Eslicarbazepine Acetate Monotherapy Long Term Study

• ClinicalTrials.gov Identifier: NCT00910247
• Recruitment Status: Completed
• First Posted: May 29, 2009
• Results First Posted: July 17, 2018
• Last Update Posted: July 17, 2018
• Sponsor: Sunovion
• Information provided by (Responsible Party): Sunovion

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Epilepsy
• Intervention: Drug: Eslicarbazepine acetate
• Enrollment: 274

Participant Flow

Recruitment Details	Subjects that participated in either study 093-045NCT00866775) or study 093-046(NCT01091662) were eligible to participate in study 093-050
Pre-assignment Details	Subjects who completed the 18-week treatment period or exited the study per protocol may be eligible to participate. Subjects who discontinued for reasons other than reaching the exit criteria may be eligible if there is no safety concern, however, subjects must have completed at least the first 3 weeks of the 18-week double-blind treatment

Arm/Group Title	Eslicarbazepine Acetate
Arm/Group Description	Open-label treatment with eslicarbazepine acetate will be at doses between 800 and 2400 mg QD Eslicarbazepine acetate: 800 to 2400 mg once daily (QD)
Period Title: Overall Study
Started	274
Completed	205
Not Completed	69
Reason Not Completed
Adverse Event	15
Death	2
Lost to Follow-up	10
Physician Decision	3
Protocol Violation	10
Withdrawal by Subject	25
Not collected	4

Baseline Characteristics

Arm/Group Title		Eslicarbazepine Acetate
Arm/Group Description		Open-label treatment with eslicarbazepine acetate will be at doses between 800 and 2400 mg QD Eslicarbazepine acetate: 800 to 2400 mg once daily (QD)
Overall Number of Baseline Participants		274
Baseline Analysis Population Description		full analysis set
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	274 participants
	<=18 years	12 4.4%
	Between 18 and 65 years	258 94.2%
	>=65 years	4 1.5%
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	274 participants
		37.9 (12.70)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	274 participants
	Female	134 48.9%
	Male	140 51.1%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	274 participants
	Hispanic or Latino	28 10.2%
	Not Hispanic or Latino	246 89.8%
	Unknown or Not Reported	0 0.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	274 participants
	American Indian or Alaska Native	2 0.7%
	Asian	5 1.8%
	Native Hawaiian or Other Pacific Islander	0 0.0%
	Black or African American	22 8.0%
	White	229 83.6%
	More than one race	2 0.7%
	Unknown or Not Reported	14 5.1%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants	Number Analyzed	274 participants
Canada		3
United States		167
Czechia		27
Ukraine		57
Bulgaria		18
Serbia		2

Outcome Measures

1. Primary Outcome

Title	Number and Percent of Subjects With Treatment Emergent Adverse Events
Description	Number and percent of subjects with treatment emergent adverse events
Time Frame	One year

Outcome Measure Data

Analysis Population Description

The Intent-to -Treat (ITT) population consisted of all subjects who had taken any open-label study medication

Arm/Group Title	Eslicarbazepine Acetate
Arm/Group Description:	Open-label treatment with eslicarbazepine acetate will be at doses between 800 and 2400 mg QD Eslicarbazepine acetate: 800 to 2400 mg once daily (QD)
Overall Number of Participants Analyzed	274
Measure Type: Count of Participants; Unit of Measure: Participants
	220 80.3%

2. Secondary Outcome

Title	Number and Percentage of Subjects With Potentially Clinically Significant Clinical Laboratory Evaluations
Description	Number and percentage of subjects with potentially clinically significant clinical laboratory evaluations
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) population consisted of all subjects who have taken any open-label study medication.

Arm/Group Title	Eslicarbazepine Acetate
Arm/Group Description:	Open-label treatment with eslicarbazepine acetate will be at doses between 800 and 2400 mg QD Eslicarbazepine acetate: 800 to 2400 mg once daily (QD)
Overall Number of Participants Analyzed	274
Measure Type: Count of Participants; Unit of Measure: Participants
	186 67.9%

3. Secondary Outcome

Title	Number and Percent of Subjects With Normal Baseline Sodium Reaching Blood Sodium ≤135 mmol/L, ≤130 mmol/L, and ≤125 mmol/L
Description	Number and percentage of subjects who had normal sodium value (i.e. >135 mEq/L) at baseline but reached <=135 mEq/L and >130 mEq/L, <=130 mEq/L and >125 mEq/L, or <=125 mEq/L at any post baseline.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

