Migraine
Conditions
Keywords
acute treatment, migraine pain, multiple attacks, headache
Brief summary
The reason for this study is to see how effective and safe the study drug known as lasmiditan is in the acute treatment of 4 migraine attacks with or without aura.
Interventions
DRUGLasmiditan
Administered orally.
DRUGPlacebo
Administered orally.
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Migraine with or without aura fulfilling the International Headache Society (IHS) diagnostic criteria 1.1 and 1.2.1 * History of disabling migraine for at least 1 year * Migraine onset before the age of 50 years * History of 3 to 8 migraine attacks per month (\<15 headache days per month) during the past 3 months * MIDAS score ≥11 * Able and willing to complete an eDiary to record the details of each migraine attack treated with study drug * Women of child-bearing potential must be using or willing to use a highly effective form of contraception * Agree not to post any personal medical data or information related to the study on any website or social media site until the entire trial has completed
Exclusion criteria
* Known hypersensitivity to lasmiditan, or to any excipient of lasmiditan oral tablets * History or evidence of hemorrhagic stroke, epilepsy, or any other condition placing the participant at increased risk of seizures * History of recurrent dizziness and/or vertigo including benign paroxysmal positional vertigo, Meniere's disease, vestibular migraine, and other vestibular disorders * History of diabetes mellitus with complications (diabetic retinopathy, nephropathy, or neuropathy) * History of orthostatic hypotension with syncope * Significant renal or hepatic impairment in the opinion of the investigator or if they meet hepatic monitoring criteria * Participants who, in the investigator's judgment, are actively suicidal and therefore deemed to be at significant risk for suicide * History, within past 12 months, of chronic migraine or other forms of primary or secondary chronic headache disorder (eg, hemicranias continua, medication overuse headache where headache frequency is ≥15 headache days per month) * Use of more than 3 doses per month of either opioids or barbiturates * Initiation of or a change in concomitant medication to reduce the frequency of migraine episodes within 3 months prior to screening * Pregnant or breast-feeding women * History of drug or alcohol abuse/dependence within 1 year prior to screening * Any medical condition or clinical laboratory test which in the judgment of the investigator makes the participant unsuitable for the study * Currently enrolled in any other clinical study involving an investigational product * Relatives of, or staff directly reporting to, the Investigator * Participants who are employees of the sponsor
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants That Are Pain Free 2 Hours Postdose During the First Attack | 2 Hours Postdose | Pain-free is defined as mild, moderate, or severe headache pain becoming none at 2 hours postdose during the first attack. |
| Percentage of Participants That Are Pain Free at 2 Hours Postdose in at Least 2 Out of 3 Attacks | 2 Hours Postdose | To evaluate the 2 out of 3 primary consistency endpoint, the results of ITT evaluable attacks in the lasmiditan 100-mg and 200-mg groups will be assessed, and the ITT-evaluable attacks treated with placebo in the control group will be used for comparison. For participants with more than 3 ITT evaluable attacks, only the first 3 will be considered. Pain-free was defined as mild, moderate, or severe headache pain becoming none at the indicated assessment time. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With 24-Hour Sustained Pain Freedom During the First Attack | 24 Hours | Sustained pain freedom defined as pain free at 2 and 24 hours with no rescue medication. |
| Percentage of Participants With 48-Hour Sustained Pain Freedom During First Attack | 48 Hours Postdose | Sustained pain freedom defined as pain free at 2 and 48 hours with no rescue medication. |
| Percentage of Participants That Are Pain Free 2 Hours Postdose During the First Attack in Triptan Insufficient Responders. | 2 Hours Postdose | Pain-free is defined as mild, moderate, or severe headache pain becoming none at 2 hours postdose during the first attack. A triptan insufficient responder is defined as having one of the following: 1) Scoring ≤5 on 4 questions from the Migraine Treatment Optimization Questionnaire (mTOQ-6) that defines participants with poor or very poor response to their current regimen; 2) Indicated they obtained pain freedom at 2 hours in 0 out of 3, or 1 out of 3 attacks when treated with the most recent triptan, or 3) are not currently taking triptan and discontinued their most recent triptan due to lack of efficacy, tolerability issue, or contradictions to a past triptan. |
| Percentage of Participants With no Disability as Measured by the Disability Item, at 2 Hours Postdose During the First Attack | 2 Hours Postdose | Percentage of participants with no disability as measured by the disability item, at 2 hours postdose during the first attack. Disability was measured by determining the level of interference with normal activities with 4 response options including not at all; mild interference, marked interference; and need complete bed rest. |
| Percentage of Participants That Are Pain Free at 2 Hours Postdose in at Least 2 Out of 3 Attacks in Triptan Insufficient Responders | 2 Hours Postdose | Headache pain-free is defined as a reduction in pain severity from mild, moderate, or severe at baseline to none at the indicated assessment time. A subject is not counted as being pain-free at a specific time point if she or he used rescue or recurrence medication at or before the specific time point. |
| Percentage of Participants Free of Most Bothersome Symptom (MBS) Associated With Migraine at 2 Hours Postdose During the First Attack | 2 Hours Postdose | MBS freedom is defined as the absence of the associated symptom of migraine (nausea, phonophobia, or photophobia) at the indicated assessment time that was identified at baseline as the most bothersome symptom. |
| Percentage of Participants Requiring Rescue Medication for Migraine Within 24 Hours of Treatment During the First Attack | 24 Hours | Percentage of participants requiring rescue medication for migraine within 2 to 24 hours of treatment during the first attack |
| Percentage of Participants That Are Free of Symptoms Associated With Migraine at 2 Hours Postdose During the First Attack | 2 Hours Postdose | Percentage of participants that are free of symptoms associated with migraine (photophobia, phonophobia, nausea, and vomiting) at 2 hours postdose during the first attack. |
| Percentage of Participants With Migraine Recurrence at 24 Hours During the First Attack | 24 Hours | Percentage of participants with migraine recurrence at 24 hours during the first attack defined as return of any headache in participants who were pain free at 2 hours. |
| Percentage of Participants With Pain Relief at 2 Hours Post Dose During the First Attack | 2 Hours Postdose | Headache pain-relief is defined as a reduction in pain severity from moderate or severe at baseline to mild or none, or a reduction in pain severity from mild at baseline to none, at the indicated assessment time. |
| Change From Baseline in Total Score as Measured by the Migraine Disability Assessment Test (MIDAS) Scale | Baseline, Week 16 | The MIDAS is a participant-rated scale which was designed to quantify headache-related disability over a 3-month period. This instrument consists of 5 items that reflect the number of days reported as missed, or with reduced productivity at work or home and social events. Each question is answered as the number of days during the past 3 months of assessment, ranging from 0 to 90, with the total score being the summation of the 5 numeric responses. A higher value is indicative of more disability. |
| Percentage of Participants Very Much or Much Better as Measured by Patient Global Impression of Change (PGI-C), at 2 Hours Postdose During the First Attack | 2 Hours Postdose | The PGI-C is a one-item questionnaire that asks participants to provide their impression of change since taking the medicine. The PGI-C is measured using a 7-point Likert scale, with 1 = very much better, 2 = much better, 3 = a little better, 4 = no change, 5 = a little worse, 6 = much worse, and 7 = very much worse. Reported are participants whose combined impression of change since taking the medicine was very much better and much better at 2 hours postdose. |
