Table 3 Summary of main inclusion and exclusion criteria for COMPEL

Inclusion Criteria

Male or female, ≥18 years of age on the day informed consent is signed.

Diagnosis of chronic migraine (≥15 days per month with headache lasting 4 hours a day or longer) with or without medication overuse.

History of chronic migraine (≥3 months).

Patients not taking oral headache prophylaxis medication must have discontinued their oral prophylaxis ≥4 weeks prior to Visit 1.

Patients who aretaking oral headache prophylaxis medication must be on a stable dose and regimen of a single oral prophylaxis treatment (prescribed for the use of headache prophylaxis) for at least 4 weeks prior to Visit 2.

If a patient is receiving a headache prophylaxis medication that is specifically prescribed for a non‐headache condition, he or she is eligible to enter the study even if they are receiving another agent on the headache prophylactic list that has been prescribed for headache, as long as the non‐headache medication regimen is stable for at least 4 weeks prior to Visit 1.

Stable medical condition, in the investigator’s opinion.

Ability to follow study instructions (including compliance with a diary) and likely to complete all required visits.

Negative urine pregnancy test at screening and on Day 1 prior to administration of onabotulinumtoxinA (for females of childbearing potential, including premenstrual women).

Documentation of ≥15 days of headache per month with headache lasting 4 hours a day or longer by IVRS patient diary. If fewer than 28 (but more than 20) days are completed in the IVRS patient diary at Day 1, a minimum of 53.6 % of recorded diary days must have a headache lasting 4 hours a day or longer.

Exclusion Criteria

Clinically significant medical condition other than the condition under evaluation (including alcohol/illicit substance abuse, significant pain condition [fibromyalgia, diabetic peripheral neuropathy, etc.]).

Any medical condition that may put the patient at increased risk with exposure to botulinum toxin therapy of any serotype for consistency and safety, including diagnosed myasthenia gravis, Eaton-Lambert syndrome, amyotrophic lateral sclerosis, or any other significant disease that might interfere with neuromuscular function.

Headache diagnosis of chronic tension-type headache (ICHD-III 2.3), cluster headache (ICHD-III 3.1), hypnic headache (ICHD-III 4.9), or hemicrania continua (ICHD-III 3.4).

Headache attributed to another disorder (ie, cervical dystonia, craniotomy, head/neck trauma).

Severe major depressive disorder defined as BDI-II score >24.

Endorsement of a non-zero response on Item 9 (“Thoughts that you would be better off dead, or hurting yourself in some way”) of the PHQ-9 (ie, Item 9 score ≠ 0).

Females who are pregnant, nursing, or are planning a pregnancy during the study.

Females of childbearing potential (including premenstrual women) who are not using a reliable means of contraception.

Previous treatment with botulinum toxin of any serotype for any reason, or immunization to any botulinum toxin serotype.

Anticipated need for botulinum toxin treatment for any reason during the study (other than study treatment).

Known allergy or sensitivity to the study medication or its components.

Previous participation in any botulinum toxin clinical trial.

Concurrent enrollment in an investigational drug or device study or participation in such a study in the 4 weeks immediately prior to Visit 1.

Patient has a condition or is in a situation that, in the investigator's opinion, may put the patient at significant risk, may confound the study results, or may interfere significantly with the patient's participation in the study.

Treatment of study target muscles using acupuncture, TENS, cranial traction, dental splints for headache, nociceptive trigeminal inhibition, occipital nerve block treatments, or injection of anesthetics/steroids within 3 months prior to screening.