Epilepsy
Conditions
Keywords
Seizures, Epilepsy, Anticonvulsant, Monotherapy, Epilepsy with simple or complete partial onset seizures
Brief summary
This is a long term, open-label, safety extension study in subjects with partial onset seizures.
Detailed description
This is a long term, multicenter, open-label, safety extension study in subjects with partial onset seizures who have just completed, discontinued, or exited the 18-week treatment phase of Protocols 093-045 or 093-046. The initial study duration is 1 year with the option of continuing study drug treatment post 1 year until a subject discontinues study, the study drug becomes clinically available in the subject's locale, or the sponsor terminates the study drug clinical development program. 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
800 to 2400 mg once daily (QD)
Sponsors
Sumitomo Pharma America, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Masking description
open label
Eligibility
Sex/Gender
ALL
Age
16 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
Subject Inclusion/
Exclusion criteria
* Subject who completed, exited, or discontinued for reasons other than safety from the 18-week treatment phase of Protocols 093-045 or 093-046 and are willing to continue participation in this study are eligible. Subject must have completed at least the first 3 weeks of the 18-week double-blind treatment period of Protocols 093-045 or 093-046 to be eligible. * Subject 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. All subjects must sign privacy authorization form, if applicable. All females of child bearing potential (≤65 years of age) must also sign the Women of Childbearing Potential Addendum. * Subjects must, in the opinion of the Investigator (with consultation with Medical Monitor as appropriate), continue to potentially benefit from continued study participation and have no new medical conditions that would preclude study participation. * If female subject, must continue the accepted method of birth control defined in Protocols 093-045 or 093-046 for the duration of this study as well * Criterion for Continuation into the Post 1 year Part of Study: For subjects to continue into the post 1 year part of the study, subjects must, in the opinion of the Investigator (with consultation with Medical Monitor, as appropriate), continue to potentially benefit from continued study participation and have no new medical conditions that would preclude study participation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number and Percent of Subjects With Treatment Emergent Adverse Events | One year | Number and percent of subjects with treatment emergent adverse events |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number and Percentage of Subjects With Potentially Clinically Significant Clinical Laboratory Evaluations | 1 year | Number and percentage of subjects with potentially clinically significant clinical laboratory evaluations |
| Number and Percent of Subjects With Normal Baseline Sodium Reaching Blood Sodium ≤135 mmol/L, ≤130 mmol/L, and ≤125 mmol/L | 1 year | Number and percentage of subjects who had normal sodium value (i.e. \>135 mEq/L) at baseline but reached \<=135 mEq/L and \>130 mEq/L, \<=130 mEq/L and \>125 mEq/L, or \<=125 mEq/L at any post baseline. |
| Percentage of Subjects With Increase of Body Weight ≥7% | 1 year | Percentage of subjects with increase of body weight ≥7% |
| Number and Percentage of Subjects With Orthostatic Effects. | 1 year | Number and percentage of subjects with orthostatic effects. |
| Number and Percentage of Subjects With QTc-F Changes (in Categories) From Baseline. | Baseline, Month 12 | Number and percentage of subjects by QT interval corrected using the Fridericia fomula (QTcF) categories Based on the numbers of subjects who had at least one post-baseline assessment, the number and percentage of subjects with QTcF values in the following categories were summarized: 1. \>500 millisecond (msec) at any post-baseline timepoint but not present at baseline 2. \>480 msec at any post-baseline timepoint but not present at baseline 3. \>450 msec at any post-baseline timepoint but not present at baseline 4. Change from Baseline \>=60 ms for at least one post-baseline measurement 5. Change from Baseline \>=30 ms for at least one post-baseline measurement and \<60 ms for all post-baseline measurement QT interval is a measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle. |
