Trial Outcomes & Findings for Eslicarbazepine Acetate Monotherapy Long Term Study (NCT NCT00910247)

NCT ID: NCT00910247

Last Updated: 2018-07-17

Results Overview

Number and percent of subjects with treatment emergent adverse events

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 274 participants
• Primary outcome timeframe: One year
• Results posted on: 2018-07-17

Participant Flow

Subjects that participated in either study 093-045NCT00866775) or study 093-046(NCT01091662) were eligible to participate in study 093-050

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

Participant milestones

Measure	Eslicarbazepine Acetate 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 Study STARTED	274
Overall Study COMPLETED	205
Overall Study NOT COMPLETED	69

Reasons for withdrawal

Measure	Eslicarbazepine Acetate 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 Study Adverse Event	15
Overall Study Death	2
Overall Study Lost to Follow-up	10
Overall Study Physician Decision	3
Overall Study Protocol Violation	10
Overall Study Withdrawal by Subject	25
Overall Study Not collected	4

Baseline Characteristics

Eslicarbazepine Acetate Monotherapy Long Term Study

Baseline characteristics by cohort

Measure	Eslicarbazepine Acetate n=274 Participants 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)
Age, Categorical <=18 years	12 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	258 Participants n=5 Participants
Age, Categorical >=65 years	4 Participants n=5 Participants
Age, Continuous	37.9 years STANDARD_DEVIATION 12.70 • n=5 Participants
Sex: Female, Male Female	134 Participants n=5 Participants
Sex: Female, Male Male	140 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	28 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	246 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	2 Participants n=5 Participants
Race (NIH/OMB) Asian	5 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	22 Participants n=5 Participants
Race (NIH/OMB) White	229 Participants n=5 Participants
Race (NIH/OMB) More than one race	2 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	14 Participants n=5 Participants
Region of Enrollment Canada	3 participants n=5 Participants
Region of Enrollment United States	167 participants n=5 Participants
Region of Enrollment Czechia	27 participants n=5 Participants
Region of Enrollment Ukraine	57 participants n=5 Participants
Region of Enrollment Bulgaria	18 participants n=5 Participants
Region of Enrollment Serbia	2 participants n=5 Participants

PRIMARY outcome

Timeframe: One year

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

Number and percent of subjects with treatment emergent adverse events

Outcome measures

Measure	Eslicarbazepine Acetate n=274 Participants 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)
Number and Percent of Subjects With Treatment Emergent Adverse Events	220 Participants

SECONDARY outcome

Timeframe: 1 year

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

Number and percentage of subjects with potentially clinically significant clinical laboratory evaluations

Outcome measures

Measure	Eslicarbazepine Acetate n=274 Participants 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)
Number and Percentage of Subjects With Potentially Clinically Significant Clinical Laboratory Evaluations	186 Participants

SECONDARY outcome

Timeframe: 1 year

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

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.

Outcome measures

Measure	Eslicarbazepine Acetate n=261 Participants 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)
Number and Percent of Subjects With Normal Baseline Sodium Reaching Blood Sodium ≤135 mmol/L, ≤130 mmol/L, and ≤125 mmol/L <=135 mEq/L and >130 mEq/L	48 Participants
Number and Percent of Subjects With Normal Baseline Sodium Reaching Blood Sodium ≤135 mmol/L, ≤130 mmol/L, and ≤125 mmol/L <=130 mEq/L and >125 mEq/L	22 Participants
Number and Percent of Subjects With Normal Baseline Sodium Reaching Blood Sodium ≤135 mmol/L, ≤130 mmol/L, and ≤125 mmol/L <=125 mEq/L	4 Participants

SECONDARY outcome

Timeframe: 1 year

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

Percentage of subjects with increase of body weight ≥7%

Outcome measures

Measure	Eslicarbazepine Acetate n=274 Participants 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)
Percentage of Subjects With Increase of Body Weight ≥7%	27 percentagae of participants

SECONDARY outcome

Timeframe: 1 year

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

Number and percentage of subjects with orthostatic effects.

Outcome measures

Measure	Eslicarbazepine Acetate n=274 Participants 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)
Number and Percentage of Subjects With Orthostatic Effects.	67 Participants

SECONDARY outcome

Timeframe: Baseline, Month 12

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

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:

1. >500 millisecond (msec) at any post-baseline timepoint but not present at baseline

2. >480 msec at any post-baseline timepoint but not present at baseline

3. >450 msec at any post-baseline timepoint but not present at baseline

4. Change from Baseline >=60 ms for at least one post-baseline measurement

5. 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.

