Non-invasive Vagus Nerve Stimulation for the Prevention of Migraines

A Randomized, Multicenter, Double-blind, Parallel, Sham-controlled Study of Non-invasive Vagus Nerve Stimulation for the Prevention of Migraines. (Premium II)

The purpose of the study is to investigate if the use of gammaCore Sapphire™ device reduces the number of migraines preventatively.

The study is a prospective randomized, multi-center, double-blind, parallel, sham-controlled study, designed for comparison of two parallel groups, gammaCore®-Sapphire (active treatment) and a sham (inactive) treatment.

The study period will begin with a four-week run-in period, during which there is no investigational treatment. The purpose of the run-in period will be to establish a baseline of the subject's headache/migraine history for longitudinal comparison.

The run-in period will be followed by a 12-week randomized period when the subjects will be randomized (1:1) to either active treatment or sham (inactive) treatment.

Subjects will dose themselves 3 times per day for 12 weeks.

Key Inclusion Criteria:

• Between the ages of 18 and 75 years
• Been previously diagnosed with migraine (with or without aura), in accordance with the ICHD-3 criteria
• Experiences between 8 to 20 headaches days per month (during the last 3 months), with at least 5 of them being migraine days
• Onset of migraine at age 50 years or younger
• Agrees to refrain from initiating or changing any prophylactic medications for indications other than migraine

Key Exclusion Criteria:

• Concomitant medical condition that will require oral or injectable steroids during the study
• Currently on a stable regime of more than 1 migraine preventative therapy
• Other significant pain problem (e.g., cancer pain, fibromyalgia, other head or facial pain disorder)
• Known or suspected severe cardiac disease (e.g., symptomatic coronary artery disease, prior myocardial infarction, congestive heart failure)
• Known or suspected cerebrovascular disease
• Previous cervical vagotomy
• Currently implanted with an electrical and/or neurostimulator device
• Been implanted with metal cervical spine hardware or has a metallic implant near the nVNS stimulation site
• Known history or suspicion of secondary headache
• Currently using marijuana (including medical marijuana) or has used marijuana (including medical marijuana) or cannabidiol oil within the last 6 months
• 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 more than 2 days per month for headaches or body pain
• Failed an adequate trial (2 months or greater) of at least 3 classes of a drug therapy for migraine prevention
• Surgery for migraine prevention
• Undergone nerve block (occipital or other) in the head or neck within the last 3 months
• Received Botox or CGRP mAb injections within the last 6 months
• Pregnant or thinking of becoming pregnant during the study period, or of childbearing years and unwilling to use an accepted form of birth control
• Previously used gammaCore