Trial Outcomes & Findings for Anti-epileptogenic Effects of Eslicarbazepine Acetate (NCT NCT06597084)

Last Updated: 2025-05-02

Results Overview

Deaths before the first US or patients without evaluable assessment of the primary endpoint will be counted as treatment failures. To show that ESL (Group A) is superior to placebo (Group B), the primary null hypothesis will be tested against the alternative hypothesis

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

129 participants

Primary outcome timeframe

First 6 months after randomisation

Results posted on

2025-05-02

Participant Flow

A total of 4 patients failed screening. Overall, of 125 patients in the randomised set, 92 patients completed the 6-month period, 86 patients completed the 12-month period, and 84 patients completed the 18-month period. A total of 41 patients prematurely terminated the trial with similar frequencies in both treatment groups. Most of them terminated the trial before Visit 3 (24 patients) with lower frequency in the ESL group (10 patients) than in the placebo group (14 patients).

Participant milestones

Participant milestones
Measure	Group A ESL 800 mg ESL 800 mg: 800 mg ESL tablets for oral administration. In case a patient is unable to swallow the whole tablet, the tablet can be crushed or divided into equal doses at the score line.	Group B Placebo Placebo: Placebo tablets for oral administration, matching the test product. In case a patient is unable to swallow the whole tablet, the tablet can be crushed or divided into equal doses at the score line.
Overall Study STARTED	62	63
Overall Study Safety Set	61	62
Overall Study Full Analysis Set	61	62
Overall Study Electroencephalogram (EEG) Analysis Subset	31	34
Overall Study COMPLETED	43	41
Overall Study NOT COMPLETED	19	22

Reasons for withdrawal

Reasons for withdrawal
Measure	Group A ESL 800 mg ESL 800 mg: 800 mg ESL tablets for oral administration. In case a patient is unable to swallow the whole tablet, the tablet can be crushed or divided into equal doses at the score line.	Group B Placebo Placebo: Placebo tablets for oral administration, matching the test product. In case a patient is unable to swallow the whole tablet, the tablet can be crushed or divided into equal doses at the score line.
Overall Study Withdrawal by Subject	4	9
Overall Study Consent was not given by the patient until V2	0	3
Overall Study Physician Decision	1	0
Overall Study Adverse Event	3	2
Overall Study Death	4	0
Overall Study Stroke more than 7 days after primary stroke	2	6
Overall Study Lost to Follow-up	4	2
Overall Study Other. Not specified	1	0

Baseline Characteristics

The percentage for females of childbearing potential is based on number of females

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Group A n=61 Participants ESL 800 mg ESL 800 mg: 800 mg ESL tablets for oral administration. In case a patient is unable to swallow the whole tablet, the tablet can be crushed or divided into equal doses at the score line.	Group B n=62 Participants Placebo Placebo: Placebo tablets for oral administration, matching the test product. In case a patient is unable to swallow the whole tablet, the tablet can be crushed or divided into equal doses at the score line.	Total n=123 Participants Total of all reporting groups
Age, Categorical <=18 years	30 Participants n=61 Participants	27 Participants n=62 Participants	57 Participants n=123 Participants
Age, Categorical Between 18 and 65 years	25 Participants n=61 Participants	33 Participants n=62 Participants	58 Participants n=123 Participants
Age, Categorical >=65 years	6 Participants n=61 Participants	2 Participants n=62 Participants	8 Participants n=123 Participants
Sex: Female, Male Female	23 Participants n=61 Participants	22 Participants n=62 Participants	45 Participants n=123 Participants
Sex: Female, Male Male	38 Participants n=61 Participants	40 Participants n=62 Participants	78 Participants n=123 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=61 Participants	0 Participants n=62 Participants	0 Participants n=123 Participants
Race (NIH/OMB) Asian	1 Participants n=61 Participants	0 Participants n=62 Participants	1 Participants n=123 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=61 Participants	0 Participants n=62 Participants	0 Participants n=123 Participants
Race (NIH/OMB) Black or African American	3 Participants n=61 Participants	1 Participants n=62 Participants	4 Participants n=123 Participants
Race (NIH/OMB) White	57 Participants n=61 Participants	60 Participants n=62 Participants	117 Participants n=123 Participants
Race (NIH/OMB) More than one race	0 Participants n=61 Participants	1 Participants n=62 Participants	1 Participants n=123 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=61 Participants	0 Participants n=62 Participants	0 Participants n=123 Participants
Female of childbearing potential Yes	5 Participants n=23 Participants • The percentage for females of childbearing potential is based on number of females	3 Participants n=22 Participants • The percentage for females of childbearing potential is based on number of females	8 Participants n=45 Participants • The percentage for females of childbearing potential is based on number of females
Female of childbearing potential No	18 Participants n=23 Participants • The percentage for females of childbearing potential is based on number of females	19 Participants n=22 Participants • The percentage for females of childbearing potential is based on number of females	37 Participants n=45 Participants • The percentage for females of childbearing potential is based on number of females

