Sustained responses to lasmiditan: Results from post-hoc analyses of two Phase 3 randomized clinical trials for acute treatment of migraine

Abstract

Background: Sustained pain freedom is an important attribute of acute migraine therapies for patients and physicians. Here we report efficacy of the centrally penetrant, highly selective, 5-HT_1F agonist lasmiditan on sustained pain freedom and other outcomes at 24 and 48 hours post-dose.

Study design and methods: Data from the similarly designed, Phase 3, double-blind studies SAMURAI (NCT02439320) and SPARTAN (NCT02605174) were pooled to more precisely estimate efficacy effects in these post-hoc analyses. In both studies, inclusion criteria were 3-8 migraine attacks per month and Migraine Disability Assessment Score of ≥ 11 (at least moderate disability). Patients were randomized equally to lasmiditan 200 mg, 100 mg, 50 mg (50 mg only in SPARTAN), or to placebo. The study drug was to be taken within 4 hours of onset of pain for non-improving headache of at least moderate severity. Sustained pain freedom was defined as being pain free at 2 hours and at the given time point (24 or 48 hours) post-dose without use of additional study drug or migraine medications. Sustained responses were assessed similarly for most bothersome symptom-free, total migraine-free, and disability-free outcomes. For comparisons with previously published data on other acute medications, an additional endpoint of modified sustained pain freedom at 24 hours was defined as being pain free at 2 hours and no moderate-to-severe headache at 24 hours post-dose without use of additional study drug or migraine medications.

Results: Significantly higher proportions of patients treated with lasmiditan versus placebo achieved headache pain freedom at 2 hours post-dose: 200 mg: 35.6%; 100 mg: 29.9%; 50 mg: 28.6%; placebo: 18.3% (all p < 0.001). Sustained pain freedom was significantly higher in patients treated with lasmiditan versus placebo at 24 hours: 200 mg: 21.2%; 100 mg: 16.9%; 50 mg: 17.4%; placebo: 10.3% (all p < 0.01); and at 48 hours: 200 mg: 18.4%; 100 mg: 15.2%; 50 mg: 14.9%; placebo: 9.6% (all p < 0.05). Similar sustained benefits of lasmiditan versus placebo at 24 and 48 hours were noted for most bothersome symptom-free, total migraine-free and disability-free responses. Modified sustained pain freedom at 24 hours was also observed in significantly higher proportions of lasmiditan-treated patients versus placebo: 200 mg: 27.0%; 100 mg: 21.7%; 50 mg: 21.7%; placebo: 12.9% (all p < 0.01).

Conclusion: Sustained responses at 24 and 48 hours were noted in significantly more patients treated with lasmiditan versus placebo for several efficacy outcomes including pain freedom, most bothersome symptom-free, total migraine-free and disability-free responses.

Clinicaltrials.gov identifier numbers: SAMURAI: NCT02439320; SPARTAN: NCT02605174.

Keywords: Lasmiditan; migraine; pain freedom; pain relief; sustained response.

Figure 1.

Proportions of patients in mITT population experiencing sustained pain freedom at 24 and 48 hours, following the first dose of placebo, lasmiditan 50 mg, 100 mg or 200 mg. from post-hoc analyses of SAMURAI and SPARTAN studies. Denominators for calculating percentages are the counts of patients experiencing mild, moderate or severe headache pain at baseline: Placebo: n = 1063; LTN 50 mg: n = 556; LTN 100 mg: n = 1035; LTN 200 mg: n = 1046. Patients in SAMURAI did not take LTN 50 mg. *p < 0.05, **p < 0.01 and ***p < 0.001, for comparisons versus placebo. Confidence interval ranges are provided for odds ratio within parentheses. LTN: lasmiditan; OR: odds ratio.

Figure 2.

Proportions of patients in mITT population experiencing sustained most bothersome symptom freedom at 24 and 48 hours, following the first dose of lasmiditan 50 mg, 100 mg, 200 mg or placebo. From a post-hoc analyses of SAMURAI and SPARTAN studies. Denominators for calculating percentages are the counts of patients who recorded their most bothersome symptom at baseline: Placebo: n = 1002; LTN 50 mg: n = 512; LTN 100 mg: n = 969; LTN 200 mg: n = 964. Patients in SAMURAI did not take LTN 50 mg. *p < 0.05, **p < 0.01 and ***p < 0.001, for comparisons versus placebo. Confidence interval ranges are provided for odds ratio within parentheses. LTN: lasmiditan; MBS: most bothersome symptom; OR: odds ratio.

Figure 3.

Side-by-side comparison of modified sustained pain freedom at 24 hours (ITT population) and sustained pain freedom at 24 hours (mITT population) from post-hoc analyses of SAMURAI and SPARTAN studies. For modified sustained pain-free response, patients had to be pain free at 2 hours, have no/mild pain at 24 hours and should not have used acute medications in between; patients with missing data at 24 hours were excluded from analysis. For the sustained pain-free response, patients had to be pain free at 2 and 24 hours, and should not have used acute medications in between; patients with missing data at 24 hours were assumed to not be pain free at 24 hours. Denominators (n) for calculating percentages in both analyses are counts of patients experiencing pain of any severity at baseline. ***p < 0.001, **p < 0.01, for comparisons versus placebo. Confidence interval ranges are provided for odds ratio within parentheses. LTN: lasmiditan; OR: odds ratio.