A Study to Investigate JNJ-40411813 in Combination With Levetiracetam or Brivaracetam in Epilepsy

A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter Study to Evaluate the Efficacy, Safety, and Tolerability of JNJ-40411813 as Adjunctive Therapy in Subjects With Focal Onset Seizures With Suboptimal Response to Levetiracetam or Brivaracetam

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04836559

Enrollment

110

Registered

2021-04-08

Start date

2021-05-18

Completion date

2024-02-08

Last updated

2025-07-03

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Focal Onset Seizures

Brief summary

The purpose of this study is to evaluate the efficacy of up to 3 dose levels of adjunctive JNJ-40411813 compared to placebo based on the time to baseline monthly seizure count in participants with focal onset seizures who are receiving levetiracetam or brivaracetam and up to 3 other anti-epileptic drugs (AEDs) (double-blind treatment period) and to evaluate the long-term efficacy and safety of adjunctive therapy with JNJ-40411813 in participants with epilepsy (open-label extension \[OLE\] period).

Detailed description

JNJ-40411813 is a positive allosteric modulator (PAM) of the metabotropic glutamate receptor-2 (mGlu2), which is abundantly expressed in the forebrain and cerebellum. The mGlu2 receptor functions as a presynaptic auto-receptor that, upon activation, decreases the release of the excitatory neurotransmitter glutamate. Positive allosteric modulation of a receptor will result in the direct enhancement of the agonist-induced signal while PAMs themselves have generally no or low intrinsic activity at the receptor. The net effect of JNJ-40411813 is hypothesized to be a normalization of hyper-glutamatergic transmission. JNJ-40411813 is being evaluated for the treatment of disorders of the central nervous systems (CNS), such as epilepsy, and has been evaluated in schizophrenia and anxious depression. This study will consist of 1 to a maximum of 3 cohorts. In each cohort, for each participant the study consists of a screening period (up to minus \[-\] 8 weeks), an 8-week prospective pretreatment baseline period, an up to 12-week double-blind treatment period and a 2-year OLE period or a follow-up telephone visit 2 weeks after the last dose of study intervention. Safety assessments including physical and neurological examination, vital signs, 12 lead electrocardiogram (ECG), clinical chemistry, hematology, and urinalysis will be performed. The total maximal duration of the study is up to 2 years and 5 months.

Interventions

DRUGJNJ-40411813

JNJ-40411813 will be administered orally.

DRUGPlacebo

Placebo will be administered orally.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to 69 Years

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
Cohort 1 and 2: Time to Baseline Monthly Seizure Count up to the End of the 12-week Double-blind (DB) Treatment Period	From DB period Day 1 up to Day 85	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.

Secondary

Measure	Time frame	Description
Cohort 1 and 2: Number of Participants With Seizure Freedom at the End of OLE Period	From OLE baseline (Day 1 of OLE) up to 24 months after start of OLE (the actual OLE starting time varied for each participant)	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.
Cohort 1 and 2: Number of Participants With at Least 50 Percent (%) Reduction (Response) in the OLE Monthly Seizure Count	From OLE baseline (Day 1 of OLE) up to 24 months after start of OLE (the actual OLE starting time varied for each participant)	Number of participants having at least a 50% reduction in the monthly seizure rate (response) during the OLE study period was reported.
OLE Period: Cohort 1 and 2: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)	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)	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.
OLE Period: Cohort 1 and 2: Number of Participants With Treatment-emergent (TE) Clinically Important Changes in Vital Signs	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)	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.
OLE Period: Cohort 1 and 2: Number of Participants With Changes in Laboratory Assessments Recorded as TEAE	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)	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.
DB Treatment Period: Cohort 1 and 2: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)	From DB period start (Day 1) up to 5 days after last dose of DB period (up to Day 90)	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.
DB Treatment Period: Cohort 1 and 2: Number of Participants With Treatment-emergent Clinically Important Changes in Vital Signs	From DB period start (Day 1) up to 5 days after last dose of DB period (up to Day 90)	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.
DB Treatment Period: Cohort 1 and 2: Number of Participants With Treatment-emergent Clinically Important Changes in Electrocardiogram (ECG)	From DB period start (Day 1) up to 5 days after last dose of DB period (up to Day 90)	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.
DB Treatment Period: Cohort 1 and 2: Number of Participants With Changes in Laboratory Assessments Recorded as TEAE	From DB period start (Day 1) up to 5 days after last dose of DB period (up to Day 90)	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.
Cohort 1 and 2: Percent Reduction in the Double-blind Period Monthly Seizure Rate	From DB period Day 1 up to Day 85	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.
Cohort 1 and 2: Percent Reduction in the Open Label Extension (OLE) Period Monthly Seizure Rate	From OLE baseline (Day 1 of OLE) up to 24 months after start of OLE (the actual OLE starting time varied for each participant)	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.
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	From DB period Day 1 up to Day 85	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.
DB Treatment Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	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)	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.
DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Levetiracetam	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	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.
DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Brivaracetam	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	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.
DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Carbamazepine	Pre-dose: Day 1, Days 29, and Day 57	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.
OLE Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	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)	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.
OLE Period: Cohort 1 and 2: Plasma Concentration of AED: Levetiracetam	OLE visit 2: 1st month; OLE visit 3: 2nd month	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.
OLE Period: Cohort 1 and 2: Plasma Concentration of AED: Brivaracetam	OLE visit 2: 1st month; OLE visit 3: 2nd month	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.
OLE Period: Plasma Concentration of AED: Carbamazepine	OLE visit 2: 1st month; OLE visit 3: 2nd month	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.
Cohort 1 and 2: Percentage of Participants With Seizure Freedom During Double-blind Period	From DB period Day 1 up to Day 85	Percentage of participants with seizure freedom during DB period was reported. Seizure freedom was defined as having no seizures over the complete DB period.

Countries

Belgium, Germany, Poland, Russia, South Korea, Spain, Ukraine, United States

Participant flow

Recruitment details

Participants with diagnosis of focal onset seizures and receiving levetiracetam or brivaracetam and up to 3 other anti-epileptic drugs (AEDs) were enrolled in study. Study consisted of cohort 1 and 2. In each cohort, participants were stratified into two groups: participants treated with a CYP3A4 enzyme inducing anti-epileptic drugs (EIAED \[induced participants\]) and those not treated with a CYP3A4 EIAED (non-induced participants).

Pre-assignment details

PK sets: randomized participants who received at least (\>=)1 dose of JNJ-40411813 and had \>=1 valid blood sample drawn for PK analysis and excluded samples with below lower limit of quantification or with inconsistent date/time or with previous dose date/time incomplete or samples with concentration \<10 nanograms per milliliter. Safety set: randomized participants who received \>=1 dose of JNJ-40411813/placebo. Due to inclusion/exclusion criteria difference, PK set count differed from safety set.

Participants by arm

Arm	Count
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
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
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
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).	41
Total	110

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003	FG004	FG005	FG006	FG007
Double Blind Period (Day 1 to Day 85)	Adverse Event	0	4	1	1	0	0	0	0
Double Blind Period (Day 1 to Day 85)	Other	1	0	0	0	0	0	0	0
Double Blind Period (Day 1 to Day 85)	Protocol Violation	1	0	0	0	0	0	0	0
Double Blind Period (Day 1 to Day 85)	Randomized by Mistake With Study Treatment	0	0	0	1	0	0	0	0
Double Blind Period (Day 1 to Day 85)	Withdrawal by Subject	0	1	1	3	0	0	0	0
OLE Period (Day 1 of OLE up to 2 Years)	Lack of Efficacy	0	0	0	0	1	7	3	4
OLE Period (Day 1 of OLE up to 2 Years)	No Longer Clinically Benefitting	0	0	0	0	0	0	0	1
OLE Period (Day 1 of OLE up to 2 Years)	Sponsor's Decision	0	0	0	0	7	14	4	24
OLE Period (Day 1 of OLE up to 2 Years)	Withdrawal by Subject	0	0	0	0	4	2	0	2

Baseline characteristics

Characteristic	DB: Cohort 2: Placebo	DB: Cohort 2: JNJ-40411813	Total	DB: Cohort 1: Placebo	DB: Cohort 1: JNJ-40411813
Age, Continuous	39.7 Years STANDARD_DEVIATION 10.84	41.3 Years STANDARD_DEVIATION 11.47	39.8 Years STANDARD_DEVIATION 11.94	41.3 Years STANDARD_DEVIATION 12.55	37.5 Years STANDARD_DEVIATION 12.4
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants	5 Participants	12 Participants	1 Participants	2 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	5 Participants	36 Participants	97 Participants	19 Participants	37 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	1 Participants	0 Participants	1 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants	1 Participants	2 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	10 Participants	26 Participants	5 Participants	11 Participants
Race (NIH/OMB) Black or African American	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	8 Participants	30 Participants	82 Participants	15 Participants	29 Participants
Region of Enrollment Belgium	0 Participants	2 Participants	2 Participants	0 Participants	0 Participants
Region of Enrollment Germany	1 Participants	3 Participants	7 Participants	1 Participants	2 Participants
Region of Enrollment Korea, South	0 Participants	9 Participants	25 Participants	5 Participants	11 Participants
Region of Enrollment Poland	3 Participants	18 Participants	37 Participants	7 Participants	9 Participants
Region of Enrollment Russian Federation	0 Participants	0 Participants	9 Participants	2 Participants	7 Participants
Region of Enrollment Spain	4 Participants	7 Participants	14 Participants	0 Participants	3 Participants
Region of Enrollment Ukraine	0 Participants	0 Participants	7 Participants	2 Participants	5 Participants
Region of Enrollment United States	1 Participants	2 Participants	9 Participants	3 Participants	3 Participants
Sex: Female, Male Female	5 Participants	23 Participants	50 Participants	5 Participants	17 Participants
Sex: Female, Male Male	4 Participants	18 Participants	60 Participants	15 Participants	23 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk	EG005 affected / at risk	EG006 affected / at risk	EG007 affected / at risk
deaths Total, all-cause mortality	0 / 20	0 / 40	0 / 9	0 / 41	0 / 12	0 / 23	0 / 7	0 / 31
other Total, other adverse events	7 / 20	16 / 40	7 / 9	19 / 41	6 / 12	12 / 23	6 / 7	12 / 31
serious Total, serious adverse events	0 / 20	1 / 40	1 / 9	2 / 41	0 / 12	5 / 23	0 / 7	1 / 31

Outcome results

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.