PRIMARY outcome

Timeframe: First 6 months after randomisation

Outcome measures

Outcome measures
Measure	Group A n=61 Participants ESL 800 mg ESL 800 mg: 800 mg ESL tablets for oral administration. In case a patient is unable to swallow the whole tablet, the tablet can be crushed or divided into equal doses at the score line.	Group B n=62 Participants Placebo Placebo: Placebo tablets for oral administration, matching the test product. In case a patient is unable to swallow the whole tablet, the tablet can be crushed or divided into equal doses at the score line.
Proportion of Patients Who Experience the First Unprovoked Seizures (US) Within the First 6 Months After Randomisation (Failure Rate) Failures - Unprovoked seizure	2 Participants	7 Participants
Proportion of Patients Who Experience the First Unprovoked Seizures (US) Within the First 6 Months After Randomisation (Failure Rate) Failures - Death	3 Participants	0 Participants
Proportion of Patients Who Experience the First Unprovoked Seizures (US) Within the First 6 Months After Randomisation (Failure Rate) Failures - Withdrawn	12 Participants	16 Participants
Proportion of Patients Who Experience the First Unprovoked Seizures (US) Within the First 6 Months After Randomisation (Failure Rate) Non-failures	44 Participants	39 Participants

SECONDARY outcome

Timeframe: First 12 months after randomisation

Outcome measures

Outcome measures
Measure	Group A n=61 Participants ESL 800 mg ESL 800 mg: 800 mg ESL tablets for oral administration. In case a patient is unable to swallow the whole tablet, the tablet can be crushed or divided into equal doses at the score line.	Group B n=62 Participants Placebo Placebo: Placebo tablets for oral administration, matching the test product. In case a patient is unable to swallow the whole tablet, the tablet can be crushed or divided into equal doses at the score line.
Proportion of Patients Who Experience the First US During the First 12 Months After Randomisation Failures - Unprovoked seizure	3 Participants	8 Participants
Proportion of Patients Who Experience the First US During the First 12 Months After Randomisation Failures - Death	3 Participants	0 Participants
Proportion of Patients Who Experience the First US During the First 12 Months After Randomisation Failures - Withdrawn	13 Participants	18 Participants
Proportion of Patients Who Experience the First US During the First 12 Months After Randomisation Non-failures	42 Participants	36 Participants

SECONDARY outcome

Timeframe: Until 18 months after randomisation

Outcome measures

Outcome measures
Measure	Group A n=61 Participants ESL 800 mg ESL 800 mg: 800 mg ESL tablets for oral administration. In case a patient is unable to swallow the whole tablet, the tablet can be crushed or divided into equal doses at the score line.	Group B n=62 Participants Placebo Placebo: Placebo tablets for oral administration, matching the test product. In case a patient is unable to swallow the whole tablet, the tablet can be crushed or divided into equal doses at the score line.
Proportion of Patients Who Experience the First US During the Course of the Trial Failures - Death	4 Participants	0 Participants
Proportion of Patients Who Experience the First US During the Course of the Trial Failures - Withdrawn	14 Participants	18 Participants
Proportion of Patients Who Experience the First US During the Course of the Trial Failures - Unprovoked seizure	5 Participants	9 Participants
Proportion of Patients Who Experience the First US During the Course of the Trial Non-failures	38 Participants	35 Participants

SECONDARY outcome

Timeframe: During the first 7 days after stroke

Number of ASSs will be summarised by means of descriptive statistics

Outcome measures

Outcome measures
Measure	Group A n=61 Participants ESL 800 mg ESL 800 mg: 800 mg ESL tablets for oral administration. In case a patient is unable to swallow the whole tablet, the tablet can be crushed or divided into equal doses at the score line.	Group B n=62 Participants Placebo Placebo: Placebo tablets for oral administration, matching the test product. In case a patient is unable to swallow the whole tablet, the tablet can be crushed or divided into equal doses at the score line.
Number of Acute Symptomatic Seizure (ASS) Patients with at least one ASS	10 Participants	15 Participants
Number of Acute Symptomatic Seizure (ASS) Patients without an ASS	51 Participants	47 Participants

SECONDARY outcome

Timeframe: Over 18 months follow-up period

Population: The time is related to 6, 12 and 18 months and the percentage means the estimated probability to experience a first US in that specific time.

The time to first US after randomisation will be analysed and presented by means of the Kaplan-Meier estimate after 6, 12 and 18 months for the failure time. The time to first US will be analysed from the day of randomisation.

Outcome measures

Outcome measures
Measure	Group A n=61 Participants ESL 800 mg ESL 800 mg: 800 mg ESL tablets for oral administration. In case a patient is unable to swallow the whole tablet, the tablet can be crushed or divided into equal doses at the score line.	Group B n=62 Participants Placebo Placebo: Placebo tablets for oral administration, matching the test product. In case a patient is unable to swallow the whole tablet, the tablet can be crushed or divided into equal doses at the score line.
Probability of Failure at 6, 12, and 18 Months After Randomization Kaplan - Meier failure probability estimate at Month 18 (Day 547)	10.34 Percentage of failure	19.17 Percentage of failure
Probability of Failure at 6, 12, and 18 Months After Randomization Kaplan - Meier failure probability estimate at Month 6 (Day 182)	3.50 Percentage of failure	14.55 Percentage of failure
Probability of Failure at 6, 12, and 18 Months After Randomization Kaplan - Meier failure probability estimate at Month 12 (Day 365)	5.74 Percentage of failure	16.86 Percentage of failure

SECONDARY outcome

Timeframe: Over 18 months follow-up period

Population: Omitted with statistical analysis plan (SAP), Final version 1.0, 22-11-2023. Secondary objective and endpoint "Time to first US after stroke occurrence" was decided to be deleted as it is closely related to the forth secondary endpoint "Time to first US after randomisation" and therefore would not really have any additional value.

