A Study to Investigate JNJ-40411813 in Combination With L... | NCT04836559

ID	Type	Description	Link
40411813EPY2001	Other Identifier	Janssen Research & Development, LLC
2020-003698-24	EudraCT Number

Status Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
JNJ-40411813	Experimental	Participants will receive JNJ-40411813 twice a day (bid) up to 12 weeks in double blind period. Up to 3 different doses (low, medium, high) of JNJ-40411813 will be administered in this study. Participants will also receive concomitant anti-epileptic drugs (AEDs) one of which must include levetiracetam or brivaracetam. Immediately after the last study drug intake by the participants in the double-blind period, participants will enter into a 2-year open label extension (OLE) period and continue receiving JNJ-40411813 as well as the AEDs during OLE period.	Drug: JNJ-40411813
Placebo	Placebo Comparator	Participants will receive JNJ-40411813 matching placebo (bid) up to 12 weeks. Participants will also receive concomitant AEDs one of which must include levetiracetam or brivaracetam during double blind period. Participants who had been receiving placebo in double blind period will start with the JNJ-40411813 dose in the OLE period.	Drug: JNJ-40411813 Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
JNJ-40411813	Drug	JNJ-40411813 will be administered orally.	JNJ-40411813 Placebo

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Cohort 1 and 2: Time to Baseline Monthly Seizure Count up to the End of the 12-week Double-blind (DB) Treatment Period	Time (in days) to baseline monthly seizure count was defined as the number of days until the participants cumulative seizure count during the DB period was equal to their baseline monthly seizure count. The baseline monthly seizure count was defined as the number of observable focal onset seizures occurred during the 8-week baseline period (Day -56 to -1), multiplied by 28/XBL, where XBL was the number of days comprising the participants baseline period. Observable focal onset seizures included focal aware seizures with motor signs, focal impaired awareness seizures and focal to bilateral tonic-clonic seizures. Focal aware seizures without motor signs, myoclonic, or other generalized seizures was not counted towards baseline monthly seizure count. Cluster seizures were counted as a single seizure. Kaplan-Meier method was used for the analysis.	From DB period Day 1 up to Day 85

Secondary Outcomes

Measure	Description	Time Frame
Cohort 1 and 2: Percent Reduction in the Open Label Extension (OLE) Period Monthly Seizure Rate	The percent reduction in the OLE monthly seizure rate was defined as 100*(baseline monthly seizure count minus OLE monthly seizure count) divided by (baseline monthly seizure count). The OLE monthly seizure count was defined as the total number of observable focal onset seizures occurred during the OLE period, multiplied by 28/XOLE, where XOLE was the number of days comprising the OLE. A positive percentage change in the OLE monthly seizure count indicated improvement. Observable seizures included focal aware seizures with motor signs, focal impaired awareness seizures and focal to bilateral tonic-clonic seizures. Focal aware seizures without motor signs, myoclonic, or other generalized seizures was not counted towards baseline monthly seizure count. Cluster seizures were counted as a single seizure.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Body mass index (BMI) between 18 and 35 kilogram per meter square (kg/m^2, inclusive (BMI = weight/height^2). Minimum body weight should be 40-kilogram (kg)
Established diagnosis of focal epilepsy, for at least 1 year using the International League Against Epilepsy (ILAE) criteria. Participants should not be enrolled if they are known to have had fewer than 3 or more than 100 seizures in any monthly period in the past 6 months. It is preferred that participants have experience in maintaining a seizure e-diary
Must have had a neuroimaging procedure within 10 years, including a computed tomography (CT) scan or magnetic resonance imaging (MRI), that excluded a progressive neurologic disorder; these procedures may be performed within the 8-week baseline period
Cohort 1: Current treatment with at least 1 and up to 4 anti-epileptic drugs (AEDs) (including levetiracetam), administered at stable dosage(s) for at least 1 month before screening, and no new AEDs added for the previous 2 months; these AEDs must remain unchanged throughout the pretreatment and double-blind treatment periods (with the exception of dosage reductions of concomitant AEDs because of suspected elevated AED levels or side effects) Cohort 2 and beyond: Current treatment with at least 1 and up to 4 AEDs (including levetiracetam or brivaracetam), administered at the appropriate dosage(s) and for a sufficient treatment period before screening. These AEDs must remain unchanged throughout the pretreatment and double-blind treatment periods (with the exception of dosage reductions of concomitant AEDs because of suspected elevated AED levels or side effects). Important note: screening of participants receiving brivaracetam will start when enrolling for Cohort 2
Currently showing inadequate response to levetiracetam, administered at the appropriate dosage(s) and for a sufficient treatment period, based on the judgment of the investigator
Healthy based on clinical laboratory tests, physical examination, medical history, vital signs, and 12-lead ECG
Men or women between 18 and 69 years old

Exclusion Criteria:

Have a generalized epileptic syndrome
Diagnosis of Lennox-Gastaut Syndrome
Currently experiencing seizures that cannot be counted accurately
History of any current or past nonepileptic seizures, including psychogenic seizures
Known allergies, hypersensitivity, or intolerance to placebo, JNJ-40411813 or its excipients
Current treatment with vagus nerve stimulation, deep brain and cortical stimulation for 1 year or less
Planned epilepsy surgery within the next 6 months or completed epilepsy surgery less than (<) 6 months ago
Current treatment with vigabatrin
History of malignancy within 5 years before screening (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy, which is considered cured with minimal risk of recurrence)
Current or past (within the past year) major psychotic disorder, such as schizophrenia, bipolar disorder, or other psychotic conditions, recent (within the past 6 months) interictal psychosis, and major depressive disorder (MDD) with psychotic features
Exacerbation of MDD within the past 6 months; antidepressant use is allowed
Has a current or recent history of clinically significant suicidal ideation within the past 6 months, corresponding to a score of 4 (active suicidal ideation with some intent to act, without specific plan) or 5 (active suicidal ideation with specific plan and intent) for ideation on the Columbia Suicide Severity Rating Scale (C-SSRS), or a history of suicidal behavior within the past 1 year, as validated by the CSSRS at screening
Has a history of at least mild drug or alcohol use disorder according to Diagnostic and Statistical Manual of Mental Disorders (5th edition) (DSM-5) criteria within 1 year before Screening

Name	Affiliation	Role
Janssen Research & Development, LLC Clinical Trial	Janssen Research & Development, LLC	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Tucson Neuroscience Research		Tucson	Arizona	85710	United States
Research Institution of Orlando, LLC

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	DB: Cohort 1: Placebo	During double-blind (DB) period, participants were randomized to receive placebo matching to JNJ-40411813 tablet orally twice a day (BID) from Day 1 up to Day 85 along with previously prescribed AEDs (one of which must include levetiracetam or brivaracetam) on Days 1, 29, and 57. Participants were screened every 4 weeks for monthly seizure counts up to Week 12. Participants who had exceeded their pre-randomization monthly seizure count had the option to discontinue the study treatment due to lack of efficacy and perform the end-of-study/early withdrawal visit, continue DB treatment, or enter the open-label extension (OLE) period. Participants who had not exceeded the pre-randomization seizure count continued the DB treatment period through Week 12 and had the option to perform DB period end-of-study visit (last visit for last participant; Day 85) or entered the OLE period. Participants who continued treatment to the end of the DB period (Week 12) and were not elected to participate in the OLE were followed up for safety up to 2 weeks after the last dose of study treatment (up to Week 14).

