A Study of Intravenous Perampanel in Japanese Participants With Epilepsy

Epilepsy Clinical Trial

Official title:

A Multicenter, Uncontrolled, Open-label Study to Evaluate the Safety and Tolerability of Intravenous Perampanel as Substitute for Oral Tablet in Subjects With Partial Onset Seizures (Including Secondarily Generalized Seizures) or Primary Generalized Tonic-clonic Seizures

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03754582
• Other study ID #: E2007-J081-240
• Status: Completed
• Phase: Phase 2
• Start date: November 27, 2018
• Est. completion date: December 10, 2019

Study information

• Verified date: November 2019
• Source: Eisai Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 21
• Est. completion date: December 10, 2019
• Est. primary completion date: December 10, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

Inclusion Criteria:

1. A diagnosis of epilepsy with POS (including secondarily generalized seizures) or PGTC seizures according to the International League Against Epilepsy (ILAE) Classification of Epileptic Seizures (1981).

2. Receiving a stable dose regimen of oral perampanel.

3. Receiving a concomitant stable dose regimen of marketed AEDs. No change of dosing regimen for concomitant AEDs is planned during the intravenous Treatment and Follow-up Phases.

4. Considered reliable and willing to be available for the study period by the investigator, and are able to record seizures and report AEs by themselves or have a caregiver who can record seizures and report AEs for them.

Exclusion Criteria:

1. A history of drug or alcohol dependency or abuse.

2. A history of status epilepticus.

3. Unsuitable for venipuncture and intravenous administration.

4. Requires medical intervention due to safety issues related to concomitant administration of AEDs.

5. A history of suicidal ideation/attempt.

6. Clinical symptoms or imaging suggest progressive central nervous system (CNS) abnormality, disorder, or brain tumor.

7. 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.

8. Clinically significant abnormal laboratory values.

9. Females of childbearing potential who:

• In the Pretreatment Phase, are breastfeeding or pregnant (as documented by a positive beta-human chorionic gonadotropin [ß-hCG] test).
• Within 28 days before Visit 1, did not use a highly effective method of

contraception, which includes any of the following:

• total abstinence (if it is their preferred and usual lifestyle).
• an intrauterine device (IUD) or intrauterine hormone-releasing system (IUS).
• a contraceptive implant.
• an oral contraceptive (with additional barrier method). (Participant must be on a stable dose of the same oral contraceptive product for at least 28 days before Day 1 of the Treatment Phase and throughout the entire study period, and for 28 days after the last dose of study drug).
• have a vasectomized partner with confirmed azoospermia.
• Do not agree to use a highly effective method of contraception (as described above) throughout the entire study period and for 28 days after the last dose of study drug.

10. 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.

11. A prolonged QT interval corrected using Fridericia's formula (QTcF) interval (greater than [>] 450 millisecond [ms]) as demonstrated by a repeated ECG.

12. A vagus nerve stimulation (VNS) implanted.

Related Conditions & MeSH terms

• Epilepsy
• Seizures

Intervention

Drug:
• Perampanel
Oral tablets.
• Perampanel
Intravenous infusion.

Locations

Country	Name	City	State
Japan	Eisai trial site 2	Asaka	Saitama
Japan	Eisai trial site 13	Hamamatsu	Shizuoka
Japan	Eisai trial site 10	Hiroshima
Japan	Eisai trial site 6	Kagoshima
Japan	Eisai trial site 8	Kodaira	Tokyo
Japan	Eisai trial site 5	Kurume	Fukuoka
Japan	Eisai trial site 1	Niigata
Japan	Eisai trial site 11	Okayama
Japan	Eisai trial site 9	Omura	Nagasaki
Japan	Eisai trial site 7	Osakasayama	Osaka
Japan	Eisai trial site 12	Sapporo	Hokkaido
Japan	Eisai trial site 3	Shizuoka
Japan	Eisai trial site 4	Yamagata

Sponsors (1)

Lead Sponsor	Collaborator
Eisai Co., Ltd.

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	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 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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
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.	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		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