| Migraine Quality of Life Questionnaire (MQoLQ) Score at 24 Hours Post First Dose of Study During First Attack | 24 Hours Post First Dose | The 24-hour Migraine Quality of Life Questionnaire (24-hr MQoLQ) has been specifically developed to measure the HRQoL of participants with migraine within a 24-hour period after having taken migraine medication A domain score is calculated by summing the responses to the 3 questions and the domain score ranges from 3 to 21, with lower scores indicating less impairment. The questionnaire will be administered 24 hours after dosing with study drug during each migraine. The analysis of variance (ANOVA) model was used with region and treatment adjusted for the overall treatment effect. |
| Percentage of Participants Satisfied With Their Treatment Measured by a 4-Item Questionnaire | Week 16 | Treatment satisfaction was evaluated at the End of Study (EoS) visit by determining the participant's level of satisfaction (ranging from extremely dissatisfied to extremely satisfied); their willingness to take this treatment again (ranging from strongly disagree to strongly agree) and if they would they recommend this treatment to another participants (ranging from strongly disagree to strongly agree). |
| Change From Baseline in Utility at 24 Hours Postdose as Measured by the EuroQol 5-Dimension 5-Level Scale (EQ-5D-5L) at 24 Hours Postdose During First Attack | Baseline, 24 Hours Postdose | The EQ-5D-5L questionnaire is a participant-rated scale that assesses health status, it consists of 2 parts. The first part assesses 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) that have 5 possible levels of response (no problems, slight problems, moderate problems, severe problems, extreme problems).The EQ-5D can be used to generate a health state index score, which is used to compute quality-adjusted life years for utilization in health economic analyses. The health state index score is calculated based on the responses to the 5 dimensions, providing a single value on a scale from less than 0 (where 0 is a health state equivalent to death) to 1 (perfect health), with higher scores indicating better health utility. ANCOVA was used to assess the effect of Lasmiditan over placebo or control. The model includes fixed categorical effect of treatment and geographic region and baseline as covariate. |
| Percentage of Participants That Are Pain Free at 2 Hours Postdose in at Least 3 Out of 4 Attacks | 2 Hours Postdose | Headache pain-free is defined as a reduction in pain severity from mild, moderate, or severe to none at the indicated assessment time (2 hours postdose). To evaluate 3 out of 4 consistency endpoints; all ITT-evaluable attacks will be used. For the control group, the results of all ITT-evaluable attacks treated with lasmiditan 50 mg or placebo will be included. The control group is used for comparison. The population for 3 out of 4 consistency endpoints with sufficient number of successes or failures is defined as all participants who experienced at least 3 successes or 2 failures during ITT-evaluable attacks. |
| Percentage of Participants With Pain Relief at 2 Hours Postdose in at Least 3 Out of 4 Attacks | 2 Hours Postdose | Headache pain-relief is defined as a reduction in pain severity from moderate or severe at baseline to mild or none, or a reduction in pain severity from mild at baseline to none, at the indicated assessment time (2 hours postdose). To evaluate 3 out of 4 consistency endpoints; all ITT-evaluable attacks will be used. For the control group, the results of all ITT-evaluable attacks treated with lasmiditan 50 mg or placebo will be included. The control group is used for comparison. The population for 3 out of 4 consistency endpoints with sufficient number of successes or failures is defined as all participants who experienced at least 3 successes or 2 failures during ITT-evaluable attacks. |
| Percentage of Participants With Associated Migraines Symptoms of Nausea, Vomiting, Photophobia, and Phonophobia Present at 2 Hours Postdose for First Attack | 2 Hours Postdose | Presence of associated migraine symptoms at 2 hours postdose at first migraine attack, including each of the following: phonophobia, photophobia, nausea, and vomiting. |
| Percentage of Participants With Pain Freedom, Pain Relief, Freedom From MBS, and No Disability Postdose During First Attack | 30 Minutes (Min) and 1 Hour (Hr) Postdose | Percentage of participants with pain freedom, pain relief, freedom from MBS, and no disability postdose during first attack. |
| Percentage of Participants With Pain Relief at 2 Hours Postdose in at Least 2 Out of 3 Attacks | 2 Hours Postdose | Headache pain relief is defined as a reduction in pain severity from moderate to severe at baseline to mild or none at 2 hours postdose in at least 2 out of 3 attacks. To evaluate at least 2 out of 3 consistency endpoints, the results of ITT-evaluable attacks in the lasmiditan 100-mg and 200-mg groups will be assessed, and the ITT-evaluable attacks treated with placebo in the control group will be used for comparison. For participants with more than 3 ITT-evaluable attacks, only the first 3 with the same treatment will be considered. |
Countries
Austria, Belgium, China, Czechia, Denmark, France, Germany, Hungary, India, Italy, Mexico, Netherlands, Russia, Spain, Switzerland, United Kingdom, United States
Participant flow
Recruitment details
Participants were considered study completers after treating 4 migraine attacks or after completing 4 months of study duration regardless of number of treated attacks in the main study. Participants may continue in Open-Label Extension (OLE) if they met OLE eligibility criteria.
Pre-assignment details
An ITT evaluable attack is defined as a treated attack of least mild pain severity with any postdose pain severity assessments at or before 2 hours postdose.
Participants by arm
| Arm | Count |
|---|---|
| 100 mg Lasmiditan Participants received one 100 mg Lasmiditan tablet with one 50 mg Lasmiditan matching placebo tablet and one 100 mg Lasmiditan matching placebo tablet to maintain blind. | 485 |
| 200 mg Lasmiditan Participants received two 100 mg Lasmiditan tablets with one 50 mg Lasmiditan matching placebo tablet to maintain blind. | 486 |
| Control Control 1: Participants received one 50 mg Lasmiditan matching placebo tablet and two100 mg Lasmiditan matching placebo tablets to maintain blind for migraine attacks 1, 2, and 4.
Participants received one50 mg Lasmiditan tablet with two 100 mg Lasmiditan matching placebo tablets to maintain blind, for migraine attack 3.
Control 2: Participants received one 50 mg Lasmiditan matching placebo tablet and two 100 mg Lasmiditan matching placebo tablets to treat migraine attacks 1, 2 and 3.
Participants received one 50 mg Lasmiditan tablet and two 100 mg Lasmiditan matching placebo tablets to treat migraine attack 4. | 500 |
| 100 mg Lasmiditan MEE Participants received one 100 mg Lasmiditan tables with one 50 mg lasmiditan matching placebo tablet and one 100 mg Lasmiditan matching placebo tablet to maintain the blind. Tablets were administered orally within 4 hours of onset of a single migraine attack, up to 4 migraine attacks. | 55 |
| 200 mg Lasmiditan MEE Participants received two 100 mg Lasmiditan tables with one 50 mg lasmiditan matching placebo tablet to maintain the blind. Tablets were administered orally within 4 hours of onset of a single migraine attack, up to 4 migraine attacks. | 53 |
| Control MEE Control 1:
Participants received one 50 mg Lasmiditan matching placebo tablet and two 100 mg Lasmiditan matching placebo tablets to maintain blind for migraine attacks 1, 2, and 4.
Participants received one 50 mg Lasmiditan tablet with two 100 mg Lasmiditan matching placebo tablets to maintain blind, for migraine attack 3.
Control 2:
Participants received one 50 mg Lasmiditan matching placebo tablet and two 100 mg Lasmiditan matching placebo tablets to maintain blind for migraine attacks 1, 2, and 3.
Participants received one 50 mg Lasmiditan tablet with two 100 mg Lasmiditan matching placebo tablets to maintain blind for migraine attack 4.
