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

Ashina, Messoud; Reuter, Uwe; Smith, Timothy R.; Krikke-Workel, Judith; Klise, Suzanne; Bragg, Sonja M; Doty, Erin G; Dowsett, Sherie A.; Lin, Qun; Krege, John H.

doi:10.1177/0333102421989232

Cited by 47 publications

(103 citation statements)

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“…Lasmiditan is a selective serotonin (5-HT 1F ) receptor agonist (ditan), approved in the US [1] and the United Arab Emirates for the acute treatment of migraine with or without aura in adults and being investigated in other geographies. In Phase 3 studies, lasmiditan was effective in the treatment of a migraine attack, as measured by pain freedom, pain relief, most bothersome symptom (MBS) freedom at 2 h, [2][3][4] and demonstrated a consistent response across attacks [4]. Common treatment emergent adverse events (TEAEs) were dizziness, paresthesia, somnolence, fatigue, nausea, muscular weakness, and hypoesthesia [4,5].…”

Section: Introductionmentioning

confidence: 99%

“…In Phase 3 studies, lasmiditan was effective in the treatment of a migraine attack, as measured by pain freedom, pain relief, most bothersome symptom (MBS) freedom at 2 h, [2][3][4] and demonstrated a consistent response across attacks [4]. Common treatment emergent adverse events (TEAEs) were dizziness, paresthesia, somnolence, fatigue, nausea, muscular weakness, and hypoesthesia [4,5].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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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

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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“…[20][21][22] The CENTURION study demonstrated the consistency in efficacy and safety of lasmiditan treatment across multiple migraine attacks. 23…”

Section: Clinical Trialsmentioning

confidence: 99%

“…A summary of study design and endpoints is found in Ashina and colleagues. 23 The duration of the study was the treatment of 4 migraine attacks or 4 months, whichever occurred sooner. Patients were directed to treat their migraine within 4 hours of an attack of moderate to severe intensity and not repeat a dose until more than 48 hours after treatment of an attack to evaluate sustained pain freedom.…”

Section: Centurionmentioning

confidence: 99%

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Lasmiditan: Acute Migraine Treatment Without Vasoconstriction. A Review

Beauchene

Levien

2021

Journal of Pharmacy Technology

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Objective: To review the efficacy and safety of the newly Food and Drug Administration approved drug lasmiditan, and its place in therapy in the treatment of acute migraine attacks. Data Sources: A literature search of Web of Science, PubMed, and Google Scholar was preformed (September 1999 to May 2021) using the following search terms: acute migraine treatment, triptans, lasmiditan, Reyvow, Rimegepant, Nurtec, Ubrogepant, Ubrelvy, migraine, vasoconstriction, and cardiovascular risk. Product labeling, https://www.clinicaltriasl.gov , and product monographs were also reviewed. Study Selection and Data Extraction: Relevant English-language studies were considered. Data Synthesis: Lasmiditan is the first in its class approved for acute migraine treatment. Lasmiditan exerts its therapeutic effect through agonism at the 5-HT1F receptor, which has been shown to produce no vasoconstriction in preclinical models. Relevance to Patient Care and Clinical Practice: It is both scientifically and clinically relevant to review lasmiditan and determine the value of an acute migraine drug that does not induce vasoconstriction. Patients with preexisting cardiovascular conditions for which current migraine therapy is contraindicated may benefit from therapeutic use of lasmiditan. However, the potential cardiovascular benefit needs to be weighed against the increased central nervous system risks observed with lasmiditan. Conclusions: Lasmiditan is an oral tablet drug that is used for acute migraine abortive treatment and data suggest that it does not induce vasoconstriction, a common side effect often observed with the current first-line abortive migraine treatment drug class, triptans. This is especially important in acute migraine patients with cardiovascular risk factors in which triptan use is contraindicated.

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Acute Treatments for Episodic Migraine in Adults

VanderPluym

Singh

Urtecho

et al. 2021

JAMA

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IMPORTANCEMigraine is common and can be associated with significant morbidity, and several treatment options exist for acute therapy.OBJECTIVE To evaluate the benefits and harms associated with acute treatments for episodic migraine in adults.DATA SOURCES Multiple databases from database inception to February 24, 2021.STUDY SELECTION Randomized clinical trials and systematic reviews that assessed effectiveness or harms of acute therapy for migraine attacks.DATA EXTRACTION AND SYNTHESIS Independent reviewers selected studies and extracted data. Meta-analysis was performed with the DerSimonian-Laird random-effects model with Hartung-Knapp-Sidik-Jonkman variance correction or by using a fixed-effect model based on the Mantel-Haenszel method if the number of studies was small. MAIN OUTCOMES AND MEASURESThe main outcomes included pain freedom, pain relief, sustained pain freedom, sustained pain relief, and adverse events. The strength of evidence (SOE) was graded with the Agency for Healthcare Research and Quality Methods Guide for Effectiveness and Comparative Effectiveness Reviews.FINDINGS Evidence on triptans and nonsteroidal anti-inflammatory drugs was summarized from 15 systematic reviews. For other interventions, 115 randomized clinical trials with 28 803 patients were included. Compared with placebo, triptans and nonsteroidal anti-inflammatory drugs used individually were significantly associated with reduced pain at 2 hours and 1 day (moderate to high SOE) and increased risk of mild and transient adverse events. Compared with placebo, calcitonin gene-related peptide receptor antagonists (low to high SOE), lasmiditan (5-HT 1F receptor agonist; high SOE), dihydroergotamine (moderate to high SOE), ergotamine plus caffeine (moderate SOE), acetaminophen (moderate SOE), antiemetics (low SOE), butorphanol (low SOE), and tramadol in combination with acetaminophen (low SOE) were significantly associated with pain reduction and increase in mild adverse events. The findings for opioids were based on low or insufficient SOE. Several nonpharmacologic treatments were significantly associated with improved pain, including remote electrical neuromodulation (moderate SOE), transcranial magnetic stimulation (low SOE), external trigeminal nerve stimulation (low SOE), and noninvasive vagus nerve stimulation (moderate SOE). No significant difference in adverse events was found between nonpharmacologic treatments and sham.CONCLUSIONS AND RELEVANCE There are several acute treatments for migraine, with varying strength of supporting evidence. Use of triptans, nonsteroidal anti-inflammatory drugs, acetaminophen, dihydroergotamine, calcitonin gene-related peptide antagonists, lasmiditan, and some nonpharmacologic treatments was associated with improved pain and function. The evidence for many other interventions, including opioids, was limited.

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

Cited by 47 publications

References 14 publications

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

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

Lasmiditan: Acute Migraine Treatment Without Vasoconstriction. A Review

Acute Treatments for Episodic Migraine in Adults

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