Effect of a rescue or recurrence dose of lasmiditan on efficacy and safety in the acute treatment of migraine: findings from the phase 3 trials (SAMURAI and SPARTAN)

DOI: https://doi.org/10.1186/s12883-019-1420-5

Abstract-Summary We studied the efficacy and safety of a second dose of lasmiditan for acute treatment of migraine.

A second dose of study drug was provided for rescue (patient not pain-free at 2 h and took a second dose 2-24 h post-first dose) or recurrence (patient pain-free at 2 h, but experienced recurrence of mild, moderate, or severe migraine pain and took a second dose 2-24 h after first dose).

The proportion of patients taking a second dose was lower with lasmiditan versus placebo, and decreased with increasing lasmiditan dose; the majority who took a second dose did so for rescue.

In patients taking lasmiditan as first dose, outcomes (pain free, most bothersome symptom [MBS] free) at 2 h after a second dose for rescue were similar whether the second dose was lasmiditan or placebo (p>0.05 in all cases).

In patients taking lasmiditan for first dose, outcomes at 2 h after a second dose for recurrence were as follows: lasmiditan pooled versus placebo - pain free, 50% vs 32% (p > 0.05); MBS free, 71% vs 41% (p = 0.02); pain relief, 77% vs 52% (p = 0.03).

In patients whose first dose was lasmiditan, the incidence of treatment emergent adverse events (TEAEs) reported after the second dose was similar whether second dose was lasmiditan or placebo.

The incidences of TEAEs were similar whether the second dose was lasmiditan

or placebo.

Extended: A second dose was taken 2–24 h after first dose if needed for rescue or

recurrence.

A second dose of lasmiditan showed some evidence of efficacy when taken for

headache recurrence.

The proportion of patients taking a second dose was lower with lasmiditan versus placebo, and the proportion decreased with increasing lasmiditan dose (placebo, 60%; lasmiditan 50 mg, 46%; lasmiditan 100 mg, 43%; lasmiditan 200 mg, 36%).

The proportion of a study population taking rescue medication at 2 h can be a useful secondary efficacy measure, reflecting the patient’s judgement of the efficacy of the investigational drug [121].

The purpose of the current study is to describe the second dose population and the efficacy and safety findings for a second dose of lasmiditan, using data from these 2 phase 3 studies.

Background Two phase 3 single migraine attack studies of lasmiditan, SAMURAI and SPARTAN, have been completed [48, 122].

4.1 Acute Treatment

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In these studies, treatment with lasmiditan (all doses) resulted in a significant increase in the proportion of patients who were headache pain-free (primary end- point) or most bothersome symptom (MBS)-free (key secondary endpoint) at 2 h (p < 0.01 versus placebo in all cases).

The percentages headache pain-free at 2 h for the lasmiditan 200 mg group ver- sus placebo were 32% versus 15% in SAMURAI and 39% versus 21% in SPARTAN. The purpose of the current study is to describe the second dose population and the efficacy and safety findings for a second dose of lasmiditan, using data from these 2 phase 3 studies.

Methods The rescue population referred to patients who did not achieve headache pain-free status at 2 h, completed the 2-h assessments, and took a second dose of study drug between 2 and 24 h post-first dose.

The recurrence population referred to patients who achieved headache pain-free status at 2 h but then experienced recurrence of mild, moderate, or severe migraine pain and took a second dose of study drug up to 24 h from the first dose.

At 0.5, 1, 1.5, 2, 3, 4, 24, and 48 h after the first dose and again at the same inter- vals after a second dose of study drug, if taken, an electronic diary was employed to ask “Do you feel anything unusual since taking the study medication that you have not felt with a migraine before?”

Efficacy analyses were performed in the intention-to-treat (ITT) second dose population, which was defined as patients who used a second dose of study drug to treat a migraine and had any post-second dose headache severity or symptom assessments.

Results Baseline characteristics in those taking 1 versus 2 doses or in second-dose rescue versus recurrence populations were generally similar.

The baseline pain severity at first dose was similar across the dose groups in both the rescue and recurrence populations, as was the baseline pain severity at second dose.

Discussion Of those patients taking lasmiditan as first dose (any dose), 68% had mild, moder- ate or severe pain at 2 h (versus 82% for placebo as first dose); of those patients with pain at 2 h, 48% took a second dose for rescue (versus 66% for placebo as first dose).

Of those patients taking lasmiditan as first dose, overall 32% were pain free at 2 h; this is similar to what has been previously reported with use of oral triptans [53, 86]. Of those who were pain free at 2 h, 7–10% took a second dose for recurrence of symptoms.

There was no evidence that a second dose of lasmiditan was effective for treating migraine in patients who were not pain free at 2 h (i.e., rescue treatment); since the second dose of study medication was either the same dose of lasmiditan as the first dose or placebo, we do not know if patients would have responded to a higher dose of lasmiditan for rescue.

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4 Treatment

Conclusion The incidences of TEAEs were similar whether the second dose was lasmiditan or placebo.

Acknowledgement A machine generated summary based on the work of Loo, Li Shen; Plato, Brian M.; Turner, Ira M.; Case, Michael G.; Raskin, Joel; Dowsett, Sherie A.; Krege, John H. 2019 in BMC Neurology.

Trajectory of migraine-related disability following long-term treatment with lasmiditan: results of the GLADIATOR study