Epilepsy With Simple or Complex Partial Onset Seizures
Conditions
Keywords
Seizure, Epilepsy, Anticonvulsant, Historical Control, Monotherapy
Brief summary
This is an 18-week, double-blind, multicenter study with gradual conversion from previous antiepileptic therapy to eslicarbazepine acetate monotherapy in subjects with partial epilepsy.
Detailed description
This is an 18-week, double-blind, randomized, historical control, multicenter study with gradual conversion to monotherapy in subjects with partial onset seizures who are not well controlled by current AEDs. The 18 week double-blind treatment period consists of a 2-week period for titration of study drug, 6-week period for taper or conversion off AEDs, and a 10-week monotherapy period. Subjects not entering an optional open-label extension study will enter a 1-week period to taper off study drug followed by an end of study visit (week 19). This study was previously posted by Sepracor Inc. In October 2009, Sepracor Inc. was acquired by Dainippon Sumitomo Pharma., and in October 2010, Sepracor Inc's name was changed to Sunovion Pharmaceuticals Inc.
Interventions
1600 mg QD
Sponsors
Sumitomo Pharma America, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
16 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of partial epilepsy as defined in the Classification of Seizures of the International League Against Epilepsy (ILAE) (simple partial seizures with observable motor component, or complex, with or without secondary generalization) a. Medical history of seizures; b. Absence of confounding factors (pseudoseizures, syncope); c. Documented EEG recording (done within 5 years prior to screening) consistent with focal onset epilepsy. * Documented CT or MRI scan conducted within 10 years prior to screening, showing the absence of a progressive structural abnormality (eg, tumor). Mesial temporal sclerosis is acceptable. * ≥4 partial onset seizures during the 8 weeks prior screening with no 28-day seizure free period. * Stable treatment with 1-2 AEDs during the last 4 weeks prior to screening. * Subjects must have the ability to comprehend the informed consent form and be willing to provide informed consent. For subjects who are unable to comprehend the written consent, a witness/caregiver who is able to describe and provide an understanding of the informed consent to the subject must sign the consent form on behalf of the subject. * Subjects must give written informed consent prior to participation in the study. For subjects \<18 years of age, the informed consent must be signed by the subject's parent or legal guardian, and, when appropriate and/or required by state or local law, minor subjects must give written informed assent prior to participation in the study. Subjects of Asian ancestry are required to give written informed consent for genotyping. All subjects must sign a HIPAA Form. All females of child bearing potential must also sign the Women of Childbearing Potential Addendum. * A female subject is eligible to enter and participate in the study if she is of: a. Non-childbearing potential (ie, physiologically incapable of becoming pregnant, including any female who is pre-menarchal or post-menopausal); b. Child-bearing potential (all females ≤65 years of age), has a negative pregnancy test at screening and agrees to satisfy contraception requirements.
Exclusion criteria
* Subjects with only simple partial seizures without a motor component. * Presence of generalized seizure syndromes (eg, juvenile myoclonic epilepsy or Lennox-Gastaut syndrome). * History of pseudo-seizures. * Current seizures related to an acute medical illness. * Seizures secondary to metabolic, toxic or infectious disorder or drug abuse. * Status epilepticus within 2 years prior to screening. * Seizures only occurring in a cluster pattern. * Subjects taking 2 of the following sodium channel blocking AEDs: phenytoin, carbamazepine, oxcarbazepine, or lamotrigine. * Subjects taking 2 AEDs with both being in the upper dose range (defined as approximately two-thirds of the defined daily dose). * Subjects taking more than 2 AEDs. * Subjects with progressive structural central nervous system lesion or progressive encephalopathy. * Psychiatric
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative 112-day Exit Rate as Estimated by Kaplan-Meier Method | Week 3 to Week 18 | Cumulative exit rate was defined as the proportion of subjects meeting at least one of the five exit criteria over a 16-wk study period (start of Antiepilectic Drugs(AED) taper/conv.period (Wk 3 to end of double blind monotherapy period (Wk 18)):1.One episode of status epilepticus.2.One secondary general partial seizure (in subjects who did not have gen. seizures during 6 months prior to screening).3.A two fold increase in any consecutive 28 day seizure rate compared to the highest consecutive 28 day seizure rate during the 8 wk baseline period. 4.A two fold increase in any consecutive 2 day seizure rate compared to the highest consecutive 2 day seizure rate during the 8 wk baseline period. If the highest number of seizures in any consecutive 2 day period during the 8 wk baseline was 1 then 3 seizures in a consecutive 2 day period was required to exit.5.Worsening of seizures or increase in seizure frequency considered serious or requiring intervention as judged by the Investigator. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects Seizure-free During the Last 4 Weeks on Eslicarbazepine Acetate Monotherapy. | Weeks 15 through 18 | Seizure-free subjects during the last four weeks of monotherapy were determined as subjects who had seizure assessments during the 4 weeks between Visits 8 and 9 (Weeks 15 through 18), and did not have any seizures. |
| Completion Rate | Week 1 to Week 18 | Subjects completing the study were determined as subjects who completed the 18 weeks of double-blind treatment. |
