Trial Outcomes & Findings for Evaluating Efficacy and Safety of E2007 (Perampanel) Given as Adjunctive Therapy in Subjects With Refractory Partial Seizures (NCT NCT00700310)

NCT ID: NCT00700310

Last Updated: 2016-01-21

Results Overview

Seizure frequency per 28 days was derived from the information recorded in the subject diaries.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

712 participants

Primary outcome timeframe

Baseline (Pre-randomization) through Week 19

Results posted on

2016-01-21

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo Placebo over 19-weeks (during 6-week Titration phase and 13-week Maintenance phase)	Perampanel 2mg Perampanel 2mg daily over 19-weeks (during 6-week Titration phase and 13-week Maintenance phase)	Perampanel 4mg Perampanel 4mg maximum daily dose (Titration from 2mg to 4mg daily over 6-weeks; Maintenance at 4 mg daily over 13-weeks)	Perampanel 8 mg Perampanel 8mg maximum daily dose (Titration from 2mg to 8mg daily over 6-weeks; Maintenance at 8 mg daily over 13-weeks)
Overall Study STARTED	187	180	174	171
Overall Study COMPLETED	166	154	158	145
Overall Study NOT COMPLETED	21	26	16	26

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Placebo over 19-weeks (during 6-week Titration phase and 13-week Maintenance phase)	Perampanel 2mg Perampanel 2mg daily over 19-weeks (during 6-week Titration phase and 13-week Maintenance phase)	Perampanel 4mg Perampanel 4mg maximum daily dose (Titration from 2mg to 4mg daily over 6-weeks; Maintenance at 4 mg daily over 13-weeks)	Perampanel 8 mg Perampanel 8mg maximum daily dose (Titration from 2mg to 8mg daily over 6-weeks; Maintenance at 8 mg daily over 13-weeks)
Overall Study Adverse Event	6	10	5	11
Overall Study Lost to Follow-up	4	1	0	1
Overall Study Withdrawal by Subject	8	9	8	8
Overall Study Lack of Efficacy	0	3	0	1
Overall Study Administrative/Other	1	3	1	3
Overall Study Randomized, Not Treated	2	0	2	2

Baseline Characteristics

Evaluating Efficacy and Safety of E2007 (Perampanel) Given as Adjunctive Therapy in Subjects With Refractory Partial Seizures

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=185 Participants Placebo over 19-weeks (during 6-week Titration phase and 13-week Maintenance phase)	Perampanel 2mg n=180 Participants Perampanel 2mg daily over 19-weeks (during 6-week Titration phase and 13-week Maintenance phase)	Perampanel 4mg n=172 Participants Perampanel 4mg maximum daily dose (Titration from 2mg to 4mg daily over 6-weeks; Maintenance at 4 mg daily over 13-weeks)	Perampanel 8 mg n=169 Participants Perampanel 8mg maximum daily dose (Titration from 2mg to 8mg daily over 6-weeks; Maintenance at 8 mg daily over 13-weeks)	Total n=706 Participants Total of all reporting groups
Age, Customized <18 Years	14 Participants n=5 Participants	21 Participants n=7 Participants	13 Participants n=5 Participants	12 Participants n=4 Participants	60 Participants n=21 Participants
Age, Customized 18-64 Years	169 Participants n=5 Participants	156 Participants n=7 Participants	158 Participants n=5 Participants	153 Participants n=4 Participants	636 Participants n=21 Participants
Age, Customized >64 Years	2 Participants n=5 Participants	3 Participants n=7 Participants	1 Participants n=5 Participants	4 Participants n=4 Participants	10 Participants n=21 Participants
Sex: Female, Male Female	90 Participants n=5 Participants	95 Participants n=7 Participants	84 Participants n=5 Participants	92 Participants n=4 Participants	361 Participants n=21 Participants
Sex: Female, Male Male	95 Participants n=5 Participants	85 Participants n=7 Participants	88 Participants n=5 Participants	77 Participants n=4 Participants	345 Participants n=21 Participants
Race/Ethnicity, Customized White	119 Participants n=5 Participants	119 Participants n=7 Participants	105 Participants n=5 Participants	116 Participants n=4 Participants	459 Participants n=21 Participants
Race/Ethnicity, Customized Asian	34 Participants n=5 Participants	35 Participants n=7 Participants	37 Participants n=5 Participants	28 Participants n=4 Participants	134 Participants n=21 Participants
Race/Ethnicity, Customized Chinese	31 Participants n=5 Participants	25 Participants n=7 Participants	29 Participants n=5 Participants	25 Participants n=4 Participants	110 Participants n=21 Participants
Race/Ethnicity, Customized Other	1 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	3 Participants n=21 Participants