Analysis of time to first US will be performed using the day of stroke (before randomisation) as Day 1. The secondary objective and endpoint "Time to first US after stroke occurrence" was decided to be deleted as it is closely related to the forth secondary endpoint "Time to first US after randomisation" and therefore would not really have any additional value.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Over 18 months follow-up period

Population: Omitted with statistical analysis plan \[SAP\], Final version 1.0, 22-NOV-2023. Secondary objective and endpoint "Time to first US after stroke occurrence" was decided to be deleted as it is closely related to the forth secondary endpoint "Time to first US after randomisation" and therefore would not really have any additional value.

The total number and rate of USs, standardised per 4 weeks, in all patients and in patients with US(s) only will be summarised by means of descriptive statistics. The secondary objective and endpoint "4-week rate of USs" was decided to be deleted as this information will not be meaningful for this trial.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Barthel Index data is collected at Baseline, V3 (+37 days), V5 (+26 weeks), V7 (+52 weeks), End of trial visit (EOT, +78 weeks) or Early discontinuation visit (EDV, on average 30 days), and Endpoint (18 months).

Population: The total BI score (possible range 0 - 100) will be calculated as the sum of the individual scores from each item. General ranges of BI describe patients' disability as follows: 80-100 - patient should be able to live independently 60-79 - minimally dependent 40-59 - partially dependent 20-39 - very dependent \<20 - total dependence

The Barthel Index at baseline and post-baseline visits of each patient will be calculated adding the individual scores from each item. Baseline is the value assessed before first IMP intake. Endpoint is the last non-missing value collected after the first IMP intake. The BI is a widely used score to measure the performance in activities of daily living of patients with stroke and other neuromuscular or musculoskeletal disorders in the following 10 categories: 1. Feeding (scored as 0, 5, 10) 2. Moving from a wheelchair to a bed and back again (scored as 0, 5, 10, 15) 3. Personal hygiene (scored as 0, 5) 4. Getting on and off the toilet (scored as 0, 5, 10) 5. Self-bathing (scored as 0, 5) 6. Walking on a level surface (scored as 0, 5, 10, 15) 7. Ascending and descending stairs (scored as 0, 5, 10) 8. Dressing (scored as 0, 5, 10) 9. Controlling bowels (scored as 0, 5, 10) 10. Controlling bladder (scored as 0, 5, 10) The minimum value means with help and maximum independent

Outcome measures

Outcome measures
Measure	Group A n=61 Participants ESL 800 mg ESL 800 mg: 800 mg ESL tablets for oral administration. In case a patient is unable to swallow the whole tablet, the tablet can be crushed or divided into equal doses at the score line.	Group B n=62 Participants Placebo Placebo: Placebo tablets for oral administration, matching the test product. In case a patient is unable to swallow the whole tablet, the tablet can be crushed or divided into equal doses at the score line.
Barthel Index (BI) Original 10-item Version Baseline - Observed Value	66.1 Score on a scale Interval 0.0 to 100.0	61.9 Score on a scale Interval 0.0 to 100.0
Barthel Index (BI) Original 10-item Version V3 - Observed Value	85.5 Score on a scale Interval 0.0 to 100.0	87.2 Score on a scale Interval 0.0 to 100.0
Barthel Index (BI) Original 10-item Version V5 - Observed Value	94.3 Score on a scale Interval 0.0 to 100.0	95.7 Score on a scale Interval 0.0 to 100.0
Barthel Index (BI) Original 10-item Version V7 - Observed Value	92.2 Score on a scale Interval 0.0 to 100.0	96.3 Score on a scale Interval 0.0 to 100.0
Barthel Index (BI) Original 10-item Version EDV - Observed Value	66.0 Score on a scale Interval 0.0 to 100.0	96.3 Score on a scale Interval 0.0 to 100.0
Barthel Index (BI) Original 10-item Version EoT - Observed Value	92.4 Score on a scale Interval 0.0 to 100.0	94.9 Score on a scale Interval 0.0 to 100.0
Barthel Index (BI) Original 10-item Version Endpoint	87.5 Score on a scale Interval 0.0 to 100.0	93.6 Score on a scale Interval 0.0 to 100.0

SECONDARY outcome

Timeframe: National Institutes of Health Stroke Scale (NIHSS) data is collected at Baseline, V3 (+37 days), V5 (+26 weeks), V7 (+52 weeks), End of trial visit (EOT, +78 weeks) or Early discontinuation visit (EDV, on average 30 days), and Endpoint (18 months).

Population: Stroke severity will be stratified based on NIHSS total score as follows: \<11 - mild and moderately severe ≥11 - severe For each patient, the total NIHSS score at baseline and each post-baseline visit will be calculated adding the individual scores from each item.

The NIHSS is a systematic assessment tool that provides a quantitative measure of stroke-related neurologic deficits. The following questions will be asked: 1a. Level of Consciousness (LOC) (scored as 0, 1, 2, 3) 1b. LOC Questions (scored as 0, 1, 2) 1c. LOC Commands (scored as 0, 1, 2) 2. Best Gaze (scored as 0, 1, 2) 3. Visual (scored as 0, 1, 2, 3) 4. Facial Palsy (scored as 0, 1, 2, 3) 5a. Motor Arm (Left Arm) (scored as 0, 1, 2, 3, 4) 5b. Motor Arm (Right Arm) (scored as 0, 1, 2, 3, 4) 6a. Motor Leg (Left Leg) (scored as 0, 1, 2, 3, 4) 6b. Motor Right (Right Leg) (scored as 0, 1, 2, 3, 4) 7. Limb Ataxia (scored as 0, 1, 2) 8. Sensory (scored as 0, 1, 2) 9. Best Language (scored as 0, 1, 2, 3) 10. Dysarthria (scored as 0, 1, 2) 11. Extinction and Inattention (formerly Neglect) (scored as 0, 1, 2) The sum of all 15 individual scores will provide the patient's total NIHSS score where 0 is "no stroke symptoms" and 42 is "severe stroke".