| Completion Rate During the 10 Weeks of Monotherapy | Weeks 8 through 18 | Monotherapy completion rate was defined as the proportion (%) of subjects entering the monotherapy period who completed the 10 weeks of monotherapy treatment. |
| Time on Eslicarbazepine Acetate Monotherapy. | Week 8 to Week 18 | The start of the monotherapy period was defined as the date of termination of all other AEDs while taking study monotherapy medication. Time on monotherapy was defined from the start of monotherapy period to the last dose of monotherapy treatment. |
| Change in Seizure Frequency From Baseline. | Week 0 to Week 18, Double-blind: weeks 1to 18; baseline:weeks-8 to -1; Titration: weeks 1 to 2; AED taper/conversion:weeks 3 to 8; monotherapy: weeks 9 to 18 | The relative (%) change in standardized seizure frequency was evaluated for four periods: titration (Weeks 1 to 2), AED taper/conversion (Weeks 3 to 8), monotherapy (Weeks 9 to 18), and double-blind (Weeks 1 to 18). |
| Responder Rate (Proportion [%] of Subjects With a ≥50% Reduction of Seizure Frequency From Baseline). | Week 0 to Week 18, Double blind: weeks to 8; baseline:weeks -8 to -1; titration: weeks 1 to 2; AED taper/conversion: weeks 3 to 8; monotherapy: weeks 9 to 18 | Responder rate was defined as the proportion (%) of subjects with a ≥ 50% reduction of seizure frequency from baseline. This analysis was done for the titration (Weeks 1 to 2), AED taper/conversion (Weeks 3 to 8), monotherapy (Weeks 9 to 18), and double-blind (Weeks 1 to 18) periods. |
| Percentage of Subjects Reaching Each of the Exit Events. | Week 1 to Week 18 | The percentage of subjects reaching each of the 5 exit criteria. 1.One episode of status epilepticus.2.One secondary general partial seizure (in subjects who did not have gen. seizures during 6 months prior to screening).3.A two fold increase in any consecutive 28 day seizure rate compared to the highest consecutive 28 day seizure rate during the 8 wk baseline period. 4.A two fold increase in any consecutive 2 day seizure rate compared to the highest consecutive 2 day seizure rate during the 8 wk baseline period. If the highest number of seizures in any consecutive 2 day period during the 8 wk baseline was 1 then 3 seizures in a consecutive 2 day period was required to exit.5.Worsening of seizures or increase in seizure frequency considered serious or requiring intervention as judged by the Investigator. |
| Percentage of Subjects That Are Seizure-free During the 10-week Double-blind Monotherapy Treatment Period. | Weeks 9 through 18 | Seizure-free subjects during the monotherapy period were determined as subjects who had seizure assessments during the monotherapy period, and did not have any seizures in the 10 weeks between Visits 6 and 9 (Weeks 9 through 18). Subjects who discontinued during this period were considered not seizure-free even if they were seizure-free at the time of discontinuation, i.e., to be considered seizure-free, subjects must complete the 10-week period without any seizures. |
| Change in Total Score From Baseline in 31-Item Quality of Life in Epilepsy (QOLIE-31). | Week 0 to Week 18, baseline: day 0: End of AED taper/conversion period: end of week 8; End of monotherapy period: end of week 18 | The QOLIE-31 overall score was obtained by using a weighted average of multi-item scale scores. The recorded responses were converted to 0-100 point scales. The mean of the individual item scores in each subgroup were calculated, with higher converted scores reflecting better quality of life. |
| Change in Total Score From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS). | Week 0 to Week 18; Baseline: day 0; End of AED taper/conversion period: end of week 8; End of monotherapy period: end of week 18 | The total score of MADRS is defined as the sum of all individual symptom scores, ranging from 0 to 60, higher score indicates more severe depression. Each of the 10 symptoms of depression on MADRS was measured on a scale of 0 to 6 with 0 representing the lowest severity of the symptom and 6 representing the highest severity |
| Change in Total Score From Baseline in MADRS in Those Subjects With a MADRS Score of ≥14 at Randomization. | Week 0 to Week 18, Baseline: Day 0; End of AED taper/conversion period: end of week 8; End of monotherapy period: end of week 18 | The total score of MADRS is defined as the sum of all individual symptom scores, ranging from 0 to 60, higher score indicates more severe depression. Each of the 10 symptoms of depression on MADRS was measured on a scale of 0 to 6 with 0 representing the lowest severity of the symptom and 6 representing the highest severity |
| Percentage of Subjects With Increase of Body Weight >= 7% | 18 Week Double-blind treatment period | — |
| Proportion (%) of Subjects With Normal Baseline Sodium Reaching Blood Sodium ≤135 mmol/L, ≤130 mmol/L, and ≤125 mmol/L | 18 Week Double-blind treatment period | Proportion (%) of Subjects With Normal Baseline Sodium Reaching Blood Sodium ≤135 mmol/L, ≤130 mmol/L, and ≤125 mmol/L |
| Standardized Seizure Frequency (SSF) by Period | Week 1 to Week 18, Double-blind: weeks 1 to 18; Baseline: weeks -8 to -1; Titration: weeks 1 to 2; AED taper/conversion: weeks 3 to 8; Monotherapy: weeks 9 to 18 | Seizure frequency was evaluated by using a standardized frequency per 4 weeks (28 days). It was evaluated for five periods: baseline (Weeks -8 to -1), titration (Weeks 1 to 2), AED taper/conversion (Weeks 3 to 8), monotherapy (Weeks 9 to 18), and double-blind (Weeks 1 to 18). |
| Proportion (%) of Events in Each Classification of the Columbia Suicide Severity Rating Scale (C SSRS). | 18 Week Double-blind treatment period | — |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Eslicarbazepine 1200 mg QD Subjects randomized to 1200 mg QD eslicarbazepine will titrate from 400 mg (Week 1) to 800 mg (Week 2) to 1200 mg (Weeks 3-18) QD and taper down from 1200 mg to 600 mg QD 3 days after the end of Week 18.
