Epilepsy
Conditions
Keywords
Seizures, Epilepsy, Anticonvulsant, Monotherapy, Historical control
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 titration period, 6-week taper or conversion period, and a 10-week monotherapy period. 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
DRUGEslicarbazepine acetate 1600 mg
1600 mg once per day
1200 once per day
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) * Medical history of seizures; * Absence of confounding factors (pseudoseizures, syncope); * 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 structural abnormality (eg, tumor or malformation) * ≥ 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: * Non-childbearing potential (ie, physiologically incapable of becoming pregnant, including any female who is pre-menarchal or post-menopausal); * 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 | From beginning of Week 3 to end of Week 18 | Cumulative exit rate was defined as the proportion of subjects meeting at least one of the following five exit criteria over a 16-week study period (from start of AED taper/con. period (Wk 3) to end of double blind monotherapy period (Wk 18)).1.One episode of status epilepticus.2.One secondary gen. partial seizure (in subjects who did not have gen.seizures during 6 mo. 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 week 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 week baseline period. If the highest number of seizures in any consecutive 2 day period during the 8 week 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. | Week 15 through 18 | Percentage of participants that were Seizure-free 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 (% of Subjects Completing the 18 Weeks of Double-blind Treatment). | 18 weeks | 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 (% of Subjects Entering the Monotherapy Period Who Complete). | Week 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. | 18 weeks, Double-blind:weeks 1-18; Baseline: weeks -8to -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 1-18; baseline: weeks -8 to -1; Titration: weeks 1-2; AED taper/conversion; weeks 3-8; monotherapy weeks 9-18 | 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. |
| Proportion (%) of Subjects Reaching Each Exit Criteria | Week 1 to Week 18, (beginning of week 1 to end of week 18) | The proportion (%) of subjects reaching each of the 5 exit criteria-1.One episode of status epilepticus.2.One secondary gen. partial seizure (in subjects who did not have gen.seizures during 6 mo. 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 week 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 week baseline period. If the highest number of seizures in any consecutive 2 day period during the 8 week 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 |
| Proportion (%) of Subjects That Are Seizure-free During the 10-week Double-blind Monotherapy Treatment Period. | Week 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 in Montgomery-Asberg Depression Rating Scale (MADRS),From Baseline . | 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 item scores. From 0-60, high score indicates more severe |
| Change in Total Score of MADRS From Baseline 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 item scores. From 0-60, higher score indicates more severe |
| Proportion (%) of Subjects With Increase of Body Weight >= 7% From Baseline | 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. | Week 0 to Week 18 | Proportion (%) of Subjects With Normal Baseline Sodium Reaching Blood Sodium ≤135 mmol/L, ≤130 mmol/L, and ≤125 mmol/L |
| Proportion (%) of Events in Each Classification of the Columbia Suicide Severity Rating Scale (C SSRS). | 18 Week Double-blind treatment period | — |
| Standardized Seizure Frequency (SSF) by Period | Double-blind: week 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). |
| 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. |
Countries
Bulgaria, Czechia, Serbia, Ukraine, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| ESL1200 mg Subjects randomized to 1200 mg QD eslicarbazepine acetate 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.. | 58 |
| ESL 1600 mg Subjects randomized to 1600 mg QD of eslicarbazepineacetate 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. | 114 |
| Total | 172 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 9 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | met exclusion criteria | 1 | 0 |
| Overall Study | met exit criteria | 7 | 13 |
| Overall Study | Physician Decision | 1 | 1 |
| Overall Study | Pregnancy | 0 | 1 |
| Overall Study | Protocol Violation | 0 | 2 |
| Overall Study | unable to swallow capsule | 0 | 1 |
| Overall Study | Withdrawal by Subject | 7 | 6 |
Baseline characteristics
| Characteristic | ESL 1600 mg | Total | ESL1200 mg |
|---|---|---|---|
| Age, Categorical <=18 years | 4 Participants | 7 Participants | 3 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 110 Participants | 165 Participants | 55 Participants |
