Safety and Efficacy of Eslicarbazepine Acetate Monotherap... | NCT00866775

Status Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Eslicarbazepine 1600 mg QD	Experimental	Subjects randomized to 1600 mg QD of eslicarbazepine acetate will titrate from 600 mg QD (Day 0) to 1200 mg QD (Week 1) to 1600 mg QD (Weeks 2-18) Subjects may continue in an open-label extension study with a starting dose of 1600 mg QD, or taper off study drug at the completion of this study The treatment period for subjects entering the open label extension study is up to 9 study visits over 18 weeks. The treatment period for subjects not entering the open-label extension study is up to 10 study visits over 19 weeks.	Drug: Eslicarbazepine acetate
Eslicarbazepine 1200 mg QD	Experimental	Subjects randomized to 1200 mg QD eslicarbazepine acetate will titrate from 400 mg QD (Day 0) to 800 mg QD (week 1) to 1200 mg QD (weeks 2-18) Subjects may continue in an open-label extension study with a starting dose of 1600 mg QD, or taper off study drug at the completion of this study The treatment period for subjects entering the open label extension study is up to 9 study visits over 18 weeks. The treatment period for subjects not entering the open-label extension study is up to 10 study visits over 19 weeks.	Drug: Eslicarbazepine acetate

Name	Type	Description	Arm Group Labels	Other Names
Eslicarbazepine acetate	Drug	1600 mg QD	Eslicarbazepine 1600 mg QD

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 five exit criteria over a 16-wk study period (start of Antiepilectic Drugs(AED) taper/conv.period (Wk 3 to end of double blind monotherapy period (Wk 18)):1.One episode of status epilepticus.2.One secondary general partial seizure (in subjects who did not have gen. seizures during 6 months prior to screening).3.A two fold increase in any consecutive 28 day seizure rate compared to the highest consecutive 28 day seizure rate during the 8 wk baseline period. 4.A two fold increase in any consecutive 2 day seizure rate compared to the highest consecutive 2 day seizure rate during the 8 wk baseline period. If the highest number of seizures in any consecutive 2 day period during the 8 wk baseline was 1 then 3 seizures in a consecutive 2 day period was required to exit.5.Worsening of seizures or increase in seizure frequency considered serious or requiring intervention as judged by the Investigator.	Week 3 to Week 18

Secondary Outcomes

Measure	Description	Time Frame
Percentage of Subjects That Are Seizure-free During the 10-week Double-blind Monotherapy Treatment Period.	Seizure-free subjects during the monotherapy period were determined as subjects who had seizure assessments during the monotherapy period, and did not have any seizures in the 10 weeks between Visits 6 and 9 (Weeks 9 through 18). Subjects who discontinued during this period were considered not seizure-free even if they were seizure-free at the time of discontinuation, i.e., to be considered seizure-free, subjects must complete the 10-week period without any seizures.

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) a. Medical history of seizures; b. Absence of confounding factors (pseudoseizures, syncope); c. Documented EEG recording (done within 5 years prior to screening) consistent with focal onset epilepsy.
Documented CT or MRI scan conducted within 10 years prior to screening, showing the absence of a progressive structural abnormality (eg, tumor). Mesial temporal sclerosis is acceptable.
≥4 partial onset seizures during the 8 weeks prior screening with no 28-day seizure free period.
Stable treatment with 1-2 AEDs during the last 4 weeks prior to screening.
Subjects must have the ability to comprehend the informed consent form and be willing to provide informed consent. For subjects who are unable to comprehend the written consent, a witness/caregiver who is able to describe and provide an understanding of the informed consent to the subject must sign the consent form on behalf of the subject.
Subjects must give written informed consent prior to participation in the study. For subjects <18 years of age, the informed consent must be signed by the subject's parent or legal guardian, and, when appropriate and/or required by state or local law, minor subjects must give written informed assent prior to participation in the study. Subjects of Asian ancestry are required to give written informed consent for genotyping. All subjects must sign a HIPAA Form. All females of child bearing potential must also sign the "Women of Childbearing Potential" Addendum.
A female subject is eligible to enter and participate in the study if she is of: a. Non-childbearing potential (ie, physiologically incapable of becoming pregnant, including any female who is pre-menarchal or post-menopausal); b. Child-bearing potential (all females ≤65 years of age), has a negative pregnancy test at screening and agrees to satisfy contraception requirements.

