Safety findings from Phase 3 lasmiditan studies for acute treatment of migraine: Results from SAMURAI and SPARTAN

Abstract

Background We assessed the safety profile of lasmiditan, a selective 5-HT1F receptor agonist without vasoconstrictive activity being developed as an acute therapy for migraine. Methods SAMURAI and SPARTAN were Phase 3 double-blind studies of patients with migraine, randomized to oral lasmiditan 50 mg (SPARTAN only), 100 mg, 200 mg, or placebo to be taken within 4 hours of onset of migraine pain. Safety data from the studies were integrated. Treatment-emergent adverse events (occurring within 48 hours of first dose) were considered in the analyses. Results The safety population comprised 1262 patients assigned placebo, and 654, 1265, and 1258 assigned lasmiditan 50 mg, 100 mg, and 200 mg, respectively. There were no deaths; serious adverse events were reported for seven patients (placebo, n = 2 [0.2%]; lasmiditan 50 mg, n = 1 [0.2%]; lasmiditan 100 mg, n = 1 [0.2%]; lasmiditan 200 mg, n = 3 [0.2%]). Patients reporting ≥ 1 treatment-emergent adverse events were: Placebo, n = 174 (13.5%); lasmiditan 50 mg, n = 166 (25.4%); lasmiditan 100 mg, n = 458 (36.2%); and lasmiditan 200 mg, n = 510 (40.6%). Treatment-emergent adverse events were generally mild or moderate in severity. The most common treatment-emergent adverse events with lasmiditan were dizziness, paresthesia, somnolence, fatigue, nausea, muscular weakness and hypoesthesia. There were no ischemic events. Conclusions As a centrally-penetrant drug, lasmiditan use was associated with neurologic treatment-emergent adverse events; most were mild or moderate in severity and self-limiting. Trial registration at clinicaltrials.gov SAMURAI (NCT02439320) and SPARTAN (NCT02605174).

Onset of Efficacy Following Oral Treatment With Lasmiditan for the Acute Treatment of Migraine: Integrated Results From 2 Randomized Double‐Blind Placebo‐Controlled Phase 3 Clinical Studies

“…18 It is possible that these TEAEs could interfere with efficacy assessments. 18 It is possible that these TEAEs could interfere with efficacy assessments.…”

“…Lasmiditan was associated with neurologic TEAEs, which were mostly mild or moderate in severity, self-limiting, and of short duration. 18 It is possible that these TEAEs could interfere with efficacy assessments. However, 2 hours posttreatment efficacy outcomes following lasmiditan treatment such as pain freedom, freedom from MBS, patient reported migraine-related functional disability and global impression of change in patients with presence or absence of these common TEAEs' were comparable.…”

“…13 Lasmiditan efficacy and safety are supported by data from the phase 2 and phase 3 studies. [14][15][16][17][18] Both phase 3 studies, SAMURAI and SPARTAN, met primary and key secondary efficacy endpoints of statistically significantly higher percentage of lasmiditan-treated patients being migraine pain free and having freedom from their most bothersome symptom (MBS) at 2 hours following their initial dose compared with patients treated with placebo. 16,17 Given the disability associated with the attacks and the patients' needs, it is important to evaluate all meaningful efficacy outcomes for acute treatment and Conflict of Interest: MA is on the advisory board and speaking bureau for Allergan, Alder, Amgen, Novartis, Eli Lilly and Company, and Teva.…”

“…10 Lasmiditan (LY573144) is a novel therapeutic agent designated as a "ditan" in development for the acute treatment of migraine. [14][15][16][17][18] Both phase 3 studies, SAMURAI and SPARTAN, met primary and key secondary efficacy endpoints of statistically significantly higher percentage of lasmiditan-treated patients being migraine pain free and having freedom from their most bothersome symptom (MBS) at 2 hours following their initial dose compared with patients treated with placebo. 12 Lasmiditan has high affinity and selectivity for 5-HT 1F receptors and lacks the vasoconstrictor activity inherent with triptans.…”

Lasmiditan: Its Development and Potential Use

“…Lasmiditan's safety profile from pooled data (SPAR-TAN and SAMURAI) demonstrated rare serious AEs, and typical side effects were dizziness (approximately 15%, 5-fold more common than placebo), paresthesia (approximately 6%, 4-fold more common than placebo), and somnolence (approximately 6%, 2.5-fold more common than placebo). 16 Additionally (from pooled data trials), lasmiditan's efficacy and cardiovascular adverse events were similar in patients with cardiovascular risk factors and those without. Cardiovascular adverse events were rare in patients with cardiovascular risk factors (lastmiditan, 0.9%; placebo, 0.4%), and only benign arrythmias reached statistical significance to be more common (palpitations, tachycardia, etc).…”