Migraine, With or Without Aura
Conditions
Brief summary
This study will evaluate the efficacy, safety, and tolerability of 2 doses of ubrogepant (25 and 50 mg) compared to placebo for the acute treatment of a single migraine attack.
Interventions
DRUGUbrogepant
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 tension-type 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, diarrhoea 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 pain severity from moderate/severe at baseline to no pain at 2 hours after the initial dose of investigational product. Participants were provided with 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 assessed. |
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 assessment of 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 assessment of determinable sustained pain relief from 2 to 24 hours after initial dose. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo 1 placebo-matching ubrogepant tablet, orally for treatment of a qualifying migraine attack. Participants had the option to take placebo-matching ubrogepant tablet or rescue medication, orally, 2 to 48 hours after initial dose. | 563 |
| Ubrogepant 25 mg 1 ubrogepant 25 mg tablet, orally for treatment of a qualifying migraine attack. Participants had the option to take a second dose, placebo-matching ubrogepant tablet or rescue medication, orally, 2 to 48 hours after initial dose. | 561 |
| Ubrogepant 50 mg 1 ubrogepant 50 mg tablet, orally for treatment of a qualifying migraine attack. Participants had the option to take a second dose, placebo-matching ubrogepant tablet or rescue medication, orally, 2 to 48 hours after initial dose. | 562 |
| Total | 1,686 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Safety Follow-up Period | Lost to Follow-up | 10 | 5 | 7 |
| Safety Follow-up Period | Pregnancy | 0 | 1 | 0 |
| Safety Follow-up Period | Protocol Violation | 0 | 1 | 1 |
| Safety Follow-up Period | Withdrawal of Consent | 1 | 8 | 6 |
| Treatment Period | Adverse Event | 1 | 1 | 2 |
| Treatment Period | Lack of Qualifying Event | 42 | 55 | 42 |
| Treatment Period | Lost to Follow-up | 17 | 20 | 20 |
| Treatment Period | Protocol Violation | 3 | 2 | 3 |
| Treatment Period | Withdrawal of Consent | 7 | 9 | 8 |
Baseline characteristics
| Characteristic | Placebo | Ubrogepant 25 mg | Ubrogepant 50 mg | Total |
|---|---|---|---|---|
| Age, Continuous | 41.5 years STANDARD_DEVIATION 12.2 | 41.6 years STANDARD_DEVIATION 12.3 | 41.0 years STANDARD_DEVIATION 12.4 | 41.4 years STANDARD_DEVIATION 12.3 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 4 Participants | 1 Participants | 4 Participants | 9 Participants |
| Race/Ethnicity, Customized Asian | 8 Participants | 6 Participants | 5 Participants | 19 Participants |
| Race/Ethnicity, Customized Black or African American | 94 Participants | 82 Participants | 93 Participants | 269 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 116 Participants | 129 Participants | 125 Participants | 370 Participants |
| Race/Ethnicity, Customized Multiple | 7 Participants | 4 Participants | 3 Participants | 14 Participants |
| Race/Ethnicity, Customized Native Hawaiian/Other Pacific Islander | 1 Participants | 1 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 447 Participants | 432 Participants | 437 Participants | 1316 Participants |
| Race/Ethnicity, Customized White | 449 Participants | 467 Participants | 456 Participants | 1372 Participants |
| Sex: Female, Male Female | 494 Participants | 501 Participants | 497 Participants | 1492 Participants |
| Sex: Female, Male Male | 69 Participants | 60 Participants | 65 Participants | 194 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 499 | 0 / 478 | 0 / 488 |
| other Total, other adverse events | 0 / 499 | 0 / 478 | 0 / 488 |
| serious Total, serious adverse events | 0 / 499 | 1 / 478 | 0 / 488 |
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 assessed.