PRIMARY outcome

Timeframe: Baseline (Pre-randomization) through Week 19

Population: Full Intent-to-Treat (ITT) Analysis Set - group of subjects who were randomized to study drug, received study drug, and had any seizure frequency data during the Double-blind Phase.

Seizure frequency per 28 days was derived from the information recorded in the subject diaries.

Outcome measures

Outcome measures
Measure	Placebo n=184 Participants Placebo over 19-weeks (during 6-week Titration phase and 13-week Maintenance phase)	Perampanel 2mg n=180 Participants Perampanel 2mg daily over 19-weeks (during 6-week Titration phase and 13-week Maintenance phase)	Perampanel 4mg n=172 Participants Perampanel 4mg maximum daily dose (Titration from 2mg to 4mg daily over 6-weeks; Maintenance at 4 mg daily over 13-weeks)	Perampanel 8 mg n=169 Participants Perampanel 8mg maximum daily dose (Titration from 2mg to 8mg daily over 6-weeks; Maintenance at 8 mg daily over 13-weeks)
Percent Change in the 28-day Seizure Frequency From Baseline to the End of the Double-blind Phase (Titration and Maintenance Phases)	-10.69 Percent Change Interval -100.0 to 420.6	-13.63 Percent Change Interval -100.0 to 346.3	-23.33 Percent Change Interval -100.0 to 416.0	-30.80 Percent Change Interval -100.0 to 390.6

SECONDARY outcome

Timeframe: Baseline (Pre-randomization) through Week 19

Population: Full ITT Analysis Set.

The responder rate for the Full ITT Analysis Set from the maintenance LOCF (Last Observation Carried Forward). A responder was a subject who had a 50 percent or greater reduction in seizure frequency per 28 days from the Pre-randomization phase.

Outcome measures

Outcome measures
Measure	Placebo n=184 Participants Placebo over 19-weeks (during 6-week Titration phase and 13-week Maintenance phase)	Perampanel 2mg n=180 Participants Perampanel 2mg daily over 19-weeks (during 6-week Titration phase and 13-week Maintenance phase)	Perampanel 4mg n=172 Participants Perampanel 4mg maximum daily dose (Titration from 2mg to 4mg daily over 6-weeks; Maintenance at 4 mg daily over 13-weeks)	Perampanel 8 mg n=169 Participants Perampanel 8mg maximum daily dose (Titration from 2mg to 8mg daily over 6-weeks; Maintenance at 8 mg daily over 13-weeks)
Responder Rate Responders (Yes)	17.9 Percentage of Participants	20.6 Percentage of Participants	28.5 Percentage of Participants	34.9 Percentage of Participants
Responder Rate Non-Responders (No)	82.1 Percentage of Participants	79.4 Percentage of Participants	71.5 Percentage of Participants	65.1 Percentage of Participants

SECONDARY outcome

Timeframe: Baseline (Pre-randomization) through Week 19

Population: Full ITT Analysis Set

Percent Change in the Seizure frequency per 28 days was derived from the information recorded in the subject diaries.

