Migraine
Conditions
Keywords
Migraine
Brief summary
Study to Evaluate the Efficacy, Safety, and Tolerability of Oral Ubrogepant in the Acute Treatment of Migraine When Administered During the Prodrome
Interventions
DRUGUbrogepant 100 mg
For each qualifying prodrome event, 2 compressed tablets containing 50 mg of ubrogepant will be taken orally when the participant is confident that a headache will follow within 1-6 hours
DRUGPlacebo
For each qualifying prodrome event, 2 compressed tablets containing placebo will be taken orally when the participant is confident that a headache will follow within 1-6 hours
Sponsors
AbbVie
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
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 ICHD-3 (International Classification of Headache Disorders 3rd edition) * Migraine onset before age 50 years * By history, the participant's migraines typically last 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 in each of the 3 months prior to the Screening Visit
Exclusion criteria
* Difficulty distinguishing migraine headache from tension-type or other headaches * Participants who overuse medication for migraine defined as use of opioids or barbiturates \> 2 days/month, triptans or ergots ≥ 10 days/month, or simple analgesics (eg, aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen) ≥ 15 days/month in the 3 months prior to Visit 1 per investigator's judgment * Has a history of migraine aura with diplopia or impairment of level of consciousness, hemiplegic migraine, or retinal migraine as defined by ICHD-3 * A current diagnosis of chronic migraine as defined by ICHD-3 or a history of 15 or more headache days per month on average in the 6 months prior to Visit 1 in the investigator's judgment. A headache day is defined as a day in which there was any occurrence of a headache of a minimum duration of 2 hours or a headache of any duration for which acute medication was taken * 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 hospital treatment of a migraine attack 3 or more times in the 6 months prior to Visit 1 * History of malignancy in the 5 years prior to Visit 1, except for adequately treated basal cell or squamous cell skin cancer, or in situ cervical cancer * History of any prior gastrointestinal conditions (eg, diarrhea syndromes, inflammatory bowel disease) that, per investigator judgment, may affect the absorption or metabolism of the study intervention; participants with prior gastric bariatric interventions (eg, Lap Band) which have been reversed are not excluded
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Reporting Absence of Headache of Moderate/Severe Intensity Within 24 Hours Post-dose | 24 hours after taking double-blind study intervention during the prodrome | The absence of a headache of moderate/severe intensity will be recorded by the participant in an electronic diary (eDiary) within 24 hours after taking double-blind study intervention during the prodrome in order to determine the attenuation of headache. The absence of moderate or severe headache are derived based on headache record and rescue use. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Reporting Absence of Headache of Moderate or Severe Intensity Within 48 Hours Post-dose | 48 hours after taking double-blind study intervention during the prodrome | The absence of a headache of moderate or severe intensity will be recorded by the participant in an eDiary within 48 hours after taking double-blind study intervention during the prodrome in order to determine the prevention of headache |
| Percentage of Participants Reporting Improvement in the Ability to Function Normally Over 24 Hours Post-dose | 24 hours after taking double-blind study intervention during the prodrome | The Functional Disability Scale (FDS) is a single item used to measure the participant's level to function normally. Participants will be asked to rate the performance of daily activities using 4 response options ranging from 0 (no disability, able to function normally) to 3 (severely impaired, cannot do all or most things, bed rest may be necessary) within 24 hours after taking double-blind study intervention during the prodrome |
| Percentage of Participants Reporting Absence of Headache of Any Intensity Within 24 Hours Post-dose | 24 hours after taking double-blind study intervention during the prodrome | The absence of a headache of moderate/severe intensity will be recorded by the participant in an electronic diary (eDiary) within 24 hours after taking double-blind study intervention during the prodrome in order to determine the attenuation of headache. The absence of moderate or severe headache are derived based on headache record and rescue use. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment Sequence A Participants randomized to Treatment Sequence A will receive placebo to treat their first qualifying prodrome event and ubrogepant 100 mg to treat their second qualifying prodrome event
