Trial Outcomes & Findings for Safety & Efficacy of Eslicarbazepine Monotherapy in Sub.w/Partial Epilepsy Not Well Controlled by Current Antiepileptic (NCT NCT01091662)

NCT ID: NCT01091662

Last Updated: 2016-10-24

Results Overview

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

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 172 participants
• Primary outcome timeframe: From beginning of Week 3 to end of Week 18
• Results posted on: 2016-10-24

Participant Flow

Participant milestones

Measure	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..	ESL1600 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.
Overall Study STARTED	58	114
Overall Study COMPLETED	41	80
Overall Study NOT COMPLETED	17	34

Reasons for withdrawal

Measure	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..	ESL1600 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.
Overall Study Adverse Event	1	9
Overall Study Physician Decision	1	1
Overall Study Withdrawal by Subject	7	6
Overall Study met exit criteria	7	13
Overall Study met exclusion criteria	1	0
Overall Study Lost to Follow-up	0	1
Overall Study Pregnancy	0	1
Overall Study Protocol Violation	0	2
Overall Study unable to swallow capsule	0	1

Baseline Characteristics

Safety & Efficacy of Eslicarbazepine Monotherapy in Sub.w/Partial Epilepsy Not Well Controlled by Current Antiepileptic

Baseline characteristics by cohort

Measure	ESL1200 mg n=58 Participants 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..	ESL 1600 mg n=114 Participants 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.	Total n=172 Participants Total of all reporting groups
Age, Categorical <=18 years	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	55 Participants n=5 Participants	110 Participants n=7 Participants	165 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Customized <18 years	3 participants n=5 Participants	4 participants n=7 Participants	7 participants n=5 Participants
Age, Customized 18-39 years	32 participants n=5 Participants	59 participants n=7 Participants	91 participants n=5 Participants
Age, Customized 40-65 years	23 participants n=5 Participants	51 participants n=7 Participants	74 participants n=5 Participants
Age, Customized >65 years	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants
Sex: Female, Male Female	27 Participants n=5 Participants	62 Participants n=7 Participants	89 Participants n=5 Participants
Sex: Female, Male Male	31 Participants n=5 Participants	52 Participants n=7 Participants	83 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	7 Participants n=7 Participants	8 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	57 Participants n=5 Participants	107 Participants n=7 Participants	164 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment Czech Republic	11 participants n=5 Participants	22 participants n=7 Participants	33 participants n=5 Participants
Region of Enrollment United States	15 participants n=5 Participants	28 participants n=7 Participants	43 participants n=5 Participants
Region of Enrollment Ukraine	26 participants n=5 Participants	42 participants n=7 Participants	68 participants n=5 Participants
Region of Enrollment Bulgaria	6 participants n=5 Participants	19 participants n=7 Participants	25 participants n=5 Participants
Region of Enrollment Serbia	0 participants n=5 Participants	3 participants n=7 Participants	3 participants n=5 Participants

PRIMARY outcome

Timeframe: From beginning of Week 3 to end of Week 18

Population: Efficacy population

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

Outcome measures

Measure	ESL1200 mg n=54 Participants 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.	ESL 1600 mg n=100 Participants 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.
Cumulative 112-day Exit Rate as Estimated by Kaplan-Meier Method	0.156 proportion of participants Interval 0.081 to 0.2874	0.128 proportion of participants Interval 0.075 to 0.2152

SECONDARY outcome

Timeframe: Week 9 through 18

Population: Efficacy population

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.

Outcome measures

Measure	ESL1200 mg n=54 Participants 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.	ESL 1600 mg n=100 Participants 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.
Proportion (%) of Subjects That Are Seizure-free During the 10-week Double-blind Monotherapy Treatment Period.	7.4 percentage of participants Interval 2.1 to 17.9	10.0 percentage of participants Interval 4.9 to 17.6

SECONDARY outcome

Timeframe: Week 15 through 18

Population: Efficacy population

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.

Outcome measures

Measure	ESL1200 mg n=54 Participants 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.	ESL 1600 mg n=100 Participants 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.
Percentage of Subjects Seizure-free During the Last 4 Weeks on Eslicarbazepine Acetate Monotherapy.	16.7 percentage of participants Interval 7.9 to 29.3	17.0 percentage of participants Interval 10.2 to 25.8

SECONDARY outcome

Timeframe: 18 weeks

Population: Efficacy population

Subjects completing the study were determined as subjects who completed the 18 weeks of double-blind treatment.