Exclusion Criteria:

Subjects with only simple partial seizures without a motor component.
Presence of generalized seizure syndromes (eg, juvenile myoclonic epilepsy or Lennox-Gastaut syndrome).
History of pseudo-seizures.
Current seizures related to an acute medical illness.
Seizures secondary to metabolic, toxic or infectious disorder or drug abuse.
Status epilepticus within 2 years prior to screening.
Seizures only occurring in a cluster pattern.
Subjects taking 2 of the following sodium channel blocking AEDs: phenytoin, carbamazepine, oxcarbazepine, or lamotrigine.
Subjects taking 2 AEDs with both being in the upper dose range (defined as approximately two-thirds of the defined daily dose).
Subjects taking more than 2 AEDs.
Subjects with progressive structural central nervous system lesion or progressive encephalopathy.
Psychiatric exclusion criteria: subjects with history of suicide attempt in last 2 years; major depressive episode within last 6 months; abuse of alcohol or substance abuse in last 2 years; significant psychiatric disorder or recurrent episodes of severe depression within 2 years prior to screening.
Medical exclusion criteria: known renal insufficiency or subject with 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
Female subjects who are currently breastfeeding or intending to breastfeed during study period.

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

Facility	Status	City	State	ZIP	Country	Contacts
Norwood Neurology		Birmingham	Alabama	35234	United States
Greystone Neurology Center

PubMed Identifier	Type	Citation	Retractions
25689448	Background	Sperling MR, Harvey J, Grinnell T, Cheng H, Blum D; 045 Study Team. Efficacy and safety of conversion to monotherapy with eslicarbazepine acetate in adults with uncontrolled partial-onset seizures: a randomized historical-control phase III study based in North America. Epilepsia. 2015 Apr;56(4):546-55. doi: 10.1111/epi.12934. Epub 2015 Feb 16.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Eslicarbazepine 1200 mg QD	Subjects randomized to 1200 mg QD eslicarbazepine will titrate from 400 mg (Week 1) to 800 mg (Week 2) to 1200 mg (Weeks 3-18) QD and taper down from 1200 mg to 600 mg QD 3 days after the end of Week 18. .
FG001	Eslicarbazepine 1600 mg QD

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

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 five exit criteria over a 16-wk study period (start of Antiepilectic Drugs(AED) taper/conv.period (Wk 3 to end of double blind monotherapy period (Wk 18)):1.One episode of status epilepticus.2.One secondary general partial seizure (in subjects who did not have gen. seizures during 6 months prior to screening).3.A two fold increase in any consecutive 28 day seizure rate compared to the highest consecutive 28 day seizure rate during the 8 wk baseline period. 4.A two fold increase in any consecutive 2 day seizure rate compared to the highest consecutive 2 day seizure rate during the 8 wk baseline period. If the highest number of seizures in any consecutive 2 day period during the 8 wk baseline was 1 then 3 seizures in a consecutive 2 day period was required to exit.5.Worsening of seizures or increase in seizure frequency considered serious or requiring intervention as judged by the Investigator.

efficacy population

Posted

Number

95% Confidence Interval

proportion of participants

Week 3 to Week 18

ID	Title	Description
OG000	Eslicarbazepine 1200 mg QD	Subjects randomized to 1200 mg QD eslicarbazepine will titrate from 400 mg (Week 1) to 800 mg (Week 2) to 1200 mg (Weeks 3-18) QD and taper down from 1200 mg to 600 mg QD 3 days after the end of Week 18. .
OG001	Eslicarbazepine 1600 mg QD	Subjects randomized to 1600 mg QD of eslicarbazepine will titrate from 600 mg (Week 1) to 1200 mg (Week 2) to 1600 mg (Weeks 3-18) QD and taper down from 1600 mg to 800 mg QD 3 days after the end of Week 18.