ITT subjects with baseline sodium and at least one post baseline sodium value

Arm/Group Title	Eslicarbazepine Acetate
Arm/Group Description:	Open-label treatment with eslicarbazepine acetate will be at doses between 800 and 2400 mg QD Eslicarbazepine acetate: 800 to 2400 mg once daily (QD)
Overall Number of Participants Analyzed	261
Measure Type: Count of Participants; Unit of Measure: Participants
<=135 mEq/L and >130 mEq/L	48 18.4%
<=130 mEq/L and >125 mEq/L	22 8.4%
<=125 mEq/L	4 1.5%

4. Secondary Outcome

Title	Percentage of Subjects With Increase of Body Weight ≥7%
Description	Percentage of subjects with increase of body weight ≥7%
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) population consisted of all subjects who have taken any open-label study medication.

Arm/Group Title	Eslicarbazepine Acetate
Arm/Group Description:	Open-label treatment with eslicarbazepine acetate will be at doses between 800 and 2400 mg QD Eslicarbazepine acetate: 800 to 2400 mg once daily (QD)
Overall Number of Participants Analyzed	274
Measure Type: Number; Unit of Measure: percentagae of participants
	27

5. Secondary Outcome

Title	Number and Percentage of Subjects With Orthostatic Effects.
Description	Number and percentage of subjects with orthostatic effects.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) population consisted of all subjects who have taken any open-label study medication.

Arm/Group Title	Eslicarbazepine Acetate
Arm/Group Description:	Open-label treatment with eslicarbazepine acetate will be at doses between 800 and 2400 mg QD Eslicarbazepine acetate: 800 to 2400 mg once daily (QD)
Overall Number of Participants Analyzed	274
Measure Type: Count of Participants; Unit of Measure: Participants
	67 24.5%

6. Secondary Outcome

Title	Number and Percentage of Subjects With QTc-F Changes (in Categories) From Baseline.
Description	Number and percentage of subjects by QT interval corrected using the Fridericia fomula (QTcF) categories Based on the numbers of subjects who had at least one post-baseline assessment, the number and percentage of subjects with QTcF values in the following categories were summarized: >500 millisecond (msec) at any post-baseline timepoint but not present at baseline; >480 msec at any post-baseline timepoint but not present at baseline; >450 msec at any post-baseline timepoint but not present at baseline; Change from Baseline >=60 ms for at least one post-baseline measurement; Change from Baseline >=30 ms for at least one post-baseline measurement and <60 ms for all post-baseline measurement QT interval is a measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle.
Time Frame	Baseline, Month 12

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) subjects with at least one post-baseline assessment

Arm/Group Title	Eslicarbazepine Acetate
Arm/Group Description:	Open-label treatment with eslicarbazepine acetate will be at doses between 800 and 2400 mg QD Eslicarbazepine acetate: 800 to 2400 mg once daily (QD)
Overall Number of Participants Analyzed	272
Measure Type: Count of Participants; Unit of Measure: Participants
>500ms at any postbaseline not present at baseli	0 0.0%
>450ms at any postbaseline not present at baseline	9 3.3%
>480ms at any postbaseline not present at baseline	1 0.4%
CFB >=60 ms for at least one post-baseline	0 0.0%
CFB>=30ms for at least one &<60ms for all PBL	42 15.4%

7. Secondary Outcome

Title	Percentage of Events in Each Classification of the Columbia Suicide Severity Rating Scale (C SSRS).
Description	The C-SSRS is an instrument designed to systematically assess and track suicidal behavior and suicidal ideation. The C-SSRS will be completed by the Investigator or Sub-Investigator (or qualified site personnel). Suicidal ideation is collected as any occurrence of wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with any methods (not plan) without intent to act, active suicidal ideation with some intent to act, without specific plan, active suicidal ideation with specific plan and intent. Suicidal behavior is collected as any occurrence of actual attempts, Non-Suicidal Self-Injurious Behavior, interrupted attempts, aborted attempts, or preparatory acts or behavior, suicidal behavior. Any suicidality is defined as having at least one occurrence of Suicidal Behavior or Suicidal Ideation.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

The Intent-to-Treat (ITT) population consisted of all subjects that received any open-label study medication

