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The purpose of the study is to evaluate the safety and tolerability of perampanel administered as a 30-minute intravenous infusion after switching from oral tablets (8 to 12 milligrams per day [mg/day]) as an adjunctive therapy in participants with epilepsy with partial onset seizures (POS) (including secondarily generalized seizures) or primary generalized tonic-clonic (PGTC) seizures.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Perampanel | Experimental | Participants with POS with or without secondarily generalized seizures or PGTC seizures will receive perampanel 8 to 12 milligram (mg), tablets, orally, once daily for 28 days (Day -28 to Day -1) in Pretreatment Phase and followed by 8 to 12 mg dose of perampanel as intravenous infusion for 30 minutes, once daily from Day 1 to Day 4 in Treatment Phase, and then again 8 to 12 mg, tablets, orally, once daily from Day 5 to Day 11 in Follow-up Phase as an adjunctive therapy, along with 1 to a maximum of 3 marketed concomitant antiepileptic drugs (AEDs). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Perampanel | Drug | Oral tablets. |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Serious Adverse Events (SAEs) | A SAE 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. | Up to 60 days (Pretreatment Phase: up to 28 days, Treatment Phase: up to 4 days, Follow-up Phase: up to 28 days after last dose) |
| Number of Participants With Adverse Events (AEs) | An AE was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an investigational product, whether or not considered related to the investigational product, any new disease or exacerbation of an existing disease, any deterioration in nonprotocol-required measurements of a laboratory value or other clinical test that resulted in symptoms, a change in treatment, or discontinuation of study drug, recurrence of an intermittent medical condition not present pretreatment, an abnormal laboratory test result was considered an AE if the identified laboratory abnormality led to any type of intervention, withdrawal of study drug, or withholding of study drug, whether prescribed in the protocol or not. | Up to 60 days (Pretreatment Phase: up to 28 days, Treatment Phase: up to 4 days, Follow-up Phase: up to 28 days after last dose) |
| Number of Participants With Markedly Abnormal Clinical Laboratory Parameter Values During Treatment and Follow-up Phase | Up to Day 11 (Treatment Phase: at Day 4, Follow-up Phase: up to 7 days after last dose) | |
| Number of Participants With Abnormal Vital Sign Values During Treatment and Follow-up Phase | Up to 11 days (Treatment Phase: up to 4 days, Follow-up Phase: up to 7 days after the last dose) |
| Measure | Description | Time Frame |
|---|---|---|
| Mean Seizure Frequency Per Day in Pretreatment Phase, Treatment Phase and Follow-up Phase | Seizure frequency was based on number of seizures per day, calculated as the number of seizures over the entire time interval divided by the number of days in the interval. | Up to 39 days (Pretreatment Phase: up to 28 days; Treatment Phase: up to 4 days; Follow-up Phase: up to 7 days after the last dose) |
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Inclusion Criteria:
Exclusion Criteria:
A history of drug or alcohol dependency or abuse.
A history of status epilepticus.
Unsuitable for venipuncture and intravenous administration.
Requires medical intervention due to safety issues related to concomitant administration of AEDs.
A history of suicidal ideation/attempt.
Clinical symptoms or imaging suggest progressive central nervous system (CNS) abnormality, disorder, or brain tumor.
Current evidence of clinically significant disease (example, cardiac, respiratory, gastrointestinal, renal disease) that in the opinion of the investigators could affect the participant's safety, interfere with the study assessments or need prohibited medications as specified in the study protocol.
Clinically significant abnormal laboratory values.
Females of childbearing potential who:
In the Pretreatment Phase, are breastfeeding or pregnant (as documented by a positive beta-human chorionic gonadotropin [β-hCG] test).
Within 28 days before Visit 1, did not use a highly effective method of contraception, which includes any of the following:
Participation in a study involving administration of an investigational drug or device within 28 days before Visit 1, or within approximately 5 half-lives of the previous investigational compound, whichever is longer.
A prolonged QT interval corrected using Fridericia's formula (QTcF) interval (greater than [>] 450 millisecond [ms]) as demonstrated by a repeated ECG.
A vagus nerve stimulation (VNS) implanted.