Outcome measures

Outcome measures
Measure	Group A n=61 Participants ESL 800 mg ESL 800 mg: 800 mg ESL tablets for oral administration. In case a patient is unable to swallow the whole tablet, the tablet can be crushed or divided into equal doses at the score line.	Group B n=62 Participants Placebo Placebo: Placebo tablets for oral administration, matching the test product. In case a patient is unable to swallow the whole tablet, the tablet can be crushed or divided into equal doses at the score line.
National Institutes of Health Stroke Scale (NIHSS) V2 - Observed Value	4.6 Score on a scale Interval 0.0 to 42.0	3.0 Score on a scale Interval 0.0 to 42.0
National Institutes of Health Stroke Scale (NIHSS) Early discontinuation visit - Observed Value	3.4 Score on a scale Interval 0.0 to 42.0	0 Score on a scale Interval 0.0 to 42.0
National Institutes of Health Stroke Scale (NIHSS) Baseline - Observed Value	8.5 Score on a scale Interval 0.0 to 42.0	8.8 Score on a scale Interval 0.0 to 42.0
National Institutes of Health Stroke Scale (NIHSS) V3 - Observed Value	2.5 Score on a scale Interval 0.0 to 42.0	1.5 Score on a scale Interval 0.0 to 42.0
National Institutes of Health Stroke Scale (NIHSS) V5 - Observed Value	1.9 Score on a scale Interval 0.0 to 42.0	0.6 Score on a scale Interval 0.0 to 42.0
National Institutes of Health Stroke Scale (NIHSS) V7 - Observed Value	1.6 Score on a scale Interval 0.0 to 42.0	0.8 Score on a scale Interval 0.0 to 42.0
National Institutes of Health Stroke Scale (NIHSS) End of trial visit - Observed Value	1.5 Score on a scale Interval 0.0 to 42.0	0.6 Score on a scale Interval 0.0 to 42.0
National Institutes of Health Stroke Scale (NIHSS) Endpoint - Observed Value	2.9 Score on a scale Interval 0.0 to 42.0	1.5 Score on a scale Interval 0.0 to 42.0

SECONDARY outcome

Timeframe: Over 18 months follow-up period

The PHQ-9 can be used for screening, diagnosing and measuring the severity of depression in stroke patients. The patient will rate on a scale from 0 (not at all) to 3 (nearly every day) how often each of the 9 symptoms occurred during the past 2 weeks. The individual scores from each item of the PHQ-9 will be added to calculate the total PHQ-9 score for each time of examination.

Outcome measures

Outcome measures
Measure	Group A n=61 Participants ESL 800 mg ESL 800 mg: 800 mg ESL tablets for oral administration. In case a patient is unable to swallow the whole tablet, the tablet can be crushed or divided into equal doses at the score line.	Group B n=62 Participants Placebo Placebo: Placebo tablets for oral administration, matching the test product. In case a patient is unable to swallow the whole tablet, the tablet can be crushed or divided into equal doses at the score line.
Patient Health Questionnaire (PHQ-9) Baseline - Observed Value	3.7 Points Standard Deviation 3.34	3.4 Points Standard Deviation 4.43
Patient Health Questionnaire (PHQ-9) Endpoint - Observed Value	4.1 Points Standard Deviation 3.96	4.3 Points Standard Deviation 5.25
Patient Health Questionnaire (PHQ-9) Endpoint - Change from Baseline	0.5 Points Standard Deviation 4.61	0.7 Points Standard Deviation 6.13

SECONDARY outcome

Timeframe: Over 18 months follow-up period

Population: Patients censored are all patients who discontinued the study due to any reason including death before study day 548. The time is related to 6, 12 and 18 months and the percentage means the probability to experience a first US in that specific time.

Overall survival (time to death relative to the date of randomization) will be analysed and presented by means of the Kaplan-Meier estimates (including censored data e.g. withdrawals) after 6 months (Day 182), 12 months (Day 365) and 18 months (Day 547) for the survival rates.

Outcome measures

Outcome measures
Measure	Group A n=61 Participants ESL 800 mg ESL 800 mg: 800 mg ESL tablets for oral administration. In case a patient is unable to swallow the whole tablet, the tablet can be crushed or divided into equal doses at the score line.	Group B n=62 Participants Placebo Placebo: Placebo tablets for oral administration, matching the test product. In case a patient is unable to swallow the whole tablet, the tablet can be crushed or divided into equal doses at the score line.
Overall Survival at 6, 12, and 18 Months After Randomization Kaplan - Meier death probability estimate at Month 6 (Day 182)	5.64 Percentage of death probability	0.00 Percentage of death probability
Overall Survival at 6, 12, and 18 Months After Randomization Kaplan - Meier death probability estimate at Month 12 (Day 365)	5.64 Percentage of death probability	0.00 Percentage of death probability
Overall Survival at 6, 12, and 18 Months After Randomization Kaplan - Meier death probability estimate at Month 18 (Day 547)	7.74 Percentage of death probability	0.00 Percentage of death probability

SECONDARY outcome

Timeframe: Over 18 months follow-up period

Population: TEAE: Adverse Event with onset or worsening after first IMP intake until 14 days after last IMP intake.

