Protocol Amendment 1 was approved and effective prior to the date of first patient first visit (FPFV). The rationale for this amendment was to integrate the USA Food and Drug Administration (FDA) recommendations regarding cardiac monitoring, received on 20 Nov 2008: - At V2, an ECG was added - Immediately after each BRV iv administration, ECGs were added - A central reader was organized for the ECG tracings - The section describing the adverse events (AEs) was updated to be consistent with the new CRF AE module - The recently defined IND number for BRV iv development was implemented

Protocol Amendment 2 was approved and effective prior to the date of FPFV. The rationale for this amendment was to integrate the USA FDA recommendations regarding cardiac monitoring, as expressed in their letter received on 19 Feb 2009, in response to the Investigational New Drug (IND) submission for BRV iv solution: - 12-lead ECGs were to be recorded; predose and at 5 minutes, 15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, and 12 hours immediately after the initiation of BRV iv administration - During the BRV iv administration, continuous live monitoring of ECG was included - There was a change in the statistical analysis of the ECG data, with only the central readings of the ECG data to be used in the descriptive and shift tables

Protocol Amendment 3 was approved and effective prior to the date of FPFV. The rationale for this amendment was to increase the total daily dose of BRV to 200 mg/day (100 mg/intake bid) from the original dose of 100 mg/day (50 mg/intake bid) in line with the recommendation of the regulatory authorities and in accordance with the oral dose that UCB had selected for Evaluation in the new Phase 3 study (N01358). The following changes were made throughout the protocol: - The dose in the LTFU study (N01379) was increased from 100 mg/day to 200 mg/day - The Down-Titration Period was increased from 2 weeks to 4 weeks with a 4-step down-titration instead of the previous 2-step down-titration - The dosing schedule for the Down-Titration Period was clarified - The duration of the iv bolus was increased from 60 seconds to 2 minutes - The maximum study and treatment durations for each subject were increased - The number of sites expected to participate in the study was increased to approximately 35 - Information on blinding during the Run-In Period and the Down-Titration Period was added - Information on the description of the study drug, packaging, and supply was updated - The timing of serum and urine pregnancy tests was revised - The randomization and IVRS processes was updated

The following changes were made throughout the protocol: - The patient-reported outcomes (PRO) questionnaires (Patient Weighted Quality of Life in Epilepsy Inventory-Form 31 [QOLIE-31-P] and Hospital Anxiety and Depression Scale [HADS]) were removed from the exploratory objectives and variables. Only baseline data were collected at V2 to allow for evaluation later in the LTFU study, N01379 - The EuroQoL-5 Dimensions questionnaire was removed - Socio-professional data were added at V2 to provide baseline data to allow for eEvaluation later in the LTFU study, N01379 - The collection and analysis of deoxyribonucleic acid (DNA) samples were removed, as this analysis will be conducted in another study - The exploratory objective for healthcare resource utilization was corrected to include this assessment at other visits as well as baseline data - The number of the LTFU study was added - The timing of the BRV and AED sampling during the iv administration was revised, and the sampling of concomitant AED levels at the SV (V8) was removed - Healthcare provider consultations not foreseen by the protocol was added as a component of the healthcare resource utilization variable - The Sponsor contact information was updated - The contract research organization (CRO) information was added - The protocol summary and introduction sections were updated - Other minor editorial changes were made to ensure consistency within the protocol and across the BRV program

Protocol Amendment 4 was approved and effective after subjects had been enrolled in the study. The rationale for this amendment was to implement the USA FDA Final Rule requirements with regard to procedures for reporting serious adverse events (SAEs) and to address the requirement of the FDA that prospective assessments for suicidality should be included in clinical studies involving all drugs for neurological indications. The following changes were made throughout the protocol: - A suicidality assessment using the Columbia-Suicide Severity Rating Scale (C-SSRS) in response to the USA FDA requirement was included - The prospective assessment for suicidality using the C-SSRS was added to the exclusion criteria, withdrawal criteria, and safety assessments - The list of Anticipated SAEs in response to the USA FDA Final Rule was added - A few minor changes were made to the protocol to update the name of the Clinical Project Manager (CPM), to clarify some study conduct details, and to correct grammatical errors