Month 3 (n=147, 184) | 0.0 seizures/28 days | Standard Deviation 0.439 |
| Lamotrigine | Median Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Seizures | Month 4 (n=139, 173) | 0.0 seizures/28 days | Standard Deviation 0.211 |
| Lamotrigine | Median Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Seizures | Month 5 (n=127, 158) | 0.0 seizures/28 days | Standard Deviation 0.823 |
| Lamotrigine | Median Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Seizures | Month 6 (n=122, 152) | 0.0 seizures/28 days | Standard Deviation 0.213 |
| Lamotrigine | Median Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Seizures | Month 7 (n=105, 136) | 0.0 seizures/28 days | Standard Deviation 2.844 |
| Lamotrigine | Median Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Seizures | Month 8 (n=1, 5) | 0.0 seizures/28 days | Standard Deviation 0 |
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.
Time frame: Week 8, Week 32, and Week 56
Population: FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pregabalin | Medical Outcomes Study Sleep Scale (MOS-SS): Optimal Sleep Subscale | Week 8: Non-optimal sleep | 103 participants |
| Pregabalin | Medical Outcomes Study Sleep Scale (MOS-SS): Optimal Sleep Subscale | Week 32: Non-optimal sleep | 97 participants |
| Pregabalin | Medical Outcomes Study Sleep Scale (MOS-SS): Optimal Sleep Subscale | Week 8: Optimal sleep | 195 participants |
| Pregabalin | Medical Outcomes Study Sleep Scale (MOS-SS): Optimal Sleep Subscale | Week 56: Optimal sleep | 152 participants |
| Pregabalin | Medical Outcomes Study Sleep Scale (MOS-SS): Optimal Sleep Subscale | Week 56: Non-optimal sleep | 82 participants |
| Pregabalin | Medical Outcomes Study Sleep Scale (MOS-SS): Optimal Sleep Subscale | Week 32: Optimal sleep | 167 participants |
| Lamotrigine | Medical Outcomes Study Sleep Scale (MOS-SS): Optimal Sleep Subscale | Week 56: Non-optimal sleep | 90 participants |
| Lamotrigine | Medical Outcomes Study Sleep Scale (MOS-SS): Optimal Sleep Subscale | Week 8: Optimal sleep | 173 participants |
| Lamotrigine | Medical Outcomes Study Sleep Scale (MOS-SS): Optimal Sleep Subscale | Week 8: Non-optimal sleep | 126 participants |
| Lamotrigine | Medical Outcomes Study Sleep Scale (MOS-SS): Optimal Sleep Subscale | Week 32: Optimal sleep | 155 participants |
| Lamotrigine | Medical Outcomes Study Sleep Scale (MOS-SS): Optimal Sleep Subscale | Week 32: Non-optimal sleep | 103 participants |
| Lamotrigine | Medical Outcomes Study Sleep Scale (MOS-SS): Optimal Sleep Subscale | Week 56: Optimal sleep | 145 participants |
Comparison: 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.p-value: 0.068395% CI: [0.98, 1.93]Regression, Logistic
Comparison: 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.p-value: 0.509695% CI: [0.78, 1.66]Regression, Logistic
Comparison: 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.p-value: 0.680495% CI: [0.73, 1.63]Regression, Logistic
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.
Time frame: Week 5 up to Week 56
Population: FAS; N = number of participants with analyzable data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pregabalin | Percentage of Participants Who Achieved at Least 6 Consecutive Months of Seizure Freedom (Responders) by Final Dosage Levels and Treatment Group | 70.5 percentage of participants |
| Lamotrigine | Percentage of Participants Who Achieved at Least 6 Consecutive Months of Seizure Freedom (Responders) by Final Dosage Levels and Treatment Group | 59.7 percentage of participants |
| Pregabalin 450 mg/Day | Percentage of Participants Who Achieved at Least 6 Consecutive Months of Seizure Freedom (Responders) by Final Dosage Levels and Treatment Group | 20.4 percentage of participants |
| Pregabalin 600 mg/Day | Percentage of Participants Who Achieved at Least 6 Consecutive Months of Seizure Freedom (Responders) by Final Dosage Levels and Treatment Group | 13.0 percentage of participants |
| Lamotrigine 100 mg/Day | Percentage of Participants Who Achieved at Least 6 Consecutive Months of Seizure Freedom (Responders) by Final Dosage Levels and Treatment Group | 80.5 percentage of participants |
| Lamotrigine 200 mg/Day | Percentage of Participants Who Achieved at Least 6 Consecutive Months of Seizure Freedom (Responders) by Final Dosage Levels and Treatment Group | 67.9 percentage of participants |
| Lamotrigine 400 mg/Day | Percentage of Participants Who Achieved at Least 6 Consecutive Months of Seizure Freedom (Responders) by Final Dosage Levels and Treatment Group | 38.2 percentage of participants |
| Lamotrigine 500 mg/Day | Percentage of Participants Who Achieved at Least 6 Consecutive Months of Seizure Freedom (Responders) by Final Dosage Levels and Treatment Group | 16.7 percentage of participants |
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.
Time frame: Week 4 up to Week 56
Population: FAS. N = number of participants who entered maintenance phase of study and had seizure efficacy data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pregabalin | Time to 6 Consecutive Months of Seizure-freedom After 4-week Dose Escalation Phase: All Seizures | 254 days |
| Lamotrigine | Time to 6 Consecutive Months of Seizure-freedom After 4-week Dose Escalation Phase: All Seizures | 183 days |
Comparison: 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.p-value: 0.003495% CI: [0.6, 0.9]Regression, Cox
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.
Time frame: Week 4 up to Week 56
Population: FAS. N = number of participants who entered maintenance phase of study and had seizure efficacy data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pregabalin | Time to First Seizure After the 4-Week Dose Escalation Phase | 85 days |
| Lamotrigine | Time to First Seizure After the 4-Week Dose Escalation Phase | 211 days |
Comparison: 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.p-value: 0.000395% CI: [1.19, 1.8]Cox proportional hazards model