Adverse events (AEs) not considered treatment-emergent according to this definition or with missing data will be medically reviewed during the data review meeting and will be considered treatment emergent if appropriate

Outcome measures

Outcome measures
Measure	Group A n=61 Participants ESL 800 mg ESL 800 mg: 800 mg ESL tablets for oral administration. In case a patient is unable to swallow the whole tablet, the tablet can be crushed or divided into equal doses at the score line.	Group B n=62 Participants Placebo Placebo: Placebo tablets for oral administration, matching the test product. In case a patient is unable to swallow the whole tablet, the tablet can be crushed or divided into equal doses at the score line.
Treatment Emergent Adverse Events (TEAEs) Incl. Findings From Physical and Neurological Examinations TEAE leading to discontinuation of IMP	16 Participants	6 Participants
Treatment Emergent Adverse Events (TEAEs) Incl. Findings From Physical and Neurological Examinations TEAE	50 Participants	51 Participants
Treatment Emergent Adverse Events (TEAEs) Incl. Findings From Physical and Neurological Examinations Non-serious TEAE	50 Participants	48 Participants
Treatment Emergent Adverse Events (TEAEs) Incl. Findings From Physical and Neurological Examinations Serious TEAE	12 Participants	13 Participants
Treatment Emergent Adverse Events (TEAEs) Incl. Findings From Physical and Neurological Examinations Related TEAE	23 Participants	12 Participants
Treatment Emergent Adverse Events (TEAEs) Incl. Findings From Physical and Neurological Examinations Serious related TEAE	3 Participants	0 Participants
Treatment Emergent Adverse Events (TEAEs) Incl. Findings From Physical and Neurological Examinations Severe TEAE	9 Participants	8 Participants
Treatment Emergent Adverse Events (TEAEs) Incl. Findings From Physical and Neurological Examinations TEAE leading to dose reduction	0 Participants	2 Participants
Treatment Emergent Adverse Events (TEAEs) Incl. Findings From Physical and Neurological Examinations TEAE requiring medication	36 Participants	46 Participants
Treatment Emergent Adverse Events (TEAEs) Incl. Findings From Physical and Neurological Examinations TEAE leading to death	2 Participants	0 Participants
Treatment Emergent Adverse Events (TEAEs) Incl. Findings From Physical and Neurological Examinations Ongoing TEAE at the end of the trial	31 Participants	30 Participants
Treatment Emergent Adverse Events (TEAEs) Incl. Findings From Physical and Neurological Examinations TEAE leading to study discontinuation	4 Participants	4 Participants

SECONDARY outcome

Timeframe: Over 18 months follow-up period

Population: Shifts of Haematology Parameters from Normal or Abnormal to Clinically Significant (CS) Abnormal at Endpoint

Based on haemoglobin, haematocrit, red blood cell count (RBC), white blood cell count (WBC), differential - neutrophils, eosinophils, lymphocytes, monocytes and basophils, and platelet count. All laboratory values will be classified as normal or abnormal according to the laboratories normal ranges and as clinically significant according to the assessment of the investigator. For these tests, approximately 12 mL of blood will be collected at each blood withdrawal.

Outcome measures

Outcome measures
Measure	Group A n=61 Participants ESL 800 mg ESL 800 mg: 800 mg ESL tablets for oral administration. In case a patient is unable to swallow the whole tablet, the tablet can be crushed or divided into equal doses at the score line.	Group B n=62 Participants Placebo Placebo: Placebo tablets for oral administration, matching the test product. In case a patient is unable to swallow the whole tablet, the tablet can be crushed or divided into equal doses at the score line.
Clinically Significant Haematology Abnormalities Eosinophils - Low to CS high	1 Participants	0 Participants
Clinically Significant Haematology Abnormalities Eosinophils abs. - Low to CS high	1 Participants	0 Participants
Clinically Significant Haematology Abnormalities Lymphocytes - Low to CS low	1 Participants	0 Participants
Clinically Significant Haematology Abnormalities Lymphocytes abs - Low to CS low	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Over 18 months follow-up period

Population: Shifts of Biochemistry Parameters from Normal or Abnormal to Clinically Significant Abnormal at Endpoint

The biochemistry analysis is based on sodium (will be monitored for signs of hyponatraemia), potassium, chloride, calcium, phosphate, blood urea nitrogen, aspartate transaminase (AST), alanine transaminase (ALT), gamma-glutamyl transferase (GGT), lactate dehydrogenase (LDH), alkaline phosphatase, creatine phosphokinase (CPK), creatinine, glucose, C-reactive protein, albumin, total protein, total cholesterol, low-density lipoproteincholesterol, high-density lipoprotein-cholesterol, triglycerides, and total bilirubin (bilirubin will be fractionated direct/indirect if elevated). eGFR will be estimated based on serum creatinine value using the according CKD-EPI formula using age, sex and race. Coagulation is based on international normalised ratio and activated partial thromboplastin time (aPTT). All laboratory values will be classified as normal or abnormal according to the laboratories normal ranges and as clinically significant according to the assessment of the investigator.