Tablets were administered orally within 4 hours of onset of a single migraine attack, up to 4 migraine attacks. | 54 |
| Total | 1,633 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 |
|---|---|---|---|---|---|---|---|---|---|---|
| Main Study | Adverse Event | 37 | 38 | 3 | 4 | 4 | 5 | 0 | 0 | 0 |
| Main Study | Lack of Efficacy | 8 | 9 | 3 | 4 | 0 | 0 | 0 | 0 | 0 |
| Main Study | Lost to Follow-up | 9 | 7 | 4 | 6 | 1 | 0 | 0 | 0 | 0 |
| Main Study | Migraines more frequent-GP advised to re-start Topiramate | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Main Study | Non-compliance with Study Drug | 0 | 2 | 3 | 0 | 0 | 0 | 0 | 1 | 0 |
| Main Study | Participant did not want to take the three other treatments | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Main Study | Physician Decision | 3 | 0 | 1 | 0 | 0 | 0 | 1 | 1 | 0 |
| Main Study | Pregnancy | 1 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Main Study | Protocol Deviation | 2 | 12 | 8 | 4 | 0 | 0 | 0 | 0 | 0 |
| Main Study | Travel and Coronavirus issues | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Main Study | Withdrawal by Subject | 21 | 21 | 8 | 9 | 5 | 2 | 1 | 1 | 0 |
| Open Label Extension | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 24 |
| Open Label Extension | COVID-19 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Open Label Extension | Death | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Open Label Extension | Lack of Efficacy | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 39 |
| Open Label Extension | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 23 |
| Open Label Extension | Non-compliance with study drug | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 5 |
| Open Label Extension | Participant didn't have disposition for OLE period | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Open Label Extension | Participant refused to comply with face mask use | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Open Label Extension | Participant wanted to become pregnant | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Open Label Extension | Physician Decision | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 |
| Open Label Extension | Pregnancy | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 3 |
| Open Label Extension | Protocol Deviation | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 5 |
| Open Label Extension | Taking medication too restrictive for lifestyle | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Open Label Extension | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 46 |
Baseline characteristics
| Characteristic | 100 mg Lasmiditan | 200 mg Lasmiditan | Control | 100 mg Lasmiditan MEE | 200 mg Lasmiditan MEE | Control MEE | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 41.90 years STANDARD_DEVIATION 12.02 | 41.70 years STANDARD_DEVIATION 11.95 | 40.60 years STANDARD_DEVIATION 12.11 | 37.20 years STANDARD_DEVIATION 9.83 | 37.20 years STANDARD_DEVIATION 9.46 | 38.60 years STANDARD_DEVIATION 8.7 | 41.30 years STANDARD_DEVIATION 11.89 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 44 Participants | 44 Participants | 47 Participants | 0 Participants | 0 Participants | 0 Participants | 135 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 393 Participants | 390 Participants | 401 Participants | 19 Participants | 14 Participants | 15 Participants | 1232 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 48 Participants | 52 Participants | 52 Participants | 36 Participants | 39 Participants | 39 Participants | 266 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 25 Participants | 28 Participants | 27 Participants | 0 Participants | 0 Participants | 0 Participants | 80 Participants |
| Race (NIH/OMB) Asian | 71 Participants | 72 Participants | 78 Participants | 53 Participants | 49 Participants | 51 Participants | 374 Participants |
| Race (NIH/OMB) Black or African American | 12 Participants | 8 Participants | 7 Participants | 0 Participants | 0 Participants | 0 Participants | 27 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 7 Participants | 7 Participants | 8 Participants | 0 Participants | 0 Participants | 0 Participants | 22 Participants |
| Race (NIH/OMB) White | 370 Participants | 368 Participants | 379 Participants | 2 Participants | 4 Participants | 3 Participants | 1126 Participants |
| Region of Enrollment Austria | 5 participants | 3 participants | 3 participants | 0 participants | 0 participants | 0 participants | 11 participants |
| Region of Enrollment Belgium | 9 participants | 10 participants | 9 participants | 0 participants | 0 participants | 0 participants | 28 participants |
| Region of Enrollment China | 45 participants | 44 participants | 47 participants | 50 participants | 48 participants | 47 participants | 281 participants |
| Region of Enrollment Czechia | 33 participants | 32 participants | 31 participants | 0 participants | 0 participants | 0 participants | 96 participants |
| Region of Enrollment Denmark | 9 participants | 10 participants | 11 participants | 0 participants | 0 participants | 0 participants | 30 participants |
| Region of Enrollment France | 7 participants | 7 participants | 8 participants | 0 participants | 0 participants | 0 participants | 22 participants |
| Region of Enrollment Germany | 92 participants | 89 participants | 94 participants | 0 participants | 0 participants | 0 participants | 275 participants |
| Region of Enrollment Hungary | 6 participants | 6 participants | 5 participants | 0 participants | 0 participants | 0 participants | 17 participants |
| Region of Enrollment India | 12 participants | 14 participants | 13 participants | 3 participants | 1 participants | 4 participants | 47 participants |
| Region of Enrollment Italy | 7 participants | 7 participants | 8 participants | 0 participants | 0 participants | 0 participants | 22 participants |
| Region of Enrollment Mexico | 29 participants | 32 participants | 34 participants | 0 participants | 0 participants | 0 participants | 95 participants |
| Region of Enrollment Netherlands | 3 participants | 4 participants | 3 participants | 0 participants | 0 participants | 0 participants | 10 participants |
| Region of Enrollment Russia | 13 participants | 12 participants | 13 participants | 2 participants | 4 participants | 3 participants | 47 participants |
| Region of Enrollment Spain | 18 participants | 21 participants | 22 participants | 0 participants | 0 participants | 0 participants | 61 participants |
| Region of Enrollment Switzerland | 5 participants | 7 participants | 7 participants | 0 participants | 0 participants | 0 participants | 19 participants |
| Region of Enrollment United Kingdom | 164 participants | 162 participants | 164 participants | 0 participants | 0 participants | 0 participants | 490 participants |
| Region of Enrollment United States | 28 participants | 26 participants | 28 participants | 0 participants | 0 participants | 0 participants | 82 participants |
| Sex: Female, Male Female | 403 Participants | 418 Participants | 416 Participants | 43 Participants | 36 Participants | 40 Participants | 1356 Participants |
| Sex: Female, Male Male | 82 Participants | 68 Participants | 84 Participants | 12 Participants | 17 Participants | 14 Participants | 277 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 485 | 0 / 486 | 0 / 500 | 0 / 55 | 0 / 53 | 0 / 54 | 1 / 477 |
| other Total, other adverse events | 331 / 485 | 355 / 486 | 184 / 500 | 31 / 55 | 40 / 53 | 16 / 54 | 326 / 477 |
| serious Total, serious adverse events | 7 / 485 | 8 / 486 | 7 / 500 | 1 / 55 | 0 / 53 | 0 / 54 | 19 / 477 |
Outcome results
Primary
Percentage of Participants That Are Pain Free 2 Hours Postdose During the First Attack
Pain-free is defined as mild, moderate, or severe headache pain becoming none at 2 hours postdose during the first attack.
Time frame: 2 Hours Postdose
Population: All randomized participants who used at least 1 dose of study drug for an Intent-to-Treat (ITT) evaluable attack, defined as a treated attack of at least mild pain severity with any postdose pain severity assessments at or before 2 hours postdose. As pre-specified in the analysis plan, outcome measures will not be reported for the Maximum Extended Enrollment (MEE) arms/groups but only for the main global study arms/groups.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 100 mg Lasmiditan | Percentage of Participants That Are Pain Free 2 Hours Postdose During the First Attack | 25.8 percentage of participants |
| 200 mg Lasmiditan | Percentage of Participants That Are Pain Free 2 Hours Postdose During the First Attack | 29.3 percentage of participants |
| Placebo | Percentage of Participants That Are Pain Free 2 Hours Postdose During the First Attack | 8.4 percentage of participants |
p-value: <0.00195% CI: [2.56, 5.73]Regression, Logistic
p-value: <0.00195% CI: [3.07, 6.77]Regression, Logistic
Primary
Percentage of Participants That Are Pain Free at 2 Hours Postdose in at Least 2 Out of 3 Attacks
To evaluate the 2 out of 3 primary consistency endpoint, the results of ITT evaluable attacks in the lasmiditan 100-mg and 200-mg groups will be assessed, and the ITT-evaluable attacks treated with placebo in the control group will be used for comparison. For participants with more than 3 ITT evaluable attacks, only the first 3 will be considered. Pain-free was defined as mild, moderate, or severe headache pain becoming none at the indicated assessment time.
Time frame: 2 Hours Postdose
Population: All randomized participants who experienced at least 2 successes or 2 failures during their first 2 or 3 ITT evaluable attacks. As pre-specified in the analysis plan, outcome measures will not be reported for the MEE arms/groups but only for the main global study arms/groups.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 100 mg Lasmiditan | Percentage of Participants That Are Pain Free at 2 Hours Postdose in at Least 2 Out of 3 Attacks | 14.4 percentage of participants |
| 200 mg Lasmiditan | Percentage of Participants That Are Pain Free at 2 Hours Postdose in at Least 2 Out of 3 Attacks | 24.4 percentage of participants |
| Placebo | Percentage of Participants That Are Pain Free at 2 Hours Postdose in at Least 2 Out of 3 Attacks | 4.3 percentage of participants |
p-value: <0.00195% CI: [2.1, 6.76]Regression, Logistic
p-value: <0.00195% CI: [4.13, 12.67]Regression, Logistic
Secondary
Change From Baseline in Total Score as Measured by the Migraine Disability Assessment Test (MIDAS) Scale
The MIDAS is a participant-rated scale which was designed to quantify headache-related disability over a 3-month period. This instrument consists of 5 items that reflect the number of days reported as missed, or with reduced productivity at work or home and social events. Each question is answered as the number of days during the past 3 months of assessment, ranging from 0 to 90, with the total score being the summation of the 5 numeric responses. A higher value is indicative of more disability.
