Long-term Extension Study to Assess Adverse Events of Oral Atogepant Tablets in Pediatric Participants (6 to 17 Years of Age) With Episodic Migraine

Study Overview
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Brief Summary
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A migraine is a moderate to severe headache on one side of the head. A migraine attack is a headache that may be accompanied by throbbing, nausea, vomiting, sensitivity to light and sound, or other symptoms. A number of treatments are available for adults with migraine but there are limited approved treatments available for participants less than 18 years of age. The main goal of the study is to evaluate the long-term safety and tolerability of atogepant in pediatric participants between the ages of 6 and 17 with episodic migraine. Atogepant is a medicine currently approved to treat adults with episodic migraine (0 to 14 migraine days per month) and is being studied in pediatric participants between the ages of 6 and 17 with a history of episodic migraine. This is a Phase 3, open-label study of atogepant in participants with a history of episodic migraine. Participants must have completed participation in another study of atogepant (lead-in study) or completed the screening period of that study. Participants must have 4 to 14 migraine days and less than 15 headache days in the 4-week screening electronic diary (eDiary; similar to a smart phone). Around 250 participants will be enrolled in the study at approximately 100 sites worldwide. Atogepant is a tablet taken once a day by mouth. Participants between the ages of 12 and 17 will receive high dose atogepant for 52 Weeks. Participants between the ages of 6 and 11 will receive an atogepant dose determined in the lead-in study for 52 Weeks. There may be a bigger responsibility for participants in this study. Participants will attend regular visits during the study at a hospital or clinic. The effects of treatment will be checked by medical assessments, blood tests, checking for side effects, and completing questionnaires.

Official Title
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A Multicenter, Open-label, Extension Study to Evaluate the Long-term Safety of Atogepant in Pediatric Subjects 6 to 17 Years of Age With Episodic Migraine

Conditions
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Episodic Migraine

Intervention / Treatment
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* Drug: Atogepant


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants must be between 6 and 17 years of age (inclusive), with a history of episodic migraine. The participant must have completed the lead-in Study M21-201, the pharmacokinetic (PK) substudy in Study M21-201, or completed the 4-week screening/baseline period and screen failed due to not meeting the number of migraine day requirements for the inclusion criteria in Study M21-201, and, in the judgment of the investigator, the participant is an appropriate candidate to be treated with a daily preventive migraine treatment with atogepant (not applicable for de novo migraine participants) Weight is >= 20 kg (44 lbs) and < 135 kg (298 lbs). A history of migraine with or without aura consistent with a diagnosis according to the International Classification of Headache Disorders, 3rd Edition (ICHD-3; 2018) for at least 6 months. Exclusion Criteria: History of migraine aura with diplopia or impairment of level of consciousness, hemiplegic migraine, or retinal migraine as defined by ICHD-3 (2018). Have a current diagnosis of chronic migraine as defined by ICHD-3 (2018). Have a current diagnosis of new persistent daily headache, trigeminal autonomic cephalgia (e.g., cluster headache), or painful cranial neuropathy as defined by ICHD-3 (2018). Have any clinically significant hematologic, endocrine, pulmonary, renal, hepatic, gastrointestinal, cardiovascular, or neurologic disease.

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Atogepant Dose A (12-17 yrs)<br>Participant aged 12-17 will receive oral tablets of atogepant Dose A once a day for up to 52 weeks. | Drug: Atogepant<br>* Oral Tablet<br>* Other names: AGN-241689;|
| Experimental: Atogepant Dose B (6-11 yrs)<br>Participants aged 6-11 will receive the highest dose of oral tablets of atogepant tested in the lead-in study M21-201. | Drug: Atogepant<br>* Oral Tablet<br>* Other names: AGN-241689;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants with Adverse Events (AEs) | AE, defined as any unfavorable medical event that is temporarily related to the use of the investigational product, which does not necessarily have a causal relationship with the investigational product. | Up to 56 Weeks | 
| Percentage of Participants with Potentially Clinically Significant Lab Values | Percentage of participants with abnormal change in clinical laboratory test results like hematology, chemistry and urinalysis will be assessed. | Up to 52 Weeks | 
| Percentage of Participants with Potentially Clinically Significant Clinical 12-lead Electrocardiogram (ECG) | 12-lead resting ECGs will be recorded. Parameters include heart rate, PR interval, QT interval, QRS duration, and QT interval corrected using Fridericia's formula (QTcF). | Up to 52 Weeks | 
| Percentage of Participants with Potentially Clinically Significant Vital Sign Parameters | Number of participants with abnormal change from baseline in vital sign measurements like systolic and diastolic blood pressure will be assessed. | Up to 52 Weeks | 
| Percentage of with Participants with Treatment-Emergent Suicidal Ideations with Intent, with or without a Plan (i.e., Type 4 or 5 on Columbia-Suicide Severity Rating Scale [C-SSRS]), or any Suicidal Behaviors | The C-SSRS is a clinician-rated instrument that reports the severity of both suicidal ideation and behavior. Suicidal ideation was classified on a 5-item scale: 1 (wish to be dead), 2 (nonspecific active suicidal thoughts), 3 (active suicidal ideation with any methods [not plan] without intent to act), 4 (active suicidal ideation with some intent to act, without specific plan), and 5 (active suicidal ideation with specific plan and intent). Suicidal behavior is classified on a 5-item scale: 0 (no suicidal behavior), 1 (preparatory acts or behavior), 2 (aborted attempt), 3 (interrupted attempt), and 4 (actual attempt). | Up to 52 Weeks | 
| Percentage of Participants with Change in Menstrual Cycle (Female Participants Only) | Female participants who have entered menarche are to be asked for the date of the first and last day of their most recent menstrual period. | Up to 52 Weeks | 
| Change from Baseline in Tanner Staging Score | Tanner's staging is used to assess growth and pubertal development. | Baseline (Week 0) through Week 52 | 
| Change from Baseline in Behavior Rating Inventory of Executive Function, 2nd Edition (BRIEF 2) questionnaire | The BRIEF 2 is an 86-item questionnaire assessing executive function. It consists of 2 indexes, Behavioral Regulation and Metacognition, which are then used to calculate an overall composite score. Higher scores indicate more executive difficulties | Baseline (Week 0) through Week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Episodic Migraine, Atogepant, QULIPTA, AGN-241689