NCT02565186: GLADIATOR

An Open-label, Long-term, Safety Study of Lasmiditan for the Acute Treatment of Migraine

Completed Phase 3 Results posted Last updated 25 August 2020

What this trial tests

Phase 3 trial testing Lasmiditan in Migraine Disorders in 2,171 participants. Completed in 20 August 2019.

Timeline

7 October 2015

Primary endpoint
20 August 2019

20 August 2019

Quick facts

Lead sponsor	Eli Lilly and Company
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	2,171
Start date	7 October 2015
Primary completion	20 August 2019
Estimated completion	20 August 2019
Sites	196 locations across United Kingdom, United States, Germany

Drugs / interventions tested

• Lasmiditan (LASMIDITAN) — full drug profile →

Conditions studied

• Migraine Disorders — all drugs for Migraine Disorders →

Sponsor

Eli Lilly and Company — full company profile →

Who can join

18 and older, any sex, with Migraine Disorders. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants With at Least 1 Treatment Emergent Adverse Event Primary · Up to 12 months

An AE with an onset on or within 48 hours after a dose of study drug, or an event that worsened in intensity within 48 hours of a dose of study drug was considered a treatment-emergent adverse event (TEAE). A summary of serious adverse events (SAEs) and other non-serious adverse events (AEs), regardless of causality, were reported in the Reported Adverse Events module.

Group	Value	95% CI
Lasmiditan 100mg	447
Lasmiditan 200mg	545

Percentage of Migraine Attacks With Pain Freedom (PF) at 2 Hours After Dose Secondary · Up to 12 months

Pain freedom is defined as a reduction in headache severity from mild (1), moderate (2), or severe (3) at baseline to none (0).

Group	Value	95% CI
Lasmiditan 100mg	26.7
Lasmiditan 200mg	32.2

Percentage of Migraine Attacks With Most Bothersome Symptom-Free (MBS) at 2 Hours After Dose Secondary · Up to 12 months

MBS-free, defined as the absence of the associated symptom of migraine (nausea, phonophobia, and/or photophobia) at 2 hours postdose that was identified predose as the most bothersome symptom.

Group	Value	95% CI
Lasmiditan 100mg	37.2
Lasmiditan 200mg	40.8

Percentage of Participants With Medical Resource Utilization Secondary · Up to 12 months

Medical Resource utilization for any cardiovascular (CV) events and/or related resource utilization, such as visits to cardiologists, procedures, hospitalizations, new treatments or treatment adjustments for CV disease and any visits to an emergency room (ER) or physician's office for treatment of migraine was reported.

Visit to cardiologist

Group	Value	95% CI
Lasmiditan 100mg	0.6
Lasmiditan 200mg	0.6

Visit to primary care

Group	Value	95% CI
Lasmiditan 100mg	0.8
Lasmiditan 200mg	0.9

Visit to Other providers

Group	Value	95% CI
Lasmiditan 100mg	0.1
Lasmiditan 200mg	0.2

Hospitalized

Group	Value	95% CI
Lasmiditan 100mg	0.5
Lasmiditan 200mg	0.2

Procedures performed

Group	Value	95% CI
Lasmiditan 100mg	0.8
Lasmiditan 200mg	0.6

ER visits or visits to Physicians Office

Group	Value	95% CI
Lasmiditan 100mg	2.6
Lasmiditan 200mg	2.6

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to 12 Months. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Lasmiditan 100mg

Serious: 29/991 (3%)

Deaths: 0/991

Lasmiditan 200mg

Serious: 36/1039 (3%)

Deaths: 0/1039

Serious adverse events (66 terms)

Reaction	System	Lasmiditan 100mg	Lasmiditan 200mg
Abortion spontaneous	Pregnancy, puerperium and perinatal conditions	—	—
Hypertension	Vascular disorders	—	—
Gastritis	Gastrointestinal disorders	—	—
Hiatus hernia	Gastrointestinal disorders	—	—
Small intestinal obstruction	Gastrointestinal disorders	—	—
Non-cardiac chest pain	General disorders	—	—
Cellulitis	Infections and infestations	—	—
Pneumonia	Infections and infestations	—	—
Intentional overdose	Injury, poisoning and procedural complications	—	—
Nephrolithiasis	Renal and urinary disorders	—	—
Angina pectoris	Cardiac disorders	—	—
Atrial fibrillation	Cardiac disorders	—	—
Atrial flutter	Cardiac disorders	—	—
Bradycardia	Cardiac disorders	—	—
Sinus node dysfunction	Cardiac disorders	—	—
Stress cardiomyopathy	Cardiac disorders	—	—
Gastrointestinal haemorrhage	Gastrointestinal disorders	—	—
Obstructive pancreatitis	Gastrointestinal disorders	—	—
Cholecystitis	Hepatobiliary disorders	—	—
Cholecystitis acute	Hepatobiliary disorders	—	—
Cholelithiasis	Hepatobiliary disorders	—	—
Gallbladder disorder	Hepatobiliary disorders	—	—
Abscess limb	Infections and infestations	—	—
Appendicitis perforated	Infections and infestations	—	—
Bronchitis	Infections and infestations	—	—

Other adverse events (296 terms — click to expand)

