A Long-term Extension Study of E2007 in Patients With Refractory Partial Seizures Uncontrolled With Other Anti-Epileptic Drugs (AEDs)

• Sponsor: Eisai Co., Ltd.
• Information provided by (Responsible Party): Eisai Inc. ( Eisai Co., Ltd. )

Study Description

Brief Summary:

The purpose of this trial is to investigate the safety and tolerability of perampanel in long- term treatment in the patients with refractory partial epilepsy (uncontrolled with other anti-epileptic drugs) who completed Week 10 of Phase II Study E2007-J081-231 study.

Condition or disease	Intervention/treatment	Phase
Refractory Partial Seizures	Drug: perampanel	Phase 2

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	21 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	A Long-term Extension Study of E2007 in Patients With Refractory Partial Seizures Uncontrolled With Other Anti-Epileptic Drugs (AEDs)
Actual Study Start Date :	June 17, 2009
Actual Primary Completion Date :	August 8, 2016
Actual Study Completion Date :	October 31, 2016

Arms and Interventions

Arm

Intervention/treatment

Experimental: Perampanel; Participants were treated with the perampanel dose that was administered in maintenance period of Study E2007-J081-231 (Study 231) [NCT00849212]. In some instances, a 1-step down-titration from the viewpoint of safety and up-titration to the maintenance dose of Study 231 was allowed. In general, 1 to 6 tablets of perampanel was administered orally as a 2-milligram (mg) tablet (2 mg to 12 mg) once daily before bedtime (under fed conditions as much as possible). The investigator, or subinvestigator, was allowed to complete the treatment by tapering the study drug after end of treatment or discontinuation (Follow-up Period), as appropriate. The taper period was 4 weeks at the longest.

Drug: perampanel; Patients will receive the same oral dosage (2 mg up to 12 mg once daily before bedtime) as used in the maintenance period of Study 231.; Other Names: E2007; Fycompa

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability of Perampanel [ Time Frame: From date of first dose up to 30 days after the last dose of study treatment, up to approximately 7 years 2 months ]
   Safety was assessed by monitoring adverse events (AEs), adverse drug reactions, clinical laboratory parameters, vital signs, 12-lead electrocardiogram, and dependency questionnaire. AEs were graded on a 3-point scale; 1) mild: (Grade 1) discomfort noticed, but no disruption of normal daily activity, 2) moderate: (Grade 2) discomfort reduced or affected normal daily activity, and 3) severe: (Grade 3) incapacitating, with inability to work or to perform normal daily activity. AE severity associated with abnormal changes in laboratory parameters was assessed using the Ministry of Health and Welfare Notification Number 80 "Classification of Severity of Adverse Drug Reactions of Medicinal Products". TEAEs were defined as AEs that emerged during treatment (absent at pretreatment [Baseline]), reemerged during treatment (were present at pretreatment but stopped before treatment), or worsened in severity during treatment relative to the pretreatment state, when the AE was continuous.

Secondary Outcome Measures :

1. Percent Change in Total Seizure Frequency Per 28 Days for the Treatment Period Summarized Until Week 316 [ Time Frame: From Week 1 through Week 316 and Follow-up Period of the Extension Study, up to approximately 7 years 2 months ]
   Seizure frequency was derived from information (seizure count and type) recorded in the participant diary. The seizure frequency per 28 days was calculated as the number of seizures over the time interval multiplied by 28 and divided by the number of days in the interval. The percent change in 28-day seizure frequency from baseline was assessed for overall seizures, overall partial seizures, overall generalized seizures, and unclassified seizures. Of the 21 participants, 20 participants concomitantly used at least 1 inducer anti-epileptic drug (AED) (carbamazepine, phenytoin, phenobarbital, or primidone), and 1 participant used only non-inducer AEDs. The data is presented as median percent change with full range.
2. Responder Rate During the Treatment Period-LOCF [ Time Frame: Week 1 through Week 316 and Follow-up period of the Extension study, up to approximately 7 years 2 months ]

   Responder rate (percentage of participants with greater than or equal to 50% reduction in seizure frequency for 28 days in the Treatment Period relative to that for 28 days in the observation period of Study 231 [responder]. If the reduction in seizure frequency is less than 50%, then the participants are considered as non-responders.

   LOCF = Last Observation Carried Forward.

3. The Patient Global Impression of Change (PGIC) at Week 52 and End of Treatment [ Time Frame: Week 52 and End of Treatment; up to approximately 7 years 2 months ]
   Each participant evaluated him/herself for PGIC at Week 52 of the Treatment Period and at the end of treatment (or discontinuation) by comparing seizure conditions during 4 weeks before Week 52 of the Treatment Period and those during 4 weeks before end of treatment (or discontinuation) of the open label extension study with those during 4 weeks before start of the Treatment Period of Study 231. Assessment was implemented based on frequency of seizure, severity of seizures, AEs, and overall conditions using the 7-grade scores. The evaluation used a 7-point scale with the scores 1: Very much improved, 2: Much improved, 3: Minimally improved, 4: No change, 5: Minimally worse, 6: Much worse, 7: Very much worse.
4. The Clinical Global Impression of Change (CGIC) at Week 52 and End of Treatment [ Time Frame: Week 52 and End of Treatment, up to approximately 7 years 2 months ]
   The investigator evaluated each participant for CGIC at Week 52 of the Treatment Period and at the end of treatment (or discontinuation) by comparing medical conditions during 4 weeks before Week 52 of the Treatment Period and those during 4 weeks before end of treatment (or discontinuation) of the open label extension study with those during 4 weeks before start of the Treatment Period of Study 231. Assessment was implemented based on frequency of seizure, severity of seizures, AEs, and overall conditions using the 7-grade scores. The evaluation used a 7-point scale with the scores 1: Very much improved, 2: Much improved, 3: Minimally improved, 4: No change, 5: Minimally worse, 6: Much worse, 7: Very much worse.

Eligibility Criteria

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Ages Eligible for Study:	20 Years to 64 Years (Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion criteria:

1. Patients who consent to the study entry on their free will before starting any trial-related activities.
2. Patients who participated in Study 231 and completed the required evaluation period (10 weeks).
3. Patients who are certainly and voluntarily able to participate in this study and record their seizures by themselves or have family members or caregivers (or nurses, if hospitalized) record the seizures. Patients who wish to continue perampanel treatment and necessitate receiving the long- term administration judged by the investigator or sub-investigator.

Exclusion criteria:

1. Pregnant or lactating women, women of child-bearing potential, women willing to become pregnant.
2. Patients who are ineligible judged by the investigator or sub investigator in light of medical history or complication at enrollment in treatment period.
3. Patients who operate heavy equipment or drive should not be recruited into the study.
4. Patients who are ineligible for study entry judged by the investigator or sub-investigator.

Contacts and Locations

Locations

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Japan
Kitakyusyu, Fukuoka, Japan
Kobe, Hyogo, Japan
Sendai, Miyagi, Japan
Komatsushima, Tokushima, Japan
Kodaira, Tokyo, Japan
Kyoto, Japan
Nagasaki, Japan
Niigata, Japan
Shizuoka, Japan

Sponsors and Collaborators

Eisai Co., Ltd.

Investigators

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Study Director:	Kazunori Saeki	Neuroscience Clinical Development Section. JAC PCU. Eisai Co., Ltd.

More Information

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Responsible Party:	Eisai Co., Ltd.
ClinicalTrials.gov Identifier:	NCT00903786 History of Changes
Other Study ID Numbers:	E2007-J081-233
First Posted:	May 18, 2009
Results First Posted:	August 29, 2018
Last Update Posted:	August 29, 2018
Last Verified:	September 2017

Keywords provided by Eisai Inc. ( Eisai Co., Ltd. ):

Seizure; epilepsy

Additional relevant MeSH terms:

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Seizures; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Anticonvulsants