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Efficacy, Tolerability, and Safety of DFN-15 (Celecoxib Oral Solution, 25 mg/mL) in the Acute Treatment of Episodic Migraine: A Randomized, Double-Blind, Placebo-Controlled Study.

ABSTRACT: OBJECTIVE:The 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. BACKGROUND:Certain 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. METHODS:A 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. RESULTS:There 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. CONCLUSIONS:DFN-15 was significantly more effective than placebo for the acute treatment of migraine, with a generally favorable tolerability and safety profile.

SUBMITTER: Lipton RB

PROVIDER: S-EPMC7003821 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Efficacy, Tolerability, and Safety of DFN-15 (Celecoxib Oral Solution, 25 mg/mL) in the Acute Treatment of Episodic Migraine: A Randomized, Double-Blind, Placebo-Controlled Study.

Lipton Richard B RB Munjal Sagar S Brand-Schieber Elimor E Tepper Stewart J SJ Dodick David W DW

Headache 20191024 1

<h4>Objective</h4>The 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.<h4>Background</h4>Certain 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 ...[more]

PMID: 31647577

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Project description:BackgroundDFN-02 is a novel intranasal spray formulation composed of sumatriptan 10 mg and a permeation-enhancing excipient comprised of 0.2% 1-O-n-Dodecyl-β-D-Maltopyranoside (DDM). This composition of DFN-02 allows sumatriptan to be rapidly absorbed into the systemic circulation and exhibit pharmacokinetics comparable to subcutaneously administered sumatriptan. Rapid rate of absorption is suggested to be important for optimal efficacy. The objective of this study was to evaluate the safety and tolerability of DFN-02 (10 mg) in the acute treatment of episodic migraine with and without aura over a 6-month period based on the incidence of treatment-emergent adverse events and the evaluation of results of clinical laboratory tests, vital signs, physical examination, and electrocardiograms.MethodsThis was a multi-center, open-label, repeat-dose safety study in adults with episodic migraine with and without aura. Subjects diagnosed with migraine with or without aura according to the criteria set forth in the International Classification of Headache Disorders, 2nd edition, who experienced 2 to 6 attacks per month with fewer than 15 headache days per month and at least 48 headache-free hours between attacks, used DFN-02 to treat their migraine attacks acutely over the course of 6 months.ResultsA total of 173 subjects was enrolled, 167 (96.5%) subjects used at least 1 dose of study medication and were evaluable for safety, and 134 (77.5%) subjects completed the 6-month study. A total of 2211 migraine attacks was reported, and 3292 doses of DFN-02 were administered; mean per subject monthly use of DFN-02 was 3.6 doses. Adverse events were those expected for triptans, as well as for nasally administered compounds. No new safety signals emerged. Dysgeusia and application site pain were the most commonly reported treatment-emergent adverse events over 6 months (21% and 30.5%, respectively). Most of the treatment-emergent adverse events were mild. There were 5 serious adverse events, all considered unrelated to the study medication; the early discontinuation rate was 22.5% over the 6-month treatment period.ConclusionDFN-02 was shown to be well tolerated when used over 6 months to treat episodic migraine acutely.

