by A. Laine Green, MSc, MD, FRCPC, FAHS

Triptans have long been used for the acute treatment of migraine. They are primarily serotonin 5HT1B, D receptor agonists. The 5HT1B effects can cause vasoconstriction. This potentially limits their use in patients with vascular disease. Acute treatments that can be used in this population (and the greater migraine population) would be useful. Lasmiditan is a serotonin (5-HT)1F receptor agonist. It does not have known vasoconstrictive properties. Lasmiditan has been FDA approved for the acute treatment of migraine based on the results of the SAMURI and SPARTAN phase 3 clinical trials. It is approved at 3 doses: 50, 100, and 200 mg. In these trials patients took one dose of Lasmiditan and recorded the effects and side effects. There is little data to know how taking multiple doses affects safety, tolerability, pharmacokinetic, and potential drug-drug interactions. This phase one study starts to add to the body of knowledge. In this phase one randomized, double-blind, placebo-controlled study on healthy adults (aged 20–63 years) 2 cohorts of patients received either 200 mg of Lasmiditan (or placebo) or 400 mg of Lasmiditan (or placebo) daily for 7 days. The cohort that received the 200 mg dose also received a combination of caffeine, midazolam, and tolubutamide on Day -3 and Day 7of Lasmiditan dosing. These latter 3 agents were used as they are metabolized by the CYP pathways and it was desired to know if Lasmiditan affected the metabolism of drugs metabolized by CYP pathways. As expected Lasmiditan peaks at 2 hrs and has a half life of 4 hrs. There was negligible concentration at 24 hrs. Dosing on subsequent days did not show a change in the pharmacokinetic profile indicating no accumulation of Lasmiditan when taken on consecutive days. Lasmiditan also did not affect the metabolism of caffeine, midazolam, and tolubutamide indicating, at least for these drugs, no effect on CYP pathways. Safety was reassuringly consistent with the previous clinical trials with dizziness being the most common side effects. One subject stopped due to a nodal heart rhythm. This was in the 400 mg cohort.

This study adds to the body of knowledge that Lasmiditan likely does not accumulate in the body with successive dosing. This is important because it is possible that in real life patients may need to take their acute treatment on multiple successive days. It is also preliminarily encouraging that Lasmiditan may not affect medications metabolized by CYP pathways. It should be noted that all the authors were employees and stock holders of Eli Lilly the makers of Lasmiditan which could introduce bias.

 

---

References:

• Phase 3 Studies (SAMURAI, SPARTAN) of Lasmiditan Compared to Placebo for Acute Treatment of Migraine (S50.008) inda A. Wietecha, Bernice Kuca, Josephine Asafu-Adjei, Sheena K. Aurora Neurology Apr 2018, 90 (15 Supplement) S50.008