. | 65 |
| Eslicarbazepine 1600 mg QD Subjects randomized to 1600 mg QD of eslicarbazepine will titrate from 600 mg (Week 1) to 1200 mg (Week 2) to 1600 mg (Weeks 3-18) QD and taper down from 1600 mg to 800 mg QD 3 days after the end of Week 18. | 128 |
| Total | 193 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 5 | 19 |
| Overall Study | Death | 1 | 0 |
| Overall Study | discontinued due to communication error | 0 | 1 |
| Overall Study | Lost to Follow-up | 0 | 4 |
| Overall Study | met exit criteria | 23 | 17 |
| Overall Study | Physician Decision | 0 | 3 |
| Overall Study | Protocol Violation | 3 | 4 |
| Overall Study | Withdrawal by Subject | 4 | 4 |
Baseline characteristics
| Characteristic | Eslicarbazepine 1200 mg QD | Eslicarbazepine 1600 mg QD | Total |
|---|---|---|---|
| Age, Customized 18-39 years | 31 participants | 61 participants | 92 participants |
| Age, Customized 40-65 years | 29 participants | 61 participants | 90 participants |
| Age, Customized greater than 65 years | 1 participants | 4 participants | 5 participants |
| Age, Customized less than 18 years | 4 participants | 2 participants | 6 participants |
| Race/Ethnicity, Customized American Indian or Alsaka Native | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Asian | 1 participants | 3 participants | 4 participants |
| Race/Ethnicity, Customized Black or African American | 4 participants | 18 participants | 22 participants |
| Race/Ethnicity, Customized More than one race | 1 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized Native Hawaiian or Pacific Islander | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Unknown or Not Reported | 6 participants | 12 participants | 18 participants |
| Race/Ethnicity, Customized White | 53 participants | 94 participants | 147 participants |
| Region of Enrollment Canada | 1 participants | 5 participants | 6 participants |
| Region of Enrollment United States | 64 participants | 123 participants | 187 participants |
| Sex: Female, Male Female | 34 Participants | 67 Participants | 101 Participants |
| Sex: Female, Male Male | 31 Participants | 61 Participants | 92 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 46 / 65 | 100 / 128 |
| serious Total, serious adverse events | 4 / 65 | 8 / 128 |
Outcome results
Primary
Cumulative 112-day Exit Rate as Estimated by Kaplan-Meier Method
Cumulative exit rate was defined as the proportion of subjects meeting at least one of the five exit criteria over a 16-wk study period (start of Antiepilectic Drugs(AED) taper/conv.period (Wk 3 to end of double blind monotherapy period (Wk 18)):1.One episode of status epilepticus.2.One secondary general partial seizure (in subjects who did not have gen. seizures during 6 months prior to screening).3.A two fold increase in any consecutive 28 day seizure rate compared to the highest consecutive 28 day seizure rate during the 8 wk baseline period. 4.A two fold increase in any consecutive 2 day seizure rate compared to the highest consecutive 2 day seizure rate during the 8 wk baseline period. If the highest number of seizures in any consecutive 2 day period during the 8 wk baseline was 1 then 3 seizures in a consecutive 2 day period was required to exit.5.Worsening of seizures or increase in seizure frequency considered serious or requiring intervention as judged by the Investigator.
Time frame: Week 3 to Week 18
Population: efficacy population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Eslicarbazepine 1200 mg QD | Cumulative 112-day Exit Rate as Estimated by Kaplan-Meier Method | 0.444 proportion of participants |
| Eslicarbazepine 1600 mg QD | Cumulative 112-day Exit Rate as Estimated by Kaplan-Meier Method | 0.287 proportion of participants |
Secondary
Change in Seizure Frequency From Baseline.
The relative (%) change in standardized seizure frequency was evaluated for four periods: titration (Weeks 1 to 2), AED taper/conversion (Weeks 3 to 8), monotherapy (Weeks 9 to 18), and double-blind (Weeks 1 to 18).