Time frame: From DB period Day 1 up to Day 85

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

Arm	Measure	Value (MEDIAN)
DB: Cohort 1: Placebo	Cohort 1 and 2: Time to Baseline Monthly Seizure Count up to the End of the 12-week Double-blind (DB) Treatment Period	32 Days
DB: Cohort 1: JNJ-40411813	Cohort 1 and 2: Time to Baseline Monthly Seizure Count up to the End of the 12-week Double-blind (DB) Treatment Period	34 Days
DB: Cohort 2: Placebo	Cohort 1 and 2: Time to Baseline Monthly Seizure Count up to the End of the 12-week Double-blind (DB) Treatment Period	29 Days
DB: Cohort 2: JNJ-40411813	Cohort 1 and 2: Time to Baseline Monthly Seizure Count up to the End of the 12-week Double-blind (DB) Treatment Period	38 Days

p-value: 0.357195% CI: [0.41, 1.38]t-test, 1 sided

p-value: 0.630695% CI: [0.4, 1.75]t-test, 1 sided

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.

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

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

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
DB: Cohort 1: Placebo	Cohort 1 and 2: Number of Participants With at Least 50 Percent (%) Reduction (Response) in the OLE Monthly Seizure Count	5 Participants
DB: Cohort 1: JNJ-40411813	Cohort 1 and 2: Number of Participants With at Least 50 Percent (%) Reduction (Response) in the OLE Monthly Seizure Count	11 Participants
DB: Cohort 2: Placebo	Cohort 1 and 2: Number of Participants With at Least 50 Percent (%) Reduction (Response) in the OLE Monthly Seizure Count	3 Participants
DB: Cohort 2: JNJ-40411813	Cohort 1 and 2: Number of Participants With at Least 50 Percent (%) Reduction (Response) in the OLE Monthly Seizure Count	16 Participants

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.

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

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

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
DB: Cohort 1: Placebo	Cohort 1 and 2: Number of Participants With Seizure Freedom at the End of OLE Period	1 Participants
DB: Cohort 1: JNJ-40411813	Cohort 1 and 2: Number of Participants With Seizure Freedom at the End of OLE Period	0 Participants
DB: Cohort 2: Placebo	Cohort 1 and 2: Number of Participants With Seizure Freedom at the End of OLE Period	0 Participants
DB: Cohort 2: JNJ-40411813	Cohort 1 and 2: Number of Participants With Seizure Freedom at the End of OLE Period	3 Participants

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.

Time frame: From DB period Day 1 up to Day 85

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

Arm	Measure	Value (NUMBER)
DB: Cohort 1: Placebo	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	15.0 Percentage of participants
DB: Cohort 1: JNJ-40411813	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	32.5 Percentage of participants
DB: Cohort 2: Placebo	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	22.2 Percentage of participants
DB: Cohort 2: JNJ-40411813	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	30.0 Percentage of participants

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.

Time frame: From DB period Day 1 up to Day 85

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

Arm	Measure	Value (NUMBER)
DB: Cohort 1: Placebo	Cohort 1 and 2: Percentage of Participants With Seizure Freedom During Double-blind Period	5.0 Percentage of participants
DB: Cohort 1: JNJ-40411813	Cohort 1 and 2: Percentage of Participants With Seizure Freedom During Double-blind Period	2.5 Percentage of participants
DB: Cohort 2: Placebo	Cohort 1 and 2: Percentage of Participants With Seizure Freedom During Double-blind Period	0.0 Percentage of participants
DB: Cohort 2: JNJ-40411813	Cohort 1 and 2: Percentage of Participants With Seizure Freedom During Double-blind Period	7.5 Percentage of participants

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.

Time frame: From DB period Day 1 up to Day 85

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

Arm	Measure	Value (MEDIAN)
DB: Cohort 1: Placebo	Cohort 1 and 2: Percent Reduction in the Double-blind Period Monthly Seizure Rate	23.0 Percent change (reduction)
DB: Cohort 1: JNJ-40411813	Cohort 1 and 2: Percent Reduction in the Double-blind Period Monthly Seizure Rate	16.2 Percent change (reduction)
DB: Cohort 2: Placebo	Cohort 1 and 2: Percent Reduction in the Double-blind Period Monthly Seizure Rate	10.1 Percent change (reduction)
DB: Cohort 2: JNJ-40411813	Cohort 1 and 2: Percent Reduction in the Double-blind Period Monthly Seizure Rate	30.1 Percent change (reduction)

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.

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

Population: 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.

Arm	Measure	Value (MEDIAN)
DB: Cohort 1: Placebo	Cohort 1 and 2: Percent Reduction in the Open Label Extension (OLE) Period Monthly Seizure Rate	39.9 Percent change (reduction)
DB: Cohort 1: JNJ-40411813	Cohort 1 and 2: Percent Reduction in the Open Label Extension (OLE) Period Monthly Seizure Rate	49.1 Percent change (reduction)
DB: Cohort 2: Placebo	Cohort 1 and 2: Percent Reduction in the Open Label Extension (OLE) Period Monthly Seizure Rate	29.1 Percent change (reduction)
DB: Cohort 2: JNJ-40411813	Cohort 1 and 2: Percent Reduction in the Open Label Extension (OLE) Period Monthly Seizure Rate	52.1 Percent change (reduction)

Secondary

DB Treatment 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.

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

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

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
DB: Cohort 1: Placebo	DB Treatment Period: Cohort 1 and 2: Number of Participants With Changes in Laboratory Assessments Recorded as TEAE	Chemistry	0 Participants
DB: Cohort 1: Placebo	DB Treatment Period: Cohort 1 and 2: Number of Participants With Changes in Laboratory Assessments Recorded as TEAE	Urinalysis	0 Participants
DB: Cohort 1: Placebo	DB Treatment Period: Cohort 1 and 2: Number of Participants With Changes in Laboratory Assessments Recorded as TEAE	Hematology	0 Participants
DB: Cohort 1: JNJ-40411813	DB Treatment Period: Cohort 1 and 2: Number of Participants With Changes in Laboratory Assessments Recorded as TEAE	Chemistry	1 Participants
DB: Cohort 1: JNJ-40411813	DB Treatment Period: Cohort 1 and 2: Number of Participants With Changes in Laboratory Assessments Recorded as TEAE	Urinalysis	0 Participants
DB: Cohort 1: JNJ-40411813	DB Treatment Period: Cohort 1 and 2: Number of Participants With Changes in Laboratory Assessments Recorded as TEAE	Hematology	0 Participants
DB: Cohort 2: Placebo	DB Treatment Period: Cohort 1 and 2: Number of Participants With Changes in Laboratory Assessments Recorded as TEAE	Hematology	0 Participants
DB: Cohort 2: Placebo	DB Treatment Period: Cohort 1 and 2: Number of Participants With Changes in Laboratory Assessments Recorded as TEAE	Chemistry	0 Participants
DB: Cohort 2: Placebo	DB Treatment Period: Cohort 1 and 2: Number of Participants With Changes in Laboratory Assessments Recorded as TEAE	Urinalysis	1 Participants
DB: Cohort 2: JNJ-40411813	DB Treatment Period: Cohort 1 and 2: Number of Participants With Changes in Laboratory Assessments Recorded as TEAE	Chemistry	1 Participants
DB: Cohort 2: JNJ-40411813	DB Treatment Period: Cohort 1 and 2: Number of Participants With Changes in Laboratory Assessments Recorded as TEAE	Urinalysis	0 Participants
DB: Cohort 2: JNJ-40411813	DB Treatment Period: Cohort 1 and 2: Number of Participants With Changes in Laboratory Assessments Recorded as TEAE	Hematology	1 Participants

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.

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

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

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
DB: Cohort 1: Placebo	DB Treatment Period: Cohort 1 and 2: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)	TEAEs	7 Participants
DB: Cohort 1: Placebo	DB Treatment Period: Cohort 1 and 2: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)	TESAEs	0 Participants
DB: Cohort 1: JNJ-40411813	DB Treatment Period: Cohort 1 and 2: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)	TESAEs	1 Participants
DB: Cohort 1: JNJ-40411813	DB Treatment Period: Cohort 1 and 2: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)	TEAEs	22 Participants
DB: Cohort 2: Placebo	DB Treatment Period: Cohort 1 and 2: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)	TEAEs	8 Participants
DB: Cohort 2: Placebo	DB Treatment Period: Cohort 1 and 2: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)	TESAEs	1 Participants
DB: Cohort 2: JNJ-40411813	DB Treatment Period: Cohort 1 and 2: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)	TEAEs	24 Participants
DB: Cohort 2: JNJ-40411813	DB Treatment Period: Cohort 1 and 2: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)	TESAEs	2 Participants

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.