Outcome measures

Outcome measures
Measure	Group A n=61 Participants ESL 800 mg ESL 800 mg: 800 mg ESL tablets for oral administration. In case a patient is unable to swallow the whole tablet, the tablet can be crushed or divided into equal doses at the score line.	Group B n=62 Participants Placebo Placebo: Placebo tablets for oral administration, matching the test product. In case a patient is unable to swallow the whole tablet, the tablet can be crushed or divided into equal doses at the score line.
Clinically Significant Biochemistry Abnormalities, Including eGFR (Estimated Glomerular Filtration Rate) and Coagulation Sodium - Normal to CS low	1 Participants	0 Participants
Clinically Significant Biochemistry Abnormalities, Including eGFR (Estimated Glomerular Filtration Rate) and Coagulation Potassium - Normal to CS low	1 Participants	0 Participants
Clinically Significant Biochemistry Abnormalities, Including eGFR (Estimated Glomerular Filtration Rate) and Coagulation Potassium - Normal to CS high	1 Participants	0 Participants
Clinically Significant Biochemistry Abnormalities, Including eGFR (Estimated Glomerular Filtration Rate) and Coagulation Potassium - Missing to CS high	1 Participants	0 Participants
Clinically Significant Biochemistry Abnormalities, Including eGFR (Estimated Glomerular Filtration Rate) and Coagulation Blood urea nitrogen - Missing to CS high	1 Participants	0 Participants
Clinically Significant Biochemistry Abnormalities, Including eGFR (Estimated Glomerular Filtration Rate) and Coagulation Aspartate transaminase - Normal to CS high	1 Participants	0 Participants
Clinically Significant Biochemistry Abnormalities, Including eGFR (Estimated Glomerular Filtration Rate) and Coagulation Alanine transaminase - Normal to CS high	1 Participants	0 Participants
Clinically Significant Biochemistry Abnormalities, Including eGFR (Estimated Glomerular Filtration Rate) and Coagulation Alanine transaminase - High to CS high	1 Participants	0 Participants
Clinically Significant Biochemistry Abnormalities, Including eGFR (Estimated Glomerular Filtration Rate) and Coagulation Gamma-glutamyl transferase - Normal to CS high	3 Participants	0 Participants
Clinically Significant Biochemistry Abnormalities, Including eGFR (Estimated Glomerular Filtration Rate) and Coagulation Lactate dehydrogenase - Low to CS high	1 Participants	0 Participants
Clinically Significant Biochemistry Abnormalities, Including eGFR (Estimated Glomerular Filtration Rate) and Coagulation Alkaline phosphatase - Normal to CS high	2 Participants	1 Participants
Clinically Significant Biochemistry Abnormalities, Including eGFR (Estimated Glomerular Filtration Rate) and Coagulation Creatinine - Normal to CS high	1 Participants	1 Participants
Clinically Significant Biochemistry Abnormalities, Including eGFR (Estimated Glomerular Filtration Rate) and Coagulation Creatinine - Missing to CS high	1 Participants	0 Participants
Clinically Significant Biochemistry Abnormalities, Including eGFR (Estimated Glomerular Filtration Rate) and Coagulation C-reactive protein - High to CS high	2 Participants	0 Participants
Clinically Significant Biochemistry Abnormalities, Including eGFR (Estimated Glomerular Filtration Rate) and Coagulation LDL-cholesterol - Normal to CS high	1 Participants	0 Participants
Clinically Significant Biochemistry Abnormalities, Including eGFR (Estimated Glomerular Filtration Rate) and Coagulation HDL-cholesterol - Normal to CS low	2 Participants	0 Participants
Clinically Significant Biochemistry Abnormalities, Including eGFR (Estimated Glomerular Filtration Rate) and Coagulation Triglycerides - Normal to CS high	0 Participants	1 Participants
Clinically Significant Biochemistry Abnormalities, Including eGFR (Estimated Glomerular Filtration Rate) and Coagulation Total bilirubin - Normal to CS high	1 Participants	0 Participants
Clinically Significant Biochemistry Abnormalities, Including eGFR (Estimated Glomerular Filtration Rate) and Coagulation Bilirubin direct - Missing to CS high	1 Participants	0 Participants
Clinically Significant Biochemistry Abnormalities, Including eGFR (Estimated Glomerular Filtration Rate) and Coagulation Glomerular filtration rate - Normal to CS low	1 Participants	0 Participants
Clinically Significant Biochemistry Abnormalities, Including eGFR (Estimated Glomerular Filtration Rate) and Coagulation International normalised ratio - High to CS high	1 Participants	0 Participants
Clinically Significant Biochemistry Abnormalities, Including eGFR (Estimated Glomerular Filtration Rate) and Coagulation Activated partial thromboplastin time - Normal to CS high	2 Participants	0 Participants

SECONDARY outcome

Timeframe: Over 18 months follow-up period

Population: The number analyzed are patients with data available

The urinalysis is based on pH, specific gravity, protein, blood, glucose, ketones, bilirubin, urobilinogen (local dipstick). Microscopy and other appropriate tests (as needed) will be performed if dipstick indicates any significant abnormality. All laboratory values will be classified as normal or abnormal according to the laboratories normal ranges and as clinically significant according to the assessment of the investigator.

Outcome measures

Outcome measures
Measure	Group A n=61 Participants ESL 800 mg ESL 800 mg: 800 mg ESL tablets for oral administration. In case a patient is unable to swallow the whole tablet, the tablet can be crushed or divided into equal doses at the score line.	Group B n=62 Participants Placebo Placebo: Placebo tablets for oral administration, matching the test product. In case a patient is unable to swallow the whole tablet, the tablet can be crushed or divided into equal doses at the score line.
Clinically Significant Urinalysis Abnormalities Clinically Significant abnormality - Baseline - No	46 Participants	42 Participants
Clinically Significant Urinalysis Abnormalities Clinically Significant abnormality - Baseline - Yes	14 Participants	14 Participants
Clinically Significant Urinalysis Abnormalities Clinically Significant abnormality - Endpoint - No	36 Participants	34 Participants
Clinically Significant Urinalysis Abnormalities Clinically Significant abnormality - Endpoint - Yes	13 Participants	9 Participants

SECONDARY outcome

Timeframe: Over 18 months follow-up period

Population: Incidence of Clinically Significant Vital Sign Abnormalities at Baseline or Endpoint

The systolic and diastolic blood pressure (mmHg) were to be measured after the patient had rested for at least 5 minutes. Painful procedures, like drawing blood, had to be performed after vital signs measurements (not before). The analyses of variables for vital sign parameters will focus on the evaluation of the change from baseline to the scheduled time points after baseline. Descriptive statistics of the time course and of changes from baseline to each post-baseline time point will be presented by treatment group.

