A Randomized, Open-Label, Multi-Center Study of Vestibular Migraine Prevention: Rimegepant Versus Flunarizine Non-inferiority Study

• Rimegepant (Drug): Rimegepant ODT 75 mg once daily
• Flunarizine (Drug): Flunarizine 10 mg once nightly

Primary outcomes

• MVSDs [from baseline to weeks 13-16]: Change from the observation phase in moderate-to-severe monthly vestibular symptom days (MVSDs) (as defined by Bárány Society) at weeks 13-16. MVSD = monthly vestibular symptom day, prorated to 28 days. Recommend not to specify that groups A and B are being compared in the description of the endpoint per se. (recommendation agreed)

Secondary outcomes

• Percentage of participants [from baseline to weeks 5-16]: Percentage of participants who complete treatment during weeks 5-16.
• MVSDs 2 [from baseline to weeks 5-8 and weeks 9-12]: Change from the observation phase in moderate-to-severe MVSDs (as defined by Bárány Society) at weeks 5-8 and weeks 9-12.
• TEAEs [from baseline to weeks 5-16]: Percentage of participants with TEAEs (treatment-emergent adverse events) during weeks 5-16.
• MVSDs3 [from baseline to weeks 13-16]: Change from the observation phase in MVSDs (as defined by Bárány Society) at weeks 13-16.
• MMDs [from baseline to weeks 5-8, weeks 9-12, and weeks 13-16]: Change from the observation phase in monthly migraine days (MMDs) at weeks 5-8, weeks 9-12, and weeks 13-16.
• ≥50% reduction [from baseline to weeks 13-16]: Percentage of participants with ≥50% reduction from the observation phase in moderate-to-severe MVSDs (as defined by Bárány Society) at weeks 13-16.
• DHI [from baseline at week 16]: Change in dizziness handicap inventory (DHI) score from baseline at week 16.
• GAD-7 [from baseline at week 16]: Change in General Anxiety Disorder-7 (GAD-7) score from baseline at week 16.
• PHQ-9 [from baseline at week 16]: Change in Patient Health Questionnaire-9 (PHQ-9) score from baseline at week 16.
• PGIC [from baseline at week 16]: Change in Patient Global Impression of Change（PGIC) scale from baseline at week 16.

Sex: All, ages: 18 Years to 75 Years

Inclusion Criteria:

* Male or female subjects aged 18 to 75 years；
* Diagnosis of definite vestibular migraine per Bárány society criteria： A. At least 5 episodes with vestibular symptoms of moderate or severe intensity, lasting 5 min to 72 hours； B. Current or previous history of migraine with or without aura according to the International Classification of Headache Disorders (ICHD)；

C. One or more migraine features with at least 50% of the vestibular episodes:

1. headache with at least two of the following characteristics:

   * one sided location
   * pulsating quality
   * moderate or severe pain intensity
   * aggravation by routine physical activity
2. photophobia and phonophobia；
3. visual aura; D. Not better accounted for by another vestibular or ICHD diagnosis.

   * Baseline (day 0 to 28) moderate or severe vestibular symptom days ≥ 4;
   * 80% adherence or better to electronic diary(eDiary) during observational phase
   * VM-PATHI2(Vestibular Migraine Patient Assessment Tool and Handicap Inventory) score > 25 at screening and baseline visit;
   * Written informed consent must be obtained before patient enrolled;
   * Fluency in local main language;
   * Access to email, and cell phone.

Exclusion Criteria:

* Vestibular hypofunction (unilateral or bilateral);
* History of ear surgery (other than ear tubes);
* Other vestibular diagnoses (excluding treated benign paroxysmal positional vertigo (BPPV)), including Meniere's disease, superior semicircular canal dehiscence syndrome, vestibular neuritis, persistent postural-perceptual dizziness, unilateral or bilateral vestibular hypofunction, cerebellar or brainstem disorders, multiple sclerosis, or motion sickness;
* Prior or current use of any prophylactic medication targeting the calcitonin gene-related peptide (CGRP);
* Prior or current treatment with flunarizine;
* Individuals are allergic to rimegepant sulfate oral disintegrating tablets or any excipients of rimegepant sulfate oral disintegrating tablets;
* Pregnant women, breastfeeding women, or those unwilling to use approved contraceptive methods during the study participation;
* History of serious medical or psychiatric disease, at the discretion of the treating physician (including significant coronary artery disease, peripheral vascular disease, cerebrovascular disease, kidney disease, liver disease, and uncontrolled psychiatric disease or past psychiatric hospitalization);
* A history of severe medical or psychiatric conditions (including significant coronary artery disease, peripheral vascular disease, cerebrovascular disease, renal disease, liver disease, Raynaud's disease, uncontrolled psychiatric disorders, or previous psychiatric hospitalizations) as determined by the treating physician;
* A history of mania, psychosis, or suicidal ideation;
* A history of drug or alcohol abuse within the 12 months prior to screening, based on the subject's medical records or self-report;
* Individuals who have received head, face, or neck botulinum toxin injections (such as Dysport®, Botox®, Xeomin®, Myobloc®, and JeuveauTM) within 4 months before screening or are scheduled for such injections during the study period;
* Unwilling to use approved form of birth control during the study;
* Other conditions judged by the investigator as unsuitable for inclusion.

• Results publication: Shao J, Fu J, Zhou M, Ren Z, Li L, Gao L, Xia Y, Zhao Z, Yang M, He J, Xue S, Wang G, He J, Liu K. Effectiveness of rimegepant in vestibular migraine: a prospective self-controlled cohort study. J Headache Pain. 2025 Dec 22;26(1):289. doi: 10.1186/s10194-025-02243-5. PMID 41430107