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Nov 17, 2022	Feb 4, 2025

Arm/Group Information

ID	Title	Description
BG000	DB: Cohort 1: Placebo	During double-blind (DB) period, participants were randomized to receive placebo matching to JNJ-40411813 tablet orally twice a day (BID) from Day 1 up to Day 85 along with previously prescribed AEDs (one of which must include levetiracetam or brivaracetam) on Days 1, 29, and 57. Participants were screened every 4 weeks for monthly seizure counts up to Week 12. Participants who had exceeded their pre-randomization monthly seizure count had the option to discontinue the study treatment due to lack of efficacy and perform the end-of-study/early withdrawal visit, continue DB treatment, or enter the open-label extension (OLE) period. Participants who had not exceeded the pre-randomization seizure count continued the DB treatment period through Week 12 and had the option to perform DB period end-of-study visit (last visit for last participant; Day 85) or entered the OLE period. Participants who continued treatment to the end of the DB period (Week 12) and were not elected to participate in the OLE were followed up for safety up to 2 weeks after the last dose of study treatment (up to Week 14).
BG001	DB: Cohort 1: JNJ-40411813	During DB period, participants were randomized to receive JNJ-40411813 100 milligrams (mg) or 50 mg tablet orally BID from Day 1 up to Day 85 along with previously prescribed AEDs (one of which must include levetiracetam or brivaracetam) on Days 1, 29, and 57. Participants treated with EIAEDs (induced) received 100 mg of JNJ-40411813 and participants not treated with EIAEDs (non-induced) received 50 mg of JNJ-40411813. Participants were screened every 4 weeks for monthly seizure counts up to Week 12. Participants who had exceeded their pre-randomization monthly seizure count had the option to discontinue the study treatment due to lack of efficacy and perform the end-of-study/early withdrawal visit, continued DB treatment, or enter the OLE period. Participants who had not exceeded the pre-randomization seizure count continued the DB treatment period through Week 12 and had the option to perform DB period end-of-study visit (last visit for last participant; Day 85) or entered the OLE period. Participants who continued treatment to the end of the DB period (Week 12) and were not elected to participate in the OLE were followed up for safety up to 2 weeks after the last dose of study treatment (up to Week 14).
BG002	DB: Cohort 2: Placebo	During DB period, participants were randomized to receive placebo matching to JNJ-40411813 tablet orally BID from Day 1 up to Day 85 along with previously prescribed AEDs (one of which must include levetiracetam or brivaracetam) on Days 1, 29, and 57. Participants were screened every 4 weeks for monthly seizure counts up to Week 12. Participants who had exceeded their pre-randomization monthly seizure count had the option to discontinue the study treatment due to lack of efficacy and perform the end-of-study/early withdrawal visit, continue DB treatment, or enter the OLE period. Participants who had not exceeded the pre-randomization seizure count continued the DB treatment period through Week 12 and had the option to perform DB period end-of-study visit (last visit for last participant; Day 85) or entered the OLE period. Participants who continued treatment to the end of the DB period (Week 12) and were not elected to participate in the OLE were followed up for safety up to 2 weeks after the last dose of study treatment (up to Week 14).
BG003	DB: Cohort 2: JNJ-40411813	During DB period, participants were randomized to receive JNJ-40411813 200 mg or 100 mg tablet orally BID from Day 1 up to Day 85 along with previously prescribed AEDs (one of which must include levetiracetam or brivaracetam) on Days 1, 29, and 57. Participants treated with EIAEDs (induced) received 200 mg of JNJ-40411813 and participants not treated with EIAEDs (non-induced) received 100 mg of JNJ-40411813. Participants were screened every 4 weeks for monthly seizure counts up to Week 12. Participants who had exceeded their pre-randomization monthly seizure count had the option to discontinue the study drug due to lack of efficacy and perform the end-of-study/early withdrawal visit, continue DB treatment, or enter the OLE period. Participants who had not exceeded the pre-randomization seizure count continued the DB treatment period through Week 12 and had the option to perform DB period end-of-study visit (last visit for last participant; Day 85) or entered the OLE period. Participants who continued treatment to the end of the DB period (Week 12) and were not elected to participate in the OLE were followed up for safety up to 2 weeks after the last dose of study treatment (up to Week 14).
BG004	Total	Total of all reporting groups

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Cohort 1 and 2: Time to Baseline Monthly Seizure Count up to the End of the 12-week Double-blind (DB) Treatment Period

Time (in days) to baseline monthly seizure count was defined as the number of days until the participants cumulative seizure count during the DB period was equal to their baseline monthly seizure count. The baseline monthly seizure count was defined as the number of observable focal onset seizures occurred during the 8-week baseline period (Day -56 to -1), multiplied by 28/XBL, where XBL was the number of days comprising the participants baseline period. Observable focal onset seizures included focal aware seizures with motor signs, focal impaired awareness seizures and focal to bilateral tonic-clonic seizures. Focal aware seizures without motor signs, myoclonic, or other generalized seizures was not counted towards baseline monthly seizure count. Cluster seizures were counted as a single seizure. Kaplan-Meier method was used for the analysis.

Full analysis set (FAS) included all randomized participants assigned to receive study intervention and had both baseline and postbaseline seizure data.

Posted

Median

95% Confidence Interval

Days

From DB period Day 1 up to Day 85

ID	Title	Description
OG000	DB: Cohort 1: Placebo	During double-blind (DB) period, participants were randomized to receive placebo matching to JNJ-40411813 tablet orally twice a day (BID) from Day 1 up to Day 85 along with previously prescribed AEDs (one of which must include levetiracetam or brivaracetam) on Days 1, 29, and 57. Participants were screened every 4 weeks for monthly seizure counts up to Week 12. Participants who had exceeded their pre-randomization monthly seizure count had the option to discontinue the study treatment due to lack of efficacy and perform the end-of-study/early withdrawal visit, continue DB treatment, or enter the open-label extension (OLE) period. Participants who had not exceeded the pre-randomization seizure count continued the DB treatment period through Week 12 and had the option to perform DB period end-of-study visit (last visit for last participant; Day 85) or entered the OLE period. Participants who continued treatment to the end of the DB period (Week 12) and were not elected to participate in the OLE were followed up for safety up to 2 weeks after the last dose of study treatment (up to Week 14).
OG001	DB: Cohort 1: JNJ-40411813	During DB period, participants were randomized to receive JNJ-40411813 100 milligrams (mg) or 50 mg tablet orally BID from Day 1 up to Day 85 along with previously prescribed AEDs (one of which must include levetiracetam or brivaracetam) on Days 1, 29, and 57. Participants treated with EIAEDs (induced) received 100 mg of JNJ-40411813 and participants not treated with EIAEDs (non-induced) received 50 mg of JNJ-40411813. Participants were screened every 4 weeks for monthly seizure counts up to Week 12. Participants who had exceeded their pre-randomization monthly seizure count had the option to discontinue the study treatment due to lack of efficacy and perform the end-of-study/early withdrawal visit, continued DB treatment, or enter the OLE period. Participants who had not exceeded the pre-randomization seizure count continued the DB treatment period through Week 12 and had the option to perform DB period end-of-study visit (last visit for last participant; Day 85) or entered the OLE period. Participants who continued treatment to the end of the DB period (Week 12) and were not elected to participate in the OLE were followed up for safety up to 2 weeks after the last dose of study treatment (up to Week 14).
OG002	DB: Cohort 2: Placebo	During DB period, participants were randomized to receive placebo matching to JNJ-40411813 tablet orally BID from Day 1 up to Day 85 along with previously prescribed AEDs (one of which must include levetiracetam or brivaracetam) on Days 1, 29, and 57. Participants were screened every 4 weeks for monthly seizure counts up to Week 12. Participants who had exceeded their pre-randomization monthly seizure count had the option to discontinue the study treatment due to lack of efficacy and perform the end-of-study/early withdrawal visit, continue DB treatment, or enter the OLE period. Participants who had not exceeded the pre-randomization seizure count continued the DB treatment period through Week 12 and had the option to perform DB period end-of-study visit (last visit for last participant; Day 85) or entered the OLE period. Participants who continued treatment to the end of the DB period (Week 12) and were not elected to participate in the OLE were followed up for safety up to 2 weeks after the last dose of study treatment (up to Week 14).

Units	Counts
Participants	OG00020 OG00140 OG0029 OG003

Title

Denominators

Categories

Title	Measurements
	OG00032(28 to 37) OG00134(27 to 48) OG00229(22 to 69) OG003

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		t-test, 1 sided		0.3571		Hazard Ratio (HR)	0.75			2-Sided	95	0.41	1.38					Superiority
OG002 OG003		t-test, 1 sided		0.6306

Secondary

Cohort 1 and 2: Percent Reduction in the Open Label Extension (OLE) Period Monthly Seizure Rate

The percent reduction in the OLE monthly seizure rate was defined as 100*(baseline monthly seizure count minus OLE monthly seizure count) divided by (baseline monthly seizure count). The OLE monthly seizure count was defined as the total number of observable focal onset seizures occurred during the OLE period, multiplied by 28/XOLE, where XOLE was the number of days comprising the OLE. A positive percentage change in the OLE monthly seizure count indicated improvement. Observable seizures included focal aware seizures with motor signs, focal impaired awareness seizures and focal to bilateral tonic-clonic seizures. Focal aware seizures without motor signs, myoclonic, or other generalized seizures was not counted towards baseline monthly seizure count. Cluster seizures were counted as a single seizure.

Full analysis set: open-label extension (FASOLE) analysis set included all FAS participants who received at least 1 dose of study intervention in the OLE period.

Posted

Median

Inter-Quartile Range

Percent change (reduction)

From OLE baseline (Day 1 of OLE) up to 24 months after start of OLE (the actual OLE starting time varied for each participant)

ID	Title	Description
OG000	OLE: Cohort 1: Placebo Followed by JNJ-40411813	During OLE period, cohort 1 participants who had received placebo during the DB period received JNJ-40411813 100 mg or 50 mg BID along with previously prescribed AEDs (one of which must include levetiracetam or brivaracetam) from Day 1 of OLE up to 2 years. Induced participants (with EIAEDs) received JNJ-40411813 100 mg, and non-induced participants (without EIAEDs) received JNJ-40411813 50 mg. The dose could be increased at the second visit (Month 1) to 200 mg of JNJ-40411813 BID for induced participants (with EIAEDs) and 100 mg of JNJ-40411813 BID for non-induced participants (without EIAEDs).