Time frame: Baseline, Week 16
Population: All randomized participants who used at least 1 dose of study drug for an ITT evaluable attack, defined as a treated attack of at least mild pain severity with any postdose pain severity assessments at or before 2 hours postdose. As pre-specified in the analysis plan, outcome measures will not be reported for the MEE arms/groups but only for the main global study arms/groups.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 100 mg Lasmiditan | Change From Baseline in Total Score as Measured by the Migraine Disability Assessment Test (MIDAS) Scale | -10.7 score on a scale | Standard Deviation 24.36 |
| 200 mg Lasmiditan | Change From Baseline in Total Score as Measured by the Migraine Disability Assessment Test (MIDAS) Scale | -12.0 score on a scale | Standard Deviation 21.38 |
| Placebo | Change From Baseline in Total Score as Measured by the Migraine Disability Assessment Test (MIDAS) Scale | -13.1 score on a scale | Standard Deviation 21.4 |
p-value: 0.092ANCOVA
p-value: 0.211ANCOVA
Secondary
Change From Baseline in Utility at 24 Hours Postdose as Measured by the EuroQol 5-Dimension 5-Level Scale (EQ-5D-5L) at 24 Hours Postdose During First Attack
The EQ-5D-5L questionnaire is a participant-rated scale that assesses health status, it consists of 2 parts. The first part assesses 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) that have 5 possible levels of response (no problems, slight problems, moderate problems, severe problems, extreme problems).The EQ-5D can be used to generate a health state index score, which is used to compute quality-adjusted life years for utilization in health economic analyses. The health state index score is calculated based on the responses to the 5 dimensions, providing a single value on a scale from less than 0 (where 0 is a health state equivalent to death) to 1 (perfect health), with higher scores indicating better health utility. ANCOVA was used to assess the effect of Lasmiditan over placebo or control. The model includes fixed categorical effect of treatment and geographic region and baseline as covariate.
Time frame: Baseline, 24 Hours Postdose
Population: All randomized participants who use at least 1 dose of study drug for an ITT evaluable attack, defined as a treated attack of at least mild pain severity with any postdose pain severity assessments at or before 2 hours postdose. As pre-specified in the analysis plan, outcome measures will not be reported for the MEE arms/groups but only for the main global study arms/groups.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 100 mg Lasmiditan | Change From Baseline in Utility at 24 Hours Postdose as Measured by the EuroQol 5-Dimension 5-Level Scale (EQ-5D-5L) at 24 Hours Postdose During First Attack | 0.2499 score on a scale | Standard Deviation 0.25788 |
| 200 mg Lasmiditan | Change From Baseline in Utility at 24 Hours Postdose as Measured by the EuroQol 5-Dimension 5-Level Scale (EQ-5D-5L) at 24 Hours Postdose During First Attack | 0.2270 score on a scale | Standard Deviation 0.29854 |
| Placebo | Change From Baseline in Utility at 24 Hours Postdose as Measured by the EuroQol 5-Dimension 5-Level Scale (EQ-5D-5L) at 24 Hours Postdose During First Attack | 0.2122 score on a scale | Standard Deviation 0.25729 |
p-value: 0.142ANCOVA
Secondary
Migraine Quality of Life Questionnaire (MQoLQ) Score at 24 Hours Post First Dose of Study During First Attack
The 24-hour Migraine Quality of Life Questionnaire (24-hr MQoLQ) has been specifically developed to measure the HRQoL of participants with migraine within a 24-hour period after having taken migraine medication A domain score is calculated by summing the responses to the 3 questions and the domain score ranges from 3 to 21, with lower scores indicating less impairment. The questionnaire will be administered 24 hours after dosing with study drug during each migraine. The analysis of variance (ANOVA) model was used with region and treatment adjusted for the overall treatment effect.
Time frame: 24 Hours Post First Dose
Population: All randomized participants who used at least 1 dose of study drug for an ITT evaluable attack, defined as a treated attack of at least mild pain severity with any postdose pain severity assessments at or before 2 hours postdose. As pre-specified in the analysis plan, outcome measures will not be reported for the MEE arms/groups but only for the main global study arms/groups.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 100 mg Lasmiditan | Migraine Quality of Life Questionnaire (MQoLQ) Score at 24 Hours Post First Dose of Study During First Attack | Feeling/Concern | 11.2 score on a scale | Standard Deviation 4.3 |
| 100 mg Lasmiditan | Migraine Quality of Life Questionnaire (MQoLQ) Score at 24 Hours Post First Dose of Study During First Attack | Migraine Symptoms | 12.4 score on a scale | Standard Deviation 4.1 |
| 100 mg Lasmiditan | Migraine Quality of Life Questionnaire (MQoLQ) Score at 24 Hours Post First Dose of Study During First Attack | Social Functioning | 12.4 score on a scale | Standard Deviation 4.8 |
| 200 mg Lasmiditan | Migraine Quality of Life Questionnaire (MQoLQ) Score at 24 Hours Post First Dose of Study During First Attack | Feeling/Concern | 11.2 score on a scale | Standard Deviation 4.5 |
| 200 mg Lasmiditan | Migraine Quality of Life Questionnaire (MQoLQ) Score at 24 Hours Post First Dose of Study During First Attack | Social Functioning | 12.1 score on a scale | Standard Deviation 4.7 |
| 200 mg Lasmiditan | Migraine Quality of Life Questionnaire (MQoLQ) Score at 24 Hours Post First Dose of Study During First Attack | Migraine Symptoms | 12.5 score on a scale | Standard Deviation 4.2 |
| Placebo | Migraine Quality of Life Questionnaire (MQoLQ) Score at 24 Hours Post First Dose of Study During First Attack | Migraine Symptoms | 11.4 score on a scale | Standard Deviation 4.4 |
| Placebo | Migraine Quality of Life Questionnaire (MQoLQ) Score at 24 Hours Post First Dose of Study During First Attack | Social Functioning | 11.7 score on a scale | Standard Deviation 4.7 |
| Placebo | Migraine Quality of Life Questionnaire (MQoLQ) Score at 24 Hours Post First Dose of Study During First Attack | Feeling/Concern | 10.3 score on a scale | Standard Deviation 4.2 |
Comparison: Social Functioningp-value: 0.056ANOVA
Comparison: Social Functioningp-value: 0.267ANOVA
Comparison: Migraine Symptoms 100 mgp-value: 0.003ANOVA
Comparison: Migraine Symptoms 200 mgp-value: 0.002ANOVA
Comparison: Feeling/Concerns 100 mgp-value: 0.014ANOVA
Comparison: Feelings/Concerns 200 mgp-value: 0.018ANOVA
Secondary
Percentage of Participants Free of Most Bothersome Symptom (MBS) Associated With Migraine at 2 Hours Postdose During the First Attack
MBS freedom is defined as the absence of the associated symptom of migraine (nausea, phonophobia, or photophobia) at the indicated assessment time that was identified at baseline as the most bothersome symptom.
Time frame: 2 Hours Postdose
Population: All randomized participants who used at least 1 dose of study drug for an ITT evaluable attack, defined as a treated attack of at least mild pain severity with any postdose pain severity assessments at or before 2 hours postdose. As pre-specified in the analysis plan, outcome measures will not be reported for the MEE arms/groups but only for the main global study arms/groups.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 100 mg Lasmiditan | Percentage of Participants Free of Most Bothersome Symptom (MBS) Associated With Migraine at 2 Hours Postdose During the First Attack | 40.4 percentage of participants |
| 200 mg Lasmiditan | Percentage of Participants Free of Most Bothersome Symptom (MBS) Associated With Migraine at 2 Hours Postdose During the First Attack | 39.0 percentage of participants |
| Placebo | Percentage of Participants Free of Most Bothersome Symptom (MBS) Associated With Migraine at 2 Hours Postdose During the First Attack | 28.0 percentage of participants |
p-value: <0.00195% CI: [1.29, 2.35]Regression, Logistic
p-value: 0.00195% CI: [1.21, 2.2]Regression, Logistic
Secondary
Percentage of Participants Requiring Rescue Medication for Migraine Within 24 Hours of Treatment During the First Attack
Percentage of participants requiring rescue medication for migraine within 2 to 24 hours of treatment during the first attack
Time frame: 24 Hours
Population: All randomized participants who used at least 1 dose of study drug for an ITT evaluable attack, defined as a treated attack of at least mild pain severity with any postdose pain severity assessments at or before 2 hours postdose. As pre-specified in the analysis plan, outcome measures will not be reported for the MEE arms/groups but only for the main global study arms/groups.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 100 mg Lasmiditan | Percentage of Participants Requiring Rescue Medication for Migraine Within 24 Hours of Treatment During the First Attack | 19.6 percentage of participants |
| 200 mg Lasmiditan | Percentage of Participants Requiring Rescue Medication for Migraine Within 24 Hours of Treatment During the First Attack | 19.2 percentage of participants |
| Placebo | Percentage of Participants Requiring Rescue Medication for Migraine Within 24 Hours of Treatment During the First Attack | 29.3 percentage of participants |
p-value: <0.00195% CI: [0.33, 0.65]Regression, Logistic
p-value: <0.00195% CI: [0.3, 0.6]Regression, Logistic
Secondary
Percentage of Participants Satisfied With Their Treatment Measured by a 4-Item Questionnaire
Treatment satisfaction was evaluated at the End of Study (EoS) visit by determining the participant's level of satisfaction (ranging from extremely dissatisfied to extremely satisfied); their willingness to take this treatment again (ranging from strongly disagree to strongly agree) and if they would they recommend this treatment to another participants (ranging from strongly disagree to strongly agree).
