Phase 2 randomized placebo‐controlled study of lasmiditan for the acute treatment of migraine in Japanese patients

Abstract

Objective: To evaluate the efficacy and safety of lasmiditan in Japanese adults with migraine.Background: Global clinical studies have demonstrated the efficacy and safety of lasmiditan in the acute treatment of migraine.Methods: This was a multicenter, randomized, double-blind, placebo-controlled, phase 2 study in Japan (NCT03962738), which enrolled adults with migraine with or without aura. Participants were randomized 7:3:7:6 to placebo, lasmiditan 50 mg, 100 mg, or 200 mg to be self-administered orally within 4 h of onset of a single moderate-to-severe migraine attack. Participants recorded their response to treatment prior to dosing and for 48 h postdose. The primary endpoint was headache pain freedom at 2 h postdose.Results: Participants (N = 846) were randomized and treated (N = 691, safety; N = 682, modified intent-to-treat). At 2 h postdose, a significantly higher proportion of participants were headache pain-free in the lasmiditan 200 mg (40.8%, 73/179; odds ratio 3.46 [95% confidence interval 2.17 to 5.54]; p < 0.001; primary objective) and 100 mg groups (32.4%, 67/207; odds ratio 2.41 [1.51 to 3.83]; p < 0.001) compared with the placebo group (16.6%, 35/211), whereas the lasmiditan 50 mg group had a numerically higher proportion of participants headache pain-free (23.5%, 20/85; odds ratio 1.55 [0.83 to 2.87]; p = 0.167) compared with placebo. A statistically significant linear doseresponse relationship for pain freedom was achieved at 2 h by a Cochran-Armitage trend test (p < 0.001). Lasmiditan treatment was also associated with headache pain relief, most bothersome symptom freedom, and improvement on disability and Patient Global Impression of Change outcomes. The majority of treatment-emergent adverse events were mild and of short duration, the most common of which were dizziness (39.4%; 188/477), somnolence (19.3%; 92/477), and malaise (10.5%; 50/477) in all lasmiditan groups, with no serious adverse events reported.This is an open access article under the terms of the Creat ive Commo ns Attri butio n-NonCo mmerc ial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Most bothersome symptoms in patients with migraine: A hospital‐based study in Taiwan

“…29,34 The only Asian-based clinical trial on MBS was conducted in Japan and revealed photophobia to be the most common MBS but at a lower frequency (37.4%). 43 In an observational study by the Japanese Adelphi Migraine Disease-Specific Programme, the most frequent physician-reported symptoms that were considered most troublesome to patients (defined as occurring in ≥5% of patients with episodic migraine [EM] or CM) were pain-related symptoms. These symptoms included unilateral pain (50.8% and 37.7% for EM and CM, respectively), pulsating/throbbing pain (20.8% and 37.7% for EM and CM, respectively), nausea (7.5% for CM), and vomiting (7.5% for CM).…”

“…27,28 To date, most of the recent clinical trials adopting MBS as a co-primary endpoint have been conducted in Europe and the United States, [29][30][31][32][33][34][35][36][37][38][39][40][41][42] except for one study in Japan. 43 These studies reported photophobia as the most common MBS, ranging from 50.6% to 59.9% in patients from Europe and the United States; however, the frequency was noticeably lower in Japan (37.4%). [29][30][31][32][33][34][35][36][37][38][39][40][41][42][43] Because regional variations likely exist in migraine prevalence and manifestations, it is of interest to explore MBS prevalence and distribution in Taiwanese patients with migraine, and we hypothesized that the MBS prevalence and distribution might differ between migraine subtypes.…”

“…43 These studies reported photophobia as the most common MBS, ranging from 50.6% to 59.9% in patients from Europe and the United States; however, the frequency was noticeably lower in Japan (37.4%). [29][30][31][32][33][34][35][36][37][38][39][40][41][42][43] Because regional variations likely exist in migraine prevalence and manifestations, it is of interest to explore MBS prevalence and distribution in Taiwanese patients with migraine, and we hypothesized that the MBS prevalence and distribution might differ between migraine subtypes. In this study, we aimed to elucidate the pattern, clinical associations, and the treatment responses of MBS in relation to prior acute treatments in a large real-world sample of patients with migraine in Taiwan.…”

“…The MBS was used as a co‐primary endpoint with the aim to better align the study outcome, 25 reduce sample size requirements, and potentially harmonize randomized controlled trial designs with “real‐world” treatment experiences 27,28 29–42 except for one study in Japan 43 29–43 …”

“…To date, most of the recent clinical trials adopting MBS as a co‐primary endpoint have been conducted in Europe and the United States, 29–42 except for one study in Japan 43 29–43 …”