Time frame: Week 0 to Week 18, Double-blind: weeks 1to 18; baseline:weeks-8 to -1; Titration: weeks 1 to 2; AED taper/conversion:weeks 3 to 8; monotherapy: weeks 9 to 18
Population: efficacy population (ESL 1200 mg) Double-blind: 60;Titration: 60; AED taper/conversion: 60; Monotherapy: 43 (ESL 1600 mg) Double-blind: 118; Titration: 118; AED taper/conversion:114; Monotherapy:93
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Eslicarbazepine 1200 mg QD | Change in Seizure Frequency From Baseline. | Relative (%) change from baselne for DB period | -30.9 percent change |
| Eslicarbazepine 1200 mg QD | Change in Seizure Frequency From Baseline. | Relative (%) change from baseline -tiration period | -29.6 percent change |
| Eslicarbazepine 1200 mg QD | Change in Seizure Frequency From Baseline. | Relative (%) change from baseline -AED t/c period | -30.2 percent change |
| Eslicarbazepine 1200 mg QD | Change in Seizure Frequency From Baseline. | Relative (%) change from baseline - mono period | -48.7 percent change |
| Eslicarbazepine 1600 mg QD | Change in Seizure Frequency From Baseline. | Relative (%) change from baseline - mono period | -38.6 percent change |
| Eslicarbazepine 1600 mg QD | Change in Seizure Frequency From Baseline. | Relative (%) change from baselne for DB period | -41.5 percent change |
| Eslicarbazepine 1600 mg QD | Change in Seizure Frequency From Baseline. | Relative (%) change from baseline -AED t/c period | -39.7 percent change |
| Eslicarbazepine 1600 mg QD | Change in Seizure Frequency From Baseline. | Relative (%) change from baseline -tiration period | -52.4 percent change |
Secondary
Change in Total Score From Baseline in 31-Item Quality of Life in Epilepsy (QOLIE-31).
The QOLIE-31 overall score was obtained by using a weighted average of multi-item scale scores. The recorded responses were converted to 0-100 point scales. The mean of the individual item scores in each subgroup were calculated, with higher converted scores reflecting better quality of life.
Time frame: Week 0 to Week 18, baseline: day 0: End of AED taper/conversion period: end of week 8; End of monotherapy period: end of week 18
Population: the numbers analyzed represent all participants for whom data were available at baseline (ESL 1200 mg)Change from baseline to end of AED taper/conversion period: 39;Change from baseline to end of monotherapy period:36 (ESL1600 mg) Change from baseline to end of AED taper/conversion period: 86;Change from baseline to end of monotherapy period: 86
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eslicarbazepine 1200 mg QD | Change in Total Score From Baseline in 31-Item Quality of Life in Epilepsy (QOLIE-31). | Change from baseline to end of AED T/C pd n=39,86 | 3.2 units on a scale | Standard Deviation 10.75 |
| Eslicarbazepine 1200 mg QD | Change in Total Score From Baseline in 31-Item Quality of Life in Epilepsy (QOLIE-31). | change from baseline to end of mono. pd n=36,86 | 7.8 units on a scale | Standard Deviation 13.78 |
| Eslicarbazepine 1600 mg QD | Change in Total Score From Baseline in 31-Item Quality of Life in Epilepsy (QOLIE-31). | Change from baseline to end of AED T/C pd n=39,86 | 6.3 units on a scale | Standard Deviation 12.42 |
| Eslicarbazepine 1600 mg QD | Change in Total Score From Baseline in 31-Item Quality of Life in Epilepsy (QOLIE-31). | change from baseline to end of mono. pd n=36,86 | 6.4 units on a scale | Standard Deviation 12.64 |
Secondary
Change in Total Score From Baseline in MADRS in Those Subjects With a MADRS Score of ≥14 at Randomization.
The total score of MADRS is defined as the sum of all individual symptom scores, ranging from 0 to 60, higher score indicates more severe depression. Each of the 10 symptoms of depression on MADRS was measured on a scale of 0 to 6 with 0 representing the lowest severity of the symptom and 6 representing the highest severity
Time frame: Week 0 to Week 18, Baseline: Day 0; End of AED taper/conversion period: end of week 8; End of monotherapy period: end of week 18
Population: efficacy population (ESL 1200 mg) Change from baseline to end of AED taper/conversation period: 7; Change from baseline to end of monotherapy period: 6 (ESL 1600 mg) Change from baseline to end of AED taper/conversation period: 13; Change from baseline to end of monotherapy period: 13
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eslicarbazepine 1200 mg QD | Change in Total Score From Baseline in MADRS in Those Subjects With a MADRS Score of ≥14 at Randomization. | Change from baseline to AED T/C pd n=7,13 | -1.3 units on a scale | Standard Deviation 3.86 |
| Eslicarbazepine 1200 mg QD | Change in Total Score From Baseline in MADRS in Those Subjects With a MADRS Score of ≥14 at Randomization. | Change from baseline to end of mono pd n=6,13 | -6.8 units on a scale | Standard Deviation 6.71 |
| Eslicarbazepine 1600 mg QD | Change in Total Score From Baseline in MADRS in Those Subjects With a MADRS Score of ≥14 at Randomization. | Change from baseline to AED T/C pd n=7,13 | -7.9 units on a scale | Standard Deviation 9.81 |
| Eslicarbazepine 1600 mg QD | Change in Total Score From Baseline in MADRS in Those Subjects With a MADRS Score of ≥14 at Randomization. | Change from baseline to end of mono pd n=6,13 | -9.6 units on a scale | Standard Deviation 8.72 |
Secondary
Change in Total Score From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS).