Outcome measures

Measure	Eslicarbazepine Acetate n=272 Participants 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)
Number and Percentage of Subjects With QTc-F Changes (in Categories) From Baseline. >500ms at any postbaseline not present at baseli	0 Participants
Number and Percentage of Subjects With QTc-F Changes (in Categories) From Baseline. >450ms at any postbaseline not present at baseline	9 Participants
Number and Percentage of Subjects With QTc-F Changes (in Categories) From Baseline. >480ms at any postbaseline not present at baseline	1 Participants
Number and Percentage of Subjects With QTc-F Changes (in Categories) From Baseline. CFB >=60 ms for at least one post-baseline	0 Participants
Number and Percentage of Subjects With QTc-F Changes (in Categories) From Baseline. CFB>=30ms for at least one &<60ms for all PBL	42 Participants

SECONDARY outcome

Timeframe: 1 year

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

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.

Outcome measures

Measure	Eslicarbazepine Acetate n=274 Participants 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)
Percentage of Events in Each Classification of the Columbia Suicide Severity Rating Scale (C SSRS). Any Suicidality	4.0 percentage of events
Percentage of Events in Each Classification of the Columbia Suicide Severity Rating Scale (C SSRS). Any suicidal behavior	0.7 percentage of events
Percentage of Events in Each Classification of the Columbia Suicide Severity Rating Scale (C SSRS). Any suicidal ideation	3.6 percentage of events

SECONDARY outcome

Timeframe: One year

Population: 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

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.

Outcome measures

Measure	Eslicarbazepine Acetate n=238 Participants 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)
Time on Eslicarbazepine Acetate Monotherapy.	NA Days Median not calculable due to lack of events

SECONDARY outcome

Timeframe: Month 12 from baseline

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

Relative (%) change in standard seizure frequency(SSF) from baseline

Outcome measures

Measure	Eslicarbazepine Acetate n=274 Participants 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)
Change in Seizure Frequency From Baseline.	-66.4 percent change Interval -88.8 to -32.3

SECONDARY outcome

Timeframe: One year

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

Responder rate (percentage of subjects with a ≥50% reduction of seizure frequency from baseline).

Outcome measures

Measure	Eslicarbazepine Acetate n=274 Participants 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)
Responder Rate (Percentage of Subjects With a ≥50% Reduction of Seizure Frequency From Baseline).	62.4 percentage of participants

SECONDARY outcome

Timeframe: 1 year

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

Percentage of subjects that are seizure-free during study

Outcome measures

Measure	Eslicarbazepine Acetate n=274 Participants 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)
Percentage of Subjects That Are Seizure-free During Study	7.3 percentage of participants

SECONDARY outcome

Timeframe: One year

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

Completion rate (% of subjects completing the one year treatment)

Outcome measures

Measure	Eslicarbazepine Acetate n=274 Participants 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)
Completion Rate (% of Subjects Completing the One Year Treatment)	74.8 percentagae of participants

SECONDARY outcome

Timeframe: One year

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

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.

Outcome measures

Measure	Eslicarbazepine Acetate n=255 Participants 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)
Treatment Retention Time (Time to Withdrawal Due to Lack of Efficacy or Adverse Events)	NA days 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.

SECONDARY outcome

Timeframe: baseline and Month 12

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

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.

Outcome measures

Measure	Eslicarbazepine Acetate n=274 Participants 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)
Change in Total Score From Baseline in 31-Item Quality of Life in Epilepsy (QOLIE-31).	6.6 units on a scale Standard Deviation 15.29

SECONDARY outcome

Timeframe: 1 year

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

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.

Outcome measures

Measure	Eslicarbazepine Acetate n=274 Participants 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)
Change in Total Score From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS).	-1.5 units on a scale Standard Deviation 6.17

SECONDARY outcome

Timeframe: baseline and Month 12

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

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.

Outcome measures

Measure	Eslicarbazepine Acetate n=274 Participants 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)
Change in Total Score From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) in Those Subjects With a MADRS Score of ≥14 at Screening	-1.5 units on a scale Standard Deviation 6.17

SECONDARY outcome

Timeframe: post 1 year

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

Completion rate (% of subjects completing each visit post-one year).

Outcome measures

Measure	Eslicarbazepine Acetate n=198 Participants 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)
Completion Rate (% of Subjects Completing Each Visit Post-one Year).	66.7 percentagae of participants

