Trial Outcomes & Findings for To Evaluate The Efficacy and Safety of E2007 (Perampanel) Given as Adjunctive Therapy in Subjects With Refractory Partial Seizures (NCT NCT00699582)

NCT ID: NCT00699582

Last Updated: 2014-07-11

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

389 participants

Primary outcome timeframe

Baseline (Pre-randomization) through Week 19

Results posted on

2014-07-11

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo	Perampanel 8mg Perampanel 8mg maximum daily dose (Titration from 2mg to 8mg daily over 6-weeks; Maintenance at 8mg daily over 13-weeks)	Perampanel 12mg Perampanel 12mg maximum daily dose (Titration from 2mg to 12mg daily over 6-weeks; Maintenance at 12mg daily over 13-weeks)
Overall Study STARTED	138	130	121
Overall Study COMPLETED	120	108	93
Overall Study NOT COMPLETED	18	22	28

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo	Perampanel 8mg Perampanel 8mg maximum daily dose (Titration from 2mg to 8mg daily over 6-weeks; Maintenance at 8mg daily over 13-weeks)	Perampanel 12mg Perampanel 12mg maximum daily dose (Titration from 2mg to 12mg daily over 6-weeks; Maintenance at 12mg daily over 13-weeks)
Overall Study Adverse Event	4	11	23
Overall Study Withdrawal by Subject	6	7	4
Overall Study Lack of Efficacy	1	0	1
Overall Study Progressive Disease	1	0	0
Overall Study Administrative/Other	4	3	0
Overall Study Randomized, Not Treated	2	1	0

Baseline Characteristics

To Evaluate The 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=138 Participants	Perampanel 8mg n=130 Participants Perampanel 8mg maximum daily dose (Titration from 2mg to 8mg daily over 6-weeks; Maintenance at 8mg daily over 13-weeks)	Perampanel 12mg n=121 Participants Perampanel 12mg maximum daily dose (Titration from 2mg to 12mg daily over 6-weeks; Maintenance at 12mg daily over 13-weeks)	Total n=389 Participants Total of all reporting groups
Age, Customized <18 years	17 participants n=39 Participants	17 participants n=41 Participants	10 participants n=35 Participants	44 participants n=31 Participants
Age, Customized 18-64 years	120 participants n=39 Participants	110 participants n=41 Participants	109 participants n=35 Participants	339 participants n=31 Participants
Age, Customized >64 years	1 participants n=39 Participants	3 participants n=41 Participants	2 participants n=35 Participants	6 participants n=31 Participants
Sex: Female, Male Female	66 Participants n=39 Participants	64 Participants n=41 Participants	71 Participants n=35 Participants	201 Participants n=31 Participants
Sex: Female, Male Male	72 Participants n=39 Participants	66 Participants n=41 Participants	50 Participants n=35 Participants	188 Participants n=31 Participants
Race/Ethnicity, Customized White	117 participants n=39 Participants	108 participants n=41 Participants	100 participants n=35 Participants	325 participants n=31 Participants
Race/Ethnicity, Customized Black or African American	1 participants n=39 Participants	2 participants n=41 Participants	1 participants n=35 Participants	4 participants n=31 Participants
Race/Ethnicity, Customized Asian	12 participants n=39 Participants	14 participants n=41 Participants	16 participants n=35 Participants	42 participants n=31 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	1 participants n=39 Participants	0 participants n=41 Participants	0 participants n=35 Participants	1 participants n=31 Participants
Race/Ethnicity, Customized Other	7 participants n=39 Participants	6 participants n=41 Participants	4 participants n=35 Participants	17 participants n=31 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 Doubleblind Phase. For Placebo arm, 2 subjects were randomized but not treated. For Perampanel 8mg arm, 1 subject was randomized but not treated.

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

Outcome measures

Outcome measures
Measure	Placebo n=136 Participants	Perampanel 8mg n=129 Participants Perampanel 8mg maximum daily dose (Titration from 2mg to 8mg daily over 6-weeks; Maintenance at 8mg daily over 13-weeks)	Perampanel 12mg n=121 Participants Perampanel 12mg maximum daily dose (Titration from 2mg to 12mg daily over 6-weeks; Maintenance at 12mg 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)	-9.72 Percent Change Interval -91.8 to 404.3	-30.52 Percent Change Interval -94.0 to 234.3	-17.57 Percent Change Interval -100.0 to 858.3

SECONDARY outcome

Timeframe: Baseline (Pre-randomization) through Week 19

Population: Full ITT Analysis Set. For Placebo arm, 2 subjects were randomized but not treated. For Perampanel 8mg arm, 1 subject was randomized but not treated.