Time frame: Week 16
Population: All randomized participants who use at least 1 dose of study drug for an ITT evaluable attack, defined as a treated attack of at least mild pain severity with any postdose pain severity assessments at or before 2 hours postdose. As pre-specified in the analysis plan, outcome measures will not be reported for the MEE arms/groups but only for the main global study arms/groups.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 100 mg Lasmiditan | Percentage of Participants Satisfied With Their Treatment Measured by a 4-Item Questionnaire | Extremely/Very Satisfied/Satisfied with Medication | 48.9 percentage of participants |
| 100 mg Lasmiditan | Percentage of Participants Satisfied With Their Treatment Measured by a 4-Item Questionnaire | Recommend Treatment - Agree/Strongly Agree | 57.2 percentage of participants |
| 100 mg Lasmiditan | Percentage of Participants Satisfied With Their Treatment Measured by a 4-Item Questionnaire | Prefer This Treatment | 31.2 percentage of participants |
| 100 mg Lasmiditan | Percentage of Participants Satisfied With Their Treatment Measured by a 4-Item Questionnaire | Willing to Take Treatment - Agree/Strongly Agree | 61.5 percentage of participants |
| 200 mg Lasmiditan | Percentage of Participants Satisfied With Their Treatment Measured by a 4-Item Questionnaire | Extremely/Very Satisfied/Satisfied with Medication | 51.6 percentage of participants |
| 200 mg Lasmiditan | Percentage of Participants Satisfied With Their Treatment Measured by a 4-Item Questionnaire | Willing to Take Treatment - Agree/Strongly Agree | 58.9 percentage of participants |
| 200 mg Lasmiditan | Percentage of Participants Satisfied With Their Treatment Measured by a 4-Item Questionnaire | Recommend Treatment - Agree/Strongly Agree | 58.1 percentage of participants |
| 200 mg Lasmiditan | Percentage of Participants Satisfied With Their Treatment Measured by a 4-Item Questionnaire | Prefer This Treatment | 32.7 percentage of participants |
| Placebo | Percentage of Participants Satisfied With Their Treatment Measured by a 4-Item Questionnaire | Willing to Take Treatment - Agree/Strongly Agree | 64.3 percentage of participants |
| Placebo | Percentage of Participants Satisfied With Their Treatment Measured by a 4-Item Questionnaire | Recommend Treatment - Agree/Strongly Agree | 52.0 percentage of participants |
| Placebo | Percentage of Participants Satisfied With Their Treatment Measured by a 4-Item Questionnaire | Prefer This Treatment | 29.1 percentage of participants |
| Placebo | Percentage of Participants Satisfied With Their Treatment Measured by a 4-Item Questionnaire | Extremely/Very Satisfied/Satisfied with Medication | 43.5 percentage of participants |
Comparison: Recommend Treatment - Agree Strongly Agreep-value: 0.10195% CI: [0.96, 1.62]Regression, Logistic
Comparison: Recommend Treatment Agree/Strongly Agreep-value: 0.06395% CI: [0.99, 1.67]Regression, Logistic
Comparison: Willing to Take This Treatment Again - Agree/Strongly Agreep-value: 0.37695% CI: [0.68, 1.16]Regression, Logistic
Comparison: Willing to Take This Treatment Again - Agree/Strongly Agreep-value: 0.08295% CI: [0.6, 1.03]Regression, Logistic
Comparison: Extremely/Very Satisfiedp-value: 0.09695% CI: [0.96, 1.62]Regression, Logistic
Comparison: Extremely/Very Satisfiedp-value: 0.01695% CI: [1.06, 1.8]Regression, Logistic
Comparison: Prefer This Treatmentp-value: 0.44595% CI: [0.84, 1.49]Regression, Logistic
p-value: 0.24395% CI: [0.89, 1.58]Regression, Logistic
Secondary
Percentage of Participants That Are Free of Symptoms Associated With Migraine at 2 Hours Postdose During the First Attack
Percentage of participants that are free of symptoms associated with migraine (photophobia, phonophobia, nausea, and vomiting) at 2 hours postdose during the first attack.
Time frame: 2 Hours Postdose
Population: All randomized participants who used at least 1 dose of study drug for an ITT evaluable attack, defined as a treated attack of at least mild pain severity with any postdose pain severity assessments at or before 2 hours postdose. As pre-specified in the analysis plan, outcome measures will not be reported for the MEE arms/groups but only for the main global study arms/groups.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 100 mg Lasmiditan | Percentage of Participants That Are Free of Symptoms Associated With Migraine at 2 Hours Postdose During the First Attack | 17.9 percentage of participants |
| 200 mg Lasmiditan | Percentage of Participants That Are Free of Symptoms Associated With Migraine at 2 Hours Postdose During the First Attack | 21.0 percentage of participants |
| Placebo | Percentage of Participants That Are Free of Symptoms Associated With Migraine at 2 Hours Postdose During the First Attack | 7.2 percentage of participants |
p-value: <0.00195% CI: [1.79, 4.28]Regression, Logistic
p-value: <0.00195% CI: [2.2, 5.15]Regression, Logistic
Secondary
Percentage of Participants That Are Pain Free 2 Hours Postdose During the First Attack in Triptan Insufficient Responders.
Pain-free is defined as mild, moderate, or severe headache pain becoming none at 2 hours postdose during the first attack. A triptan insufficient responder is defined as having one of the following: 1) Scoring ≤5 on 4 questions from the Migraine Treatment Optimization Questionnaire (mTOQ-6) that defines participants with poor or very poor response to their current regimen; 2) Indicated they obtained pain freedom at 2 hours in 0 out of 3, or 1 out of 3 attacks when treated with the most recent triptan, or 3) are not currently taking triptan and discontinued their most recent triptan due to lack of efficacy, tolerability issue, or contradictions to a past triptan.
Time frame: 2 Hours Postdose
Population: All randomized participants who were triptan insufficient responders and used at least 1 dose of study drug for an ITT evaluable attack, defined as a treated attack of at least mild pain severity with any postdose pain severity assessments at or before 2 hours postdose. As pre-specified in the analysis plan, outcome measures will not be reported for the MEE arms/groups but only for the main global study arms/groups.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 100 mg Lasmiditan | Percentage of Participants That Are Pain Free 2 Hours Postdose During the First Attack in Triptan Insufficient Responders. | 24.0 percentage of participants |
| 200 mg Lasmiditan | Percentage of Participants That Are Pain Free 2 Hours Postdose During the First Attack in Triptan Insufficient Responders. | 25.6 percentage of participants |
| Placebo | Percentage of Participants That Are Pain Free 2 Hours Postdose During the First Attack in Triptan Insufficient Responders. | 8.8 percentage of participants |
p-value: <0.00195% CI: [1.8, 6.02]Regression, Logistic
p-value: <0.00195% CI: [1.97, 6.42]Regression, Logistic
Secondary
Percentage of Participants That Are Pain Free at 2 Hours Postdose in at Least 2 Out of 3 Attacks in Triptan Insufficient Responders
Headache pain-free is defined as a reduction in pain severity from mild, moderate, or severe at baseline to none at the indicated assessment time. A subject is not counted as being pain-free at a specific time point if she or he used rescue or recurrence medication at or before the specific time point.