Secondary

Cohort 1 and 2: Number of Participants With Seizure Freedom at the End of OLE Period

Number of participants with seizure freedom at the end of OLE period was reported. Seizure freedom was defined as having no seizures over the complete OLE study period.

FASOLE analysis set included all FAS participants who received at least 1 dose of study intervention in the OLE period.

Posted

Count of Participants

Participants

From OLE baseline (Day 1 of OLE) up to 24 months after start of OLE (the actual OLE starting time varied for each participant)

ID	Title	Description
OG000	OLE: Cohort 1: Placebo Followed by JNJ-40411813	During OLE period, cohort 1 participants who had received placebo during the DB period received JNJ-40411813 100 mg or 50 mg BID along with previously prescribed AEDs (one of which must include levetiracetam or brivaracetam) from Day 1 of OLE up to 2 years. Induced participants (with EIAEDs) received JNJ-40411813 100 mg, and non-induced participants (without EIAEDs) received JNJ-40411813 50 mg. The dose could be increased at the second visit (Month 1) to 200 mg of JNJ-40411813 BID for induced participants (with EIAEDs) and 100 mg of JNJ-40411813 BID for non-induced participants (without EIAEDs).
OG001	OLE: Cohort 1: JNJ-40411813 Followed by JNJ-40411813	During OLE period, cohort 1 participants who had received JNJ-40411813 during the DB period continued to receive JNJ-40411813 100 mg or 50 mg BID along with previously prescribed AEDs (one of which must include levetiracetam or brivaracetam) from Day 1 of OLE up to 2 years. Induced participants (with EIAEDs) received JNJ-40411813 100 mg, and non-induced participants (without EIAEDs) received JNJ-40411813 50 mg. The dose could be increased at the second visit (Month 1) to 200 mg of JNJ-40411813 BID for induced participants (with EIAEDs) and 100 mg of JNJ-40411813 BID for non-induced participants (without EIAEDs).

Secondary

Cohort 1 and 2: Number of Participants With at Least 50 Percent (%) Reduction (Response) in the OLE Monthly Seizure Count

Number of participants having at least a 50% reduction in the monthly seizure rate (response) during the OLE study period was reported.

FASOLE analysis set included all FAS participants who received at least 1 dose of study intervention in the OLE period.

Posted

Count of Participants

Participants

From OLE baseline (Day 1 of OLE) up to 24 months after start of OLE (the actual OLE starting time varied for each participant)

ID	Title	Description
OG000	OLE: Cohort 1: Placebo Followed by JNJ-40411813	During OLE period, cohort 1 participants who had received placebo during the DB period received JNJ-40411813 100 mg or 50 mg BID along with previously prescribed AEDs (one of which must include levetiracetam or brivaracetam) from Day 1 of OLE up to 2 years. Induced participants (with EIAEDs) received JNJ-40411813 100 mg, and non-induced participants (without EIAEDs) received JNJ-40411813 50 mg. The dose could be increased at the second visit (Month 1) to 200 mg of JNJ-40411813 BID for induced participants (with EIAEDs) and 100 mg of JNJ-40411813 BID for non-induced participants (without EIAEDs).
OG001	OLE: Cohort 1: JNJ-40411813 Followed by JNJ-40411813	During OLE period, cohort 1 participants who had received JNJ-40411813 during the DB period continued to receive JNJ-40411813 along with previously prescribed AEDs (one of which must include levetiracetam or brivaracetam) from Day 1 of OLE up to 2 years. Induced participants (with EIAEDs) received JNJ-40411813 100 mg BID, and non-induced participants (without EIAEDs) received JNJ-40411813 50 mg BID. The dose could be increased at the second visit (Month 1) to 200 mg of JNJ-40411813 BID for induced participants (with EIAEDs) and 100 mg of JNJ-40411813 BID for non-induced participants (without EIAEDs).

Secondary

OLE Period: Cohort 1 and 2: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)

Number of participants with TEAEs and TESAEs were reported. An adverse event (AE) was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. A serious AE was defined as any untoward medical occurrence that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a suspected transmission of any infectious agent via a medicinal product, or was medically important. TEAE/TESAE was defined as any AE/SAE occurred at or after the initial administration of study intervention through the day of last dose plus 5 days. TEAEs included serious and non-serious events.

Safety open label extension (SAFOLE) analysis set included all randomized participants who received at least 1 dose of study intervention in the OLE period.

Posted

Count of Participants

Participants

From OLE baseline (Day 1 of OLE) up to 5 days after last dose of OLE period (5 days + 24 months after start of OLE) (the actual OLE starting time varied for each participant)

ID	Title	Description
OG000	OLE: Cohort 1: Placebo Followed by JNJ-40411813	During OLE period, cohort 1 participants who had received placebo during the DB period received JNJ-40411813 100 mg or 50 mg BID along with previously prescribed AEDs (one of which must include levetiracetam or brivaracetam) from Day 1 of OLE up to 2 years. Induced participants (with EIAEDs) received JNJ-40411813 100 mg, and non-induced participants (without EIAEDs) received JNJ-40411813 50 mg. The dose could be increased at the second visit (Month 1) to 200 mg of JNJ-40411813 BID for induced participants (with EIAEDs) and 100 mg of JNJ-40411813 BID for non-induced participants (without EIAEDs).

Secondary

OLE Period: Cohort 1 and 2: Number of Participants With Treatment-emergent (TE) Clinically Important Changes in Vital Signs

TE clinically important changes in vital signs (VS) were pulse rate (PR) greater than (>)100 beats per min [bpm] and with >30bpm increase from baseline (BL), PR less than (<)50 bpm and with >20bpm decrease from BL, systolic blood pressure (SBP) >140 millimeters of mercury (mmHg) and with >40mm Hg increase from BL, SBP <90mmHg and with >30mmHg decrease from BL), diastolic blood pressure (DBP) >90mmHg and with >30mmHg increase from BL, DBP <50mmHg and with >20 mmHg decrease from BL, and temperature >38 degree Celsius(C) and with greater than or equal to (>=)1degree C increase from BL. TE: post BL value was above upper limit and BL value was below upper limit (example: Normal or Low). Same applied to post BL value being below lower limit with BL value being above lower limit (example: Normal or High). TEVS: VS which occurred as at or after initial administration of study intervention through last dose plus 5 days. Only categories in which at least 1 participant had data were reported.

SAFOLE analysis set included all randomized participants who received at least 1 dose of study intervention in the OLE period. Here 'N' (overall number of participants analyzed) refers to the number of participants with at least 1 postbaseline value for the specified vital sign parameter and 'n' (number analyzed) refers to number of participants evaluable at specified parameter. n=0 indicates that there was no evaluable participant for specified parameter.

Posted

Count of Participants

Participants

From OLE baseline (Day 1 of OLE) up to 24 months + 5 days after start of OLE (the actual OLE starting time varied for each participant)

ID	Title	Description
OG000	OLE: Cohort 1: Placebo Followed by JNJ-40411813

Secondary

OLE Period: Cohort 1 and 2: Number of Participants With Changes in Laboratory Assessments Recorded as TEAE

Number of participants with changes in laboratory assessments recorded as TEAE were reported. Laboratory assessments included clinical chemistry, hematology and urinalysis. Postbaseline abnormalities were compared with baseline values: if postbaseline value exceeding the upper limit (with baseline below upper limit) or falling below the lower limit (with baseline above lower limit) was considered treatment-emergent (TE); if baseline values were missing then any postbaseline abnormality was considered TE. TEAE was defined as any AE occurring at or after the initial administration of study intervention through the day of last dose plus 5 days.

SAFOLE analysis set included all randomized participants who received at least 1 dose of study intervention in the OLE period.

Posted

Count of Participants

Participants

From OLE baseline (Day 1 of OLE) up to 24 months + 5 days after start of OLE (the actual OLE starting time varied for each subject)

ID	Title	Description
OG000	OLE: Cohort 1: Placebo Followed by JNJ-40411813	During OLE period, cohort 1 participants who had received placebo during the DB period received JNJ-40411813 100 mg or 50 mg BID along with previously prescribed AEDs (one of which must include levetiracetam or brivaracetam) from Day 1 of OLE up to 2 years. Induced participants (with EIAEDs) received JNJ-40411813 100 mg, and non-induced participants (without EIAEDs) received JNJ-40411813 50 mg. The dose could be increased at the second visit (Month 1) to 200 mg of JNJ-40411813 BID for induced participants (with EIAEDs) and 100 mg of JNJ-40411813 BID for non-induced participants (without EIAEDs).

