Efficacy, Safety, and Tolerability of Atogepant in the Preventive Treatment of Menstrual Migraine: A Phase 3 Randomized, Double-Blind, Placebo-Controlled Study

The primary objective of this study is to evaluate the **efficacy** of atogepant, administered consecutively for 7 days, compared to placebo, for the preventive treatment of **menstrual migraine**. This is clinically relevant as menstrual migraine can significantly impact the quality of life, and effective preventive treatments are essential for managing this condition.

The secondary objective is to assess the **safety** and **tolerability** of atogepant treatment in subjects with menstrual migraine. Understanding the safety profile and tolerability is crucial for ensuring that the treatment is not only effective but also safe for long-term use in patients.

The clinical trial investigating the efficacy of atogepant for the preventive treatment of **menstrual migraine** involves a total of 183 participants. The study population consists exclusively of adult female individuals, aged 18 years and older, who have a documented history of regular menstrual cycles ranging from 21 to 35 days. Participants were selected based on their history of migraine, with or without aura, as defined by the International Classification of Headache Disorders, 3rd edition (ICHD-3), for at least 12 months prior to the screening visit. The trial excludes male subjects and does not involve any vulnerable populations. Participants are required to have experienced migraine onset before the age of 50 and must meet specific criteria for pure menstrual migraine or menstrually-related migraine, as confirmed by eDiary records during the screening period. Lifestyle factors such as diet and physical activity are not specified as part of the selection criteria for this study.

The clinical trial is a **Phase 3**, multicenter, randomized, double-blind, placebo-controlled study with an open-label extension designed to evaluate the efficacy, safety, and tolerability of **Atogepant** for the preventive treatment of **menstrual migraine**. The trial aims to assess the primary objective of evaluating the efficacy of Atogepant taken consecutively for 7 days compared to placebo. The study is expected to commence recruitment on February 24, 2025, and conclude by August 8, 2027. Participants will be involved in the study for a maximum treatment period of 232 days.

The trial will include several study visits, beginning with an inclusion (screening) visit where eligibility criteria are confirmed. Participants must be adults aged 18 or older with a history of migraine, as defined by the International Classification of Headache Disorders (ICHD-3), and regular menstrual cycles. The screening period involves recording three perimenstrual periods (PMPs) in an electronic diary, with at least two PMPs showing migraine attacks. Following successful screening, participants will be randomized to receive either Atogepant or placebo in a double-blind manner.

Subsequent follow-up visits will occur throughout the double-blind period, during which the primary endpoint will be assessed: the change from baseline in the number of migraine days during the PMP averaged across three menstrual cycles. Secondary endpoints include the reduction in migraine days, acute medication use, and headache days, as well as the assessment of disability or impairment. The trial will conclude with an end-of-study visit, where final assessments and evaluations will be conducted.

Participants may be withdrawn from the study early if they experience adverse events, fail to comply with study procedures, or withdraw consent. The trial is structured to ensure rigorous data collection and analysis, maintaining the integrity of the study's findings. The use of a placebo control and double-blind design minimizes bias and enhances the reliability of the results.

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 primary objective of the trial is to evaluate the efficacy of Atogepant for the preventive treatment of menstrual migraine. Participants will receive Atogepant consecutively for 7 days. The specific dosage in milligrams is not detailed in the provided data, but the maximum treatment period is specified as 232 days. Compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the protocol.

The study also includes a **placebo** group to serve as a control for comparison with the active treatment. The placebo is designed to mimic the Atogepant tablet in appearance but does not contain the active substance. The placebo will be administered orally, following the same schedule as the Atogepant group, to maintain the double-blind nature of the trial. This ensures that neither the participants nor the investigators are aware of the treatment assignments, thereby reducing bias in the assessment of the treatment's efficacy and safety.

The efficacy of Atogepant for the preventive treatment of **menstrual migraine** will be assessed in a Phase 3, multicenter, randomized, double-blind, placebo-controlled study with an open-label extension. The primary endpoint for evaluating efficacy is the change from baseline in the number of migraine days occurring during the perimenstrual period (PMP), averaged across three menstrual cycles during the double-blind period. Secondary endpoints include the change from baseline in the number of migraine days with moderate or severe headache during the PMP, a 50% or greater reduction from baseline in the number of migraine days, the change from baseline in the number of acute medication use days, and the change from baseline in the number of moderate or severe headache days during the PMP. Additionally, a 100% reduction from baseline in the number of migraine days, no disability or mild impairment for 100% of PMP days assessed by the Functional Disability Scale (FDS), and the change from baseline in the number of headache days during the PMP will also be evaluated.