A Study of LY2951742 in Participants With Migraine

Study Overview
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Brief Summary
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To assess the efficacy and safety of LY2951742 in the prevention of migraine headache in migraineurs with or without aura during 3 months of treatment.

Detailed Description
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The study is comprised of 4 trial periods: Screening and washout (5-45 days) Baseline for assessment of the type, frequency, and severity of headaches (28-38 days) Treatment (12 weeks) Follow-up (12 weeks)

Official Title
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A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study of LY2951742 in Patients With Migraine

Conditions
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Migraine Headache

Intervention / Treatment
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* Drug: LY2951742
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have a history of migraine as defined by the International Headache Society (IHS) International Classification of Headache Disorders II guidelines 1.1 and 1.2 (ICHD-II, Cephalgia 2004) of at least 1 year prior to enrollment, migraine onset prior to age 50, and a moderate frequency of migraine headaches Women of child-bearing potential (not surgically sterile or at least 1 year post-menopause) must test negative for pregnancy at the time of screening based on a serum pregnancy test and must agree to use a reliable method of birth control during the study and for 3 months following completion of participation in the study Have clinical laboratory test results within normal reference ranges or, if outside the normal range, judged not clinically significant by the Investigator Must not be on any migraine prevention therapy, including botulinum toxin (Botox) Agree not to post any personal medical data related to the study or information related to the study on any website or social media site (for example, Facebook, Twitter, et cetera) until the trial has completed Exclusion Criteria: Current enrollment in, or discontinuation within the last 30 days from, a clinical trial involving any investigational drug or device, or concurrent enrollment in any other type of medical research judged not to be scientifically or medically compatible with this study Previous completion or withdrawal from this study or any other study investigating LY2951742 or other therapeutic antibodies that target calcitonin gene-related peptide (CGRP) History of chronic migraine or migraine subtypes including hemiplegic (sporadic or familial) migraine, ophthalmoplegic migraine, and basilar-type migraine History of headache (for example, cluster headache or Medication Overuse Headache [MOH]) other than migraine or tension type headache as defined by IHS ICHD-II within 12 months prior to randomization Evidence of significant active psychiatric disease including, but not limited to, manic depressive illness, schizophrenia, generalized anxiety disorder, obsessive compulsive disorder, personality disorders, or other serious mood, anxiety, depression, or substance use disorders Have a history or presence of any other medical illness that in the judgment of the Investigator, indicates a medical problem that would preclude study participation Women who are pregnant or nursing Confirmed corrected QT (QTc) interval >470 milliseconds (msec) for women and >450 for men Excessive alcohol, opiate, or barbiturate use; history of drug abuse or dependence In the opinion of the Investigator, have no other issues that would interfere with compliance with the study requirements and completion of evaluations required for this study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LY2951742<br>LY2951742: 150 milligrams (mg), subcutaneous (SC) injection on Day 1 and then once every other week for a total of 6 doses during the 12-week Treatment Period. | Drug: LY2951742<br> <br> |
| Placebo Comparator: Placebo<br>Placebo: 0.9% Sodium Chloride, Untied States Pharmacopoeia (USP), subcutaneous (SC) injection on Day 1 and then once every other week for a total of 6 doses during the 12-week Treatment Period. | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in the Number of Migraine Headache Days in the Last 28-day Period of the 12-week Treatment Phase | The criteria for a migraine headache was adapted from the standard International Headache Society (IHS) International Classification of Headache Disorders II guidelines 1.1 and 1.2 (ICHD-II, Cephalgia 2004). The definition of a migraine headache was a headache with or without aura, of ≥30 minutes (min) duration, and with both (A and B) required features from the IHS ICHD-II definition. Required feature A includes at least 2 of the following headache characteristics: unilateral location, pulsatile quality, moderate or severe pain intensity, or aggravation by or causing avoidance of routine physical activity. Required feature B includes at least 1 of the following during the headache: nausea and/or vomiting, or photophobia and phonophobia. Least square (LS) means were calculated using mixed model repeated measures (MMRM) with baseline value, treatment, month, and treatment-by-month interaction as fixed effects and participant as random effect. | Baseline, 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in the Number of Headache Days in the Last 28-day Period of the 12-week Treatment Phase | Number of calendar days on which a headache lasts ≥4 hours which includes migraines, probable migraines (PM) and nonmigraines. Criteria for migraine headache (MH) was adapted from standard IHS ICHD-II guidelines 1.1 and 1.2 (Cephalgia 2004). Definition of MH was headache with or without aura, of ≥30 min duration, and with both (A and B) required features from IHS ICHD-II definition. Required feature A includes ≥2 of following headache characteristics: unilateral location, pulsatile quality, moderate or severe pain intensity, or aggravation by or causing avoidance of routine physical activity. Required feature B includes at least 1 of following during headache: nausea and/or vomiting, or photophobia and phonophobia. PM is headache with or without aura, but missing 1 feature needed to fulfill all criteria for MH. LS means were calculated using MMRM with baseline value, gender, treatment, month, and treatment-by-month interaction as fixed effects and participant as random effect. | Baseline, 12 weeks | 
| Mean Change From Baseline in the Number of Migraine Attacks in the Last 28-day Period of the 12-week Treatment Phase | A migraine attack was defined as beginning on any day a migraine headache day was recorded and ending when a migraine headache-free day occurred. The criteria for a migraine headache was adapted from the standard IHS ICHD-II guidelines 1.1 and 1.2 (Cephalgia 2004). The definition of a migraine headache was a headache with or without aura, of ≥30 minutes duration, and with both (A and B) required features from the IHS ICHD-II definition. Required feature A includes at least 2 of the following headache characteristics: unilateral location, pulsatile quality, moderate or severe pain intensity, or aggravation by or causing avoidance of routine physical activity. Required feature B includes at least 1 of the following during the headache: nausea and/or vomiting, or photophobia and phonophobia. LS means were calculated using MMRM with baseline value, gender, treatment, month, and treatment-by-month interaction as fixed effects and participant as random effect. | Baseline, 12 weeks | 
| Percentage of Responders | Percentage of participants with greater than 50% reduction in the number of migraine headache days in a 28-day period. The criteria for a migraine headache was adapted from the standard International Headache Society (IHS) International Classification of Headache Disorders II guidelines 1.1 and 1.2 (ICHD-II, Cephalgia 2004). The definition of a migraine headache was a headache with or without aura, of ≥30 minutes duration, and with both (A and B) required features from the IHS ICHD-II definition. Required feature A includes at least 2 of the following headache characteristics: unilateral location, pulsatile quality, moderate or severe pain intensity, or aggravation by or causing avoidance of routine physical activity. Required feature B includes at least 1 of the following during the headache: nausea and/or vomiting, or photophobia and phonophobia. | Baseline, 4, 8, and 12 weeks |