Randomized, controlled trial of lasmiditan over four migraine attacks: Findings from the CENTURION study

Abstract

Background: We present findings from the multicenter, double-blind Phase 3 study, CENTURION. This study was designed to assess the efficacy of and consistency of response to lasmiditan in the acute treatment of migraine across four attacks.

Methods: Patients were randomized 1:1:1 to one of three treatment groups - lasmiditan 200 mg; lasmiditan 100 mg; or a control group that received placebo for three attacks and lasmiditan 50 mg for either the third or fourth attack. The primary endpoints were pain freedom at 2 h (first attack) and pain freedom at 2 h in ≥2/3 attacks. Secondary endpoints included pain relief, sustained pain freedom and disability freedom. Statistical testing used a logistic regression model and graphical methodology to control for multiplicity.

Results: Overall, 1471 patients treated ≥1 migraine attack with the study drug. Both primary endpoints were met for lasmiditan 100 mg and 200 mg (p < 0.001). All gated secondary endpoints were met. The incidence of treatment-emergent adverse events (TEAEs) was highest during the first attack. The most common TEAEs with lasmiditan were dizziness, paresthesia, fatigue, and nausea; these were generally mild or moderate in severity.

Conclusions: These results confirm the early and sustained efficacy of lasmiditan 100 mg and 200 mg and demonstrate consistency of response across multiple attacks.Trial Registration Number: NCT03670810.

Keywords: 5-HT1F receptor agonist; Phase 3; consistency; efficacy; lasmiditan.

Conflict of interest statement

Declaration of conflicting interests: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: JKW, JHK, MA, TS, QL, SRK, SB, EGD, and SAD are full-time employees and minor stockholders at Eli Lilly and Company.

MA is a consultant, speaker or scientific advisor for Allergan, Amgen, Eli Lilly and Company, Lundbeck, Novartis, and Teva, primary investigator for Alder, Allergan, Amgen, Eli Lilly and Company, Lundbeck Novartis and Teva trials; he has no ownership interest and does not own stocks of any pharmaceutical company; he serves as associate editor of Cephalalgia, Headache, and Journal of Headache and Pain; he is the President of the International Headache Society.

TS reports financial relationships with Alder-Lundbeck, Allergan, Amgen, Biohaven, Charleston Labs, Electrocore, Impel, Eli Lilly and Company, Novartis Novo Nordisk, Satsuma, Theranica, United Health Group, and Vorso Technologies.

UR has received speaker fees and honorarium for consulting from Abbvie, Amgen, Allergan, Co-Lucid, Eli Lilly and Company, Lundbeck, Medscape, Novartis, StreaMedUp, and TEVA Pharma; he serves as associated editor of the Journal of Headache and Pain and Frontiers in Neurology and as Board Member of the European Headache Federation.

Figures

Figure 1.

Study design.Abbreviations: LTN, lasmiditan; PBO, placebo; m, monthaVisits at 2 and 3 months applicable where patients had not already treated 4 attacks before these timepoints.bEnd of study visit occurred at ≥7 days after treating the last migraine attack or at 4 months after randomization.

Figure 2.

Flow of patients through study.Abbreviations: AE, adverse event; W/D, withdrawal.aN for “Completed study” includes 78 patients with no final disposition (e.g., no final onsite visit at clinic completed at time of data cut-off due to Covid-19).

Figure 3.

Percentage of patients achieving (a) pain freedom and (b) pain relief after first dose.‡ p

Figure 4.

Time-to-event analysis (a) pain freedom and (b) pain relief after first dose.

Figure 5.

Percentage of patients achieving (a) pain freedom and (b) pain relief after first dose across the four attacks.No formal statistical comparisons. Percentages are shown above bars. For Attacks 3 and 4, patients in the control group received either placebo/lasmiditan 50 mg or lasmiditan 50 mg/placebo. Only placebo data are shown on the figure for Attacks 3 and 4 (lasmiditan 50 mg data is presented in Supplemental Figure 1).