Prospective, single-site, open-label, non-controlled pilot study consisting of two parallel trials. Participants will receive rimegepant or zavegepant for acute migraine treatment during a single Emergency Department visit, with post-discharge follow-up through 28 days. Participants will be allocated to either the rimegepant trial or the zavegepant trial. The study design does not include a placebo or active comparator control group, and the two gepant study drugs are not designed to function as active comparator groups. The objective in this investigation is to examine relief from either rimegepant or zavegepant in separate parallel trials.

Inclusion Criteria:

• • At least 18 years of age

  • Capacity to provide informed consent (without a Representative)
  • Emergency Department presentation for a headache consistent with migraine, based either on the treating clinical team's judgement, or fulfillment of International Classification of Headache Disorders (ICHD-3) criteria for migraine without aura or with typical aura, or for probable migraine without aura or with typical aura. It is acceptable if current headache duration is >72 hours. Must have been headache free for >48 hours prior to current attack.
  • Willing to participate in post-discharge telephone assessments
  • English and/or Spanish speaking patients

Exclusion Criteria:

• • Use of intranasal decongestants within 1 hour prior to study drug administration, due to the potential to decrease absorption of intranasal zavegepant.

  • Use of analgesics or abortive headache medications within 60 minutes of study medication administration

  • Use of the following drug/food categories with potential for drug interactions within 7 days or 5 half-lives, whichever is longer: 1) CYP3A strong or moderate inducers, 2) CYP3A4 strong inhibitors, 3) P-glycoprotein (P-gp) inhibitors, 4) OATP1B3 transporter potent inhibitors/inducers, 5) NTCP transporter potent inhibitors/inducers

  • History of ischemic cardiovascular disease, diabetes, or hypertension (diagnosed or likely based on multiple readings), that was recently diagnosed within 3 months of screening or is currently uncontrolled or unstable

  • History of any stroke within 3 months, or any lifetime stroke and age ≥65 years

  • History of significant peripheral vascular disease, as assessed by the investigator or qualified delegate

  • History of Raynaud's Phenomenon (medically diagnosed, or non-medically diagnosed with affirmative responses to both unusual sensitivity and finger color change with cold exposure)

  • History of severe hepatic impairment, as assessed by the investigator or qualified delegate

  • History of kidney disease stage 4 (eGFR <30 mL/min/1.73 m2)

  • History of hypersensitivity reaction to rimegepant, zavegepant, or to any included inactive ingredients

  • Lifetime use of CGRP-targeting acute or preventive migraine medications

  • In custody of law enforcement

  • Current pregnancy or lactation

    • All individuals of childbearing potential must have a negative pregnancy test at screening (urine or serum).
    • A person is considered to be of childbearing potential if possessing female reproductive organs at birth, post-menarchal, has not reached a post-menopausal state (≥12 continuous months of amenorrhea with no cause identified other than menopause), and is not permanently infertile due to surgery (i.e., removal of ovaries, fallopian tubes, and uterus) or another cause as determined by the investigator (e.g., Müllerian agenesis).