BACKGROUND: Lasmiditan (COL-144) is a novel, centrally acting, highly selective 
5-HT(1F) receptor agonist without vasoconstrictor activity that seemed effective 
when given as an intravenous infusion in a proof-of-concept migraine study. We 
aimed to assess the efficacy and safety of oral lasmiditan for the acute 
treatment of migraine.
METHODS: In this multicentre, double-blind, parallel-group, dose-ranging study 
in 43 headache centres in five European countries, patients with migraine with 
and without aura and who were not using prophylaxis were randomly assigned 
(1:1:1:1:1) to treat one moderate or severe attack at home with 50 mg, 100 mg, 
200 mg, or 400 mg lasmiditan, or placebo. Study drug and placebo were supplied 
in identical numbered tablet packs. The randomisation code was generated by an 
independent statistician. Patients and investigators were masked to treatment 
allocation. The primary endpoint was dose response for headache relief (moderate 
or severe becoming mild or none) at 2 h. The primary analysis was done in the 
modified intention-to-treat population. This study is registered with 
ClinicalTrials.gov, number NCT00883051.
FINDINGS: Between July 8 2009, and Feb 18, 2010, 512 patients were randomly 
assigned to treatment, 391 of whom received treatment. 86 patients received 
placebo (81 included in primary analysis) and 305 received lasmiditan (50 mg 
n=79, 100 mg n=81, 200 mg n=69, and 400 mg n=68 included in primary analysis). 
There was a linear association between headache response rate at 2 h and 
lasmiditan dose (Cochran-Armitage test p<0·0001). Every lasmiditan treatment 
dose significantly improved headache response at 2 h compared with placebo 
(lasmiditan 50 mg: difference 17·9%, 95% CI 3·9-32·1, p=0·022; 100 mg: 38·2%, 
24·1-52·4, p<0·0001; 200 mg: 28·8%, 9·6-39·9, p=0·0018; 400 mg: 38·7%, 
23·9-53·6, p<0·0001). The proportion of patients with treatment-emergent adverse 
events increased with increasing doses (53/82 [65%], 59/82 [72%], 61/71 [86%], 
and 59/70 [84%] for lasmiditan 50, 100, 200, and 400 mg, respectively vs 19/86 
[22%] for placebo). Most adverse events were mild or moderate in intensity, with 
16 of 82 (20%), 23 of 82 (28%), 28 of 71 (39%), and 31 of 70 (44%) of patients 
on lasmiditan 50, 100, 200, and 400 mg, respectively reporting a severe adverse 
event compared with five of 86 (6%) on placebo. The most common adverse events 
were CNS related and included dizziness, fatigue, vertigo, paraesthesia, and 
somnolence.
INTERPRETATION: Oral lasmiditan seems to be safe and effective in the acute 
treatment of migraine. Further assessment in larger placebo-controlled and 
triptan-controlled trials are needed to assess the potential role of lasmiditan 
in acute migraine therapy.
FUNDING: CoLucid Pharmaceuticals.