Time frame: 2 Hours Postdose
Population: All randomized participants who were triptan insufficient responders and experienced a sufficient number of successes or failures, (2 successes or 2 failures ) during their first 2 or 3 ITT-evaluable attacks. As pre-specified in the analysis plan, outcome measures will not be reported for the MEE arms/groups but only for the main global study arms/groups.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 100 mg Lasmiditan | Percentage of Participants That Are Pain Free at 2 Hours Postdose in at Least 2 Out of 3 Attacks in Triptan Insufficient Responders | 11.0 percentage of participants |
| 200 mg Lasmiditan | Percentage of Participants That Are Pain Free at 2 Hours Postdose in at Least 2 Out of 3 Attacks in Triptan Insufficient Responders | 20.1 percentage of participants |
| Placebo | Percentage of Participants That Are Pain Free at 2 Hours Postdose in at Least 2 Out of 3 Attacks in Triptan Insufficient Responders | 4.3 percentage of participants |
p-value: 0.03195% CI: [1.1, 6.78]Regression, Logistic
p-value: <0.00195% CI: [2.4, 13.25]Regression, Logistic
Secondary
Percentage of Participants That Are Pain Free at 2 Hours Postdose in at Least 3 Out of 4 Attacks
Headache pain-free is defined as a reduction in pain severity from mild, moderate, or severe to none at the indicated assessment time (2 hours postdose). To evaluate 3 out of 4 consistency endpoints; all ITT-evaluable attacks will be used. For the control group, the results of all ITT-evaluable attacks treated with lasmiditan 50 mg or placebo will be included. The control group is used for comparison. The population for 3 out of 4 consistency endpoints with sufficient number of successes or failures is defined as all participants who experienced at least 3 successes or 2 failures during ITT-evaluable attacks.
Time frame: 2 Hours Postdose
Population: All randomized participants who experienced a sufficient number of successes or failures, (3 out of 4 attacks) during ITT evaluable attacks for any of the consistency analyses. As pre-specified in the analysis plan, outcome measures will not be reported for the MEE arms/groups but only for the main global study arms/groups.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 100 mg Lasmiditan | Percentage of Participants That Are Pain Free at 2 Hours Postdose in at Least 3 Out of 4 Attacks | 7.4 percentage of participants |
| 200 mg Lasmiditan | Percentage of Participants That Are Pain Free at 2 Hours Postdose in at Least 3 Out of 4 Attacks | 10.8 percentage of participants |
| Placebo | Percentage of Participants That Are Pain Free at 2 Hours Postdose in at Least 3 Out of 4 Attacks | 2.6 percentage of participants |
p-value: 0.00495% CI: [1.42, 6.4]Regression, Logistic
p-value: <0.00195% CI: [2.22, 9.47]Regression, Logistic
Secondary
Percentage of Participants Very Much or Much Better as Measured by Patient Global Impression of Change (PGI-C), at 2 Hours Postdose During the First Attack
The PGI-C is a one-item questionnaire that asks participants to provide their impression of change since taking the medicine. The PGI-C is measured using a 7-point Likert scale, with 1 = very much better, 2 = much better, 3 = a little better, 4 = no change, 5 = a little worse, 6 = much worse, and 7 = very much worse. Reported are participants whose combined impression of change since taking the medicine was very much better and much better at 2 hours postdose.
Time frame: 2 Hours Postdose
Population: All randomized participants who used at least 1 dose of study drug for an ITT evaluable attack, defined as a treated attack of at least mild pain severity with any postdose pain severity assessments at or before 2 hours postdose. As pre-specified in the analysis plan, outcome measures will not be reported for the MEE arms/groups but only for the main global study arms/groups.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 100 mg Lasmiditan | Percentage of Participants Very Much or Much Better as Measured by Patient Global Impression of Change (PGI-C), at 2 Hours Postdose During the First Attack | 29.8 percentage of participants |
| 200 mg Lasmiditan | Percentage of Participants Very Much or Much Better as Measured by Patient Global Impression of Change (PGI-C), at 2 Hours Postdose During the First Attack | 30.0 percentage of participants |
| Placebo | Percentage of Participants Very Much or Much Better as Measured by Patient Global Impression of Change (PGI-C), at 2 Hours Postdose During the First Attack | 13.3 percentage of participants |
p-value: <0.00195% CI: [2.01, 4.05]Regression, Logistic
p-value: <0.00195% CI: [2.12, 4.26]Regression, Logistic
Secondary
Percentage of Participants With 24-Hour Sustained Pain Freedom During the First Attack
Sustained pain freedom defined as pain free at 2 and 24 hours with no rescue medication.
Time frame: 24 Hours
Population: All randomized participants who received at least 1 dose of study drug for an ITT evaluable attack, defined as a treated attack of at least mild pain severity with any postdose pain severity assessments at or before 2 hours postdose. As pre-specified in the analysis plan, outcome measures will not be reported for the MEE arms/groups but only for the main global study arms/groups.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 100 mg Lasmiditan | Percentage of Participants With 24-Hour Sustained Pain Freedom During the First Attack | 13.6 percentage of participants |
| 200 mg Lasmiditan | Percentage of Participants With 24-Hour Sustained Pain Freedom During the First Attack | 17.3 percentage of participants |
| Placebo | Percentage of Participants With 24-Hour Sustained Pain Freedom During the First Attack | 4.3 percentage of participants |
p-value: <0.00195% CI: [2.05, 6.02]Regression, Logistic
p-value: <0.00195% CI: [2.77, 7.88]Regression, Logistic
Secondary
Percentage of Participants With 48-Hour Sustained Pain Freedom During First Attack
Sustained pain freedom defined as pain free at 2 and 48 hours with no rescue medication.
Time frame: 48 Hours Postdose
Population: All randomized participants who received at least 1 dose of study drug for an ITT evaluable attack, defined as a treated attack of at least mild pain severity with any postdose pain severity assessments at or before 2 hours postdose. As pre-specified in the analysis plan, outcome measures will not be reported for the MEE arms/groups but only for the main global study arms/groups.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 100 mg Lasmiditan | Percentage of Participants With 48-Hour Sustained Pain Freedom During First Attack | 9.3 percentage of participants |
| 200 mg Lasmiditan | Percentage of Participants With 48-Hour Sustained Pain Freedom During First Attack | 15.4 percentage of participants |
| Placebo | Percentage of Participants With 48-Hour Sustained Pain Freedom During First Attack | 4.3 percentage of participants |
p-value: 0.00495% CI: [1.3, 4.04]Regression, Logistic
p-value: <0.00195% CI: [2.41, 6.94]Regression, Logistic
Secondary
Percentage of Participants With Associated Migraines Symptoms of Nausea, Vomiting, Photophobia, and Phonophobia Present at 2 Hours Postdose for First Attack
Presence of associated migraine symptoms at 2 hours postdose at first migraine attack, including each of the following: phonophobia, photophobia, nausea, and vomiting.
