Zavegepant for Migraine

Recruiting at 1 trial location

Overseen By Todd J Schwedt, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Mayo Clinic

Must be taking: CGRP-targeting preventives

Disqualifiers: Other primary headaches, Zavegepant allergy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

200 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how well a nasal spray called zavegepant works for individuals who experience migraines, even if they are already using preventive migraine medications targeting CGRP (a protein involved in migraine attacks). The researchers aim to determine if this treatment can effectively stop migraines once they start and assess its tolerability. Candidates may be suitable if they experience 2 to 8 migraine attacks per month and are on a stable dose of a CGRP-targeting preventive migraine medication like atogepant or erenumab. As a Phase 4 trial, this research seeks to understand how the already FDA-approved and effective treatment benefits a broader patient population.

Will I have to stop taking my current medications?

The trial does not require you to stop taking your current medications. In fact, you need to be on a stable dose of a CGRP-targeting preventive migraine medication for at least two months before starting the trial.

What is the safety track record for this treatment?

Research has shown that zavegepant is a safe and well-tolerated treatment for migraines. One study found that using zavegepant as a nasal spray effectively treats migraines and is generally safe, without causing serious side effects like medication overuse headaches or heart issues.

Another review highlighted that zavegepant is safer compared to some other migraine treatments. However, its safety when used more than eight times a month remains unknown. Overall, zavegepant is considered a safe choice for those needing quick relief from migraines. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Zavegepant is unique because it's a CGRP receptor antagonist, which targets and blocks the calcitonin gene-related peptide pathway involved in migraine attacks. Unlike traditional treatments like triptans, which constrict blood vessels, Zavegepant offers a novel approach by directly interfering with the migraine process itself without the vascular effects. Additionally, Zavegepant is administered intranasally, potentially offering faster relief compared to oral medications, which has researchers hopeful for a quicker onset of action in treating migraines.

What is the effectiveness track record for Zavegepant in treating migraines?

Research has shown that Zavegepant, which participants in this trial will receive, effectively treats migraines. A review of studies found that Zavegepant nasal spray significantly alleviates pain and other symptoms during migraine attacks. Other research indicates that a 10 mg dose of Zavegepant provides quick relief and is as safe as taking pills. Additionally, trials demonstrated that Zavegepant was both effective and well tolerated compared to a placebo. This evidence supports its use for quickly relieving migraine symptoms. ^{4 6 7 8 9}

Who Is on the Research Team?

Todd Schwedt, MD

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

This trial is for adults who experience 2-8 migraine attacks monthly and have been on stable CGRP-targeting preventive medications for at least two months. They must meet the criteria for migraines with or without aura and can be using additional stable migraine preventives.

Inclusion Criteria

I experience 2-8 migraine attacks each month.

I suffer from migraines, whether occasionally or frequently.

I have previously used zavegepant or other gepant medications.

Exclusion Criteria

History of hypersensitivity reaction to rimegepant or to any of the components of rimegepant

History of hypersensitivity reaction to zavegepant or to any of the components of zavegepant

I have a headache condition, but it's not migraine, except for tension-type headaches.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive zavegepant to treat up to 8 migraine attacks over 24 weeks

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Optional Extension

Participants receiving rimegepant for migraine prevention may continue for up to 32 consecutive weeks

32 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Zavegepant

Trial Overview The study tests Zavegepant's effectiveness in treating acute migraines among those already using other CGRP-targeting preventive treatments. It aims to understand how well Zavegepant works when taken during a migraine attack by people on these preventives.

How Is the Trial Designed?

Group I: Zavegepant Treatment Experimental Treatment 1 Intervention

Participants will receive zavegepant to treat up to 8 migraine attacks over 24 weeks.

Zavegepant is already approved in United States for the following indications:

Approved in United States as Zavzpret for:

• Acute treatment of migraine with or without aura in adults

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Published Research Related to This Trial

In phase 2/3 trials, intranasal zavegepant at doses of 10 mg and 20 mg significantly improved pain relief and freedom from bothersome migraine symptoms compared to placebo, with 22.5% and 23.1% of patients achieving pain freedom, respectively.