Outcome measures

Outcome measures
Measure	Group A n=61 Participants ESL 800 mg ESL 800 mg: 800 mg ESL tablets for oral administration. In case a patient is unable to swallow the whole tablet, the tablet can be crushed or divided into equal doses at the score line.	Group B n=62 Participants Placebo Placebo: Placebo tablets for oral administration, matching the test product. In case a patient is unable to swallow the whole tablet, the tablet can be crushed or divided into equal doses at the score line.
Clinically Significant Vital Sign Abnormalities: Blood Pressure Diastolic blood pressure [mmHg] - Endpoint - CS low	0 Participants	1 Participants
Clinically Significant Vital Sign Abnormalities: Blood Pressure Systolic blood pressure [mmHg] - Baseline - CS high	1 Participants	3 Participants
Clinically Significant Vital Sign Abnormalities: Blood Pressure Diastolic blood pressure [mmHg] - Baseline - CS low	0 Participants	0 Participants
Clinically Significant Vital Sign Abnormalities: Blood Pressure Diastolic blood pressure [mmHg] - Baseline - CS high	0 Participants	1 Participants
Clinically Significant Vital Sign Abnormalities: Blood Pressure Systolic blood pressure [mmHg] - Endpoint - CS high	1 Participants	1 Participants
Clinically Significant Vital Sign Abnormalities: Blood Pressure Diastolic blood pressure [mmHg] - Endpoint - CS high	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Over 18 months follow-up period

Population: Incidence of Clinically Significant Vital Sign Abnormalities at Baseline or Endpoint

The Heart Rate (bpm) were to be measured after the patient had rested for at least 5 minutes. Painful procedures, like drawing blood, had to be performed after vital signs measurements (not before). The analyses of variables for vital sign parameters will focus on the evaluation of the change from baseline to the scheduled time points after baseline. Descriptive statistics of the time course and of changes from baseline to each post-baseline time point will be presented by treatment group.

Outcome measures

Outcome measures
Measure	Group A n=61 Participants ESL 800 mg ESL 800 mg: 800 mg ESL tablets for oral administration. In case a patient is unable to swallow the whole tablet, the tablet can be crushed or divided into equal doses at the score line.	Group B n=62 Participants Placebo Placebo: Placebo tablets for oral administration, matching the test product. In case a patient is unable to swallow the whole tablet, the tablet can be crushed or divided into equal doses at the score line.
Clinically Significant Vital Sign Abnormalities: Heart Rate Pulse rate [bpm] - Baseline - CS high	0 Participants	0 Participants
Clinically Significant Vital Sign Abnormalities: Heart Rate Pulse rate [bpm] - Endpoint - CS high	0 Participants	1 Participants

SECONDARY outcome

Timeframe: A standard 12-lead electrocardiogram (ECG) is performed at Baseline, V2 (+7 days), V3 (+37 days), Early discontinuation visit (if EDV performed before V3, on average 30 days).

Population: The number analyzed are patients with data available

The ECG equipment is to be calibrated to 1 cm/mV and recording is to be done at 25 mm/sec and performed for a minimum of 10 sec. At V1a the investigator should examine the ECG for signs of cardiac disease that should exclude the patient from the trial. An assessment of normal or abnormal will be recorded and if the ECG abnormality is considered clinically significant, the abnormality will be documented in the electronic case report form (eCRF). If an ECG was done after primary stroke, the results should be used and the examination does not need to be repeated at V1a. After each recording of a simultaneous 12-lead resting ECG, a copy of the originally printed ECG records will be printed, assessed and filed by the investigator, in order to ensure that maintenance of the data will not be affected by thermolability of the paper.

Outcome measures

Outcome measures
Measure	Group A n=61 Participants ESL 800 mg ESL 800 mg: 800 mg ESL tablets for oral administration. In case a patient is unable to swallow the whole tablet, the tablet can be crushed or divided into equal doses at the score line.	Group B n=62 Participants Placebo Placebo: Placebo tablets for oral administration, matching the test product. In case a patient is unable to swallow the whole tablet, the tablet can be crushed or divided into equal doses at the score line.
Electrocardiogram (ECG) Endpoint	4 Participants	3 Participants
Electrocardiogram (ECG) Baseline - Clinically Significant abnormal	9 Participants	8 Participants
Electrocardiogram (ECG) V2 - Clinically Significant abnormal	4 Participants	3 Participants
Electrocardiogram (ECG) V3 - Clinically Significant abnormal	4 Participants	3 Participants
Electrocardiogram (ECG) Early discontinuation visit - Clinically Significant abnormal	0 Participants	0 Participants

SECONDARY outcome

Timeframe: The PHQ-9 will be collected at Baseline, V3 (+37 Days), V5 (+26 weeks), V7 (+52 weeks), End of trial visit (EOT, +78 weeks) or Early discontinuation visit (if EDV performed before V3, on average 30 days), and Endpoint (18 months).

