Efficacy, Safety, and Tolerability Study of Oral Ubrogepant in the Acute Treatment of Migraine

Study Overview
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Brief Summary
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This study will evaluate the efficacy, safety, and tolerability of 2 doses of ubrogepant (50 and 100 mg) compared to placebo for the acute treatment of a single migraine attack.

Official Title
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A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Single Attack Study to Evaluate the Efficacy, Safety, and Tolerability of Oral Ubrogepant in the Acute Treatment of Migraine

Conditions
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Migraine, With or Without Aura

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: At least a 1-year history of migraine with or without aura consistent with a diagnosis according to the International Classification of Headache Disorders, 3rd edition, beta version Migraine onset before age 50 History of migraines typically lasting between 4 and 72 hours if untreated or treated unsuccessfully and migraine episodes are separated by at least 48 hours of headache pain freedom History of 2 to 8 migraine attacks per month with moderate to severe headache pain in each of the previous 3 months. Exclusion Criteria: Difficulty distinguishing migraine headache from other headaches Has taken medication for acute treatment of headache (including acetaminophen, nonsteroidal anti-inflammatory drugs [NSAIDs], triptans, ergotamine, opioids, or combination analgesics) on 10 or more days per month in the previous 3 months Has a history of migraine aura with diplopia or impairment of level of consciousness, hemiplegic migraine, or retinal migraine Has a current diagnosis of new persistent daily headache, trigeminal autonomic cephalgia (eg, cluster headache), or painful cranial neuropathy Required hospital treatment of a migraine attack 3 or more times in the previous 6 months Has a chronic non-headache pain condition requiring daily pain medication Has a history of malignancy in the prior 5 years, except for adequately treated basal cell or squamous cell skin cancer, or in situ cervical cancer Has a history of any prior gastrointestinal conditions (eg, diarrhea syndromes, inflammatory bowel disease) that may affect the absorption or metabolism of investigational product; participants with prior gastric bariatric interventions which have been reversed are not excluded Has a history of hepatitis within previous 6 months.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ubrogepant 50 mg<br>1 ubrogepant 50 mg tablet and 1 placebo-matching ubrogepant 50 mg tablet, orally for treatment of a qualifying migraine attack. Participants had the option to take a second dose, 2 placebo-matching ubrogepant tablets or rescue medication, orally 2 to 48 hours after initial treatment. | Drug: Ubrogepant<br>* 50 mg ubrogepant tablet(s) orally for the treatment of a qualifying migraine attack.<br>Drug: Placebo-matching Ubrogepant<br>* Placebo-matching ubrogepant tablet(s) orally for the treatment of a qualifying migraine attack.<br>|
| Experimental: Ubrogepant 100 mg<br>2 Ubrogepant 50 mg tablets, orally for treatment of a qualifying migraine attack. Participants had the option to take a second dose, 2 placebo-matching ubrogepant tablets or rescue medication, orally 2 to 48 hours after initial treatment. | Drug: Ubrogepant<br>* 50 mg ubrogepant tablet(s) orally for the treatment of a qualifying migraine attack.<br>Drug: Placebo-matching Ubrogepant<br>* Placebo-matching ubrogepant tablet(s) orally for the treatment of a qualifying migraine attack.<br>|
| Placebo Comparator: Placebo<br>2 placebo-matching ubrogepant 50 mg tablets, orally for treatment of a qualifying migraine attack. Participants had the option to take 2-placebo-matching ubrogepant tablets or rescue medication, orally 2 to 48 hours after initial treatment. | Drug: Placebo-matching Ubrogepant<br>* Placebo-matching ubrogepant tablet(s) orally for the treatment of a qualifying migraine attack.<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 Initial Dose | Pain freedom was defined as a reduction in headache severity from moderate/severe at baseline to no pain at 2 hours after the initial dose. Participants were provided with an electronic diary (eDiary) to rate headache severity on a scale from no pain to severe pain. Number analyzed is the number of participants with non-missing postdose pain severity assessment at or before 2 hours after initial dose. | 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 | 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'. Participants were provided with an eDiary to record absence or presence of migraine-associated symptoms. Number analyzed is the number of participants with non-missing postdose most bothersome migraine-associated symptoms. | Baseline (Predose) to 2 hours after initial dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Pain Relief at 2 Hours After the Initial Dose | Pain relief was defined as a reduction of a moderate/severe migraine headache to a mild headache or to no headache. Participants were provided with an eDiary to rate headache severity on a scale from no pain to severe pain. Number analyzed is the number of participants with non-missing pain severity assessment at or before 2 hours after initial dose. | Baseline (Predose) to 2 hours after initial dose | 
| Percentage of Participants With Sustained Pain Relief From 2 to 24 Hours After Initial Dose | Sustained pain relief was defined as a pain relief at 2 hours with no administration of either rescue medication or the second dose of study drug, and with no occurrence thereafter of a moderate/severe headache up to 24 hours after dosing with study drug. Participants were provided with an eDiary to rate headache severity on a scale from no pain to severe pain. Determinable cases: participants for whom sustained pain relief from 2 to 24 hours status can be determined based on the observed headache severity at scheduled time points, use of rescue medication or optional second dose between 2 and 24 hours, and the answer to the headache recurrence question at 24 hours. Number analyzed is the number of participants with determinable sustained pain relief from 2 to 24 hours after initial dose. | 2 to 24 hours after initial dose | 
| Percentage of Participants With Sustained Pain Freedom From 2 to 24 Hours After Initial Dose | 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. Participants were provided with an eDiary to rate headache severity on a scale from no pain to severe pain. Determinable cases: participants for whom sustained pain relief from 2 to 24 hours status can be determined based on the observed headache severity at scheduled time points, use of rescue medication or optional second dose between 2 and 24 hours, and the answer to the headache recurrence question at 24 hours. Number analyzed is the number of participants with determinable sustained pain freedom from 2 to 24 hours after initial dose. | 2 to 24 hours after initial dose | 
| Percentage of Participants With the Absence of Photophobia at 2 Hours After the Initial Dose | Photophobia was defined as sensitivity to light, a migraine-associated symptom. Participants were provided with an eDiary to record absence or presence photophobia. Number analyzed is the number of participants with non-missing postdose photophobia assessment at or before 2 hours after initial dose. | 2 hours after initial dose | 
| Percentage of Participants With the Absence of Phonophobia at 2 Hours After the Initial Dose | Phonophobia was defined as sensitivity to sound, a migraine-associated symptom. Participants were provided with an eDiary to record absence or presence of phonophobia. Number analyzed is the number of participants with non-missing postdose phonophobia assessment at or before 2 hours after initial dose. | 2 hours after initial dose | 
| Percentage of Participants With Absence of Nausea at 2 Hours After the Initial Dose | Nausea was a migraine-associated symptom. Participants were provided with an eDiary to record absence or presence of nausea. Number analyzed is the number of participants with non-missing postdose nausea assessment at or before 2 hours after initial dose. | 2 hours after initial dose |