| Percentage of Events in Each Classification of the Columbia Suicide Severity Rating Scale (C SSRS). | 1 year | The C-SSRS is an instrument designed to systematically assess and track suicidal behavior and suicidal ideation. The C-SSRS will be completed by the Investigator or Sub-Investigator (or qualified site personnel). Suicidal ideation is collected as any occurrence of wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with any methods (not plan) without intent to act, active suicidal ideation with some intent to act, without specific plan, active suicidal ideation with specific plan and intent. Suicidal behavior is collected as any occurrence of actual attempts, Non-Suicidal Self-Injurious Behavior, interrupted attempts, aborted attempts, or preparatory acts or behavior, suicidal behavior. Any suicidality is defined as having at least one occurrence of Suicidal Behavior or Suicidal Ideation. |
| Time on Eslicarbazepine Acetate Monotherapy. | One year | The start of the monotherapy period was defined as the date of termination of all other anti-epileptic drugs while taking study medication. Time on eslicarbazepine acetate monotherapy is defined from the date of the first monotherapy dose in 093-045 or 093-046 study to the last known dose of monotherapy treatment, regardless of dose change and the time gap between the parent studies and the current study. |
| Completion Rate (% of Subjects Completing the One Year Treatment) | One year | Completion rate (% of subjects completing the one year treatment) |
| Responder Rate (Percentage of Subjects With a ≥50% Reduction of Seizure Frequency From Baseline). | One year | Responder rate (percentage of subjects with a ≥50% reduction of seizure frequency from baseline). |
| Percentage of Subjects That Are Seizure-free During Study | 1 year | Percentage of subjects that are seizure-free during study |
| Treatment Retention Time (Time to Withdrawal Due to Lack of Efficacy or Adverse Events) | One year | The retention time is defined from the start of eslicarbazepine acetate monotherapy period in 093-045 or 093-046 to the last known dose of open-label eslicarbazepine acetate. The time may include taking eslicarbazepine acetate concomitantly with other anti-epileptic drugs. If a subject's termination reason(s) includes: withdrawal of consent, lost to follow-up, physician decision or other, then it was assumed the subject terminated the study due to lack of efficacy. |
| Change in Total Score From Baseline in 31-Item Quality of Life in Epilepsy (QOLIE-31). | baseline and Month 12 | Change in the overall 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. |
| Change in Total Score From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS). | 1 year | The total score of MADRS is defined as the sum of all individual item scores. Each of the 10 symptoms of depression on MADRS is 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 Montgomery-Asberg Depression Rating Scale (MADRS) in Those Subjects With a MADRS Score of ≥14 at Screening | baseline and Month 12 | The total score of MADRS is defined as the sum of all individual item scores . Each of the 10 symptoms of depression on MADRS is measured on a scale of 0 to 6 with 0 representing the lowest severity of the symptom and 6 representing the highest severity. |
| Completion Rate (% of Subjects Completing Each Visit Post-one Year). | post 1 year | Completion rate (% of subjects completing each visit post-one year). |
| Change in Seizure Frequency From Baseline. | Month 12 from baseline | Relative (%) change in standard seizure frequency(SSF) from baseline |
Countries
Bulgaria, Canada, Czechia, Serbia, Ukraine, United States
Participant flow
Recruitment details
Subjects that participated in either study 093-045NCT00866775) or study 093-046(NCT01091662) were eligible to participate in study 093-050
Pre-assignment details
Subjects who completed the 18-week treatment period or exited the study per protocol may be eligible to participate. Subjects who discontinued for reasons other than reaching the exit criteria may be eligible if there is no safety concern, however, subjects must have completed at least the first 3 weeks of the 18-week double-blind treatment
Participants by arm
| Arm | Count |
|---|---|
| Eslicarbazepine Acetate Open-label treatment with eslicarbazepine acetate will be at doses between 800 and 2400 mg QD
Eslicarbazepine acetate: 800 to 2400 mg once daily (QD) | 274 |
| Total | 274 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 15 |
| Overall Study | Death | 2 |
| Overall Study | Lost to Follow-up | 10 |
| Overall Study | Not collected | 4 |
| Overall Study | Physician Decision | 3 |
| Overall Study | Protocol Violation | 10 |
| Overall Study | Withdrawal by Subject | 25 |
Baseline characteristics
| Characteristic | Eslicarbazepine Acetate |
|---|---|
| Age, Categorical <=18 years | 12 Participants |
| Age, Categorical >=65 years | 4 Participants |
| Age, Categorical Between 18 and 65 years | 258 Participants |
