Acute Treatment of Migraine with Celecoxib Oral Solution: Results of a Randomized, Placebo-Controlled Clinical Trial

Abstract

Background Nonsteroidal anti-inflammatory drugs are widely used for migraine, but gastrointestinal tolerability limits use. We previously reported results from the first treatment period of this 2-period, randomized, controlled study comparing DFN-15—an oral, ready-made liquid solution of a selective cyclo-oxygenase-2 inhibitor celecoxib—with placebo for the acute treatment of a moderate-severe migraine attack. Herein, we report the effects of treatment for the second treatment period. Methods In the first treatment period of this trial, adults with migraine were randomized to double-blind trial treatment of attacks of moderate or severe pain with DFN-15,120 mg or placebo. For the second treatment period, reported herein, participants were re-randomized to treat an attack of any baseline pain intensity (mild, moderate, or severe). Co-primary efficacy endpoints specified for the first attack were not specified for the second attack. Results Of the 531 patients who completed the first treatment period, 491 (n = 243 DFN-15; n = 248 placebo; 87% female, mean age 41 years) were re-randomized into the second double-blind treatment period. Baseline pain intensity was mild in 17.2% (85/493) of patients, moderate in 58.4% (288/493) of patients, and severe in 22.9% (113/493) of patients. At 2 hours post-dose, DFN-15 was superior to placebo for freedom from pain (46.2% [110/238] vs 31.1% [76/244], p ≤ 0.001) and the most bothersome symptom (63.4% [121/191] vs 50.0% [98/196], p = 0.010). Treatment-emergent adverse events (TEAEs) occurred in 7.1% (35/493) of patients (DFN-15: 6.1% [15/244]; placebo 8.0% [20/249]). Study drug-related TEAEs occurred in 5.1% (25/493) of patients (DFN-15: 4.5% [11/244]; placebo 5.6% [14/249]); nausea (1% [5/493]) and dysgeusia (0.8% [4/493]) were most common. No serious TEAEs, severe TEAEs, or TEAEs leading to study drug termination were reported. Conclusions DFN-15 was superior to placebo for pain freedom and freedom from the most bothersome symptom when patients treat a migraine attack of any baseline pain intensity. Rates of TEAEs did not differ between treatment groups.

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

“…Our study results contrasted to other recent clinical trials conducting in the United States, the United Kingdom, and Germany, of which, the most commonly reported MBS was photophobia (range: 50.6%-59.9%), followed by nausea (16.4%-31.5%) and phonophobia (13.4%-29.8%). [29][30][31][32][33][34][35][36][37][38][39][40][41][42] Of note, most participants in those trials were White (range: 74.0%-88.2%). 30,35 In addition, two large-scale observational studies in the United States also reported photophobia as the most common MBS.…”

“…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 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%).…”

“…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.…”

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy, Tolerability, and Safety of Celecoxib Oral Solution (ELYXYB) in Acute Treatment of Episodic Migraine with or without Aura

“…29 However, celecoxib capsules are slow to provide pain relief, with a median T max of 2.5 hours. 30 Because rapid pain relief is an important treatment goal, 30 , 31 and due to GI issues with oral NSAIDs, 30 celecoxib capsules have not been approved for the acute treatment of migraine in the U.S. 32 …”

“…29 However, celecoxib capsules are slow to provide pain relief, with a median T max of 2.5 hours. 30 Because rapid pain relief is an important treatment goal, 30,31 and due to GI issues with oral NSAIDs, 30 celecoxib capsules have not been approved for the acute treatment of migraine in the U.S. 32 ELYXYB (celecoxib oral solution, 25 mg/mL, previously known as DFN-15) is a new liquid formulation of celecoxib, approved in May 2020 for the acute treatment of migraine with or without aura in adults. 33 It has a shorter demonstrated T max (median 0.7 hours) than available celecoxib capsule formulations, 30 and has been evaluated and found effective versus placebo in a prior phase 3 randomized, double-blind, placebo-controlled trial of patients with episodic migraine (N=622).…”