- The Screening and Baseline Periods were separated. - Statistical analyses were updated. - Notes were added to the schedule of assessments (SOA) to clarify activities. - Optional substudy assessments were put under separate SOA. - References to some exploratory objectives were removed. - Benefit risk-assessment language was updated to reflect current assessments. - End of study language edited to reflect current template format. - Added exclusion criteria 215: “Initiation, discontinuation, or change of dosing of migraine prophylactic medications within 2 months prior to the start of the baseline period, during the baseline period or planned during the study”. - Screen failure and rescreening language updated: a subject may be rescreened once if in the opinion of the investigator, the reason for the initial screen failure has been resolved or is no longer applicable. - Excluded treatments, medical devices, and/or procedures during the study period sections were updated. - Hepatotoxicity sections were removed per template language regarding it as optional.

- Reduced the sample size from 2000 participants to 1400 participants throughout the protocol as the study centers were not able to achieve the enrollment target and it was determined that a lower sample would still provide sufficient analytical power. - Updated sample size determination to align with the sample size. - Updated section on serious adverse events after the protocol-required reporting period, product complaints, adverse device effect definition, serious adverse event reporting by electronic data collection tool as per the latest template text.