Secondary

DB Treatment Period: Cohort 1 and 2: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)

Number of participants with TEAEs and TESAEs were reported. An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. A serious AE was defined as any untoward medical occurrence that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a suspected transmission of any infectious agent via a medicinal product, or was medically important. TEAE/TESAE was defined as any AE/SAE occurred at or after the initial administration of study intervention through the day of last dose plus 5 days. TEAEs included serious and non-serious events.

Safety analysis set (SAF) included all randomized participants who received at least 1 dose of JNJ-40411813 or placebo in the double-blind period.

Posted

Count of Participants

Participants

From DB period start (Day 1) up to 5 days after last dose of DB period (up to Day 90)

ID	Title	Description
OG000	DB: Cohort 1: Placebo	During double-blind (DB) period, participants were randomized to receive placebo matching to JNJ-40411813 tablet orally twice a day (BID) from Day 1 up to Day 85 along with previously prescribed AEDs (one of which must include levetiracetam or brivaracetam) on Days 1, 29, and 57. Participants were screened every 4 weeks for monthly seizure counts up to Week 12. Participants who had exceeded their pre-randomization monthly seizure count had the option to discontinue the study treatment due to lack of efficacy and perform the end-of-study/early withdrawal visit, continue DB treatment, or enter the open-label extension (OLE) period. Participants who had not exceeded the pre-randomization seizure count continued the DB treatment period through Week 12 and had the option to perform DB period end-of-study visit (last visit for last participant; Day 85) or entered the OLE period. Participants who continued treatment to the end of the DB period (Week 12) and were not elected to participate in the OLE were followed up for safety up to 2 weeks after the last dose of study treatment (up to Week 14).

Secondary

DB Treatment Period: Cohort 1 and 2: Number of Participants With Treatment-emergent Clinically Important Changes in Vital Signs

Treatment-emergent clinically important changes in vital signs defined as PR >100 bpm and with >30 bpm increase from baseline, PR <50 bpm and with >20 bpm decrease from baseline, SBP >140 mm Hg and with >40 mm Hg increase from baseline, SBP <90 mm Hg and with >30 mm Hg decrease from baseline, DBP >90 mm Hg and with >30 mm Hg increase from baseline, DBP <50 mm Hg and with >20 mm Hg decrease from baseline, temperature >38 degree C and with >=1 degree C increase from baseline. TE clinically important changes: if postbaseline value was above upper limit and baseline value was below upper limit (example: Normal or Low). Same applied to postbaseline value being below lower limit with baseline value being above lower limit (example: Normal or High). Only those categories in which at least 1 participant had data were reported in this outcome measure. TE vital signs included vital signs which occurred as at or after initial administration of study intervention through last dose plus 5 days.

Safety analysis set included all randomized participants who received at least 1 dose of JNJ-40411813 or placebo in the double-blind period. Here 'N' (overall number of participants analyzed) refers to the number of participants with at least 1 postbaseline value for the specified vital sign parameter and 'n' (number analyzed) refers to number of participants evaluable at specified parameter. n=0 indicates that there was no evaluable participant for specified parameter.

Posted

Count of Participants

Participants

From DB period start (Day 1) up to 5 days after last dose of DB period (up to Day 90)

ID	Title	Description
OG000	DB: Cohort 1: Placebo

Secondary

DB Treatment Period: Cohort 1 and 2: Number of Participants With Treatment-emergent Clinically Important Changes in Electrocardiogram (ECG)

The ECG parameters analyzed: heart rate, PR interval, RR interval, QRS interval, QT interval, and corrected QT (QTc) interval using the correction methods: Bazett's formula (QTcB), Fridericia's formula (QTcF). TE clinically important changes ECG values (relative to baseline) were defined as heart rate (bpm): <45 and >100; PR interval (millisecond [msec]): <120 and >200; QRS interval (msec): >120; QTc (msec): >470 in women and >450 in men. TE was concluded if the postbaseline value was above the upper limit and the baseline value was below the upper limit (example: Normal or Low). The same applied to the postbaseline value being below the lower limit with the baseline value being above the lower limit (example: Normal or High). TE ECGs: clinically important ECGs which occurred as at or after initial administration of study intervention through last dose plus 5 days. Only categories in which at least 1 participant had data were reported in this outcome measure.

Safety analysis set included all randomized participants who received at least 1 dose of JNJ-40411813 or placebo in the double-blind period. Here 'n' (number analyzed) refers to number of participants with at least 1 postbaseline value for the specified parameter.

Posted

Count of Participants

Participants

From DB period start (Day 1) up to 5 days after last dose of DB period (up to Day 90)

ID	Title	Description
OG000	DB: Cohort 1: Placebo	During double-blind (DB) period, participants were randomized to receive placebo matching to JNJ-40411813 tablet orally twice a day (BID) from Day 1 up to Day 85 along with previously prescribed AEDs (one of which must include levetiracetam or brivaracetam) on Days 1, 29, and 57. Participants were screened every 4 weeks for monthly seizure counts up to Week 12. Participants who had exceeded their pre-randomization monthly seizure count had the option to discontinue the study treatment due to lack of efficacy and perform the end-of-study/early withdrawal visit, continue DB treatment, or enter the open-label extension (OLE) period. Participants who had not exceeded the pre-randomization seizure count continued the DB treatment period through Week 12 and had the option to perform DB period end-of-study visit (last visit for last participant; Day 85) or entered the OLE period. Participants who continued treatment to the end of the DB period (Week 12) and were not elected to participate in the OLE were followed up for safety up to 2 weeks after the last dose of study treatment (up to Week 14).

Secondary

DB Treatment Period: Cohort 1 and 2: Number of Participants With Changes in Laboratory Assessments Recorded as TEAE

Safety analysis set included all randomized participants who received at least 1 dose of JNJ-40411813 or placebo in the double-blind period.

Posted

Count of Participants

Participants

From DB period start (Day 1) up to 5 days after last dose of DB period (up to Day 90)

ID	Title	Description
OG000	DB: Cohort 1: Placebo	During double-blind (DB) period, participants were randomized to receive placebo matching to JNJ-40411813 tablet orally twice a day (BID) from Day 1 up to Day 85 along with previously prescribed AEDs (one of which must include levetiracetam or brivaracetam) on Days 1, 29, and 57. Participants were screened every 4 weeks for monthly seizure counts up to Week 12. Participants who had exceeded their pre-randomization monthly seizure count had the option to discontinue the study treatment due to lack of efficacy and perform the end-of-study/early withdrawal visit, continue DB treatment, or enter the open-label extension (OLE) period. Participants who had not exceeded the pre-randomization seizure count continued the DB treatment period through Week 12 and had the option to perform the end-of-study for DB period visit (last visit for last participant; Day 85) or enter the OLE period. Participants who continued treatment to the end of the DB period (Week 12) and were not elected to participate in the OLE were followed up for safety up to 2 weeks after the last dose of study treatment (up to Week 14).

Secondary

Cohort 1 and 2: Percent Reduction in the Double-blind Period Monthly Seizure Rate

The percent reduction in the DB monthly seizure rate was defined as 100*(baseline monthly seizure count minus DB monthly seizure count) divided by (baseline monthly seizure count). The DB monthly seizure count was defined as the total number of observable focal onset seizures occurring during the 12-week DB period, multiplied by 28/XDB, where XDB was the number of days comprising the DB period. A positive percentage change in the double-blind monthly seizure count indicates improvement. Observable focal onset seizures included focal aware seizures with motor signs, focal impaired awareness seizures and focal to bilateral tonic-clonic seizures. Focal aware seizures without motor signs, myoclonic, or other generalized seizures was not counted towards baseline monthly seizure count.

FAS included all randomized participants assigned to receive study intervention and had both baseline and postbaseline seizure data.

Posted

Median

Inter-Quartile Range

Percent change (reduction)

From DB period Day 1 up to Day 85

ID	Title	Description
OG000	DB: Cohort 1: Placebo	During double-blind (DB) period, participants were randomized to receive placebo matching to JNJ-40411813 tablet orally twice a day (BID) from Day 1 up to Day 85 along with previously prescribed AEDs (one of which must include levetiracetam or brivaracetam) on Days 1, 29, and 57. Participants were screened every 4 weeks for monthly seizure counts up to Week 12. Participants who had exceeded their pre-randomization monthly seizure count had the option to discontinue the study treatment due to lack of efficacy and perform the end-of-study/early withdrawal visit, continue DB treatment, or enter the open-label extension (OLE) period. Participants who had not exceeded the pre-randomization seizure count continued the DB treatment period through Week 12 and had the option to perform the end-of-study for DB period visit (last visit for last participant; Day 85) or enter the OLE period. Participants who continued treatment to the end of the DB period (Week 12) and were not elected to participate in the OLE were followed up for safety up to 2 weeks after the last dose of study treatment (up to Week 14).