The total score of MADRS is defined as the sum of all individual symptom scores, ranging from 0 to 60, higher score indicates more severe depression. Each of the 10 symptoms of depression on MADRS was measured on a scale of 0 to 6 with 0 representing the lowest severity of the symptom and 6 representing the highest severity
Time frame: Week 0 to Week 18; Baseline: day 0; End of AED taper/conversion period: end of week 8; End of monotherapy period: end of week 18
Population: efficacy population (ESL 1200 mg) Change from baseline to end of AED taper/conversion period: 45; Change from baseline to end of monotherapy period: 41 (ESL 1600 mg) Change from baseline to end of AED taper/conversion period: 92; Change from baseline to end of monotherapy period: 91
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eslicarbazepine 1200 mg QD | Change in Total Score From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS). | Change from baseline to AED T/C period | -0.4 units on a scale | Standard Deviation 4.35 |
| Eslicarbazepine 1200 mg QD | Change in Total Score From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS). | Change from baseline to end of mono period | -1.1 units on a scale | Standard Deviation 5.55 |
| Eslicarbazepine 1600 mg QD | Change in Total Score From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS). | Change from baseline to AED T/C period | -2.0 units on a scale | Standard Deviation 5.99 |
| Eslicarbazepine 1600 mg QD | Change in Total Score From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS). | Change from baseline to end of mono period | -2.4 units on a scale | Standard Deviation 5.77 |
Secondary
Completion Rate
Subjects completing the study were determined as subjects who completed the 18 weeks of double-blind treatment.
Time frame: Week 1 to Week 18
Population: efficacy population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Eslicarbazepine 1200 mg QD | Completion Rate | 48.3 percentage of participants |
| Eslicarbazepine 1600 mg QD | Completion Rate | 64.4 percentage of participants |
Secondary
Completion Rate During the 10 Weeks of Monotherapy
Monotherapy completion rate was defined as the proportion (%) of subjects entering the monotherapy period who completed the 10 weeks of monotherapy treatment.
Time frame: Weeks 8 through 18
Population: efficacy population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Eslicarbazepine 1200 mg QD | Completion Rate During the 10 Weeks of Monotherapy | 64.4 percentage of participants |
| Eslicarbazepine 1600 mg QD | Completion Rate During the 10 Weeks of Monotherapy | 81.7 percentage of participants |
Secondary
Percentage of Subjects Reaching Each of the Exit Events.
The percentage of subjects reaching each of the 5 exit criteria. 1.One episode of status epilepticus.2.One secondary general partial seizure (in subjects who did not have gen. seizures during 6 months prior to screening).3.A two fold increase in any consecutive 28 day seizure rate compared to the highest consecutive 28 day seizure rate during the 8 wk baseline period. 4.A two fold increase in any consecutive 2 day seizure rate compared to the highest consecutive 2 day seizure rate during the 8 wk baseline period. If the highest number of seizures in any consecutive 2 day period during the 8 wk baseline was 1 then 3 seizures in a consecutive 2 day period was required to exit.5.Worsening of seizures or increase in seizure frequency considered serious or requiring intervention as judged by the Investigator.
Time frame: Week 1 to Week 18
Population: efficacy population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Eslicarbazepine 1200 mg QD | Percentage of Subjects Reaching Each of the Exit Events. | exit criterion 3 (investigator prog. assessment) | 10.0 percentage of participants |
| Eslicarbazepine 1200 mg QD | Percentage of Subjects Reaching Each of the Exit Events. | exit criterion 4 (investigaor prog. assessment) | 8.3 percentage of participants |
| Eslicarbazepine 1200 mg QD | Percentage of Subjects Reaching Each of the Exit Events. | exit criterion 2 | 6.7 percentage of participants |
| Eslicarbazepine 1200 mg QD | Percentage of Subjects Reaching Each of the Exit Events. | exit criterion 4 (sponsor prog. assessment) | 10.0 percentage of participants |
| Eslicarbazepine 1200 mg QD | Percentage of Subjects Reaching Each of the Exit Events. | exit criterion 3 (sponsors prog. assessment) | 8.3 percentage of participants |
| Eslicarbazepine 1200 mg QD | Percentage of Subjects Reaching Each of the Exit Events. | exit criterion 5 | 13.3 percentage of participants |
| Eslicarbazepine 1200 mg QD | Percentage of Subjects Reaching Each of the Exit Events. | exit criterion 1 | 0 percentage of participants |
| Eslicarbazepine 1600 mg QD | Percentage of Subjects Reaching Each of the Exit Events. | exit criterion 5 | 3.4 percentage of participants |
| Eslicarbazepine 1600 mg QD | Percentage of Subjects Reaching Each of the Exit Events. | exit criterion 1 | 0.8 percentage of participants |
| Eslicarbazepine 1600 mg QD | Percentage of Subjects Reaching Each of the Exit Events. | exit criterion 2 | 0.8 percentage of participants |
| Eslicarbazepine 1600 mg QD | Percentage of Subjects Reaching Each of the Exit Events. | exit criterion 3 (investigator prog. assessment) | 4.2 percentage of participants |
| Eslicarbazepine 1600 mg QD | Percentage of Subjects Reaching Each of the Exit Events. | exit criterion 3 (sponsors prog. assessment) | 5.9 percentage of participants |
| Eslicarbazepine 1600 mg QD | Percentage of Subjects Reaching Each of the Exit Events. | exit criterion 4 (investigaor prog. assessment) | 5.1 percentage of participants |
| Eslicarbazepine 1600 mg QD | Percentage of Subjects Reaching Each of the Exit Events. | exit criterion 4 (sponsor prog. assessment) | 5.9 percentage of participants |
Secondary
Percentage of Subjects Seizure-free During the Last 4 Weeks on Eslicarbazepine Acetate Monotherapy.
