Study to Assess Adverse Events and Disease Activity of Oral Ubrogepant Tablets for the Acute Treatment of Migraine in Children and Adolescents (Ages 6-17)

Study Overview
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Brief Summary
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Migraine is a common neurological disorder typically characterized by attacks of throbbing, moderate to severe headache, often associated with nausea, vomiting, and sensitivity to light and sound. Migraine is extremely common and disabling in children. The purpose of this study is to evaluate how safe and effective ubrogepant is in the acute treatment of migraine in children and adolescents. Ubrogepant is a drug approved for the acute treatment of migraine in adults. Children and adolescents (aged 6-17 years) with a history of migraine will be enrolled. The study will include 2 cohorts of participants - PK Cohort and Main Study (non-PK cohort). Participants aged 6-11 years in the PK Cohort will receive Dose A or Dose B of Ubrogepant for PK analysis to determine dose selection for the main study. In the main study, after dose selection, children aged 6-11 years will be randomized to receive either low or high dose of Ubrogepant or placebo. There is a 1 in 3 chance that a participant will be assigned to placebo. Adolescents aged 12-17 years will be randomized to receive either low or high dose of Ubrogepant or placebo with a 1 in 3 chance of placebo assignment. For qualifying migraine attacks, participants will receive oral tablets of the double-blind study intervention. There will be an option to take a second dose of double-blind study intervention (identical to initial dose), or rescue medication, 2 to 24 hours after the initial dose, for headache of moderate/severe intensity. Around 1059 participants will be enrolled in the study in approximately 120 sites in the United States. The study duration will be up to 6 months. There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.

Official Title
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A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled, Single-attack Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacokinetics of Oral Ubrogepant in the Acute Treatment of Migraine With or Without Aura in Children and Adolescents (Ages 6-17)

Conditions
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Migraine

Intervention / Treatment
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* Drug: Ubrogepant
* Drug: Placebo-Matching Ubrogepant


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A history of migraine with or without aura consistent with a diagnosis according to the International Classification of Headache Disorders (ICHD-3) for at least 6 months. By history, the participant's migraines typically last between 3 and 72 hours if untreated or treated unsuccessfully and migraine episodes are separated by at least 48 hours of headache pain freedom. History of 1 to 14 migraine attacks per month with moderate to severe headache in each of the 2 months prior to screening (Visit 1). Current or past use of at least 1 oral medication (over-the-counter medication or prescription medication) for the acute treatment of migraine. For main study participants, treatment of a qualifying migraine with single-blind placebo during the screening period and completion of 2-hour headache pain assessment. Weight is ≥ 20 kg (44 pounds) and < 135 kg (298 pounds) Per investigator judgment, participant is able to swallow or can learn to swallow study intervention. The participant is able to understand and complete the study questionnaires and eDiary. Participants who need assistance with reading the assessments may be assisted by a parent or guardian. Exclusion Criteria: Any clinically significant hematologic, endocrine, pulmonary, renal, hepatic, gastrointestinal, cardiovascular or neurologic disease. In the opinion of the investigator, other confounding pain syndromes, confounding psychiatric conditions, or other significant neurological disorders other than migraine. History of malignancy in the 5 years prior to Visit 1. History of any prior gastrointestinal conditions (eg, diarrhea syndromes, inflammatory bowel disease) that may affect the absorption or metabolism of the study intervention. Significant risk of self-harm, based on clinical interview and responses on the Columbia-Suicide Severity Rating Scale (C-SSRS), or of harm to others; participants must be excluded if they report suicidal ideation with intent, with or without a plan, (ie, Type 4 or 5 on the C-SSRS) in the past 6 months or report suicidal behavior in the last 6 months prior to Visit 1 or Visit 2 assessments. At Visit 1, current alcohol or drug abuse or dependence per investigator's judgment. For main study participants, no headache at the 2-hour post dose assessment after taking single-blind placebo for a qualifying migraine during screening period (ie, placebo responder). A current diagnosis of chronic migraine as defined by ICHD-3 Participants who overuse medication for migraine defined as use of opioids or barbiturates > 2 days/month, triptans or ergots ≥ 10 days/month, simple analgesics (eg, aspirin, NSAIDs, acetaminophen) ≥ 15 days/month or any combination of triptans, ergots, or simple analgesics (eg, aspirin, NSAIDs, acetaminophen) ≥ 10 days/month in the 3 months prior to Visit 1 per investigator's judgment. Difficulty distinguishing migraine headache from tension-type or other headaches. Has a history of migraine aura with diplopia or impairment of level of consciousness, hemiplegic migraine, or retinal migraine as defined by ICHD-3. Has a current diagnosis of new persistent daily headache, trigeminal autonomic cephalgia (eg, cluster headache), or painful cranial neuropathy as defined by ICHD-3 Required in-hospital (excluding emergency department visits) treatment for migraines 3 or more times in the 6 months prior to Visit 1. Requirement for any medication (eg, barbiturates) or diet (eg, grapefruit juice) that is on the list of prohibited concomitant medications that cannot be discontinued or switched to an allowable, alternative medication at Visit 1. Previous exposure, within the last 6 months, to injectable monoclonal antibodies blocking the calcitonin gene-related peptide (CGRP) pathway History of hypersensitivity or clinically significant adverse reaction to a CGRP receptor antagonist or hypersensitivity to any component of the study interventions, ubrogepant or placebo. Currently participating or has participated in a study with an investigational compound or device within 30 days prior to Visit 1