Outcome measures

Measure	ESL1200 mg n=54 Participants 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.	ESL 1600 mg n=100 Participants 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.
Completion Rate (% of Subjects Completing the 18 Weeks of Double-blind Treatment).	75.9 percentage of participants Interval 62.4 to 86.5	80.0 percentage of participants Interval 70.8 to 87.3

SECONDARY outcome

Timeframe: Week 8 through 18

Population: Efficacy population

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

Outcome measures

Measure	ESL1200 mg n=54 Participants 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.	ESL 1600 mg n=100 Participants 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.
Completion Rate During the 10 Weeks of Monotherapy (% of Subjects Entering the Monotherapy Period Who Complete).	85.4 percentage of participants Interval 72.2 to 93.9	90.9 percentage of participants Interval 82.9 to 96.0

SECONDARY outcome

Timeframe: Week 8 to Week 18

Population: Efficacy population

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.

Outcome measures

Measure	ESL1200 mg n=54 Participants 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.	ESL 1600 mg n=100 Participants 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.
Time on Eslicarbazepine Acetate Monotherapy.	NA days median not calculable due to lack of events	NA days median not calculable due to lack of events

SECONDARY outcome

Timeframe: 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

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).

Outcome measures

Measure	ESL1200 mg n=54 Participants 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.	ESL 1600 mg n=98 Participants 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.
Change in Seizure Frequency From Baseline. Relative(%) change from baseline fo DB pd n=54,98	-36.1 Percent change Interval -59.2 to -17.1	-47.5 Percent change Interval -70.8 to -11.3
Change in Seizure Frequency From Baseline. Relative(%)chg from baseline for titrat pd n=54,98	-19.3 Percent change Interval -57.9 to 3.3	-35.6 Percent change Interval -72.4 to -9.4
Change in Seizure Frequency From Baseline. Relative (%) chg from baseline-AED t/c pd n=54,98	-39.4 Percent change Interval -54.0 to 0.0	-42.9 Percent change Interval -73.8 to -12.1
Change in Seizure Frequency From Baseline. Relative (%) change from baseline-mono pd n=48,87	-45.7 Percent change Interval -72.1 to -20.1	-52.1 Percent change Interval -81.6 to -21.8

SECONDARY outcome

Timeframe: 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

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.

Outcome measures

Measure	ESL1200 mg n=54 Participants 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.	ESL 1600 mg n=100 Participants 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.
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 Interval 22.7 to 49.4	46.0 percentage of participants Interval 36.0 to 56.3
Responder Rate (Proportion [%] of Subjects With a ≥50% Reduction of Seizure Frequency From Baseline). responder rate during titration period	29.6 percentage of participants Interval 18.0 to 43.6	37.0 percentage of participants Interval 27.6 to 47.2
Responder Rate (Proportion [%] of Subjects With a ≥50% Reduction of Seizure Frequency From Baseline). responder rate during the AED	29.6 percentage of participants Interval 18.0 to 43.6	39.0 percentage of participants Interval 29.4 to 49.3
Responder Rate (Proportion [%] of Subjects With a ≥50% Reduction of Seizure Frequency From Baseline). responder rate during monotherapy period	38.9 percentage of participants Interval 29.5 to 58.8	46.0 percentage of participants Interval 41.4 to 63.0

SECONDARY outcome

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

Population: Efficacy population

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

Outcome measures

Measure	ESL1200 mg n=54 Participants 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.	ESL 1600 mg n=100 Participants 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.
Proportion (%) of Subjects Reaching Each Exit Criteria exit criterion 1	0 percentage of participants	0 percentage of participants
Proportion (%) of Subjects Reaching Each Exit Criteria exit criterion 2	1.9 percentage of participants	0 percentage of participants
Proportion (%) of Subjects Reaching Each Exit Criteria exit criterion investigator prog. assessment)	5.6 percentage of participants	2.0 percentage of participants
Proportion (%) of Subjects Reaching Each Exit Criteria exit criterion 3 (sponsors prog. assessment)	3.7 percentage of participants	1.0 percentage of participants
Proportion (%) of Subjects Reaching Each Exit Criteria exit criterion 4 (investigaor prog. assessment)	1.9 percentage of participants	5.0 percentage of participants
Proportion (%) of Subjects Reaching Each Exit Criteria exit criterion 4 (sponsor prog. assessment)	3.7 percentage of participants	6.0 percentage of participants
Proportion (%) of Subjects Reaching Each Exit Criteria exit criterion 5	3.7 percentage of participants	5.0 percentage of participants

SECONDARY outcome

Timeframe: 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

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.