Ubrogepant 100mg: For each qualifying prodrome event, 2 compressed tablets containing 50 mg of ubrogepant will be taken orally when the participant is confident that a headache will follow within 1-6 hours
Placebo: For each qualifying prodrome event, 2 compressed tablets containing placebo will be taken orally when the participant is confident that a headache will follow within 1-6 hours | 247 |
| Treatment Sequence B Participants randomized to Treatment Sequence B will receive ubrogepant 100 mg to treat their first qualifying prodrome event and placebo to treat their second qualifying prodrome event
Ubrogepant 100mg: For each qualifying prodrome event, 2 compressed tablets containing 50 mg of ubrogepant will be taken orally when the participant is confident that a headache will follow within 1-6 hours
Placebo: For each qualifying prodrome event, 2 compressed tablets containing placebo will be taken orally when the participant is confident that a headache will follow within 1-6 hours | 233 |
| Total | 480 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 3 |
| Overall Study | Lack of Qualifying Event | 25 | 27 |
| Overall Study | Lost to Follow-up | 4 | 3 |
| Overall Study | Non-compliance with Study Drug | 2 | 1 |
| Overall Study | Protocol Violation | 5 | 2 |
| Overall Study | Withdrawal by Subject | 4 | 3 |
Baseline characteristics
| Characteristic | Treatment Sequence A | Treatment Sequence B | Total |
|---|---|---|---|
| Age, Continuous | 41.7 years STANDARD_DEVIATION 12.63 | 42.9 years STANDARD_DEVIATION 13.1 | 42.3 years STANDARD_DEVIATION 12.86 |
| Age, Customized < 20 | 5 Participants | 2 Participants | 7 Participants |
| Age, Customized 20 - 29 | 42 Participants | 38 Participants | 80 Participants |
| Age, Customized 30 - 39 | 62 Participants | 60 Participants | 122 Participants |
| Age, Customized 40 - 49 | 68 Participants | 64 Participants | 132 Participants |
| Age, Customized 50 - 59 | 48 Participants | 37 Participants | 85 Participants |
| Age, Customized 60 - 69 | 18 Participants | 28 Participants | 46 Participants |
| Age, Customized >= 70 | 4 Participants | 4 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 17 Participants | 15 Participants | 32 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 229 Participants | 216 Participants | 445 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 7 Participants | 4 Participants | 11 Participants |
| Race (NIH/OMB) Black or African American | 22 Participants | 15 Participants | 37 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 4 Participants | 6 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 214 Participants | 209 Participants | 423 Participants |
| Sex: Female, Male Female | 216 Participants | 205 Participants | 421 Participants |
| Sex: Female, Male Male | 31 Participants | 28 Participants | 59 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 462 | 0 / 456 |
| other Total, other adverse events | 35 / 462 | 50 / 456 |
| serious Total, serious adverse events | 1 / 462 | 0 / 456 |
Outcome results
Primary
Percentage of Participants Reporting Absence of Headache of Moderate/Severe Intensity Within 24 Hours Post-dose
The absence of a headache of moderate/severe intensity will be recorded by the participant in an electronic diary (eDiary) within 24 hours after taking double-blind study intervention during the prodrome in order to determine the attenuation of headache. The absence of moderate or severe headache are derived based on headache record and rescue use.
Time frame: 24 hours after taking double-blind study intervention during the prodrome
Population: The Modified Intent-to-Treat (mITT) population consists of all randomized participants with at least 1 assessment of headache occurrence within 24 hours after taking double-blind study intervention for at least 1 qualifying prodrome event during the double-blind treatment period
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Percentage of Participants Reporting Absence of Headache of Moderate/Severe Intensity Within 24 Hours Post-dose | 121 Participants |
| Ubrogepant 100 mg | Percentage of Participants Reporting Absence of Headache of Moderate/Severe Intensity Within 24 Hours Post-dose | 190 Participants |
p-value: <0.000195% CI: [1.63, 2.69]generalized linear mixed model (GLMM)
Secondary
Percentage of Participants Reporting Absence of Headache of Any Intensity Within 24 Hours Post-dose
The absence of a headache of moderate/severe intensity will be recorded by the participant in an electronic diary (eDiary) within 24 hours after taking double-blind study intervention during the prodrome in order to determine the attenuation of headache. The absence of moderate or severe headache are derived based on headache record and rescue use.
