Safety findings from CENTURION, a phase 3 consistency study of lasmiditan for the acute treatment of migraine

Abstract

Background: Lasmiditan (LTN) is a selective 5-HT1F receptor agonist for the acute treatment of migraine in adults. We present detailed safety findings from the placebo-controlled, double-blind Phase 3 study, of LTN treatment across 4 attacks (CENTURION).

Methods: Patients were randomized 1:1:1 to LTN 200 mg (LTN200), LTN100, or a control group that received placebo for 3 attacks and LTN50 for either the 3rd or 4th attack (1:1). Safety analyses were conducted for patients who took ≥1 dose of study drug and, in some cases, those who took all 4 doses.

Results: Overall, 1471 patients treated 4494 attacks. The incidences of treatment-emergent serious adverse events (SAEs) were - placebo, n=2 (0.4 %); LTN100, n=1 (0.2 %); LTN200, n=2 (0.4 %); no specific treatment-emergent SAE was reported in more than one patient. The most common treatment emergent adverse events (TEAEs) with lasmiditan were dizziness, paresthesia, fatigue, nausea, vertigo, and somnolence; the vast majority were mild or moderate in severity. The incidences of these TEAEs were highest during the first attack and decreased during subsequent attacks. For patients who experienced a common TEAE with the first attack, less than 45 % experienced the same event in subsequent attacks. Patients who did not experience an event in the 1st attack infrequently experienced the same event in subsequent attacks. The time of onset of the common TEAE ranged from ~40 min to 1 h (dependent upon TEAE) and, for individual TEAE, the onset was similar across attacks. Duration was dependent upon TEAE and attack. It was shortest for paresthesia (< 2 h for all attacks); it ranged from 1.8 to 5.5 h for other common TEAEs and was generally similar across attacks. Serotonin syndrome was reported for 2 patients post LTN dosing; there were no meaningful differences across treatment groups in suicidality; there was no evidence of an increase in motor vehicle accidents.

Conclusion: In this blinded, controlled, multiple-attack study, LTN was associated with generally mild or moderate CNS-related TEAEs of short duration. TEAEs tended to decrease in frequency across the 4 attacks.

Trial registration: NCT03670810.

Keywords: Adverse events; Clinical trial; Consistency; Lasmiditan; Migraine; Multiple attacks; Safety.

Conflict of interest statement

CT has received fees for advisory boards or scientific lecturing from Allergan/Abbvie, Eli Lilly and Company, Novartis, and TEVA; and institutional payments for clinical trials from Allergan/Abbvie, Eli Lilly and Company, Novartis, and TEVA. SB, JHK, EGD, PAA, DR, SAD are full time employees and minor stockholders at Eli Lilly and Company. Within the prior 24 months, TS has consulted with Alder, Allergan, Amgen, Biohaven, Click Therapeutics, Eli Lilly and Company, Equinox, Ipsen, Lundbeck, Novartis, Tonix, Weber and Weber, and XoC; received research grants from Amgen; and has stock options with Aural Analytics and Nocira.

© 2021. The Author(s).

Figures

Fig. 1

Incidence of dizziness with lasmiditan across attacks in patients who treated 4 attacks

Fig. 2

Severity of common TEAEs (Attack 1)

Fig. 3

Severity of dizziness by attack in patients who treated ≥ 1 attack