INTRODUCTION: Lasmiditan (COL-144; LY573144) is a novel, highly selective and 
potent agonist at 5-HT(1F) receptors that lacks vasoconstrictor activity. 
Preclinical and early clinical experiments predict acute antimigraine efficacy 
of COL-144 that is mediated through a non-vascular, primarily neural, mechanism.
SUBJECTS AND METHODS: In a randomised, multicentre, placebo-controlled, 
double-blind, group-sequential, adaptive treatment-assignment, proof-of-concept 
and dose-finding study, we treated 130 subjects in-hospital during a migraine 
attack. Subjects were allocated to an intravenous dose level of lasmiditan or 
placebo in small cohorts. The starting dose was 2.5 mg. Subsequent doses were 
adjusted, up or down, according to the safety and efficacy seen in the preceding 
cohort. The primary outcome measure was headache response defined as improvement 
from moderate or severe headache at baseline to mild or no headache at 2 h 
post-dose. The study was designed to explore the overall dose response 
relationship but was not powered to differentiate individual doses from placebo, 
nor to detect effect differences for other migraine symptoms.
RESULTS: Forty-two subjects received placebo and 88 received lasmiditan in doses 
of 2.5-45 mg. Subjects were observed in the clinic for 4 h after treatment and 
used a diary card to record symptoms and adverse events for up to 24 h. The 
study was terminated when the 20 mg dose met predefined efficacy stopping rules. 
Of subjects treated in the 10, 20, 30 and 45 mg lasmiditan dose groups, 54-75% 
showed a 2 h headache response, compared to 45% in the placebo group (P = 0.0126 
for the linear association between response rates and dose levels). Patient 
global impression at 2 h and lack of need for rescue medication also showed 
statistically significant linear correlations with dose. Lasmiditan was 
generally well tolerated. Adverse events were reported by 65% of subjects on 
lasmiditan and by 43% on placebo and were generally mild. Dizziness, paresthesia 
and sensations of heaviness (usually limb) were more common on lasmiditan.
CONCLUSIONS: At intravenous doses of 20 mg and higher, lasmiditan proved 
effective in the acute treatment of migraine. Further studies to assess the 
optimal oral dose and full efficacy and tolerability profile are under way. The 
non-vascular, neural mechanism of action of lasmiditan may offer an alternative 
means to treat migraine especially in patients who have contra-indications for 
agents with vasoconstrictor activity. The clinicaltrials.gov identifier for this 
study is NCT00384774.