Adverse Events

Eslicarbazepine Acetate

Serious events: 32 serious events

Other events: 166 other events

Deaths: 2 deaths

Serious adverse events

Measure	Eslicarbazepine Acetate n=274 participants at risk 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)
Cardiac disorders sinus tachycardia	0.36% 1/274 • Number of events 1 • 1 year
Ear and labyrinth disorders vertigo	0.36% 1/274 • Number of events 1 • 1 year
Gastrointestinal disorders abdominal pain upper	0.36% 1/274 • Number of events 1 • 1 year
Gastrointestinal disorders colitis	0.36% 1/274 • Number of events 1 • 1 year
Gastrointestinal disorders pancreatitis	0.36% 1/274 • Number of events 1 • 1 year
Gastrointestinal disorders vomiting	0.36% 1/274 • Number of events 1 • 1 year
General disorders non-cardiac chest pain	1.1% 3/274 • Number of events 3 • 1 year
General disorders irritability	0.36% 1/274 • Number of events 1 • 1 year
General disorders sudden unexplained death in epilepsy	0.36% 1/274 • Number of events 1 • 1 year
Hepatobiliary disorders cholelithiasis obstructive	0.36% 1/274 • Number of events 1 • 1 year
Infections and infestations chronic sinusitis	0.36% 1/274 • Number of events 1 • 1 year
Infections and infestations histoplasmosis	0.36% 1/274 • Number of events 1 • 1 year
Infections and infestations pneumonia	0.36% 1/274 • Number of events 1 • 1 year
Infections and infestations tooth infection	0.36% 1/274 • Number of events 1 • 1 year
Injury, poisoning and procedural complications accidental overdose	0.36% 1/274 • Number of events 1 • 1 year
Injury, poisoning and procedural complications collapse of lung	0.36% 1/274 • Number of events 1 • 1 year
Injury, poisoning and procedural complications fall	0.36% 1/274 • Number of events 1 • 1 year
Injury, poisoning and procedural complications post concussion syndrome	0.36% 1/274 • Number of events 1 • 1 year
Injury, poisoning and procedural complications Therapeutic agent toxicity	0.36% 1/274 • Number of events 1 • 1 year
Investigations electroencephalogram	0.36% 1/274 • Number of events 1 • 1 year
Metabolism and nutrition disorders failure to thrive	0.36% 1/274 • Number of events 1 • 1 year
Musculoskeletal and connective tissue disorders arthritis	0.36% 1/274 • Number of events 1 • 1 year
Musculoskeletal and connective tissue disorders muscle twitching	0.36% 1/274 • Number of events 1 • 1 year
Musculoskeletal and connective tissue disorders Osteoarthritis	0.36% 1/274 • Number of events 1 • 1 year
Neoplasms benign, malignant and unspecified (incl cysts and polyps) fallopian tube cancer	0.36% 1/274 • Number of events 1 • 1 year
Neoplasms benign, malignant and unspecified (incl cysts and polyps) non-small cel lung cancer metastatic	0.36% 1/274 • Number of events 1 • 1 year
Neoplasms benign, malignant and unspecified (incl cysts and polyps) ovarian cancer	0.36% 1/274 • Number of events 1 • 1 year
Nervous system disorders partial seizures with secondary generalisation	2.6% 7/274 • Number of events 7 • 1 year
Nervous system disorders complex partial seizures	1.1% 3/274 • Number of events 3 • 1 year
Nervous system disorders simple partial seizures	0.73% 2/274 • Number of events 2 • 1 year
Nervous system disorders akathisia	0.36% 1/274 • Number of events 1 • 1 year
Nervous system disorders grand mal convulsion	0.36% 1/274 • Number of events 1 • 1 year
Nervous system disorders postictal paralysis	0.36% 1/274 • Number of events 1 • 1 year
Nervous system disorders status epilepticus	0.36% 1/274 • Number of events 1 • 1 year
Psychiatric disorders depression	0.36% 1/274 • Number of events 1 • 1 year
Psychiatric disorders suicidal ideation	0.36% 1/274 • Number of events 1 • 1 year
Renal and urinary disorders nephrolithiasis	0.36% 1/274 • Number of events 1 • 1 year
Respiratory, thoracic and mediastinal disorders emphysema	0.36% 1/274 • Number of events 1 • 1 year
Vascular disorders accelerated hypertension	0.36% 1/274 • Number of events 1 • 1 year

Other adverse events

Measure	Eslicarbazepine Acetate n=274 participants at risk 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)
Gastrointestinal disorders nausea	8.8% 24/274 • Number of events 31 • 1 year
Gastrointestinal disorders vomiting	5.8% 16/274 • Number of events 20 • 1 year
Gastrointestinal disorders diarrhoea	5.5% 15/274 • Number of events 19 • 1 year
General disorders fatigue	8.4% 23/274 • Number of events 25 • 1 year
Infections and infestations nasopharyngitis	8.8% 24/274 • Number of events 35 • 1 year
Infections and infestations influenza	5.1% 14/274 • Number of events 15 • 1 year
Injury, poisoning and procedural complications fall	7.3% 20/274 • Number of events 33 • 1 year
Musculoskeletal and connective tissue disorders back pain	5.8% 16/274 • Number of events 16 • 1 year
Nervous system disorders headache	23.4% 64/274 • Number of events 144 • 1 year
Nervous system disorders dizziness	16.8% 46/274 • Number of events 81 • 1 year
Nervous system disorders complex partial seizures	5.1% 14/274 • Number of events 18 • 1 year
Psychiatric disorders depression	6.6% 18/274 • Number of events 19 • 1 year
Psychiatric disorders insomnia	5.5% 15/274 • Number of events 18 • 1 year

Additional Information

CNS Medical Director

Sunovion Pharmaceuticals Inc.

Phone: 1-866-503-6351

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