Reaction	System	Lasmiditan 100mg	Lasmiditan 200mg
Dizziness	Nervous system disorders	—	—
Somnolence	Nervous system disorders	—	—
Paraesthesia	Nervous system disorders	—	—
Fatigue	General disorders	—	—
Nausea	Gastrointestinal disorders	—	—
Vertigo	Ear and labyrinth disorders	—	—
Asthenia	General disorders	—	—
Hypoaesthesia	Nervous system disorders	—	—
Lethargy	Nervous system disorders	—	—
Balance disorder	Nervous system disorders	—	—
Vomiting	Gastrointestinal disorders	—	—
Muscular weakness	Musculoskeletal and connective tissue disorders	—	—
Tremor	Nervous system disorders	—	—
Euphoric mood	Psychiatric disorders	—	—
Diarrhoea	Gastrointestinal disorders	—	—
Upper respiratory tract infection	Infections and infestations	—	—
Nasopharyngitis	Infections and infestations	—	—
Limb discomfort	Musculoskeletal and connective tissue disorders	—	—
Migraine	Nervous system disorders	—	—
Anxiety	Psychiatric disorders	—	—
Visual impairment	Eye disorders	—	—
Feeling abnormal	General disorders	—	—
Sinusitis	Infections and infestations	—	—
Disorientation	Psychiatric disorders	—	—
Feeling jittery	General disorders	—	—
Muscle twitching	Musculoskeletal and connective tissue disorders	—	—
Ataxia	Nervous system disorders	—	—
Insomnia	Psychiatric disorders	—	—
Vision blurred	Eye disorders	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—
Muscle spasms	Musculoskeletal and connective tissue disorders	—	—
Disturbance in attention	Nervous system disorders	—	—
Abnormal dreams	Psychiatric disorders	—	—
Restlessness	Psychiatric disorders	—	—
Palpitations	Cardiac disorders	—	—
Photopsia	Eye disorders	—	—
Abdominal discomfort	Gastrointestinal disorders	—	—
Urinary tract infection	Infections and infestations	—	—
Head discomfort	Nervous system disorders	—	—
Headache	Nervous system disorders	—	—

Most-reported serious reactions: Abortion spontaneous, Hypertension, Gastritis, Hiatus hernia, Small intestinal obstruction, Non-cardiac chest pain, Cellulitis, Pneumonia.

Data from ClinicalTrials.gov NCT02565186 adverse events section.

Sponsor's own description

This is a prospective, randomized, open-label study in subjects with migraine who have completed the Phase 3 studies, COL MIG 301/LAHJ (NCT02439320) or COL MIG-302/LAHK (NCT02605174) or for a subset of lasmiditan-naïve subjects with migraine. The study is designed to evaluate the safety and tolerability of long-term intermittent use of lasmiditan 100 mg and of lasmiditan 200 mg, as the first dose and as a second dose, for the acute treatment of migraine. Long term efficacy will also be evaluated.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Phase 3 randomized, placebo-controlled, double-blind study of lasmiditan for acute treatment of migraine.
   Goadsby PJ, Wietecha LA, Dennehy EB, Kuca B, et al · · 2019 · cited 161× · PMID 31132795 · DOI 10.1093/brain/awz134
2. Therapeutic novelties in migraine: new drugs, new hope?
   Do TP, Guo S, Ashina M. · · 2019 · cited 79× · PMID 30995909 · DOI 10.1186/s10194-019-0974-3
3. Lasmiditan for acute treatment of migraine in patients with cardiovascular risk factors: post-hoc analysis of pooled results from 2 randomized, double-blind, placebo-controlled, phase 3 trials.
   Shapiro RE, Hochstetler HM, Dennehy EB, Khanna R, et al · · 2019 · cited 64× · PMID 31464581 · DOI 10.1186/s10194-019-1044-6
4. Interim results of a prospective, randomized, open-label, Phase 3 study of the long-term safety and efficacy of lasmiditan for acute treatment of migraine (the GLADIATOR study).
   Brandes JL, Klise S, Krege JH, Case M, et al · · 2019 · cited 60× · PMID 31433669 · DOI 10.1177/0333102419864132
5. Serotonin receptor agonists in the acute treatment of migraine: a review on their therapeutic potential.
   Negro A, Koverech A, Martelletti P. · · 2018 · cited 57× · PMID 29563831 · DOI 10.2147/jpr.s132833
6. Trajectory of migraine-related disability following long-term treatment with lasmiditan: results of the GLADIATOR study.
   Lipton RB, Lombard L, Ruff DD, Krege JH, et al · · 2020 · cited 26× · PMID 32093628 · DOI 10.1186/s10194-020-01088-4
7. Lasmiditan for the treatment of acute migraine: a review and potential role in clinical practice.
   Oswald JC, Schuster NM. · · 2018 · cited 23× · PMID 30323656 · DOI 10.2147/jpr.s152216
8. CGRP Receptor Antagonists and 5-HT1F Receptor Agonist in the Treatment of Migraine.
   Capi M, De Angelis V, De Bernardini D, De Luca O, et al · · 2021 · cited 19× · PMID 33916043 · DOI 10.3390/jcm10071429