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

Population: 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.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
DB: Cohort 1: Placebo	DB Treatment Period: Cohort 1 and 2: Number of Participants With Treatment-emergent Clinically Important Changes in Electrocardiogram (ECG)	PR Interval (<120 msec)	1 Participants
DB: Cohort 1: Placebo	DB Treatment Period: Cohort 1 and 2: Number of Participants With Treatment-emergent Clinically Important Changes in Electrocardiogram (ECG)	QTcF Interval (male) (>450 msec)	0 Participants
DB: Cohort 1: Placebo	DB Treatment Period: Cohort 1 and 2: Number of Participants With Treatment-emergent Clinically Important Changes in Electrocardiogram (ECG)	QTcB Interval (male) (>450 msec)	0 Participants
DB: Cohort 1: Placebo	DB Treatment Period: Cohort 1 and 2: Number of Participants With Treatment-emergent Clinically Important Changes in Electrocardiogram (ECG)	PR Interval (>200 msec)	0 Participants
DB: Cohort 1: Placebo	DB Treatment Period: Cohort 1 and 2: Number of Participants With Treatment-emergent Clinically Important Changes in Electrocardiogram (ECG)	Heart Rate >100 beats/min	0 Participants
DB: Cohort 1: Placebo	DB Treatment Period: Cohort 1 and 2: Number of Participants With Treatment-emergent Clinically Important Changes in Electrocardiogram (ECG)	QRS Duration (>120 msec)	0 Participants
DB: Cohort 1: Placebo	DB Treatment Period: Cohort 1 and 2: Number of Participants With Treatment-emergent Clinically Important Changes in Electrocardiogram (ECG)	QTcB Interval (Female) (>470 msec)	1 Participants
DB: Cohort 1: JNJ-40411813	DB Treatment Period: Cohort 1 and 2: Number of Participants With Treatment-emergent Clinically Important Changes in Electrocardiogram (ECG)	QTcF Interval (male) (>450 msec)	0 Participants
DB: Cohort 1: JNJ-40411813	DB Treatment Period: Cohort 1 and 2: Number of Participants With Treatment-emergent Clinically Important Changes in Electrocardiogram (ECG)	QTcB Interval (Female) (>470 msec)	0 Participants
DB: Cohort 1: JNJ-40411813	DB Treatment Period: Cohort 1 and 2: Number of Participants With Treatment-emergent Clinically Important Changes in Electrocardiogram (ECG)	QRS Duration (>120 msec)	2 Participants
DB: Cohort 1: JNJ-40411813	DB Treatment Period: Cohort 1 and 2: Number of Participants With Treatment-emergent Clinically Important Changes in Electrocardiogram (ECG)	QTcB Interval (male) (>450 msec)	1 Participants
DB: Cohort 1: JNJ-40411813	DB Treatment Period: Cohort 1 and 2: Number of Participants With Treatment-emergent Clinically Important Changes in Electrocardiogram (ECG)	Heart Rate >100 beats/min	0 Participants
DB: Cohort 1: JNJ-40411813	DB Treatment Period: Cohort 1 and 2: Number of Participants With Treatment-emergent Clinically Important Changes in Electrocardiogram (ECG)	PR Interval (>200 msec)	2 Participants
DB: Cohort 1: JNJ-40411813	DB Treatment Period: Cohort 1 and 2: Number of Participants With Treatment-emergent Clinically Important Changes in Electrocardiogram (ECG)	PR Interval (<120 msec)	2 Participants
DB: Cohort 2: Placebo	DB Treatment Period: Cohort 1 and 2: Number of Participants With Treatment-emergent Clinically Important Changes in Electrocardiogram (ECG)	QTcB Interval (Female) (>470 msec)	0 Participants
DB: Cohort 2: Placebo	DB Treatment Period: Cohort 1 and 2: Number of Participants With Treatment-emergent Clinically Important Changes in Electrocardiogram (ECG)	PR Interval (<120 msec)	0 Participants
DB: Cohort 2: Placebo	DB Treatment Period: Cohort 1 and 2: Number of Participants With Treatment-emergent Clinically Important Changes in Electrocardiogram (ECG)	PR Interval (>200 msec)	1 Participants
DB: Cohort 2: Placebo	DB Treatment Period: Cohort 1 and 2: Number of Participants With Treatment-emergent Clinically Important Changes in Electrocardiogram (ECG)	QRS Duration (>120 msec)	0 Participants
DB: Cohort 2: Placebo	DB Treatment Period: Cohort 1 and 2: Number of Participants With Treatment-emergent Clinically Important Changes in Electrocardiogram (ECG)	QTcB Interval (male) (>450 msec)	0 Participants
DB: Cohort 2: Placebo	DB Treatment Period: Cohort 1 and 2: Number of Participants With Treatment-emergent Clinically Important Changes in Electrocardiogram (ECG)	QTcF Interval (male) (>450 msec)	0 Participants
DB: Cohort 2: Placebo	DB Treatment Period: Cohort 1 and 2: Number of Participants With Treatment-emergent Clinically Important Changes in Electrocardiogram (ECG)	Heart Rate >100 beats/min	0 Participants
DB: Cohort 2: JNJ-40411813	DB Treatment Period: Cohort 1 and 2: Number of Participants With Treatment-emergent Clinically Important Changes in Electrocardiogram (ECG)	QRS Duration (>120 msec)	1 Participants
DB: Cohort 2: JNJ-40411813	DB Treatment Period: Cohort 1 and 2: Number of Participants With Treatment-emergent Clinically Important Changes in Electrocardiogram (ECG)	Heart Rate >100 beats/min	1 Participants
DB: Cohort 2: JNJ-40411813	DB Treatment Period: Cohort 1 and 2: Number of Participants With Treatment-emergent Clinically Important Changes in Electrocardiogram (ECG)	QTcF Interval (male) (>450 msec)	1 Participants
DB: Cohort 2: JNJ-40411813	DB Treatment Period: Cohort 1 and 2: Number of Participants With Treatment-emergent Clinically Important Changes in Electrocardiogram (ECG)	PR Interval (>200 msec)	2 Participants
DB: Cohort 2: JNJ-40411813	DB Treatment Period: Cohort 1 and 2: Number of Participants With Treatment-emergent Clinically Important Changes in Electrocardiogram (ECG)	PR Interval (<120 msec)	2 Participants
DB: Cohort 2: JNJ-40411813	DB Treatment Period: Cohort 1 and 2: Number of Participants With Treatment-emergent Clinically Important Changes in Electrocardiogram (ECG)	QTcB Interval (male) (>450 msec)	2 Participants
DB: Cohort 2: JNJ-40411813	DB Treatment Period: Cohort 1 and 2: Number of Participants With Treatment-emergent Clinically Important Changes in Electrocardiogram (ECG)	QTcB Interval (Female) (>470 msec)	0 Participants

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.

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

Population: 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.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
DB: Cohort 1: Placebo	DB Treatment Period: Cohort 1 and 2: Number of Participants With Treatment-emergent Clinically Important Changes in Vital Signs	DBP >90 mm Hg and with >30 mm Hg increase from BL	1 Participants
DB: Cohort 1: JNJ-40411813	DB Treatment Period: Cohort 1 and 2: Number of Participants With Treatment-emergent Clinically Important Changes in Vital Signs	PR >100 bpm, >30 bpm increase from BL	1 Participants
DB: Cohort 1: JNJ-40411813	DB Treatment Period: Cohort 1 and 2: Number of Participants With Treatment-emergent Clinically Important Changes in Vital Signs	SBP >140 mm Hg; with >40 mm Hg increase from BL	1 Participants
DB: Cohort 2: JNJ-40411813	DB Treatment Period: Cohort 1 and 2: Number of Participants With Treatment-emergent Clinically Important Changes in Vital Signs	PR >100 bpm, >30 bpm increase from BL	2 Participants

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.

Time frame: 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

Population: 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.