| Age, Customized 18-39 years | 59 participants | 91 participants | 32 participants |
| Age, Customized <18 years | 4 participants | 7 participants | 3 participants |
| Age, Customized 40-65 years | 51 participants | 74 participants | 23 participants |
| Age, Customized >65 years | 0 participants | 0 participants | 0 participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants | 8 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 107 Participants | 164 Participants | 57 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Bulgaria | 19 participants | 25 participants | 6 participants |
| Region of Enrollment Czech Republic | 22 participants | 33 participants | 11 participants |
| Region of Enrollment Serbia | 3 participants | 3 participants | 0 participants |
| Region of Enrollment Ukraine | 42 participants | 68 participants | 26 participants |
| Region of Enrollment United States | 28 participants | 43 participants | 15 participants |
| Sex: Female, Male Female | 62 Participants | 89 Participants | 27 Participants |
| Sex: Female, Male Male | 52 Participants | 83 Participants | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 29 / 58 | 64 / 114 |
| serious Total, serious adverse events | 1 / 58 | 8 / 114 |
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 following five exit criteria over a 16-week study period (from start of AED taper/con. period (Wk 3) to end of double blind monotherapy period (Wk 18)).1.One episode of status epilepticus.2.One secondary gen. partial seizure (in subjects who did not have gen.seizures during 6 mo. 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 week 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 week baseline period. If the highest number of seizures in any consecutive 2 day period during the 8 week 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: From beginning of Week 3 to end of Week 18
Population: Efficacy population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ESL1200 mg | Cumulative 112-day Exit Rate as Estimated by Kaplan-Meier Method | 0.156 proportion of participants |
| ESL 1600 mg | Cumulative 112-day Exit Rate as Estimated by Kaplan-Meier Method | 0.128 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: 18 weeks, Double-blind:weeks 1-18; Baseline: weeks -8to -1; titration: weeks 1 to 2; AED taper/conversion: weeks 3 to 8; monotherapy; weeks 9 to 18
Population: Efficacy population (ESL 1200mg) Double-blind: 54; Titration: 54; AED taper/conversion:54; Monotherapy: 48 (ESL1600 mg) Double-blind:98; Titration: 98; AED taper/conversion: 98; Monotherapy: 87
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| ESL1200 mg | Change in Seizure Frequency From Baseline. | Relative(%) change from baseline fo DB pd n=54,98 | -36.1 Percent change |
| ESL1200 mg | Change in Seizure Frequency From Baseline. | Relative(%)chg from baseline for titrat pd n=54,98 | -19.3 Percent change |
| ESL1200 mg | Change in Seizure Frequency From Baseline. | Relative (%) chg from baseline-AED t/c pd n=54,98 | -39.4 Percent change |
| ESL1200 mg | Change in Seizure Frequency From Baseline. | Relative (%) change from baseline-mono pd n=48,87 | -45.7 Percent change |
| ESL 1600 mg | Change in Seizure Frequency From Baseline. | Relative (%) change from baseline-mono pd n=48,87 | -52.1 Percent change |
| ESL 1600 mg | Change in Seizure Frequency From Baseline. | Relative(%) change from baseline fo DB pd n=54,98 | -47.5 Percent change |
| ESL 1600 mg | Change in Seizure Frequency From Baseline. | Relative (%) chg from baseline-AED t/c pd n=54,98 | -42.9 Percent change |
| ESL 1600 mg | Change in Seizure Frequency From Baseline. | Relative(%)chg from baseline for titrat pd n=54,98 | -35.6 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: Efficacy Population (ESL 1200 mg) Change from baseline to end of AED taper/conversion period: 45; Change from baseline to end of monotherapy period:50 (ESL1600 mg) Change from baseline to end of AED taper/conversion period: 85; Change from baseline to end of monotherapy period:96
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ESL1200 mg | Change in Total Score From Baseline in 31-Item Quality of Life in Epilepsy (QOLIE-31). | chg from baseline-end of AED taper/covn.pd n=45,85 | 3.4 units on a scale | Standard Deviation 12.03 |
| ESL1200 mg | Change in Total Score From Baseline in 31-Item Quality of Life in Epilepsy (QOLIE-31). | change from baseline-end of monotherapy pd n=50,96 | 4.0 units on a scale | Standard Deviation 11.48 |
| ESL 1600 mg | Change in Total Score From Baseline in 31-Item Quality of Life in Epilepsy (QOLIE-31). | chg from baseline-end of AED taper/covn.pd n=45,85 | 5.8 units on a scale | Standard Deviation 11.77 |
| ESL 1600 mg | Change in Total Score From Baseline in 31-Item Quality of Life in Epilepsy (QOLIE-31). | change from baseline-end of monotherapy pd n=50,96 | 4.7 units on a scale | Standard Deviation 13.7 |
Secondary
Change in Total Score in Montgomery-Asberg Depression Rating Scale (MADRS),From Baseline .