Units	Counts
Participants	OG00060 OG001118

Title

Denominators

Categories

Title	Measurements
	OG0000.444(0.3252 to 0.5832) OG0010.287(0.2124 to 0.3813)

Secondary

Percentage of Subjects That Are Seizure-free During the 10-week Double-blind Monotherapy Treatment Period.

Seizure-free subjects during the monotherapy period were determined as subjects who had seizure assessments during the monotherapy period, and did not have any seizures in the 10 weeks between Visits 6 and 9 (Weeks 9 through 18). Subjects who discontinued during this period were considered not seizure-free even if they were seizure-free at the time of discontinuation, i.e., to be considered seizure-free, subjects must complete the 10-week period without any seizures.

efficacy population

Posted

Number

95% Confidence Interval

percentage of participants

Weeks 9 through 18

ID	Title	Description
OG000	Eslicarbazepine 1200 mg QD	Subjects randomized to 1200 mg QD eslicarbazepine will titrate from 400 mg (Week 1) to 800 mg (Week 2) to 1200 mg (Weeks 3-18) QD and taper down from 1200 mg to 600 mg QD 3 days after the end of Week 18. .
OG001	Eslicarbazepine 1600 mg QD	Subjects randomized to 1600 mg QD of eslicarbazepine will titrate from 600 mg (Week 1) to 1200 mg (Week 2) to 1600 mg (Weeks 3-18) QD and taper down from 1600 mg to 800 mg QD 3 days after the end of Week 18.

Units

Secondary

Percentage of Subjects Seizure-free During the Last 4 Weeks on Eslicarbazepine Acetate Monotherapy.

Seizure-free subjects during the last four weeks of monotherapy were determined as subjects who had seizure assessments during the 4 weeks between Visits 8 and 9 (Weeks 15 through 18), and did not have any seizures.

efficacy population

Posted

Number

95% Confidence Interval

percentage of participants

Weeks 15 through 18

ID	Title	Description
OG000	Eslicarbazepine 1200 mg QD	Subjects randomized to 1200 mg QD eslicarbazepine will titrate from 400 mg (Week 1) to 800 mg (Week 2) to 1200 mg (Weeks 3-18) QD and taper down from 1200 mg to 600 mg QD 3 days after the end of Week 18. .
OG001	Eslicarbazepine 1600 mg QD	Subjects randomized to 1600 mg QD of eslicarbazepine will titrate from 600 mg (Week 1) to 1200 mg (Week 2) to 1600 mg (Weeks 3-18) QD and taper down from 1600 mg to 800 mg QD 3 days after the end of Week 18.

Units	Counts
Participants

Secondary

Completion Rate

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

Week 1 to Week 18

ID	Title	Description
OG000	Eslicarbazepine 1200 mg QD	Subjects randomized to 1200 mg QD eslicarbazepine will titrate from 400 mg (Week 1) to 800 mg (Week 2) to 1200 mg (Weeks 3-18) QD and taper down from 1200 mg to 600 mg QD 3 days after the end of Week 18. .
OG001	Eslicarbazepine 1600 mg QD	Subjects randomized to 1600 mg QD of eslicarbazepine will titrate from 600 mg (Week 1) to 1200 mg (Week 2) to 1600 mg (Weeks 3-18) QD and taper down from 1600 mg to 800 mg QD 3 days after the end of Week 18.

Units	Counts
Participants	OG000

Secondary

Completion Rate During the 10 Weeks of Monotherapy

Monotherapy completion rate was defined as the proportion (%) of subjects entering the monotherapy period who completed the 10 weeks of monotherapy treatment.

efficacy population

Posted

Number

95% Confidence Interval

percentage of participants

Weeks 8 through 18

ID	Title	Description
OG000	Eslicarbazepine 1200 mg QD	Subjects randomized to 1200 mg QD eslicarbazepine will titrate from 400 mg (Week 1) to 800 mg (Week 2) to 1200 mg (Weeks 3-18) QD and taper down from 1200 mg to 600 mg QD 3 days after the end of Week 18. .
OG001	Eslicarbazepine 1600 mg QD	Subjects randomized to 1600 mg QD of eslicarbazepine will titrate from 600 mg (Week 1) to 1200 mg (Week 2) to 1600 mg (Weeks 3-18) QD and taper down from 1600 mg to 800 mg QD 3 days after the end of Week 18.