Outcome measures

Measure	ESL1200 mg n=50 Participants 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.	ESL 1600 mg n=96 Participants 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.
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	5.8 units on a scale Standard Deviation 11.77
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	4.7 units on a scale Standard Deviation 13.70

SECONDARY outcome

Timeframe: 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

The total score of MADRS is defined as the sum of all individual item scores. From 0-60, high score indicates more severe

Outcome measures

Measure	ESL1200 mg n=54 Participants 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.	ESL 1600 mg n=100 Participants 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.
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	-1.8 units on a scale Standard Deviation 4.01
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	-1.6 units on a scale Standard Deviation 4.54

SECONDARY outcome

Timeframe: 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

The total score of MADRS is defined as the sum of all individual item scores. From 0-60, higher score indicates more severe

Outcome measures

Measure	ESL1200 mg n=50 Participants 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.	ESL 1600 mg n=100 Participants 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.
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 4.30	-6.6 units on a scale Standard Deviation 4.15
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	-4.1 units on a scale Standard Deviation 7.58

SECONDARY outcome

Timeframe: 18 Week Double-blind treatment period

Population: ITT population

Outcome measures

Measure	ESL1200 mg n=58 Participants 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.	ESL 1600 mg n=114 Participants 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.
Proportion (%) of Subjects With Increase of Body Weight >= 7% From Baseline	1.8 percentage of participants	11.7 percentage of participants

SECONDARY outcome

Timeframe: Week 0 to Week 18

Population: ITT population

Proportion (%) of Subjects With Normal Baseline Sodium Reaching Blood Sodium ≤135 mmol/L, ≤130 mmol/L, and ≤125 mmol/L

Outcome measures

Measure	ESL1200 mg n=58 Participants 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.	ESL 1600 mg n=114 Participants 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.
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	54.5 percentage of participants
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	20.9 percentage of participants
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	0 percentage of participants

SECONDARY outcome

Timeframe: 18 Week Double-blind treatment period

Population: ITT population

Outcome measures

Measure	ESL1200 mg n=58 Participants 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.	ESL 1600 mg n=114 Participants 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.
Proportion (%) of Events in Each Classification of the Columbia Suicide Severity Rating Scale (C SSRS). Actual Attempt	3.4 Percent of particiants	0 Percent of particiants
Proportion (%) of Events in Each Classification of the Columbia Suicide Severity Rating Scale (C SSRS). Non-suicidal Self-Injurious Behavior	0 Percent of particiants	0.9 Percent of particiants
Proportion (%) of Events in Each Classification of the Columbia Suicide Severity Rating Scale (C SSRS). Interrupted Attempt	0 Percent of particiants	0 Percent of particiants
Proportion (%) of Events in Each Classification of the Columbia Suicide Severity Rating Scale (C SSRS). Aborted Attempt	0 Percent of particiants	0 Percent of particiants
Proportion (%) of Events in Each Classification of the Columbia Suicide Severity Rating Scale (C SSRS). Preparatory Attempts	0 Percent of particiants	0 Percent of particiants
Proportion (%) of Events in Each Classification of the Columbia Suicide Severity Rating Scale (C SSRS). Suicidal Behavior	3.4 Percent of particiants	0 Percent of particiants
Proportion (%) of Events in Each Classification of the Columbia Suicide Severity Rating Scale (C SSRS). Wish to be Dead	1.7 Percent of particiants	0.9 Percent of particiants
Proportion (%) of Events in Each Classification of the Columbia Suicide Severity Rating Scale (C SSRS). Non-specific Active Suicidal Thoughts	0 Percent of particiants	1 Percent of particiants
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	0 Percent of particiants
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	0.9 Percent of particiants
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	0 Percent of particiants

SECONDARY outcome

Timeframe: 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

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).

Outcome measures

Measure	ESL1200 mg n=54 Participants 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.	ESL 1600 mg n=100 Participants 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.
Standardized Seizure Frequency (SSF) by Period SSF during double-blind pd n=54,100	5.5 seizures in 28 days Standard Deviation 7.75	5.2 seizures in 28 days Standard Deviation 5.38
Standardized Seizure Frequency (SSF) by Period SSF druing baseline pd n=54,98	7.4 seizures in 28 days Standard Deviation 5.89	8.7 seizures in 28 days Standard Deviation 7.20
Standardized Seizure Frequency (SSF) by Period SSF during titration pd n=54,100	6.0 seizures in 28 days Standard Deviation 6.16	6.4 seizures in 28 days Standard Deviation 8.11
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	5.1 seizures in 28 days Standard Deviation 5.26
Standardized Seizure Frequency (SSF) by Period SSF during monotherapy pd n=48,88	4.7 seizures in 28 days Standard Deviation 6.10	5.0 seizures in 28 days Standard Deviation 5.62

