Effect of a rescue or recurrence dose of lasmiditan on efficacy and safety in the acute treatment of migraine: findings from the phase 3 trials (SAMURAI and SPARTAN)

Li Shen Loo, Brian M Plato, Ira M Turner, Michael G Case, Joel Raskin, Sherie A Dowsett, John H Krege, Li Shen Loo, Brian M Plato, Ira M Turner, Michael G Case, Joel Raskin, Sherie A Dowsett, John H Krege

Abstract

Background: We studied the efficacy and safety of a second dose of lasmiditan for acute treatment of migraine.

Methods: SAMURAI and SPARTAN were double-blind, placebo-controlled Phase 3 studies in which individuals with migraine were randomized to oral lasmiditan 50 mg (SPARTAN only), 100 mg, 200 mg, or placebo. Study drug was to be taken within 4 h (h) of onset of a migraine attack (moderate or severe pain). A second dose of study drug was provided for rescue (patient not pain-free at 2 h and took a second dose 2-24 h post-first dose) or recurrence (patient pain-free at 2 h, but experienced recurrence of mild, moderate, or severe migraine pain and took a second dose 2-24 h after first dose). Randomization to second dose occurred at baseline; patients originally assigned lasmiditan were randomized to the same lasmiditan dose or placebo (2:1 ratio), and those originally assigned placebo received placebo. Data from SAMURAI and SPARTAN were pooled for efficacy and safety assessment of a second dose of lasmiditan.

Results: The proportion of patients taking a second dose was lower with lasmiditan versus placebo, and decreased with increasing lasmiditan dose; the majority who took a second dose did so for rescue. In patients taking lasmiditan as first dose, outcomes (pain free, most bothersome symptom [MBS] free) at 2 h after a second dose for rescue were similar whether the second dose was lasmiditan or placebo (p > 0.05 in all cases). In patients taking lasmiditan for first dose, outcomes at 2 h after a second dose for recurrence were as follows: lasmiditan pooled versus placebo - pain free, 50% vs 32% (p > 0.05); MBS free, 71% vs 41% (p = 0.02); pain relief, 77% vs 52% (p = 0.03). In patients whose first dose was lasmiditan, the incidence of treatment emergent adverse events (TEAEs) reported after the second dose was similar whether second dose was lasmiditan or placebo.

Conclusions: A second dose of lasmiditan showed some evidence of efficacy when taken for headache recurrence. There was no clear benefit of a second dose of lasmiditan for rescue treatment. The incidences of TEAEs were similar whether the second dose was lasmiditan or placebo.

Trial registration: SAMURAI ( NCT02439320 ) [April 2015]. SPARTAN ( NCT02605174 ) [May 2016].

Keywords: Lasmiditan; Phase 3; Recurrence; Rescue; Second dose.

Conflict of interest statement

LSL, MGC, RJ, SAD and JHK are full time employees and minor stockholders at Eli Lilly and Company.

BMP reports no competing interests.

IMT has served as investigator, as consultant, as speaker and on advisory boards of companies manufacturing branded migraine products.

Figures

Fig. 1
Fig. 1
Time from first dose to second dose of study drug for a patients who were not pain free at 2 h and took a second dose of study drug or other migraine medication for rescue and b patients who were pain free at 2 h and took a second dose of study drug or other migraine medication for recurrence
Fig. 2
Fig. 2
Outcomes at 2 h after second dose of study drug for the recurrence population

References

    1. Dodick DW, Lipsy R. Advances in migraine management: implications for managed care organizations. Manag Care. 2004;13:45–51.
    1. Tepper S, Tepper D. How do I do it reference for the acute treatment of migraine. Am Headache Soc. 2008; .
    1. Cameron C, Kelly S, Hsieh SC, Murphy M, Chen L, Kotb A, et al. Triptans in the acute treatment of migraine: a systematic review and network meta-analysis. Headache. 2015;55:221–235. doi: 10.1111/head.12601.
    1. Ferrari MD, Roon KI, Lipton RB, Goadsby PJ. Oral triptans (serotonin 5-HT1B/1D agonists) in acute migraine treatment: a meta-analysis of 53 trials. Lancet. 2001;358:1668–1675. doi: 10.1016/S0140-6736(01)06711-3.
    1. Vila-Pueyo M. Targeted 5-HT1F therapies for migraine. Neurotherapeutics. 2018;15:291–303. doi: 10.1007/s13311-018-0615-6.
    1. Kuca B, Silberstein SD, Wietecha L, Berg PH, Dozier G, Lipton RB, et al. Lasmiditan is an effective acute treatment for migraine: a phase 3 randomized study. Neurology. 2018;91:e2222–e2e32. doi: 10.1212/WNL.0000000000006641.
    1. Goadsby PJLL, Dennehy EB, Kuca B, Case MG, Aurora SK, Gaul C. Phase 3 randomized, placebo-controlled, double-blind study of lasmiditan for acute treatment of migraine. Brain. 2019;142:1894–1904. doi: 10.1093/brain/awz134.
    1. CTAD 2017 – Highlights, November 1-2 . Clinical Trials in Alzheimer’s Disease. 2017.
    1. Diener Hans-Christoph, Tassorelli Cristina, Dodick David W, Silberstein Stephen D, Lipton Richard B, Ashina Messoud, Becker Werner J, Ferrari Michel D, Goadsby Peter J, Pozo-Rosich Patricia, Wang Shuu-Jiun, Mandrekar Jay. Guidelines of the International Headache Society for controlled trials of acute treatment of migraine attacks in adults: Fourth edition. Cephalalgia. 2019;39(6):687–710. doi: 10.1177/0333102419828967.
    1. Diamond ML, Hettiarachchi J, Hilliard B, Sands G, Nett R. Effectiveness of eletriptan in acute migraine: primary care for Excedrin nonresponders. Headache. 2004;44:209–216. doi: 10.1111/j.1526-4610.2004.04049.x.
    1. Scott RJ, Aitchison WRC, Barker PR, McLaren GI. Oral sumatriptan in the acute treatment of migraine and migraine recurrence in general practice. QJM. 1996;89:613–622. doi: 10.1093/qjmed/89.8.613.
    1. Teall J, Tuchman M, Cutler N, Gross M, Willoughby E, Smith B, et al. Rizatriptan (MAXALT) for the acute treatment of migraine and migraine recurrence. A placebo-controlled, outpatient study. Rizatriptan 022 study group. Headache. 1998;38:281–287. doi: 10.1046/j.1526-4610.1998.3804281.x.
    1. Ferrari MD, James MH, Bates D, Pilgrim A, Ashford E, Anderson BA, et al. Oral sumatriptan: effect of a second dose, and incidence and treatment of headache recurrences. Cephalalgia. 1994;14:330–338. doi: 10.1046/j.1468-2982.1994.1405330.x.
    1. Pfaffenrath V, Cunin G, Sjonell G, Prendergast S. Efficacy and safety of sumatriptan tablets (25 mg, 50 mg, and 100 mg) in the acute treatment of migraine: defining the optimum doses of oral sumatriptan. Headache. 1998;38:184–190. doi: 10.1046/j.1526-4610.1998.3803184.x.
    1. Loo L, Plato BM, Turner IM, Case MG, Raskin J, Dowsett SA, Krege JH. Effect of a rescue or recurrence dose of lasmiditan on efficacy and safety in the acute treatment of migraine: findings from the phase 3 trials (SUMURAI and SPARTAN) Headache. 2019;59(S1):94. doi: 10.1111/head.13549.

Source: PubMed

Sponsorzy i współpracownicy

Warunki medyczne

Interwencje lekowe

3
Subskrybuj