Secondary

Cohort 1 and 2: Percentage of Participants With Seizure Freedom During Double-blind Period

Percentage of participants with seizure freedom during DB period was reported. Seizure freedom was defined as having no seizures over the complete DB period.

FAS included all randomized participants assigned to receive study intervention and had both baseline and postbaseline seizure data.

Posted

Number

Percentage of participants

From DB period Day 1 up to Day 85

ID	Title	Description
OG000	DB: Cohort 1: Placebo	During double-blind (DB) period, participants were randomized to receive placebo matching to JNJ-40411813 tablet orally twice a day (BID) from Day 1 up to Day 85 along with previously prescribed AEDs (one of which must include levetiracetam or brivaracetam) on Days 1, 29, and 57. Participants were screened every 4 weeks for monthly seizure counts up to Week 12. Participants who had exceeded their pre-randomization monthly seizure count had the option to discontinue the study treatment due to lack of efficacy and perform the end-of-study/early withdrawal visit, continue DB treatment, or enter the open-label extension (OLE) period. Participants who had not exceeded the pre-randomization seizure count continued the DB treatment period through Week 12 and had the option to perform the end-of-study for DB period visit (last visit for last participant; Day 85) or enter the OLE period. Participants who continued treatment to the end of the DB period (Week 12) and were not elected to participate in the OLE were followed up for safety up to 2 weeks after the last dose of study treatment (up to Week 14).

Secondary

Cohort 1 and 2: Percentage of Participants Who Achieved a More Than (>) 50 Percent (%) Reduction (Response) in Double-blind Monthly Seizure Count Relative to Baseline Monthly Seizure Count

Percentage of participants who achieved a >50% reduction (response) in the DB monthly seizure count relative to baseline monthly seizure count during the DB period was reported. The baseline monthly seizure count was defined as the number of observable focal onset seizures occurred during the 8-week baseline period (Day -56 to -1), multiplied by 28/XBL, where XBL was the number of days comprising the participants baseline period. Observable focal onset seizures included focal aware seizures with motor signs, focal impaired awareness seizures and focal to bilateral tonic-clonic seizures. Focal aware seizures without motor signs, myoclonic, or other generalized seizures was not counted towards baseline monthly seizure count.

FAS included all randomized participants assigned to receive study intervention and had both baseline and postbaseline seizure data.

Posted

Number

Percentage of participants

From DB period Day 1 up to Day 85

ID	Title	Description
OG000	DB: Cohort 1: Placebo	During double-blind (DB) period, participants were randomized to receive placebo matching to JNJ-40411813 tablet orally twice a day (BID) from Day 1 up to Day 85 along with previously prescribed AEDs (one of which must include levetiracetam or brivaracetam) on Days 1, 29, and 57. Participants were screened every 4 weeks for monthly seizure counts up to Week 12. Participants who had exceeded their pre-randomization monthly seizure count had the option to discontinue the study treatment due to lack of efficacy and perform the end-of-study/early withdrawal visit, continue DB treatment, or enter the open-label extension (OLE) period. Participants who had not exceeded the pre-randomization seizure count continued the DB treatment period through Week 12 and had the option to perform the end-of-study for DB period visit (last visit for last participant; Day 85) or enter the OLE period. Participants who continued treatment to the end of the DB period (Week 12) and were not elected to participate in the OLE were followed up for safety up to 2 weeks after the last dose of study treatment (up to Week 14).

Secondary

DB Treatment Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47

DB treatment period: Cohort 1 and 2: plasma concentration of JNJ-40411813 and its metabolites (M30, M45 and M47) were reported. The concentrations of JNJ-40411813 and its metabolites (M30, M45 and M47) were measured using a validated, specific, and sensitive liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) method. Data for this outcome measure was not planned to be collected and analyzed for Cohort 1 and 2 placebo arms. Here, 'n' (number analyzed)=number of participants evaluable at each specified category.

Pharmacokinetic (PK) set: all randomized participants who received at least 1 dose of JNJ-40411813 and had at least 1 valid blood sample drawn for PK analysis and excluded samples with below lower limit of quantification or samples with inconsistent date/time or samples with previous dose date/time incomplete or samples with concentration less than (<) 10 nanograms per milliliter (ng/mL).

Posted

Mean

Standard Deviation

Nanograms per milliliter

Day 1: 2 hours post-dose, Days 29: pre-dose and 1 hour post-dose, Day 57: pre-dose and Day 85: post-dose/Early withdrawal (EW)

ID	Title	Description
OG000	DB: Cohort 1: JNJ-40411813 Non-induced	During DB period, participants not treated with EIAEDs (non-induced) received 50 mg JNJ-40411813 tablet orally BID from Day 1 up to Day 85 along with previously prescribed AEDs (one of which must include levetiracetam or brivaracetam) on Days 1, 29, and 57. Participants were screened every 4 weeks for monthly seizure counts up to Week 12. Participants who had exceeded their pre-randomization monthly seizure count had the option to discontinue the study treatment due to lack of efficacy and perform the end-of-study/early withdrawal visit, continued DB treatment, or enter the OLE period. Participants who had not exceeded the pre-randomization seizure count continued the DB treatment period through Week 12 and had the option to perform the end-of-study for DB period visit (last visit for last participant; Day 85) or enter the OLE period. Participants who continued treatment to the end of the DB period (Week 12) and were not elected to participate in the OLE were followed up for safety up to 2 weeks after the last dose of study treatment (up to Week 14).

Secondary

DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Levetiracetam

DB treatment period: Cohort 1 and 2: plasma concentration of AED: levetiracetam were reported. The concentrations of levetiracetam were measured using a validated, specific, and sensitive LC-MS/MS method.

PK set was used. Here, 'N' (overall number of participants analyzed)=number of participants evaluable for this OM; 'n' (number analyzed) = number of participants evaluable at each specified category.

Posted

Mean

Standard Deviation

Nanograms per milliliter

Day 1: pre-dose and 2 hours post-dose, Day 29: pre-dose and 1 hour post-dose, Day 57: pre-dose and Day 85: post-dose/Early withdrawal

ID	Title	Description
OG000	DB: Cohort 1: Placebo Non-induced	During DB period, participants not treated with EIAEDs (non-induced) received placebo matching to JNJ-40411813 tablet orally twice a day (BID) from Day 1 up to Day 85 along with previously prescribed AEDs (one of which must include levetiracetam or brivaracetam) on Days 1, 29, and 57. Participants were screened every 4 weeks for monthly seizure counts up to Week 12. Participants who had exceeded their pre-randomization monthly seizure count had the option to discontinue the study treatment due to lack of efficacy and perform the end-of-study/early withdrawal visit, continue DB treatment, or enter the open-label extension (OLE) period. Participants who had not exceeded the pre-randomization seizure count continued the DB treatment period through Week 12 and had the option to perform DB period end-of-study visit (last visit for last participant; Day 85) or entered the OLE period. Participants who continued treatment to the end of the DB period (Week 12) and were not elected to participate in the OLE were followed up for safety up to 2 weeks after the last dose of study treatment (up to Week 14).

Secondary

DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Brivaracetam

DB treatment period: Cohort 1 and 2: plasma concentration of AED: brivaracetam were reported. The concentrations of brivaracetam were measured using a validated, specific, and sensitive LC-MS/MS method.

PK set was used for the analysis. Here, 'N' (overall number of participants analyzed)=number of participants evaluable for this OM; 'n' (number analyzed) = number of participants evaluable at each specified category. Here, N=0 signifies that no participant received brivaracetam; n=0 in arm 'DB: Cohort 2: Placebo Non-induced' at timepoint 'Day 57: pre-dose' signifies that no participant was available at specific visit and thus, no data was collected and analyzed.

Posted

Mean

Standard Deviation

Nanograms per milliliter

Day 1: pre-dose and 2 hours post-dose, Days 29: pre-dose and 1 hour post-dose, Day 57: pre-dose and Day 85: post-dose/Early withdrawal

ID	Title	Description
OG000	DB: Cohort 1: Placebo Non-induced	During DB period, participants not treated with EIAEDs (non-induced) received placebo matching to JNJ-40411813 tablet orally twice a day (BID) from Day 1 up to Day 85 along with previously prescribed AEDs (one of which must include levetiracetam or brivaracetam) on Days 1, 29, and 57. Participants were screened every 4 weeks for monthly seizure counts up to Week 12. Participants who had exceeded their pre-randomization monthly seizure count had the option to discontinue the study treatment due to lack of efficacy and perform the end-of-study/early withdrawal visit, continue DB treatment, or enter the open-label extension (OLE) period. Participants who had not exceeded the pre-randomization seizure count continued the DB treatment period through Week 12 and had the option to perform DB period end-of-study visit (last visit for last participant; Day 85) or entered the OLE period. Participants who continued treatment to the end of the DB period (Week 12) and were not elected to participate in the OLE were followed up for safety up to 2 weeks after the last dose of study treatment (up to Week 14).

