Effect of Atogepant on the Vestibulo-Ocular Reflex in Healthy Adults and Adults With Migraine

NCT07826910 | Not Yet Recruiting Phase 4

• 1 other identifier: BASEC 2024-02190
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

Researchers want to find out how a substance in the body called CGRP affects balance. CGRP (calcitonin gene-related peptide) is a small protein involved in migraine. Several approved migraine medicines work by blocking it. Studies in animals suggest that CGRP also helps a reflex called the vestibulo-ocular reflex, or VOR. The VOR keeps vision steady when the head moves: when the head turns, the eyes move the opposite way by the same amount, so the world does not appear to jump. Animals that lack the CGRP receptor have a weaker VOR. It is not known whether blocking CGRP weakens the VOR in people. This study tests whether a single dose of atogepant changes the VOR in people. Atogepant is approved in Switzerland for the prevention of migraine and blocks the CGRP receptor. In this study it is used in a different way than it is approved for. Eighty people will take part at the University Hospital Zurich. The study runs in two parts. First, 40 healthy people join. After that, 40 people who have episodic or chronic migraine join. Everyone receives both of the following, in random order: one capsule containing atogepant 60 mg one capsule containing placebo (a capsule with no active medicine) The two test visits are at least 5 days apart. A computer decides which capsule each person receives first. Neither the participants nor the study team know which capsule is which until the study is finished. At each test visit, the participant swallows the capsule at the study centre and stays for at least 90 minutes. Balance and eye-movement tests then begin, about 90 to 120 minutes after the capsule. The tests record eye movements while the head is moved quickly, while warm and cool air or water is placed in the ear canal, while a chair turns gently from side to side, and while the whole body is tilted. Participants also answer short questionnaires about nausea and dizziness before and after the tests. Each test visit lasts about 2 hours and 45 minutes. A short follow-up visit or telephone call takes place within 7 days after the second test visit. People aged 18 to 65 can take part if they have no balance disorder and meet the other study requirements. People cannot take part if, for example, they are allergic to atogepant, have taken a CGRP-blocking medicine in the past 6 months, have severe kidney or liver problems, have unstable heart disease, have a pacemaker, or are pregnant or breastfeeding. Participants are not expected to get a health benefit from taking part. The study is done to learn more about how CGRP works in the balance system, which may help in developing treatments for dizziness and migraine in the future.

Conditions

Migraine Disorders, Brain; Healthy Adult Participants; Vestibulo-Ocular Reflex

Keywords

CGRP; Calcitonin Gene-Related Peptide; CGRP receptor antagonist; Gepant; Atogepant; Vestibulo-ocular reflex; VOR gain; Vestibular function; Otolith function; Video head impulse test; vHIT; Caloric testing; Rotary chair; Sinusoidal harmonic acceleration; Prepulse inhibition; Blink reflex; Cross-over study; Healthy volunteers; Migraine

Outcome Measures

Primary Outcomes (1)

• Change in vestibulo-ocular reflex (VOR) gain measured by video head impulse test (vHIT)

  VOR gain of the horizontal semicircular canals, measured by video head impulse test as the ratio of eye velocity to head velocity (unitless), under atogepant 60 mg compared with placebo. The intra-individual difference between the atogepant condition and the placebo condition is the quantity of interest. A difference of 0.10 in VOR gain is considered clinically meaningful.

  Assessed 90-120 minutes after dosing in each of the two treatment periods (Visit 1 and Visit 2, separated by a washout of at least 5 days)

Secondary Outcomes (8)

• Caloric response

  Assessed 90-120 minutes after dosing in each of the two treatment periods (Visit 1 and Visit 2, separated by a washout of at least 5 days)

• Rotary chair VOR gain (sinusoidal harmonic acceleration)

  Assessed 90-120 minutes after dosing in each of the two treatment periods (Visit 1 and Visit 2, separated by a washout of at least 5 days)

• Nausea assessed by visual analogue scale

  Immediately before and immediately after the vestibular test battery at each of the two treatment visits (approximately 90 and 180 minutes after dosing)

• Motion sickness symptoms assessed by the Motion Sickness Assessment Questionnaire (MSAQ)

  Immediately before and immediately after the vestibular test battery at each of the two treatment visits (approximately 90 and 180 minutes after dosing)

• Spinning vertigo assessed by visual analogue scale

  Immediately before and immediately after the vestibular test battery at each of the two treatment visits (approximately 90 and 180 minutes after dosing)

Study Arms (2)

Sequence AB: Atogepant then Placebo

EXPERIMENTAL

Drug: Atogepant; Drug: Placebo

Drug: Atogepant 60 mg; Drug: Placebo

Sequence BA: Placebo then Atogepant

EXPERIMENTAL

Drug: Placebo; Drug: Atogepant

Drug: Atogepant 60 mg; Drug: Placebo

Interventions

Atogepant 60 mg DRUG

Single oral dose of atogepant 60 mg, administered once during the trial. The marketed Aquipta® 60 mg film-coated tablet, authorised in Switzerland, is over-encapsulated into a size 000 hard-gelatine capsule filled with mannitol (Ph. Eur.) by an independent pharmacy in order to maintain blinding; the active substance and the tablet itself are not modified. The capsule is swallowed with a glass of water under the direct supervision of the investigator, and the date and time of administration are documented.