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: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PK Cohort: Ubrogepant Dose A<br>Participants aged 6 to 11 will receive oral tablets of ubrogepant for PK analysis to determine appropriate dose for main study. | Drug: Ubrogepant<br>* Oral Tablet<br>* Other names: Ubrelvy;|
| Experimental: PK Cohort: Ubrogepant Dose B<br>Participants aged 6 to 11 will receive oral tablets of ubrogepant for PK analysis to determine appropriate dose for main study. | Drug: Ubrogepant<br>* Oral Tablet<br>* Other names: Ubrelvy;|
| Experimental: Main Study: Children Ubrogepant Low Dose<br>Participants aged 6 to 11 (after dose selection) will receive oral tablets of low dose ubrogepant for qualifying migraine attack. Participants have the option to take a second dose of ubrogepant or rescue medication, 2 to 24 hours after initial dose for headache of moderate/severe intensity. | Drug: Ubrogepant<br>* Oral Tablet<br>* Other names: Ubrelvy;|
| Experimental: Main Study: Children Ubrogepant High Dose<br>Participants aged 6 to 11 (after dose selection) will receive oral tablets of high dose ubrogepant Dose B for qualifying migraine attack. Participants have the option to take a second dose of ubrogepant or rescue medication, 2 to 24 hours after initial dose for headache of moderate/severe intensity. | Drug: Ubrogepant<br>* Oral Tablet<br>* Other names: Ubrelvy;|
| Placebo Comparator: Main Study: Children Ubrogepant Placebo<br>Participants aged 6 to 11 (after dose selection) will receive oral tablets of placebo-matching ubrogepant for qualifying migraine attack. Participants have the option to take a second dose of placebo-matching ubrogepant or rescue medication, 2 to 24 hours after initial dose for headache of moderate/severe intensity. | Drug: Placebo-Matching Ubrogepant<br>* Oral Tablet<br>|
| Experimental: Main Study: Adolescents Ubrogepant Low Dose<br>Participants aged 12 to 17 will receive oral tablets of ubrogepant low dose for qualifying migraine attack. Participants have the option to take a second dose of ubrogepant or rescue medication, 2 to 24 hours after initial dose for headache of moderate/severe intensity. | Drug: Ubrogepant<br>* Oral Tablet<br>* Other names: Ubrelvy;|
| Experimental: Main Study: Adolescents Ubrogepant High Dose<br>Participants aged 12 to 17 will receive oral tablets of ubrogepant high dose or qualifying migraine attack. Participants have the option to take a second dose of ubrogepant or rescue medication, 2 to 24 hours after initial dose for headache of moderate/severe intensity. | Drug: Ubrogepant<br>* Oral Tablet<br>* Other names: Ubrelvy;|
| Placebo Comparator: Main Study: Adolescents Ubrogepant Placebo<br>Participants aged 12 to 17 will receive oral tablets of placebo-matching ubrogepant for qualifying migraine attack. Participants have the option to take a second dose of placebo-matching ubrogepant or rescue medication, 2 to 24 hours after initial dose for headache of moderate/severe intensity. | Drug: Placebo-Matching Ubrogepant<br>* Oral Tablet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants with Pain Freedom at 2 Hours After the Initial Dose in pediatric participants aged 6 to 17 years | Pain Freedom is defined as a reduction in headache severity from moderate/severe at baseline to no pain. | 2 hours after initial dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants with Pain Freedom at 2 Hours After the Initial Dose in pediatric participants aged 12 to 17 years | Pain Freedom is defined as a reduction in headache severity from moderate/severe at baseline to | 2 hours after initial dose | 
