Evaluation of the Efficacy of Diclofenac Potassium and Rimegepant for the Acute Treatment of Migraine (ATOM)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Rigshospitalet

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

4 May 2022 → 30 Apr 2025

Decision date (initial)

2025-01-29

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-517128-21-02

EudraCT number

2021-001057-31

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

The percentage of subjects who become pain free at 2 hours(h) after treatment, before the use of any rescue medication is the primary measure of efficacy.

Conditions and MedDRA coding

Migraine

Study design 1 period

Regulatory references

Plan to share IPD

No

IPD plan description

This has not been described in the protocol.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. History of migraine (with or without aura) for greater than or equal to 12 months before screening according to the ICHD-33 criteria based on medical records and/or patient selfreport
2. Subject has provided informed consent prior to initiation of any study-specific activities/procedures.
3. Aged 18 to 65 years upon entry into screening
4. Not more than 12 attacks per month with moderate to severe headache pain in each of the previous 3 months.

Exclusion criteria 22

1. Greater than 50 years of age at migraine onset
2. History of cluster headache or hemiplegic migraine headache
3. Inability to differentiate between migraine from other headaches
4. Has taken medication for acute treatment of headache (including acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), triptans, ergotamine, opioids, or combination analgesics) on 10 or more days per months in the previous 3 months
5. Has a history of migraine aura with diplopia or impairment of levels of consciousness, hemiplegic migraine, or retinal migraine.
6. Required hospital treatment of a migraine attack 3 or more times in the previous 6 months.
7. The subject is at risk of self-harm or harm to others as evidenced by past suicidal behavior
8. Has a chronic non-headache pain condition requiring daily pain medication
9. Has a history of any prior gastrointestinal conditions (e.g., diarrhea syndromes, inflammatory bowel disease) that may affect the absorption or metabolism of investigational product; participants with prior gastric bariatric interventions which have been reversed are not excluded.
10. Has a history of malignancy in the prior 5 years, except for adequately treated basal cell or squamous cell skin cancer, or in situ cervical cancer.
11. History or evidence of any other clinically significant disorder, condition or disease (except for those outlined above) that, in the opinion of the investigator would pose a risk to subject safety or interfere with the study evaluation, procedures or completion
12. Start of new preventive migraine treatment within the last two months
13. Change in dosage of ongoing preventive migraine treatment within the last two months
14. Current preventive treatment with monoclonal antibodies targeting calcitonin gene related peptide (CGRP) or CGRP receptors, or current use of small-molecule CGRP receptor antagonist (e.g. erenumab, fremanezumab, galcanezumab, atogepant or rimegepant)
15. Changes in treatment with Selective serotonin reuptake inhibitors (SSRI) or serotonin norepinephrine reuptake inhibitors (SNRI) within the last two months
16. Use of the following medication within 30 days prior to screening: o Strong and moderate cytochrome P450 3A4 (CYP3A4) inhibitors, including but not limited to systemic (oral/IV) itraconazole, ketoconazole, fluconazole; erythromycin, clarithromycin, telithromycin; diltiazem, verapamil; aprepitant; cyclosporine; nefazodone; cimetidine; quinine; and HIV protease inhibitors o Strong and moderate CYP3A4 inducers, including but not limited to barbiturates (eg, phenobarbital and primidone), systemic (oral/IV) glucocorticoids, nevirapine, efavirenz, pioglitazone, carbamazepine, phenytoin, rifampin, rifabutin, and St. John’s wort o Inhibitors of the BCRP (breast cancer resistance protein) transporter (eg, rifampicin) o Drugs with narrow therapeutic margins (eg, digoxin, warfarin)
17. Female subjects of childbearing potential with a positive pregnancy test assessed at screening or day 1 by a urine pregnancy test.
18. Female subject is pregnant or breastfeeding or planning to become pregnant or breastfeed during treatment and for an additional 16 weeks after the last dose of investigational product.
19. Female subjects of childbearing potential unwilling to use 1 acceptable method of effective contraception during treatment and for an additional 16 weeks after the last dose of investigational product.
20. Evidence of current pregnancy or breastfeeding per subject self-report or medical records
21. Subject has known sensitivity to any of the products or components to be administered during dosing.
22. Subject likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures (e.g, Clinical Outcome Assessments) to the best of the subject and investigator's knowledge

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The percentage of subjects who become pain free at 2 hours(h) after treatment, before the use of any rescue medication is the primary measure of efficacy.

Secondary endpoints 9

1. Absence of the most bothersome symptom (MBS) at 2 hours
2. Relapse
3. Headache intensity
4. Rescue medication
5. Global evaluation
6. Associated symptom – nausea
7. Associated symptom – photophobia
8. Associated symptom – phonophobia
9. Adverse events

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Rigshospitalet

Sponsor organisation

Rigshospitalet

Address

Valdemar Hansens Vej 1-23

City

Glostrup

Postcode

2600

Country

Denmark

Scientific contact point

Organisation

Rigshospitalet

Contact name

Messoud Ashina

Public contact point

Organisation

Rigshospitalet

Contact name

Messoud Ashina

Third parties 1

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 7 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications