Migraine With Aura, Migraine Without Aura
Conditions
Brief summary
In a real-world population of adults with migraine, the investigators would like to investigate whether 12.5 mg almotriptan is non-inferior to 50 mg ubrogepant in terms of pain freedom at 2 hours after drug intake.
Detailed description
The study is a randomized, open-label, parallel-group, single-attack study with 12.5 mg almotriptan and 50 mg ubrogepant. 645 patients with migraine with or without aura according to the third edition of the International Classification of Headache Disorders (ICHD-3) will be included. Each subject will randomly be allocated to one treatment, and given 42 days to treat a single qualifying migraine attack of moderate to severe intensity.
Interventions
DRUGAlmotriptan 12.5 Mg Oral Tablet
Treatment for an acute, moderate to severe migraine attack
DRUGUbrogepant 50Mg Tab
Treatment for an acute, moderate to severe migraine attack
Sponsors
Messoud Ashina, MD
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Subject has provided informed consent prior to initiation of any study-specific activities/procedures. * Aged 18 to 65 years upon entry into screening * History of migraine (with or without aura) for greater than or equal to 12 months before screening according to the ICHD-3 criteria based on medical records and/or patient self-report. * Not more than 12 attacks per month with moderate to severe headache pain in each of the previous 3 months.
Exclusion criteria
Disease Related * Greater than 50 years of age at migraine onset * History of cluster headache or hemiplegic migraine headache * Inability to differentiate between migraine from other headaches * 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 * Has a history of migraine aura with diplopia or impairment of levels of consciousness, hemiplegic migraine, or retinal migraine. * Required hospital treatment of a migraine attack 3 or more times in the previous 6 months. Other Medical Conditions * The subject is at risk of self-harm or harm to others as evidenced by past suicidal behavior * Has a chronic non-headache pain condition requiring daily pain medication * 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. * 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 Medication related * Start of new preventive migraine treatment within the last two months * Change in dosage of ongoing preventive migraine treatment within the last two months * Current treatment with monoclonal antibodies targeting calcitonin gene related piptide (CGRP) or CGRP receptors, or current use of small-molecule CGRP receptor antagonist (e.g. erenumab, fremanezumab, galcaneszumab or atogeptant) * 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: * 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 * 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 * Inhibitors of the BCRP (breast cancer resistance protein) transporter (eg, rifampicin) * Drugs with narrow therapeutic margins (eg, digoxin, warfarin) Other Exclusions * Female subjects of childbearing potential with a positive pregnancy test assessed at screening or day 1 by a urine pregnancy test. * 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. * 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pain freedom at 2 hours | 2 hours after initial dose | Pain freedom will be subjectively rated by the patient in a headache diary (yes or no). |
Other
| Measure | Time frame | Description |
|---|---|---|
| Relapse | 48 hours after initial dose | Patients, who were pain free 2 hours after the investigational treatment was administered, are to subjectively evaluate if they experienced reoccurrence of headache of any severity within 48 hours of the intake of given treatment (relapse of headache or no headache). |
| Headache intensity | Predose, and 0.5, 1, 1.5, 2, 3, 4, 12, 24 and 48 hours after initial dose | Headache intensity will be subjectively rated by the patient at predefined timepoints on a 4-point scale where 0 = no headache; 1 = mild headache; 2 = moderate headache; 3 = severe headache. |
| Rescue medication | 48 hours after initial dose | The patient will record if they take any rescue medication 2 hours after intake of test medication and within 48 hours. |
| Global evaluation | 48 hours after initial dose | The patient will subjectively rate their global impression of the test medication based on Likert-type verbal scale (e.g., very poor, poor, no opinion, good, very good). |
| Absence of the most bothersome symptom (MBS) at 2 hours | 2 hours after initial dose | Patients are to select their MBS prior to randomization, and then only treat an attack that occurs with the pre-specified MBS. 2 hours after initial dose, patients are to subjectively rate if the MBS have disappeared fully or if it is still present (present or not present). |
| Associated symptom - photophobia | Predose, 2, 4, 8, 12, 24- and 48-hours after initial dose | The presence or absence of photophobia. |
| Associated symptom - phonophobia | Predose, 2, 4, 8, 12, 24- and 48-hours after initial dose | The presence or absence of phonophobia. |
| Adverse events | Up to 48 hours after initial dose. | Any untowards medical events are to be recorded in the diary by the patients. Furthermore, the patient will be instructed to inform the investigator in such case. |
| Associated symptom - nausea | Predose, 2, 4, 8, 12, 24- and 48-hours after initial dose | The presence or absence of nausea. |
Countries
Denmark
Outcome results
None listed