The total score of MADRS is defined as the sum of all individual item scores. From 0-60, high score indicates more severe
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: 48; Change from baseline to end of monotherapy period: 54 (ESL 1600 mg) Change from baseline to end of AED taper/conversion period: 88; Change from baseline to end of monotherapy period: 98
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ESL1200 mg | Change in Total Score in Montgomery-Asberg Depression Rating Scale (MADRS),From Baseline . | chg from baseline-end of AED taper/covn.pd n=48,88 | -1.2 units on a scale | Standard Deviation 3.69 |
| ESL1200 mg | Change in Total Score in Montgomery-Asberg Depression Rating Scale (MADRS),From Baseline . | chg from baseline-end of monotherapy pd n=54,98 | 0.0 units on a scale | Standard Deviation 6.47 |
| ESL 1600 mg | Change in Total Score in Montgomery-Asberg Depression Rating Scale (MADRS),From Baseline . | chg from baseline-end of AED taper/covn.pd n=48,88 | -1.8 units on a scale | Standard Deviation 4.01 |
| ESL 1600 mg | Change in Total Score in Montgomery-Asberg Depression Rating Scale (MADRS),From Baseline . | chg from baseline-end of monotherapy pd n=54,98 | -1.6 units on a scale | Standard Deviation 4.54 |
Secondary
Change in Total Score of MADRS From Baseline in Those Subjects With a MADRS Score of ≥14 at Randomization.
The total score of MADRS is defined as the sum of all individual item scores. From 0-60, higher score indicates more severe
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: 7; Change from baseline to end of monotherapy period: 7 (ESL 1600 mg) Change from baseline to end of AED taper/conversion period: 16; Change from baseline to end of monotherapy period: 18
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ESL1200 mg | Change in Total Score of MADRS From Baseline in Those Subjects With a MADRS Score of ≥14 at Randomization. | chge from baseline-end of AED taper/covn.pd n=7,16 | -3.9 units on a scale | Standard Deviation 4.3 |
| ESL1200 mg | Change in Total Score of MADRS From Baseline in Those Subjects With a MADRS Score of ≥14 at Randomization. | chg from baseline-end of monotherapy pd n=7,18 | -6.1 units on a scale | Standard Deviation 6.72 |
| ESL 1600 mg | Change in Total Score of MADRS From Baseline in Those Subjects With a MADRS Score of ≥14 at Randomization. | chge from baseline-end of AED taper/covn.pd n=7,16 | -6.6 units on a scale | Standard Deviation 4.15 |
| ESL 1600 mg | Change in Total Score of MADRS From Baseline in Those Subjects With a MADRS Score of ≥14 at Randomization. | chg from baseline-end of monotherapy pd n=7,18 | -4.1 units on a scale | Standard Deviation 7.58 |
Secondary
Completion Rate During the 10 Weeks of Monotherapy (% of Subjects Entering the Monotherapy Period Who Complete).
Monotherapy completion rate was defined as the proportion (%) of subjects entering the monotherapy period who completed the 10 weeks of monotherapy treatment.
Time frame: Week 8 through 18
Population: Efficacy population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ESL1200 mg | Completion Rate During the 10 Weeks of Monotherapy (% of Subjects Entering the Monotherapy Period Who Complete). | 85.4 percentage of participants |
| ESL 1600 mg | Completion Rate During the 10 Weeks of Monotherapy (% of Subjects Entering the Monotherapy Period Who Complete). | 90.9 percentage of participants |
Secondary
Completion Rate (% of Subjects Completing the 18 Weeks of Double-blind Treatment).
Subjects completing the study were determined as subjects who completed the 18 weeks of double-blind treatment.
Time frame: 18 weeks
Population: Efficacy population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ESL1200 mg | Completion Rate (% of Subjects Completing the 18 Weeks of Double-blind Treatment). | 75.9 percentage of participants |
| ESL 1600 mg | Completion Rate (% of Subjects Completing the 18 Weeks of Double-blind Treatment). | 80.0 percentage of participants |
Secondary
Percentage of Subjects Seizure-free During the Last 4 Weeks on Eslicarbazepine Acetate Monotherapy.
