Lasmiditan Compared to Placebo in the Acute Treatment of Migraine:

Study Overview
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Brief Summary
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This is a prospective randomized, double-blind, placebo-controlled study in participants with disabling migraine (Migraine Disability Assessment (MIDAS) score ≥ 11).

Detailed Description
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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 a screening visit (Visit 1) with a telephone contact within 7 days to confirm eligibility, a Treatment Period of up to 8 weeks, and an End-of-Study (EoS) visit (Visit 2) within one week (7 days) of treating a single migraine attack. The total time on study is approximately 11 weeks.

Official Title
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A Study of Two Doses of LAsMiditan (100 mg and 200 mg) Compared to Placebo in the AcUte Treatment of MigRAIne: A Randomized, Double-blind, Placebo-controlled Parallel Group Study

Conditions
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Acute Migraine

Intervention / Treatment
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* Drug: Lasmiditan 100 mg
* Drug: Lasmiditan 200 mg
* Drug: Placebo (matches lasmiditan doses)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able and willing to give written informed consent. 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. 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. Exclusion Criteria: Pregnant or breast-feeding women. Women of child-bearing potential not using or not willing to use highly effective contraception. Known coronary artery disease, clinically significant arrhythmia or uncontrolled hypertension. 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 C-SSRS) or had a suicide attempt within six months prior to the screening visit. 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 greater than 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lasmiditan 100 mg<br>Oral tablet. Lasmiditan 100 mg plus placebo (to match 200 mg tablet). One dose for acute treatment of migraine. Second dose for rescue or recurrence of migraine allowed within 24 hours. | Drug: Lasmiditan 100 mg<br> <br> * Other names: LY573144;Drug: Placebo (matches lasmiditan doses)<br> <br> |
| Experimental: Lasmiditan 200 mg<br>Oral tablet. Lasmiditan 200 mg plus placebo (to match 100 mg tablet). One dose for acute treatment of migraine. Second dose for rescue or recurrence of migraine allowed within 24 hours. | Drug: Lasmiditan 200 mg<br> <br> * Other names: LY573144;Drug: Placebo (matches lasmiditan doses)<br> <br> |
| Placebo Comparator: Placebo<br>Oral tablet. Placebo tablets match lasmiditan 100 mg and lasmiditan 200 mg. One dose for acute treatment of migraine. Second dose for rescue or recurrence of migraine allowed within 24 hours. | Drug: Placebo (matches lasmiditan doses)<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Are Headache Pain Free | The percentage of participants defined as mild, moderate, or severe headache pain becoming none. | 2 hours post dose | 
| 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. | 2 hours post dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Have Headache Relief After First Dose | The percentage of participants with headache pain moderate or severe which became mild or none or with headache pain mild which became none. | 2 hours post dose | 
| Percentage of Participants With Headache Recurrence | Participants who received study drug and which became pain free at 2 hours post-dose and worsened again up to 48 hours post-dose. | From 2 hours post dose up to 48 hours | 
| Percentage of Participants Who Used Rescue Medication | Rescue medication was permitted after completion of the 2 hour assessment if the migraine did not respond (participant was not pain free). | 2 hours post dose | 
| Percentage of Participants Who Used Rescue Medication | Rescue medication was permitted after completion of the 2 hour assessment if the migraine did not respond (participant was not pain free). | Anytime between 2-24 hours post dose | 
| Percentage of Participants Who Used Rescue Medication | Rescue medication was permitted after completion of the 2 hour assessment if the migraine did not respond (participant was not pain free). | Anytime 24-48 hours post dose | 
| Percentage of Participants Nausea Free | The percentage of participants without nausea. | 2 hours post dose | 
| Percentage of Participants Phonophobia Free | The percentage of participants without phonophobia. | 2 hours post dose | 
| Percentage of Participants Photophobia Free | The percentage of participants without photophobia. | 2 hours post dose | 
| Participants With Serious Adverse Events (SAE) | 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 | Baseline up to 11 weeks |