Project description:BACKGROUND:DFN-11, a 3 mg sumatriptan subcutaneous (SC) autoinjector for acute treatment of migraine, has not been assessed previously in multiple attacks. The objective of this study was to evaluate the efficacy, tolerability, and safety of DFN-11 in the acute treatment of multiple migraine attacks. METHODS:This was an 8-week open-label extension of multicenter, randomized, double-blind, placebo-controlled US study. Subjects averaging 2 to 6 episodic migraine attacks per month were randomized to DFN-11 or placebo to treat a single attack of moderate-to-severe intensity and then entered the extension study to assess the efficacy, tolerability, and safety of DFN-11 in multiple attacks of any pain intensity. RESULTS:Overall, 234 subjects enrolled in the open-label period, and 29 (12.4%) discontinued early. A total of 848 migraine episodes were treated with 1042 doses of open-label DFN-11 and subjects treated a mean (SD) of 3.9 (2.3) attacks. At 2 h postdose in attacks 1 (N?=?216), 2 (N?=?186), 3 (N?=?142) and 4 (N?=?110), respectively, pain freedom rates were 57.6%, 64.6%, 61.6%, and 66.3%; pain relief rates were 83.4%, 88.4%, 84.1%, and 81.7%; most bothersome symptom (MBS)-free rates were 69.0%, 76.5%, 77.7%, and 74.7%; nausea-free rates were 78.1%, 84.6%, 86.5%, and 85.7%; photophobia-free rates were 75.3%, 76.4%, 72.3%, and 77.5%; and phonophobia-free rates were 75.2%, 77.5%, 73.6%, and 76.0%. Overall, 40.6% (89/219) of subjects reported treatment-emergent adverse events (TEAE), the most common of which were associated with the injection site: swelling (12.8%), pain (11.4%), irritation (6.4%), and bruising (6.4%). Most subjects (65.2%, 58/89) had mild TEAEs; severe TEAEs were reported by 1 subject (treatment-related jaw tightness). Five subjects (2.1%) discontinued due to adverse events, which included mild throat tightness (n?=?2), moderate hernia pain (n?=?1), moderate hypersensitivity (n?=?1), and 1 subject with mild nausea and moderate injection site swelling. There were no serious TEAEs and no new or unexpected safety findings. CONCLUSION:DFN-11 was effective, tolerable, and safe in the acute treatment of 4 migraine attacks over 8 weeks, with consistent responses on pain and associated symptoms. Most TEAEs were mild, with a very low incidence of triptan-related TEAEs. DFN-11 is potentially an effective and safe alternative for the acute treatment of migraine. TRIAL REGISTRATION:ClinicalTrials.gov, NCT02569853 . Registered 07 October 2015.

Project description:BACKGROUND:In a previous randomized, double-blind, proof-of-concept study in rapidly escalating migraine, a 3 mg dose of subcutaneous sumatriptan (DFN-11) was associated with fewer and shorter triptan sensations than a 6 mg dose. The primary objective of the study was to assess the efficacy and safety of acute treatment with DFN-11 compared with placebo in episodic migraine. METHODS:This was a multicenter, randomized, double-blind, placebo-controlled efficacy and safety study of DFN-11 in the acute treatment of adults with episodic migraine (study RESTOR). The primary endpoint was the proportion of subjects taking DFN-11 who were pain free at 2 h postdose in the double-blind period compared with placebo. Secondary endpoints included earlier postdose timepoints, assessments of pain relief and subjects' freedom from their most bothersome symptom (MBS) (among nausea, photophobia, and phonophobia). Safety and tolerability were assessed. RESULTS:A total of 392 subjects was screened, 268 (68.4%) were randomized, and 234 (87.3% of those randomized) completed the double-blind treatment period. The proportion of subjects who were pain free at 2 h postdose was significantly greater in the DFN-11 group than in the placebo group (51.0% vs 30.8%, P??=??0.0023). Compared with placebo, significantly higher proportions of subjects treated with DFN-11 were also pain free at 30, 60, and 90 min postdose (P?????0.0195). DFN-11 was significantly superior to placebo for pain relief at 60 min, 90 min, and 2 h postdose (P???0.0179). At 2 h postdose, DFN-11 was also significantly superior to placebo for freedom from photophobia (P??=??0.0056) and phonophobia (P??=??0.0167). Overall, 33.3% (37/111) who received DFN-11 and 13.4% (16/119) who received placebo experienced at least 1 treatment-emergent adverse event (TEAE), the most common of which were injection site swelling (7.2% vs 0.8%) and pain (7.2% vs 5.9%). Chest discomfort was about half as common in the DFN-11 treatment group as it was in the placebo group (0.9% vs 1.7%). CONCLUSIONS:This study met its primary endpoint, pain freedom at 2 h postdose, with DFN-11 significantly better than placebo, and the incidence of TEAEs and triptan sensations with DFN-11 was low. The 3 mg dose of sumatriptan in DFN-11 appears to be an effective alternative to a 6 mg SC dose of sumatriptan, with good safety and tolerability. ( clinicaltrials.gov : NCT02569853; registered 07 October 2015).

