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

Messoud Ashina, Raghavendra Vasudeva, Leah Jin, Louise Lombard, Elizabeth Gray, Erin G Doty, Laura Yunes-Medina, Kraig S Kinchen, Cristina Tassorelli, Messoud Ashina, Raghavendra Vasudeva, Leah Jin, Louise Lombard, Elizabeth Gray, Erin G Doty, Laura Yunes-Medina, Kraig S Kinchen, Cristina Tassorelli

Abstract

Objective: To expand on available information on the efficacy of oral lasmiditan for the acute treatment of migraine with particular focus on the timing of the effect and on its impact on migraine-associated symptoms.

Background: Lasmiditan is a novel selective 5-hydroxytryptamine 1F receptor agonist that lacks vasoconstrictive activity. In 2 phase 3 studies, SAMURAI and SPARTAN, lasmiditan met primary and key secondary efficacy endpoints at 2 hours following initial dose.

Methods: Integrated analyses were completed from 2 phase 3 clinical trials, SPARTAN and SAMURAI. Baseline data and data collected every 30 minutes up to 2 hours after taking lasmiditan (50, 100, or 200 mg) or placebo were analyzed to determine the onset of efficacy. A total of 5236 patients were randomized to be treated with placebo (N = 1493), lasmiditan 50 mg (N = 750), lasmiditan 100 mg (N = 1498), or lasmiditan 200 mg (N = 1495). Data were analyzed to determine the onset of improvement for the following efficacy measures: pain freedom, most bothersome symptom freedom, pain relief, freedom from associated individual symptoms (photophobia, phonophobia, or nausea), total migraine freedom (defined as pain freedom and freedom from associated symptoms), and freedom from migraine-related functional disability. Time to meaningful headache relief and time to first become pain free were also analyzed.

Results: Significantly higher rates of pain freedom (100 mg, 10.0%, P = .012; 200 mg, 15.5%, P < .001; Placebo, 7.0%) and total migraine freedom (100 mg, 8.9%, P = .017; 200 mg, 12.4%, P < .001; Placebo, 6.1%) were achieved starting at 60 minutes in 100- and 200-mg lasmiditan-treated groups compared with placebo group. Rates of freedom from most bothersome symptom (100 mg, 11.1%, P = .015; 200 mg, 13.0%, P < .001; Placebo, 7.9%), and pain relief (100 mg, 17.5%, P = .007; 200 mg, 19.1%, P < .001; Placebo, 13.4%) were significantly higher starting as early as 30 minutes in lasmiditan 100- and 200-mg lasmiditan-treated groups. A significantly higher percentage of patients in the 200-mg lasmiditan-treated group achieved freedom from photophobia (13.7%, P = .005; Placebo, 9.2%) and phonophobia (17.4%, P = .042; Placebo, 13.4%) starting at 30 minutes. A significantly greater proportion of patients in the 200-mg lasmiditan-treated group achieved freedom from migraine-related functional disability starting at 60 minutes (16.4%, P < .001; Placebo, 11.1%). All efficacy measures, except for freedom from nausea, were statistically significant after lasmiditan treatment (50, 100, or 200 mg) compared with placebo at 90 and 120 minutes. Finally, patients taking lasmiditan had a higher likelihood of achieving meaningful headache relief and becoming headache pain free within 24 hours compared with those taking placebo (P < .001).

Conclusions: Patients treated with lasmiditan for a migraine attack reported an earlier onset of efficacy compared with those treated with placebo. Some of the efficacy measures such as pain relief demonstrated improvement as early as the first assessment at 30 minutes after 100- or 200-mg lasmiditan treatment.

Trial registration: ClinicalTrials.gov NCT02439320 NCT02605174.

Keywords: acute treatment; ditan class; lasmiditan; migraine; onset of efficacy; onset of response.

© 2019 Eli Lilly and Company. Headache: The Journal of Head and Face Pain published by Wiley Periodicals, Inc. on behalf of American Headache Society.