Arm/Group Title	Eslicarbazepine Acetate
Arm/Group Description:	Open-label treatment with eslicarbazepine acetate will be at doses between 800 and 2400 mg QD Eslicarbazepine acetate: 800 to 2400 mg once daily (QD)
Overall Number of Participants Analyzed	274
Measure Type: Number; Unit of Measure: percentage of events
Any Suicidality	4.0
Any suicidal behavior	0.7
Any suicidal ideation	3.6

8. Secondary Outcome

Title	Time on Eslicarbazepine Acetate Monotherapy.
Description	The start of the monotherapy period was defined as the date of termination of all other anti-epileptic drugs while taking study medication. Time on eslicarbazepine acetate monotherapy is defined from the date of the first monotherapy dose in 093-045 or 093-046 study to the last known dose of monotherapy treatment, regardless of dose change and the time gap between the parent studies and the current study.
Time Frame	One year

Outcome Measure Data

Analysis Population Description

ITT Subjects who started the monotherapy period (Visit 6/Week 8) in 093-045 or 093-046 and did not add a non-rescue/emergency Antiepileptic drug (AED) during the start date of the monotherapy period

Arm/Group Title	Eslicarbazepine Acetate
Arm/Group Description:	Open-label treatment with eslicarbazepine acetate will be at doses between 800 and 2400 mg QD Eslicarbazepine acetate: 800 to 2400 mg once daily (QD)
Overall Number of Participants Analyzed	238
Median (95% Confidence Interval); Unit of Measure: Days
	NA [1]; (NA to NA)

[1]

Median not calculable due to lack of events

9. Secondary Outcome

Title	Change in Seizure Frequency From Baseline.
Description	Relative (%) change in standard seizure frequency(SSF) from baseline
Time Frame	Month 12 from baseline

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population consisted of all subjects who had taken any open-label study medication

Arm/Group Title	Eslicarbazepine Acetate
Arm/Group Description:	Open-label treatment with eslicarbazepine acetate will be at doses between 800 and 2400 mg QD Eslicarbazepine acetate: 800 to 2400 mg once daily (QD)
Overall Number of Participants Analyzed	274
Median (Inter-Quartile Range); Unit of Measure: percent change
	-66.4; (-88.8 to -32.3)

10. Secondary Outcome

Title	Responder Rate (Percentage of Subjects With a ≥50% Reduction of Seizure Frequency From Baseline).
Description	Responder rate (percentage of subjects with a ≥50% reduction of seizure frequency from baseline).
Time Frame	One year

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) population consisted of all subjects who have taken any open-label study medication.

Arm/Group Title	Eslicarbazepine Acetate
Arm/Group Description:	Open-label treatment with eslicarbazepine acetate will be at doses between 800 and 2400 mg QD Eslicarbazepine acetate: 800 to 2400 mg once daily (QD)
Overall Number of Participants Analyzed	274
Measure Type: Number; Unit of Measure: percentage of participants
	62.4

11. Secondary Outcome

Title	Percentage of Subjects That Are Seizure-free During Study
Description	Percentage of subjects that are seizure-free during study
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) population consisted of all subjects who have taken any open-label study medication.

Arm/Group Title	Eslicarbazepine Acetate
Arm/Group Description:	Open-label treatment with eslicarbazepine acetate will be at doses between 800 and 2400 mg QD Eslicarbazepine acetate: 800 to 2400 mg once daily (QD)
Overall Number of Participants Analyzed	274
Measure Type: Number; Unit of Measure: percentage of participants
	7.3

12. Secondary Outcome

Title	Completion Rate (% of Subjects Completing the One Year Treatment)
Description	Completion rate (% of subjects completing the one year treatment)
Time Frame	One year

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) population consisted of all subjects who have taken any open-label study medication.

Arm/Group Title	Eslicarbazepine Acetate
Arm/Group Description:	Open-label treatment with eslicarbazepine acetate will be at doses between 800 and 2400 mg QD Eslicarbazepine acetate: 800 to 2400 mg once daily (QD)
Overall Number of Participants Analyzed	274
Measure Type: Number; Unit of Measure: percentagae of participants
	74.8

13. Secondary Outcome

Title	Treatment Retention Time (Time to Withdrawal Due to Lack of Efficacy or Adverse Events)
Description	The retention time is defined from the start of eslicarbazepine acetate monotherapy period in 093-045 or 093-046 to the last known dose of open-label eslicarbazepine acetate. The time may include taking eslicarbazepine acetate concomitantly with other anti-epileptic drugs. If a subject's termination reason(s) includes: withdrawal of consent, lost to follow-up, physician decision or other, then it was assumed the subject terminated the study due to lack of efficacy.
Time Frame	One year