Percentage of participants that were Seizure-free 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: Week 15 through 18
Population: Efficacy population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ESL1200 mg | Percentage of Subjects Seizure-free During the Last 4 Weeks on Eslicarbazepine Acetate Monotherapy. | 16.7 percentage of participants |
| ESL 1600 mg | Percentage of Subjects Seizure-free During the Last 4 Weeks on Eslicarbazepine Acetate Monotherapy. | 17.0 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) |
|---|---|---|---|
| ESL1200 mg | Proportion (%) of Events in Each Classification of the Columbia Suicide Severity Rating Scale (C SSRS). | Aborted Attempt | 0 Percent of particiants |
| ESL1200 mg | Proportion (%) of Events in Each Classification of the Columbia Suicide Severity Rating Scale (C SSRS). | Wish to be Dead | 1.7 Percent of particiants |
| ESL1200 mg | Proportion (%) of Events in Each Classification of the Columbia Suicide Severity Rating Scale (C SSRS). | Interrupted Attempt | 0 Percent of particiants |
| ESL1200 mg | Proportion (%) of Events in Each Classification of the Columbia Suicide Severity Rating Scale (C SSRS). | Non-specific Active Suicidal Thoughts | 0 Percent of particiants |
| ESL1200 mg | Proportion (%) of Events in Each Classification of the Columbia Suicide Severity Rating Scale (C SSRS). | Preparatory Attempts | 0 Percent of particiants |
| ESL1200 mg | 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 Percent of particiants |
| ESL1200 mg | Proportion (%) of Events in Each Classification of the Columbia Suicide Severity Rating Scale (C SSRS). | Non-suicidal Self-Injurious Behavior | 0 Percent of particiants |
| ESL1200 mg | 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 particiants |
| ESL1200 mg | Proportion (%) of Events in Each Classification of the Columbia Suicide Severity Rating Scale (C SSRS). | Suicidal Behavior | 3.4 Percent of particiants |
| ESL1200 mg | 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 particiants |
| ESL1200 mg | Proportion (%) of Events in Each Classification of the Columbia Suicide Severity Rating Scale (C SSRS). | Actual Attempt | 3.4 Percent of particiants |
| ESL 1600 mg | 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 particiants |
| ESL 1600 mg | Proportion (%) of Events in Each Classification of the Columbia Suicide Severity Rating Scale (C SSRS). | Actual Attempt | 0 Percent of particiants |
| ESL 1600 mg | Proportion (%) of Events in Each Classification of the Columbia Suicide Severity Rating Scale (C SSRS). | Non-suicidal Self-Injurious Behavior | 0.9 Percent of particiants |
| ESL 1600 mg | Proportion (%) of Events in Each Classification of the Columbia Suicide Severity Rating Scale (C SSRS). | Interrupted Attempt | 0 Percent of particiants |
| ESL 1600 mg | Proportion (%) of Events in Each Classification of the Columbia Suicide Severity Rating Scale (C SSRS). | Aborted Attempt | 0 Percent of particiants |
| ESL 1600 mg | Proportion (%) of Events in Each Classification of the Columbia Suicide Severity Rating Scale (C SSRS). | Preparatory Attempts | 0 Percent of particiants |
| ESL 1600 mg | Proportion (%) of Events in Each Classification of the Columbia Suicide Severity Rating Scale (C SSRS). | Suicidal Behavior | 0 Percent of particiants |
| ESL 1600 mg | Proportion (%) of Events in Each Classification of the Columbia Suicide Severity Rating Scale (C SSRS). | Wish to be Dead | 0.9 Percent of particiants |
| ESL 1600 mg | Proportion (%) of Events in Each Classification of the Columbia Suicide Severity Rating Scale (C SSRS). | Non-specific Active Suicidal Thoughts | 1 Percent of particiants |
| ESL 1600 mg | 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 Percent of particiants |
| ESL 1600 mg | 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 | 0.9 Percent of particiants |
Secondary
Proportion (%) of Subjects Reaching Each Exit Criteria