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Eisai trial site 5 | Kurume | Fukuoka | Japan | |||
| Eisai trial site 12 |
Eisai's data sharing commitment and further information on how to request data can be found on our website http://eisaiclinicaltrials.com/.
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A total of 27 participants were consented, of which 6 were screen failures and 21 were enrolled and received the study treatment.
Participants took part in this study at 13 investigative sites in Japan from 27 November 2018 to 10 December 2019.
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| ID | Title | Description |
|---|---|---|
| FG000 | Pretreatment Phase: Oral Perampanel 8 to 12 mg/Day | Participants with partial onset-seizures (POS) with or without secondarily generalized seizures or primary generalized tonic clonic (PGTC) seizures received perampanel 8 milligram (mg) up to 12 mg (stable-dosage), tablets, orally, once daily for 28 days (Day -28 to Day -1) as an adjunctive therapy along with 1 to a maximum of 3 marketed concomitant antiepileptic drugs (AEDs). Eligible participants who completed Pretreatment Phase entered in Treatment Phase. |
| FG001 | Treatment Phase: Intravenous Perampanel 8 to 12 mg/Day | Participants with POS with or without secondarily generalized seizures or PGTC seizures were hospitalized and received perampanel 8 mg up to 12 mg (stable-dosage) equivalent to the oral dose, as intravenous infusion for 30 minutes, once daily on Day 1 to Day 4 as an adjunctive therapy along with 1 to a maximum of 3 marketed concomitant AEDs. Eligible participants who completed Treatment Phase entered Follow-up Phase. |
| FG002 | Follow-up Phase: Oral Perampanel 8 to 12 mg/Day | Participants with POS with or without secondarily generalized seizures or PGTC seizures received perampanel 8 mg up to 12 mg (stable-dosage), tablets, orally, once daily on Day 5 to Day 11 (Follow-up Visit) as an adjunctive therapy along with 1 to a maximum of 3 marketed concomitant AEDs. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Pretreatment Phase |
| |||||||||||||
| Treatment Phase |
| |||||||||||||
| Follow-up Phase |
|
All participants who received at least 1 dose of study drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | Perampanel 8 to 12 mg/Day | Participants with POS with or without secondarily generalized seizures or PGTC seizures received maintenance dose of perampanel 8 to 12 mg, tablets, orally, once daily for 28 days (Day -28 to Day -1) in Pretreatment Phase followed by 8 to 12 mg maintenance dose of perampanel equivalent to the oral dose, as intravenous infusion for 30 minutes, once daily from Day 1 to Day 4 in Treatment Phase, and then 8 to 12 mg maintenance dose of perampanel, tablets, orally, once daily from Day 5 to Day 11 (Follow-up Visit) in Follow-up Phase as an adjunctive therapy along with 1 to a maximum of 3 marketed concomitant AEDs. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With Serious Adverse Events (SAEs) | A SAE 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. | All participants who received at least 1 dose of study drug. | Posted | Count of Participants | Participants | Up to 60 days (Pretreatment Phase: up to 28 days, Treatment Phase: up to 4 days, Follow-up Phase: up to 28 days after last dose) |
|
Up to 60 days (Pretreatment Phase: up to 28 days, Treatment Phase: up to 4 days, Follow-up Phase: up to 28 days after the last dose)
All participants who received at least 1 dose of study drug.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Pretreatment Phase: Oral Perampanel 8 to 12 mg/Day | Participants with POS with or without secondarily generalized seizures or PGTC seizures received perampanel 8 mg up to 12 mg (stable-dosage), tablets, orally, once daily for 28 days (Day -28 to Day -1) as an adjunctive therapy along with 1 to a maximum of 3 marketed concomitant AEDs. Eligible participants who completed Pretreatment Phase entered in Treatment Phase. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hypoaesthesia | Nervous system disorders | MedDRA (22.1) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | MedDRA (22.1) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Eisai Medical Information | Eisai Co., Ltd. | +1-888-274-2378 | esi_medinfo@eisai.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Oct 9, 2018 | Dec 8, 2020 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Feb 14, 2020 | Dec 8, 2020 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D004827 | Epilepsy |
