PDF: Lasmiditan for acute migraine
(2019)Objective
To confirm the efficacy and safety of three doses of oral lasmiditan (200 mg, 100 mg, and 50 mg) versus placebo for the acute treatment of a single migraine attack in patients with migraine, including those with a cardiovascular medical history.
Study Summary
• A significantly higher proportion of patients treated with lasmiditan were headache pain-free and most bothersome symptom-free at 2 hours post-dose compared to placebo.
Intervention
Patients received a single oral dose of lasmiditan (200 mg, 100 mg, or 50 mg) or placebo within 4 hours of onset of a moderate-to-severe migraine attack. A second dose was permitted for rescue or recurrence between 2 and 24 hours after the initial dose.
Inclusion Criteria
Adults >=18 years with a history of disabling migraine (with or without aura), a MIDAS score >=11, onset before age 50, and 3-8 migraine attacks per month.
Study Design
Arms: Lasmiditan 200 mg vs. Lasmiditan 100 mg vs. Lasmiditan 50 mg vs. Placebo
Patients per Arm: Lasmiditan 200 mg: 528; Lasmiditan 100 mg: 532; Lasmiditan 50 mg: 556; Placebo: 540 (in the primary analysis set)
Outcome
Bottom Line
Lasmiditan at all doses (200 mg, 100 mg, and 50 mg) was effective and relatively well-tolerated for the acute treatment of a single migraine attack. A significantly higher proportion of patients treated with lasmiditan were headache pain-free and most bothersome symptom-free at 2 hours post-dose compared to placebo.
Major Points
- The study was a prospective, randomized, double-blind, placebo-controlled, multicenter phase 3 trial.
- Patients were randomized in a 1:1:1:1 ratio to receive oral lasmiditan (200 mg, 100 mg, 50 mg) or placebo.
- The primary efficacy objectives were to assess the proportion of patients who were headache pain-free and most bothersome symptom-free (MBS-free) at 2 hours post-dose.
- A total of 2583 patients were included in the safety population, and 2156 in the full analysis set.
- Lasmiditan was associated with significantly more headache pain freedom and MBS freedom at 2 hours compared to placebo.
- Most adverse events were CNS-related and included dizziness, somnolence, and paraesthesia.
Study Design
- Study Type
- Prospective, randomized, double-blind, placebo-controlled, multicenter phase 3 study
- Randomization
- Yes
- Blinding
- double-blind
- Sample Size
- 3005
- Follow-up
- Up to 11 weeks (up to 8-week treatment period and 1-week end of study visit)
- Centers
- 125
- Countries
- USA, UK, Germany
Primary Outcome
Definition: Proportion of patients who were headache pain-free and most bothersome symptom-free (MBS-free) at 2 hours post-dose.
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| Pain-free: 21.3%; MBS-free: 33.5% | Pain-free: 38.8% (200 mg), 31.4% (100 mg), 28.6% (50 mg); MBS-free: 48.7% (200 mg), 44.2% (100 mg), 40.8% (50 mg) | - (Pain-free: 200 mg: (1.8, 3.1); 100 mg: (1.3, 2.2); 50 mg: (1.1, 1.9). MBS-free: 200 mg: (1.4, 2.4); 100 mg: (1.2, 2.0); 50 mg: (1.1, 1.8)) | Pain-free: 200 mg: <0.001, 100 mg: <0.001, 50 mg: 0.003. MBS-free: 200 mg: <0.001, 100 mg: <0.001, 50 mg: 0.009 |
Limitations & Criticisms
- Because enrolled patients were primarily middle-aged white females, these findings may not extrapolate to other patient populations.
- The study enrolled low numbers of patients with pre-existing cardiovascular disease, and further data are needed to confirm efficacy and safety in this more seriously ill patient population.
- Study findings were limited to primarily a single dose, so safety and tolerability will need to be validated following continued dosing.
- Safety/tolerability parameters were not collected near the time of dosing and may have limited clinical relevance, with the exception of adverse events.
Citation
BRAIN 2019: 142: 1894-1904. doi: 10.1093/brain/awz134