A Study of Intravenous Perampanel in Japanese Participants With Epilepsy

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

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03754582

Enrollment

Registered

2018-11-27

Start date

2018-11-27

Completion date

2019-12-10

Last updated

2021-01-05

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

Conditions

Epilepsy, Seizures

Keywords

Partial Onset Seizures, Secondarily Generalized Seizures, Primary Generalized Tonic-Clonic Seizures

Brief 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.

Interventions

DRUGPerampanel

Oral tablets.

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

12 Years to No maximum

Healthy volunteers

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 \[β-hCG\] 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.

Design outcomes

Primary

Measure	Time frame	Description
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)	—
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)	—
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 Serious Adverse Events (SAEs)	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)	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.
Number of Participants With Adverse Events (AEs)	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)	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.
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)	—

Secondary

Measure	Time frame	Description
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	—
Mean Seizure Frequency Per Day in Pretreatment Phase, Treatment Phase and Follow-up Phase	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)	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.

Countries

Japan

Participant flow

Recruitment details

Participants took part in this study at 13 investigative sites in Japan from 27 November 2018 to 10 December 2019.

Pre-assignment details

A total of 27 participants were consented, of which 6 were screen failures and 21 were enrolled and received the study treatment.

Participants by arm

Arm	Count
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.	21
Total	21

Arm

Count

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.

Total

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002
Follow-up Phase	Other	0	0	1
Treatment Phase	Adverse Event	0	1	0

Baseline characteristics

Characteristic	Perampanel 8 to 12 mg/Day
Age, Continuous	40.7 years STANDARD_DEVIATION 12.76
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants
Race/Ethnicity, Customized Japanese	21 Participants
Sex: Female, Male Female	12 Participants
Sex: Female, Male Male	9 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	0 / 21	0 / 21	0 / 21
other Total, other adverse events	2 / 21	11 / 21	1 / 21
serious Total, serious adverse events	0 / 21	1 / 21	2 / 21

Outcome results

Primary

Number of Participants With Abnormal Body Weight During Treatment and Follow-up Phase

Time frame: Up to 11 days (Treatment Phase: up to 4 days, Follow-up Phase: up to 7 days after the last dose)