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 baseline migraine headache severity measurement, had ≥1 postdose migraine headache severity/migraine-associated symptom measurement at/before 2-hour timepoint, LOCF. Number analyzed is participants with data available for analysis.
| 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 | 27.4 percentage of participants |
| Ubrogepant 25 mg | Percentage of Participants With Absence of the Most Bothersome Migraine-Associated Symptom Identified at Baseline at 2-Hours After Initial Dose | 34.1 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 | 38.9 percentage of participants |
p-value: 0.071195% CI: [1.02, 1.83]Regression, Logistic
p-value: 0.012995% CI: [1.25, 2.2]Regression, Logistic
Primary
Percentage of Participants With Pain Freedom at 2 Hours After Initial Dose
Pain freedom was defined as a reduction in headache pain severity from moderate/severe at baseline to no pain at 2 hours after the initial dose of investigational product. Participants were provided with 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 | 14.3 percentage of participants |
| Ubrogepant 25 mg | Percentage of Participants With Pain Freedom at 2 Hours After Initial Dose | 20.7 percentage of participants |
| Ubrogepant 50 mg | Percentage of Participants With Pain Freedom at 2 Hours After Initial Dose | 21.8 percentage of participants |
p-value: 0.028595% CI: [1.09, 2.22]Regression, Logistic
p-value: 0.012995% CI: [1.14, 2.29]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 | 70.0 percentage of participants |
| Ubrogepant 25 mg | Percentage of Participants With Absence of Nausea at 2 Hours After the Initial Dose | 70.6 percentage of participants |
| Ubrogepant 50 mg | Percentage of Participants With Absence of Nausea at 2 Hours After the Initial Dose | 71.3 percentage of participants |
p-value: 0.952295% CI: [0.81, 1.49]Regression, Logistic
p-value: 0.952295% CI: [0.83, 1.51]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 | 48.2 percentage of participants |
| Ubrogepant 25 mg | Percentage of Participants With Pain Relief at 2 Hours After the Initial Dose | 60.5 percentage of participants |
| Ubrogepant 50 mg | Percentage of Participants With Pain Relief at 2 Hours After the Initial Dose | 62.7 percentage of participants |
p-value: 0.071195% CI: [1.25, 2.17]Regression, Logistic
p-value: 0.012995% CI: [1.35, 2.32]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 assessment of 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 | 8.2 percentage of participants |
| Ubrogepant 25 mg | Percentage of Participants With Sustained Pain Freedom From 2 to 24 Hours After Initial Dose | 12.7 percentage of participants |
| Ubrogepant 50 mg | Percentage of Participants With Sustained Pain Freedom From 2 to 24 Hours After Initial Dose | 14.4 percentage of participants |
p-value: 0.071195% CI: [1.04, 2.53]Regression, Logistic
p-value: 0.012995% CI: [1.2, 2.83]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 assessment of 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 | 21.0 percentage of participants |
| Ubrogepant 25 mg | Percentage of Participants With Sustained Pain Relief From 2 to 24 Hours After Initial Dose | 32.5 percentage of participants |
| Ubrogepant 50 mg | Percentage of Participants With Sustained Pain Relief From 2 to 24 Hours After Initial Dose | 36.7 percentage of participants |
p-value: 0.071195% CI: [1.33, 2.48]Regression, Logistic
p-value: 0.012995% CI: [1.59, 2.92]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 | 46.3 percentage of participants |
| Ubrogepant 25 mg | Percentage of Participants With the Absence of Phonophobia at 2 Hours After the Initial Dose | 53.6 percentage of participants |
| Ubrogepant 50 mg | Percentage of Participants With the Absence of Phonophobia at 2 Hours After the Initial Dose | 54.1 percentage of participants |
p-value: 0.106695% CI: [1.04, 1.83]Regression, Logistic
p-value: 0.04495% CI: [1.05, 1.84]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 | 35.5 percentage of participants |
| Ubrogepant 25 mg | Percentage of Participants With the Absence of Photophobia at 2 Hours After the Initial Dose | 39.3 percentage of participants |
| Ubrogepant 50 mg | Percentage of Participants With the Absence of Photophobia at 2 Hours After the Initial Dose | 43.8 percentage of participants |
p-value: 0.183395% CI: [0.96, 1.72]Regression, Logistic
p-value: 0.016795% CI: [1.14, 2.02]Regression, Logistic