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=136 Participants	Perampanel 8mg n=129 Participants Perampanel 8mg maximum daily dose (Titration from 2mg to 8mg daily over 6-weeks; Maintenance at 8mg daily over 13-weeks)	Perampanel 12mg n=121 Participants Perampanel 12mg maximum daily dose (Titration from 2mg to 12mg daily over 6-weeks; Maintenance at 12mg daily over 13-weeks)
Responder Rate Responders (Yes)	14.7 Percentage of Participants	33.3 Percentage of Participants	33.9 Percentage of Participants
Responder Rate Non-Responders(No)	85.3 Percentage of Participants	66.7 Percentage of Participants	66.1 Percentage of Participants

SECONDARY outcome

Timeframe: Baseline (Pre-randomization) through Week 19

Population: Full ITT Analysis Set with Complex Partial plus Secondarily Generalized Seizures at Pre-randomization. For Placebo arm, 2 subjects were randomized but not treated. For Perampanel 8mg arm, 1 subject was randomized but not treated.

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=126 Participants	Perampanel 8mg n=119 Participants Perampanel 8mg maximum daily dose (Titration from 2mg to 8mg daily over 6-weeks; Maintenance at 8mg daily over 13-weeks)	Perampanel 12mg n=113 Participants Perampanel 12mg maximum daily dose (Titration from 2mg to 12mg daily over 6-weeks; Maintenance at 12mg 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)	-8.05 Percent Change Interval -100.0 to 382.4	-32.72 Percent Change Interval -100.0 to 1023.2	-21.89 Percent Change Interval -100.0 to 733.3

Adverse Events

Placebo

Serious events: 7 serious events

Other events: 55 other events

Deaths: 0 deaths

Perampanel 8mg

Serious events: 10 serious events

Other events: 90 other events

Deaths: 0 deaths

Perampanel 12mg

Serious events: 12 serious events

Other events: 90 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo n=136 participants at risk	Perampanel 8mg n=129 participants at risk Perampanel 8mg maximum daily dose (Titration from 2mg to 8mg daily over 6-weeks; Maintenance at 8mg daily over 13-weeks)	Perampanel 12mg n=121 participants at risk Perampanel 12mg maximum daily dose (Titration from 2mg to 12mg daily over 6-weeks; Maintenance at 12mg daily over 13-weeks)
Gastrointestinal disorders Constipation	2.9% 4/136 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events (AE) 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.	3.1% 4/129 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events (AE) 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.	5.8% 7/121 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events (AE) 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.
Gastrointestinal disorders Nausea	3.7% 5/136 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events (AE) 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.	8.5% 11/129 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events (AE) 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.	9.9% 12/121 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events (AE) 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 Fatigue	8.1% 11/136 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events (AE) 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.	13.2% 17/129 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events (AE) 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.	16.5% 20/121 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events (AE) 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 Irritability	3.7% 5/136 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events (AE) 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.	9.3% 12/129 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events (AE) 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.	9.1% 11/121 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events (AE) 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	6.6% 9/136 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events (AE) 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.	7.8% 10/129 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events (AE) 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.	4.1% 5/121 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events (AE) 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	3.7% 5/136 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events (AE) 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.	7.0% 9/129 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events (AE) 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.	4.1% 5/121 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events (AE) 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.
Injury, poisoning and procedural complications Fall	2.9% 4/136 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events (AE) 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.	4.7% 6/129 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events (AE) 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.	7.4% 9/121 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events (AE) 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.
Investigations Weight Increased	2.2% 3/136 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events (AE) 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.	5.4% 7/129 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events (AE) 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.	5.8% 7/121 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events (AE) 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.
Musculoskeletal and connective tissue disorders Back Pain	1.5% 2/136 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events (AE) 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.	2.3% 3/129 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events (AE) 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.	5.8% 7/121 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events (AE) 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 Balance Disorder	0.74% 1/136 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events (AE) 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.	5.4% 7/129 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events (AE) 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.	2.5% 3/121 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events (AE) 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 Convulsion	5.1% 7/136 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events (AE) 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.	2.3% 3/129 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events (AE) 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.	4.1% 5/121 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events (AE) 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	7.4% 10/136 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events (AE) 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.	31.8% 41/129 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events (AE) 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.	47.9% 58/121 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events (AE) 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	12.5% 17/136 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events (AE) 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.	8.5% 11/129 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events (AE) 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.	12.4% 15/121 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events (AE) 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	2.9% 4/136 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events (AE) 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.	12.4% 16/129 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events (AE) 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.	17.4% 21/121 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events (AE) 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