Secondary

DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Carbamazepine

DB treatment period: Cohort 1 and 2: plasma concentration of AED: carbamazepine were reported. The concentrations of carbamazepine were measured using a validated, specific, and sensitive LC-MS/MS method.

PK set was used for the analysis. Here, 'N' (overall number of participants analyzed)=number of participants evaluable for this OM; 'n' (number analyzed) = number of participants evaluable at each specified category. Here, N=0 signifies that non-induced arms were not applicable to this outcome measure as carbamazepine itself is a CYP3A4-inducing AED.

Posted

Mean

Standard Deviation

Nanograms per milliliter

Pre-dose: Day 1, Days 29, and Day 57

ID	Title	Description
OG000	DB: Cohort 1: Placebo Non-induced	During DB period, participants not treated with EIAEDs (non-induced) received placebo matching to JNJ-40411813 tablet orally twice a day (BID) from Day 1 up to Day 85 along with previously prescribed AEDs (one of which must include levetiracetam or brivaracetam) on Days 1, 29, and 57. Participants were screened every 4 weeks for monthly seizure counts up to Week 12. Participants who had exceeded their pre-randomization monthly seizure count had the option to discontinue the study treatment due to lack of efficacy and perform the end-of-study/early withdrawal visit, continue DB treatment, or enter the open-label extension (OLE) period. Participants who had not exceeded the pre-randomization seizure count continued the DB treatment period through Week 12 and had the option to perform DB period end-of-study visit (last visit for last participant; Day 85) or entered the OLE period. Participants who continued treatment to the end of the DB period (Week 12) and were not elected to participate in the OLE were followed up for safety up to 2 weeks after the last dose of study treatment (up to Week 14).

Secondary

OLE Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47

OLE period: Cohort 1 and 2: plasma concentration of JNJ-40411813 and its metabolites (M30, M45 and M47) were reported. The concentrations of JNJ-40411813 and its metabolites (M30, M45 and M47) were measured using a validated, specific, and sensitive LC-MS/MS method. Data for this outcome measure was not planned to be collected and analyzed for Cohort 1 and 2 placebo arms. OLE baseline was Day 1 of OLE period.

PK set was used for the analysis. Here, n=0 signifies that none of the participants were evaluable for assessment in the specified arm for specified time point. Here, 'n' (number analyzed)=number of participants evaluable at each specified category.

Posted

Mean

Standard Deviation

Nanograms per milliliter

Cohort 1:OLE visit 2 (1 month post OLE baseline[BL]), OLE visit 3 (2 months post OLE BL), OLE visit 4 to 7 (up to 1year post OLE BL);Cohort 2:OLE visit 2 (1 month post OLE BL), OLE visit 3 (2 months post OLE BL), OLE visit 4 to 5 (up to 1year post OLE BL)

ID	Title	Description
OG000	OLE: Cohort 1: JNJ-40411813 Non-induced	During OLE period, cohort 1 non-induced participants (without EIAEDs) received JNJ-40411813 50 mg BID along with previously prescribed AEDs (one of which must include levetiracetam or brivaracetam) from Day 1 of OLE up to 2 years. The dose could be increased at the second visit (Month 1) to 100 mg JNJ-40411813 BID.
OG001	OLE: Cohort 1: JNJ-40411813 Induced

Secondary

OLE Period: Cohort 1 and 2: Plasma Concentration of AED: Levetiracetam

OLE period: Cohort 1 and 2: plasma concentration of AED: levetiracetam were reported. The concentrations of levetiracetam were measured using a validated, specific, and sensitive LC-MS/MS method.

PK set was used. Here, 'N' (overall number of participants analyzed)=number of participants evaluable for this OM; 'n' (number analyzed) = number of participants evaluable at each specified category.

Posted

Mean

Standard Deviation

Nanograms per milliliter

OLE visit 2: 1st month; OLE visit 3: 2nd month

ID	Title	Description
OG000	OLE: Cohort 1: Placebo Followed by JNJ-40411813 Non-induced	During OLE period, cohort 1 non-induced participants (without EIAEDs) who had received placebo matched to JNJ-40411813 during the DB period received JNJ-40411813 50 mg BID along with previously prescribed AEDs (one of which must include levetiracetam or brivaracetam) from Day 1 of OLE up to 2 years. The dose could be increased at the second visit (Month 1) to 100 mg of JNJ-40411813 BID for non-induced participants (without EIAEDs).
OG001	OLE: Cohort 1: Placebo Followed by JNJ-40411813 Induced	During OLE period, cohort 1 induced participants (with EIAEDs) who had received placebo matched to JNJ-40411813 during the DB period received JNJ-40411813 100 mg BID along with previously prescribed AEDs (one of which must include levetiracetam or brivaracetam) from Day 1 of OLE up to 2 years. The dose could be increased at the second visit (Month 1) to 200 mg of JNJ-40411813 BID for induced participants (with EIAEDs).

Secondary

OLE Period: Cohort 1 and 2: Plasma Concentration of AED: Brivaracetam

OLE period: Cohort 1 and 2: plasma concentration of AED: brivaracetam were reported. The concentrations of brivaracetam were measured using a validated, specific, and sensitive LC-MS/MS method.

PK set was used. 'N' (overall number of participants analyzed)=number of participants evaluable for this OM; 'n' (number analyzed)=number of participants evaluable at each specified category. Cohort (C) 1: N=0=no participant received brivaracetam; C 2: N=0=no participant was available and thus, no data was collected and analyzed; n=0 in arm 'OLE: C 2: JNJ-40411813 Non-induced' timepoint 'OLE visit 3'= no participant was available at specific visit and thus, no data was collected and analyzed.

Posted

Mean

Standard Deviation

Nanograms per milliliter

OLE visit 2: 1st month; OLE visit 3: 2nd month

ID	Title	Description
OG000	OLE: Cohort 1: Placebo Followed by JNJ-40411813 Non-induced	During OLE period, cohort 1 non-induced participants (without EIAEDs) who had received placebo matched to JNJ-40411813 during the DB period received JNJ-40411813 50 mg BID along with previously prescribed AEDs (one of which must include levetiracetam or brivaracetam) from Day 1 of OLE up to 2 years. The dose could be increased at the second visit (Month 1) to 100 mg of JNJ-40411813 BID for non-induced participants (without EIAEDs).
OG001	OLE: Cohort 1: Placebo Followed by JNJ-40411813 Induced

Secondary

OLE Period: Plasma Concentration of AED: Carbamazepine

OLE period: Cohort 1 and 2: plasma concentration of AED: carbamazepine were reported. The concentrations of carbamazepine were measured using a validated, specific, and sensitive LC-MS/MS method.

PK set used. 'N' (overall number of participants analyzed)=number of participants evaluable for this OM; 'n' (number analyzed) = number of participants evaluable at each specified category. N=0 of all non-induced arms signifies that these arms were not applicable to this outcome measure as carbamazepine itself is a CYP3A4-inducing AED; For 'OLE: Cohort 2: Placebo Followed by JNJ-40411813 Induced' arm: N=0 signifies that no participant was available and thus, no data was collected and analyzed.

Posted

Mean

Standard Deviation

Nanograms per milliliter

OLE visit 2: 1st month; OLE visit 3: 2nd month

ID	Title	Description
OG000	OLE: Cohort 1: Placebo Followed by JNJ-40411813 Non-induced	During OLE period, cohort 1 non-induced participants (without EIAEDs) who had received placebo matched to JNJ-40411813 during the DB period received JNJ-40411813 50 mg BID along with previously prescribed AEDs (one of which must include levetiracetam or brivaracetam) from Day 1 of OLE up to 2 years. The dose could be increased at the second visit (Month 1) to 100 mg of JNJ-40411813 BID for non-induced participants (without EIAEDs).
OG001	OLE: Cohort 1: Placebo Followed by JNJ-40411813 Induced	During OLE period, cohort 1 induced participants (with EIAEDs) who had received placebo matched to JNJ-40411813 during the DB period received JNJ-40411813 100 mg BID along with previously prescribed AEDs (one of which must include levetiracetam or brivaracetam) from Day 1 of OLE up to 2 years. The dose could be increased at the second visit (Month 1) to 200 mg of JNJ-40411813 BID for induced participants (with EIAEDs).

