Migraine, With or Without Aura
Conditions
Brief summary
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.
Interventions
DRUGUbrogepant
50 mg ubrogepant tablet(s) orally for the treatment of a qualifying migraine attack.
Placebo-matching ubrogepant tablet(s) orally for the treatment of a qualifying migraine attack.
Sponsors
Allergan
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Pain Freedom at 2 Hours After Initial Dose | Baseline (Predose) to 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. |
| Percentage of Participants With Absence of the Most Bothersome Migraine-Associated Symptom Identified at Baseline at 2-Hours After Initial Dose | Baseline (Predose) to 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Sustained Pain Freedom From 2 to 24 Hours After Initial Dose | 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. |
| Percentage of Participants With the Absence of Photophobia at 2 Hours After the Initial Dose | 2 hours after 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. |
| Percentage of Participants With Pain Relief at 2 Hours After the Initial Dose | Baseline (Predose) to 2 hours after 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. |
| Percentage of Participants With Absence of Nausea at 2 Hours After the Initial Dose | 2 hours after 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. |
| Percentage of Participants With the Absence of Phonophobia at 2 Hours After the Initial Dose | 2 hours after 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. |
| Percentage of Participants With Sustained Pain Relief From 2 to 24 Hours After Initial Dose | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo 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. | 559 |
| Ubrogepant 50 mg 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. | 556 |
| Ubrogepant 100 mg 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. | 557 |
| Total | 1,672 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Safety Follow-up Period | Lost to Follow-up | 9 | 8 | 11 |
| Safety Follow-up Period | Other Miscellaneous Reasons | 1 | 0 | 0 |
| Safety Follow-up Period | Protocol Violation | 0 | 2 | 1 |
| Safety Follow-up Period | Withdrawal of Consent | 10 | 8 | 7 |
| Treatment Period | Adverse Event | 3 | 1 | 1 |
| Treatment Period | Lack of Qualifying Event | 44 | 53 | 43 |
| Treatment Period | Lost to Follow-up | 21 | 24 | 18 |
| Treatment Period | Other Miscellaneous Reasons | 0 | 1 | 0 |
| Treatment Period | Pregnancy | 0 | 2 | 0 |
| Treatment Period | Protocol Violation | 2 | 4 | 7 |
| Treatment Period | Withdrawal of Consent | 10 | 14 | 9 |
Baseline characteristics
| Characteristic | Placebo | Ubrogepant 50 mg | Ubrogepant 100 mg | Total |
|---|---|---|---|---|
| Age, Continuous | 41.1 years STANDARD_DEVIATION 11.9 | 40.2 years STANDARD_DEVIATION 12 | 40.7 years STANDARD_DEVIATION 12.4 | 40.7 years STANDARD_DEVIATION 12.1 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 3 Participants | 3 Participants | 5 Participants | 11 Participants |
| Race/Ethnicity, Customized Asian | 10 Participants | 9 Participants | 8 Participants | 27 Participants |
| Race/Ethnicity, Customized Black or African American | 65 Participants | 77 Participants | 88 Participants | 230 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 60 Participants | 67 Participants | 66 Participants | 193 Participants |
| Race/Ethnicity, Customized Multiple | 7 Participants | 7 Participants | 4 Participants | 18 Participants |
| Race/Ethnicity, Customized Native Hawaiian/Other Pacific Islander | 3 Participants | 1 Participants | 5 Participants | 9 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 499 Participants | 489 Participants | 491 Participants | 1479 Participants |
| Race/Ethnicity, Customized White | 471 Participants | 459 Participants | 447 Participants | 1377 Participants |
| Sex: Female, Male Female | 491 Participants | 493 Participants | 479 Participants | 1463 Participants |
| Sex: Female, Male Male | 68 Participants | 63 Participants | 78 Participants | 209 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 485 | 0 / 466 | 0 / 485 |
| other Total, other adverse events | 0 / 485 | 0 / 466 | 0 / 485 |
| serious Total, serious adverse events | 0 / 485 | 3 / 466 | 2 / 485 |
Outcome results
Primary
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.
Time frame: Baseline (Predose) to 2 hours after initial dose
Population: mITT population included all randomized participants who received at least 1 dose of investigational product, recorded a baseline migraine headache severity measurement, and had ≥ 1 postdose migraine headache severity or migraine-associated symptom measurement at or before the 2-hour timepoint, LOCF.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Absence of the Most Bothersome Migraine-Associated Symptom Identified at Baseline at 2-Hours After Initial Dose | 27.8 percentage of participants |
| Ubrogepant 50 mg | Percentage of Participants With Absence of the Most Bothersome Migraine-Associated Symptom Identified at Baseline at 2-Hours After Initial Dose | 38.6 percentage of participants |
| Ubrogepant 100 mg | Percentage of Participants With Absence of the Most Bothersome Migraine-Associated Symptom Identified at Baseline at 2-Hours After Initial Dose | 37.7 percentage of participants |
p-value: 0.002395% CI: [1.27, 2.28]Regression, Logistic
p-value: 0.002395% CI: [1.22, 2.17]Regression, Logistic
Primary
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.
Time frame: Baseline (Predose) to 2 hours after initial dose
Population: Modified Intent-to-Treat (mITT) population included all randomized participants who received at least 1 dose of study drug, recorded a baseline migraine headache severity measurement, and had ≥ 1 postdose migraine headache severity or migraine-associated symptom measurement at or before the 2-hour timepoint, last observation carried forward (LOCF).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Pain Freedom at 2 Hours After Initial Dose | 11.8 percentage of participants |
| Ubrogepant 50 mg | Percentage of Participants With Pain Freedom at 2 Hours After Initial Dose | 19.2 percentage of participants |
| Ubrogepant 100 mg | Percentage of Participants With Pain Freedom at 2 Hours After Initial Dose | 21.2 percentage of participants |
p-value: 0.002395% CI: [1.25, 2.66]Regression, Logistic
p-value: 0.000395% CI: [1.41, 2.95]Regression, Logistic
Secondary
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.