Time frame: 2 Hours Postdose
Population: All randomized participants who used at least 1 dose of study drug for an Intent-to-Treat (ITT) evaluable attack, defined as a treated attack of at least mild pain severity with any postdose pain severity assessments at or before 2 hours postdose. As pre-specified in the analysis plan, outcome measures will not be reported for the MEE arms/groups but only for the main global study arms/groups.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 100 mg Lasmiditan | Percentage of Participants With Associated Migraines Symptoms of Nausea, Vomiting, Photophobia, and Phonophobia Present at 2 Hours Postdose for First Attack | Nausea | 29.1 percentage of participants |
| 100 mg Lasmiditan | Percentage of Participants With Associated Migraines Symptoms of Nausea, Vomiting, Photophobia, and Phonophobia Present at 2 Hours Postdose for First Attack | Phonophobia | 26.7 percentage of participants |
| 100 mg Lasmiditan | Percentage of Participants With Associated Migraines Symptoms of Nausea, Vomiting, Photophobia, and Phonophobia Present at 2 Hours Postdose for First Attack | Photophobia | 38.2 percentage of participants |
| 100 mg Lasmiditan | Percentage of Participants With Associated Migraines Symptoms of Nausea, Vomiting, Photophobia, and Phonophobia Present at 2 Hours Postdose for First Attack | Vomiting | 1.2 percentage of participants |
| 200 mg Lasmiditan | Percentage of Participants With Associated Migraines Symptoms of Nausea, Vomiting, Photophobia, and Phonophobia Present at 2 Hours Postdose for First Attack | Vomiting | 3.0 percentage of participants |
| 200 mg Lasmiditan | Percentage of Participants With Associated Migraines Symptoms of Nausea, Vomiting, Photophobia, and Phonophobia Present at 2 Hours Postdose for First Attack | Nausea | 29.0 percentage of participants |
| 200 mg Lasmiditan | Percentage of Participants With Associated Migraines Symptoms of Nausea, Vomiting, Photophobia, and Phonophobia Present at 2 Hours Postdose for First Attack | Photophobia | 39.9 percentage of participants |
| 200 mg Lasmiditan | Percentage of Participants With Associated Migraines Symptoms of Nausea, Vomiting, Photophobia, and Phonophobia Present at 2 Hours Postdose for First Attack | Phonophobia | 23.5 percentage of participants |
| Placebo | Percentage of Participants With Associated Migraines Symptoms of Nausea, Vomiting, Photophobia, and Phonophobia Present at 2 Hours Postdose for First Attack | Vomiting | 2.7 percentage of participants |
| Placebo | Percentage of Participants With Associated Migraines Symptoms of Nausea, Vomiting, Photophobia, and Phonophobia Present at 2 Hours Postdose for First Attack | Phonophobia | 40.6 percentage of participants |
| Placebo | Percentage of Participants With Associated Migraines Symptoms of Nausea, Vomiting, Photophobia, and Phonophobia Present at 2 Hours Postdose for First Attack | Photophobia | 55.3 percentage of participants |
| Placebo | Percentage of Participants With Associated Migraines Symptoms of Nausea, Vomiting, Photophobia, and Phonophobia Present at 2 Hours Postdose for First Attack | Nausea | 29.1 percentage of participants |
Comparison: Nauseap-value: 0.95395% CI: [0.75, 1.36]Regression, Logistic
Comparison: Nauseap-value: 0.76895% CI: [0.78, 1.41]Regression, Logistic
Comparison: Phonophobiap-value: <0.00195% CI: [0.39, 0.71]Regression, Logistic
Comparison: Phonophobiap-value: <0.00195% CI: [0.34, 0.62]Regression, Linear
Comparison: Photophobiap-value: <0.00195% CI: [0.36, 0.63]Regression, Logistic
Comparison: Photophobiap-value: <0.00195% CI: [0.4, 0.71]Regression, Logistic
Comparison: Vomitingp-value: 0.12995% CI: [0.17, 1.25]Regression, Logistic
Comparison: Vomitingp-value: 0.76995% CI: [0.52, 2.43]Regression, Logistic
Secondary
Percentage of Participants With Migraine Recurrence at 24 Hours During the First Attack
Percentage of participants with migraine recurrence at 24 hours during the first attack defined as return of any headache in participants who were pain free at 2 hours.
Time frame: 24 Hours
Population: All randomized participants who used at least 1 dose of study drug for an ITT evaluable attack, defined as a treated attack of at least mild pain severity with any postdose pain severity assessments at or before 2 hours postdose. As pre-specified in the analysis plan, outcome measures will not be reported for the MEE arms/groups but only for the main global study arms/groups.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 100 mg Lasmiditan | Percentage of Participants With Migraine Recurrence at 24 Hours During the First Attack | 30.6 percentage of participants |
| 200 mg Lasmiditan | Percentage of Participants With Migraine Recurrence at 24 Hours During the First Attack | 22.0 percentage of participants |
| Placebo | Percentage of Participants With Migraine Recurrence at 24 Hours During the First Attack | 37.8 percentage of participants |
Secondary
Percentage of Participants With no Disability as Measured by the Disability Item, at 2 Hours Postdose During the First Attack
Percentage of participants with no disability as measured by the disability item, at 2 hours postdose during the first attack. Disability was measured by determining the level of interference with normal activities with 4 response options including not at all; mild interference, marked interference; and need complete bed rest.
Time frame: 2 Hours Postdose
Population: All randomized participants who used at least 1 dose of study drug for an ITT evaluable attack, defined as a treated attack of at least mild pain severity with any postdose pain severity assessments at or before 2 hours postdose. As pre-specified in the analysis plan, outcome measures will not be reported for the MEE arms/groups but only for the main global study arms/groups.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 100 mg Lasmiditan | Percentage of Participants With no Disability as Measured by the Disability Item, at 2 Hours Postdose During the First Attack | 18.6 percentage of participants |
| 200 mg Lasmiditan | Percentage of Participants With no Disability as Measured by the Disability Item, at 2 Hours Postdose During the First Attack | 19.8 percentage of participants |
| Placebo | Percentage of Participants With no Disability as Measured by the Disability Item, at 2 Hours Postdose During the First Attack | 9.5 percentage of participants |
p-value: <0.00195% CI: [1.48, 3.33]Regression, Logistic
p-value: <0.00195% CI: [1.65, 3.67]Regression, Logistic
Secondary
Percentage of Participants With Pain Freedom, Pain Relief, Freedom From MBS, and No Disability Postdose During First Attack
Percentage of participants with pain freedom, pain relief, freedom from MBS, and no disability postdose during first attack.
Time frame: 30 Minutes (Min) and 1 Hour (Hr) Postdose
Population: All randomized participants who used at least 1 dose of study drug for an ITT evaluable attack, defined as a treated attack of at least mild pain severity with any postdose pain severity assessments at or before 2 hours postdose. As pre-specified in the analysis plan, outcome measures will not be reported for the MEE arms/groups but only for the main global study arms/groups.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 100 mg Lasmiditan | Percentage of Participants With Pain Freedom, Pain Relief, Freedom From MBS, and No Disability Postdose During First Attack | Pain Freedom (1Hr) | 6.0 percentage of participants |
| 100 mg Lasmiditan | Percentage of Participants With Pain Freedom, Pain Relief, Freedom From MBS, and No Disability Postdose During First Attack | Pain Relief (1 Hr) | 48.7 percentage of participants |
| 100 mg Lasmiditan | Percentage of Participants With Pain Freedom, Pain Relief, Freedom From MBS, and No Disability Postdose During First Attack | Pain Relief (30 Min) | 18.6 percentage of participants |
| 100 mg Lasmiditan | Percentage of Participants With Pain Freedom, Pain Relief, Freedom From MBS, and No Disability Postdose During First Attack | No Disability Postdose During First Attack (1 Hr) | 6.0 percentage of participants |
| 100 mg Lasmiditan | Percentage of Participants With Pain Freedom, Pain Relief, Freedom From MBS, and No Disability Postdose During First Attack | Pain Freedom (30 Min) | 1.4 percentage of participants |
| 100 mg Lasmiditan | Percentage of Participants With Pain Freedom, Pain Relief, Freedom From MBS, and No Disability Postdose During First Attack | Freedom from MBS (30 Min) | 12.5 percentage of participants |
| 100 mg Lasmiditan | Percentage of Participants With Pain Freedom, Pain Relief, Freedom From MBS, and No Disability Postdose During First Attack | No Disability Postdose During First Attack (30 Min) | 3.1 percentage of participants |
| 100 mg Lasmiditan | Percentage of Participants With Pain Freedom, Pain Relief, Freedom From MBS, and No Disability Postdose During First Attack | Freedom from MBS (1 Hr) | 23.7 percentage of participants |
| 200 mg Lasmiditan | Percentage of Participants With Pain Freedom, Pain Relief, Freedom From MBS, and No Disability Postdose During First Attack | Pain Freedom (30 Min) | 1.6 percentage of participants |
