Phase 3 Multicenter Open-Label Study on Long-Term Safety and Tolerability of Rimegepant for Acute Migraine Treatment in Pediatric Patients Aged 6 to 17 Years

The primary objective of this study is to evaluate the **safety** and tolerability of rimegepant in children and adolescents aged 6 to less than 18 years with acute migraine, with or without aura. This is clinically relevant as it aims to ensure that rimegepant, a medication used for acute migraine treatment, is safe for use in a younger population, potentially expanding treatment options for this age group.

Secondary objectives include assessing the frequency and severity of hepatic-related adverse events and the frequency of hepatic-related treatment discontinuations in the same demographic. These objectives are crucial for understanding the hepatic safety profile of rimegepant in pediatric patients, which is essential for long-term treatment planning and risk management.

The clinical trial involves a total of **502 participants** diagnosed with **acute migraine** (with or without aura). The study population comprises children and adolescents aged 6 to less than 18 years, including both male and female subjects. Participants were selected based on a history of migraine for at least six months prior to screening and experiencing one to eight moderate or severe attacks per month in the two months preceding the screening. The trial includes individuals who can verbally distinguish between migraine and other types of headaches and have a body weight greater than 15 kg, with specific weight criteria for participants aged 12 to less than 18 years in EU countries. Participants are allowed to continue prophylactic migraine medication if the dosage has been stable for at least 12 weeks before the screening visit. The study population is characterized by adequate venous access for blood sampling and includes a vulnerable population, as defined by the trial's criteria. Lifestyle factors such as diet and physical activity are not specified in the available data.

The clinical trial is a **Phase 3**, multicenter, open-label study designed to assess the long-term safety and tolerability of **rimegepant** for the acute treatment of **migraine** (with or without aura) in children and adolescents aged 6 to less than 18 years. The trial is expected to run from March 15, 2021, to September 1, 2025. Participants will be administered **rimegepant** in the form of an oral lyophilisate, with a maximum daily dose of 75 mg or 50 mg, depending on the formulation. The trial will involve a series of study visits, beginning with a screening visit to confirm eligibility based on criteria such as a history of migraine for at least six months and the ability to distinguish between migraine and other headaches. Participants must also have a stable dose of any prophylactic migraine medication for at least 12 weeks prior to the screening visit.

Following the screening, participants will enter the treatment phase, which will last up to 50 days. During this period, the frequency and severity of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) will be closely monitored. The primary endpoint focuses on the occurrence of TEAEs in at least 5% of participants, while secondary endpoints include the frequency and severity of hepatic-related adverse events. Participants will have regular follow-up visits to assess safety and tolerability, with blood samples collected to monitor clinically significant laboratory abnormalities. The study will conclude with an end-of-study visit to evaluate the overall safety profile of the treatment.

Participant involvement is expected to last for the duration of the treatment period, with conditions for early termination including the occurrence of severe adverse events or clinically significant laboratory abnormalities. The trial is not categorized as low intervention, and the study design does not include a control group, as it is open-label. The trial aims to provide valuable data on the safety and tolerability of **rimegepant** in a pediatric population, contributing to the understanding of its use in treating acute migraine in this age group.

The clinical trial involves the administration of **Rimegepant**, an experimental medication, in two different formulations. The first formulation is **VYDURA 75 mg oral lyophilisate**, which is designed for oral administration. This pharmaceutical form is a lyophilized tablet that dissolves in the mouth, facilitating ease of use. The maximum daily dose for this formulation is 75 mg, with a total treatment period not exceeding 50 days. The active substance, **Rimegepant**, is a chemical compound known for its potential efficacy in treating migraine. The administration route is strictly oral, and the formulation is not specifically designed for pediatric use. Compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the protocol.

The second formulation used in the trial is a **25 mg oral lyophilisate**. Similar to the 75 mg version, this formulation is also administered orally and is designed to dissolve in the mouth. The maximum daily dose for this formulation is 50 mg, with the same treatment period limit of 50 days. The active ingredient remains **Rimegepant**, and the formulation is chemically identical to the 75 mg version, differing only in dosage. This formulation is also not specifically tailored for pediatric patients. Participant compliance is closely monitored to ensure the integrity of the trial data.

Both formulations are produced by Pfizer, with the 75 mg version being authorized under the marketing authorization number EU/1/22/1645/002 and the 25 mg version currently holding a different authorization status. The trial does not include any non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments. The primary objective of the trial is to evaluate the safety and tolerability of **Rimegepant** in children and adolescents aged 6 to less than 18 years, specifically for the acute treatment of migraine, with or without aura.

The efficacy of the clinical trial will be assessed through the evaluation of the frequency and severity of on-treatment and treatment-emergent adverse events (TEAEs) occurring in at least 5% of treated participants. Additionally, the frequency of serious adverse events (SAEs), adverse events (AEs) leading to discontinuation, and clinically significant laboratory abnormalities during the treatment period will be analyzed. Clinically significant laboratory abnormalities are defined as on-treatment Grade 3 to 4 laboratory test results. The trial will also assess the frequency and severity of hepatic-related adverse events (AEs) and the frequency of hepatic-related AEs leading to treatment discontinuation. These will be tabulated from case report forms and based on unique participants reporting such events, with severity assessed as the worst severity observed while the participant is on treatment.