Population: The patient will rate on a scale from 0 (not at all) to 3 (nearly every day) how often each of the 9 symptoms occurred during the past 2 weeks. The PHQ-9 total score will be categorised as follows: ≤4 - minimal depression \>4 - mild to severe depression

The individual scores from each item of the PHQ-9 will be added to calculate the total PHQ-9 score for each time of examination.Over the last 2 weeks, how often have you been bothered by any of the following problems? 1. Little interest or pleasure in doing things 2. Feeling down, depressed, or hopeless 3. Trouble falling or staying asleep, or sleeping too much 4. Feeling tired or having little energy 5. Poor appetite or overeating 6. Feeling bad about yourself - or that you are a failure or have let yourself or your family down 7. Trouble concentrating on things, such as reading the newspaper or watching television 8. Moving or speaking so slowly that other could have noticed. Or the opposite - being so fidgety or restless that you have been moving around a lot more than usual 9. Thoughts that you would be better off dead or of hurting yourself in some way The individual scores from each item of the PHQ-9 will be added to calculate the total PHQ-9 score for each time of examination.

Outcome measures

Outcome measures
Measure	Group A n=61 Participants ESL 800 mg ESL 800 mg: 800 mg ESL tablets for oral administration. In case a patient is unable to swallow the whole tablet, the tablet can be crushed or divided into equal doses at the score line.	Group B n=62 Participants Placebo Placebo: Placebo tablets for oral administration, matching the test product. In case a patient is unable to swallow the whole tablet, the tablet can be crushed or divided into equal doses at the score line.
Suicidal Ideation and Behaviour, Assessed by PHQ-9 (Question 9) Baseline - Observed Value	3.7 Score on a scale Standard Deviation 3.34	3.4 Score on a scale Standard Deviation 4.43
Suicidal Ideation and Behaviour, Assessed by PHQ-9 (Question 9) V3 - Observed Value	5.0 Score on a scale Standard Deviation 5.57	4.5 Score on a scale Standard Deviation 5.12
Suicidal Ideation and Behaviour, Assessed by PHQ-9 (Question 9) V5 - Observed Value	5.0 Score on a scale Standard Deviation 4.72	5.5 Score on a scale Standard Deviation 5.91
Suicidal Ideation and Behaviour, Assessed by PHQ-9 (Question 9) V7 - Observed Value	3.9 Score on a scale Standard Deviation 4.08	4.4 Score on a scale Standard Deviation 5.12
Suicidal Ideation and Behaviour, Assessed by PHQ-9 (Question 9) Early discontinuation visit - Observed Value	2.0 Score on a scale Standard Deviation 0.82	3.8 Score on a scale Standard Deviation 4.35
Suicidal Ideation and Behaviour, Assessed by PHQ-9 (Question 9) End of trial visit - Observed Value	3.8 Score on a scale Standard Deviation 3.85	3.9 Score on a scale Standard Deviation 5.50
Suicidal Ideation and Behaviour, Assessed by PHQ-9 (Question 9) Endpoint - Observed Value	4.1 Score on a scale Standard Deviation 3.96	4.3 Score on a scale Standard Deviation 5.25

SECONDARY outcome

Timeframe: Two recordings were provided: one carried out before in the initial phase of enrollment into the trial at V1a (< 96 hours) and the second one after termination of eslicarpazepine acetate intake (EOT, +78 weeks).

Population: The preprocessed EEG data was then analysed in two different ways; (i) we performed a power analyses and (ii) we calculated multivariate autoregressive models to investigate connectivity between channels. For both analyses the following frequency bands were defined and used to group the results: delta (1 - 3.9 Hz), theta (4 - 7.9 Hz), alpha (8 - 12.9 Hz), beta (13 - 39.9 Hz), gamma (\>40Hz).

Routine EEG assessment (standard 10-20 set of electrodes, digital recording with 256 Hz sampling rate) for a minimum of 20 min will be performed at the discretion of the investigator. The EEG will be performed as exploratory analysis to support the development of a predictor for the development of post-stroke epilepsy and is therefore an optional assessment. All EEG analyses will be presented for the EEG analysis subset (all patients in the full analysis set with a baseline and a post-baseline EEG recording available). EEG parameters will be evaluated exploratively using descriptive statistics. For this outcome was decided that results would be possibly explored in an manuscript.

Outcome measures

Outcome measures
Measure	Group A n=31 Participants ESL 800 mg ESL 800 mg: 800 mg ESL tablets for oral administration. In case a patient is unable to swallow the whole tablet, the tablet can be crushed or divided into equal doses at the score line.	Group B n=34 Participants Placebo Placebo: Placebo tablets for oral administration, matching the test product. In case a patient is unable to swallow the whole tablet, the tablet can be crushed or divided into equal doses at the score line.
Number of Participants With and Without Seizures Based on Electroencephalogram (EEG) EEG recordings of V1a - Patients with seizures	16 Participants	24 Participants
Number of Participants With and Without Seizures Based on Electroencephalogram (EEG) EEG recordings of EoT - Patients without seizures	5 Participants	10 Participants
Number of Participants With and Without Seizures Based on Electroencephalogram (EEG) Differences between EoT-V1a - Patients with seizures	3 Participants	0 Participants
Number of Participants With and Without Seizures Based on Electroencephalogram (EEG) Differences between EoT-V1a - Patients without seizures	0 Participants	7 Participants

Adverse Events

Group A

Serious events: 12 serious events

Other events: 50 other events

Deaths: 6 deaths

Group B

Serious events: 13 serious events

Other events: 48 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Responsible of Clinical Operations

BIAL - Portela & Ca, SA

Phone: +351229866100

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER