Trial Outcomes & Findings for Safety and Efficacy of Eslicarbazepine Acetate Monotherapy in Subjects With Partial Epilepsy Not Well Controlled by Current Antiepileptic Drugs (NCT NCT00866775)
NCT ID: NCT00866775
Last Updated: 2016-03-11
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
193 participants
Primary outcome timeframe
Week 3 to Week 18
Results posted on
2016-03-11
Participant Flow
Participant milestones
| Measure |
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.
.
|
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.
|
|---|---|---|
|
Overall Study
STARTED
|
65
|
128
|
|
Overall Study
COMPLETED
|
29
|
76
|
|
Overall Study
NOT COMPLETED
|
36
|
52
|
Reasons for withdrawal
| Measure |
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.
.
|
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.
|
|---|---|---|
|
Overall Study
Adverse Event
|
5
|
19
|
|
Overall Study
Death
|
1
|
0
|
|
Overall Study
Lost to Follow-up
|
0
|
4
|
|
Overall Study
Physician Decision
|
0
|
3
|
|
Overall Study
Protocol Violation
|
3
|
4
|
|
Overall Study
Withdrawal by Subject
|
4
|
4
|
|
Overall Study
met exit criteria
|
23
|
17
|
|
Overall Study
discontinued due to communication error
|
0
|
1
|
Baseline Characteristics
Safety and Efficacy of Eslicarbazepine Acetate Monotherapy in Subjects With Partial Epilepsy Not Well Controlled by Current Antiepileptic Drugs
Baseline characteristics by cohort
| Measure |
Eslicarbazepine 1200 mg QD
n=65 Participants
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.
.
|
Eslicarbazepine 1600 mg QD
n=128 Participants
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.
|
Total
n=193 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Customized
less than 18 years
|
4 participants
n=5 Participants
|
2 participants
n=7 Participants
|
6 participants
n=5 Participants
|
|
Age, Customized
18-39 years
|
31 participants
n=5 Participants
|
61 participants
n=7 Participants
|
92 participants
n=5 Participants
|
|
Age, Customized
40-65 years
|
29 participants
n=5 Participants
|
61 participants
n=7 Participants
|
90 participants
n=5 Participants
|
|
Age, Customized
greater than 65 years
|
1 participants
n=5 Participants
|
4 participants
n=7 Participants
|
5 participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
34 Participants
n=5 Participants
|
67 Participants
n=7 Participants
|
101 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
31 Participants
n=5 Participants
|
61 Participants
n=7 Participants
|
92 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alsaka Native
|
0 participants
n=5 Participants
|
1 participants
n=7 Participants
|
1 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
1 participants
n=5 Participants
|
3 participants
n=7 Participants
|
4 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Native Hawaiian or Pacific Islander
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
4 participants
n=5 Participants
|
18 participants
n=7 Participants
|
22 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
53 participants
n=5 Participants
|
94 participants
n=7 Participants
|
147 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
More than one race
|
1 participants
n=5 Participants
|
0 participants
n=7 Participants
|
1 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Unknown or Not Reported
|
6 participants
n=5 Participants
|
12 participants
n=7 Participants
|
18 participants
n=5 Participants
|
|
Region of Enrollment
Canada
|
1 participants
n=5 Participants
|
5 participants
n=7 Participants
|
6 participants
n=5 Participants
|
|
Region of Enrollment
United States
|
64 participants
n=5 Participants
|
123 participants
n=7 Participants
|
187 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Week 3 to Week 18Population: efficacy population
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.
Outcome measures
| Measure |
Eslicarbazepine 1200 mg QD
n=60 Participants
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.
.
|
Eslicarbazepine 1600 mg QD
n=118 Participants
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.
|
|---|---|---|
|
Cumulative 112-day Exit Rate as Estimated by Kaplan-Meier Method
|
0.444 proportion of participants
Interval 0.3252 to 0.5832
|
0.287 proportion of participants
Interval 0.2124 to 0.3813
|
SECONDARY outcome
Timeframe: Weeks 9 through 18Population: 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 |
Eslicarbazepine 1200 mg QD
n=60 Participants
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.
.
|
Eslicarbazepine 1600 mg QD
n=118 Participants
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.
|
|---|---|---|
|
Percentage of Subjects That Are Seizure-free During the 10-week Double-blind Monotherapy Treatment Period.
|
8.3 percentage of participants
Interval 2.8 to 18.4
|
7.6 percentage of participants
Interval 3.5 to 14.0
|
SECONDARY outcome
Timeframe: Weeks 15 through 18Population: efficacy population
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.
