Migraine With or Without Aura
Conditions
Brief summary
This is a prospective randomized, double-blind, placebo-controlled study in participants with disabling migraine (Migraine Disability Assessment (MIDAS) score ≥ 11).
Detailed description
Participants will be asked to treat a migraine attack with study drug on an outpatient basis. Participants will be provided with a dosing card containing a dose for initial treatment and a second dose to be used for rescue or recurrence of migraine. Each participant's study participation will consist of screening (Visit 1) with a telephone contact within 7 days to confirm eligibility, a Treatment Period of up to 8 weeks, and End-of-Study (EoS) (Visit 2) within one week (7 days) of treating a single migraine attack. The total time on study is approximately up to 11 weeks.
Interventions
DRUGLasmiditan 50 mg
One tablet lasmiditan 50 mg plus one placebo tablet (matching one of the lasmiditan doses)
One tablet lasmiditan 100 mg plus one placebo tablet (matching one of the lasmiditan doses)
One tablet lasmiditan 200 mg plus one placebo tablet (matching one of the lasmiditan doses)
DRUGPlacebo
Two placebo tablets to match lasmiditan doses.
Sponsors
CoLucid Pharmaceuticals
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Able and willing to give written informed consent and authorize HIPAA. * Participants with migraine with or without aura fulfilling the International Headache Society (IHS) diagnostic criteria 1.1 and 1.2.1 (International Headache Classification (ICHD) 2004). * History of disabling migraine for at least 1 year. * Migraine Disability Association (MIDAS) score ≥11. * Migraine onset before the age of 50 years. * History of 3 - 8 migraine attacks per month (\< 15 headache days per month). * Male or female, aged 18 years or above. * Females of child-bearing potential must be using or willing to use a highly effective form of contraception (e.g. combined oral contraceptive, intrauterine device (IUD), abstinence or vasectomized partner). * Able and willing to complete an electronic diary to record details of the migraine attack treated with study drug.
Exclusion criteria
* Any medical condition or clinical laboratory test which in the judgment of the Investigator makes the participant unsuitable for the study. * Pregnant or breast-feeding women. * Women of child-bearing potential not using or not willing to use highly effective contraception. * Known hypersensitivity to lasmiditan or to any excipient of lasmiditan oral tablets, or any sensitivity to lasmiditan. * 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 (BPPV), Meniere's disease, vestibular migraine, and other vestibular disorders. * History of diabetes mellitus with complications (diabetic retinopathy, nephropathy or neuropathy). * History within the previous three years or current evidence of abuse of any drug, prescription or illicit, or alcohol. * History of orthostatic hypotension with syncope. * Significant renal or hepatic impairment. * Participant is at imminent risk of suicide (positive response to question 4 or 5) on the Columbia-Suicide Severity Rating Scale (C-SSRS) or had a suicide attempt within six months prior to screening. * Previous participation in this clinical trial. * Participation in any clinical trial of an experimental drug or device in the previous 30 days. * Known Hepatitis B or C or HIV infection. * History, within past 12 months, of chronic migraine or other forms of primary or secondary chronic headache disorder (e.g. hemicranias continua, medication overuse headache) where headache frequency is ≥15 headache days per month. * Use of more than 3 doses per month of either opiates or barbiturates. * Initiation of or a change in concomitant medication to reduce the frequency of migraine episodes within three (3) months prior to Screening/Visit 1. * Participants who are employees of the sponsor. * Relatives of, or staff directly reporting to, the Investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Headache Pain Free at 2 Hours Post Dose | 2 hours post dose | The percentage of participants defined as mild, moderate, or severe headache pain becoming none. |
| Percentage of Participants Who Are Most Bothersome Symptom (MBS) Free | 2 hours post dose | The percentage of participants defined as the associated symptom present and identified as MBS (nausea, photophobia, or phonophobia) prior to dosing being absent. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Use of Rescue Medication | 2 hours post dose | The percentage of participants who used rescue medication. |
| Percentage of Participants Nausea Free | 2 hours post dose | The percentage of participant without nausea. |
| Percentage of Participants With Phonophobia Free | 2 hours post dose | The percentage of participants without phonophobia. |
| Percentage of Participants With Headache Relief | 2 hours post dose | The percentage of participants with headache pain moderate or severe which became mild or none or with headache pain mild which became none. |
| Percentage of Participants With Resource Utilization | 6 Months Prior to Enrolling in Study to End of Study (Up to 11 Weeks) Within 7 Days of Treating a Single Migraine Attack | Use of health care for treatment 6 months prior to enrolling in the study and information reported during time on study |
| Number of Participants With Treatment Emergent Events | From Baseline Up to End of Study (Up to 11 Weeks) | Safety and Tolerability was assessed by the number of participants with at least 1 treatment emergent event (TEAE). A summary of other non-serious adverse events and all serious adverse events, regardless of causality, is located in the Reported Adverse Events Section |
| Percentage of Participants With Photophobia Free | 2 hours post dose | The percentage of participants without photophobia. |
| Number of Participants With Headache Recurrence | From 2 Hours Post Dose Up to 48 Hours | The number of participants with headache recurrence (moderate or severe at baseline which became pain-free at 2 hours post dose and worsened again up to 48 hours post dose) |
Countries
United States
Participant flow
Pre-assignment details
Participants were randomly assigned to 1 of 7 sequences and received lasmiditan 50 mg (L50 mg), lasmiditan 100 mg (L100 mg) or lasmiditan 200 mg (L200 mg) or placebo (P) for the first dose and the second dose, if needed for rescue or recurrence of migraine.