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	Eslicarbazepine 1200 mg QD	Subjects randomized to 1200 mg QD eslicarbazepine will titrate from 400 mg (Week 1) to 800 mg (Week 2) to 1200 mg (Weeks 3-18) QD and taper down from 1200 mg to 600 mg QD 3 days after the end of Week 18. .
OG001	Eslicarbazepine 1600 mg QD	Subjects randomized to 1600 mg QD of eslicarbazepine will titrate from 600 mg (Week 1) to 1200 mg (Week 2) to 1600 mg (Weeks 3-18) QD and taper down from 1600 mg to 800 mg QD 3 days after the end of Week 18.

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 1200 mg) Double-blind: 60;Titration: 60; AED taper/conversion: 60; Monotherapy: 43 (ESL 1600 mg) Double-blind: 118; Titration: 118; AED taper/conversion:114; Monotherapy:93

Posted

Median

Inter-Quartile Range

percent change

Week 0 to Week 18, Double-blind: weeks 1to 18; baseline:weeks-8 to -1; Titration: weeks 1 to 2; AED taper/conversion:weeks 3 to 8; monotherapy: weeks 9 to 18

ID	Title	Description
OG000	Eslicarbazepine 1200 mg QD	Subjects randomized to 1200 mg QD eslicarbazepine will titrate from 400 mg (Week 1) to 800 mg (Week 2) to 1200 mg (Weeks 3-18) QD and taper down from 1200 mg to 600 mg QD 3 days after the end of Week 18. .
OG001	Eslicarbazepine 1600 mg QD	Subjects randomized to 1600 mg QD of eslicarbazepine will titrate from 600 mg (Week 1) to 1200 mg (Week 2) to 1600 mg (Weeks 3-18) QD and taper down from 1600 mg to 800 mg QD 3 days after the end of Week 18.

Units	Counts

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 to 8; 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	Eslicarbazepine 1200 mg QD	Subjects randomized to 1200 mg QD eslicarbazepine will titrate from 400 mg (Week 1) to 800 mg (Week 2) to 1200 mg (Weeks 3-18) QD and taper down from 1200 mg to 600 mg QD 3 days after the end of Week 18. .
OG001	Eslicarbazepine 1600 mg QD	Subjects randomized to 1600 mg QD of eslicarbazepine will titrate from 600 mg (Week 1) to 1200 mg (Week 2) to 1600 mg (Weeks 3-18) QD and taper down from 1600 mg to 800 mg QD 3 days after the end of Week 18.

Units	Counts

Secondary

Percentage of Subjects Reaching Each of the Exit Events.

The percentage of subjects reaching each of the 5 exit criteria. 1.One episode of status epilepticus.2.One secondary general partial seizure (in subjects who did not have gen. seizures during 6 months prior to screening).3.A two fold increase in any consecutive 28 day seizure rate compared to the highest consecutive 28 day seizure rate during the 8 wk baseline period. 4.A two fold increase in any consecutive 2 day seizure rate compared to the highest consecutive 2 day seizure rate during the 8 wk baseline period. If the highest number of seizures in any consecutive 2 day period during the 8 wk baseline was 1 then 3 seizures in a consecutive 2 day period was required to exit.5.Worsening of seizures or increase in seizure frequency considered serious or requiring intervention as judged by the Investigator.

efficacy population

Posted

Number

percentage of participants

Week 1 to Week 18

ID	Title	Description
OG000	Eslicarbazepine 1200 mg QD	Subjects randomized to 1200 mg QD eslicarbazepine will titrate from 400 mg (Week 1) to 800 mg (Week 2) to 1200 mg (Weeks 3-18) QD and taper down from 1200 mg to 600 mg QD 3 days after the end of Week 18. .
OG001	Eslicarbazepine 1600 mg QD	Subjects randomized to 1600 mg QD of eslicarbazepine will titrate from 600 mg (Week 1) to 1200 mg (Week 2) to 1600 mg (Weeks 3-18) QD and taper down from 1600 mg to 800 mg QD 3 days after the end of Week 18.