The proportion (%) of subjects reaching each of the 5 exit criteria-1.One episode of status epilepticus.2.One secondary gen. partial seizure (in subjects who did not have gen.seizures during 6 mo. 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 week 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 week baseline period. If the highest number of seizures in any consecutive 2 day period during the 8 week 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, (beginning of week 1 to end of week 18)
Population: Efficacy population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ESL1200 mg | Proportion (%) of Subjects Reaching Each Exit Criteria | exit criterion 3 (sponsors prog. assessment) | 3.7 percentage of participants |
| ESL1200 mg | Proportion (%) of Subjects Reaching Each Exit Criteria | exit criterion 4 (investigaor prog. assessment) | 1.9 percentage of participants |
| ESL1200 mg | Proportion (%) of Subjects Reaching Each Exit Criteria | exit criterion 2 | 1.9 percentage of participants |
| ESL1200 mg | Proportion (%) of Subjects Reaching Each Exit Criteria | exit criterion 4 (sponsor prog. assessment) | 3.7 percentage of participants |
| ESL1200 mg | Proportion (%) of Subjects Reaching Each Exit Criteria | exit criterion investigator prog. assessment) | 5.6 percentage of participants |
| ESL1200 mg | Proportion (%) of Subjects Reaching Each Exit Criteria | exit criterion 5 | 3.7 percentage of participants |
| ESL1200 mg | Proportion (%) of Subjects Reaching Each Exit Criteria | exit criterion 1 | 0 percentage of participants |
| ESL 1600 mg | Proportion (%) of Subjects Reaching Each Exit Criteria | exit criterion 5 | 5.0 percentage of participants |
| ESL 1600 mg | Proportion (%) of Subjects Reaching Each Exit Criteria | exit criterion 1 | 0 percentage of participants |
| ESL 1600 mg | Proportion (%) of Subjects Reaching Each Exit Criteria | exit criterion 3 (sponsors prog. assessment) | 1.0 percentage of participants |
| ESL 1600 mg | Proportion (%) of Subjects Reaching Each Exit Criteria | exit criterion 2 | 0 percentage of participants |
| ESL 1600 mg | Proportion (%) of Subjects Reaching Each Exit Criteria | exit criterion investigator prog. assessment) | 2.0 percentage of participants |
| ESL 1600 mg | Proportion (%) of Subjects Reaching Each Exit Criteria | exit criterion 4 (investigaor prog. assessment) | 5.0 percentage of participants |
| ESL 1600 mg | Proportion (%) of Subjects Reaching Each Exit Criteria | exit criterion 4 (sponsor prog. assessment) | 6.0 percentage of participants |
Secondary
Proportion (%) 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: Week 9 through 18
Population: Efficacy population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ESL1200 mg | Proportion (%) of Subjects That Are Seizure-free During the 10-week Double-blind Monotherapy Treatment Period. | 7.4 percentage of participants |
| ESL 1600 mg | Proportion (%) of Subjects That Are Seizure-free During the 10-week Double-blind Monotherapy Treatment Period. | 10.0 percentage of participants |
Secondary
Proportion (%) of Subjects With Increase of Body Weight >= 7% From Baseline
Time frame: 18 Week Double-blind treatment period
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ESL1200 mg | Proportion (%) of Subjects With Increase of Body Weight >= 7% From Baseline | 1.8 percentage of participants |
| ESL 1600 mg | Proportion (%) of Subjects With Increase of Body Weight >= 7% From Baseline | 11.7 percentage 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: Week 0 to Week 18
Population: ITT population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ESL1200 mg | 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 | 49.1 percentage of participants |
| ESL1200 mg | Proportion (%) of Subjects With Normal Baseline Sodium Reaching Blood Sodium ≤135 mmol/L, ≤130 mmol/L, and ≤125 mmol/L. | ≤ 130 and > 125 mEq/L | 8.8 percentage of participants |
| ESL1200 mg | Proportion (%) of Subjects With Normal Baseline Sodium Reaching Blood Sodium ≤135 mmol/L, ≤130 mmol/L, and ≤125 mmol/L. | ≤ 125 mEq/L | 0 percentage of participants |
| ESL 1600 mg | 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 | 54.5 percentage of participants |
| ESL 1600 mg | Proportion (%) of Subjects With Normal Baseline Sodium Reaching Blood Sodium ≤135 mmol/L, ≤130 mmol/L, and ≤125 mmol/L. | ≤ 130 and > 125 mEq/L | 20.9 percentage of participants |
