Dataset Information

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.

SUBMITTER: Lipton RB

PROVIDER: S-EPMC7920610 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Publications

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

Lipton Richard B RB Munjal Sagar S Dodick David W DW Tepper Stewart J SJ Serrano Daniel D Iaconangelo Charlie C

Journal of pain research 20210225

<h4>Background</h4>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.<h ...[more]

PMID: 33658842

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Project description:ObjectiveThe objective of this study was to evaluate the efficacy, tolerability, and safety of 120 mg DFN-15 vs placebo for the acute treatment of migraine.BackgroundCertain nonsteroidal anti-inflammatory drugs (NSAIDs) are guideline-recommended therapies for the acute treatment of migraine, but patients who use them may have issues with gastrointestinal tolerability. Celecoxib, a selective inhibitor of cyclooxygenase-2, produces analgesia similar to nonselective NSAIDs. DFN-15 is an oral, ready-made liquid solution of celecoxib being investigated for the acute treatment of migraine.MethodsA randomized, double-blind, placebo-controlled, efficacy, tolerability, and safety study in adults with migraine was conducted. Subjects treated a single migraine attack with 120 mg DFN-15 or placebo as soon as possible after the onset of pain of moderate to severe intensity. The 2 independent coprimary efficacy endpoints were the proportion of subjects with freedom from pain and the absence of the most bothersome symptom (MBS) at 2 hours postdose. A second double-blind treatment period followed the first, but did not contribute to the primary outcomes and will be reported elsewhere.ResultsThere were 622 subjects randomized (1:1) to double-blind treatment with either 120 mg DFN-15 or placebo, and 567 (91.2%) treated a migraine with study drug (n = 285 DFN-15; n = 282 placebo). Groups were balanced in demographic characteristics; the mean age was 40, and most subjects were female (87% [494/567]). At 2 hours postdose, DFN-15 was significantly superior to placebo for pain freedom (35.6% [98/275] vs 21.7% [57/263], P < .001), with an odds ratio (95% CI) of 2.00 (1.36, 2.94) and for freedom from the MBS (57.8% [134/232] vs 44.8% [104/232], P = .007), with an odds ratio (95% CI) of 1.68 (1.17, 2.43). A total of 13.3% (38/285) of DFN-15-treated subjects and 8.9% (25/282) of placebo-treated subjects reported a treatment-emergent adverse event (TEAE). Study drug-related TEAEs were reported by 9.1% (26/285) of DFN-15 subjects and 6.0% (17/282) of placebo subjects, the most common of which were dysgeusia (4.2% [12/285] vs 1.4% [4/282]) and nausea (3.2% [9/285] vs 1.8% [5/282]). No subjects treated with DFN-15 reported TEAEs that were severe or led to withdrawal, and no serious TEAEs or deaths were reported in the study.ConclusionsDFN-15 was significantly more effective than placebo for the acute treatment of migraine, with a generally favorable tolerability and safety profile.

Project description:BackgroundSafe, effective, oral therapies are needed for acute treatment of migraine. This clinical trial assessed the efficacy, tolerability, and safety of celecoxib oral solution (ELYXYB) in a single migraine attack associated with moderate-to-severe pain.MethodsThis was a phase III, randomized (1:1), double-blind, placebo-controlled trial, conducted at 41 US centers from December 2016 to October 2017. Adults with episodic migraine (with or without aura) for ≥1 year were treated with a single 4.8 mL dose of 120-mg celecoxib oral solution or placebo. Co-primary endpoints were the proportion of patients who were pain-free and free from the most bothersome migraine symptom (MBS) at 2 hours post-dose. The MBS was identified at screening from among nausea, photophobia, or phonophobia.ResultsSix hundred thirty-one patients were randomized (celecoxib oral solution, n=316; placebo, n=315; mean age 41 years, range 18-75; 84.3% female). One study site met prespecified outlier criteria (defined as a treatment effect estimate that was at least twice as large as all other sites) and was excluded from efficacy analyses. This site had a mean 2-hour pain freedom placebo response rate of 75% vs a combined mean of 23.5% for all other sites. In subsequent analysis, 2-hour post-dose pain freedom response rates were significantly higher in the celecoxib oral solution group vs placebo (32.8%, [27.2%, 38.8%]) vs 23.5%, [18.5%, 29.2%]; P=0.020). For 2-hour post-dose MBS freedom, response rates were significantly higher in the celecoxib oral solution group vs placebo (58.1% [51.4%, 64.5%] vs 43.9% [37.2%, 50.7%]; P=0.003). A total of 10.7% (31/289) of patients treated with celecoxib oral solution and 9.9% (28/283) of placebo-treated patients reported a treatment-emergent adverse event (TEAE). Study drug-related TEAEs were reported by 7.3% (21/289) and 7.4% (21/283) of celecoxib oral solution and placebo patients, respectively; the most common were nausea (celecoxib oral solution: 1.4% [4/289] vs placebo: 1.8% [5/283]) and dysgeusia (celecoxib oral solution: 1.7% [5/289] vs placebo: 1.1% [3/283]). No serious TEAEs, deaths, or drug-related TEAEs leading to withdrawal were reported.ConclusionCelecoxib oral solution is a safe, effective COX-2-selective nonsteroidal anti-inflammatory drug for the treatment of acute migraine. In this analysis, celecoxib oral solution was significantly more effective than placebo and was also associated with a low rate of gastric TEAEs. Celecoxib oral solution may provide a convenient, alternate option to currently available treatments.Trial registrationClinicalTrials.gov Identifier: NCT03009019; registered January 4, 2017; retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03009019.