| Age, Continuous | 37.9 years STANDARD_DEVIATION 12.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 28 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 246 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants |
| Race (NIH/OMB) Asian | 5 Participants |
| Race (NIH/OMB) Black or African American | 22 Participants |
| Race (NIH/OMB) More than one race | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 14 Participants |
| Race (NIH/OMB) White | 229 Participants |
| Region of Enrollment Bulgaria | 18 participants |
| Region of Enrollment Canada | 3 participants |
| Region of Enrollment Czechia | 27 participants |
| Region of Enrollment Serbia | 2 participants |
| Region of Enrollment Ukraine | 57 participants |
| Region of Enrollment United States | 167 participants |
| Sex: Female, Male Female | 134 Participants |
| Sex: Female, Male Male | 140 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 274 |
| other Total, other adverse events | 166 / 274 |
| serious Total, serious adverse events | 32 / 274 |
Outcome results
Primary
Number and Percent of Subjects With Treatment Emergent Adverse Events
Number and percent of subjects with treatment emergent adverse events
Time frame: One year
Population: The Intent-to -Treat (ITT) population consisted of all subjects who had taken any open-label study medication
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Eslicarbazepine Acetate | Number and Percent of Subjects With Treatment Emergent Adverse Events | 220 Participants |
Secondary
Change in Seizure Frequency From Baseline.
Relative (%) change in standard seizure frequency(SSF) from baseline
Time frame: Month 12 from baseline
Population: Intent-to-treat (ITT) population consisted of all subjects who had taken any open-label study medication
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Eslicarbazepine Acetate | Change in Seizure Frequency From Baseline. | -66.4 percent change |
Secondary
Change in Total Score From Baseline in 31-Item Quality of Life in Epilepsy (QOLIE-31).
Change in the overall 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: baseline and Month 12
Population: The intent-to-treat (ITT) population consisted of all subjects who have taken any open-label study medication.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Eslicarbazepine Acetate | Change in Total Score From Baseline in 31-Item Quality of Life in Epilepsy (QOLIE-31). | 6.6 units on a scale | Standard Deviation 15.29 |
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 item scores. Each of the 10 symptoms of depression on MADRS is 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: 1 year
Population: The intent-to-treat (ITT) population consisted of all subjects who have taken any open-label study medication.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Eslicarbazepine Acetate | Change in Total Score From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS). | -1.5 units on a scale | Standard Deviation 6.17 |
Secondary
Change in Total Score From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) in Those Subjects With a MADRS Score of ≥14 at Screening
The total score of MADRS is defined as the sum of all individual item scores . Each of the 10 symptoms of depression on MADRS is 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: baseline and Month 12
Population: The intent-to-treat (ITT) population consisted of all subjects who have taken any open-label study medication.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Eslicarbazepine Acetate | Change in Total Score From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) in Those Subjects With a MADRS Score of ≥14 at Screening | -1.5 units on a scale | Standard Deviation 6.17 |
Secondary
Completion Rate (% of Subjects Completing Each Visit Post-one Year).
Completion rate (% of subjects completing each visit post-one year).
Time frame: post 1 year
Population: The intent-to-treat (ITT) subjects who entered the post - 1- year open -label period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Eslicarbazepine Acetate | Completion Rate (% of Subjects Completing Each Visit Post-one Year). | 66.7 percentagae of participants |
Secondary
Completion Rate (% of Subjects Completing the One Year Treatment)
Completion rate (% of subjects completing the one year treatment)
Time frame: One year
Population: The intent-to-treat (ITT) population consisted of all subjects who have taken any open-label study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Eslicarbazepine Acetate | Completion Rate (% of Subjects Completing the One Year Treatment) | 74.8 percentagae of participants |
Secondary
Number and Percentage of Subjects With Orthostatic Effects.
Number and percentage of subjects with orthostatic effects.