Arm/Groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	DB: Cohort 1: Placebo	During double-blind (DB) period, participants were randomized to receive placebo matching to JNJ-40411813 tablet orally twice a day (BID) from Day 1 up to Day 85 along with previously prescribed AEDs (one of which must include levetiracetam or brivaracetam) on Days 1, 29, and 57. Participants were screened every 4 weeks for monthly seizure counts up to Week 12. Participants who had exceeded their pre-randomization monthly seizure count had the option to discontinue the study treatment due to lack of efficacy and perform the end-of-study/early withdrawal visit, continue DB treatment, or enter the open-label extension (OLE) period. Participants who had not exceeded the pre-randomization seizure count continued the DB treatment period through Week 12 and had the option to perform DB period end-of-study visit (last visit for last participant; Day 85) or entered the OLE period. Participants who continued treatment to the end of the DB period (Week 12) and were not elected to participate in the OLE were followed up for safety up to 2 weeks after the last dose of study treatment (up to Week 14).	20	0	20	7	20
EG001	DB: Cohort 1: JNJ-40411813	During DB period, participants were randomized to receive JNJ-40411813 100 milligrams (mg) or 50 mg tablet orally BID from Day 1 up to Day 85 along with previously prescribed AEDs (one of which must include levetiracetam or brivaracetam) on Days 1, 29, and 57. Participants treated with EIAEDs (induced) received 100 mg of JNJ-40411813 and participants not treated with EIAEDs (non-induced) received 50 mg of JNJ-40411813. Participants were screened every 4 weeks for monthly seizure counts up to Week 12. Participants who had exceeded their pre-randomization monthly seizure count had the option to discontinue the study treatment due to lack of efficacy and perform the end-of-study/early withdrawal visit, continued DB treatment, or enter the OLE period. Participants who had not exceeded the pre-randomization seizure count continued the DB treatment period through Week 12 and had the option to perform DB period end-of-study visit (last visit for last participant; Day 85) or entered the OLE period. Participants who continued treatment to the end of the DB period (Week 12) and were not elected to participate in the OLE were followed up for safety up to 2 weeks after the last dose of study treatment (up to Week 14).	40	1	40	16	40
EG002	DB: Cohort 2: Placebo	During DB period, participants were randomized to receive placebo matching to JNJ-40411813 tablet orally BID from Day 1 up to Day 85 along with previously prescribed AEDs (one of which must include levetiracetam or brivaracetam) on Days 1, 29, and 57. Participants were screened every 4 weeks for monthly seizure counts up to Week 12. Participants who had exceeded their pre-randomization monthly seizure count had the option to discontinue the study treatment due to lack of efficacy and perform the end-of-study/early withdrawal visit, continue DB treatment, or enter the OLE period. Participants who had not exceeded the pre-randomization seizure count continued the DB treatment period through Week 12 and had the option to perform DB period end-of-study visit (last visit for last participant; Day 85) or entered the OLE period. Participants who continued treatment to the end of the DB period (Week 12) and were not elected to participate in the OLE were followed up for safety up to 2 weeks after the last dose of study treatment (up to Week 14).	9	1	9	7	9
EG003	DB: Cohort 2: JNJ-40411813	During DB period, participants were randomized to receive JNJ-40411813 200 mg or 100 mg tablet orally BID from Day 1 up to Day 85 along with previously prescribed AEDs (one of which must include levetiracetam or brivaracetam) on Days 1, 29, and 57. Participants treated with EIAEDs (induced) received 200 mg of JNJ-40411813 and participants not treated with EIAEDs (non-induced) received 100 mg of JNJ-40411813. Participants were screened every 4 weeks for monthly seizure counts up to Week 12. Participants who had exceeded their pre-randomization monthly seizure count had the option to discontinue the study treatment due to lack of efficacy and perform the end-of-study/early withdrawal visit, continue DB treatment, or enter the OLE period. Participants who had not exceeded the pre-randomization seizure count continued the DB treatment period through Week 12 and had the option to perform DB period end-of-study visit (last visit for last participant; Day 85) or entered the OLE period. Participants who continued treatment to the end of the DB period (Week 12) and were not elected to participate in the OLE were followed up for safety up to 2 weeks after the last dose of study treatment (up to Week 14).	41	2	41	19	41
EG004	OLE: Cohort 1: Placebo Followed by JNJ-40411813	During OLE period, cohort 1 participants who had received placebo during the DB period received JNJ-40411813 along with previously prescribed AEDs (one of which must include levetiracetam or brivaracetam) from Day 1 of OLE up to 2 years. Induced participants (with EIAEDs) received JNJ-40411813 100 mg BID, and non-induced participants (without EIAEDs) received JNJ-40411813 50 mg BID. The dose could be increased at the second visit (Month 1) to 200 mg JNJ-40411813 BID for induced participants (with EIAEDs) and 100 mg JNJ-40411813 BID for non-induced participants (without EIAEDs).	12	0	12	6	12
EG005	OLE: Cohort 1: JNJ-40411813 Followed by JNJ-40411813	During OLE period, cohort 1 participants who had received JNJ-40411813 during the DB period continued to receive JNJ-40411813 along with previously prescribed AEDs (one of which must include levetiracetam or brivaracetam) from Day 1 of OLE up to 2 years. Induced participants (with EIAEDs) received JNJ-40411813 100 mg BID, and non-induced participants (without EIAEDs) received JNJ-40411813 50 mg BID. The dose could be increased at the second visit (Month1) to 200 mg JNJ-40411813 BID for induced participants (with EIAEDs) and 100 mg JNJ-40411813 BID for non-induced participants (without EIAEDs).	23	5	23	12	23
EG006	OLE: Cohort 2: Placebo Followed by JNJ-40411813	During the OLE period, cohort 2 participants who had received placebo during the DB period received JNJ-40411813 along with previously prescribed AEDs (one of which must include levetiracetam or brivaracetam) from Day 1 of OLE up to 2 years. Participants started with JNJ-40411813 100 mg BID. Induced participants (with EIAEDs) had their dose increased to JNJ-40411813 200 mg BID on Day 8 of the OLE. Non-induced participants (without EIAEDs) continued with JNJ-40411813 100 mg BID.	7	0	7	6	7
EG007	OLE: Cohort 2: JNJ-40411813 Followed by JNJ-40411813	During OLE period, cohort 2 participants who had received JNJ-40411813 during the DB period continued to receive JNJ-40411813 along with previously prescribed AEDs (one of which must include levetiracetam or brivaracetam) from Day 1 of OLE up to 2 years. Participants started with JNJ-40411813 100 mg BID. Induced participants (with EIAEDs) had their dose increased to JNJ-40411813 200 mg BID on Day 8 of the OLE. Non-induced participants (without EIAEDs) continued with JNJ-40411813 100 mg BID.	31	1	31	12	31