Participants by arm
| Arm | Count |
|---|---|
| Lasmiditan 50 mg Lasmiditan 50 mg was administered orally, once for acute treatment of migraine. A second optional dose was administered between 2 and 24 hours for rescue or recurrence of migraine. | 654 |
| Lasmiditan 100 mg Lasmiditan 100 mg was administered orally, once for acute treatment of migraine. A second optional dose was administered between 2 and 24 hours for rescue or recurrence of migraine. | 635 |
| Lasmiditan 200 mg Lasmiditan 200 mg was administered orally, once for acute treatment of migraine. A second optional dose was administered between 2 and 24 hours for rescue or recurrence of migraine. | 649 |
| Placebo Placebo tablets match each of the lasmiditan doses (50 mg, 100 mg and 200 mg) was administered orally, once for acute treatment of migraine. A second optional dose was administered between 2 and 24 hours for rescue or recurrence of migraine. | 645 |
| Total | 2,583 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 1 | 0 | 4 | 0 | 0 |
| Overall Study | Lost to Follow-up | 20 | 7 | 27 | 10 | 20 | 10 | 29 |
| Overall Study | Physician Decision | 2 | 0 | 0 | 0 | 0 | 0 | 3 |
| Overall Study | Pregnancy | 1 | 0 | 0 | 2 | 0 | 0 | 0 |
| Overall Study | Protocol Violation | 10 | 4 | 14 | 6 | 7 | 7 | 12 |
| Overall Study | Randomization Failure | 22 | 6 | 20 | 7 | 16 | 11 | 30 |
| Overall Study | Withdrawal by Subject | 9 | 6 | 14 | 11 | 6 | 4 | 15 |
Baseline characteristics
| Characteristic | Lasmiditan 50 mg | Lasmiditan 100 mg | Lasmiditan 200 mg | Placebo | Total |
|---|---|---|---|---|---|
| Age, Continuous | 42.8 years STANDARD_DEVIATION 13.2 | 43.4 years STANDARD_DEVIATION 12.59 | 41.8 years STANDARD_DEVIATION 12.4 | 42.6 years STANDARD_DEVIATION 12.9 | 42.7 years STANDARD_DEVIATION 12.79 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 3 Participants | 2 Participants | 2 Participants | 5 Participants | 12 Participants |
| Race/Ethnicity, Customized Asian | 5 Participants | 6 Participants | 7 Participants | 3 Participants | 21 Participants |
| Race/Ethnicity, Customized Black or African American | 106 Participants | 104 Participants | 106 Participants | 110 Participants | 426 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 135 Participants | 137 Participants | 136 Participants | 124 Participants | 532 Participants |
| Race/Ethnicity, Customized Missing | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Multiple | 8 Participants | 5 Participants | 5 Participants | 5 Participants | 23 Participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander | 2 Participants | 1 Participants | 2 Participants | 2 Participants | 7 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 515 Participants | 493 Participants | 511 Participants | 518 Participants | 2037 Participants |
| Race/Ethnicity, Customized Not Reported | 3 Participants | 3 Participants | 0 Participants | 3 Participants | 9 Participants |
| Race/Ethnicity, Customized Other | 6 Participants | 8 Participants | 4 Participants | 4 Participants | 22 Participants |
| Race/Ethnicity, Customized Unknown | 1 Participants | 2 Participants | 1 Participants | 0 Participants | 4 Participants |
| Race/Ethnicity, Customized White | 524 Participants | 509 Participants | 522 Participants | 516 Participants | 2071 Participants |
| Region of Enrollment Germany | 77 Participants | 79 Participants | 77 Participants | 77 Participants | 310 Participants |
| Region of Enrollment United Kingdom | 48 Participants | 48 Participants | 47 Participants | 48 Participants | 191 Participants |
| Region of Enrollment United States | 625 Participants | 627 Participants | 626 Participants | 626 Participants | 2504 Participants |
| Sex: Female, Male Female | 554 Participants | 539 Participants | 536 Participants | 545 Participants | 2174 Participants |
| Sex: Female, Male Male | 100 Participants | 96 Participants | 113 Participants | 100 Participants | 409 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 / 429 | 0 / 225 | 0 / 423 | 0 / 212 | 0 / 435 | 0 / 217 | 0 / 646 |
| other Total, other adverse events | 118 / 429 | 61 / 225 | 149 / 423 | 94 / 212 | 177 / 435 | 87 / 217 | 80 / 646 |