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) subjects who started the monotherapy period in 093-045 or 093-046 (visi t6/week 8)

Arm/Group Title	Eslicarbazepine Acetate
Arm/Group Description:	Open-label treatment with eslicarbazepine acetate will be at doses between 800 and 2400 mg QD Eslicarbazepine acetate: 800 to 2400 mg once daily (QD)
Overall Number of Participants Analyzed	255
Median (95% Confidence Interval); Unit of Measure: days
	NA [1]; (NA to NA)

[1]

Median time in Days is NA so the 95% CI cannot be calculated since median not calculable due to lack of events during the 1 year open-label period.

14. Secondary Outcome

Title	Change in Total Score From Baseline in 31-Item Quality of Life in Epilepsy (QOLIE-31).
Description	Change in the overall score from baseline in 31-Item Quality of Life in Epilepsy (QOLIE-31 ) The QOLIE-31 overall score was obtained by using a weighted average of multi-item scale scores. The recorded responses were converted to 0-100 point scales. The mean of the individual item scores in each subgroup were calculated, with higher converted scores reflecting better quality of life.
Time Frame	baseline and Month 12

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) population consisted of all subjects who have taken any open-label study medication.

Arm/Group Title	Eslicarbazepine Acetate
Arm/Group Description:	Open-label treatment with eslicarbazepine acetate will be at doses between 800 and 2400 mg QD Eslicarbazepine acetate: 800 to 2400 mg once daily (QD)
Overall Number of Participants Analyzed	274
Mean (Standard Deviation); Unit of Measure: units on a scale
	6.6 (15.29)

15. Secondary Outcome

Title	Change in Total Score From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS).
Description	The total score of MADRS is defined as the sum of all individual item scores. Each of the 10 symptoms of depression on MADRS is measured on a scale of 0 to 6 with 0 representing the lowest severity of the symptom and 6 representing the highest severity.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) population consisted of all subjects who have taken any open-label study medication.

Arm/Group Title	Eslicarbazepine Acetate
Arm/Group Description:	Open-label treatment with eslicarbazepine acetate will be at doses between 800 and 2400 mg QD Eslicarbazepine acetate: 800 to 2400 mg once daily (QD)
Overall Number of Participants Analyzed	274
Mean (Standard Deviation); Unit of Measure: units on a scale
	-1.5 (6.17)

16. Secondary Outcome

Title	Change in Total Score From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) in Those Subjects With a MADRS Score of ≥14 at Screening
Description	The total score of MADRS is defined as the sum of all individual item scores . Each of the 10 symptoms of depression on MADRS is measured on a scale of 0 to 6 with 0 representing the lowest severity of the symptom and 6 representing the highest severity.
Time Frame	baseline and Month 12

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) population consisted of all subjects who have taken any open-label study medication.

Arm/Group Title	Eslicarbazepine Acetate
Arm/Group Description:	Open-label treatment with eslicarbazepine acetate will be at doses between 800 and 2400 mg QD Eslicarbazepine acetate: 800 to 2400 mg once daily (QD)
Overall Number of Participants Analyzed	274
Mean (Standard Deviation); Unit of Measure: units on a scale
	-1.5 (6.17)

17. Secondary Outcome

Title	Completion Rate (% of Subjects Completing Each Visit Post-one Year).
Description	Completion rate (% of subjects completing each visit post-one year).
Time Frame	post 1 year

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) subjects who entered the post - 1- year open -label period.

Arm/Group Title	Eslicarbazepine Acetate
Arm/Group Description:	Open-label treatment with eslicarbazepine acetate will be at doses between 800 and 2400 mg QD Eslicarbazepine acetate: 800 to 2400 mg once daily (QD)
Overall Number of Participants Analyzed	198
Measure Type: Number; Unit of Measure: percentagae of participants
	66.7

