Trial Outcomes & Findings for An add-on Study of E2007 in Patients With Refractory Partial Seizures Uncontrolled With Other Anti-epileptic Drugs (AEDs) (NCT NCT00849212)

Last Updated: 2013-02-07

Results Overview

MTD was defined by participants. For participants who completed treatment, MTD was dose at last administration. For subjects who discontinued due to adverse event (AE), the MTD depended on the number of days within down-titration. If these criteria were not applied, the MTD was determined based on suggestions from the Tolerability and Safety Evaluation Committee.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

30 participants

Primary outcome timeframe

10 weeks (Titration and Maintenance Periods)

Results posted on

2013-02-07

Participant Flow

Participant milestones

Participant milestones
Measure	Perampanel Orally administered E2007 (2, 4, 6, 8, 10, and 12 mg) once daily before bedtime (in fed administration insofar as possible). The dose started from 2 mg and up-titrated weekly in 2 mg increments up to the maximum 12 mg unless subjects met the following judgment on dose titration: 1.) If meeting titration limiting criteria, 2.) If subjects refused up-titration due to AEs, 3.) If the investigator judged it difficult to up-titrate due to AEs, or 4.) If treatment duration was less than 5 days. Total duration of treatment was 10 weeks from the initial dose.
Overall Study STARTED	30
Overall Study COMPLETED	23
Overall Study NOT COMPLETED	7

Reasons for withdrawal

Reasons for withdrawal
Measure	Perampanel Orally administered E2007 (2, 4, 6, 8, 10, and 12 mg) once daily before bedtime (in fed administration insofar as possible). The dose started from 2 mg and up-titrated weekly in 2 mg increments up to the maximum 12 mg unless subjects met the following judgment on dose titration: 1.) If meeting titration limiting criteria, 2.) If subjects refused up-titration due to AEs, 3.) If the investigator judged it difficult to up-titrate due to AEs, or 4.) If treatment duration was less than 5 days. Total duration of treatment was 10 weeks from the initial dose.
Overall Study Lack of Efficacy	1
Overall Study Withdrawal by Subject	3
Overall Study Adverse Event	2
Overall Study Miscellaneous	1

Baseline Characteristics

An add-on Study of E2007 in Patients With Refractory Partial Seizures Uncontrolled With Other Anti-epileptic Drugs (AEDs)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Perampanel n=30 Participants Orally administered E2007 (2, 4, 6, 8, 10, and 12 mg) once daily before bedtime (in fed administration insofar as possible). The dose started from 2 mg and up-titrated weekly in 2 mg increments up to the maximum 12 mg unless subjects met the following judgment on dose titration: 1.) If meeting titration limiting criteria, 2.) If subjects refused up-titration due to AEs, 3.) If the investigator judged it difficult to up-titrate due to AEs, or 4.) If treatment duration was less than 5 days. Total duration of treatment was 10 weeks from the initial dose.
Age Continuous	35.4 Years STANDARD_DEVIATION 10.6 • n=93 Participants
Sex: Female, Male Female	14 Participants n=93 Participants
Sex: Female, Male Male	16 Participants n=93 Participants

PRIMARY outcome

Timeframe: 10 weeks (Titration and Maintenance Periods)

Population: Safety analysis set

Outcome measures

Outcome measures
Measure	Perampanel n=30 Participants Orally administered E2007 (2, 4, 6, 8, 10, and 12 mg) once daily before bedtime (in fed administration insofar as possible). The dose started from 2 mg and up-titrated weekly in 2 mg increments up to the maximum 12 mg unless subjects met the following judgment on dose titration: 1.) If meeting titration limiting criteria, 2.) If subjects refused up-titration due to AEs, 3.) If the investigator judged it difficult to up-titrate due to AEs, or 4.) If treatment duration was less than 5 days. Total duration of treatment was 10 weeks from the initial dose.
Maximum Tolerated Dose (MTD) 4 mg	1 Participants
Maximum Tolerated Dose (MTD) 8 mg	6 Participants
Maximum Tolerated Dose (MTD) 10 mg	5 Participants
Maximum Tolerated Dose (MTD) 0 mg	0 Participants
Maximum Tolerated Dose (MTD) 2 mg	2 Participants
Maximum Tolerated Dose (MTD) 6 mg	6 Participants
Maximum Tolerated Dose (MTD) 12 mg	10 Participants

SECONDARY outcome

Timeframe: Baseline (Day -28 to Day 0), Week 1 to Week 10

Population: Efficacy analysis set: Population after excluding : (a) Patients who do not meet the inclusion criteria, (b) Patients who meet the exclusion criteria which affect efficacy evaluation of E2007, (c) Patients untreated,(d) Patients with no evaluable data on efficacy,(e) Patients with \<80% treatment compliance

The percent change in seizure frequency per 28 days during the maintenance period was collected via patient diary cards. This was calculated using the last observation carried forward (LOCF) method.

Outcome measures

Outcome measures
Measure	Perampanel n=27 Participants Orally administered E2007 (2, 4, 6, 8, 10, and 12 mg) once daily before bedtime (in fed administration insofar as possible). The dose started from 2 mg and up-titrated weekly in 2 mg increments up to the maximum 12 mg unless subjects met the following judgment on dose titration: 1.) If meeting titration limiting criteria, 2.) If subjects refused up-titration due to AEs, 3.) If the investigator judged it difficult to up-titrate due to AEs, or 4.) If treatment duration was less than 5 days. Total duration of treatment was 10 weeks from the initial dose.
Percent Change in Total Seizure Frequency Per 28 Days From Baseline (Maintenance Period) ; LOCF	-35 Percent change Interval -100.0 to 312.8

Adverse Events

Perampanel

Serious events: 0 serious events

Other events: 27 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Perampanel n=30 participants at risk Orally administered E2007 (2, 4, 6, 8, 10, and 12 mg) once daily before bedtime (in fed administration insofar as possible). The dose started from 2 mg and up-titrated weekly in 2 mg increments up to the maximum 12 mg unless subjects met the following judgment on dose titration: 1.) If meeting titration limiting criteria, 2.) If subjects refused up-titration due to AEs, 3.) If the investigator judged it difficult to up-titrate due to AEs, or 4.) If treatment duration was less than 5 days. Total duration of treatment was 10 weeks from the initial dose.
Infections and infestations Nasopharyngitis	16.7% 5/30
Nervous system disorders Dizziness	53.3% 16/30
Nervous system disorders Somnolence	46.7% 14/30
Nervous system disorders Headache	10.0% 3/30
Respiratory, thoracic and mediastinal disorders Upper respiratory tract inflammation	10.0% 3/30
Gastrointestinal disorders Vomiting	6.7% 2/30
General disorders Irritability	10.0% 3/30
General disorders Malaise	6.7% 2/30
Investigations Blood creatine phosphokinase increased	6.7% 2/30
Investigations Blood glucose decreased	6.7% 2/30
Injury, poisoning and procedural complications Contusion	13.3% 4/30
Injury, poisoning and procedural complications Fall	6.7% 2/30

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