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Phase 2 Completed N=110 Randomized Double-blind Treatment

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

Focal Onset Seizures
Source: ClinicalTrials.gov NCT04836559 ↗
Enrolled (actual)
110
Serious AEs
5.5%
Results posted
Jul 2025
Primary outcomePrimary: Cohort 1 and 2: Time to Baseline Monthly Seizure Count up to the End of the 12-week Double-blind (DB) Treatment Period — 32; 34; 29; 38 Days — p=0.3571

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).

Outcome Measures

OutcomeResultp-value
PRIMARY
Cohort 1 and 2: Time to Baseline Monthly Seizure Count up to the End of the 12-week Double-blind (DB) Treatment Period
32; 34; 29; 38 0.3571
SECONDARY
Cohort 1 and 2: Percent Reduction in the Open Label Extension (OLE) Period Monthly Seizure Rate
39.9; 49.1; 29.1; 52.1
SECONDARY
Cohort 1 and 2: Number of Participants With Seizure Freedom at the End of OLE Period
1; 0; 0; 3
SECONDARY
Cohort 1 and 2: Number of Participants With at Least 50 Percent (%) Reduction (Response) in the OLE Monthly Seizure Count
5; 11; 3; 16
SECONDARY
OLE Period: Cohort 1 and 2: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
6; 16; 6; 17; 0; 5
SECONDARY
OLE Period: Cohort 1 and 2: Number of Participants With Treatment-emergent (TE) Clinically Important Changes in Vital Signs
1; 1; 1; 1
SECONDARY
OLE Period: Cohort 1 and 2: Number of Participants With Changes in Laboratory Assessments Recorded as TEAE
2; 4; 0; 2; 0; 1
SECONDARY
DB Treatment Period: Cohort 1 and 2: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
7; 22; 8; 24; 0; 1
SECONDARY
DB Treatment Period: Cohort 1 and 2: Number of Participants With Treatment-emergent Clinically Important Changes in Vital Signs
1; 2; 1; 1
SECONDARY
DB Treatment Period: Cohort 1 and 2: Number of Participants With Treatment-emergent Clinically Important Changes in Electrocardiogram (ECG)
1; 2; 0; 2; 0; 2
SECONDARY
DB Treatment Period: Cohort 1 and 2: Number of Participants With Changes in Laboratory Assessments Recorded as TEAE
0; 1; 0; 1; 0; 0
SECONDARY
Cohort 1 and 2: Percent Reduction in the Double-blind Period Monthly Seizure Rate
23.0; 16.2; 10.1; 30.1
SECONDARY
Cohort 1 and 2: Percentage of Participants With Seizure Freedom During Double-blind Period
5.0; 2.5; 0.0; 7.5
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
15.0; 32.5; 22.2; 30.0
SECONDARY
DB Treatment Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47
228; 268; 212; 379; 272; 356
SECONDARY
DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Levetiracetam
9443; 9664; 12719; 10836; 28950; 23190
SECONDARY
DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Brivaracetam
556; 1040; 1604; 838; 2150; 2970
SECONDARY
DB Treatment Period: Cohort 1 and 2: Plasma Concentration of AED: Carbamazepine
7618; 5071; 7450; 7431; 8270; 4713
SECONDARY
OLE Period: Cohort 1 and 2: Plasma Concentration of JNJ-40411813 and Its Metabolites: M30, M45 and M47
272; 372; 524; 930; 280; 333
SECONDARY
OLE Period: Cohort 1 and 2: Plasma Concentration of AED: Levetiracetam
12980; 9752; 15787; 11719; 15000; 7410
SECONDARY
OLE Period: Cohort 1 and 2: Plasma Concentration of AED: Brivaracetam
1030; 611; 834; 1010; 694
SECONDARY
OLE Period: Plasma Concentration of AED: Carbamazepine
5970; 3780; 6266; 5780; 5814; 6638

Eligibility Criteria

Inclusion Criteria

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

Exclusion Criteria

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

Data sourced from ClinicalTrials.gov (NCT04836559). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.

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