The following major changes were introduced in Protocol Amendment 1 dated 26 Oct 2018: • The original protocol allowed study participants without access to a Managed Access Plan to continue participation in EP0093 after the second year and until a Marketing Authorization was granted by any health authority for the adjunctive treatment of FOS in adults with drug-resistant epilepsy. This amendment limited the duration of participation of all study participants to 2 years. Study participants without access to a Managed Access Plan were offered the option to transfer to another study if approved by the relevant country agencies. • The number of sites increased from 150 to approximately 350. • The proposed indication statement was modified (drug-resistant was removed). • The study objectives specified that study participants had FOS as well as drug-resistant epilepsy. • In the analysis of the primary efficacy variable, the observable FOS frequency instead of the log-transformed observable FOS frequency was measured. • The “other” efficacy variable, time to discontinuation, was added. • It was specified that follow-up echocardiograms at 1 and 6 months after the last PSL intake were required. • China was added to the anticipated regions and countries in which the study was conducted. • The Schedule of Study Assessments was revised consistent with the main change in the amendment. This included a split of the EDV and EOT (called End of Study) visits into separate visits. • Valvular abnormality grading criteria, withdrawal criterion pertaining to echocardiographic findings, description of the measurements and observations included in the echocardiograms, laboratory measurements and prohibited concomitant treatments were made consistent with the feeder studies. • The prohibited concomitant treatments were revised to make them consistent with the feeder studies.

Continuation of Protocol Amendment 1 • A clarification of the description of the interpretation of echocardiograms was made. The local physician was required to examine the echocardiograms for suitability for central reading and for determination if an expedited review by the central reader was required. It was made explicit that the central reader is a cardiologist. • The Treatment Satisfaction Questionnaire for Medication (TSQM)-9 was added to study assessments. • A preference was specified for the QOLIE-31-P, SSG, and HADS questionnaires to be completed by the study participants. However, assistance from the study staff or caregiver was permitted.

The following major changes were introduced in Protocol Amendment 2 dated 04 Feb 2020: • The primary rationale for this global amendment was to update the name of the legal form of the Sponsor, UCB Biopharma. Belgium adopted a new Code of Companies and Associations, resulting in a mandatory change of the name of the legal form of the entity “société privée à responsabilité limitée”, abbreviated “SPRL”, to “société à responsabilité limitée”, abbreviated “SRL”. This change did not involve any change to the legal form itself, and the company name, company number and VAT number of UCB Biopharma remained the same. • A benefit risk assessment to comply with Section 6 of the ICH-GCP was added. • The specified dosage of 400mg/day as starting dose was deleted to allow more flexibility when adding further parent studies. The individual starting dose of each study participant was the one recommended at the end of the parent study.

Protocol Amendment 2 Addendum A dated 20 May 2020 was introduced in Bulgaria, Finland, France, and Norway due to the exceptional circumstances of the evolving COVID-19 pandemic. UCB proposed to implement measures to reduce the impact on the local health care provision and reduce the inherent risk of study driven hospital/site visits. For details on the visit schedule, drug accountability, and Investigational Medicinal Product (IMP) distribution under exceptional circumstances, see Protocol Amendment 2 Addendum A.