Adverse Events

Time Frame	1 year
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Eslicarbazepine Acetate
Arm/Group Description	Open-label treatment with eslicarbazepine acetate will be at doses between 800 and 2400 mg QD Eslicarbazepine acetate: 800 to 2400 mg once daily (QD)
All-Cause Mortality
	Eslicarbazepine Acetate
	Affected / at Risk (%)
Total	2/274 (0.73%)
Serious Adverse Events
	Eslicarbazepine Acetate
	Affected / at Risk (%)	# Events
Total	32/274 (11.68%)
Cardiac disorders
sinus tachycardia † 1	1/274 (0.36%)	1
Ear and labyrinth disorders
vertigo † 1	1/274 (0.36%)	1
Gastrointestinal disorders
abdominal pain upper † 1	1/274 (0.36%)	1
colitis † 1	1/274 (0.36%)	1
pancreatitis † 1	1/274 (0.36%)	1
vomiting † 1	1/274 (0.36%)	1
General disorders
non-cardiac chest pain † 1	3/274 (1.09%)	3
irritability † 1	1/274 (0.36%)	1
sudden unexplained death in epilepsy † 1	1/274 (0.36%)	1
Hepatobiliary disorders
cholelithiasis obstructive † 1	1/274 (0.36%)	1
Infections and infestations
chronic sinusitis † 1	1/274 (0.36%)	1
histoplasmosis † 1	1/274 (0.36%)	1
pneumonia † 1	1/274 (0.36%)	1
tooth infection † 1	1/274 (0.36%)	1
Injury, poisoning and procedural complications
accidental overdose † 1	1/274 (0.36%)	1
collapse of lung † 1	1/274 (0.36%)	1
fall † 1	1/274 (0.36%)	1
post concussion syndrome † 1	1/274 (0.36%)	1
Therapeutic agent toxicity † 1	1/274 (0.36%)	1
Investigations
electroencephalogram † 1	1/274 (0.36%)	1
Metabolism and nutrition disorders
failure to thrive † 1	1/274 (0.36%)	1
Musculoskeletal and connective tissue disorders
arthritis † 1	1/274 (0.36%)	1
muscle twitching † 1	1/274 (0.36%)	1
Osteoarthritis † 1	1/274 (0.36%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
fallopian tube cancer † 1	1/274 (0.36%)	1
non-small cel lung cancer metastatic † 1	1/274 (0.36%)	1
ovarian cancer † 1	1/274 (0.36%)	1
Nervous system disorders
partial seizures with secondary generalisation † 1	7/274 (2.55%)	7
complex partial seizures † 1	3/274 (1.09%)	3
simple partial seizures † 1	2/274 (0.73%)	2
akathisia † 1	1/274 (0.36%)	1
grand mal convulsion † 1	1/274 (0.36%)	1
postictal paralysis † 1	1/274 (0.36%)	1
status epilepticus † 1	1/274 (0.36%)	1
Psychiatric disorders
depression † 1	1/274 (0.36%)	1
suicidal ideation † 1	1/274 (0.36%)	1
Renal and urinary disorders
nephrolithiasis † 1	1/274 (0.36%)	1
Respiratory, thoracic and mediastinal disorders
emphysema † 1	1/274 (0.36%)	1
Vascular disorders
accelerated hypertension † 1	1/274 (0.36%)	1
1 Term from vocabulary, MedDRA (13.1); † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Eslicarbazepine Acetate
	Affected / at Risk (%)	# Events
Total	166/274 (60.58%)
Gastrointestinal disorders
nausea † 1	24/274 (8.76%)	31
vomiting † 1	16/274 (5.84%)	20
diarrhoea † 1	15/274 (5.47%)	19
General disorders
fatigue † 1	23/274 (8.39%)	25
Infections and infestations
nasopharyngitis † 1	24/274 (8.76%)	35
influenza † 1	14/274 (5.11%)	15
Injury, poisoning and procedural complications
fall † 1	20/274 (7.30%)	33
Musculoskeletal and connective tissue disorders
back pain † 1	16/274 (5.84%)	16
Nervous system disorders
headache † 1	64/274 (23.36%)	144
dizziness † 1	46/274 (16.79%)	81
complex partial seizures † 1	14/274 (5.11%)	18
Psychiatric disorders
depression † 1	18/274 (6.57%)	19
insomnia † 1	15/274 (5.47%)	18
1 Term from vocabulary, MedDRA (13.1); † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

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.

Results Point of Contact

• Name/Title: CNS Medical Director
• Organization: Sunovion Pharmaceuticals Inc.
• Phone: 1-866-503-6351
• EMail: clinicaltrialsdisclosure@sunovion.com

• Responsible Party: Sunovion
• ClinicalTrials.gov Identifier: NCT00910247
• Other Study ID Numbers: 093-050
• First Submitted: May 27, 2009
• First Posted: May 29, 2009
• Results First Submitted: April 13, 2018
• Results First Posted: July 17, 2018
• Last Update Posted: July 17, 2018