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Cervical Vertebral Fracture	Injury, poisoning and procedural complications	MedDRA Version 26.1	Non-systematic Assessment	EG0000 affected20 at risk EG0010 affected40 at risk EG0020 affected9 at risk EG0031 affected41 at risk EG004
Head Injury	Injury, poisoning and procedural complications	MedDRA Version 26.1	Non-systematic Assessment	EG0000 affected20 at risk EG0010 affected40 at risk EG0020 affected9 at risk EG003
Limb Traumatic Amputation	Injury, poisoning and procedural complications	MedDRA Version 26.1	Non-systematic Assessment	EG0000 affected20 at risk EG0011 affected40 at risk EG0020 affected9 at risk EG003
Pituitary Tumour Benign	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 26.1	Non-systematic Assessment	EG0000 affected20 at risk EG0010 affected40 at risk EG0020 affected9 at risk EG003
Change in Seizure Presentation	Nervous system disorders	MedDRA Version 26.1	Non-systematic Assessment	EG0000 affected20 at risk EG0010 affected40 at risk EG0021 affected9 at risk EG003
Epilepsy	Nervous system disorders	MedDRA Version 26.1	Non-systematic Assessment	EG0000 affected20 at risk EG0010 affected40 at risk EG0020 affected9 at risk EG003
Seizure	Nervous system disorders	MedDRA Version 26.1	Non-systematic Assessment	EG0000 affected20 at risk EG0010 affected40 at risk EG0020 affected9 at risk EG003
Status Epilepticus	Nervous system disorders	MedDRA Version 26.1	Non-systematic Assessment	EG0000 affected20 at risk EG0010 affected40 at risk EG0020 affected9 at risk EG003
Pulmonary Mass	Respiratory, thoracic and mediastinal disorders	MedDRA Version 26.1	Non-systematic Assessment	EG0000 affected20 at risk EG0010 affected40 at risk EG0020 affected9 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Vertigo	Ear and labyrinth disorders	MedDRA Version 26.1	Non-systematic Assessment	EG0000 affected20 at risk EG0010 affected40 at risk EG0021 affected9 at risk EG0035 affected41 at risk EG0040 affected12 at risk EG0051 affected23 at risk EG0061 affected7 at risk EG0070 affected31 at risk
Diplopia	Eye disorders	MedDRA Version 26.1	Non-systematic Assessment	EG0000 affected20 at risk EG0011 affected40 at risk EG0020 affected9 at risk EG003
Vision Blurred	Eye disorders	MedDRA Version 26.1	Non-systematic Assessment	EG0000 affected20 at risk EG0010 affected40 at risk EG0020 affected9 at risk EG003
Abdominal Pain Upper	Gastrointestinal disorders	MedDRA Version 26.1	Non-systematic Assessment	EG0000 affected20 at risk EG0010 affected40 at risk EG0020 affected9 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA Version 26.1	Non-systematic Assessment	EG0000 affected20 at risk EG0010 affected40 at risk EG0021 affected9 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA Version 26.1	Non-systematic Assessment	EG0000 affected20 at risk EG0012 affected40 at risk EG0020 affected9 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA Version 26.1	Non-systematic Assessment	EG0000 affected20 at risk EG0010 affected40 at risk EG0021 affected9 at risk EG003
Gastrooesophageal Reflux Disease	Gastrointestinal disorders	MedDRA Version 26.1	Non-systematic Assessment	EG0001 affected20 at risk EG0010 affected40 at risk EG0020 affected9 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA Version 26.1	Non-systematic Assessment	EG0000 affected20 at risk EG0013 affected40 at risk EG0020 affected9 at risk EG003
Fatigue	General disorders	MedDRA Version 26.1	Non-systematic Assessment	EG0000 affected20 at risk EG0012 affected40 at risk EG0020 affected9 at risk EG003
Gait Disturbance	General disorders	MedDRA Version 26.1	Non-systematic Assessment	EG0000 affected20 at risk EG0011 affected40 at risk EG0020 affected9 at risk EG003
Malaise	General disorders	MedDRA Version 26.1	Non-systematic Assessment	EG0000 affected20 at risk EG0012 affected40 at risk EG0020 affected9 at risk EG003
Covid-19	Infections and infestations	MedDRA Version 26.1	Non-systematic Assessment	EG0000 affected20 at risk EG0012 affected40 at risk EG0020 affected9 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA Version 26.1	Non-systematic Assessment	EG0002 affected20 at risk EG0012 affected40 at risk EG0020 affected9 at risk EG003
Respiratory Tract Infection Viral	Infections and infestations	MedDRA Version 26.1	Non-systematic Assessment	EG0001 affected20 at risk EG0011 affected40 at risk EG0020 affected9 at risk EG003
Arthropod Bite	Injury, poisoning and procedural complications	MedDRA Version 26.1	Non-systematic Assessment	EG0000 affected20 at risk EG0010 affected40 at risk EG0021 affected9 at risk EG003
Contusion	Injury, poisoning and procedural complications	MedDRA Version 26.1	Non-systematic Assessment	EG0000 affected20 at risk EG0010 affected40 at risk EG0020 affected9 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA Version 26.1	Non-systematic Assessment	EG0000 affected20 at risk EG0010 affected40 at risk EG0020 affected9 at risk EG003
Head Injury	Injury, poisoning and procedural complications	MedDRA Version 26.1	Non-systematic Assessment	EG0001 affected20 at risk EG0011 affected40 at risk EG0020 affected9 at risk EG003
Ligament Sprain	Injury, poisoning and procedural complications	MedDRA Version 26.1	Non-systematic Assessment	EG0000 affected20 at risk EG0010 affected40 at risk EG0020 affected9 at risk EG003
Wound	Injury, poisoning and procedural complications	MedDRA Version 26.1	Non-systematic Assessment	EG0000 affected20 at risk EG0010 affected40 at risk EG0020 affected9 at risk EG003
Aspartate Aminotransferase Increased	Investigations	MedDRA Version 26.1	Non-systematic Assessment	EG0000 affected20 at risk EG0010 affected40 at risk EG0020 affected9 at risk EG003
Blood Chloride Increased	Investigations	MedDRA Version 26.1	Non-systematic Assessment	EG0000 affected20 at risk EG0010 affected40 at risk EG0020 affected9 at risk EG003
Blood Creatine Phosphokinase Increased	Investigations	MedDRA Version 26.1	Non-systematic Assessment	EG0000 affected20 at risk EG0011 affected40 at risk EG0020 affected9 at risk EG003
Hypernatraemia	Metabolism and nutrition disorders	MedDRA Version 26.1	Non-systematic Assessment	EG0000 affected20 at risk EG0010 affected40 at risk EG0020 affected9 at risk EG003
Joint Swelling	Musculoskeletal and connective tissue disorders	MedDRA Version 26.1	Non-systematic Assessment	EG0001 affected20 at risk EG0010 affected40 at risk EG0020 affected9 at risk EG003
Muscle Contracture	Musculoskeletal and connective tissue disorders	MedDRA Version 26.1	Non-systematic Assessment	EG0000 affected20 at risk EG0010 affected40 at risk EG0020 affected9 at risk EG003
Dizziness	Nervous system disorders	MedDRA Version 26.1	Non-systematic Assessment	EG0000 affected20 at risk EG0011 affected40 at risk EG0020 affected9 at risk EG003
Dizziness Postural	Nervous system disorders	MedDRA Version 26.1	Non-systematic Assessment	EG0000 affected20 at risk EG0011 affected40 at risk EG0020 affected9 at risk EG003
Dysarthria	Nervous system disorders	MedDRA Version 26.1	Non-systematic Assessment	EG0000 affected20 at risk EG0010 affected40 at risk EG0020 affected9 at risk EG003
Headache	Nervous system disorders	MedDRA Version 26.1	Non-systematic Assessment	EG0001 affected20 at risk EG0012 affected40 at risk EG0020 affected9 at risk EG003
Memory Impairment	Nervous system disorders	MedDRA Version 26.1	Non-systematic Assessment	EG0000 affected20 at risk EG0010 affected40 at risk EG0020 affected9 at risk EG003
Migraine	Nervous system disorders	MedDRA Version 26.1	Non-systematic Assessment	EG0000 affected20 at risk EG0010 affected40 at risk EG0020 affected9 at risk EG003
Seizure	Nervous system disorders	MedDRA Version 26.1	Non-systematic Assessment	EG0000 affected20 at risk EG0012 affected40 at risk EG0020 affected9 at risk EG003
Somnolence	Nervous system disorders	MedDRA Version 26.1	Non-systematic Assessment	EG0002 affected20 at risk EG0013 affected40 at risk EG0021 affected9 at risk EG003
Syncope	Nervous system disorders	MedDRA Version 26.1	Non-systematic Assessment	EG0000 affected20 at risk EG0010 affected40 at risk EG0021 affected9 at risk EG003
Tremor	Nervous system disorders	MedDRA Version 26.1	Non-systematic Assessment	EG0000 affected20 at risk EG0012 affected40 at risk EG0020 affected9 at risk EG003
Insomnia	Psychiatric disorders	MedDRA Version 26.1	Non-systematic Assessment	EG0000 affected20 at risk EG0010 affected40 at risk EG0021 affected9 at risk EG003
Suicidal Ideation	Psychiatric disorders	MedDRA Version 26.1	Non-systematic Assessment	EG0000 affected20 at risk EG0010 affected40 at risk EG0021 affected9 at risk EG003
Haematuria	Renal and urinary disorders	MedDRA Version 26.1	Non-systematic Assessment	EG0000 affected20 at risk EG0010 affected40 at risk EG0021 affected9 at risk EG003
Choking	Respiratory, thoracic and mediastinal disorders	MedDRA Version 26.1	Non-systematic Assessment	EG0000 affected20 at risk EG0010 affected40 at risk EG0021 affected9 at risk EG003
Wheezing	Respiratory, thoracic and mediastinal disorders	MedDRA Version 26.1	Non-systematic Assessment	EG0000 affected20 at risk EG0010 affected40 at risk EG0021 affected9 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA Version 26.1	Non-systematic Assessment	EG0000 affected20 at risk EG0010 affected40 at risk EG0021 affected9 at risk EG003
Hypertension	Vascular disorders	MedDRA Version 26.1	Non-systematic Assessment	EG0000 affected20 at risk EG0010 affected40 at risk EG0020 affected9 at risk EG003

ID	Term
D009461	Neurologic Manifestations
D009422	Nervous System Diseases
D012816	Signs and Symptoms
D013568	Pathological Conditions, Signs and Symptoms