Outcome measures
| Measure |
Eslicarbazepine 1200 mg QD
n=60 Participants
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.
.
|
Eslicarbazepine 1600 mg QD
n=118 Participants
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.
|
|---|---|---|
|
Percentage of Subjects Seizure-free During the Last 4 Weeks on Eslicarbazepine Acetate Monotherapy.
|
13.3 percentage of participants
Interval 5.9 to 24.6
|
14.4 percentage of participants
Interval 8.6 to 22.1
|
SECONDARY outcome
Timeframe: Week 1 to Week 18Population: efficacy population
Subjects completing the study were determined as subjects who completed the 18 weeks of double-blind treatment.
Outcome measures
| Measure |
Eslicarbazepine 1200 mg QD
n=60 Participants
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.
.
|
Eslicarbazepine 1600 mg QD
n=118 Participants
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.
|
|---|---|---|
|
Completion Rate
|
48.3 percentage of participants
Interval 35.2 to 61.6
|
64.4 percentage of participants
Interval 55.1 to 73.0
|
SECONDARY outcome
Timeframe: Weeks 8 through 18Population: 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 |
Eslicarbazepine 1200 mg QD
n=45 Participants
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.
.
|
Eslicarbazepine 1600 mg QD
n=93 Participants
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.
|
|---|---|---|
|
Completion Rate During the 10 Weeks of Monotherapy
|
64.4 percentage of participants
Interval 48.8 to 78.1
|
81.7 percentage of participants
Interval 72.4 to 89.0
|
SECONDARY outcome
Timeframe: Week 8 to Week 18Population: 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 |
Eslicarbazepine 1200 mg QD
n=60 Participants
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.
.
|
Eslicarbazepine 1600 mg QD
n=118 Participants
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.
|
|---|---|---|
|
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: 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 18Population: 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
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 |
Eslicarbazepine 1200 mg QD
n=60 Participants
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.
.
|
Eslicarbazepine 1600 mg QD
n=118 Participants
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.
|
|---|---|---|
|
Change in Seizure Frequency From Baseline.
Relative (%) change from baseline -AED t/c period
|
-30.2 percent change
Interval -69.5 to 25.9
|
-39.7 percent change
Interval -78.3 to 1.6
|
|
Change in Seizure Frequency From Baseline.
Relative (%) change from baseline -tiration period
|
-29.6 percent change
Interval -100.0 to 1.8
|
-52.4 percent change
Interval -100.0 to -11.4
|
|
Change in Seizure Frequency From Baseline.
Relative (%) change from baselne for DB period
|
-30.9 percent change
Interval -63.3 to 30.9
|
-41.5 percent change
Interval -65.6 to -9.5
|
|
Change in Seizure Frequency From Baseline.
Relative (%) change from baseline - mono period
|
-48.7 percent change
Interval -73.2 to 43.3
|
-38.6 percent change
Interval -77.1 to -7.9
|
SECONDARY outcome
Timeframe: 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 18Population: 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 |
Eslicarbazepine 1200 mg QD
n=60 Participants
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.
.
|
Eslicarbazepine 1600 mg QD
n=118 Participants
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.
|
|---|---|---|
|
Responder Rate (Proportion [%] of Subjects With a ≥50% Reduction of Seizure Frequency From Baseline).
Responder rate during double blind period
|
36.7 percentage of participants
Interval 24.6 to 50.1
|
39.8 percentage of participants
Interval 30.9 to 49.3
|
|
Responder Rate (Proportion [%] of Subjects With a ≥50% Reduction of Seizure Frequency From Baseline).
Responder Rate during the AED T/C period
|
41.7 percentage of participants
Interval 29.1 to 55.1
|
43.2 percentage of participants
Interval 34.1 to 52.7
|
|
Responder Rate (Proportion [%] of Subjects With a ≥50% Reduction of Seizure Frequency From Baseline).
Responder rate during the titration period
|
46.7 percentage of participants
Interval 33.7 to 60.0
|
51.7 percentage of participants
Interval 42.3 to 61.0
|
|
Responder Rate (Proportion [%] of Subjects With a ≥50% Reduction of Seizure Frequency From Baseline).
Responder rate during monotherapy period
|
35.0 percentage of participants
Interval 23.1 to 48.4
|
32.2 percentage of participants
Interval 23.9 to 41.4
|
SECONDARY outcome
Timeframe: Week 1 to Week 18Population: efficacy population
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.
Outcome measures
| Measure |
Eslicarbazepine 1200 mg QD
n=60 Participants
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.
.
|
Eslicarbazepine 1600 mg QD
n=118 Participants
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.
|
|---|---|---|
|
Percentage of Subjects Reaching Each of the Exit Events.
exit criterion 1
|
0 percentage of participants
|
0.8 percentage of participants
|
|
Percentage of Subjects Reaching Each of the Exit Events.
exit criterion 4 (sponsor prog. assessment)
|
10.0 percentage of participants
|
5.9 percentage of participants
|
|
Percentage of Subjects Reaching Each of the Exit Events.
exit criterion 2
|
6.7 percentage of participants
|
0.8 percentage of participants
|
|
Percentage of Subjects Reaching Each of the Exit Events.
exit criterion 3 (investigator prog. assessment)
|
10.0 percentage of participants
|
4.2 percentage of participants
|
|
Percentage of Subjects Reaching Each of the Exit Events.
exit criterion 3 (sponsors prog. assessment)
|
8.3 percentage of participants
|
5.9 percentage of participants
|
|
Percentage of Subjects Reaching Each of the Exit Events.
exit criterion 4 (investigaor prog. assessment)
|
8.3 percentage of participants
|
5.1 percentage of participants
|
|
Percentage of Subjects Reaching Each of the Exit Events.
exit criterion 5
|
13.3 percentage of participants
|
3.4 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 18Population: 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
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 |
Eslicarbazepine 1200 mg QD
n=54 Participants
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.
.
|
Eslicarbazepine 1600 mg QD
n=113 Participants
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.
|
|---|---|---|
|
Change in Total Score From Baseline in 31-Item Quality of Life in Epilepsy (QOLIE-31).
Change from baseline to end of AED T/C pd n=39,86
|
3.2 units on a scale
Standard Deviation 10.75
|
6.3 units on a scale
Standard Deviation 12.42
|
|
Change in Total Score From Baseline in 31-Item Quality of Life in Epilepsy (QOLIE-31).
change from baseline to end of mono. pd n=36,86
|
7.8 units on a scale
Standard Deviation 13.78
|
6.4 units on a scale
Standard Deviation 12.64
|
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 18Population: 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
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
Outcome measures
| Measure |
Eslicarbazepine 1200 mg QD
n=60 Participants
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.
.
|
Eslicarbazepine 1600 mg QD
n=118 Participants
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.
|
|---|---|---|
|
Change in Total Score From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS).
Change from baseline to AED T/C period
|
-0.4 units on a scale
Standard Deviation 4.35
|
-2.0 units on a scale
Standard Deviation 5.99
|
|
Change in Total Score From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS).
Change from baseline to end of mono period
|
-1.1 units on a scale
Standard Deviation 5.55
|
-2.4 units on a scale
Standard Deviation 5.77
|
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 18Population: 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
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
Outcome measures
| Measure |
Eslicarbazepine 1200 mg QD
n=9 Participants
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.
.
|
Eslicarbazepine 1600 mg QD
n=17 Participants
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.
|
|---|---|---|
|
Change in Total Score From Baseline in MADRS in Those Subjects With a MADRS Score of ≥14 at Randomization.
Change from baseline to AED T/C pd n=7,13
|
-1.3 units on a scale
Standard Deviation 3.86
|
-7.9 units on a scale
Standard Deviation 9.81
|
|
Change in Total Score From Baseline in MADRS in Those Subjects With a MADRS Score of ≥14 at Randomization.
Change from baseline to end of mono pd n=6,13
|
-6.8 units on a scale
Standard Deviation 6.71
|
-9.6 units on a scale
Standard Deviation 8.72
|
SECONDARY outcome
Timeframe: 18 Week Double-blind treatment periodPopulation: ITT population
Outcome measures
| Measure |
Eslicarbazepine 1200 mg QD
n=65 Participants
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.
.
|
Eslicarbazepine 1600 mg QD
n=128 Participants
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.
|
|---|---|---|
|
Percentage of Subjects With Increase of Body Weight >= 7%
|
2 Percentage of participants
|
9 Percentage of participants
|
SECONDARY outcome
Timeframe: 18 Week Double-blind treatment periodPopulation: 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 |
Eslicarbazepine 1200 mg QD
n=65 Participants
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.
.
|
Eslicarbazepine 1600 mg QD
n=128 Participants
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.
|
|---|---|---|
|
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
|
29 Percent
|
61 Percent
|
|
Proportion (%) of Subjects With Normal Baseline Sodium Reaching Blood Sodium ≤135 mmol/L, ≤130 mmol/L, and ≤125 mmol/L
≤ 13- amd > 125 mEq/L
|
6 Percent
|
11 Percent
|
|
Proportion (%) of Subjects With Normal Baseline Sodium Reaching Blood Sodium ≤135 mmol/L, ≤130 mmol/L, and ≤125 mmol/L
≤125 mEq/L
|
3 Percent
|
5 Percent
|
SECONDARY outcome
Timeframe: 18 Week Double-blind treatment periodPopulation: ITT population
Outcome measures
| Measure |
Eslicarbazepine 1200 mg QD
n=65 Participants
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.
.
|
Eslicarbazepine 1600 mg QD
n=128 Participants
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.
|
|---|---|---|
|
Proportion (%) of Events in Each Classification of the Columbia Suicide Severity Rating Scale (C SSRS).
Actual Attempt
|
0 Percent of participants
|
0 Percent of participants
|
|
Proportion (%) of Events in Each Classification of the Columbia Suicide Severity Rating Scale (C SSRS).
Non-suicidal Self-Injurious Behavior
|
0 Percent of participants
|
0 Percent of participants
|
|
Proportion (%) of Events in Each Classification of the Columbia Suicide Severity Rating Scale (C SSRS).
Interrupted Attempt
|
1.5 Percent of participants
|
0 Percent of participants
|
|
Proportion (%) of Events in Each Classification of the Columbia Suicide Severity Rating Scale (C SSRS).
Aborted Attempt
|
0 Percent of participants
|
0 Percent of participants
|
|
Proportion (%) of Events in Each Classification of the Columbia Suicide Severity Rating Scale (C SSRS).
Preparatory Attempts
|
1.5 Percent of participants
|
0 Percent of participants
|
|
Proportion (%) of Events in Each Classification of the Columbia Suicide Severity Rating Scale (C SSRS).
SuicidalBehavior
|
0 Percent of participants
|
0 Percent of participants
|
|
Proportion (%) of Events in Each Classification of the Columbia Suicide Severity Rating Scale (C SSRS).
Wish to be Dead
|
4.6 Percent of participants
|
3.1 Percent of participants
|
|
Proportion (%) of Events in Each Classification of the Columbia Suicide Severity Rating Scale (C SSRS).
Non-specific Active Suicidal Thoughts
|
4.6 Percent of participants
|
0.8 Percent of participants
|
|
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
|
1.5 Percent of participants
|
0.8 Percent of participants
|
|
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 participants
|
0 Percent of participants
|
|
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 participants
|
0 Percent of participants
|
SECONDARY outcome
Timeframe: 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 18Population: 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
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 |
Eslicarbazepine 1200 mg QD
n=65 Participants
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.
.
|
Eslicarbazepine 1600 mg QD
n=128 Participants
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.
|
|---|---|---|
|
Standardized Seizure Frequency (SSF) by Period
SSF during double-blind period
|
8.8 Number of seizures in 28 days
Standard Deviation 12.89
|
6.9 Number of seizures in 28 days
Standard Deviation 6.50
|
|
Standardized Seizure Frequency (SSF) by Period
SSF during baseline
|
8.7 Number of seizures in 28 days
Standard Deviation 5.63
|
10.9 Number of seizures in 28 days
Standard Deviation 7.70
|
|
Standardized Seizure Frequency (SSF) by Period
SSF during titration period
|
6.2 Number of seizures in 28 days
Standard Deviation 7.77
|
6.4 Number of seizures in 28 days
Standard Deviation 7.53
|
|
Standardized Seizure Frequency (SSF) by Period
SSF during AED taper/conversion period
|
8.7 Number of seizures in 28 days
Standard Deviation 14.78
|
6.9 Number of seizures in 28 days
Standard Deviation 6.90
|
|
Standardized Seizure Frequency (SSF) by Period
SSF during monotherapy period
|
13.2 Number of seizures in 28 days
Standard Deviation 29.52
|
6.8 Number of seizures in 28 days
Standard Deviation 7.65
|
Adverse Events
Eslicarbazepine 1200 mg QD
Serious events: 4 serious events
Other events: 46 other events
Deaths: 0 deaths
Eslicarbazepine 1600 mg QD
Serious events: 8 serious events
Other events: 100 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Eslicarbazepine 1200 mg QD
n=65 participants at risk
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.
.
|
Eslicarbazepine 1600 mg QD
n=128 participants at risk
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.
|
|---|---|---|
|
Cardiac disorders
cardiogenic shock
|
1.5%
1/65 • Number of events 1 • 18 weeks double-blind treatment period
|
0.00%
0/128 • 18 weeks double-blind treatment period
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/65 • 18 weeks double-blind treatment period
|
0.78%
1/128 • Number of events 1 • 18 weeks double-blind treatment period
|
|
Gastrointestinal disorders
vomiting
|
0.00%
0/65 • 18 weeks double-blind treatment period
|
0.78%
1/128 • Number of events 1 • 18 weeks double-blind treatment period
|
|
General disorders
Oedema peripheral
|
1.5%
1/65 • Number of events 1 • 18 weeks double-blind treatment period
|
0.00%
0/128 • 18 weeks double-blind treatment period
|
|
Injury, poisoning and procedural complications
Accidnetal overdose
|
0.00%
0/65 • 18 weeks double-blind treatment period
|
0.78%
1/128 • Number of events 1 • 18 weeks double-blind treatment period
|
|
Injury, poisoning and procedural complications
Multiple injuries
|
1.5%
1/65 • Number of events 1 • 18 weeks double-blind treatment period
|
0.00%
0/128 • 18 weeks double-blind treatment period
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
1.5%
1/65 • Number of events 1 • 18 weeks double-blind treatment period
|
0.00%
0/128 • 18 weeks double-blind treatment period
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.00%
0/65 • 18 weeks double-blind treatment period
|
1.6%
2/128 • Number of events 2 • 18 weeks double-blind treatment period
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pancreatic neoplasm
|
1.5%
1/65 • Number of events 1 • 18 weeks double-blind treatment period
|
0.00%
0/128 • 18 weeks double-blind treatment period
|
|
Nervous system disorders
Cerebral cyst
|
0.00%
0/65 • 18 weeks double-blind treatment period
|
0.78%
1/128 • Number of events 1 • 18 weeks double-blind treatment period
|
|
Nervous system disorders
complex partial seizers
|
0.00%
0/65 • 18 weeks double-blind treatment period
|
0.78%
1/128 • Number of events 1 • 18 weeks double-blind treatment period
|
|
Nervous system disorders
Hypoaesthesia
|
0.00%
0/65 • 18 weeks double-blind treatment period
|
0.78%
1/128 • Number of events 1 • 18 weeks double-blind treatment period
|
|
Nervous system disorders
Partial seizures with secondary generalisation
|
1.5%
1/65 • Number of events 1 • 18 weeks double-blind treatment period
|
0.00%
0/128 • 18 weeks double-blind treatment period
|
|
Nervous system disorders
Status epilepticus
|
0.00%
0/65 • 18 weeks double-blind treatment period
|
0.78%
1/128 • Number of events 1 • 18 weeks double-blind treatment period
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/65 • 18 weeks double-blind treatment period
|
0.78%
1/128 • Number of events 1 • 18 weeks double-blind treatment period
|
|
Psychiatric disorders
Depression
|
0.00%
0/65 • 18 weeks double-blind treatment period
|
0.78%
1/128 • Number of events 1 • 18 weeks double-blind treatment period
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/65 • 18 weeks double-blind treatment period
|
0.78%
1/128 • Number of events 1 • 18 weeks double-blind treatment period
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary oedema
|
1.5%
1/65 • Number of events 1 • 18 weeks double-blind treatment period
|
0.00%
0/128 • 18 weeks double-blind treatment period
|
|
Vascular disorders
Hypertension
|
0.00%
0/65 • 18 weeks double-blind treatment period
|
0.78%
1/128 • Number of events 1 • 18 weeks double-blind treatment period
|
Other adverse events
| Measure |
Eslicarbazepine 1200 mg QD
n=65 participants at risk
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.