Arm	Measure	Group	Value (MEAN)	Dispersion
DB: Cohort 2: Placebo Non-induced	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Brivaracetam	Day 1: pre-dose	556 Nanograms per milliliter	—
DB: Cohort 2: Placebo Non-induced	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Brivaracetam	Day 29: 1 hour post-dose	3230 Nanograms per milliliter	—
DB: Cohort 2: Placebo Non-induced	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Brivaracetam	Day 29: pre-dose	750 Nanograms per milliliter	—
DB: Cohort 2: Placebo Non-induced	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Brivaracetam	Day 85: post-dose/EW	743 Nanograms per milliliter	—
DB: Cohort 2: Placebo Non-induced	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Brivaracetam	Day 1: 2 hours post-dose	2150 Nanograms per milliliter	—
DB: Cohort 2: Placebo Induced	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Brivaracetam	Day 57: pre-dose	1020 Nanograms per milliliter	—
DB: Cohort 2: Placebo Induced	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Brivaracetam	Day 1: 2 hours post-dose	2970 Nanograms per milliliter	—
DB: Cohort 2: Placebo Induced	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Brivaracetam	Day 85: post-dose/EW	3330 Nanograms per milliliter	—
DB: Cohort 2: Placebo Induced	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Brivaracetam	Day 29: pre-dose	991 Nanograms per milliliter	—
DB: Cohort 2: Placebo Induced	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Brivaracetam	Day 1: pre-dose	1040 Nanograms per milliliter	—
DB: Cohort 2: Placebo Induced	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Brivaracetam	Day 29: 1 hour post-dose	2950 Nanograms per milliliter	—
DB: Cohort 2: JNJ-40411813 Non-induced	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Brivaracetam	Day 85: post-dose/EW	2499 Nanograms per milliliter	Standard Deviation 2547
DB: Cohort 2: JNJ-40411813 Non-induced	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Brivaracetam	Day 1: 2 hours post-dose	2320 Nanograms per milliliter	—
DB: Cohort 2: JNJ-40411813 Non-induced	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Brivaracetam	Day 57: pre-dose	950 Nanograms per milliliter	Standard Deviation 284
DB: Cohort 2: JNJ-40411813 Non-induced	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Brivaracetam	Day 1: pre-dose	1604 Nanograms per milliliter	Standard Deviation 1394
DB: Cohort 2: JNJ-40411813 Non-induced	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Brivaracetam	Day 29: 1 hour post-dose	3930 Nanograms per milliliter	Standard Deviation 85
DB: Cohort 2: JNJ-40411813 Non-induced	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Brivaracetam	Day 29: pre-dose	2495 Nanograms per milliliter	Standard Deviation 1619
DB: Cohort 2: JNJ-40411813 Induced	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Brivaracetam	Day 85: post-dose/EW	1258 Nanograms per milliliter	Standard Deviation 1444
DB: Cohort 2: JNJ-40411813 Induced	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Brivaracetam	Day 1: pre-dose	838 Nanograms per milliliter	Standard Deviation 622
DB: Cohort 2: JNJ-40411813 Induced	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Brivaracetam	Day 1: 2 hours post-dose	2540 Nanograms per milliliter	Standard Deviation 1659
DB: Cohort 2: JNJ-40411813 Induced	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Brivaracetam	Day 29: pre-dose	734 Nanograms per milliliter	Standard Deviation 658
DB: Cohort 2: JNJ-40411813 Induced	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Brivaracetam	Day 29: 1 hour post-dose	2343 Nanograms per milliliter	Standard Deviation 1149
DB: Cohort 2: JNJ-40411813 Induced	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Brivaracetam	Day 57: pre-dose	709 Nanograms per milliliter	Standard Deviation 719

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.

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

Population: 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.

Arm	Measure	Group	Value (MEAN)	Dispersion
DB: Cohort 1: JNJ-40411813	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Carbamazepine	Day 29: pre-dose	8270 Nanograms per milliliter	Standard Deviation 1481
DB: Cohort 1: JNJ-40411813	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Carbamazepine	Day 1: pre-dose	7618 Nanograms per milliliter	Standard Deviation 3305
DB: Cohort 1: JNJ-40411813	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Carbamazepine	Day 57: pre-dose	7943 Nanograms per milliliter	Standard Deviation 1975
DB: Cohort 2: JNJ-40411813	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Carbamazepine	Day 1: pre-dose	5071 Nanograms per milliliter	Standard Deviation 3773
DB: Cohort 2: JNJ-40411813	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Carbamazepine	Day 29: pre-dose	4713 Nanograms per milliliter	Standard Deviation 4198
DB: Cohort 2: JNJ-40411813	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Carbamazepine	Day 57: pre-dose	4526 Nanograms per milliliter	Standard Deviation 2765
DB: Cohort 2: Placebo Induced	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Carbamazepine	Day 1: pre-dose	7450 Nanograms per milliliter	Standard Deviation 1966
DB: Cohort 2: Placebo Induced	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Carbamazepine	Day 57: pre-dose	6390 Nanograms per milliliter	—
DB: Cohort 2: Placebo Induced	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Carbamazepine	Day 29: pre-dose	6990 Nanograms per milliliter	Standard Deviation 269
DB: Cohort 2: JNJ-40411813 Induced	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Carbamazepine	Day 29: pre-dose	6476 Nanograms per milliliter	Standard Deviation 1895
DB: Cohort 2: JNJ-40411813 Induced	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Carbamazepine	Day 1: pre-dose	7431 Nanograms per milliliter	Standard Deviation 1214
DB: Cohort 2: JNJ-40411813 Induced	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Carbamazepine	Day 57: pre-dose	5573 Nanograms per milliliter	Standard Deviation 915

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.

Time frame: 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

Population: 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.

Arm	Measure	Group	Value (MEAN)	Dispersion
DB: Cohort 1: Placebo	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Levetiracetam	Day 85: post-dose/EW	19834 Nanograms per milliliter	Standard Deviation 19271
DB: Cohort 1: Placebo	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Levetiracetam	Day 1: pre-dose	9443 Nanograms per milliliter	Standard Deviation 7244
DB: Cohort 1: Placebo	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Levetiracetam	Day 1: 2 hours post-dose	28926 Nanograms per milliliter	Standard Deviation 16762
DB: Cohort 1: Placebo	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Levetiracetam	Day 29: pre-dose	12420 Nanograms per milliliter	Standard Deviation 9133
DB: Cohort 1: Placebo	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Levetiracetam	Day 57: pre-dose	14066 Nanograms per milliliter	Standard Deviation 11366
DB: Cohort 1: Placebo	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Levetiracetam	Day 29: 1 hour post-dose	27510 Nanograms per milliliter	Standard Deviation 24608
DB: Cohort 1: JNJ-40411813	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Levetiracetam	Day 29: pre-dose	16546 Nanograms per milliliter	Standard Deviation 13963
DB: Cohort 1: JNJ-40411813	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Levetiracetam	Day 1: pre-dose	9664 Nanograms per milliliter	Standard Deviation 4210
DB: Cohort 1: JNJ-40411813	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Levetiracetam	Day 29: 1 hour post-dose	30999 Nanograms per milliliter	Standard Deviation 15392
DB: Cohort 1: JNJ-40411813	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Levetiracetam	Day 85: post-dose/EW	19671 Nanograms per milliliter	Standard Deviation 14617
DB: Cohort 1: JNJ-40411813	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Levetiracetam	Day 1: 2 hours post-dose	28859 Nanograms per milliliter	Standard Deviation 15629
DB: Cohort 1: JNJ-40411813	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Levetiracetam	Day 57: pre-dose	12992 Nanograms per milliliter	Standard Deviation 8088
DB: Cohort 2: Placebo	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Levetiracetam	Day 57: pre-dose	12927 Nanograms per milliliter	Standard Deviation 6140
DB: Cohort 2: Placebo	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Levetiracetam	Day 29: pre-dose	17583 Nanograms per milliliter	Standard Deviation 11268
DB: Cohort 2: Placebo	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Levetiracetam	Day 1: 2 hours post-dose	29782 Nanograms per milliliter	Standard Deviation 19304
DB: Cohort 2: Placebo	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Levetiracetam	Day 29: 1 hour post-dose	28709 Nanograms per milliliter	Standard Deviation 14885
DB: Cohort 2: Placebo	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Levetiracetam	Day 85: post-dose/EW	23461 Nanograms per milliliter	Standard Deviation 20193
DB: Cohort 2: Placebo	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Levetiracetam	Day 1: pre-dose	12719 Nanograms per milliliter	Standard Deviation 8734
DB: Cohort 2: JNJ-40411813	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Levetiracetam	Day 57: pre-dose	10403 Nanograms per milliliter	Standard Deviation 8785
DB: Cohort 2: JNJ-40411813	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Levetiracetam	Day 1: pre-dose	10836 Nanograms per milliliter	Standard Deviation 7328
DB: Cohort 2: JNJ-40411813	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Levetiracetam	Day 1: 2 hours post-dose	21593 Nanograms per milliliter	Standard Deviation 13973
DB: Cohort 2: JNJ-40411813	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Levetiracetam	Day 29: pre-dose	8926 Nanograms per milliliter	Standard Deviation 6665
DB: Cohort 2: JNJ-40411813	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Levetiracetam	Day 29: 1 hour post-dose	24383 Nanograms per milliliter	Standard Deviation 23858
DB: Cohort 2: JNJ-40411813	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Levetiracetam	Day 85: post-dose/EW	15451 Nanograms per milliliter	Standard Deviation 12004
DB: Cohort 2: Placebo Non-induced	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Levetiracetam	Day 57: pre-dose	9680 Nanograms per milliliter	Standard Deviation 10493
DB: Cohort 2: Placebo Non-induced	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Levetiracetam	Day 1: 2 hours post-dose	35450 Nanograms per milliliter	Standard Deviation 2475
DB: Cohort 2: Placebo Non-induced	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Levetiracetam	Day 85: post-dose/EW	40000 Nanograms per milliliter	Standard Deviation 2970
DB: Cohort 2: Placebo Non-induced	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Levetiracetam	Day 1: pre-dose	28950 Nanograms per milliliter	Standard Deviation 17748
DB: Cohort 2: Placebo Non-induced	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Levetiracetam	Day 29: 1 hour post-dose	28050 Nanograms per milliliter	Standard Deviation 18031
DB: Cohort 2: Placebo Non-induced	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Levetiracetam	Day 29: pre-dose	14400 Nanograms per milliliter	—
DB: Cohort 2: Placebo Induced	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Levetiracetam	Day 29: pre-dose	7137 Nanograms per milliliter	Standard Deviation 247
DB: Cohort 2: Placebo Induced	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Levetiracetam	Day 29: 1 hour post-dose	27950 Nanograms per milliliter	Standard Deviation 3041
DB: Cohort 2: Placebo Induced	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Levetiracetam	Day 1: 2 hours post-dose	27300 Nanograms per milliliter	Standard Deviation 11876
DB: Cohort 2: Placebo Induced	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Levetiracetam	Day 57: pre-dose	23900 Nanograms per milliliter	Standard Deviation 18950
DB: Cohort 2: Placebo Induced	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Levetiracetam	Day 1: pre-dose	23190 Nanograms per milliliter	Standard Deviation 26095
DB: Cohort 2: Placebo Induced	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Levetiracetam	Day 85: post-dose/EW	22950 Nanograms per milliliter	Standard Deviation 17466
DB: Cohort 2: JNJ-40411813 Non-induced	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Levetiracetam	Day 29: 1 hour post-dose	22102 Nanograms per milliliter	Standard Deviation 14695
DB: Cohort 2: JNJ-40411813 Non-induced	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Levetiracetam	Day 57: pre-dose	18090 Nanograms per milliliter	Standard Deviation 11580
DB: Cohort 2: JNJ-40411813 Non-induced	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Levetiracetam	Day 1: pre-dose	18844 Nanograms per milliliter	Standard Deviation 16282
DB: Cohort 2: JNJ-40411813 Non-induced	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Levetiracetam	Day 29: pre-dose	17369 Nanograms per milliliter	Standard Deviation 11404
DB: Cohort 2: JNJ-40411813 Non-induced	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Levetiracetam	Day 85: post-dose/EW	20680 Nanograms per milliliter	Standard Deviation 15826
DB: Cohort 2: JNJ-40411813 Non-induced	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Levetiracetam	Day 1: 2 hours post-dose	24638 Nanograms per milliliter	Standard Deviation 13687
DB: Cohort 2: JNJ-40411813 Induced	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Levetiracetam	Day 29: 1 hour post-dose	30887 Nanograms per milliliter	Standard Deviation 16987
DB: Cohort 2: JNJ-40411813 Induced	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Levetiracetam	Day 29: pre-dose	7651 Nanograms per milliliter	Standard Deviation 5505
DB: Cohort 2: JNJ-40411813 Induced	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Levetiracetam	Day 85: post-dose/EW	16053 Nanograms per milliliter	Standard Deviation 22950
DB: Cohort 2: JNJ-40411813 Induced	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Levetiracetam	Day 57: pre-dose	6786 Nanograms per milliliter	Standard Deviation 8500
DB: Cohort 2: JNJ-40411813 Induced	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Levetiracetam	Day 1: pre-dose	11648 Nanograms per milliliter	Standard Deviation 11371
DB: Cohort 2: JNJ-40411813 Induced	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Levetiracetam	Day 1: 2 hours post-dose	22894 Nanograms per milliliter	Standard Deviation 13656

