A Study of LY2951742 (Galcanezumab) in Japanese Participants With Episodic Migraine

Study Overview
=================
Brief Summary
-----------------
The main purpose of this study is to determine the efficacy of the study drug Galcanezumab in Japanese participants with episodic migraine.

Official Title
-----------------
A Randomized, Double-Blind, Placebo-Controlled Study of LY2951742 (Galcanezumab) in Japanese Patients With Episodic Migraine

Conditions
-----------------
Migraine

Intervention / Treatment
-----------------
* Drug: Galcanezumab
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Have a diagnosis of migraine as defined by International Headache Society (IHS) International Classification of Headache Disorders (ICHD)-3 beta guidelines (1.1 or 1.2) (ICHD-3 2013), with a history of migraine headaches of at least 1 year prior to screening, and migraine onset prior to age 50. Exclusion Criteria: Are currently enrolled in or have participated within the last 30 days or within 5 half-lives (whichever is longer) in a clinical trial involving an investigational product. Current use or prior exposure to Galcanezumab or other antibodies to CGRP or its receptor. Known hypersensitivity to multiple drugs, monoclonal antibodies or other therapeutic proteins, or to Galcanezumab and the excipients in the investigational product. History of persistent daily headache, cluster headache or migraine subtypes including hemiplegic (sporadic or familial) migraine, ophthalmoplegic migraine, and migraine with brainstem aura (basilar-type migraine) defined by IHS ICHD-3 beta.