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.

the numbers analyzed represent all participants for whom data were available at baseline (ESL 1200 mg)Change from baseline to end of AED taper/conversion period: 39;Change from baseline to end of monotherapy period:36 (ESL1600 mg) Change from baseline to end of AED taper/conversion period: 86;Change from baseline to end of monotherapy period: 86

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	Eslicarbazepine 1200 mg QD	Subjects randomized to 1200 mg QD eslicarbazepine will titrate from 400 mg (Week 1) to 800 mg (Week 2) to 1200 mg (Weeks 3-18) QD and taper down from 1200 mg to 600 mg QD 3 days after the end of Week 18. .
OG001	Eslicarbazepine 1600 mg QD	Subjects randomized to 1600 mg QD of eslicarbazepine will titrate from 600 mg (Week 1) to 1200 mg (Week 2) to 1600 mg (Weeks 3-18) QD and taper down from 1600 mg to 800 mg QD 3 days after the end of Week 18.

Secondary

Change in Total Score From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS).

The total score of MADRS is defined as the sum of all individual symptom scores, ranging from 0 to 60, higher score indicates more severe depression. Each of the 10 symptoms of depression on MADRS was measured on a scale of 0 to 6 with 0 representing the lowest severity of the symptom and 6 representing the highest severity

efficacy population (ESL 1200 mg) Change from baseline to end of AED taper/conversion period: 45; Change from baseline to end of monotherapy period: 41 (ESL 1600 mg) Change from baseline to end of AED taper/conversion period: 92; Change from baseline to end of monotherapy period: 91

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	Eslicarbazepine 1200 mg QD	Subjects randomized to 1200 mg QD eslicarbazepine will titrate from 400 mg (Week 1) to 800 mg (Week 2) to 1200 mg (Weeks 3-18) QD and taper down from 1200 mg to 600 mg QD 3 days after the end of Week 18. .
OG001	Eslicarbazepine 1600 mg QD	Subjects randomized to 1600 mg QD of eslicarbazepine will titrate from 600 mg (Week 1) to 1200 mg (Week 2) to 1600 mg (Weeks 3-18) QD and taper down from 1600 mg to 800 mg QD 3 days after the end of Week 18.

Secondary

Change in Total Score From Baseline in MADRS in Those Subjects With a MADRS Score of ≥14 at Randomization.

efficacy population (ESL 1200 mg) Change from baseline to end of AED taper/conversation period: 7; Change from baseline to end of monotherapy period: 6 (ESL 1600 mg) Change from baseline to end of AED taper/conversation period: 13; Change from baseline to end of monotherapy period: 13

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	Eslicarbazepine 1200 mg QD	Subjects randomized to 1200 mg QD eslicarbazepine will titrate from 400 mg (Week 1) to 800 mg (Week 2) to 1200 mg (Weeks 3-18) QD and taper down from 1200 mg to 600 mg QD 3 days after the end of Week 18. .
OG001	Eslicarbazepine 1600 mg QD	Subjects randomized to 1600 mg QD of eslicarbazepine will titrate from 600 mg (Week 1) to 1200 mg (Week 2) to 1600 mg (Weeks 3-18) QD and taper down from 1600 mg to 800 mg QD 3 days after the end of Week 18.

Secondary

Percentage of Subjects With Increase of Body Weight >= 7%

ITT population

Posted

Number

Percentage of participants

18 Week Double-blind treatment period

ID	Title	Description
OG000	Eslicarbazepine 1200 mg QD	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	Eslicarbazepine 1600 mg QD	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

ITT population

Posted

Number

Percent

18 Week Double-blind treatment period

ID	Title	Description
OG000	Eslicarbazepine 1200 mg QD	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	Eslicarbazepine 1600 mg QD	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 participants

18 Week Double-blind treatment period

ID	Title	Description
OG000	Eslicarbazepine 1200 mg QD	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	Eslicarbazepine 1600 mg QD	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: 60; Baseline: 60; Titration: 60; AED taper/conversion: 60; Monotherapy: 43 (ESL 1600 mg) Double-blind: 118; Baseline: 118; Titration: 118; AED taper/conversion: 114; Monotherapy: 93