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.

Time frame: 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)

Population: 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).

Arm	Measure	Group	Value (MEAN)	Dispersion
DB: Cohort 1: Placebo	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M47: Day 1: 2 hours post-dose	25.8 Nanograms per milliliter	Standard Deviation 14
DB: Cohort 1: Placebo	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M45: Day 29: pre-dose	107 Nanograms per milliliter	Standard Deviation 60.1
DB: Cohort 1: Placebo	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	JNJ: Day 57: pre-dose	276 Nanograms per milliliter	Standard Deviation 205
DB: Cohort 1: Placebo	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M45: Day 85: post-dose/EW	101 Nanograms per milliliter	Standard Deviation 57.9
DB: Cohort 1: Placebo	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M45: Day 29: 1 hour post-dose	106 Nanograms per milliliter	Standard Deviation 54.8
DB: Cohort 1: Placebo	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	JNJ: Day 1: 2 hours post-dose	228 Nanograms per milliliter	Standard Deviation 116
DB: Cohort 1: Placebo	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M45: Day 57: pre-dose	103 Nanograms per milliliter	Standard Deviation 55.7
DB: Cohort 1: Placebo	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	JNJ: Day 29: pre-dose	272 Nanograms per milliliter	Standard Deviation 178
DB: Cohort 1: Placebo	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M47: Day 57: pre-dose	53.3 Nanograms per milliliter	Standard Deviation 47.5
DB: Cohort 1: Placebo	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	JNJ: Day 85:post-dose/EW	354 Nanograms per milliliter	Standard Deviation 385
DB: Cohort 1: Placebo	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M30: Day 1: 2 hours post-dose	20.8 Nanograms per milliliter	Standard Deviation 11.7
DB: Cohort 1: Placebo	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M47: Day 29: 1 hour post-dose	53.5 Nanograms per milliliter	Standard Deviation 30.5
DB: Cohort 1: Placebo	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M30: Day 29: pre-dose	326 Nanograms per milliliter	Standard Deviation 116
DB: Cohort 1: Placebo	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M47: Day 85: post-dose/EW	52.9 Nanograms per milliliter	Standard Deviation 58.8
DB: Cohort 1: Placebo	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M30: Day 29: 1 hour post-dose	295 Nanograms per milliliter	Standard Deviation 108
DB: Cohort 1: Placebo	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	JNJ: Day 29: 1 hour post-dose	403 Nanograms per milliliter	Standard Deviation 285
DB: Cohort 1: Placebo	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M47: Day 29: pre-dose	51.9 Nanograms per milliliter	Standard Deviation 36.1
DB: Cohort 1: Placebo	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M30: Day 57: pre-dose	291 Nanograms per milliliter	Standard Deviation 150
DB: Cohort 1: Placebo	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M30: Day 85:post-dose/EW	299 Nanograms per milliliter	Standard Deviation 123
DB: Cohort 1: Placebo	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M45: Day 1: 2 hours post-dose	58.9 Nanograms per milliliter	Standard Deviation 24.2
DB: Cohort 1: JNJ-40411813	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M47: Day 1: 2 hours post-dose	34.7 Nanograms per milliliter	Standard Deviation 19.7
DB: Cohort 1: JNJ-40411813	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M45: Day 1: 2 hours post-dose	49.8 Nanograms per milliliter	Standard Deviation 31
DB: Cohort 1: JNJ-40411813	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M47: Day 57: pre-dose	61.7 Nanograms per milliliter	Standard Deviation 26.2
DB: Cohort 1: JNJ-40411813	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M45: Day 85: post-dose/EW	62.3 Nanograms per milliliter	Standard Deviation 41.6
DB: Cohort 1: JNJ-40411813	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M30: Day 1: 2 hours post-dose	21.5 Nanograms per milliliter	Standard Deviation 15.5
DB: Cohort 1: JNJ-40411813	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M45: Day 29: pre-dose	65.4 Nanograms per milliliter	Standard Deviation 45.7
DB: Cohort 1: JNJ-40411813	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	JNJ: Day 1: 2 hours post-dose	268 Nanograms per milliliter	Standard Deviation 139
DB: Cohort 1: JNJ-40411813	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M47: Day 85: post-dose/EW	60.2 Nanograms per milliliter	Standard Deviation 37.8
DB: Cohort 1: JNJ-40411813	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M30: Day 85:post-dose/EW	191 Nanograms per milliliter	Standard Deviation 122
DB: Cohort 1: JNJ-40411813	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M45: Day 29: 1 hour post-dose	68.9 Nanograms per milliliter	Standard Deviation 36.3
DB: Cohort 1: JNJ-40411813	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M30: Day 29: pre-dose	232 Nanograms per milliliter	Standard Deviation 109
DB: Cohort 1: JNJ-40411813	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M45: Day 57: pre-dose	63.6 Nanograms per milliliter	Standard Deviation 42.9
DB: Cohort 1: JNJ-40411813	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M30: Day 57: pre-dose	219 Nanograms per milliliter	Standard Deviation 108
DB: Cohort 1: JNJ-40411813	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	JNJ: Day 57: pre-dose	360 Nanograms per milliliter	Standard Deviation 187
DB: Cohort 1: JNJ-40411813	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M47: Day 29: pre-dose	63.7 Nanograms per milliliter	Standard Deviation 31.7
DB: Cohort 1: JNJ-40411813	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	JNJ: Day 29: 1 hour post-dose	560 Nanograms per milliliter	Standard Deviation 281
DB: Cohort 1: JNJ-40411813	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M30: Day 29: 1 hour post-dose	211 Nanograms per milliliter	Standard Deviation 105
DB: Cohort 1: JNJ-40411813	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	JNJ: Day 85:post-dose/EW	440 Nanograms per milliliter	Standard Deviation 343
DB: Cohort 1: JNJ-40411813	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	JNJ: Day 29: pre-dose	356 Nanograms per milliliter	Standard Deviation 192
DB: Cohort 1: JNJ-40411813	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M47: Day 29: 1 hour post-dose	69.7 Nanograms per milliliter	Standard Deviation 29.2
DB: Cohort 2: Placebo	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M45: Day 29: 1 hour post-dose	115 Nanograms per milliliter	Standard Deviation 56
DB: Cohort 2: Placebo	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	JNJ: Day 1: 2 hours post-dose	212 Nanograms per milliliter	Standard Deviation 113
DB: Cohort 2: Placebo	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	JNJ: Day 29: pre-dose	506 Nanograms per milliliter	Standard Deviation 283
DB: Cohort 2: Placebo	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	JNJ: Day 29: 1 hour post-dose	633 Nanograms per milliliter	Standard Deviation 289
DB: Cohort 2: Placebo	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	JNJ: Day 57: pre-dose	516 Nanograms per milliliter	Standard Deviation 216
DB: Cohort 2: Placebo	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	JNJ: Day 85:post-dose/EW	515 Nanograms per milliliter	Standard Deviation 267
DB: Cohort 2: Placebo	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M30: Day 1: 2 hours post-dose	12.6 Nanograms per milliliter	Standard Deviation 8.85
DB: Cohort 2: Placebo	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M30: Day 29: pre-dose	294 Nanograms per milliliter	Standard Deviation 119
DB: Cohort 2: Placebo	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M30: Day 29: 1 hour post-dose	275 Nanograms per milliliter	Standard Deviation 119
DB: Cohort 2: Placebo	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M30: Day 57: pre-dose	289 Nanograms per milliliter	Standard Deviation 135
DB: Cohort 2: Placebo	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M30: Day 85:post-dose/EW	248 Nanograms per milliliter	Standard Deviation 121
DB: Cohort 2: Placebo	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M45: Day 1: 2 hours post-dose	45.1 Nanograms per milliliter	Standard Deviation 21.6
DB: Cohort 2: Placebo	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M45: Day 29: pre-dose	122 Nanograms per milliliter	Standard Deviation 64.9
DB: Cohort 2: Placebo	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M45: Day 57: pre-dose	113 Nanograms per milliliter	Standard Deviation 56.8
DB: Cohort 2: Placebo	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M45: Day 85: post-dose/EW	113 Nanograms per milliliter	Standard Deviation 64.2
DB: Cohort 2: Placebo	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M47: Day 1: 2 hours post-dose	19.4 Nanograms per milliliter	Standard Deviation 10.5
DB: Cohort 2: Placebo	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M47: Day 29: pre-dose	81.6 Nanograms per milliliter	Standard Deviation 41.5
DB: Cohort 2: Placebo	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M47: Day 29: 1 hour post-dose	77.3 Nanograms per milliliter	Standard Deviation 36.4
DB: Cohort 2: Placebo	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M47: Day 57: pre-dose	84.0 Nanograms per milliliter	Standard Deviation 41.7
DB: Cohort 2: Placebo	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M47: Day 85: post-dose/EW	97.4 Nanograms per milliliter	Standard Deviation 27.8
DB: Cohort 2: JNJ-40411813	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M30: Day 85:post-dose/EW	274 Nanograms per milliliter	Standard Deviation 93.7
DB: Cohort 2: JNJ-40411813	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M30: Day 57: pre-dose	277 Nanograms per milliliter	Standard Deviation 111
DB: Cohort 2: JNJ-40411813	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M47: Day 57: pre-dose	94.3 Nanograms per milliliter	Standard Deviation 30.1
DB: Cohort 2: JNJ-40411813	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M47: Day 1: 2 hours post-dose	36.8 Nanograms per milliliter	Standard Deviation 20.3
DB: Cohort 2: JNJ-40411813	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M30: Day 29: 1 hour post-dose	220 Nanograms per milliliter	Standard Deviation 116
DB: Cohort 2: JNJ-40411813	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M30: Day 29: pre-dose	239 Nanograms per milliliter	Standard Deviation 100
DB: Cohort 2: JNJ-40411813	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	JNJ: Day 29: pre-dose	797 Nanograms per milliliter	Standard Deviation 412
DB: Cohort 2: JNJ-40411813	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M47: Day 29: pre-dose	93.8 Nanograms per milliliter	Standard Deviation 42.9
DB: Cohort 2: JNJ-40411813	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M30: Day 1: 2 hours post-dose	24.8 Nanograms per milliliter	Standard Deviation 20.4
DB: Cohort 2: JNJ-40411813	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	JNJ: Day 85:post-dose/EW	785 Nanograms per milliliter	Standard Deviation 394
DB: Cohort 2: JNJ-40411813	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	JNJ: Day 1: 2 hours post-dose	379 Nanograms per milliliter	Standard Deviation 192
DB: Cohort 2: JNJ-40411813	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M47: Day 29: 1 hour post-dose	90.1 Nanograms per milliliter	Standard Deviation 45.3
DB: Cohort 2: JNJ-40411813	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	JNJ: Day 57: pre-dose	687 Nanograms per milliliter	Standard Deviation 248
DB: Cohort 2: JNJ-40411813	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M45: Day 29: 1 hour post-dose	74.5 Nanograms per milliliter	Standard Deviation 28.4
DB: Cohort 2: JNJ-40411813	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	JNJ: Day 29: 1 hour post-dose	958 Nanograms per milliliter	Standard Deviation 465
DB: Cohort 2: JNJ-40411813	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M45: Day 57: pre-dose	76.0 Nanograms per milliliter	Standard Deviation 32.1
DB: Cohort 2: JNJ-40411813	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M45: Day 29: pre-dose	76.3 Nanograms per milliliter	Standard Deviation 35.2
DB: Cohort 2: JNJ-40411813	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M45: Day 1: 2 hours post-dose	52.5 Nanograms per milliliter	Standard Deviation 22.5
DB: Cohort 2: JNJ-40411813	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M47: Day 85: post-dose/EW	100 Nanograms per milliliter	Standard Deviation 39.9
DB: Cohort 2: JNJ-40411813	DB Treatment Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M45: Day 85: post-dose/EW	73.5 Nanograms per milliliter	Standard Deviation 40.1

