A Study of the Safety and Efficacy of MK-6096 for Migraine Prophylaxis in Participants With Episodic Migraine (MK-6096-020)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and efficacy of MK-6096 versus placebo for preventing migraines in participants with episodic migraine. After a 28-day Screening period during which baseline number of monthly migraine days was assessed, participants were randomized to receive MK-6096 or placebo for a 12-week Treatment Period. Participants who completed all 12 weeks of the Treatment Period received drug or placebo for an additional 2 weeks in the Run-out Period. Treatment assignment in the Run-out Period was determined at the initial randomization. In the Run-out Period, participants who received placebo in the Treatment Period continued to receive placebo and participants who received MK-6096 in the Treatment Period 2 received either MK-6096 or placebo in a 1:1 ratio. The hypothesis tested in the study is that MK-6096 10 mg is superior to placebo in reducing migraine frequency as measured by the mean change from baseline in monthly migraine days averaged over the 12- week treatment period.

Official Title
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A Phase IIa, Multicenter, Randomized, Placebo-Controlled Clinical Trial to Evaluate the Safety and Efficacy of MK-6096 for Migraine Prophylaxis in Patients With Episodic Migraine

Conditions
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Migraine, Headache

Intervention / Treatment
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* Drug: MK-6096
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: History of migraine with or without aura for >1 year and with ≥4 and ≤14 migraine days per month in the 3 months prior to study Male, female not of reproductive potential, or female of reproductive potential who is not pregnant by pregnancy test and agrees to use acceptable contraception Exclusion Criteria: Pregnancy, breast-feeding, or expecting to become pregnant Planning to donate egg or sperm during the study or within 90 days after last dose of study medication Basilar or hemiplegic migraine headache >50 years old at the age of migraine onset ≥15 headache-days per month or medication taken for acute migraine or other headaches on more than 10 days per month in any of the three months prior to study Migraine prophylactic medication (defined as medication taken daily to prevent migraines) taken in the 30 days prior to study History of narcolepsy, cataplexy, circadian rhythm disorder, parasomnia, sleep related breathing disorder, restless legs syndrome, periodic limb movement disorder, excessive daytime sleepiness or difficulty sleeping due to a medical condition (e.g., asthma, gastroesophageal reflux disease, etc.) Clinical, laboratory, or electrocardiogram (ECG) evidence of uncontrolled hypertension, uncontrolled diabetes, human immunodeficiency virus (HIV) disease, or significant pulmonary, renal, hepatic, endocrine, or other systemic disease Myocardial infarction, unstable angina, coronary artery bypass surgery, or other revascularization procedure, stroke, or transient ischemic attack within 3 months of study Other confounding pain syndromes (i.e., condition requiring daily use of opioids), psychiatric conditions such as uncontrolled major depression, dementia or significant neurological disorders other than migraine Imminent risk of self-harm, based on clinical interview and responses on the Columbia Suicidality Severity Rating Scale (C-SSRS), or of harm to others. Exclude any prospective participant reporting suicidal ideation with intent, with or without a plan in the past 2 months or suicidal behavior in the past 6 months History of malignancy ≤5 years prior to study, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer History of hypersensitivity to more than two chemical classes of drugs, including prescription and over-the-counter medications Recent history (within the past 1 year) or current evidence of drug or alcohol abuse or recreational use of illicit drugs or prescription medications Donated blood products or has had phlebotomy of >300 ml within 8 weeks of study, or intends to donate blood products or receive blood products within 30 days before study and throughout study Consumption of 3 or more alcoholic drinks per day Body Mass Index >40 kg/m^2 History of transmeridian travel (across >3 time zones) or shift work (defined as permanent night shift or rotating day/night shift work) within the past 2 weeks or anticipates needing to travel (across >3 time zones) at any time during the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MK-6096<br>Participants were randomized to receive double-blind MK-6096, two 5 mg tablets (10 mg dose), orally, once daily for 12 weeks in the Treatment Period. Those who completed the Treatment Period were randomized 1:1 to receive double-blind MK-6096 or placebo once daily in the 2-week Run-out Period. | Drug: MK-6096<br>* MK-6096, two 5 mg tablets (total 10 mg dose), orally, once daily<br>Drug: Placebo<br>* Placebo, 2 tablets, orally, once daily<br>|
| Placebo Comparator: Placebo<br>Participants were randomized to receive double-blind placebo, two tablets, orally, once daily for 12 weeks in the Treatment Period. Those who completed the Treatment Period continued to receive double-blind placebo once daily in the 2-week Run-out Period. | Drug: Placebo<br>* Placebo, 2 tablets, orally, once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in Monthly Migraine Days | Participants recorded data in the electronic migraine headache diary in the evening approximately one hour before bed and prior to taking study medication during Screening and the Treatment Period. A migraine was defined as a headache with at least one associated symptom of aura, photophobia, phonophobia, nausea, or vomiting. Change in the mean monthly migraine days during Screening (Baseline) versus during the 12-week Treatment Period was assessed. A negative number indicates a reduction in mean monthly migraine days. | Baseline and average over Treatment Period (Weeks 0-12) | 
| Percentage of Participants With One or More Adverse Events | An adverse event was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the sponsor's product, whether or not considered related to the use of the product. Any worsening of a preexisting condition which is temporally associated with the use of the sponsor's product, is also an adverse event. Statistical analysis compared the Treatment Period arms only. | Treatment Period: Weeks 0-12; Run-out Period: Weeks 13-14 | 
| Percentage of Participants Discontinued From Study Medication Due to an Adverse Event | An adverse event was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the sponsor's product, whether or not considered related to the use of the product. Any worsening of a preexisting condition which is temporally associated with the use of the sponsor's product, is also an adverse event. Statistical analysis compared the Treatment Period arms only. | Treatment Period: Weeks 0-12; Run-out Period: Weeks 13-14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in Monthly Headache Days | Participants recorded data in the electronic migraine headache diary in the evening approximately one hour before bed and prior to taking study medication during Screening and the Treatment Period. A headache was defined as headache pain of at least 30 minutes duration or for any duration for which headache treatment was administered. Change in the mean monthly headache days during Screening (Baseline) versus during the 12-week Treatment Period was assessed. A negative number indicates a reduction in mean monthly headache days. | Baseline and average over Treatment Period (Weeks 0-12) | 
| Percentage of Participants With at Least a 50% Reduction From Baseline in Monthly Migraine Days | Participants recorded data in the electronic migraine headache diary in the evening approximately one hour before bed and prior to taking study medication during Screening and the Treatment Period. A migraine was defined as a headache with at least one associated symptom of aura, photophobia, phonophobia, nausea, or vomiting. Percentage of participants with at least 50% reduction in the monthly migraine days during the 12-week Treatment Period versus during Screening (Baseline) was analyzed using a generalized linear mixed effects model. | Baseline and average over Treatment Period (Weeks 0-12) | 
| Percentage of Participants With at Least a 30% Reduction From Baseline in Monthly Migraine Days | Participants recorded data in the electronic migraine headache diary in the evening approximately one hour before bed and prior to taking study medication during Screening and the Treatment Period. A migraine was defined as a headache with at least one associated symptom of aura, photophobia, phonophobia, nausea, or vomiting. Percentage of participants with at least 30% reduction in the monthly migraine days during Screening (Baseline) versus during the 12-week Treatment Period was analyzed using a generalized linear mixed effects model. | Baseline and average over Treatment Period (Weeks 0-12) |