Safety & Efficacy of Eslicarbazepine Monotherapy in Sub.w... | NCT01091662

NCT01091662

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
eslicarbazepine acetate 1600 mg	Experimental	Subjects randomized to 1600 mg QD of eslicarbazepine acetate will titrate from 600 mg QD(Day 0) to 1200 mg once a day(Week 2) to 1600 mg QD (Weeks 3-18) and may taper down from 1600 mg to 800 mg QD 3 days after the Week 18 visit.	Drug: Eslicarbazepine acetate 1600 mg
eslicarbazepine acetate 1200 mg	Experimental	Subjects randomized to 1200 mg QD eslicarbazepine acetate will titrate from 400 mg QD (Day0) to 800 mg QDweek2) to 1200 mg QD(weeks 3-18) and may taper down from 1200 mg to 600 mg QD 3 days after the Week 18 visit. Subjects may continue in an open-label extension study with a starting dose of 1200 mg QD, or taper off their previous antiepileptic drugs during weeks 2-8.	Drug: Eslicarbazepine acetate 1200 mg

Name	Type	Description	Arm Group Labels	Other Names
Eslicarbazepine acetate 1600 mg	Drug	1600 mg once per day	eslicarbazepine acetate 1600 mg

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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	From beginning of Week 3 to end of Week 18

Secondary Outcomes

Measure	Description	Time Frame
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.

Eligibility Module

Eligibility Criteria

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 exclusion criteria
Medical exclusion criteria: known renal insufficiency (estimated creatinine clearance [CrCL]) <60 mL/min based on serum creatinine using the Cockcroft-Gault formula
Clinical and laboratory exclusion criteria: Subjects of Asian ancestry who tests positive for the presence of the HLA-B*1502 allele
Subjects who have been on benzodiazepines, phenobarbital, or primidone on a regular basis within 3 months prior to screening
Subjects taking antipsychotics, tricyclic antidepressants, anxiolytics, sedative hypnotics including non-benzodiazepines, central opioid agonists/antagonists, monoamine oxidase inhibitors (MAOIs) within at least 5 half lives (or for at least 2 weeks whichever is longer) prior to randomization
Subjects presently on felbamate or vigabatrin

Contacts/Locations Module

Name	Affiliation	Role
CNS Medical Dirctor	Sumitomo Pharma America, Inc.	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
University of Arizona Health Sciences Center		Tucson	Arizona	85724	United States
Arkansas Neurology

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
25880756	Background	Jacobson MP, Pazdera L, Bhatia P, Grinnell T, Cheng H, Blum D; study 046 team. Efficacy and safety of conversion to monotherapy with eslicarbazepine acetate in adults with uncontrolled partial-onset seizures: a historical-control phase III study. BMC Neurol. 2015 Mar 28;15:46. doi: 10.1186/s12883-015-0305-5.

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	ESL 1200 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..
FG001	ESL1600 mg

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

Type of Units Analyzed

Arm/Group Information

ID	Title	Description
BG000	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..
BG001	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.
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Categorical

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
<=18 years	BG0003 BG0014 BG0027
Between 18 and 65 years

Age, Customized

Number

participants

Title

Denominators

Categories

<18 years

Title	Measurements
	BG0003 BG0014 BG002

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00027 BG00162 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG0001 BG0017 BG002

Region of Enrollment

Number

participants

Title

Denominators

Categories

Czech Republic

Title	Measurements
	BG00011 BG00122 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

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

Efficacy population

Posted

Number

95% Confidence Interval

proportion of participants

From beginning of Week 3 to end of Week 18

ID	Title	Description
OG000	ESL1200 mg	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.
OG001	ESL 1600 mg	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.

Units	Counts
Participants	OG00054 OG001100

Title

Denominators

Categories

Title	Measurements
	OG0000.156(0.0810 to 0.2874) OG0010.128(0.0750 to 0.2152)

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.

Efficacy population

Posted

Number

95% Confidence Interval

percentage of participants

Week 9 through 18

ID	Title	Description
OG000	ESL1200 mg	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.
OG001	ESL 1600 mg	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.

Units	Counts
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.

Efficacy population

Posted

Number

95% Confidence Interval

percentage of participants

Week 15 through 18

ID	Title	Description
OG000	ESL1200 mg	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.
OG001	ESL 1600 mg	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.

Units	Counts
Participants	OG000

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.