Secondary

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

Time frame: 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)

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

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
DB: Cohort 1: Placebo	OLE Period: Cohort 1 and 2: Number of Participants With Changes in Laboratory Assessments Recorded as TEAE	Chemistry	2 Participants
DB: Cohort 1: Placebo	OLE Period: Cohort 1 and 2: Number of Participants With Changes in Laboratory Assessments Recorded as TEAE	Hematology	0 Participants
DB: Cohort 1: Placebo	OLE Period: Cohort 1 and 2: Number of Participants With Changes in Laboratory Assessments Recorded as TEAE	Urinalysis	0 Participants
DB: Cohort 1: JNJ-40411813	OLE Period: Cohort 1 and 2: Number of Participants With Changes in Laboratory Assessments Recorded as TEAE	Chemistry	4 Participants
DB: Cohort 1: JNJ-40411813	OLE Period: Cohort 1 and 2: Number of Participants With Changes in Laboratory Assessments Recorded as TEAE	Hematology	1 Participants
DB: Cohort 1: JNJ-40411813	OLE Period: Cohort 1 and 2: Number of Participants With Changes in Laboratory Assessments Recorded as TEAE	Urinalysis	2 Participants
DB: Cohort 2: Placebo	OLE Period: Cohort 1 and 2: Number of Participants With Changes in Laboratory Assessments Recorded as TEAE	Urinalysis	0 Participants
DB: Cohort 2: Placebo	OLE Period: Cohort 1 and 2: Number of Participants With Changes in Laboratory Assessments Recorded as TEAE	Chemistry	0 Participants
DB: Cohort 2: Placebo	OLE Period: Cohort 1 and 2: Number of Participants With Changes in Laboratory Assessments Recorded as TEAE	Hematology	0 Participants
DB: Cohort 2: JNJ-40411813	OLE Period: Cohort 1 and 2: Number of Participants With Changes in Laboratory Assessments Recorded as TEAE	Hematology	1 Participants
DB: Cohort 2: JNJ-40411813	OLE Period: Cohort 1 and 2: Number of Participants With Changes in Laboratory Assessments Recorded as TEAE	Urinalysis	0 Participants
DB: Cohort 2: JNJ-40411813	OLE Period: Cohort 1 and 2: Number of Participants With Changes in Laboratory Assessments Recorded as TEAE	Chemistry	2 Participants

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.

Time frame: 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)

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

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
DB: Cohort 1: Placebo	OLE Period: Cohort 1 and 2: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)	TEAEs	6 Participants
DB: Cohort 1: Placebo	OLE Period: Cohort 1 and 2: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)	TESAEs	0 Participants
DB: Cohort 1: JNJ-40411813	OLE Period: Cohort 1 and 2: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)	TESAEs	5 Participants
DB: Cohort 1: JNJ-40411813	OLE Period: Cohort 1 and 2: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)	TEAEs	16 Participants
DB: Cohort 2: Placebo	OLE Period: Cohort 1 and 2: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)	TEAEs	6 Participants
DB: Cohort 2: Placebo	OLE Period: Cohort 1 and 2: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)	TESAEs	0 Participants
DB: Cohort 2: JNJ-40411813	OLE Period: Cohort 1 and 2: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)	TEAEs	17 Participants
DB: Cohort 2: JNJ-40411813	OLE Period: Cohort 1 and 2: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)	TESAEs	1 Participants

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.