Figures

Figure 1
Figure 1
Percentage of patients experiencing (A) pain freedom and (B) pain relief. ***P ≤ .001; **P ≤ .01; *P ≤ .05 vs placebo.
Figure 2
Figure 2
Percentage of patients experiencing freedom from (A) photophobia, (B) phonophobia, (C) nausea, and (D) MBS. ***P ≤ .001, **P ≤ .01, *P ≤ .05 vs placebo. MBS = most bothersome symptom (nausea, phonophobia, and/or photophobia) selected by the patient.
Figure 3
Figure 3
Percentage of patients (A) Experiencing total migraine freedom and (B) Freedom from migraine‐related functional disability. ***P ≤ .001, **P ≤ .01, *P ≤ .05 vs placebo.
Figure 4
Figure 4
Time to meaningful headache relief: Cumulative probability of experiencing meaningful headache relief after treatment.
Figure 5
Figure 5
Time to first become headache pain free.

References

    1. Diener HC, Tassorelli C, Dodick DW, et al. Guidelines of the International Headache Society for controlled trials of acute treatment of migraine attacks in adults: Fourth edition. Cephalalgia. 2019;39:687‐710.
    1. Silberstein SD. Practice parameter: Evidence‐based guidelines for migraine headache (an evidence‐based review): Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2000;55:754‐762.
    1. Smelt AF, Louter MA, Kies DA, et al. What do patients consider to be the most important outcomes for effectiveness studies on migraine treatment? Results of a Delphi study. PLoS ONE. 2014;9:e98933.
    1. Davies GM, Santanello N, Lipton R. Determinants of patient satisfaction with migraine therapy. Cephalalgia. 2000;20:554‐560.
    1. Hamelsky SW, Lipton R, Stewart WF. An assessment of the burden of migraine using the willingness to pay model. Cephalalgia. 2005;25:87‐100.
    1. Lipton RB, Hamelsky SW, Dayno JM. What do patients with migraine want from acute migraine treatment? Headache. 2002;42:3‐9.
    1. Mafi JN, Edwards ST, Pedersen NP, et al. Trends in the ambulatory management of headache: Analysis of NAMCS and NHAMCS data 1999‐2010. J Gen Intern Med. 2015;30:548‐555.
    1. Molina KC, Fairman KA, Sclar DA. Concomitant use of opioid medications with triptans or serotonergic antidepressants in US office‐based physician visits. Drug Healthc Patient Saf. 2018;10:37‐43.
    1. Ferrari MD, Goadsby PJ, Roon KI, Lipton RB. Triptans (serotonin, 5‐HT1B/1D agonists) in migraine: Detailed results and methods of a meta‐analysis of 53 trials. Cephalalgia. 2002;22:633‐658.
    1. Dodick D, Lipton RB, Martin V, et al. Consensus statement: Cardiovascular safety profile of triptans (5‐HT agonists) in the acute treatment of migraine. Headache. 2004;44:414‐425.
    1. Neeb L, Reuter U. Lasmiditan for acute migraine treatment. Future Neurol. 2013;8:631‐638.
    1. Capi M, de Andres F, Lionetto L, et al. Lasmiditan for the treatment of migraine. Expert Opin Investig Drugs. 2017;26:227‐234.
    1. Nelson DL, Phebus LA, Johnson KW, et al. Preclinical pharmacological profile of the selective 5‐HT1F receptor agonist lasmiditan. Cephalalgia. 2010;30:1159‐1169.
    1. Ferrari MD, Färkkilä M, Reuter U, et al. Acute treatment of migraine with the selective 5‐HT1F receptor agonist lasmiditan – A randomised proof‐of‐concept trial. Cephalalgia. 2010;10:1170‐1178.
    1. Färkkilä M, Diener HC, Géraud G, et al. Efficacy and tolerability of lasmiditan, an oral 5‐HT1F receptor agonist, for the acute treatment of migraine: A phase 2 randomised, placebo‐controlled, parallel‐group, dose‐ranging study. Lancet Neurol. 2012;11:405‐413.