Seizure-free subjects during the last four weeks of monotherapy were determined as subjects who had seizure assessments during the 4 weeks between Visits 8 and 9 (Weeks 15 through 18), and did not have any seizures.
Time frame: Weeks 15 through 18
Population: efficacy population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Eslicarbazepine 1200 mg QD | Percentage of Subjects Seizure-free During the Last 4 Weeks on Eslicarbazepine Acetate Monotherapy. | 13.3 percentage of participants |
| Eslicarbazepine 1600 mg QD | Percentage of Subjects Seizure-free During the Last 4 Weeks on Eslicarbazepine Acetate Monotherapy. | 14.4 percentage of participants |
Secondary
Percentage of Subjects That Are Seizure-free During the 10-week Double-blind Monotherapy Treatment Period.
Seizure-free subjects during the monotherapy period were determined as subjects who had seizure assessments during the monotherapy period, and did not have any seizures in the 10 weeks between Visits 6 and 9 (Weeks 9 through 18). Subjects who discontinued during this period were considered not seizure-free even if they were seizure-free at the time of discontinuation, i.e., to be considered seizure-free, subjects must complete the 10-week period without any seizures.
Time frame: Weeks 9 through 18
Population: efficacy population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Eslicarbazepine 1200 mg QD | Percentage of Subjects That Are Seizure-free During the 10-week Double-blind Monotherapy Treatment Period. | 8.3 percentage of participants |
| Eslicarbazepine 1600 mg QD | Percentage of Subjects That Are Seizure-free During the 10-week Double-blind Monotherapy Treatment Period. | 7.6 percentage of participants |
Secondary
Percentage of Subjects With Increase of Body Weight >= 7%
Time frame: 18 Week Double-blind treatment period
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Eslicarbazepine 1200 mg QD | Percentage of Subjects With Increase of Body Weight >= 7% | 2 Percentage of participants |
| Eslicarbazepine 1600 mg QD | Percentage of Subjects With Increase of Body Weight >= 7% | 9 Percentage of participants |
Secondary
Proportion (%) of Events in Each Classification of the Columbia Suicide Severity Rating Scale (C SSRS).
Time frame: 18 Week Double-blind treatment period
Population: ITT population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Eslicarbazepine 1200 mg QD | Proportion (%) of Events in Each Classification of the Columbia Suicide Severity Rating Scale (C SSRS). | SuicidalBehavior | 0 Percent of participants |
| Eslicarbazepine 1200 mg QD | Proportion (%) of Events in Each Classification of the Columbia Suicide Severity Rating Scale (C SSRS). | Non-suicidal Self-Injurious Behavior | 0 Percent of participants |
| Eslicarbazepine 1200 mg QD | Proportion (%) of Events in Each Classification of the Columbia Suicide Severity Rating Scale (C SSRS). | Wish to be Dead | 4.6 Percent of participants |
| Eslicarbazepine 1200 mg QD | Proportion (%) of Events in Each Classification of the Columbia Suicide Severity Rating Scale (C SSRS). | Aborted Attempt | 0 Percent of participants |
| Eslicarbazepine 1200 mg QD | Proportion (%) of Events in Each Classification of the Columbia Suicide Severity Rating Scale (C SSRS). | Non-specific Active Suicidal Thoughts | 4.6 Percent of participants |
| Eslicarbazepine 1200 mg QD | Proportion (%) of Events in Each Classification of the Columbia Suicide Severity Rating Scale (C SSRS). | Actual Attempt | 0 Percent of participants |
| Eslicarbazepine 1200 mg QD | Proportion (%) of Events in Each Classification of the Columbia Suicide Severity Rating Scale (C SSRS). | Act. Suicidal Idea. w/any method-no intent to act | 1.5 Percent of participants |
| Eslicarbazepine 1200 mg QD | Proportion (%) of Events in Each Classification of the Columbia Suicide Severity Rating Scale (C SSRS). | Preparatory Attempts | 1.5 Percent of participants |
| Eslicarbazepine 1200 mg QD | Proportion (%) of Events in Each Classification of the Columbia Suicide Severity Rating Scale (C SSRS). | Act. Suicidal Idea.w/any method-some intent to act | 0 Percent of participants |
| Eslicarbazepine 1200 mg QD | Proportion (%) of Events in Each Classification of the Columbia Suicide Severity Rating Scale (C SSRS). | Act. Suicidal Idea. w/any method-Spec. Plan to act | 0 Percent of participants |