Outcome measures

Outcome measures
Measure	Placebo n=169 Participants Placebo over 19-weeks (during 6-week Titration phase and 13-week Maintenance phase)	Perampanel 2mg n=167 Participants Perampanel 2mg daily over 19-weeks (during 6-week Titration phase and 13-week Maintenance phase)	Perampanel 4mg n=157 Participants Perampanel 4mg maximum daily dose (Titration from 2mg to 4mg daily over 6-weeks; Maintenance at 4 mg daily over 13-weeks)	Perampanel 8 mg n=154 Participants Perampanel 8mg maximum daily dose (Titration from 2mg to 8mg daily over 6-weeks; Maintenance at 8 mg daily over 13-weeks)
Percent Change in the 28-day Complex Partial Plus Secondarily Generalized Seizure Frequency From Baseline to the End of the Double-blind Phase (Titration and Maintenance Phases)	-17.63 Percent Change Interval -100.0 to 602.9	-20.50 Percent Change Interval -100.0 to 13744.2	-31.18 Percent Change Interval -100.0 to 416.0	-38.69 Percent Change Interval -100.0 to 583.3

Adverse Events

Placebo

Serious events: 9 serious events

Other events: 48 other events

Deaths: 0 deaths

Perampanel 2mg

Serious events: 6 serious events

Other events: 61 other events

Deaths: 0 deaths

Perampanel 4mg

Serious events: 6 serious events

Other events: 66 other events

Deaths: 0 deaths

Perampanel 8 mg

Serious events: 6 serious events

Other events: 79 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo n=185 participants at risk Placebo over 19-weeks (during 6-week Titration phase and 13-week Maintenance phase)	Perampanel 2mg n=180 participants at risk Perampanel 2mg daily over 19-weeks (during 6-week Titration phase and 13-week Maintenance phase)	Perampanel 4mg n=172 participants at risk Perampanel 4mg maximum daily dose (Titration from 2mg to 4mg daily over 6-weeks; Maintenance at 4 mg daily over 13-weeks)	Perampanel 8 mg n=169 participants at risk Perampanel 8mg maximum daily dose (Titration from 2mg to 8mg daily over 6-weeks; Maintenance at 8 mg daily over 13-weeks)
General disorders Fatigue	2.7% 5/185 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations; and by telephone interviews/contact.	4.4% 8/180 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations; and by telephone interviews/contact.	7.6% 13/172 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations; and by telephone interviews/contact.	5.3% 9/169 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations; and by telephone interviews/contact.
General disorders Gait disturbance	1.1% 2/185 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations; and by telephone interviews/contact.	0.56% 1/180 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations; and by telephone interviews/contact.	1.2% 2/172 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations; and by telephone interviews/contact.	5.3% 9/169 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations; and by telephone interviews/contact.
Infections and infestations Nasopharyngitis	1.6% 3/185 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations; and by telephone interviews/contact.	3.9% 7/180 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations; and by telephone interviews/contact.	5.2% 9/172 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations; and by telephone interviews/contact.	1.8% 3/169 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations; and by telephone interviews/contact.
Infections and infestations Upper respiratory tract infection	2.7% 5/185 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations; and by telephone interviews/contact.	6.1% 11/180 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations; and by telephone interviews/contact.	3.5% 6/172 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations; and by telephone interviews/contact.	1.8% 3/169 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations; and by telephone interviews/contact.
Nervous system disorders Dizziness	9.7% 18/185 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations; and by telephone interviews/contact.	10.0% 18/180 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations; and by telephone interviews/contact.	16.3% 28/172 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations; and by telephone interviews/contact.	26.6% 45/169 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations; and by telephone interviews/contact.
Nervous system disorders Headache	8.6% 16/185 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations; and by telephone interviews/contact.	8.9% 16/180 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations; and by telephone interviews/contact.	11.0% 19/172 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations; and by telephone interviews/contact.	10.7% 18/169 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations; and by telephone interviews/contact.
Nervous system disorders Somnolence	6.5% 12/185 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations; and by telephone interviews/contact.	12.2% 22/180 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations; and by telephone interviews/contact.	8.7% 15/172 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations; and by telephone interviews/contact.	16.0% 27/169 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations; and by telephone interviews/contact.

Additional Information

Eisai Inc.

Eisai Call Center

Phone: 888-422-4743

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place