Posted

Mean

Standard Deviation

Number of seizures in 28 days

Week 1 to Week 18, Double-blind: weeks 1 to 18; Baseline: weeks -8 to -1; Titration: weeks 1 to 2; AED taper/conversion: weeks 3 to 8; Monotherapy: weeks 9 to 18

ID	Title	Description
OG000	Eslicarbazepine 1200 mg QD	Subjects randomized to 1200 mg QD eslicarbazepine will titrate from 400 mg (Week 1) to 800 mg (Week 2) to 1200 mg (Weeks 3-18) QD and taper down from 1200 mg to 600 mg QD 3 days after the end of Week 18. .
OG001	Eslicarbazepine 1600 mg QD	Subjects randomized to 1600 mg QD of eslicarbazepine will titrate from 600 mg (Week 1) to 1200 mg (Week 2) to 1600 mg (Weeks 3-18) QD and taper down from 1600 mg to 800 mg QD 3 days after the end of Week 18.

Serious Adverse Events

Term	Organ System	Source Vocabulary	Statistical Information
cardiogenic shock	Cardiac disorders	MedDRA version 13.1	EG0001 events1 affected65 at risk EG0010 events0 affected128 at risk
Nausea	Gastrointestinal disorders	MedDRA version 13.1	EG0000 events0 affected65 at risk EG0011 events1 affected128 at risk
vomiting	Gastrointestinal disorders	MedDRA version 13.1	EG0000 events0 affected65 at risk EG0011 events1 affected128 at risk
Oedema peripheral	General disorders	MedDRA version 13.1	EG0001 events1 affected65 at risk EG0010 events0 affected128 at risk
Accidnetal overdose	Injury, poisoning and procedural complications	MedDRA version 13.1	EG0000 events0 affected65 at risk EG0011 events1 affected128 at risk
Multiple injuries	Injury, poisoning and procedural complications	MedDRA version 13.1	EG0001 events1 affected65 at risk EG0010 events0 affected128 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA version 13.1	EG0001 events1 affected65 at risk EG0010 events0 affected128 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA version 13.1	EG0000 events0 affected65 at risk EG0012 events2 affected128 at risk
Pancreatic neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 13.1	EG0001 events1 affected65 at risk EG0010 events0 affected128 at risk
Cerebral cyst	Nervous system disorders	MedDRA version 13.1	EG0000 events0 affected65 at risk EG0011 events1 affected128 at risk
complex partial seizers	Nervous system disorders	MedDRA version 13.1	EG0000 events0 affected65 at risk EG0011 events1 affected128 at risk
Hypoaesthesia	Nervous system disorders	MedDRA version 13.1	EG0000 events0 affected65 at risk EG0011 events1 affected128 at risk
Partial seizures with secondary generalisation	Nervous system disorders	MedDRA version 13.1	EG0001 events1 affected65 at risk EG0010 events0 affected128 at risk
Status epilepticus	Nervous system disorders	MedDRA version 13.1	EG0000 events0 affected65 at risk EG0011 events1 affected128 at risk
Anxiety	Psychiatric disorders	MedDRA version 13.1	EG0000 events0 affected65 at risk EG0011 events1 affected128 at risk
Depression	Psychiatric disorders	MedDRA version 13.1	EG0000 events0 affected65 at risk EG0011 events1 affected128 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA version 13.1	EG0000 events0 affected65 at risk EG0011 events1 affected128 at risk
Pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA version 13.1	EG0001 events1 affected65 at risk EG0010 events0 affected128 at risk
Hypertension	Vascular disorders	MedDRA version 13.1	EG0000 events0 affected65 at risk EG0011 events1 affected128 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Statistical Information
Diplopia	Eye disorders	MedDRA version 13.1	EG0005 events5 affected65 at risk EG0016 events6 affected128 at risk
Vision blurred	Eye disorders	MedDRA version 13.1	EG0006 events6 affected65 at risk EG00115 events12 affected128 at risk
Abdominal discomfort	Gastrointestinal disorders	MedDRA version 13.1	EG0006 events4 affected65 at risk EG0014 events4 affected128 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA version 13.1	EG0006 events5 affected65 at risk EG00112 events9 affected128 at risk
Nausea	Gastrointestinal disorders	MedDRA version 13.1	EG0009 events7 affected65 at risk EG00128 events18 affected128 at risk
Toothache	Gastrointestinal disorders	MedDRA version 13.1	EG0004 events4 affected65 at risk EG0011 events1 affected128 at risk
Vomiting	Gastrointestinal disorders	MedDRA version 13.1	EG0007 events6 affected65 at risk EG00114 events11 affected128 at risk
Fatigue	General disorders	MedDRA version 13.1	EG00014 events13 affected65 at risk EG00125 events20 affected128 at risk
Gastroenteritis viral	Infections and infestations	MedDRA version 13.1	EG0004 events4 affected65 at risk EG0014 events4 affected128 at risk
Influenza	Infections and infestations	MedDRA version 13.1	EG0004 events4 affected65 at risk EG0015 events5 affected128 at risk
Nasopharyngitis	Infections and infestations	MedDRA version 13.1	EG0007 events7 affected65 at risk EG00115 events14 affected128 at risk
Confusion	Injury, poisoning and procedural complications	MedDRA version 13.1	EG0004 events4 affected65 at risk EG0018 events7 affected128 at risk
Fall	Injury, poisoning and procedural complications	MedDRA version 13.1	EG0005 events4 affected65 at risk EG0013 events3 affected128 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA version 13.1	EG0006 events4 affected65 at risk EG0019 events8 affected128 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA version 13.1	EG00011 events10 affected65 at risk EG0016 events6 affected128 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA version 13.1	EG0006 events5 affected65 at risk EG0012 events2 affected128 at risk
Dizziness	Nervous system disorders	MedDRA version 13.1	EG00031 events18 affected65 at risk EG00142 events31 affected128 at risk
Headache	Nervous system disorders	MedDRA version 13.1	EG00028 events14 affected65 at risk EG00133 events26 affected128 at risk
Memory impariment	Nervous system disorders	MedDRA version 13.1	EG0005 events5 affected65 at risk EG0012 events2 affected128 at risk
Partial seizures with secondary generalisation	Nervous system disorders	MedDRA version 13.1	EG0006 events6 affected65 at risk EG0011 events1 affected128 at risk
Somnolence	Nervous system disorders	MedDRA version 13.1	EG0008 events7 affected65 at risk EG00133 events23 affected128 at risk
Insomnia	Psychiatric disorders	MedDRA version 13.1	EG0003 events3 affected65 at risk EG0019 events8 affected128 at risk

