Protocol amendment #1 dated 13 Oct 2005: • Site number was increased from 30 to 50 sites to meet planned enrollment numbers. • Language was added to address the addition of European and North American sites and the deletion of US sites to this study in “Contact Details. • Language was added to clarify that Week 52 assessments should be performed at Week 52 or if patient prematurely terminates from the study. • Miscellaneous changes such as added European contact information for shipment of laboratory samples; ESL personnel contact information; EudraCT number; IND number; and clarification that patients with clinically significant laboratory abnormalities may be discontinued from the study at the investigator’s discretion. • The International System of Units (SI) equivalent was added to the WBC and absolute neutrophil values • The controlled room temperature was revised to meet European standards. • Laboratory assessments were revised. • Revised current version of Declaration of Helsinki with the 1996 version. • Administrative changes, correction of minor spelling and typographical errors.

Protocol amendment #2 dated 07-JUN-2006 • The title was changed to reflect the extended study timeframe. • Administrative changes that do not impact the scientific meaning of the trial. • Twice a day (BID) dosing may not be necessary and was removed as an option in protocol. • Once a day (QD) vs BID efficacy comparison was removed as a secondary objective. • Determination of E2007 levels was removed as a secondary objective in protocol since ample PK data was collected from core Phase II and III studies. • The duration of the Titration Phase was reduced to 6 weeks. The Maintenance Phase was increased to allow patients to receive E2007 at the highest tolerated dose for 52 weeks. • Additional sites were added to increase enrollment. • Revisions to protocol for clarification purpose. • Revisions to inclusion and exclusion criteria. • Revisions in the test assessments to maintain consistency across all sites globally and to clarify the procedures. • Anti-epileptic drugs (AED) sampling was removed as it was not necessary to the main purpose of this study. • Clinical and Patient Global Impressions of change scales were removed.

Protocol amendment #3 dated 19-NOV-2006 • Incorporate recent preclinical findings of in vitro phototoxicity into the safety information. • Clarified that the study drug would be taken at bedtime based on current tolerability data. • Clarified timing for enrollment from the double-blind study into the open-label study. • Revised criterion for excluding patients with ECG abnormalities to be uniform for males and females. • Updated SAE Reporting section with contract research organization (CRO) information (previously unavailable), and with updated SAE text concerning follow-up. • Revised Visit 5 window to adjust for drug packaging. • Inhibitors of CYP3A4/5 not excluded. • Editorial, formatting, and typo corrections.

Protocol amendment #4 dated 15-FEB-2007 • Incorporation of patients from E2007-G000-208 (Phase IIb, double blind, placebo controlled, maximum tolerated dose (MTD) trial, 48 patients, up to 12mg/day E2007) into E2007-G000-207 (open label extension) so that there is one extension study for both E2007-A001-206 (double blind, placebo-controlled, Phase II, proof-of-concept (PoC) epilepsy trial, 153 randomized, up to 4mg/day E2007) and E2007-G000-208 patients. • Allow the former E2007-A001-206 patients a chance to access higher doses (up to 12mg/dayE2007) if up to 4mg/day E2007 (original OLE) is insufficient in controlling seizures (at least 3 partial seizures per month on average) during the maintenance phase of the open label extension study (E2007-A001-207). • Harmonize remaining aspects of E2007-A001-206 and E2007-G000-208 • Miscellaneous changes such as clarifications to protocol sections; revise formulation and packaging; revise contact information; revise the AED and non AED dosing plan to allow flexibility; updated SAE reporting information to clarify hospitalization; and editorial and formatting changes. • Revise rationale for dose selection based on data PK data for concomitant use of CYP3A-inducing AEDs and/or non-CYP3A-inducing AEDs.

Protocol amendment #5 dated 04-JUN-2007 • Updated phototoxicity / photoallergy results from in vivo studies. • Extended the open label extension phase to an additional 3 years to monitor long-term safety of E2007 given as adjunctive, long-term treatment in patients with refractory partial onset seizures. • Administrative changes, miscellaneous editorial/format changes.

Protocol amendment #6 dated 08 June 2009, v2.0 • Study title was revised to remove the study duration from the title to avoid the need for additional amendments should the study duration be extended in the future • Change in sponsor name and address from Eisai Medical Research, Inc. to Eisai Inc., • Clarify that tolerability is also a component of the primary objective • Study design, treatment, synopsis, rational, duration, Physical and Neurological Examination, vital signs, etc. was revised to consolidate the text for consistency and clarity (ie, subjects from the preceding double-blind studies are treated similarly except where noted) and to remove redundancy throughout the protocol • Revised protocol deviation/violation text for consistency with other ongoing perampanel studies. • To clarify that 1 mg tablets are no longer permitted for dispensing in the study and that all subjects on an odd dose (eg, 1, 3, 5 mg) should be titrated to an even dose (eg, 2, 4, 6 mg). • To update the number of concomitant AEDs allowed (as subject may now discontinue all concomitant AEDs). • To revise the list of prohibited medications. • Miscellaneous changes such as change assessment times specified from Weeks to Visits, provide the abbreviation for lactate dehydrogenase, corrected for consistency of terminology throughout protocol, clarify durations (all text references to months have been converted to weeks eg, 1 month = 4 weeks), update SAE reporting fax and phone numbers according to the reassignment of CRO responsibilities, etc. • To clarify the instructions in regard to early terminations and the Sponsor’s position on the need for down titrations upon early termination. • To update the protocol with Eisai’s current standard Pregnancy reporting text. • To generalize text to ensure consistency in instructions with study drug labeling and Investigator’s Brochure.

Protocol amendment 7 v1.0 dated 08-Jul-2010 • Secondary objective, study procedures, efficacy assessments, statistics was revised to evaluate the long term maintenance of E2007 efficacy to the last efficacy collecting visit of the E2007-A001-207 study as dispensing, collection, and review of seizure diaries will no longer be required, as sufficient and more standardized data for efficacy has been collected in the Phase 3 program for perampanel. • Extension of study duration for an additional 216 weeks for a total duration of approximately 8 years. Revised relevant protocol sections to implement this change. • Orthostatic vitals will no longer be required (only standard sitting vitals), as the current information on the • Revise safety profile of perampanel to indicate that only standard sitting vitals need be collected. • Miscellaneous changes such as update status of studies E2007-A001-206 and E2007-A001-208. • Added information on the instructions regarding study drug compliance when phone visits. • To allow flexibility in the timing of electrocardiograms (ECGs) in relation to blood draws.

Protocol amendment 8 dated 26 June 2012 • Corrected Eisai US Address. • The perampanel Phase 3 program in partial onset seizures (POS) has been completed, and Regulatory submissions to seek approval for marketing have been made to several countries. Therefore, Study E2007-A001-207 will be closed and the protocol was revised to schedule the EOT visit. • Miscellaneous changes such as update abbreviation table.

Protocol amendment 9 dated 11 Feb 2013 • Revised definition of study end in the United States- Upon implementation of Amendment 08, the sponsor will be closing the study protocol. The study will end after European Union (EU) Marketing Authorization Application (MAA) approval (EU countries) and after United States (US) launch (US). However, if it is the opinion of the treating physician that the patient would benefit significantly from further treatment with perampanel after the trial concludes, then it is Eisai’s intent to make perampanel available under Eisai’s compassionate use policy (available upon request) and according to local country legislative provision. Perampanel treatment via local country legislative provision will be available until the time perampanel is commercially available in the country in which the patient resides.