Also known as: Aquipta, Qulipta

Sequence AB: Atogepant then Placebo; Sequence BA: Placebo then Atogepant

Placebo DRUG

Sequence AB: Atogepant then Placebo · Sequence BA: Placebo then Atogepant

Sequence AB: Atogepant then Placebo; Sequence BA: Placebo then Atogepant

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy participants (Phase 1 of enrolment):
• Age 18 to 65 years
• No functional or structural vestibular disorder
• No history of unilateral or bilateral vestibulopathy
• No diagnosis of migraine
• Written informed consent provided by the participant
• Participants with migraine (Phase 2 of enrolment):
• Diagnosis of episodic or chronic migraine according to the ICHD-3 criteria
• Age 18 to 65 years
• No functional or structural vestibular disorder
• No history of unilateral or bilateral vestibulopathy
• Written informed consent provided by the participant

You may not qualify if:

• Hypersensitivity to atogepant
• Intake of any CGRP-antagonist medication within the last 6 months
• Known impaired kidney function with a creatinine clearance below 30 mL/min, or known impaired liver function (Child-Pugh B or C)
• Insufficiently controlled, unstable or newly diagnosed cardiovascular disease, for example ischaemic coronary disease, coronary vasospasm or cerebral ischaemia
• Myocardial infarction, acute coronary syndrome, percutaneous coronary intervention, cardiac surgery, stroke of any kind or transient ischaemic attack within the last 6 months (24 weeks)
• Medication overuse headache
• Cardiac pacemaker or other implanted electronic device
• Concomitant use of strong CYP3A4 inhibitors, of strong or moderate CYP3A4 inducers, or of OATP1B1/OATP1B3 inhibitors
• Pregnancy or breastfeeding; women of childbearing potential not using effective contraception during the study
• Participation in another clinical trial with an investigational medicinal product within 30 days before the screening visit
• Inability to understand the participant information or to give written informed consent

Sponsors & Collaborators

• Konrad Peter Weber: lead

Study Sites (1)

University Hospital Zurich, Department of Neurology

Zurich, Canton of Zurich, 8091, Switzerland

Location

Related Publications (6)

• Gianaros PJ, Muth ER, Mordkoff JT, Levine ME, Stern RM. A questionnaire for the assessment of the multiple dimensions of motion sickness. Aviat Space Environ Med. 2001 Feb;72(2):115-9.

  PMID: 11211039 BACKGROUND

• MacDougall HG, Weber KP, McGarvie LA, Halmagyi GM, Curthoys IS. The video head impulse test: diagnostic accuracy in peripheral vestibulopathy. Neurology. 2009 Oct 6;73(14):1134-41. doi: 10.1212/WNL.0b013e3181bacf85.

  PMID: 19805730 BACKGROUND

• Ailani J, Lipton RB, Goadsby PJ, Guo H, Miceli R, Severt L, Finnegan M, Trugman JM; ADVANCE Study Group. Atogepant for the Preventive Treatment of Migraine. N Engl J Med. 2021 Aug 19;385(8):695-706. doi: 10.1056/NEJMoa2035908.

  PMID: 34407343 BACKGROUND

• Edvinsson L, Haanes KA, Warfvinge K, Krause DN. CGRP as the target of new migraine therapies - successful translation from bench to clinic. Nat Rev Neurol. 2018 Jun;14(6):338-350. doi: 10.1038/s41582-018-0003-1.

  PMID: 29691490 BACKGROUND

• Jones SM, Vijayakumar S, Dow SA, Holt JC, Jordan PM, Luebke AE. Loss of alpha-Calcitonin Gene-Related Peptide (alphaCGRP) Reduces Otolith Activation Timing Dynamics and Impairs Balance. Front Mol Neurosci. 2018 Aug 24;11:289. doi: 10.3389/fnmol.2018.00289. eCollection 2018.

  PMID: 30197585 BACKGROUND

• Luebke AE, Holt JC, Jordan PM, Wong YS, Caldwell JS, Cullen KE. Loss of alpha-calcitonin gene-related peptide (alphaCGRP) reduces the efficacy of the Vestibulo-ocular Reflex (VOR). J Neurosci. 2014 Jul 30;34(31):10453-8. doi: 10.1523/JNEUROSCI.3336-13.2014.

  PMID: 25080603 BACKGROUND

MeSH Terms

Conditions

Migraine Disorders

Interventions

atogepant

Condition Hierarchy (Ancestors)

Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Konrad P Weber, Prof.

  University Hospital Zurich, Department of Neurology

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Vergil V Mavrodiev, MD

CONTACT

+41 43 253 64 03; Vergil.Mavrodiev@usz.ch

Konrad P Weber, Prof.

CONTACT

+41 44 255 55 49; Konrad.Weber@usz.ch

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: In addition to the participants, the care providers, the investigators and the outcomes assessors, the person performing the statistical analysis and the independent trial monitor also remain blinded to the treatment allocation until database lock. The only unblinded persons are the independent physician who generates and holds the randomisation list, who takes no part in the conduct, data collection or analysis of the trial, and the designated staff of the independent pharmacy who label the study kits. Blinding is maintained by over-encapsulating the marketed film-coated tablet in a hard-gelatine capsule identical in appearance to the mannitol-filled placebo capsule; kit labels carry only the study identifier, randomisation number, treatment period, batch number and expiry date.
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prof. Dr. med.

Model Details: Two-period, two-sequence (AB/BA) cross-over design. Each participant receives a single oral dose of atogepant 60 mg in one period and a single oral dose of matching placebo in the other, separated by a washout period of at least 5 days. The trial is conducted in two consecutive phases: 40 healthy participants are enrolled first, and enrolment of 40 participants with episodic or chronic migraine begins only after enrolment in the healthy group is complete. Randomisation is stratified by group, so allocation is balanced within each phase.

Study Record Dates

• First Submitted: September 10, 2026
• First Posted: September 17, 2026
• Study Start (Estimated): January 1, 2027
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: September 17, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)