Project description:OBJECTIVE:To assess the efficacy and safety of a remote electrical neuromodulation (REN) device for the acute treatment of migraine. BACKGROUND:There is a significant unmet need for novel effective well-tolerated acute migraine treatments. REN is a novel acute migraine treatment that stimulates upper arm peripheral nerves to induce conditioned pain modulation - an endogenous analgesic mechanism in which conditioning stimulation inhibits pain in remote body regions. A recent pilot study showed that REN can significantly reduce headache. We have conducted a randomized, double-blind, sham-controlled study to further evaluate the efficacy and safety of REN for the acute treatment of migraine. METHODS:This was a randomized, double-blind, sham-controlled, multicenter study conducted at 7 sites in the United States and 5 sites in Israel. Two hundred and fifty-two adults meeting the International Classification of Headache Disorders criteria for migraine with 2-8 migraine headaches per month were randomized in a 1:1 ratio to active or sham stimulation. A smartphone-controlled wireless device was applied for 30-45 minutes on the upper arm within 1 hour of attack onset; electrical stimulation was at a perceptible but non-painful intensity level. Migraine pain levels were recorded at baseline, 2, and 48 hours post-treatment. Most bothersome symptoms (MBS) were also recorded. The primary efficacy endpoint was the proportion of participants achieving pain relief at 2 hours post-treatment (improvement from severe or moderate pain to mild or none, or from mild pain to none). Relief of MBS and pain-free at 2 hours were key secondary endpoints. RESULTS:Active stimulation was more effective than sham stimulation in achieving pain relief (66.7% [66/99] vs 38.8% [40/103]; therapeutic gain of 27.9% [CI95% , 15.6-40.2]; P < .0001), pain-free (37.4% vs 18.4%, P = .003), and MBS relief (46.3% vs 22.2%, P = .0008) at 2 hours post-treatment. The pain relief and pain-free superiority of the active treatment was sustained 48 hours post-treatment. The incidence of device-related adverse events was low and similar between treatment groups (4.8% [6/126] vs 2.4% [3/126], P = .499). CONCLUSIONS:REN provides superior clinically meaningful relief of migraine pain and MBS compared to placebo, offering a safe and effective non-pharmacological alternative for acute migraine treatment.

Project description:ObjectiveTo assess the nocioceptive input of habitual nocturnal jaw clenching that acts as a contributing factor in migraine pathogenesis.BackgroundHabitual nocturnal jaw clenching has been implicated as a trigger, particularly in those whose headaches are present upon waking or shortly thereafter. Nocturnal EMG studies of patients diagnosed with migraine show nearly twice the temporalis clenching EMG levels and double the bite force as matched asymptomatic controls, leading to the speculation that parafunctional clenching activity may have some role in headache pathogenesis. The NTI (Nociceptive Trigeminal Inhibition) oral device is a dental splint designed to reduce nocturnal jaw clenching intensity and is FDA approved for the prevention of medically diagnosed migraine pain based on open label studies. There are no prior placebo-controlled trials to assess the migraine prevention efficacy of the NTI splint. This is the first placebo-controlled cross-over study to assess the efficacy of the NTI splint in patients with Chronic Migraine.MethodA placebo controlled, single-blinded cross-over study was done with IRB oversight assessing the efficacy of the NTI splint compared to placebo using the change in the HIT-6 score as the outcome measure.Results68% of refractory chronic migraine sufferers using the NTI as measured by sequential HIT 6 scores had at least a one-category improvement (severe to substantial, or substantial to some, or some to none) compared to 12% when using a placebo device. 36% of subjects using the NTI device reported a two-category improvement in their HIT-6 score, compared to 0% when using placebo.ConclusionThe improvement in HIT-6 scores produced by the NTI device, suggests that patients with Chronic Migraine may have intense nocturnal jaw clenching as a contributing factor to their headache related disability. An NTI device is one method of assessing whether jaw-clenching is a contributing factor to ongoing migraine.Trial registrationCurrent Controlled Trials NCT04871581. 04/05/2021. Retrospectively registered.

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

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