Efficacy population

Posted

Number

95% Confidence Interval

percentage of participants

18 weeks

ID	Title	Description
OG000	ESL1200 mg	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.
OG001	ESL 1600 mg	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.

Units	Counts
Participants	OG000

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.

Efficacy population

Posted

Number

95% Confidence Interval

percentage of participants

Week 8 through 18

ID	Title	Description
OG000	ESL1200 mg	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.
OG001	ESL 1600 mg	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.

Units	Counts
Participants	OG000

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.

Efficacy population

Posted

Median

95% Confidence Interval

days

Week 8 to Week 18

ID	Title	Description
OG000	ESL1200 mg	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.
OG001	ESL 1600 mg	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.

Units	Counts
Participants	OG000

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).

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

Posted

Median

Inter-Quartile Range

Percent change

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

ID	Title	Description
OG000	ESL 1200 mg	Titrate from 400 mg (Week 1) to 800 mg (Week2) to 1200 mg (Weeks 3-18) QD and taper down from 1200 mg to 600 mg QD 3 days after end of Week 18.
OG001	ESL 1600 mg	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 end of Week 18.

Units	Counts
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.

Efficacy population

Posted

Number

95% Confidence Interval

percentage of participants

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

ID	Title	Description
OG000	ESL1200 mg	Titrate from 400 mg (Week 1) to 800 mg (Week2) to 1200 mg (Weeks 3-18) QD and taper down from 1200 mg to 600 mg QD 3 days after end of Week 18.
OG001	ESL 1600 mg	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 end of Week 18.

Units	Counts
Participants

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

Efficacy population

Posted

Number

percentage of participants

Week 1 to Week 18, (beginning of week 1 to end of week 18)

ID	Title	Description
OG000	ESL1200 mg	Titrate from 400 mg (Week 1) to 800 mg (Week2) to 1200 mg (Weeks 3-18) QD and taper down from 1200 mg to 600 mg QD 3 days after end of Week 18.
OG001	ESL 1600 mg	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 end of Week 18.

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.

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

Posted

Mean

Standard Deviation

units on a scale

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

ID	Title	Description
OG000	ESL1200 mg	Titrate from 400 mg (Week 1) to 800 mg (Week2) to 1200 mg (Weeks 3-18) QD and taper down from 1200 mg to 600 mg QD 3 days after end of Week 18.
OG001	ESL 1600 mg	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 end of Week 18.

Units

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

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

Posted

Mean

Standard Deviation

units on a scale

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

ID	Title	Description
OG000	ESL1200 mg	Titrate from 400 mg (Week 1) to 800 mg (Week2) to 1200 mg (Weeks 3-18) QD and taper down from 1200 mg to 600 mg QD 3 days after end of Week 18.
OG001	ESL 1600 mg	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 end of Week 18.

Units	Counts
Participants

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

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

Posted

Mean

Standard Deviation

units on a scale

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

ID	Title	Description
OG000	ESL1200 mg	Titrate from 400 mg (Week 1) to 800 mg (Week2) to 1200 mg (Weeks 3-18) QD and taper down from 1200 mg to 600 mg QD 3 days after end of Week 18.
OG001	ESL 1600 mg	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 end of Week 18.

Units	Counts
Participants

Secondary

Proportion (%) of Subjects With Increase of Body Weight >= 7% From Baseline

ITT population

Posted

Number

percentage of participants

18 Week Double-blind treatment period

ID	Title	Description
OG000	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.
OG001	ESL 1600 mg	Subjects randomized to 1600 mg QD of eslicarbazepine acetate 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.

Units	Counts
Participants	OG000

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

ITT population

Posted

Number

percentage of participants

Week 0 to Week 18

ID	Title	Description
OG000	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.
OG001	ESL 1600 mg	Subjects randomized to 1600 mg QD of eslicarbazepine acetate 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.

Units	Counts
Participants	OG000

Secondary

Proportion (%) of Events in Each Classification of the Columbia Suicide Severity Rating Scale (C SSRS).

ITT population

Posted

Number

Percent of particiants

18 Week Double-blind treatment period

ID	Title	Description
OG000	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.
OG001	ESL 1600 mg	Subjects randomized to 1600 mg QD of eslicarbazepine acetate 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.

Units	Counts
Participants	OG000

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).

