A Multicenter, Open-label, Extension Study to Evaluate the Long-term Safety and Tolerability of Atogepant in Pediatric Subjects 6 to 17 years of age with Migraine

The primary objective of this multicenter, open-label extension study is to evaluate the long-term **safety** and tolerability of **atogepant** treatment for the prevention of **migraine** in pediatric participants aged 6 to 17 years. This objective is clinically relevant as it aims to ensure that atogepant, a medication administered orally in tablet form, is safe for long-term use in a younger population, which is crucial for managing migraine effectively in this age group. No secondary objectives are specified for this study.

The clinical trial involves a total of **163 participants** who are pediatric subjects aged between **6 and 17 years**. The study population includes both **male and female** participants, with a focus on individuals who have a history of **migraine**, either episodic or chronic. Participants were selected based on their completion of prior studies, specifically the lead-in Study M21-201, the pharmacokinetic substudy in Study M21-201, or the lead-in Study M23-712. The trial includes individuals with a weight range of **20 kg to 135 kg**. The study population is characterized by a history of migraine with or without aura, consistent with the **International Classification of Headache Disorders, 3rd Edition (ICHD-3; 2018)**, for at least six months. The trial does not specify any particular lifestyle considerations such as diet or physical activity. The inclusion of a vulnerable population is noted, although specific details are not provided.

The clinical trial is designed to evaluate the long-term safety and tolerability of **atogepant** in pediatric participants aged 6 to 17 years with **migraine**. This is an open-label, extension study, which means that all participants will receive the investigational product, and both the researchers and participants will know the treatment being administered. The trial is expected to run until November 16, 2029, with recruitment having commenced on September 15, 2023. Participants will be involved in the study for a maximum treatment period of 52 weeks, during which they will receive **atogepant** in tablet form, administered orally, with a maximum daily dose of 60 mg.

The study will include several key visits. Initially, there will be a screening visit to confirm eligibility based on criteria such as age, weight, and a history of **migraine** consistent with the International Classification of Headache Disorders, 3rd Edition. Participants must have completed a prior lead-in study or pharmacokinetic substudy. Follow-up visits will be scheduled to monitor safety and tolerability, including adverse event monitoring, clinical laboratory testing, electrocardiogram variables, vital sign measurements, and assessments specific to female participants and developmental stages. The end-of-study visit will conclude the participant's involvement, ensuring all safety parameters are reviewed.

Participants may be withdrawn from the study early if they experience significant adverse events, fail to adhere to the study protocol, or if the investigator deems it necessary for the participant's safety. The primary endpoints focus on the safety and tolerability of **atogepant**, with secondary endpoints not specified. The study aims to provide comprehensive data on the long-term use of **atogepant** in the pediatric population for the prevention of **migraine**.

The clinical trial involves the administration of **Atogepant**, a chemical compound developed by Allergan Sales, LLC, a subsidiary of AbbVie Inc. Atogepant is provided in the form of a **tablet** and is intended for oral administration. The maximum daily dose of Atogepant is 60 mg, with a total maximum dose of 21,840 mg over the course of the study. The treatment period extends up to 52 weeks. The primary objective of the trial is to evaluate the long-term safety and tolerability of Atogepant in pediatric subjects aged 6 to 17 years with **migraine**.

Participants in the study will receive Atogepant as the experimental medication. The dosing schedule is designed to ensure consistent administration, with participants taking the medication orally once daily. Compliance with the dosing regimen will be monitored throughout the study to ensure adherence to the protocol. No non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are specified for this trial. The study is structured as an open-label extension, allowing for the observation of long-term effects and tolerability of Atogepant in the specified pediatric population.

The efficacy of the clinical trial involving **Atogepant** will be assessed primarily through the evaluation of safety and tolerability parameters. The primary endpoints include monitoring adverse events (AEs) for severity and incidence, including adverse events of special interest (AESIs). Clinical laboratory tests such as hematology, chemistry, and urinalysis will be conducted to gather relevant data. Electrocardiogram (ECG) variables and vital sign measurements will also be part of the assessment to ensure comprehensive safety monitoring.

Additional assessments will include the evaluation of treatment-emergent suicidal ideations with intent, using the Columbia-Suicide Severity Rating Scale (C-SSRS), and any suicidal behaviors. For female subjects, menstrual cycle assessments will be conducted, and the Tanner Stage scale will be used to evaluate pubertal development. The Behavior Rating Inventory of Executive Function, 2nd Edition (BRIEF2), will be utilized to assess executive function behavior. These assessments will be conducted at various timepoints throughout the trial to ensure a thorough evaluation of the long-term safety and tolerability of **Atogepant** in pediatric subjects aged 6 to 17 years with migraine.