| Eslicarbazepine 1200 mg QD | Proportion (%) of Events in Each Classification of the Columbia Suicide Severity Rating Scale (C SSRS). | Interrupted Attempt | 1.5 Percent of participants |
| Eslicarbazepine 1600 mg QD | Proportion (%) of Events in Each Classification of the Columbia Suicide Severity Rating Scale (C SSRS). | Act. Suicidal Idea. w/any method-Spec. Plan to act | 0 Percent of participants |
| Eslicarbazepine 1600 mg QD | Proportion (%) of Events in Each Classification of the Columbia Suicide Severity Rating Scale (C SSRS). | Actual Attempt | 0 Percent of participants |
| Eslicarbazepine 1600 mg QD | Proportion (%) of Events in Each Classification of the Columbia Suicide Severity Rating Scale (C SSRS). | Non-suicidal Self-Injurious Behavior | 0 Percent of participants |
| Eslicarbazepine 1600 mg QD | Proportion (%) of Events in Each Classification of the Columbia Suicide Severity Rating Scale (C SSRS). | Interrupted Attempt | 0 Percent of participants |
| Eslicarbazepine 1600 mg QD | Proportion (%) of Events in Each Classification of the Columbia Suicide Severity Rating Scale (C SSRS). | Aborted Attempt | 0 Percent of participants |
| Eslicarbazepine 1600 mg QD | Proportion (%) of Events in Each Classification of the Columbia Suicide Severity Rating Scale (C SSRS). | Preparatory Attempts | 0 Percent of participants |
| Eslicarbazepine 1600 mg QD | Proportion (%) of Events in Each Classification of the Columbia Suicide Severity Rating Scale (C SSRS). | SuicidalBehavior | 0 Percent of participants |
| Eslicarbazepine 1600 mg QD | Proportion (%) of Events in Each Classification of the Columbia Suicide Severity Rating Scale (C SSRS). | Wish to be Dead | 3.1 Percent of participants |
| Eslicarbazepine 1600 mg QD | Proportion (%) of Events in Each Classification of the Columbia Suicide Severity Rating Scale (C SSRS). | Non-specific Active Suicidal Thoughts | 0.8 Percent of participants |
| Eslicarbazepine 1600 mg QD | Proportion (%) of Events in Each Classification of the Columbia Suicide Severity Rating Scale (C SSRS). | Act. Suicidal Idea. w/any method-no intent to act | 0.8 Percent of participants |
| Eslicarbazepine 1600 mg QD | Proportion (%) of Events in Each Classification of the Columbia Suicide Severity Rating Scale (C SSRS). | Act. Suicidal Idea.w/any method-some intent to act | 0 Percent of participants |
Secondary
Proportion (%) of Subjects With Normal Baseline Sodium Reaching Blood Sodium ≤135 mmol/L, ≤130 mmol/L, and ≤125 mmol/L
Proportion (%) of Subjects With Normal Baseline Sodium Reaching Blood Sodium ≤135 mmol/L, ≤130 mmol/L, and ≤125 mmol/L
Time frame: 18 Week Double-blind treatment period
Population: ITT population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Eslicarbazepine 1200 mg QD | Proportion (%) of Subjects With Normal Baseline Sodium Reaching Blood Sodium ≤135 mmol/L, ≤130 mmol/L, and ≤125 mmol/L | ≤ 135 and > 130 mEq/L | 29 Percent |
| Eslicarbazepine 1200 mg QD | Proportion (%) of Subjects With Normal Baseline Sodium Reaching Blood Sodium ≤135 mmol/L, ≤130 mmol/L, and ≤125 mmol/L | ≤ 13- amd > 125 mEq/L | 6 Percent |
| Eslicarbazepine 1200 mg QD | Proportion (%) of Subjects With Normal Baseline Sodium Reaching Blood Sodium ≤135 mmol/L, ≤130 mmol/L, and ≤125 mmol/L | ≤125 mEq/L | 3 Percent |
| Eslicarbazepine 1600 mg QD | Proportion (%) of Subjects With Normal Baseline Sodium Reaching Blood Sodium ≤135 mmol/L, ≤130 mmol/L, and ≤125 mmol/L | ≤ 135 and > 130 mEq/L | 61 Percent |
| Eslicarbazepine 1600 mg QD | Proportion (%) of Subjects With Normal Baseline Sodium Reaching Blood Sodium ≤135 mmol/L, ≤130 mmol/L, and ≤125 mmol/L | ≤ 13- amd > 125 mEq/L | 11 Percent |
| Eslicarbazepine 1600 mg QD | Proportion (%) of Subjects With Normal Baseline Sodium Reaching Blood Sodium ≤135 mmol/L, ≤130 mmol/L, and ≤125 mmol/L | ≤125 mEq/L | 5 Percent |
Secondary
Responder Rate (Proportion [%] of Subjects With a ≥50% Reduction of Seizure Frequency From Baseline).
Responder rate was defined as the proportion (%) of subjects with a ≥ 50% reduction of seizure frequency from baseline. This analysis was done for the titration (Weeks 1 to 2), AED taper/conversion (Weeks 3 to 8), monotherapy (Weeks 9 to 18), and double-blind (Weeks 1 to 18) periods.