| Percentage of participants with Pain Relief at 2 Hours After the Initial Dose in pediatric participants aged 12 to 17 years | Pain Relief is defined as a reduction in headache severity from moderate/severe at baseline to mild or no pain. | 2 hours after initial dose | 
| Percentage of Participants With Sustained Pain Freedom From 2 to 24 Hours After Initial Dose in pediatric participants aged 6 to 17 years | Sustained pain freedom was defined as a pain freedom at 2 hours with no administration of either rescue medication or the second dose of study drug, and with no occurrence thereafter of a mild/moderate/severe headache up to 24 hours after dosing with study drug. | 2 to 24 hours after initial dose | 
| Percentage of participants that used rescue medication (including a second dose of study intervention) within 24 hours after the initial dose in pediatric participants aged 6 to 17 years |  | 24 hours after initial dose | 
| Percentage of Participants With Absence of the Most Bothersome Migraine-Associated Symptom Identified at Baseline at 2-Hours After Initial Dose in pediatric participants aged 6 to 17 years | The most bothersome migraine-associated symptom was the symptom (photophobia, phonophobia or nausea) present at pre-dose baseline identified by the participant to be 'most bothersome'. | Baseline (Predose) to 2 hours after initial dose | 
| Percentage of Participants With Absence of the Most Bothersome Migraine-Associated Symptom Identified at Baseline at 2-Hours After Initial Dose in pediatric participants aged 12 to 17 years | The most bothersome migraine-associated symptom was the symptom (photophobia, phonophobia or nausea) present at pre-dose baseline identified by the participant to be 'most bothersome'. | Baseline (Predose) to 2 hours after initial dose | 
| Percentage of participants with Pain Freedom at 2 Hours After the Initial Dose in pediatric participants aged 6 to 11 years | Pain Freedom is defined as a reduction in headache severity from moderate/severe at baseline to no pain. | 2 hours after initial dose | 
| Percentage of Participants With the Absence of Photophobia at 2 Hours After the Initial Dose in pediatric participants aged 6 to 17 years | Photophobia was defined as sensitivity to light, a migraine-associated symptom. | 2 hours after initial dose | 
| Percentage of Participants With the Absence of Phonophobia at 2 Hours After the Initial Dose in pediatric participants aged 6 to 17 years | Phonophobia was defined as sensitivity to sound, a migraine-associated symptom. | 2 hours after initial dose | 
| Percentage of Participants With the Absence of Nausea at 2 Hours After the Initial Dose in pediatric participants aged 6 to 17 years | Nausea was a migraine-associated symptom. | 2 hours after initial dose | 
| Number of Participants with Adverse Events (AE) | An AE is any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. | Up to 6 months | 
| Percentage of Participants with Abnormal Change in Clinical Laboratory Test Results Like Hematology will be Assessed in pediatric participants aged 6 to 17 years | Percentage of participants with abnormal change in clinical laboratory test results like hematology will be assessed. | Up to 6 months | 
| Change From Baseline in Electrocardiograms (ECGs) in pediatric participants aged 6 to 17 years | 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 6 months | 
| Percentage of Participants with Abnormal Change From Baseline in Vital Sign Measurements in pediatric participants aged 6 to 17 years | Percentage of participants with abnormal change from baseline in vital sign measurements like systolic and diastolic blood pressure will be assessed. | Up to 6 months | 
| Percentage of patients with suicidal ideation or suicidal behavior |  | Up to 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Migraine, Ubrogepant, Ubrelvy, PERISCOPE