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

Prior treatment

• 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)
• Changes in treatment with Selective serotonin reuptake inhibitors (SSRI) or serotonin norepinephrine reuptake inhibitors (SNRI) within the last two months
• 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)
• 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.
• 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.
• 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
• Required hospital treatment of a migraine attack 3 or more times in the previous 6 months.
• 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.

Other illness

• 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.
• 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
• History of cluster headache or hemiplegic migraine headache
• Has a history of migraine aura with diplopia or impairment of levels of consciousness, hemiplegic migraine, or retinal migraine.
• Has a chronic non-headache pain condition requiring daily pain medication

Age

• Greater than 50 years of age at migraine onset

Other

• Start of new preventive migraine treatment within the last two months
• Change in dosage of ongoing preventive migraine treatment within the last two months
• Female subjects of childbearing potential with a positive pregnancy test assessed at screening or day 1 by a urine pregnancy test.
• Evidence of current pregnancy or breastfeeding per subject self-report or medical records
• Subject has known sensitivity to any of the products or components to be administered during dosing.
• 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
• Inability to differentiate between migraine from other headaches
• The subject is at risk of self-harm or harm to others as evidenced by past suicidal behavior

• 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
• Subject has provided informed consent prior to initiation of any study-specific activities/procedures.
• Aged 18 to 65 years upon entry into screening
• Not more than 12 attacks per month with moderate to severe headache pain in each of the previous 3 months.