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Safety findings from CENTURION, a phase 3 consistency study of lasmiditan for the acute treatment of migraine
BACKGROUND: Lasmiditan (LTN) is a selective 5-HT(1F) 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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Springer Milan
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8572440/ https://www.ncbi.nlm.nih.gov/pubmed/34742230 http://dx.doi.org/10.1186/s10194-021-01343-2 |
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author | Tassorelli, C Bragg, S Krege, JH Doty, EG Ardayfio, PA Ruff, D Dowsett, SA Schwedt, T |
author_facet | Tassorelli, C Bragg, S Krege, JH Doty, EG Ardayfio, PA Ruff, D Dowsett, SA Schwedt, T |
author_sort | Tassorelli, C |
collection | PubMed |
description | BACKGROUND: Lasmiditan (LTN) is a selective 5-HT(1F) 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 SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s10194-021-01343-2. |
format | Online Article Text |
id | pubmed-8572440 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Springer Milan |
record_format | MEDLINE/PubMed |
spelling | pubmed-85724402021-11-08 Safety findings from CENTURION, a phase 3 consistency study of lasmiditan for the acute treatment of migraine Tassorelli, C Bragg, S Krege, JH Doty, EG Ardayfio, PA Ruff, D Dowsett, SA Schwedt, T J Headache Pain Research Article BACKGROUND: Lasmiditan (LTN) is a selective 5-HT(1F) 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 SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s10194-021-01343-2. Springer Milan 2021-11-06 /pmc/articles/PMC8572440/ /pubmed/34742230 http://dx.doi.org/10.1186/s10194-021-01343-2 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Article Tassorelli, C Bragg, S Krege, JH Doty, EG Ardayfio, PA Ruff, D Dowsett, SA Schwedt, T Safety findings from CENTURION, a phase 3 consistency study of lasmiditan for the acute treatment of migraine |
title | Safety findings from CENTURION, a phase 3 consistency study of lasmiditan for the acute treatment of migraine |
title_full | Safety findings from CENTURION, a phase 3 consistency study of lasmiditan for the acute treatment of migraine |
title_fullStr | Safety findings from CENTURION, a phase 3 consistency study of lasmiditan for the acute treatment of migraine |
title_full_unstemmed | Safety findings from CENTURION, a phase 3 consistency study of lasmiditan for the acute treatment of migraine |
title_short | Safety findings from CENTURION, a phase 3 consistency study of lasmiditan for the acute treatment of migraine |
title_sort | safety findings from centurion, a phase 3 consistency study of lasmiditan for the acute treatment of migraine |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8572440/ https://www.ncbi.nlm.nih.gov/pubmed/34742230 http://dx.doi.org/10.1186/s10194-021-01343-2 |
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