Project description:A 6-mg dose of SC sumatriptan is the most efficacious and fast-acting acute treatment for migraine, but a 3-mg dose of SC sumatriptan may improve tolerability while maintaining efficacy.This randomized, double-blind, crossover study compared the efficacy and tolerability of 3 mg subcutaneous (SC) sumatriptan (DFN-11) with 6 mg SC sumatriptan in 20 adults with rapidly-escalating migraine attacks. Eligible subjects were randomized (1:1) to treat 1 attack with DFN-11 and matching placebo autoinjector consecutively or 2 DFN-11 autoinjectors consecutively and a second attack similarly but with the alternative dose (3 mg or 6 mg).The proportions of subjects who were pain-free at 60 min postdose, the primary endpoint, were similar following treatment with 3 mg SC sumatriptan and 6 mg SC sumatriptan (50% vs 52.6%, P??=??.87). The proportions of subjects experiencing pain relief (P?????.48); reductions in migraine pain intensity (P?????.78); and relief from nausea, photophobia, or phonophobia (P?????.88) with 3 mg SC sumatriptan and 6 mg SC sumatriptan were similar, as were the mean scores for satisfaction with treatment (M??=??2.6 vs M??=??2.4, P??=??.81) and the mean number of rescue medications used (M??=??.11 vs M??=??.26, P??=??.32). The most common adverse events with the 3- and 6-mg doses were triptan sensations - paresthesia, neck pain, flushing, and involuntary muscle contractions of the neck - and the incidence of adverse events with both doses was similar (32 events total: 3 mg, n??=??14 [44%]; 6 mg, n??=??18 [56%], P??=??.60). Triptan sensations affected 4 subjects with the 6-mg dose only, 1 subject with the 3-mg dose only, and 7 subjects with both sumatriptan doses. Chest pain affected 2 subjects (10%) treated with the 6-mg dose and no subjects (0%) treated with the 3-mg dose of DFN-11. There were no serious adverse events.The 3-mg SC dose of sumatriptan in DFN-11 provided relief of migraine pain and associated symptoms comparable to a 6-mg SC dose of sumatriptan. Tolerability was similar with both study medications; DFN-11 treatment was associated with fewer triptan sensations than the 6-mg dose. DFN-11, with its 3-mg dose of sumatriptan, may be a clinically useful alternative to higher-dose autoinjectors.

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:BackgroundThe feline lungworm Aelurostrongylus abstrusus affects the lower respiratory tract in cats worldwide. As infections may lead to chronic respiratory changes or even death, preventive treatment in cats with outdoor access is warranted.MethodsThe preventive efficacy of a spot-on solution (Bravecto® Plus spot-on solution for cats, MSD) against cat aelurostrongylosis was evaluated using three different preventive treatment regimes in a negative controlled, randomized and partially blinded laboratory efficacy study with 31 purposed-bred cats. The minimum recommended dose of 2.0 mg moxidectin + 40 mg fluralaner/kg bodyweight was applied once 12 (Group [G]1), 8 (G2) or 4 (G3) weeks before experimental infection with 300 third-stage larvae (L3) of A. abstrusus. Another group served as untreated control (G4). Individual faecal samples were analysed as of day 30 post infection (pi) to monitor larvae excretion. Necropsy was performed at days 47-50 pi. The lungs were examined macroscopically for pathological findings and (pre-)adult worms were counted to assess preventive efficacy.ResultsBeginning at day 32-40 pi, all cats of the control group were constantly shedding larvae of A. abstrusus, whereas only one animal of G1 excreted larvae at several consecutive days. In addition, two cats of G1 and G3 and three of G2 were positive on a single occasion. The geometric mean (GM) of the maximum number of excreted larvae was 7574.29 in the control group compared to 1.10 (G1), 1.19 (G2) and 0.53 (G3), resulting in a GM reduction of > 99.9% in all treatment groups. All lungs of the control animals showed severe or very severe alterations at necropsy, while in 94.44% of the treated cats lung pathology was rated as absent or mild. The GM number of (pre-)adult A. abstrusus retrieved from the lungs was 26.57 in the control group, 0.09 in G1 and 0.00 in G2 and G3. Thus, GM worm count reduction was 99.66% in G1 and 100% in G2 and G3.ConclusionsA single application of Bravecto® Plus spot-on solution at a dose of 2.0 mg moxidectin + 40 mg fluralaner/kg bodyweight reliably prevents cat aelurostrongylosis for at least 12 weeks.

Project description:BackgroundNonsteroidal 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.MethodsIn 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.ResultsOf 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.ConclusionsDFN-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.

Dataset Information

Efficacy, Tolerability, and Safety of DFN-15 (Celecoxib Oral Solution, 25 mg/mL) in the Acute Treatment of Episodic Migraine: A Randomized, Double-Blind, Placebo-Controlled Study.

Publications

Efficacy, Tolerability, and Safety of DFN-15 (Celecoxib Oral Solution, 25 mg/mL) in the Acute Treatment of Episodic Migraine: A Randomized, Double-Blind, Placebo-Controlled Study.

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