Time frame: 2 hours after initial dose
Population: mITT population included all randomized participants who received at least 1 dose of investigational product, recorded a baseline migraine headache severity measurement, and had ≥ 1 postdose migraine headache severity or migraine-associated symptom measurement at or before the 2-hour timepoint, LOCF.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Absence of Nausea at 2 Hours After the Initial Dose | 62.3 percentage of participants |
| Ubrogepant 50 mg | Percentage of Participants With Absence of Nausea at 2 Hours After the Initial Dose | 70.2 percentage of participants |
| Ubrogepant 100 mg | Percentage of Participants With Absence of Nausea at 2 Hours After the Initial Dose | 69.2 percentage of participants |
p-value: 0.096295% CI: [0.96, 1.79]Regression, Logistic
p-value: 0.096295% CI: [1, 1.83]Regression, Logistic
Secondary
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.
Time frame: Baseline (Predose) to 2 hours after initial dose
Population: mITT population included all randomized participants who received at least 1 dose of investigational product, recorded a baseline migraine headache severity measurement, and had ≥ 1 postdose migraine headache severity or migraine-associated symptom measurement at or before the 2-hour timepoint, LOCF.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Pain Relief at 2 Hours After the Initial Dose | 49.1 percentage of participants |
| Ubrogepant 50 mg | Percentage of Participants With Pain Relief at 2 Hours After the Initial Dose | 60.7 percentage of participants |
| Ubrogepant 100 mg | Percentage of Participants With Pain Relief at 2 Hours After the Initial Dose | 61.4 percentage of participants |
p-value: 0.002395% CI: [1.28, 2.23]Regression, Logistic
p-value: 0.002395% CI: [1.28, 2.21]Regression, Logistic
Secondary
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.
Time frame: 2 to 24 hours after initial dose
Population: mITT population included all randomized participants who received at least 1 dose of investigational product, recorded a baseline migraine headache severity measurement, and had ≥ 1 postdose migraine headache severity or migraine-associated symptom measurement at or before the 2-hour timepoint, determinable cases.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Sustained Pain Freedom From 2 to 24 Hours After Initial Dose | 8.6 percentage of participants |
| Ubrogepant 50 mg | Percentage of Participants With Sustained Pain Freedom From 2 to 24 Hours After Initial Dose | 12.7 percentage of participants |
| Ubrogepant 100 mg | Percentage of Participants With Sustained Pain Freedom From 2 to 24 Hours After Initial Dose | 15.4 percentage of participants |
p-value: 0.057795% CI: [1.01, 2.44]Regression, Logistic
p-value: 0.003795% CI: [1.28, 2.97]Regression, Logistic
Secondary
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.
Time frame: 2 to 24 hours after initial dose
Population: mITT population included all randomized participants who received at least 1 dose of investigational product, recorded a baseline migraine headache severity measurement, and had ≥ 1 postdose migraine headache severity or migraine-associated symptom measurement at or before the 2-hour timepoint, determinable cases.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Sustained Pain Relief From 2 to 24 Hours After Initial Dose | 20.8 percentage of participants |
| Ubrogepant 50 mg | Percentage of Participants With Sustained Pain Relief From 2 to 24 Hours After Initial Dose | 36.3 percentage of participants |
| Ubrogepant 100 mg | Percentage of Participants With Sustained Pain Relief From 2 to 24 Hours After Initial Dose | 38.0 percentage of participants |
p-value: 0.002395% CI: [1.65, 3.07]Regression, Logistic
p-value: 0.002395% CI: [1.77, 3.24]Regression, Logistic
Secondary
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.
Time frame: 2 hours after initial dose
Population: mITT population included all randomized participants who received at least 1 dose of investigational product, recorded a baseline migraine headache severity measurement, and had ≥ 1 postdose migraine headache severity or migraine-associated symptom measurement at or before the 2-hour timepoint, LOCF.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With the Absence of Phonophobia at 2 Hours After the Initial Dose | 47.1 percentage of participants |
| Ubrogepant 50 mg | Percentage of Participants With the Absence of Phonophobia at 2 Hours After the Initial Dose | 57.9 percentage of participants |
| Ubrogepant 100 mg | Percentage of Participants With the Absence of Phonophobia at 2 Hours After the Initial Dose | 54.5 percentage of participants |
p-value: 0.057795% CI: [1.16, 2.09]Regression, Logistic
p-value: 0.057795% CI: [1.1, 1.95]Regression, Logistic
Secondary
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.
Time frame: 2 hours after initial dose
Population: mITT population included all randomized participants who received at least 1 dose of investigational product, recorded a baseline migraine headache severity measurement, and had ≥ 1 postdose migraine headache severity or migraine-associated symptom measurement at or before the 2-hour timepoint, LOCF.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With the Absence of Photophobia at 2 Hours After the Initial Dose | 31.4 percentage of participants |
| Ubrogepant 50 mg | Percentage of Participants With the Absence of Photophobia at 2 Hours After the Initial Dose | 40.7 percentage of participants |
| Ubrogepant 100 mg | Percentage of Participants With the Absence of Photophobia at 2 Hours After the Initial Dose | 45.8 percentage of participants |
p-value: 0.057795% CI: [1.22, 2.19]Regression, Logistic
p-value: 0.003795% CI: [1.36, 2.42]Regression, Logistic