Time frame: 24 hours after taking double-blind study intervention during the prodrome
Population: The Modified Intent-to-Treat (mITT) population consists of all randomized participants with at least 1 assessment of headache occurrence within 24 hours after taking double-blind study intervention for at least 1 qualifying prodrome event during the double-blind treatment period
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Percentage of Participants Reporting Absence of Headache of Any Intensity Within 24 Hours Post-dose | 61 Participants |
| Ubrogepant 100 mg | Percentage of Participants Reporting Absence of Headache of Any Intensity Within 24 Hours Post-dose | 103 Participants |
p-value: <0.000195% CI: [1.39, 2.66]generalized linear mixed model (GLMM)
Secondary
Percentage of Participants Reporting Absence of Headache of Moderate or Severe Intensity Within 48 Hours Post-dose
The absence of a headache of moderate or severe intensity will be recorded by the participant in an eDiary within 48 hours after taking double-blind study intervention during the prodrome in order to determine the prevention of headache
Time frame: 48 hours after taking double-blind study intervention during the prodrome
Population: The Modified Intent-to-Treat (mITT) population consists of all randomized participants with at least 1 assessment of headache occurrence within 24 hours after taking double-blind study intervention for at least 1 qualifying prodrome event during the double-blind treatment period
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Percentage of Participants Reporting Absence of Headache of Moderate or Severe Intensity Within 48 Hours Post-dose | 100 Participants |
| Ubrogepant 100 mg | Percentage of Participants Reporting Absence of Headache of Moderate or Severe Intensity Within 48 Hours Post-dose | 159 Participants |
p-value: <0.000195% CI: [1.63, 2.78]generalized linear mixed model (GLMM)
Secondary
Percentage of Participants Reporting Improvement in the Ability to Function Normally Over 24 Hours Post-dose
The Functional Disability Scale (FDS) is a single item used to measure the participant's level to function normally. Participants will be asked to rate the performance of daily activities using 4 response options ranging from 0 (no disability, able to function normally) to 3 (severely impaired, cannot do all or most things, bed rest may be necessary) within 24 hours after taking double-blind study intervention during the prodrome
Time frame: 24 hours after taking double-blind study intervention during the prodrome
Population: Modified Intent-to-Treat Population (randomized participants with at least 1 assessment of headache occurrence within 24 hours after taking double-blind study intervention for at least 1 qualifying prodrome event during the double-blind treatment period) with non-missing ability to function normally assessment at each timepoint after dose.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Placebo | Percentage of Participants Reporting Improvement in the Ability to Function Normally Over 24 Hours Post-dose | 1 Hour | Responder | 96 Participants |
| Placebo | Percentage of Participants Reporting Improvement in the Ability to Function Normally Over 24 Hours Post-dose | 1 Hour | Nonresponder | 336 Participants |
| Placebo | Percentage of Participants Reporting Improvement in the Ability to Function Normally Over 24 Hours Post-dose | 2 Hours | Responder | 110 Participants |
| Placebo | Percentage of Participants Reporting Improvement in the Ability to Function Normally Over 24 Hours Post-dose | 2 Hours | Nonresponder | 311 Participants |
| Placebo | Percentage of Participants Reporting Improvement in the Ability to Function Normally Over 24 Hours Post-dose | 3 Hours | Responder | 150 Participants |
| Placebo | Percentage of Participants Reporting Improvement in the Ability to Function Normally Over 24 Hours Post-dose | 3 Hours | Nonresponder | 269 Participants |
