Rimegepant for Cluster Headache

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Mayo Clinic

Must not be taking: Opioids, Barbiturates, Verapamil, others

Disqualifiers: Cardiovascular disease, Pregnancy, Psychiatric conditions, 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 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 1 week

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether rimegepant, a medication, can prevent cluster headaches. These severe headaches occur on one side of the head, often accompanied by eye or nasal symptoms. The trial aims to determine if the medicine can reduce the number and severity of these headaches. Individuals who frequently experience distinct cluster headache attacks, with symptoms like eye watering or nasal congestion, might be suitable candidates. Participants will track their headaches for a week before starting the treatment. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

If you're taking verapamil, you'll need to stop using it during the study. However, if you're on other headache prevention medications, you can continue them as long as your dose has been stable for at least 2 months before the study and won't change during the study.

Is there any evidence suggesting that rimegepant is likely to be safe for humans?

Research has shown that rimegepant is generally safe. In studies, people using rimegepant for migraines tolerated it well, even over long periods, up to a year. This suggests it is usually safe to use. However, some people might experience side effects like allergic reactions, which can include trouble breathing or a rash. These reactions might occur days after taking the drug. When considering joining a trial, it's important to weigh these possible side effects, although they appear to be quite rare. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for cluster headache?

Rimegepant is unique because it offers a new approach for treating cluster headaches by targeting the calcitonin gene-related peptide (CGRP) pathway. Most current treatments for cluster headaches rely on triptans or oxygen therapy, which have been the standard options. Rimegepant stands out with its oral administration and potential for rapid relief, making it a convenient option compared to injectable treatments. Researchers are excited about rimegepant's novel mechanism and its potential to provide effective relief with fewer side effects than existing therapies.

What evidence suggests that rimegepant might be an effective treatment for cluster headache?

Research has shown that rimegepant works well for treating migraines. In studies, participants taking rimegepant reported significantly more pain relief than those taking a placebo, which contains no active medicine. About half of the participants experienced no pain within two hours. These findings suggest that rimegepant can effectively reduce headache symptoms. This trial will focus on cluster headaches. While previous success in treating migraines suggests potential benefits, this study will specifically evaluate rimegepant's effectiveness for cluster headaches. ^{3 6 7 8 9}

Who Is on the Research Team?

Carrie Robertson, MD

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

This trial is for individuals with recurrent cluster headaches not caused by another disorder. Participants must have had MR imaging to rule out other causes, experience specific symptoms like severe unilateral pain and restlessness during attacks, and have a certain frequency of headaches. They can't join if they're near the end of a cluster cycle, have recent serious heart issues or are pregnant. Those on stable doses of certain headache medicines may be eligible.

Inclusion Criteria

This criterion requires that a headache is accompanied by at least one of the following:

You have been diagnosed with recurrent cluster headaches according to specific guidelines.

Subjects agree to refrain from starting a new prophylactic cluster headache medicine, including steroids and nerve blocks, during the course of the study.

Exclusion Criteria

You have been experiencing cluster headaches that are likely ending within the last 4 weeks.

You have had heart problems like a heart attack, heart surgery, or stroke in the past 6 months.

Pregnancy (negative serum pregnancy testing at enrollment and use of contraception considered to be effective).

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Baseline

Participants track their headaches for a one-week baseline headache diary

1 week

Treatment

Participants take rimegepant on an every other day schedule for a total of 4 doses over 8 days

1 week

1 visit (in-person) for final evaluation and collection of headache diaries

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Rimegepant

Trial Overview The study tests rimegepant's effectiveness as a preventive treatment for cluster headaches. It aims to see if taking rimegepant reduces the frequency or severity of headache episodes in participants who meet strict criteria based on their headache patterns and associated symptoms.

How Is the Trial Designed?

Group I: Cluster Headache Subjects Experimental Treatment 1 Intervention

Subjects with cluster headaches will track their headaches for a one-week baseline headache diary. After establishing the baseline headache frequency, severity, and abortive medicine use, subjects will be asked to start their first dose of rimegepant with their next moderate to severe cluster headache.

Rimegepant is already approved in United States, European Union, Canada, United Kingdom for the following indications:

Approved in United States as Nurtec ODT for:

• Acute treatment of migraine with or without aura in adults
• Preventative treatment of episodic migraine in adults

Approved in European Union as Vydura for:

• Prophylaxis and acute treatment of migraine in adults

Approved in Canada as Nurtec ODT for:

• Acute treatment of migraine with or without aura in adults
• Preventative treatment of episodic migraine in adults

Approved in United Kingdom as Vydura for:

• Prophylaxis and acute treatment of migraine 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

Rimegepant, an orally disintegrating tablet approved by the FDA, has been shown in three phase 3 trials to significantly improve pain relief and reduce bothersome migraine symptoms within 2 hours of administration.

This medication offers a new mechanism of action for treating migraines, making it a suitable option for patients who do not respond well to traditional treatments like triptans or who experience adverse effects from them.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rimegepant Orally Disintegrating Tablet for Acute Migraine Treatment: A Review. DeFalco, AP., Lazim, R., Cope, NE.[2021]

Rimegepant, an oral CGRP receptor antagonist, has shown significant efficacy in treating migraines, providing pain relief and symptom improvement for up to 48 hours after a single dose, based on completed phase II and III trials.