| 200 mg Lasmiditan | Percentage of Participants With Pain Freedom, Pain Relief, Freedom From MBS, and No Disability Postdose During First Attack | Freedom from MBS (1 Hr) | 28.9 percentage of participants |
| 200 mg Lasmiditan | Percentage of Participants With Pain Freedom, Pain Relief, Freedom From MBS, and No Disability Postdose During First Attack | Pain Relief (1 Hr) | 47.2 percentage of participants |
| 200 mg Lasmiditan | Percentage of Participants With Pain Freedom, Pain Relief, Freedom From MBS, and No Disability Postdose During First Attack | No Disability Postdose During First Attack (30 Min) | 2.3 percentage of participants |
| 200 mg Lasmiditan | Percentage of Participants With Pain Freedom, Pain Relief, Freedom From MBS, and No Disability Postdose During First Attack | No Disability Postdose During First Attack (1 Hr) | 9.9 percentage of participants |
| 200 mg Lasmiditan | Percentage of Participants With Pain Freedom, Pain Relief, Freedom From MBS, and No Disability Postdose During First Attack | Pain Freedom (1Hr) | 12.7 percentage of participants |
| 200 mg Lasmiditan | Percentage of Participants With Pain Freedom, Pain Relief, Freedom From MBS, and No Disability Postdose During First Attack | Pain Relief (30 Min) | 22.4 percentage of participants |
| 200 mg Lasmiditan | Percentage of Participants With Pain Freedom, Pain Relief, Freedom From MBS, and No Disability Postdose During First Attack | Freedom from MBS (30 Min) | 14.4 percentage of participants |
| Placebo | Percentage of Participants With Pain Freedom, Pain Relief, Freedom From MBS, and No Disability Postdose During First Attack | Pain Relief (1 Hr) | 29.3 percentage of participants |
| Placebo | Percentage of Participants With Pain Freedom, Pain Relief, Freedom From MBS, and No Disability Postdose During First Attack | No Disability Postdose During First Attack (1 Hr) | 5.0 percentage of participants |
| Placebo | Percentage of Participants With Pain Freedom, Pain Relief, Freedom From MBS, and No Disability Postdose During First Attack | Pain Freedom (30 Min) | 0.2 percentage of participants |
| Placebo | Percentage of Participants With Pain Freedom, Pain Relief, Freedom From MBS, and No Disability Postdose During First Attack | Pain Freedom (1Hr) | 2.0 percentage of participants |
| Placebo | Percentage of Participants With Pain Freedom, Pain Relief, Freedom From MBS, and No Disability Postdose During First Attack | Pain Relief (30 Min) | 14.0 percentage of participants |
| Placebo | Percentage of Participants With Pain Freedom, Pain Relief, Freedom From MBS, and No Disability Postdose During First Attack | Freedom from MBS (30 Min) | 11.4 percentage of participants |
| Placebo | Percentage of Participants With Pain Freedom, Pain Relief, Freedom From MBS, and No Disability Postdose During First Attack | Freedom from MBS (1 Hr) | 22.0 percentage of participants |
| Placebo | Percentage of Participants With Pain Freedom, Pain Relief, Freedom From MBS, and No Disability Postdose During First Attack | No Disability Postdose During First Attack (30 Min) | 2.3 percentage of participants |
Comparison: Pain Freedom 30 Min. Postdosep-value: 0.08695% CI: [0.77, 53.37]Regression, Logistic
Comparison: Pain Freedom 30 Min. Postdosep-value: 0.06595% CI: [0.89, 59.08]Regression, Logistic
Comparison: Pain Free 1 Hour Postdosep-value: 0.00495% CI: [1.42, 6.68]Regression, Logistic
Comparison: Pain Free 1 Hour Postdosep-value: <0.00195% CI: [3.43, 14.44]Regression, Logistic
Comparison: Pain Relief 30 Min Postdose 100 mgp-value: 0.06595% CI: [0.98, 2.03]Regression, Logistic
Comparison: Pain Relief 30 Min. Postdose 200 mgp-value: 0.00195% CI: [1.25, 2.52]Regression, Logistic
Comparison: Pain Relief 1 Hour Postdose 100 mgp-value: <0.00195% CI: [1.74, 3.06]Regression, Logistic
Comparison: Pain Relief 1 Hour Postdose 200 mgp-value: <0.00195% CI: [1.64, 2.88]Regression, Logistic
Comparison: Freedom from MBS 30 Min 100 mgp-value: 0.65195% CI: [0.71, 1.71]Regression, Logistic
Comparison: Freedom from MBS 30 Min. 200 mgp-value: 0.2295% CI: [0.85, 1.98]Regression, Logistic
Comparison: Freedom from MBS 1 Hour 100 mgp-value: 0.59395% CI: [0.78, 1.54]Regression, Logistic
Comparison: Freedom from MBS 1 Hour 200 mgp-value: 0.0395% CI: [1.04, 1.98]Regression, Logistic
Secondary
Percentage of Participants With Pain Relief at 2 Hours Post Dose During the First Attack
Headache pain-relief is defined as a reduction in pain severity from moderate or severe at baseline to mild or none, or a reduction in pain severity from mild at baseline to none, at the indicated assessment time.
Time frame: 2 Hours Postdose
Population: All randomized participants who use at least 1 dose of study drug for an ITT evaluable attack, defined as a treated attack of at least mild pain severity with any postdose pain severity assessments at or before 2 hours postdose. As pre-specified in the analysis plan, outcome measures will not be reported for the MEE arms/groups but only for the main global study arms/groups.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 100 mg Lasmiditan | Percentage of Participants With Pain Relief at 2 Hours Post Dose During the First Attack | 65.4 percentage of participants |
| 200 mg Lasmiditan | Percentage of Participants With Pain Relief at 2 Hours Post Dose During the First Attack | 65.2 percentage of participants |
| Placebo | Percentage of Participants With Pain Relief at 2 Hours Post Dose During the First Attack | 41.3 percentage of participants |
p-value: <0.00195% CI: [2.05, 3.57]Regression, Logistic
p-value: <0.00195% CI: [2.04, 3.53]Regression, Logistic
Secondary
Percentage of Participants With Pain Relief at 2 Hours Postdose in at Least 2 Out of 3 Attacks
Headache pain relief is defined as a reduction in pain severity from moderate to severe at baseline to mild or none at 2 hours postdose in at least 2 out of 3 attacks. To evaluate at least 2 out of 3 consistency endpoints, the results of ITT-evaluable attacks in the lasmiditan 100-mg and 200-mg groups will be assessed, and the ITT-evaluable attacks treated with placebo in the control group will be used for comparison. For participants with more than 3 ITT-evaluable attacks, only the first 3 with the same treatment will be considered.
Time frame: 2 Hours Postdose
Population: All randomized participants who experienced a sufficient number of successes or failures, (2 successes or 2 failures ) during their first 2 or 3 ITT-evaluable attacks. As pre-specified in the analysis plan, outcome measures will not be reported for the MEE arms/groups but only for the main global study arms/groups.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 100 mg Lasmiditan | Percentage of Participants With Pain Relief at 2 Hours Postdose in at Least 2 Out of 3 Attacks | 62.3 percentage of participants |
| 200 mg Lasmiditan | Percentage of Participants With Pain Relief at 2 Hours Postdose in at Least 2 Out of 3 Attacks | 66.7 percentage of participants |
| Placebo | Percentage of Participants With Pain Relief at 2 Hours Postdose in at Least 2 Out of 3 Attacks | 36.9 percentage of participants |
p-value: <0.00195% CI: [2.11, 4.01]Regression, Logistic
p-value: <0.00195% CI: [2.53, 4.85]Regression, Logistic
Secondary
Percentage of Participants With Pain Relief at 2 Hours Postdose in at Least 3 Out of 4 Attacks
Headache pain-relief is defined as a reduction in pain severity from moderate or severe at baseline to mild or none, or a reduction in pain severity from mild at baseline to none, at the indicated assessment time (2 hours postdose). To evaluate 3 out of 4 consistency endpoints; all ITT-evaluable attacks will be used. For the control group, the results of all ITT-evaluable attacks treated with lasmiditan 50 mg or placebo will be included. The control group is used for comparison. The population for 3 out of 4 consistency endpoints with sufficient number of successes or failures is defined as all participants who experienced at least 3 successes or 2 failures during ITT-evaluable attacks.
Time frame: 2 Hours Postdose
Population: All randomized participants who experienced a sufficient number of successes or failures, (3 successes or 2 failures ) during ITT-evaluable attacks for any of the consistency analyses. As pre-specified in the analysis plan, outcome measures will not be reported for the MEE arms/groups but only for the main global study arms/groups.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 100 mg Lasmiditan | Percentage of Participants With Pain Relief at 2 Hours Postdose in at Least 3 Out of 4 Attacks | 40.8 percentage of participants |
| 200 mg Lasmiditan | Percentage of Participants With Pain Relief at 2 Hours Postdose in at Least 3 Out of 4 Attacks | 49.8 percentage of participants |
| Placebo | Percentage of Participants With Pain Relief at 2 Hours Postdose in at Least 3 Out of 4 Attacks | 21.8 percentage of participants |
p-value: <0.00195% CI: [1.74, 3.62]Regression, Logistic
p-value: <0.00195% CI: [2.5, 5.2]Regression, Logistic