Section number	Summary guidance
1.1 Subject selection
1.1.1 Migraine definition	Use ICHD diagnostic criteria
1.1.2 Other primary headaches	Permitted if infrequent and clearly recognized by the patient
1.1.3 Secondary headaches	Not permitted
1.1.4 Frequency of attacks	2–8 migraine attacks; ≤ 1 per month for other headache types (including non-target)
1.1.5 Duration of migraine	≥ 1 year
1.1.6 Age at onset	< 50 years
1.1.7 Age at entry	18–65 years
1.1.8 Sex	Females and males
1.1.9 Concomitant drug use	See text
1.2 Trial design
1.2.1 Blinding	Use double-blind
1.2.2 Placebo control	Recommended
1.2.3 Design types	Parallel-group and crossover
1.2.4 Randomization	Recommended
1.2.5 Stratification	Generally not necessary
1.2.6 Intention to treat	Should be defined, see text
1.2.8 Route of administration	Oral route is preferable if appropriate for the PK profile
1.2.9 Timing of administration	Should be prospectively defined in the protocol
1.2.10 Number of attacks treated	One, generally the first, see text
1.2.11 Rescue medication	Allowed any time after the first primary efficacy time point
1.2.12 Consistency of response	Evaluate ≥ 4 attacks, with ≥ 1 treated with placebo
1.3 Evaluation of results
1.3.1 Attack report form (diary)	An easy-to-use electronic diary that captures predefined endpoints
1.3.2 Primary endpoint	Pain freedom at 2 hours
1.3.3 Co-primary endpoint	Absence of the most bothersome associated symptom at 2 hours
1.3.4 Secondary endpoints
1.3.4.1 Relapse	Secondary endpoint, see text
1.3.4.2 Sustained pain-free	Secondary endpoint, see text
1.3.4.3 Total freedom from migraine	Secondary endpoint, see text
1.3.4.4 Headache intensity	Secondary endpoint, on a 4-point verbal rating scale
1.3.4.5 Headache relief	Secondary endpoint, see text
1.3.4.6 Time to meaningful relief	Secondary endpoint, see text
1.3.4.7 Time to pain freedom	Secondary endpoint, measured with a survival analysis of pain freedom at time points before 2 hours
1.3.4.8 Duration of attacks	Not recommended
1.3.4.9 Rescue medication	Secondary endpoint, see text
1.3.4.10 Global evaluation	Secondary endpoint, see text
1.3.4.11 Global impact (functional disability and quality of life)	Secondary endpoint, on a 4-point verbal rating scale
1.3.4.12 Associated symptoms — nausea and vomiting	Secondary endpoint, recorded at the time treatment is administered and at the time of assessment of the primary endpoint
1.3.4.13 Associated symptoms — photophobia	Secondary endpoint, recorded at the time treatment is administered and at the time of assessment of the primary endpoint
1.3.4.14 Associated symptoms — phonophobia	Secondary endpoint, recorded at the time treatment is administered and at the time of assessment of the primary endpoint
1.3.4.15 Time between headache onset and treatment intake	Secondary outcome measure
1.3.4.16 Treatment preference	Exploratory and hypothesis-generating global assessment method for crossover trials
1.3.4.17 Blinding assessment	Secondary outcome measure
1.3.4.18 Treatment of relapse	Secondary outcome measure, see text
1.3.4.19 Adverse events	Record and report all events, see text
1.4 Statistics
1.4.1 Hierarchy of endpoints	Recommended for use in trial design, conduct, and reporting

ICHD, International Classification of Headache Disorders