The medication was well tolerated with only mild to moderate adverse events reported, leading to its FDA approval for acute migraine treatment on February 27, 2020.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rimegepant for the treatment of migraine. Negro, A., Martelletti, P.[2021]

In a study involving 13 patients with migraines, rimegepant was found to be well tolerated when used as an acute treatment alongside CGRP monoclonal antibodies (mAbs) for preventive treatment, with no serious adverse events reported.

Out of the patients, 38% experienced mild to moderate adverse events, primarily nasopharyngitis, indicating that while some side effects occurred, they were generally not severe and did not lead to treatment discontinuation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Rimegepant, an Oral CGRP Receptor Antagonist, Plus CGRP Monoclonal Antibodies for Migraine. Berman, G., Croop, R., Kudrow, D., et al.[2021]

Rimegepant is an effective treatment for migraines, showing significant pain relief and reduction in bothersome symptoms compared to placebo in phase III trials, and it can also reduce the number of monthly migraine days when used preventively.

The medication is generally well tolerated, with no signs of liver or heart-related side effects, making it a safe option for adults managing migraines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rimegepant: A Review in the Acute Treatment and Preventive Treatment of Migraine. Blair, HA.[2023]

Rimegepant, taken every other day, significantly reduced the mean number of migraine days per month compared to placebo, with a difference of -0.8 days, indicating its efficacy as a preventive treatment for migraines.

The safety profile of rimegepant was comparable to that of placebo, with similar rates of adverse events and no serious safety concerns reported during the study involving 747 participants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral rimegepant for preventive treatment of migraine: a phase 2/3, randomised, double-blind, placebo-controlled trial. Croop, R., Lipton, RB., Kudrow, D., et al.[2021]

Rimegepant (NURTEC ODT®) is an orally disintegrating tablet that acts as a highly-selective antagonist of calcitonin gene-related peptide, specifically designed for the acute treatment of migraines.

In February 2020, rimegepant ODT received its first global approval in the USA for treating migraines with or without aura in adults, marking a significant milestone in its development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rimegepant: First Approval. Scott, LJ.[2022]

In a phase 3 trial involving 1466 participants, the orally disintegrating tablet formulation of rimegepant (75 mg) was significantly more effective than placebo in providing freedom from pain (21% vs 11%) and freedom from the most bothersome symptom (35% vs 27%) at 2 hours post-dose.

The safety profile of rimegepant was comparable to placebo, with no serious adverse events reported, and the most common side effects were mild, such as nausea and urinary tract infections, indicating good tolerability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy, safety, and tolerability of rimegepant orally disintegrating tablet for the acute treatment of migraine: a randomised, phase 3, double-blind, placebo-controlled trial. Croop, R., Goadsby, PJ., Stock, DA., et al.[2020]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10299922/

Rimegepant: A Review in the Acute Treatment and ... Rimegepant was also significantly more effective than placebo irrespective of migraine attack frequency (≤ 4 or > 4 attacks per month) [32], ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03732638

NCT03732638 | Efficacy and Safety Trial of Rimegepant for ... The purpose of this is study is to compare the efficacy of BHV-3000 (rimegepant) to placebo as a preventive treatment for migraine, as measured by the ...

3. practicalneurology.com practicalneurology.com/news/study-compares-nurtec-odt-vs-14-other-treatments-for-acute-migraine/2475275/

Study Compares Nurtec ODT vs 14 Other Treatments for Acute ... 50.0% of participants treated with Nurtec ODT achieved ≥50% pain freedom within 2 hours, which was higher than or similar to other medications ...

4. thejournalofheadacheandpain.biomedcentral.com thejournalofheadacheandpain.biomedcentral.com/articles/10.1186/s10194-024-01935-8

Effectiveness and tolerability of rimegepant in the acute ... Our data confirms rimegepant effectiveness and safety in the acute migraine treatment in a real-world setting in a cohort of participants.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8903552/

Monthly migraine days, tablet utilization, and quality of life ... Acute treatment of migraine with rimegepant 75 mg on a PRN basis over one-year of follow-up was found to be associated with reduced MMD. In addition there was ...

6. nurtec.com nurtec.com/side-effects

Safety Profile | Nurtec® ODT (rimegepant) Nurtec ODT may cause serious side effects including allergic reactions, including trouble breathing and rash. This can happen days after you take Nurtec ODT.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11127653/

Safety of Rimegepant in Patients Using Preventive ... Acute treatment of migraine with rimegepant 75 mg for up to 52 weeks was well tolerated and had a favorable safety profile in adults who were concomitantly ...

8. headachejournal.onlinelibrary.wiley.com headachejournal.onlinelibrary.wiley.com/doi/full/10.1111/head.14995

Efficacy and safety of rimegepant for the preventive treatment ... Rimegepant 75 mg EOD demonstrated efficacy superior to that of placebo for the preventive treatment of migraine, with a favorable safety profile ...

9. ema.europa.eu ema.europa.eu/en/medicines/human/EPAR/vydura

Vydura | European Medicines Agency (EMA) Vydura was shown to be more effective than placebo at reducing headaches and other migraine symptoms and at reducing the number of days patients experienced ...