.
|
Eslicarbazepine 1600 mg QD
n=128 participants at risk
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.
|
|---|---|---|
|
Eye disorders
Diplopia
|
7.7%
5/65 • Number of events 5 • 18 weeks double-blind treatment period
|
4.7%
6/128 • Number of events 6 • 18 weeks double-blind treatment period
|
|
Eye disorders
Vision blurred
|
9.2%
6/65 • Number of events 6 • 18 weeks double-blind treatment period
|
9.4%
12/128 • Number of events 15 • 18 weeks double-blind treatment period
|
|
Gastrointestinal disorders
Abdominal discomfort
|
6.2%
4/65 • Number of events 6 • 18 weeks double-blind treatment period
|
3.1%
4/128 • Number of events 4 • 18 weeks double-blind treatment period
|
|
Gastrointestinal disorders
Diarrhoea
|
7.7%
5/65 • Number of events 6 • 18 weeks double-blind treatment period
|
7.0%
9/128 • Number of events 12 • 18 weeks double-blind treatment period
|
|
Gastrointestinal disorders
Nausea
|
10.8%
7/65 • Number of events 9 • 18 weeks double-blind treatment period
|
14.1%
18/128 • Number of events 28 • 18 weeks double-blind treatment period
|
|
Gastrointestinal disorders
Toothache
|
6.2%
4/65 • Number of events 4 • 18 weeks double-blind treatment period
|
0.78%
1/128 • Number of events 1 • 18 weeks double-blind treatment period
|
|
Gastrointestinal disorders
Vomiting
|
9.2%
6/65 • Number of events 7 • 18 weeks double-blind treatment period
|
8.6%
11/128 • Number of events 14 • 18 weeks double-blind treatment period
|
|
General disorders
Fatigue
|
20.0%
13/65 • Number of events 14 • 18 weeks double-blind treatment period
|
15.6%
20/128 • Number of events 25 • 18 weeks double-blind treatment period
|
|
Infections and infestations
Gastroenteritis viral
|
6.2%
4/65 • Number of events 4 • 18 weeks double-blind treatment period
|
3.1%
4/128 • Number of events 4 • 18 weeks double-blind treatment period
|
|
Infections and infestations
Influenza
|
6.2%
4/65 • Number of events 4 • 18 weeks double-blind treatment period
|
3.9%
5/128 • Number of events 5 • 18 weeks double-blind treatment period
|
|
Infections and infestations
Nasopharyngitis
|
10.8%
7/65 • Number of events 7 • 18 weeks double-blind treatment period
|
10.9%
14/128 • Number of events 15 • 18 weeks double-blind treatment period
|
|
Injury, poisoning and procedural complications
Confusion
|
6.2%
4/65 • Number of events 4 • 18 weeks double-blind treatment period
|
5.5%
7/128 • Number of events 8 • 18 weeks double-blind treatment period
|
|
Injury, poisoning and procedural complications
Fall
|
6.2%
4/65 • Number of events 5 • 18 weeks double-blind treatment period
|
2.3%
3/128 • Number of events 3 • 18 weeks double-blind treatment period
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
6.2%
4/65 • Number of events 6 • 18 weeks double-blind treatment period
|
6.2%
8/128 • Number of events 9 • 18 weeks double-blind treatment period
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
15.4%
10/65 • Number of events 11 • 18 weeks double-blind treatment period
|
4.7%
6/128 • Number of events 6 • 18 weeks double-blind treatment period
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
7.7%
5/65 • Number of events 6 • 18 weeks double-blind treatment period
|
1.6%
2/128 • Number of events 2 • 18 weeks double-blind treatment period
|
|
Nervous system disorders
Dizziness
|
27.7%
18/65 • Number of events 31 • 18 weeks double-blind treatment period
|
24.2%
31/128 • Number of events 42 • 18 weeks double-blind treatment period
|
|
Nervous system disorders
Headache
|
21.5%
14/65 • Number of events 28 • 18 weeks double-blind treatment period
|
20.3%
26/128 • Number of events 33 • 18 weeks double-blind treatment period
|
|
Nervous system disorders
Memory impariment
|
7.7%
5/65 • Number of events 5 • 18 weeks double-blind treatment period
|
1.6%
2/128 • Number of events 2 • 18 weeks double-blind treatment period
|
|
Nervous system disorders
Partial seizures with secondary generalisation
|
9.2%
6/65 • Number of events 6 • 18 weeks double-blind treatment period
|
0.78%
1/128 • Number of events 1 • 18 weeks double-blind treatment period
|
|
Nervous system disorders
Somnolence
|
10.8%
7/65 • Number of events 8 • 18 weeks double-blind treatment period
|
18.0%
23/128 • Number of events 33 • 18 weeks double-blind treatment period
|
|
Psychiatric disorders
Insomnia
|
4.6%
3/65 • Number of events 3 • 18 weeks double-blind treatment period
|
6.2%
8/128 • Number of events 9 • 18 weeks double-blind treatment period
|
Additional Information
Eslicarbazepine acetate Medical Director
Sunovion Phamaceuticals Inc.
Phone: 866-503-7813
Email: [email protected]
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