| D012640 | Seizures |
| ID | Term |
|---|---|
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D009461 | Neurologic Manifestations |
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| ID | Term |
|---|---|
| C551441 | perampanel |
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| Perampanel |
| Drug |
Intravenous infusion. |
|
|
| Number of Participants With Abnormal Body Weight During Treatment and Follow-up Phase | Up to 11 days (Treatment Phase: up to 4 days, Follow-up Phase: up to 7 days after the last dose) |
| Number of Participants With Clinically Significant Markedly Abnormal Electrocardiogram (ECG) Value During Treatment and Follow-up Phase | Up to Day 11 (Treatment Phase: at Day 4, Follow-up Phase: up to 7 days after the last dose) |
| Plasma Concentration of Perampanel Before and After Switching From Oral Perampanel to 30-minute Intravenous Infusions of Perampanel | Pretreatment Phase-Day -1: Pre-dose, 0.5 hours, 1 hours and 1.5 hours post-dose; Treatment Phase-Day 1, Day 2, Day 3 and Day 4: Pre-dose and 0.5 hours after start of intravenous infusions |
| Sapporo |
| Hokkaido |
| Japan |
| Eisai trial site 9 | Ōmura | Nagasaki | Japan |
| Eisai trial site 7 | Sayama | Osaka | Japan |
| Eisai trial site 2 | Asaka | Saitama | Japan |
| Eisai trial site 13 | Hamamatsu | Shizuoka | Japan |
| Eisai trial site 8 | Kodaira | Tokyo | Japan |
| Eisai trial site 10 | Hiroshima | Japan |
| Eisai trial site 6 | Kagoshima | Japan |
| Eisai trial site 1 | Niigata | Japan |
| Eisai trial site 11 | Okayama | Japan |
| Eisai trial site 3 | Shizuoka | Japan |
| Eisai trial site 4 | Yamagata | Japan |
| NOT COMPLETED |
|
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| NOT COMPLETED |
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|
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| OG001 | Treatment Phase: Intravenous Perampanel 8 to 12 mg/Day | Participants with POS with or without secondarily generalized seizures or PGTC seizures were hospitalized and received perampanel 8 mg up to 12 mg (stable-dosage) equivalent to the oral dose, as intravenous infusion for 30 minutes, once daily on Day 1 to Day 4 as an adjunctive therapy along with 1 to a maximum of 3 marketed concomitant AEDs. Eligible participants who completed Treatment Phase entered Follow-up Phase. |
| OG002 | Follow-up Phase: Oral Perampanel 8 to 12 mg/Day | Participants with POS with or without secondarily generalized seizures or PGTC seizures received perampanel 8 mg up to 12 mg (stable-dosage), tablets, orally, once daily on Day 5 to Day 11 (Follow-up Visit) as an adjunctive therapy along with 1 to a maximum of 3 marketed concomitant AEDs. |
|
|
| Primary | Number of Participants With Adverse Events (AEs) | An AE was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an investigational product, whether or not considered related to the investigational product, any new disease or exacerbation of an existing disease, any deterioration in nonprotocol-required measurements of a laboratory value or other clinical test that resulted in symptoms, a change in treatment, or discontinuation of study drug, recurrence of an intermittent medical condition not present pretreatment, an abnormal laboratory test result was considered an AE if the identified laboratory abnormality led to any type of intervention, withdrawal of study drug, or withholding of study drug, whether prescribed in the protocol or not. | All participants who received at least 1 dose of study drug. | Posted | Count of Participants | Participants | Up to 60 days (Pretreatment Phase: up to 28 days, Treatment Phase: up to 4 days, Follow-up Phase: up to 28 days after last dose) |
|
|
|
| Primary | Number of Participants With Markedly Abnormal Clinical Laboratory Parameter Values During Treatment and Follow-up Phase | All participants who received at least 1 dose of study drug. | Posted | Count of Participants | Participants | Up to Day 11 (Treatment Phase: at Day 4, Follow-up Phase: up to 7 days after last dose) |
|
|
|
| Primary | Number of Participants With Abnormal Vital Sign Values During Treatment and Follow-up Phase | All participants who received at least 1 dose of study drug. | Posted | Count of Participants | Participants | Up to 11 days (Treatment Phase: up to 4 days, Follow-up Phase: up to 7 days after the last dose) |
|
|
|