| serious Total, serious adverse events | 1 / 429 | 0 / 225 | 1 / 423 | 1 / 212 | 3 / 435 | 0 / 217 | 2 / 646 |
Outcome results
Primary
Percentage of Participants Headache Pain Free at 2 Hours Post Dose
The percentage of participants defined as mild, moderate, or severe headache pain becoming none.
Time frame: 2 hours post dose
Population: All randomized participants who received at least one dose of study drug and had evaluable headache pain free data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lasmiditan 50 mg | Percentage of Participants Headache Pain Free at 2 Hours Post Dose | 28.6 percentage of participants |
| Lasmiditan 100 mg | Percentage of Participants Headache Pain Free at 2 Hours Post Dose | 31.4 percentage of participants |
| Lasmiditan 200 mg | Percentage of Participants Headache Pain Free at 2 Hours Post Dose | 38.8 percentage of participants |
| Placebo | Percentage of Participants Headache Pain Free at 2 Hours Post Dose | 21.3 percentage of participants |
p-value: 0.00395% CI: [1.1, 1.9]Regression, Logistic
p-value: <0.00195% CI: [1.3, 2.2]Regression, Logistic
p-value: <0.00195% CI: [1.8, 3.1]Regression, Logistic
Primary
Percentage of Participants Who Are Most Bothersome Symptom (MBS) Free
The percentage of participants defined as the associated symptom present and identified as MBS (nausea, photophobia, or phonophobia) prior to dosing being absent.
Time frame: 2 hours post dose
Population: All randomized participants who received at least one dose of study drug and had evaluable MBS data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lasmiditan 50 mg | Percentage of Participants Who Are Most Bothersome Symptom (MBS) Free | 40.8 percentage of participants |
| Lasmiditan 100 mg | Percentage of Participants Who Are Most Bothersome Symptom (MBS) Free | 44.2 percentage of participants |
| Lasmiditan 200 mg | Percentage of Participants Who Are Most Bothersome Symptom (MBS) Free | 48.7 percentage of participants |
| Placebo | Percentage of Participants Who Are Most Bothersome Symptom (MBS) Free | 33.5 percentage of participants |
p-value: 0.00995% CI: [1.1, 1.8]Regression, Logistic
p-value: <0.00195% CI: [1.2, 2]Regression, Logistic
p-value: <0.00195% CI: [1.4, 2.4]Regression, Logistic
Other Pre-specified
Number of Participants With Headache Recurrence
The number of participants with headache recurrence (moderate or severe at baseline which became pain-free at 2 hours post dose and worsened again up to 48 hours post dose)
Time frame: From 2 Hours Post Dose Up to 48 Hours
Population: All randomized participants who received at least one dose of study drug and had evaluable headache recurrence data.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lasmiditan 50 mg | Number of Participants With Headache Recurrence | 38 Participants |
| Lasmiditan 100 mg | Number of Participants With Headache Recurrence | 44 Participants |
| Lasmiditan 200 mg | Number of Participants With Headache Recurrence | 52 Participants |
| Placebo | Number of Participants With Headache Recurrence | 26 Participants |
Other Pre-specified
Number of Participants With Treatment Emergent Events
Safety and Tolerability was assessed by the number of participants with at least 1 treatment emergent event (TEAE). A summary of other non-serious adverse events and all serious adverse events, regardless of causality, is located in the Reported Adverse Events Section
Time frame: From Baseline Up to End of Study (Up to 11 Weeks)
Population: All randomized participants who had received at least one dose of study drug. Results are displayed by the first dose taken.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lasmiditan 50 mg | Number of Participants With Treatment Emergent Events | 167 participants |
| Lasmiditan 100 mg | Number of Participants With Treatment Emergent Events | 230 participants |
| Lasmiditan 200 mg | Number of Participants With Treatment Emergent Events | 253 participants |
| Placebo | Number of Participants With Treatment Emergent Events | 75 participants |
Other Pre-specified
Percentage of Participants Nausea Free
The percentage of participant without nausea.