Time frame: 1 year
Population: The intent-to-treat (ITT) population consisted of all subjects who have taken any open-label study medication.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Eslicarbazepine Acetate | Number and Percentage of Subjects With Orthostatic Effects. | 67 Participants |
Secondary
Number and Percentage of Subjects With Potentially Clinically Significant Clinical Laboratory Evaluations
Number and percentage of subjects with potentially clinically significant clinical laboratory evaluations
Time frame: 1 year
Population: The intent-to-treat (ITT) population consisted of all subjects who have taken any open-label study medication.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Eslicarbazepine Acetate | Number and Percentage of Subjects With Potentially Clinically Significant Clinical Laboratory Evaluations | 186 Participants |
Secondary
Number and Percentage of Subjects With QTc-F Changes (in Categories) From Baseline.
Number and percentage of subjects by QT interval corrected using the Fridericia fomula (QTcF) categories Based on the numbers of subjects who had at least one post-baseline assessment, the number and percentage of subjects with QTcF values in the following categories were summarized: 1. \>500 millisecond (msec) at any post-baseline timepoint but not present at baseline 2. \>480 msec at any post-baseline timepoint but not present at baseline 3. \>450 msec at any post-baseline timepoint but not present at baseline 4. Change from Baseline \>=60 ms for at least one post-baseline measurement 5. Change from Baseline \>=30 ms for at least one post-baseline measurement and \<60 ms for all post-baseline measurement QT interval is a measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle.
Time frame: Baseline, Month 12
Population: The intent-to-treat (ITT) subjects with at least one post-baseline assessment
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Eslicarbazepine Acetate | Number and Percentage of Subjects With QTc-F Changes (in Categories) From Baseline. | >450ms at any postbaseline not present at baseline | 9 Participants |
| Eslicarbazepine Acetate | Number and Percentage of Subjects With QTc-F Changes (in Categories) From Baseline. | CFB >=60 ms for at least one post-baseline | 0 Participants |
| Eslicarbazepine Acetate | Number and Percentage of Subjects With QTc-F Changes (in Categories) From Baseline. | CFB>=30ms for at least one &<60ms for all PBL | 42 Participants |
| Eslicarbazepine Acetate | Number and Percentage of Subjects With QTc-F Changes (in Categories) From Baseline. | >500ms at any postbaseline not present at baseli | 0 Participants |
| Eslicarbazepine Acetate | Number and Percentage of Subjects With QTc-F Changes (in Categories) From Baseline. | >480ms at any postbaseline not present at baseline | 1 Participants |
Secondary
Number and Percent of Subjects With Normal Baseline Sodium Reaching Blood Sodium ≤135 mmol/L, ≤130 mmol/L, and ≤125 mmol/L
Number and percentage of subjects who had normal sodium value (i.e. \>135 mEq/L) at baseline but reached \<=135 mEq/L and \>130 mEq/L, \<=130 mEq/L and \>125 mEq/L, or \<=125 mEq/L at any post baseline.
Time frame: 1 year
Population: ITT subjects with baseline sodium and at least one post baseline sodium value
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Eslicarbazepine Acetate | Number and Percent of Subjects With Normal Baseline Sodium Reaching Blood Sodium ≤135 mmol/L, ≤130 mmol/L, and ≤125 mmol/L | <=135 mEq/L and >130 mEq/L | 48 Participants |
| Eslicarbazepine Acetate | Number and Percent of Subjects With Normal Baseline Sodium Reaching Blood Sodium ≤135 mmol/L, ≤130 mmol/L, and ≤125 mmol/L | <=130 mEq/L and >125 mEq/L | 22 Participants |
| Eslicarbazepine Acetate | Number and Percent of Subjects With Normal Baseline Sodium Reaching Blood Sodium ≤135 mmol/L, ≤130 mmol/L, and ≤125 mmol/L | <=125 mEq/L | 4 Participants |
Secondary
Percentage of Events in Each Classification of the Columbia Suicide Severity Rating Scale (C SSRS).
