Assess consistency for the intention-to-treat (ITT) population and predefined subset of patients who were triptan insufficient responders (TIR).   

Lasmiditan (LTN) is a selective 5-HT_1F receptor agonist for the acute treatment of migraine in adults. CENTURION was designed to assess the consistency of lasmiditan for the acute treatment of migraine.

Patients were randomized in double blind fashion 1:1:1 to lasmiditan 200mg (LTN200); LTN100; or a control group which received PBO for 3 attacks and LTN50 for either the 3^rd/4^th attack. This modified parallel design enabled comparisons of the consistency for LTN vs PBO. Patients were asked to treat 4 migraine attacks, preferably consecutively. The primary endpoints were pain freedom at 2h (first attack) and pain freedom at 2h in ≥2/3 attacks. Statistical testing used a logistic regression model and multiplicity methodology to preserve overall type I error.

1471 patients (mean age 41; 84% female; MIDAS mean score 31.6) treated ≥1 migraine attack with study drug. All primary and gated secondary endpoints and additional analyses presented were statistically significant for lasmiditan vs placebo (p<0.001 except as indicated). Both LTN doses were significantly superior to PBO for pain freedom (LTN100 14.4%, LTN200 24.4%, PBO 4.3%) and pain relief (62.3%, 66.7%, 36.9%, respectively) at 2h in ≥2/3 attacks in the ITT; similar results were observed in TIR (11% [P<.03], 20.1%, and 4.3%, respectively, for pain free consistency and 55.6%, 62.7%, and 33.6%, respectively, for pain relief consistency). The most frequent treatment emergent adverse events with LTN were dizziness, paresthesia, fatigue, nausea, vertigo, somnolence, hypoesthesia, muscle weakness, asthenia, and feeling abnormal; the incidence of TEAEs was highest during the 1^st attack.

LTN was superior to PBO for all gated endpoints. Intra-patient consistency of response was superior with LTN compared with PBO, both overall and in the TIR subset.