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 120 milligrams (mg) Galcanezumab<br>120 mg galcanezumab (LY2951742) administered subcutaneously (SC) once a month for 6 months. | Drug: Galcanezumab<br>* Administered SC<br>* Other names: LY2951742;|
| Experimental: 240 mg Galcanezumab<br>120 mg galcanezumab (LY2951742) administered SC once a month for 6 months. | Drug: Galcanezumab<br>* Administered SC<br>* Other names: LY2951742;|
| Placebo Comparator: Placebo<br>Placebo administered SC once a month for 6 months. | Drug: Placebo<br>* Administered SC<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Mean Change From Baseline in the Number of Monthly Migraine Headache Days (MHD) | Migraine Headache Day (MHD):A calendar day on which a migraine headache or probable migraine headache occurred. Migraine Headache : A headache, with or without aura, of ≥30 minutes duration with both of the following required features (A and B): A) At least 2 of the following headache characteristics: Unilateral location; Pulsatile quality; Moderate or severe pain intensity; Aggravation by or causing avoidance of routine physical activity; AND B) During headache at least one of the following: Nausea and/or vomiting; Photophobia and phonophobia; The overall mean is derived from the average of months 1 to 6 from mixed model repeat measures (MMRM) model. Least Square Mean (LSMEAN) was calculated using MMRM models with fixed categorical effects of treatment, month, and treatment-by-month interaction, as well as the continuous, fixed covariates of baseline value and baseline-by-month interaction. | Baseline, Month 1 through Month 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With a 50% or Greater Reduction From Baseline in Monthly Migraine Headache Days | Migraine Headache Day (MHD): A calendar day on which a migraine headache or probable migraine headache occurred. A 50% responder in a particular month is any participant who has a ≥50% reduction from baseline in the monthly number of migraine headache attacks in a 30-day interval. It is derived from the average of months 1 to 6 from generalized linear mixed model repeated measures. Mean percentages of participants were calculated with a generalized linear mixed model repeated measures method with treatment, month and treatment by month, and baseline MHD category as fixed factors. | Baseline, Month 1 through Month 6 | 
| Percentage of Participants With a 75% or Greater Reduction From Baseline in Monthly Migraine Headache Days | Migraine Headache Day (MHD): A calendar day on which a migraine headache or probable migraine headache occurred. A 75% responder in a particular month is any participant who has a ≥75% reduction from baseline in the monthly number of migraine headache attacks in a 30-day interval. It is derived from the average of months 1 to 6 from generalized linear mixed model repeated measures. Mean percentages of participants were calculated with a generalized linear mixed model repeated measures method with treatment, month and treatment by month, and baseline MHD category as fixed factors. | Baseline, Month 1 through Month 6 | 
| Percentage of Participants With a 100% Reduction From Baseline in Monthly Migraine Headache Days | Migraine Headache Day (MHD): A calendar day on which a migraine headache or probable migraine headache occurred. A 100% responder in a particular month is any participant who has a 100% reduction from baseline in the monthly number of migraine headache attacks in a 30-day interval. It is derived from the average of months 1 to 6 from generalized linear mixed model repeated measures. Mean percentages of participants were calculated with a generalized linear mixed model repeated measures method with treatment, month and treatment by month, and baseline MHD category as fixed factors. | Baseline, Month 1 through Month 6 | 
| Overall Mean Change From Baseline on the Migraine-Specific Quality (MSQ) of Life Questionnaire | MSQ version 2.1 is a health status instrument consists of 14 items addressing 3 domains:(1)Role Function-Restrictive (items 1-7);(2)Role Function- Preventive (items 8-11);&(3)Emotional Function (items 12-14).Response options range from none of the time (value 1) to all of the time (value 6), & are reverse-recoded (value 6 to 1) before the domain scores are calculated. Total raw scores for each domain is the sum of the final item value for all of the items in that domain. After total raw score is computed for each domain & total score, they are transformed to a 0-100 scale with higher scores indicating a better health status & a positive change in scores reflecting functional improvement. The overall mean is derived from the average of months 4 to 6 from MMRM model. LSMean was calculated using MMRM model with treatment, month, treatment by month, baseline by month and baseline MHD category as fixed factors. | Baseline, Month 4 through Month 6 | 
| Overall Mean Change From Baseline in Number of Migraine Headache Days With Acute Medication Use | Migraine Headache Day (MHD) with Acute Medication Use: Calendar days on which migraine or probable migraine occurs, requiring acute medication. The overall mean is derived from the average of months 1 to 6 from MMRM model. LSMean was calculated using MMRM model with treatment, month, treatment by month, baseline, baseline by month, and baseline MHD category as fixed effects. | Baseline, Month 1 through Month 6 | 
| Mean Change From Baseline in the Patient Global Impression of Severity (PGI-S) Score | The PGI-S scale is a patient-rated instrument that measures patients own global impression of their illness severity. The patient was instructed as follows: Considering migraine as a chronic condition, how would you rate your level of illness? Response options were from 1 (normal, not at all ill) to 7 (extremely ill). Mean is derived from the average of months 4 to 6 from MMRM model. Least square mean (LSM) was calculated using an MMRM model with treatment, month, treatment by month, baseline, baseline by month, and baseline MHD category as fixed effects. | Baseline, Month 4 through Month 6 | 
| Overall Mean Change From Baseline in Headache Hours | Headache Hours is calculated as the total number of headache hours on which a headache occurred. Overall mean is derived from the average of months 1 to 6 from MMRM model. LSMean was calculated using the MMRM model with treatment, month, treatment by month, baseline, baseline by month and baseline MHD category. | Baseline, Month 1 through Month 6 | 
| Mean Change From Baseline on the Migraine Disability Assessment Test (MIDAS) Total Score | The MIDAS is a participant-rated scale which was designed to quantify headache-related disability over a 3-month period. This instrument consists of five items that reflect the number of days reported as missing or with reduced productivity at work or home, and the number of days of missed social events. Each item has a numeric response range from 0 to 90 days, if days are missed from work or home they are not counted as days with reduced productivity at work or home. The numeric responses are summed to produce a total score ranging from 0 to 270, in which a higher value is indicative of more disability. LSMean was calculated using MMRM model with treatment, month, treatment by month, baseline, baseline by month, and baseline MHD category as fixed factors. | Baseline, Month 6 | 
| Percentage of Participants With Positive Responses on Patient Satisfaction With Medication Questionnaire-Modified (PSMQ-M) | The PSMQ-M is a self-rated scale which measures participants level of satisfaction with study medication.The scale has been modified for use in this study, assessing 3 items related to the clinical trial treatment over the past 4 weeks: satisfaction, preference, and side effects. Satisfaction responses range from very unsatisfied to very satisfied with the current treatment. Preference compares the current study medication to previous medications, with responses from much rather prefer my previous medication to much rather prefer the medication administered to me during the study | Month 6 | 
| Number of Participants With Suicidal Ideations Collected by Columbia - Suicide Severity Rating Scale (C-SSRS) | C-SSRS captures the occurrence, severity, and frequency of suicide-related thoughts during the assessment period. The scale includes suggested questions to solicit the type of information needed to determine if a suicide-related thoughts occurred. Some questions are binary responses (yes/no) and some are on a scale of 1 (low severity) to 5 (high severity). Suicidal ideation (SI): a yes answer to any of 5 suicidal ideation questions: wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with any methods without intent to act, active suicidal ideation with some intent to act without specific plan, active suicidal ideation with specific plan and intent | Month 1 through Month 6 | 
| Number of Participants With Suicidal Behaviors Assessed by Columbia - Suicide Severity Rating Scale (C-SSRS) | C -SSRS captures occurrence, severity, and frequency of suicide-related thoughts and behaviors. Suicidal behavior is defined as a yes answer to any of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Suicidal ideation is defined as a yes answer to any one of 5 suicidal ideation questions: wish to be dead, and 4 different categories of active suicidal ideation. | Month 1 through Month 6 | 
| Percentage of Participants Developing Anti-Drug Antibodies (ADA) to Galcanezumab | Treatment emergent ADA will be defined as any of the following: A negative baseline result and a positive post-baseline ADA result with a titer ≥20. This is also called treatment-induced ADA. A positive baseline result and a positive post-baseline ADA result with a ≥4-fold increase in titers (for example, baseline titer of 10 increasing to ≥40 post-baseline). This is called treatment-boosted ADA. | Baseline through Month 6 | 
| Pharmacokinetics (PK): Serum Concentration of Galcanezumab | Pharmacokinetics (PK): Serum Concentration of Galcanezumab | Month 6 | 
| Total Plasma Concentration of Calcitonin Gene-Related Peptide (CGRP) | Total Plasma Concentration of Calcitonin Gene-Related Peptide (CGRP) | Month 6 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
prevention, prophylaxis, headache