The C-SSRS is an instrument designed to systematically assess and track suicidal behavior and suicidal ideation. The C-SSRS will be completed by the Investigator or Sub-Investigator (or qualified site personnel). Suicidal ideation is collected as any occurrence of wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with any methods (not plan) without intent to act, active suicidal ideation with some intent to act, without specific plan, active suicidal ideation with specific plan and intent. Suicidal behavior is collected as any occurrence of actual attempts, Non-Suicidal Self-Injurious Behavior, interrupted attempts, aborted attempts, or preparatory acts or behavior, suicidal behavior. Any suicidality is defined as having at least one occurrence of Suicidal Behavior or Suicidal Ideation.
Time frame: 1 year
Population: The Intent-to-Treat (ITT) population consisted of all subjects that received any open-label study medication
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Eslicarbazepine Acetate | Percentage of Events in Each Classification of the Columbia Suicide Severity Rating Scale (C SSRS). | Any Suicidality | 4.0 percentage of events |
| Eslicarbazepine Acetate | Percentage of Events in Each Classification of the Columbia Suicide Severity Rating Scale (C SSRS). | Any suicidal ideation | 3.6 percentage of events |
| Eslicarbazepine Acetate | Percentage of Events in Each Classification of the Columbia Suicide Severity Rating Scale (C SSRS). | Any suicidal behavior | 0.7 percentage of events |
Secondary
Percentage of Subjects That Are Seizure-free During Study
Percentage of subjects that are seizure-free during study
Time frame: 1 year
Population: The intent-to-treat (ITT) population consisted of all subjects who have taken any open-label study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Eslicarbazepine Acetate | Percentage of Subjects That Are Seizure-free During Study | 7.3 percentage of participants |
Secondary
Percentage of Subjects With Increase of Body Weight ≥7%
Percentage of subjects with increase of body weight ≥7%
Time frame: 1 year
Population: The intent-to-treat (ITT) population consisted of all subjects who have taken any open-label study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Eslicarbazepine Acetate | Percentage of Subjects With Increase of Body Weight ≥7% | 27 percentagae of participants |
Secondary
Responder Rate (Percentage of Subjects With a ≥50% Reduction of Seizure Frequency From Baseline).
Responder rate (percentage of subjects with a ≥50% reduction of seizure frequency from baseline).
Time frame: One year
Population: The intent-to-treat (ITT) population consisted of all subjects who have taken any open-label study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Eslicarbazepine Acetate | Responder Rate (Percentage of Subjects With a ≥50% Reduction of Seizure Frequency From Baseline). | 62.4 percentage of participants |
Secondary
Time on Eslicarbazepine Acetate Monotherapy.
The start of the monotherapy period was defined as the date of termination of all other anti-epileptic drugs while taking study medication. Time on eslicarbazepine acetate monotherapy is defined from the date of the first monotherapy dose in 093-045 or 093-046 study to the last known dose of monotherapy treatment, regardless of dose change and the time gap between the parent studies and the current study.
Time frame: One year
Population: ITT Subjects who started the monotherapy period (Visit 6/Week 8) in 093-045 or 093-046 and did not add a non-rescue/emergency Antiepileptic drug (AED) during the start date of the monotherapy period
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Eslicarbazepine Acetate | Time on Eslicarbazepine Acetate Monotherapy. | NA Days |
Secondary
Treatment Retention Time (Time to Withdrawal Due to Lack of Efficacy or Adverse Events)
The retention time is defined from the start of eslicarbazepine acetate monotherapy period in 093-045 or 093-046 to the last known dose of open-label eslicarbazepine acetate. The time may include taking eslicarbazepine acetate concomitantly with other anti-epileptic drugs. If a subject's termination reason(s) includes: withdrawal of consent, lost to follow-up, physician decision or other, then it was assumed the subject terminated the study due to lack of efficacy.
Time frame: One year
Population: Intent-to-treat (ITT) subjects who started the monotherapy period in 093-045 or 093-046 (visi t6/week 8)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Eslicarbazepine Acetate | Treatment Retention Time (Time to Withdrawal Due to Lack of Efficacy or Adverse Events) | NA days |