Time frame: 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)

Population: 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.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
DB: Cohort 1: JNJ-40411813	OLE Period: Cohort 1 and 2: Number of Participants With Treatment-emergent (TE) Clinically Important Changes in Vital Signs	PR>100bpm with >30bpm increase from BL	1 Participants
DB: Cohort 1: JNJ-40411813	OLE Period: Cohort 1 and 2: Number of Participants With Treatment-emergent (TE) Clinically Important Changes in Vital Signs	SBP >140 mm Hg and with >40 mm Hg increase from BL	1 Participants
DB: Cohort 1: JNJ-40411813	OLE Period: Cohort 1 and 2: Number of Participants With Treatment-emergent (TE) Clinically Important Changes in Vital Signs	DBP >90 mm Hg, with >30 mm Hg increase from BL	1 Participants
DB: Cohort 2: JNJ-40411813	OLE Period: Cohort 1 and 2: Number of Participants With Treatment-emergent (TE) Clinically Important Changes in Vital Signs	PR>100bpm with >30bpm increase from BL	1 Participants

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.

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

Population: 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.

Arm	Measure	Group	Value (MEAN)	Dispersion
DB: Cohort 2: Placebo Induced	OLE Period: Cohort 1 and 2: Plasma Concentration of AED: Brivaracetam	OLE visit 2	1030 Nanograms per milliliter	—
DB: Cohort 2: Placebo Induced	OLE Period: Cohort 1 and 2: Plasma Concentration of AED: Brivaracetam	OLE visit 3	1010 Nanograms per milliliter	—
DB: Cohort 2: JNJ-40411813 Non-induced	OLE Period: Cohort 1 and 2: Plasma Concentration of AED: Brivaracetam	OLE visit 2	611 Nanograms per milliliter	—
DB: Cohort 2: JNJ-40411813 Induced	OLE Period: Cohort 1 and 2: Plasma Concentration of AED: Brivaracetam	OLE visit 2	834 Nanograms per milliliter	Standard Deviation 707
DB: Cohort 2: JNJ-40411813 Induced	OLE Period: Cohort 1 and 2: Plasma Concentration of AED: Brivaracetam	OLE visit 3	694 Nanograms per milliliter	Standard Deviation 746

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.

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

Arm	Measure	Group	Value (MEAN)	Dispersion
DB: Cohort 1: Placebo	OLE Period: Cohort 1 and 2: Plasma Concentration of AED: Levetiracetam	OLE visit 3	10400 Nanograms per milliliter	—
DB: Cohort 1: Placebo	OLE Period: Cohort 1 and 2: Plasma Concentration of AED: Levetiracetam	OLE visit 2	12980 Nanograms per milliliter	Standard Deviation 6817
DB: Cohort 1: JNJ-40411813	OLE Period: Cohort 1 and 2: Plasma Concentration of AED: Levetiracetam	OLE visit 3	8310 Nanograms per milliliter	Standard Deviation 3019
DB: Cohort 1: JNJ-40411813	OLE Period: Cohort 1 and 2: Plasma Concentration of AED: Levetiracetam	OLE visit 2	9752 Nanograms per milliliter	Standard Deviation 2937
DB: Cohort 2: Placebo	OLE Period: Cohort 1 and 2: Plasma Concentration of AED: Levetiracetam	OLE visit 3	15734 Nanograms per milliliter	Standard Deviation 7392
DB: Cohort 2: Placebo	OLE Period: Cohort 1 and 2: Plasma Concentration of AED: Levetiracetam	OLE visit 2	15787 Nanograms per milliliter	Standard Deviation 6029
DB: Cohort 2: JNJ-40411813	OLE Period: Cohort 1 and 2: Plasma Concentration of AED: Levetiracetam	OLE visit 3	10643 Nanograms per milliliter	Standard Deviation 7986
DB: Cohort 2: JNJ-40411813	OLE Period: Cohort 1 and 2: Plasma Concentration of AED: Levetiracetam	OLE visit 2	11719 Nanograms per milliliter	Standard Deviation 7661
DB: Cohort 2: Placebo Non-induced	OLE Period: Cohort 1 and 2: Plasma Concentration of AED: Levetiracetam	OLE visit 2	15000 Nanograms per milliliter	Standard Deviation 849
DB: Cohort 2: Placebo Non-induced	OLE Period: Cohort 1 and 2: Plasma Concentration of AED: Levetiracetam	OLE visit 3	12100 Nanograms per milliliter	Standard Deviation 1273
DB: Cohort 2: Placebo Induced	OLE Period: Cohort 1 and 2: Plasma Concentration of AED: Levetiracetam	OLE visit 2	7410 Nanograms per milliliter	—
DB: Cohort 2: Placebo Induced	OLE Period: Cohort 1 and 2: Plasma Concentration of AED: Levetiracetam	OLE visit 3	29100 Nanograms per milliliter	—
DB: Cohort 2: JNJ-40411813 Non-induced	OLE Period: Cohort 1 and 2: Plasma Concentration of AED: Levetiracetam	OLE visit 2	15406 Nanograms per milliliter	Standard Deviation 7870
DB: Cohort 2: JNJ-40411813 Non-induced	OLE Period: Cohort 1 and 2: Plasma Concentration of AED: Levetiracetam	OLE visit 3	13760 Nanograms per milliliter	Standard Deviation 4972
DB: Cohort 2: JNJ-40411813 Induced	OLE Period: Cohort 1 and 2: Plasma Concentration of AED: Levetiracetam	OLE visit 3	5068 Nanograms per milliliter	Standard Deviation 5040
DB: Cohort 2: JNJ-40411813 Induced	OLE Period: Cohort 1 and 2: Plasma Concentration of AED: Levetiracetam	OLE visit 2	11929 Nanograms per milliliter	Standard Deviation 13102

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.

Time frame: 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)

Population: 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.