Time frame: 2 hours post dose
Population: All randomized participants who received at least one dose of study drug and had evaluable nausea free data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lasmiditan 50 mg | Percentage of Participants Nausea Free | 68.7 percentage of participants |
| Lasmiditan 100 mg | Percentage of Participants Nausea Free | 71.8 percentage of participants |
| Lasmiditan 200 mg | Percentage of Participants Nausea Free | 70.4 percentage of participants |
| Placebo | Percentage of Participants Nausea Free | 70.3 percentage of participants |
p-value: 0.52295% CI: [0.7, 1.2]Regression, Logistic
p-value: 0.62295% CI: [0.8, 1.4]Regression, Logistic
p-value: 0.99295% CI: [0.8, 1.3]Regression, Logistic
Other Pre-specified
Percentage of Participants Use of Rescue Medication
The percentage of participants who used rescue medication.
Time frame: 2 hours post dose
Population: All randomized participants who received at least one dose of study drug and had evaluable use of rescue medication data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lasmiditan 50 mg | Percentage of Participants Use of Rescue Medication | 31.9 percentage of participants |
| Lasmiditan 100 mg | Percentage of Participants Use of Rescue Medication | 26.4 percentage of participants |
| Lasmiditan 200 mg | Percentage of Participants Use of Rescue Medication | 18.9 percentage of participants |
| Placebo | Percentage of Participants Use of Rescue Medication | 40.8 percentage of participants |
p-value: 0.00295% CI: [0.5, 0.9]Regression, Logistic
p-value: <0.00195% CI: [0.4, 0.7]Regression, Logistic
p-value: <0.00195% CI: [0.3, 0.4]Regression, Logistic
Other Pre-specified
Percentage of Participants Use of Rescue Medication
The percentage of participants who used rescue medication.
Time frame: From 2 Hours Post Dose Up to 24 Hours
Population: All randomized participants who received at least one dose of study drug and had evaluable use of rescue medication data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lasmiditan 50 mg | Percentage of Participants Use of Rescue Medication | 8.9 percentage of participants |
| Lasmiditan 100 mg | Percentage of Participants Use of Rescue Medication | 6.3 percentage of participants |
| Lasmiditan 200 mg | Percentage of Participants Use of Rescue Medication | 7.4 percentage of participants |
| Placebo | Percentage of Participants Use of Rescue Medication | 8.7 percentage of participants |
p-value: 0.91795% CI: [0.7, 1.5]Regression, Logistic
p-value: 0.12995% CI: [0.5, 1.1]Regression, Logistic
p-value: 0.45695% CI: [0.6, 1.3]Regression, Logistic
Other Pre-specified
Percentage of Participants Use of Rescue Medication
The percentage of participants who used rescue medication.
Time frame: From 24 Post Dose Up to 48 Hours
Population: All randomized participants who received at least one dose of study drug and had evaluable use of rescue medication data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lasmiditan 50 mg | Percentage of Participants Use of Rescue Medication | 0.0 percentage of participants |
| Lasmiditan 100 mg | Percentage of Participants Use of Rescue Medication | 0.0 percentage of participants |
| Lasmiditan 200 mg | Percentage of Participants Use of Rescue Medication | 0.0 percentage of participants |
| Placebo | Percentage of Participants Use of Rescue Medication | 0.0 percentage of participants |
Other Pre-specified
Percentage of Participants With Headache Relief
The percentage of participants with headache pain moderate or severe which became mild or none or with headache pain mild which became none.
Time frame: 2 hours post dose
Population: All randomized participants who received at least one dose of study drug and had evaluable headache relief data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lasmiditan 50 mg | Percentage of Participants With Headache Relief | 59.0 percentage of participants |
| Lasmiditan 100 mg | Percentage of Participants With Headache Relief | 64.8 percentage of participants |
| Lasmiditan 200 mg | Percentage of Participants With Headache Relief | 65.0 percentage of participants |
| Placebo | Percentage of Participants With Headache Relief | 47.7 percentage of participants |
p-value: <0.00195% CI: [1.3, 2.2]Regression, Logistic
p-value: <0.00195% CI: [1.7, 2.9]Regression, Logistic
p-value: <0.00195% CI: [1.8, 3.1]Regression, Logistic
Other Pre-specified
Percentage of Participants With Phonophobia Free
The percentage of participants without phonophobia.
Time frame: 2 hours post dose
Population: All randomized participants who received at least one dose of study drug and had evaluable phonophobia free data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lasmiditan 50 mg | Percentage of Participants With Phonophobia Free | 61.2 percentage of participants |
| Lasmiditan 100 mg | Percentage of Participants With Phonophobia Free | 64.8 percentage of participants |
| Lasmiditan 200 mg | Percentage of Participants With Phonophobia Free | 65.3 percentage of participants |
| Placebo | Percentage of Participants With Phonophobia Free | 53.5 percentage of participants |
p-value: 0.00895% CI: [1.1, 1.7]Regression, Logistic
p-value: <0.00195% CI: [1.3, 2]Regression, Logistic
p-value: <0.00195% CI: [1.3, 2.1]Regression, Logistic
Other Pre-specified
Percentage of Participants With Photophobia Free
The percentage of participants without photophobia.
Time frame: 2 hours post dose
Population: All randomized participants who received at least one dose of study drug and had evaluable photophobia free data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lasmiditan 50 mg | Percentage of Participants With Photophobia Free | 51.2 percentage of participants |
| Lasmiditan 100 mg | Percentage of Participants With Photophobia Free | 56.4 percentage of participants |
| Lasmiditan 200 mg | Percentage of Participants With Photophobia Free | 58.2 percentage of participants |
| Placebo | Percentage of Participants With Photophobia Free | 43.2 percentage of participants |
p-value: 0.00795% CI: [1.1, 1.7]Regression, Logistic
p-value: <0.00195% CI: [1.3, 2.1]Regression, Logistic
p-value: <0.00195% CI: [1.4, 2.3]Regression, Logistic
Other Pre-specified
Percentage of Participants With Resource Utilization
Use of health care for treatment 6 months prior to enrolling in the study and information reported during time on study
Time frame: 6 Months Prior to Enrolling in Study to End of Study (Up to 11 Weeks) Within 7 Days of Treating a Single Migraine Attack
Population: All randomized participants who had received at least one dose of study drug and had evaluable resource utilization data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Lasmiditan 50 mg | Percentage of Participants With Resource Utilization | 6 months prior to enrolling | 4.7 percentage of participants |
| Lasmiditan 50 mg | Percentage of Participants With Resource Utilization | During time of study | 0.5 percentage of participants |
| Lasmiditan 100 mg | Percentage of Participants With Resource Utilization | 6 months prior to enrolling | 2.2 percentage of participants |
| Lasmiditan 100 mg | Percentage of Participants With Resource Utilization | During time of study | 0 percentage of participants |
| Lasmiditan 200 mg | Percentage of Participants With Resource Utilization | 6 months prior to enrolling | 2.8 percentage of participants |
| Lasmiditan 200 mg | Percentage of Participants With Resource Utilization | During time of study | 0.5 percentage of participants |
| Placebo | Percentage of Participants With Resource Utilization | 6 months prior to enrolling | 2.4 percentage of participants |
| Placebo | Percentage of Participants With Resource Utilization | During time of study | 0 percentage of participants |
| Lasmiditan 200 mg/Lasmiditan 200 mg | Percentage of Participants With Resource Utilization | 6 months prior to enrolling | 3.2 percentage of participants |
| Lasmiditan 200 mg/Lasmiditan 200 mg | Percentage of Participants With Resource Utilization | During time of study | 0.9 percentage of participants |
| Lasmiditan 200 mg/Placebo | Percentage of Participants With Resource Utilization | 6 months prior to enrolling | 3.3 percentage of participants |
| Lasmiditan 200 mg/Placebo | Percentage of Participants With Resource Utilization | During time of study | 0.5 percentage of participants |
| Placebo/Placebo | Percentage of Participants With Resource Utilization | 6 months prior to enrolling | 2.9 percentage of participants |
| Placebo/Placebo | Percentage of Participants With Resource Utilization | During time of study | 0.6 percentage of participants |