A pivotal phase 3 study of lasmiditan (CoLucid Pharmaceuticals) has achieved its primary and key secondary efficacy endpoints in patients with migraine headache pain. The study was designed to evaluate the efficacy and safety of lasmiditan in comparison with placebo.
Lasmiditan selectively targets 5-hydroxytryptamine 1F (5-HT1F) receptors expressed in the trigeminal pathway. Lasmiditan has been given the generic stem name “ditan,” which distinguishes it from other drug classes, including triptans, the current standard of care for migraine.
A total of 2,231 patients participated in the randomized, double-blind, placebo-controlled, parallel-group SAMURAI trial to treat a single episode of migraine. The patients’ mean age was 42 years; 83% were women; and 74% were Caucasian, with a mean migraine history of more than 19 years. The patients experienced an average of more than five migraines per month and had severe disability from migraine, with an average Migraine Disability Assessment (MIDAS) score of 31.
More than one-quarter of the patients used prophylactic medications to reduce the frequency of migraine. Most of the patients (82%) had multiple cardiovascular risk factors (CVRFs) or cardiovascular conditions. The most prevalent CVRFs included obesity, a family history of coronary artery disease, smoking, hypertension, postmenopausal women, men older than 40 years of age, hyperlipidemia, and type-2 diabetes. The most common cardiovascular conditions included arrhythmias, mitral valve disease, angina, atrial fibrillation, congestive heart failure, prior myocardial infarction, Raynaud’s disease, deep-vein thrombosis, ischemic stroke, and cerebral infarction.
The trial’s primary endpoint was the efficacy of lasmiditan (100 mg and 200 mg) compared with that of placebo based on freedom from migraine headache pain at two hours after dosing. The key secondary endpoint was the efficacy of lasmiditan based on freedom from the most bothersome associated symptom (MBS) of migraine (i.e., nausea, phonophobia, or photophobia) at two hours after dosing.
Data from the study were collected using electronic diaries during the treated attack. Beginning pre-dose, patients indicated their degree of headache pain on a four-point scale (0 = no pain; 1 = mild pain; 2 = moderate pain; or 3 = severe pain). Patients also indicated the presence or absence of nausea, phonophobia, or photophobia, and identified the associated symptom that was “most bothersome” at the pre-dose time point. At each time-point assessment, the patients were asked to indicate the degree of headache pain and the presence or absence of each associated symptom. The MBS endpoint was patient-centric and measured the treatment effect of the study drug on associated symptoms.
Of the patients treated with lasmiditan 100 mg or 200 mg, 28% and 32% were migraine headache pain-free at two hours after dosing, respectively, compared with 15% of the placebo-treated patients (P P
The new findings will be presented at the Fifth European Headache and Migraine Trust International Congress, to be held on September 17 in Glasgow, Scotland.
Source: CoLucid Pharmaceuticals; September 6, 2016.