Arm	Measure	Group	Value (MEAN)	Dispersion
DB: Cohort 1: Placebo	OLE Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M30: OLE visit 3	293 Nanograms per milliliter	Standard Deviation 135
DB: Cohort 1: Placebo	OLE Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	JNJ-40411813: OLE visit 4	311 Nanograms per milliliter	Standard Deviation 207
DB: Cohort 1: Placebo	OLE Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M45: OLE visit 4	81.1 Nanograms per milliliter	Standard Deviation 40.9
DB: Cohort 1: Placebo	OLE Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M45: OLE visit 3	93.8 Nanograms per milliliter	Standard Deviation 41.2
DB: Cohort 1: Placebo	OLE Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M30: OLE visit 4	265 Nanograms per milliliter	Standard Deviation 120
DB: Cohort 1: Placebo	OLE Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M47: OLE visit 7	70.3 Nanograms per milliliter	Standard Deviation 80.7
DB: Cohort 1: Placebo	OLE Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M45: OLE visit 2	85.3 Nanograms per milliliter	Standard Deviation 37.8
DB: Cohort 1: Placebo	OLE Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M30: OLE visit 7	364 Nanograms per milliliter	Standard Deviation 64.7
DB: Cohort 1: Placebo	OLE Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M30: OLE visit 5	301 Nanograms per milliliter	Standard Deviation 154
DB: Cohort 1: Placebo	OLE Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M47: OLE visit 4	59.1 Nanograms per milliliter	Standard Deviation 66
DB: Cohort 1: Placebo	OLE Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M30: OLE visit 6	286 Nanograms per milliliter	Standard Deviation 91.8
DB: Cohort 1: Placebo	OLE Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M47: OLE visit 3	52.8 Nanograms per milliliter	Standard Deviation 58.2
DB: Cohort 1: Placebo	OLE Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	JNJ-40411813: OLE visit 5	285 Nanograms per milliliter	Standard Deviation 241
DB: Cohort 1: Placebo	OLE Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	JNJ-40411813: OLE visit 3	280 Nanograms per milliliter	Standard Deviation 217
DB: Cohort 1: Placebo	OLE Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M47: OLE visit 2	59.3 Nanograms per milliliter	Standard Deviation 71
DB: Cohort 1: Placebo	OLE Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M45: OLE visit 7	71.8 Nanograms per milliliter	Standard Deviation 51.9
DB: Cohort 1: Placebo	OLE Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	JNJ-40411813: OLE visit 6	442 Nanograms per milliliter	Standard Deviation 493
DB: Cohort 1: Placebo	OLE Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	JNJ-40411813: OLE visit 2	272 Nanograms per milliliter	Standard Deviation 233
DB: Cohort 1: Placebo	OLE Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	JNJ-40411813: OLE visit 7	330 Nanograms per milliliter	Standard Deviation 252
DB: Cohort 1: Placebo	OLE Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M47: OLE visit 6	70.1 Nanograms per milliliter	Standard Deviation 90.8
DB: Cohort 1: Placebo	OLE Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M30: OLE visit 2	298 Nanograms per milliliter	Standard Deviation 91.3
DB: Cohort 1: Placebo	OLE Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M47: OLE visit 5	62.8 Nanograms per milliliter	Standard Deviation 79.1
DB: Cohort 1: Placebo	OLE Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M45: OLE visit 6	72.1 Nanograms per milliliter	Standard Deviation 49.8
DB: Cohort 1: Placebo	OLE Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M45: OLE visit 5	75.7 Nanograms per milliliter	Standard Deviation 45.2
DB: Cohort 1: JNJ-40411813	OLE Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M47: OLE visit 7	69.8 Nanograms per milliliter	Standard Deviation 30.4
DB: Cohort 1: JNJ-40411813	OLE Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	JNJ-40411813: OLE visit 2	372 Nanograms per milliliter	Standard Deviation 241
DB: Cohort 1: JNJ-40411813	OLE Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	JNJ-40411813: OLE visit 3	333 Nanograms per milliliter	Standard Deviation 157
DB: Cohort 1: JNJ-40411813	OLE Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	JNJ-40411813: OLE visit 4	392 Nanograms per milliliter	Standard Deviation 288
DB: Cohort 1: JNJ-40411813	OLE Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	JNJ-40411813: OLE visit 5	315 Nanograms per milliliter	Standard Deviation 197
DB: Cohort 1: JNJ-40411813	OLE Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	JNJ-40411813: OLE visit 6	349 Nanograms per milliliter	Standard Deviation 214
DB: Cohort 1: JNJ-40411813	OLE Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	JNJ-40411813: OLE visit 7	385 Nanograms per milliliter	Standard Deviation 269
DB: Cohort 1: JNJ-40411813	OLE Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M30: OLE visit 2	225 Nanograms per milliliter	Standard Deviation 136
DB: Cohort 1: JNJ-40411813	OLE Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M30: OLE visit 3	224 Nanograms per milliliter	Standard Deviation 172
DB: Cohort 1: JNJ-40411813	OLE Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M30: OLE visit 4	263 Nanograms per milliliter	Standard Deviation 161
DB: Cohort 1: JNJ-40411813	OLE Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M30: OLE visit 5	259 Nanograms per milliliter	Standard Deviation 169
DB: Cohort 1: JNJ-40411813	OLE Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M30: OLE visit 6	236 Nanograms per milliliter	Standard Deviation 141
DB: Cohort 1: JNJ-40411813	OLE Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M30: OLE visit 7	265 Nanograms per milliliter	Standard Deviation 115
DB: Cohort 1: JNJ-40411813	OLE Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M45: OLE visit 2	57.7 Nanograms per milliliter	Standard Deviation 29.2
DB: Cohort 1: JNJ-40411813	OLE Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M45: OLE visit 3	56.0 Nanograms per milliliter	Standard Deviation 28
DB: Cohort 1: JNJ-40411813	OLE Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M45: OLE visit 4	64.0 Nanograms per milliliter	Standard Deviation 32.4
DB: Cohort 1: JNJ-40411813	OLE Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M45: OLE visit 5	65.7 Nanograms per milliliter	Standard Deviation 38
DB: Cohort 1: JNJ-40411813	OLE Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M45: OLE visit 6	61.6 Nanograms per milliliter	Standard Deviation 41.9
DB: Cohort 1: JNJ-40411813	OLE Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M45: OLE visit 7	59.3 Nanograms per milliliter	Standard Deviation 28.4
DB: Cohort 1: JNJ-40411813	OLE Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M47: OLE visit 2	58.0 Nanograms per milliliter	Standard Deviation 31.4
DB: Cohort 1: JNJ-40411813	OLE Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M47: OLE visit 3	58.7 Nanograms per milliliter	Standard Deviation 24.5
DB: Cohort 1: JNJ-40411813	OLE Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M47: OLE visit 4	65.6 Nanograms per milliliter	Standard Deviation 34.1
DB: Cohort 1: JNJ-40411813	OLE Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M47: OLE visit 5	57.6 Nanograms per milliliter	Standard Deviation 25.1
DB: Cohort 1: JNJ-40411813	OLE Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M47: OLE visit 6	66.9 Nanograms per milliliter	Standard Deviation 44.9
DB: Cohort 2: Placebo	OLE Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M45: OLE visit 4	112 Nanograms per milliliter	Standard Deviation 77
DB: Cohort 2: Placebo	OLE Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	JNJ-40411813: OLE visit 3	515 Nanograms per milliliter	Standard Deviation 172
DB: Cohort 2: Placebo	OLE Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M47: OLE visit 3	81.7 Nanograms per milliliter	Standard Deviation 28.6
DB: Cohort 2: Placebo	OLE Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M47: OLE visit 5	78.0 Nanograms per milliliter	Standard Deviation 13.9
DB: Cohort 2: Placebo	OLE Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M30: OLE visit 5	349 Nanograms per milliliter	Standard Deviation 223
DB: Cohort 2: Placebo	OLE Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	JNJ-40411813: OLE visit 5	532 Nanograms per milliliter	Standard Deviation 105
DB: Cohort 2: Placebo	OLE Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M30: OLE visit 2	316 Nanograms per milliliter	Standard Deviation 129
DB: Cohort 2: Placebo	OLE Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	JNJ-40411813: OLE visit 4	539 Nanograms per milliliter	Standard Deviation 147
DB: Cohort 2: Placebo	OLE Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M30: OLE visit 4	333 Nanograms per milliliter	Standard Deviation 125
DB: Cohort 2: Placebo	OLE Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	JNJ-40411813: OLE visit 2	524 Nanograms per milliliter	Standard Deviation 149
DB: Cohort 2: Placebo	OLE Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M45: OLE visit 2	101 Nanograms per milliliter	Standard Deviation 34.9
DB: Cohort 2: Placebo	OLE Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M47: OLE visit 2	98.9 Nanograms per milliliter	Standard Deviation 34.6
DB: Cohort 2: Placebo	OLE Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M45: OLE visit 5	89.2 Nanograms per milliliter	Standard Deviation 9.69
DB: Cohort 2: Placebo	OLE Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M47: OLE visit 4	80.3 Nanograms per milliliter	Standard Deviation 12.4
DB: Cohort 2: Placebo	OLE Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M45: OLE visit 3	101 Nanograms per milliliter	Standard Deviation 54.5
DB: Cohort 2: Placebo	OLE Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M30: OLE visit 3	356 Nanograms per milliliter	Standard Deviation 113
DB: Cohort 2: JNJ-40411813	OLE Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M45: OLE visit 3	85.5 Nanograms per milliliter	Standard Deviation 29
DB: Cohort 2: JNJ-40411813	OLE Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M47: OLE visit 4	118 Nanograms per milliliter	Standard Deviation 47.1
DB: Cohort 2: JNJ-40411813	OLE Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M45: OLE visit 4	84.0 Nanograms per milliliter	Standard Deviation 30.7
DB: Cohort 2: JNJ-40411813	OLE Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M30: OLE visit 2	249 Nanograms per milliliter	Standard Deviation 94.9
DB: Cohort 2: JNJ-40411813	OLE Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	JNJ-40411813: OLE visit 3	993 Nanograms per milliliter	Standard Deviation 361
DB: Cohort 2: JNJ-40411813	OLE Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M45: OLE visit 5	91.7 Nanograms per milliliter	Standard Deviation 6.22
DB: Cohort 2: JNJ-40411813	OLE Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	JNJ-40411813: OLE visit 2	930 Nanograms per milliliter	Standard Deviation 370
DB: Cohort 2: JNJ-40411813	OLE Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	JNJ-40411813: OLE visit 5	1610 Nanograms per milliliter	Standard Deviation 255
DB: Cohort 2: JNJ-40411813	OLE Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M47: OLE visit 5	157 Nanograms per milliliter	Standard Deviation 58
DB: Cohort 2: JNJ-40411813	OLE Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M47: OLE visit 2	107 Nanograms per milliliter	Standard Deviation 30.8
DB: Cohort 2: JNJ-40411813	OLE Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	JNJ-40411813: OLE visit 4	921 Nanograms per milliliter	Standard Deviation 464
DB: Cohort 2: JNJ-40411813	OLE Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M30: OLE visit 5	274 Nanograms per milliliter	Standard Deviation 65.1
DB: Cohort 2: JNJ-40411813	OLE Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M47: OLE visit 3	122 Nanograms per milliliter	Standard Deviation 45.4
DB: Cohort 2: JNJ-40411813	OLE Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M30: OLE visit 4	251 Nanograms per milliliter	Standard Deviation 54.6
DB: Cohort 2: JNJ-40411813	OLE Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M45: OLE visit 2	87.4 Nanograms per milliliter	Standard Deviation 27.8
DB: Cohort 2: JNJ-40411813	OLE Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47	M30: OLE visit 3	234 Nanograms per milliliter	Standard Deviation 73.7

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.

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

Population: 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.

Arm	Measure	Group	Value (MEAN)	Dispersion
DB: Cohort 1: JNJ-40411813	OLE Period: Plasma Concentration of AED: Carbamazepine	OLE visit 2	5970 Nanograms per milliliter	—
DB: Cohort 1: JNJ-40411813	OLE Period: Plasma Concentration of AED: Carbamazepine	OLE visit 3	5780 Nanograms per milliliter	—
DB: Cohort 2: JNJ-40411813	OLE Period: Plasma Concentration of AED: Carbamazepine	OLE visit 2	3780 Nanograms per milliliter	Standard Deviation 2604
DB: Cohort 2: JNJ-40411813	OLE Period: Plasma Concentration of AED: Carbamazepine	OLE visit 3	5814 Nanograms per milliliter	Standard Deviation 4617
DB: Cohort 2: JNJ-40411813 Induced	OLE Period: Plasma Concentration of AED: Carbamazepine	OLE visit 2	6266 Nanograms per milliliter	Standard Deviation 1370
DB: Cohort 2: JNJ-40411813 Induced	OLE Period: Plasma Concentration of AED: Carbamazepine	OLE visit 3	6638 Nanograms per milliliter	Standard Deviation 1868

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026

A Study to Investigate JNJ-40411813 in Combination With Levetiracetam or Brivaracetam in Epilepsy

Conditions

Brief summary

Detailed description

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Recruitment details

Pre-assignment details

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

OLE Period: Plasma Concentration of AED: Carbamazepine