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

ID	Title	Description
BG000	Eslicarbazepine 1200 mg QD	Subjects randomized to 1200 mg QD eslicarbazepine will titrate from 400 mg (Week 1) to 800 mg (Week 2) to 1200 mg (Weeks 3-18) QD and taper down from 1200 mg to 600 mg QD 3 days after the end of Week 18. .
BG001	Eslicarbazepine 1600 mg QD	Subjects randomized to 1600 mg QD of eslicarbazepine will titrate from 600 mg (Week 1) to 1200 mg (Week 2) to 1600 mg (Weeks 3-18) QD and taper down from 1600 mg to 800 mg QD 3 days after the end of Week 18.
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Eslicarbazepine 1200 mg QD	Subjects randomized to 1200 mg QD eslicarbazepine will titrate from 400 mg (Week 1) to 800 mg (Week 2) to 1200 mg (Weeks 3-18) QD and taper down from 1200 mg to 600 mg QD 3 days after the end of Week 18. .			4	65	46	65
EG001	Eslicarbazepine 1600 mg QD	Subjects randomized to 1600 mg QD of eslicarbazepine will titrate from 600 mg (Week 1) to 1200 mg (Week 2) to 1600 mg (Weeks 3-18) QD and taper down from 1600 mg to 800 mg QD 3 days after the end of Week 18.			8	128	100	128