| Primary | Number of Participants With Abnormal Body Weight During Treatment and Follow-up Phase | All participants who received at least 1 dose of study drug. | Posted | Count of Participants | Participants | Up to 11 days (Treatment Phase: up to 4 days, Follow-up Phase: up to 7 days after the last dose) |
|
|
|
| Primary | Number of Participants With Clinically Significant Markedly Abnormal Electrocardiogram (ECG) Value During Treatment and Follow-up Phase | All participants who received at least 1 dose of study drug. | Posted | Count of Participants | Participants | Up to Day 11 (Treatment Phase: at Day 4, Follow-up Phase: up to 7 days after the last dose) |
|
|
|
| Secondary | Mean Seizure Frequency Per Day in Pretreatment Phase, Treatment Phase and Follow-up Phase | Seizure frequency was based on number of seizures per day, calculated as the number of seizures over the entire time interval divided by the number of days in the interval. | All participants who received at least 1 dose of study drug. Here "Number Analyzed" signifies participants who were evaluable for this outcome measure for POS and PGTC seizures. | Posted | Mean | Standard Deviation | seizures per day | Up to 39 days (Pretreatment Phase: up to 28 days; Treatment Phase: up to 4 days; Follow-up Phase: up to 7 days after the last dose) |
|
|
|
| Secondary | Plasma Concentration of Perampanel Before and After Switching From Oral Perampanel to 30-minute Intravenous Infusions of Perampanel | All participants who received at least 1 dose of study drug. Here "Number Analyzed" signifies participants who were evaluable for this outcome measure at given time points. | Posted | Mean | Standard Deviation | nanogram per milliliter (ng/mL) | Pretreatment Phase-Day -1: Pre-dose, 0.5 hours, 1 hours and 1.5 hours post-dose; Treatment Phase-Day 1, Day 2, Day 3 and Day 4: Pre-dose and 0.5 hours after start of intravenous infusions |
|
|
|
| 0 |
| 21 |
| 0 |
| 21 |
| 2 |
| 21 |
| EG001 | Treatment Phase: Intravenous Perampanel 8 to 12 mg/Day | Participants with POS with or without secondarily generalized seizures or PGTC seizures were hospitalized and received perampanel 8 mg up to 12 mg (stable-dosage) equivalent to the oral dose, as intravenous infusion for 30 minutes, once daily on Day 1 to Day 4 as an adjunctive therapy along with 1 to a maximum of 3 marketed concomitant AEDs. Eligible participants who completed Treatment Phase entered Follow-up Phase. | 0 | 21 | 1 | 21 | 11 | 21 |
| EG002 | Follow-up Phase: Oral Perampanel 8 to 12 mg/Day | Participants with POS with or without secondarily generalized seizures or PGTC seizures received perampanel 8 mg up to 12 mg (stable-dosage), tablets, orally, once daily on Day 5 to Day 11 (Follow-up Visit) as an adjunctive therapy along with 1 to a maximum of 3 marketed concomitant AEDs. | 0 | 21 | 2 | 21 | 1 | 21 |
| Delusion | Psychiatric disorders | MedDRA (22.1) | Systematic Assessment |
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| Loss of consciousness | Nervous system disorders | MedDRA (22.1) | Systematic Assessment |
|
| Feeling abnormal | General disorders | MedDRA (22.1) | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA (22.1) | Systematic Assessment |
|
| Hypoaesthesia | Nervous system disorders | MedDRA (22.1) | Systematic Assessment |
|
| Somnolence | Nervous system disorders | MedDRA (22.1) | Systematic Assessment |
|
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| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| PGTC Seizures |
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| Day -1: 0.5 hour post-dose |
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| Day -1: 1 hour post-dose |
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| Day -1: 1.5 hour post-dose |
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| Day 1: Pre-dose |
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| Day 1: 0.5 hour post-dose |
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| Day 2: Pre-dose |
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| Day 2: 0.5 hour post-dose |
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| Day 3: Pre-dose |
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| Day 3: 0.5 hour post-dose |
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| Day 4: Pre-dose |
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| Day 4: 0.5 hour post-dose |
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