    1. Kuca B, Silberstein SD, Wietecha L, et al. Lasmiditan is an effective acute treatment for migraine: A Phase 3 randomized study . Neurology. 2018;91:e1‐e11.
    1. Goadsby PJ, Wietecha LA, Dennehy EB, et al. Phase 3 randomized, placebo‐controlled, double‐blind study of lasmiditan for acute treatment of migraine. Brain. 2019;142:1894‐1904.
    1. Krege JH, Rizzoli PB, Liffick E, et al. Safety findings from Phase 3 lasmiditan studies for acute treatment of migraine: Results from SAMURAI and SPARTAN. Cephalalgia. 2019;39:957‐966.
    1. Headache Classification Subcommittee of the International Headache Society . The International Classification of Headache Disorders: 2nd edition. Cephalalgia. 2004;24(Suppl. 1):9‐160.
    1. Lipton RB, McGinley JS, Shulman KJ, et al. Faster improvement in migraine pain intensity and migraine‐related disability at early time points with AVP‐825 (sumatriptan nasal powder delivery system) versus oral sumatriptan: A comparative randomized clinical trial across multiple attacks from the COMPASS study. Headache. 2017;57:1570‐1582.
    1. Rodgers AJ, Hustad CM, Cady RK, et al. Total migraine freedom, a potential primary endpoint to assess acute treatment in migraine: Comparison to the current FDA requirement using the complete rizatriptan study database. Headache. 2011;51:356‐368.
    1. Pascual J, Falk RM, Piessens F, et al. Consistent effficacy and tolerability of almotriptan in the acute treatment of multiple migraine attacks: Results of a large, randomized, double‐blind, placebo‐controlled study. Cephalalgia. 2000;20:588‐596.
    1. Pascual J, Cabarrocas X. Within‐patient early versus delayed treatment of migraine attacks with almotriptan: The sooner the better. Headache. 2002;42:28‐31.
    1. Chen LC, Ashcroft DM. Meta‐analysis examining the efficacy and safety of almotriptan in the acute treatment of migraine. Headache. 2007;47:1169‐1177.
    1. Sheftell F, Ryan R, Pitman V, et al. Efficacy, safety, and tolerability of oral eletriptan for treatment of acute migraine: A multicenter, double‐blind, placebo‐controlled study conducted in the United States. Headache. 2003;43:202‐213.
    1. Stark R, Dahlöf C, Haughie S, et al. Efficacy, safety and tolerability of oral elitriptan in the acute treatment of migraine: results of a phase III, multicenter, placebo‐controlled study across three attacks. Cephalalgia. 2002;22:23‐32.
    1. Ryan R, Géraud G, Goldstein J, et al. Clinical efficacy of frovatriptan: Placebo‐controlled studies. Headache. 2002;42(Suppl. 2):S84‐S92.
    1. Havanka H, Dahliif C, Pop PHM, et al. Efficacy of naratriptan tablets in the acute treatment of migraine: A dose‐ranging study. Clin Ther. 2000;22:970‐980.
    1. Klassen A, Elkind A, Asgharnejad M, et al. Naratriptan is effective and well tolerated in the acute treatment of migraine. Results of a double‐blind, placebo‐controlled, parallel‐group study. Headache. 1997;37:640‐645.
    1. Ferrari E, Loder E, McCarroll KA, et al. Meta‐analysis of rizatriptan efficacy in randomized controlled clinical trials. Cephalalgia. 2001;21:129‐136.
    1. Pfaffenrath V, Cunin G, Sjonell G, et al. Efficacy and safety of sumatriptan tablets (25, 50, and 100 mg) in the acute treatment of migraine: Defining the optimum doses of oral sumatriptan. Headache. 1998;38:184‐190.
    1. Dowson AJ, MacGregor EA, Purdy RA, et al. Zolmitriptan orally disintegrating tablet is effective in the acute treatment of migraine. Cephalalgia. 2002;22:101‐106.

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