| ESL 1600 mg | Proportion (%) of Subjects With Normal Baseline Sodium Reaching Blood Sodium ≤135 mmol/L, ≤130 mmol/L, and ≤125 mmol/L. | ≤ 125 mEq/L | 0 percentage of participants |
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 1-18; baseline: weeks -8 to -1; Titration: weeks 1-2; AED taper/conversion; weeks 3-8; monotherapy weeks 9-18
Population: Efficacy population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ESL1200 mg | Responder Rate (Proportion [%] of Subjects With a ≥50% Reduction of Seizure Frequency From Baseline). | responder rate during the AED | 29.6 percentage of participants |
| ESL1200 mg | Responder Rate (Proportion [%] of Subjects With a ≥50% Reduction of Seizure Frequency From Baseline). | responder rate during the DB period | 35.2 percentage of participants |
| ESL1200 mg | Responder Rate (Proportion [%] of Subjects With a ≥50% Reduction of Seizure Frequency From Baseline). | responder rate during monotherapy period | 38.9 percentage of participants |
| ESL1200 mg | Responder Rate (Proportion [%] of Subjects With a ≥50% Reduction of Seizure Frequency From Baseline). | responder rate during titration period | 29.6 percentage of participants |
| ESL 1600 mg | Responder Rate (Proportion [%] of Subjects With a ≥50% Reduction of Seizure Frequency From Baseline). | responder rate during monotherapy period | 46.0 percentage of participants |
| ESL 1600 mg | Responder Rate (Proportion [%] of Subjects With a ≥50% Reduction of Seizure Frequency From Baseline). | responder rate during titration period | 37.0 percentage of participants |
| ESL 1600 mg | Responder Rate (Proportion [%] of Subjects With a ≥50% Reduction of Seizure Frequency From Baseline). | responder rate during the AED | 39.0 percentage of participants |
| ESL 1600 mg | Responder Rate (Proportion [%] of Subjects With a ≥50% Reduction of Seizure Frequency From Baseline). | responder rate during the DB period | 46.0 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: Double-blind: week 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: 54; Baseline: 54; Titration: 54; AED taper/conversion; 54; Monotherapy: 48 (ESL 1600 mg) Double-blind: 100; Baseline: 98; Titration: 100; AED taper/conversion; 100; Monotherapy: 88
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ESL1200 mg | Standardized Seizure Frequency (SSF) by Period | SSF during double-blind pd n=54,100 | 5.5 seizures in 28 days | Standard Deviation 7.75 |
| ESL1200 mg | Standardized Seizure Frequency (SSF) by Period | SSF during monotherapy pd n=48,88 | 4.7 seizures in 28 days | Standard Deviation 6.1 |
| ESL1200 mg | Standardized Seizure Frequency (SSF) by Period | SSF druing baseline pd n=54,98 | 7.4 seizures in 28 days | Standard Deviation 5.89 |
| ESL1200 mg | Standardized Seizure Frequency (SSF) by Period | SSF during titration pd n=54,100 | 6.0 seizures in 28 days | Standard Deviation 6.16 |
| ESL1200 mg | Standardized Seizure Frequency (SSF) by Period | SSF during AED taper/conversion pd n=54,100 | 6.0 seizures in 28 days | Standard Deviation 9.68 |
| ESL 1600 mg | Standardized Seizure Frequency (SSF) by Period | SSF during AED taper/conversion pd n=54,100 | 5.1 seizures in 28 days | Standard Deviation 5.26 |
| ESL 1600 mg | Standardized Seizure Frequency (SSF) by Period | SSF during double-blind pd n=54,100 | 5.2 seizures in 28 days | Standard Deviation 5.38 |
| ESL 1600 mg | Standardized Seizure Frequency (SSF) by Period | SSF during titration pd n=54,100 | 6.4 seizures in 28 days | Standard Deviation 8.11 |
| ESL 1600 mg | Standardized Seizure Frequency (SSF) by Period | SSF during monotherapy pd n=48,88 | 5.0 seizures in 28 days | Standard Deviation 5.62 |
| ESL 1600 mg | Standardized Seizure Frequency (SSF) by Period | SSF druing baseline pd n=54,98 | 8.7 seizures in 28 days | Standard Deviation 7.2 |
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) |
|---|---|---|
| ESL1200 mg | Time on Eslicarbazepine Acetate Monotherapy. | NA days |
| ESL 1600 mg | Time on Eslicarbazepine Acetate Monotherapy. | NA days |