Time frame: Week 0 to Week 18, Double blind: weeks to 8; baseline:weeks -8 to -1; titration: weeks 1 to 2; AED taper/conversion: weeks 3 to 8; monotherapy: weeks 9 to 18
Population: efficacy population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Eslicarbazepine 1200 mg QD | Responder Rate (Proportion [%] of Subjects With a ≥50% Reduction of Seizure Frequency From Baseline). | Responder rate during double blind period | 36.7 percentage of participants |
| Eslicarbazepine 1200 mg QD | Responder Rate (Proportion [%] of Subjects With a ≥50% Reduction of Seizure Frequency From Baseline). | Responder rate during the titration period | 46.7 percentage of participants |
| Eslicarbazepine 1200 mg QD | Responder Rate (Proportion [%] of Subjects With a ≥50% Reduction of Seizure Frequency From Baseline). | Responder Rate during the AED T/C period | 41.7 percentage of participants |
| Eslicarbazepine 1200 mg QD | Responder Rate (Proportion [%] of Subjects With a ≥50% Reduction of Seizure Frequency From Baseline). | Responder rate during monotherapy period | 35.0 percentage of participants |
| Eslicarbazepine 1600 mg QD | Responder Rate (Proportion [%] of Subjects With a ≥50% Reduction of Seizure Frequency From Baseline). | Responder rate during monotherapy period | 32.2 percentage of participants |
| Eslicarbazepine 1600 mg QD | Responder Rate (Proportion [%] of Subjects With a ≥50% Reduction of Seizure Frequency From Baseline). | Responder rate during double blind period | 39.8 percentage of participants |
| Eslicarbazepine 1600 mg QD | Responder Rate (Proportion [%] of Subjects With a ≥50% Reduction of Seizure Frequency From Baseline). | Responder Rate during the AED T/C period | 43.2 percentage of participants |
| Eslicarbazepine 1600 mg QD | Responder Rate (Proportion [%] of Subjects With a ≥50% Reduction of Seizure Frequency From Baseline). | Responder rate during the titration period | 51.7 percentage of participants |
Secondary
Standardized Seizure Frequency (SSF) by Period
Seizure frequency was evaluated by using a standardized frequency per 4 weeks (28 days). It was evaluated for five periods: baseline (Weeks -8 to -1), titration (Weeks 1 to 2), AED taper/conversion (Weeks 3 to 8), monotherapy (Weeks 9 to 18), and double-blind (Weeks 1 to 18).
Time frame: Week 1 to Week 18, Double-blind: weeks 1 to 18; Baseline: weeks -8 to -1; Titration: weeks 1 to 2; AED taper/conversion: weeks 3 to 8; Monotherapy: weeks 9 to 18
Population: efficacy population (ESL 1200 mg) Double-blind: 60; Baseline: 60; Titration: 60; AED taper/conversion: 60; Monotherapy: 43 (ESL 1600 mg) Double-blind: 118; Baseline: 118; Titration: 118; AED taper/conversion: 114; Monotherapy: 93
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eslicarbazepine 1200 mg QD | Standardized Seizure Frequency (SSF) by Period | SSF during baseline | 8.7 Number of seizures in 28 days | Standard Deviation 5.63 |
| Eslicarbazepine 1200 mg QD | Standardized Seizure Frequency (SSF) by Period | SSF during AED taper/conversion period | 8.7 Number of seizures in 28 days | Standard Deviation 14.78 |
| Eslicarbazepine 1200 mg QD | Standardized Seizure Frequency (SSF) by Period | SSF during titration period | 6.2 Number of seizures in 28 days | Standard Deviation 7.77 |
| Eslicarbazepine 1200 mg QD | Standardized Seizure Frequency (SSF) by Period | SSF during monotherapy period | 13.2 Number of seizures in 28 days | Standard Deviation 29.52 |
| Eslicarbazepine 1200 mg QD | Standardized Seizure Frequency (SSF) by Period | SSF during double-blind period | 8.8 Number of seizures in 28 days | Standard Deviation 12.89 |
| Eslicarbazepine 1600 mg QD | Standardized Seizure Frequency (SSF) by Period | SSF during monotherapy period | 6.8 Number of seizures in 28 days | Standard Deviation 7.65 |
| Eslicarbazepine 1600 mg QD | Standardized Seizure Frequency (SSF) by Period | SSF during double-blind period | 6.9 Number of seizures in 28 days | Standard Deviation 6.5 |
| Eslicarbazepine 1600 mg QD | Standardized Seizure Frequency (SSF) by Period | SSF during baseline | 10.9 Number of seizures in 28 days | Standard Deviation 7.7 |
| Eslicarbazepine 1600 mg QD | Standardized Seizure Frequency (SSF) by Period | SSF during titration period | 6.4 Number of seizures in 28 days | Standard Deviation 7.53 |
| Eslicarbazepine 1600 mg QD | Standardized Seizure Frequency (SSF) by Period | SSF during AED taper/conversion period | 6.9 Number of seizures in 28 days | Standard Deviation 6.9 |
Secondary
Time on Eslicarbazepine Acetate Monotherapy.
The start of the monotherapy period was defined as the date of termination of all other AEDs while taking study monotherapy medication. Time on monotherapy was defined from the start of monotherapy period to the last dose of monotherapy treatment.
Time frame: Week 8 to Week 18
Population: efficacy population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Eslicarbazepine 1200 mg QD | Time on Eslicarbazepine Acetate Monotherapy. | NA days |
| Eslicarbazepine 1600 mg QD | Time on Eslicarbazepine Acetate Monotherapy. | NA days |