Adverse Events

ESL1200 mg

Serious events: 1 serious events

Other events: 29 other events

Deaths: 0 deaths

ESL 1600 mg

Serious events: 8 serious events

Other events: 64 other events

Deaths: 0 deaths

Serious adverse events

Measure	ESL1200 mg n=58 participants at risk 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.	ESL 1600 mg n=114 participants at risk 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.
Cardiac disorders Atrial flutter	1.7% 1/58 • Number of events 1 • 18 week double-blind treatment period	0.88% 1/114 • Number of events 1 • 18 week double-blind treatment period
Injury, poisoning and procedural complications ankle fracture	0.00% 0/58 • 18 week double-blind treatment period	0.88% 1/114 • Number of events 1 • 18 week double-blind treatment period
Injury, poisoning and procedural complications Post concussion syndrome	0.00% 0/58 • 18 week double-blind treatment period	0.88% 1/114 • Number of events 1 • 18 week double-blind treatment period
Injury, poisoning and procedural complications Tibia fracture	0.00% 0/58 • 18 week double-blind treatment period	0.88% 1/114 • Number of events 1 • 18 week double-blind treatment period
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/58 • 18 week double-blind treatment period	0.88% 1/114 • Number of events 1 • 18 week double-blind treatment period
Nervous system disorders Complex partial seizures	0.00% 0/58 • 18 week double-blind treatment period	0.88% 1/114 • Number of events 1 • 18 week double-blind treatment period
Nervous system disorders Partial seizures with secondary generalisation	0.00% 0/58 • 18 week double-blind treatment period	0.88% 1/114 • Number of events 1 • 18 week double-blind treatment period
Nervous system disorders Synocope	0.00% 0/58 • 18 week double-blind treatment period	0.88% 1/114 • Number of events 1 • 18 week double-blind treatment period
Pregnancy, puerperium and perinatal conditions Abortion spontaneous	0.00% 0/58 • 18 week double-blind treatment period	0.88% 1/114 • Number of events 1 • 18 week double-blind treatment period
Skin and subcutaneous tissue disorders Drug rash with eosinophilia and systemic symptoms	0.00% 0/58 • 18 week double-blind treatment period	0.88% 1/114 • Number of events 1 • 18 week double-blind treatment period
Skin and subcutaneous tissue disorders Rash pruritic	0.00% 0/58 • 18 week double-blind treatment period	0.88% 1/114 • Number of events 1 • 18 week double-blind treatment period

Other adverse events

Measure	ESL1200 mg n=58 participants at risk 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.	ESL 1600 mg n=114 participants at risk 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.
Gastrointestinal disorders Nausea	10.3% 6/58 • Number of events 8 • 18 week double-blind treatment period	6.1% 7/114 • Number of events 12 • 18 week double-blind treatment period
General disorders Fatigue	6.9% 4/58 • Number of events 5 • 18 week double-blind treatment period	5.3% 6/114 • Number of events 7 • 18 week double-blind treatment period
Infections and infestations Influenza	5.2% 3/58 • Number of events 3 • 18 week double-blind treatment period	0.88% 1/114 • Number of events 1 • 18 week double-blind treatment period
Infections and infestations Nasopharyngitis	6.9% 4/58 • Number of events 4 • 18 week double-blind treatment period	7.9% 9/114 • Number of events 9 • 18 week double-blind treatment period
Musculoskeletal and connective tissue disorders Back pain	5.2% 3/58 • Number of events 3 • 18 week double-blind treatment period	5.3% 6/114 • Number of events 7 • 18 week double-blind treatment period
Nervous system disorders Dizziness	10.3% 6/58 • Number of events 7 • 18 week double-blind treatment period	21.1% 24/114 • Number of events 37 • 18 week double-blind treatment period
Nervous system disorders Headache	19.0% 11/58 • Number of events 16 • 18 week double-blind treatment period	28.1% 32/114 • Number of events 87 • 18 week double-blind treatment period
Nervous system disorders Solmnolence	3.4% 2/58 • Number of events 2 • 18 week double-blind treatment period	8.8% 10/114 • Number of events 12 • 18 week double-blind treatment period
Psychiatric disorders Anxiety	5.2% 3/58 • Number of events 4 • 18 week double-blind treatment period	0.88% 1/114 • Number of events 1 • 18 week double-blind treatment period
Psychiatric disorders Insomnia	6.9% 4/58 • Number of events 4 • 18 week double-blind treatment period	2.6% 3/114 • Number of events 3 • 18 week double-blind treatment period

Additional Information

Eslicarbazepine acetate Medical Director

Sunovion Phamaceuticals Inc.

Phone: 866-503-7813

Email: clinicaltrialsdisclosure@sunovion.com

Results disclosure agreements

• Principal investigator is a sponsor employee In the event the Study is part of a multi-center study, the first publication of the results of the study shall be made in conjunction with the results of other participating study sites as a multi-center publication; provided however, if a multi-center publication is not forthcoming within twenty-four (24) months following completion of the Study at all sites, Institution and Investigator shall be free to publish.
• Publication restrictions are in place

Restriction type: OTHER