Fremanezumab, Migraine and Sleep

Inclusion Criteria:

• Between the ages of 18 and 65 years

• Been previously diagnosed with migraine (with or without aura), in accordance withthe ICHD-3 criteria

• Experiences between 10 to 25 headaches days per month (during the last 3 months),with at least 8 of them being migraine days during which the migraines lasted morethan 4 hours if untreated

• Onset of migraine at age 50 years or younger

• Agrees to refrain from initiating or changing the type, dosage, or frequency of anyprophylactic medications for indications other than migraine that may interfere withthe study objectives (e.g., antidepressants, anticonvulsants, beta-adrenergicblockers, etc.)

• Able to provide written informed consent

• Scoring 10 or higher on the Insomnia Severity Index (8-14 = subthreshold insomnia, 15-21 = clinical insomnia of moderate severity, 22-28 = clinical insomnia of severeseverity)

Exclusion Criteria:

• Currently on a regimen of 1 or more migraine preventative therapy

• Other significant pain problem (e.g., cancer pain, fibromyalgia, other head orfacial pain disorder) that may confound the study assessments

• Known or suspected severe cardiac disease (e.g., symptomatic coronary arterydisease, prior myocardial infarction, congestive heart failure)

• Known or suspected cerebrovascular disease (e.g., prior stroke or transient ischemicattack, symptomatic carotid artery disease, prior carotid endarterectomy or othervascular neck surgery)

• Abnormal baseline electrocardiogram (ECG) within the last year (e.g., second orthird-degree heart block, prolonged QT interval, atrial fibrillation, atrialflutter, history of ventricular tachycardia or ventricular fibrillation, clinicallysignificant premature ventricular contraction)

• Uncontrolled high blood pressure (systolic >160 mm HG, diastolic >100 mm Hg) after 3measurements within 24 hours

• Known history or suspicion of secondary headache

• Known history or suspicion of substance abuse or addiction (within the last 5 years)

• Currently using marijuana (including medical marijuana) or has used marijuana (including medical marijuana) or cannabidiol oil within the last 1 year

• Currently takes simple analgesics or NSAIDs >15 days per month or triptans, ergots,or combined analgesics >10 days per month for headaches or other body pain

• Currently takes prescription opioids for headaches or body pain

• Undergone nerve block (occipital or other) in the head or neck within the last 3months

• Received botulinum toxin or anti-CGRP-mAb injections within the last 6 months

• Nursing, pregnant or thinking of becoming pregnant during the study period, or ofchildbearing years and unwilling to use an accepted form of birth control

• Participating in any other therapeutic clinical investigation or has participated ina clinical trial in the preceding 30 days

• Belongs to a vulnerable population or has any condition such that his or her abilityto provide informed consent, comply with the follow-up requirements, or provideself-assessments is compromised.

• A relative of or an employee of the Investigator or the clinical study site

• Psychiatric or cognitive disorder and/or behavioral problems that, in the opinion ofthe clinician, may interfere with the study

• History of claustrophobia

• Diagnosis of obstructive sleep apnea or restless legs syndrome

• BMI of 30 or greater

• Daily use of sleep-promoting drugs. These include eszopiclone; zaleplon; zolpidem;benzodiazepines (estazolam, flurazepam, quazepam, temazepam, triazolam);barbiturates (amobarbital, amobarbital-secobarbital, chloral hydrate); doxepin;quetiapine; ramelteon; trazodone; suvorexant; lemborexant; OTC nighttime meds (doxyalamine; diphenydrame); and melatonin.