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

Posted

Mean

Standard Deviation

seizures in 28 days

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

ID	Title	Description
OG000	ESL1200 mg	Titrate from 400 mg (Week 1) to 800 mg (Week2) to 1200 mg (Weeks 3-18) QD and taper down from 1200 mg to 600 mg QD 3 days after end of Week 18.
OG001	ESL 1600 mg	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 end of Week 18.

Units	Counts
Participants

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	ESL1200 mg	Titrate from 400 mg (Week 1) to 800 mg (Week2) to 1200 mg (Weeks 3-18) QD and taper down from 1200 mg to 600 mg QD 3 days after end of Week 18.			1	58	29	58
EG001	ESL 1600 mg	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 end of Week 18.			8	114	64	114

Serious Adverse Events

Term	Organ System	Source Vocabulary	Statistical Information
Atrial flutter	Cardiac disorders	MedDRA ersion 13.1	EG0001 events1 affected58 at risk EG0011 events1 affected114 at risk
ankle fracture	Injury, poisoning and procedural complications	MedDRA ersion 13.1	EG0000 events0 affected58 at risk EG0011 events1 affected114 at risk
Post concussion syndrome	Injury, poisoning and procedural complications	MedDRA ersion 13.1	EG0000 events0 affected58 at risk EG0011 events1 affected114 at risk
Tibia fracture	Injury, poisoning and procedural complications	MedDRA ersion 13.1	EG0000 events0 affected58 at risk EG0011 events1 affected114 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA ersion 13.1	EG0000 events0 affected58 at risk EG0011 events1 affected114 at risk
Complex partial seizures	Nervous system disorders	MedDRA ersion 13.1	EG0000 events0 affected58 at risk EG0011 events1 affected114 at risk
Partial seizures with secondary generalisation	Nervous system disorders	MedDRA ersion 13.1	EG0000 events0 affected58 at risk EG0011 events1 affected114 at risk
Synocope	Nervous system disorders	MedDRA ersion 13.1	EG0000 events0 affected58 at risk EG0011 events1 affected114 at risk
Abortion spontaneous	Pregnancy, puerperium and perinatal conditions	MedDRA ersion 13.1	EG0000 events0 affected58 at risk EG0011 events1 affected114 at risk
Drug rash with eosinophilia and systemic symptoms	Skin and subcutaneous tissue disorders	MedDRA ersion 13.1	EG0000 events0 affected58 at risk EG0011 events1 affected114 at risk
Rash pruritic	Skin and subcutaneous tissue disorders	MedDRA ersion 13.1	EG0000 events0 affected58 at risk EG0011 events1 affected114 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Statistical Information
Nausea	Gastrointestinal disorders	MedDRA ersion 13.1	EG0008 events6 affected58 at risk EG00112 events7 affected114 at risk
Fatigue	General disorders	MedDRA ersion 13.1	EG0005 events4 affected58 at risk EG0017 events6 affected114 at risk
Influenza	Infections and infestations	MedDRA ersion 13.1	EG0003 events3 affected58 at risk EG0011 events1 affected114 at risk
Nasopharyngitis	Infections and infestations	MedDRA ersion 13.1	EG0004 events4 affected58 at risk EG0019 events9 affected114 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA ersion 13.1	EG0003 events3 affected58 at risk EG0017 events6 affected114 at risk
Dizziness	Nervous system disorders	MedDRA ersion 13.1	EG0007 events6 affected58 at risk EG00137 events24 affected114 at risk
Headache	Nervous system disorders	MedDRA ersion 13.1	EG00016 events11 affected58 at risk EG00187 events32 affected114 at risk
Solmnolence	Nervous system disorders	MedDRA ersion 13.1	EG0002 events2 affected58 at risk EG00112 events10 affected114 at risk
Anxiety	Psychiatric disorders	MedDRA ersion 13.1	EG0004 events3 affected58 at risk EG0011 events1 affected114 at risk
Insomnia	Psychiatric disorders	MedDRA ersion 13.1	EG0004 events4 affected58 at risk EG0013 events3 affected114 at risk

ID	Term
D004827	Epilepsy
D012640	Seizures

Ancestor Terms

ID	Term
D001927	Brain Diseases
D002493	Central Nervous System Diseases
D009422	Nervous System Diseases
D009461	Neurologic Manifestations
D012816	Signs and Symptoms
D013568	Pathological Conditions, Signs and Symptoms

ID	Term
C416835	eslicarbazepine acetate

Units	Counts
Participants	OG00054 OG001100