| Placebo | Percentage of Participants Reporting Improvement in the Ability to Function Normally Over 24 Hours Post-dose | 4 Hours | Responder | 173 Participants |
| Placebo | Percentage of Participants Reporting Improvement in the Ability to Function Normally Over 24 Hours Post-dose | 4 Hours | Nonresponder | 244 Participants |
| Placebo | Percentage of Participants Reporting Improvement in the Ability to Function Normally Over 24 Hours Post-dose | 6 Hours | Responder | 210 Participants |
| Placebo | Percentage of Participants Reporting Improvement in the Ability to Function Normally Over 24 Hours Post-dose | 6 Hours | Nonresponder | 190 Participants |
| Placebo | Percentage of Participants Reporting Improvement in the Ability to Function Normally Over 24 Hours Post-dose | 8 Hours | Responder | 239 Participants |
| Placebo | Percentage of Participants Reporting Improvement in the Ability to Function Normally Over 24 Hours Post-dose | 8 Hours | Nonresponder | 155 Participants |
| Placebo | Percentage of Participants Reporting Improvement in the Ability to Function Normally Over 24 Hours Post-dose | 24 Hours | Responder | 342 Participants |
| Placebo | Percentage of Participants Reporting Improvement in the Ability to Function Normally Over 24 Hours Post-dose | 24 Hours | Nonresponder | 62 Participants |
| Ubrogepant 100 mg | Percentage of Participants Reporting Improvement in the Ability to Function Normally Over 24 Hours Post-dose | 8 Hours | Responder | 291 Participants |
| Ubrogepant 100 mg | Percentage of Participants Reporting Improvement in the Ability to Function Normally Over 24 Hours Post-dose | 1 Hour | Responder | 107 Participants |
| Ubrogepant 100 mg | Percentage of Participants Reporting Improvement in the Ability to Function Normally Over 24 Hours Post-dose | 4 Hours | Nonresponder | 170 Participants |
| Ubrogepant 100 mg | Percentage of Participants Reporting Improvement in the Ability to Function Normally Over 24 Hours Post-dose | 1 Hour | Nonresponder | 311 Participants |
| Ubrogepant 100 mg | Percentage of Participants Reporting Improvement in the Ability to Function Normally Over 24 Hours Post-dose | 24 Hours | Responder | 367 Participants |
| Ubrogepant 100 mg | Percentage of Participants Reporting Improvement in the Ability to Function Normally Over 24 Hours Post-dose | 2 Hours | Responder | 156 Participants |
| Ubrogepant 100 mg | Percentage of Participants Reporting Improvement in the Ability to Function Normally Over 24 Hours Post-dose | 6 Hours | Responder | 266 Participants |
| Ubrogepant 100 mg | Percentage of Participants Reporting Improvement in the Ability to Function Normally Over 24 Hours Post-dose | 2 Hours | Nonresponder | 266 Participants |
| Ubrogepant 100 mg | Percentage of Participants Reporting Improvement in the Ability to Function Normally Over 24 Hours Post-dose | 8 Hours | Nonresponder | 97 Participants |
| Ubrogepant 100 mg | Percentage of Participants Reporting Improvement in the Ability to Function Normally Over 24 Hours Post-dose | 3 Hours | Responder | 199 Participants |
| Ubrogepant 100 mg | Percentage of Participants Reporting Improvement in the Ability to Function Normally Over 24 Hours Post-dose | 6 Hours | Nonresponder | 129 Participants |
| Ubrogepant 100 mg | Percentage of Participants Reporting Improvement in the Ability to Function Normally Over 24 Hours Post-dose | 3 Hours | Nonresponder | 213 Participants |
| Ubrogepant 100 mg | Percentage of Participants Reporting Improvement in the Ability to Function Normally Over 24 Hours Post-dose | 24 Hours | Nonresponder | 46 Participants |
| Ubrogepant 100 mg | Percentage of Participants Reporting Improvement in the Ability to Function Normally Over 24 Hours Post-dose | 4 Hours | Responder | 245 Participants |
p-value: <0.000195% CI: [1.4, 1.96]generalized estimating equation (GEE)