Efficacy and safety of lasmiditan in patients using concomitant migraine preventive medications: findings from SAMURAI and SPARTAN, two randomized phase 3 trials

Abstract

Objective: To study the efficacy and safety of lasmiditan for acute treatment of migraine in patients using migraine preventive medications.

Background: While lasmiditan has been proven to be an effective acute treatment for migraine, its effectiveness has not been examined when used concurrently with migraine preventives.

Methods: SAMURAI and SPARTAN were similarly designed, double-blind, phase 3, placebo-controlled studies of patients 18 years or older with 3 to 8 migraine attacks per month. Patients were randomized to treat a migraine attack with oral lasmiditan 50 mg (SPARTAN only), 100 mg, 200 mg, or placebo. Migraine preventives were allowed as long as doses were stable for 3 months prior to screening and were unchanged during the study. Preventive medications with established or probable efficacy, as recommended by the American Academy of Neurology, the American Headache Society, and the European Headache Federation, plus botulinum toxin type A and candesartan, were included. Within the subgroups of patients using and not using preventive therapies, lasmiditan and placebo groups were analyzed for the outcome of pain-free at 2 h and other efficacy outcomes. The subgroups of patients using and not using preventive therapies were compared and interaction p-values were calculated for safety and efficacy outcomes.

Results: In these trials, 698 of 3981 patients (17.5%) used migraine preventive treatments. Among patients using preventives, all lasmiditan doses resulted in significantly more patients being pain-free at 2 h, compared to placebo (p < 0.05). Primary efficacy outcome (pain-free at 2 h), key secondary outcome (most bothersome symptom-free at 2 h) and all other efficacy outcomes were not significantly different between patients using or not using migraine preventives (all interaction p-values ≥0.1). Rates of adverse events were similar for patients using and not using preventive medications.

Conclusions: Lasmiditan was more effective than placebo for the acute treatment of migraine in patients concurrently using migraine preventive medications. Lasmiditan efficacy and safety measures were similar for patients using and not using preventive medications.

Trial registration: SAMURAI (NCT02439320) and SPARTAN (NCT02605174). Registered 18 March 2015.

Keywords: Acute treatment; Concomitant; Ditan; Efficacy; Lasmiditan; Migraine; Migraine medication; Migraine preventive; Migraine prophylaxis.

Conflict of interest statement

LSL is an employee of Eli Lilly and Company and/or one of its subsidiaries, Indianapolis, IN, USA and is a minor stockholder of Eli Lilly and Company.

JA has received personal compensation from Alder, Amgen, Allergan, Avanir, Avent, electroCore, Eli Lilly, Impel, Miller Communications, Promius, Satsuma, Teva for consulting and speaking. She has served as a section editor for Current Pain and Headache Reports. She has received research support from the American Migraine Foundation and the ARMR registry.

JS received personal compensation from Acorda, Alder, Allergan, Amgen, Avanir, Depomed, electroCore, Eli Lilly, Novartis, Pernix, Promius, Supernus, Teva, and Upsher-Smith for consulting and speaking. He has received research support from Alder, Allergan, Amgen, electroCore, Eli Lilly, and Teva.

SB is an employee of Eli Lilly and Company and/or one of its subsidiaries, Indianapolis, IN, USA and is a minor stockholder of Eli Lilly and Company.

HPH is an employee of Eli Lilly and Company and/or one of its subsidiaries, Indianapolis, IN, USA and is a minor stockholder of Eli Lilly and Company.

MP is an employee of Eli Lilly and Company and/or one of its subsidiaries, Indianapolis, IN, USA and is a minor stockholder of Eli Lilly and Company.

JHK is an employee of Eli Lilly and Company and/or one of its subsidiaries, Indianapolis, IN, USA and is a minor stockholder of Eli Lilly and Company.

Figures

Fig. 1

Pain-free and most bothersome symptom-free (MBS-free) at 2 h following lasmiditan treatment were similar in patients using and not using migraine preventive medications. Patients using and not using migraine preventive medications treated a migraine headache with lasmiditan (LTN) 50 mg, 100 mg, or 200 mg or placebo (PBO). At 2 h postdose, patients rated their pain and presence or absence of nausea, phonophobia, or photophobia. Colored bars show the percentages of patients reporting a complete absence of pain (1a) or MBS (1b) at 2 h. Comparisons of lasmiditan effect in the group of patients using versus not using preventive medications were not significant for any treatment group for either pain-free or MBS-free (all interaction p-values > 0.1)

Fig. 2

Pain freedom occurred at similar time points in patients using versus not using preventive medications. Patients using (2a) and not using (2b) migraine preventive medications treated a migraine attack with lasmiditan (LTN) 50 mg, 100 mg, or 200 mg of or placebo (PBO). They then rated their pain at 0.5, 1, 1.5, and 2 h postdose. The percentages of patients reporting no pain at each time point are shown in the graph. *p < 0.05 compared to PBO, **p < 0.001 compared with PBO