Zavegepant demonstrated a safety profile similar to placebo, with common side effects including dysgeusia and nasal discomfort, making it a potentially convenient alternative to traditional migraine treatments like triptans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Zavegepant Intranasal Spray for Migraines. Martirosov, AL., Giuliano, C., Shupp, M., et al.[2023]

Zavegepant (Zavzpret) is an effective nasal spray approved for treating acute migraines in adults, but it is not intended for preventive use.

Common side effects include taste disorders, nausea, nasal discomfort, and vomiting, and it should not be used with intranasal decongestants as they can reduce its effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Nasal Spray for Migraine Headaches. Aschenbrenner, DS.[2023]

Zavegepant, a new CGRP receptor antagonist developed by Pfizer, was approved in March 2023 as a nasal spray for the acute treatment of migraines in adults, marking a significant advancement in migraine therapy.

An oral formulation of zavegepant is also in development, indicating ongoing efforts to provide more treatment options for individuals suffering from chronic and episodic migraines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Zavegepant: First Approval. Dhillon, S.[2023]

In a Phase 2/3 trial involving 1673 participants, zavegepant nasal spray at doses of 10 mg and 20 mg was found to be effective in achieving pain freedom and alleviating the most bothersome migraine symptoms within 2 hours, outperforming placebo.

The safety profile of zavegepant was favorable, with most adverse events being mild to moderate, such as dysgeusia and nausea, and no indication of serious liver toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Zavegepant nasal spray for the acute treatment of migraine: A Phase 2/3 double-blind, randomized, placebo-controlled, dose-ranging trial. Croop, R., Madonia, J., Stock, DA., et al.[2023]

Zavegepant nasal spray is significantly more effective than placebo in achieving pain freedom and relief from the most bothersome symptoms of migraine within 2 hours, with odds ratios of 1.6 and 1.4 respectively.

The nasal spray also shows a higher likelihood of sustained pain freedom between 2 and 48 hours (OR = 1.74), although the difference in pain relapse rates was not statistically significant, indicating a need for further research on its long-term safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Zavegepant nasal spray for the acute treatment of migraine: A meta analysis. Waqas, M., Ansari, FUR., Nazir, A., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10615551/

Zavegepant nasal spray for the acute treatment of migraine This meta-analysis confirms the effectiveness of Zavegepant nasal spray in treating acute migraine, with significant improvements in pain and symptom relief.

2. jmcp.org jmcp.org/doi/10.18553/jmcp.2025.31.6.598

Clinical evaluation of zavegepant for the acute treatment ... Zavegepant 10 mg showed the smallest treatment effect compared with placebo of all included treatments. REAL-WORLD EFFECTIVENESS. Zavegepant ...

3. zavzpret.pfizerpro.com zavzpret.pfizerpro.com/about/efficacy

Efficacy Info & Study Results Efficacy and safety of zavegepant nasal spray for the acute treatment of migraine: results of phase 3 double-blind, randomized, placebo controlled trial.

4. thejournalofheadacheandpain.biomedcentral.com thejournalofheadacheandpain.biomedcentral.com/articles/10.1186/s10194-025-01984-7

The efficacy and safety of zavegepant nasal inhalation versus ... Zavegepant 10 mg can quickly relieve symptoms and has no significant difference in safety compared with oral drugs, which can provide rapid and safe efficacy.

5. neurology.org neurology.org/doi/10.1212/WNL.0000000000204345

Efficacy and Safety of Zavegepant for the Acute Treatment ... Zavegepant 10 mg was effective and well tolerated compared with placebo for the acute treatment of migraine in women.

6. zavzpret.com zavzpret.com/

ZAVZPRET™ (zavegepant) Migraine Medication | Safety Info ZAVZPRET is not used to prevent migraine attacks. It is not known if ZAVZPRET is safe and effective in children.

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2023/216386s000lbl.pdf

ZAVZPRET (zavegepant) nasal spray - accessdata.fda.gov The safety of treating more than 8 migraines in a 30-day period has not been established. 3 DOSAGE FORMS AND STRENGTHS. Nasal spray: 10 mg of zavegepant per ...

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36804093/

Safety, tolerability, and efficacy of zavegepant 10 mg nasal ... Interpretation: Zavegepant 10 mg nasal spray was efficacious in the acute treatment of migraine, with favourable tolerability and safety profiles.

9. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40391567/

Long-term safety and tolerability of zavegepant 10-mg ... No AEs related to medication-overuse headache, suicidality, or cardiovascular events occurred. No clinically meaningful trends in laboratory ...