DFN‐02 (Sumatriptan 10 mg With a Permeation Enhancer) Nasal Spray vs Placebo in the Acute Treatment of Migraine: A Double‐Blind, Placebo‐Controlled Study

Lipton, Richard B.; Munjal, Sagar; Brand-Schieber, Elimor; Rapoport, Alan M.

doi:10.1111/head.13309

Cited by 32 publications

(35 citation statements)

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“…In many trials, the most common MBS was photophobia, occurring in roughly half of respondents. [5][6][7][8][9][10][11][12][13][14][15][16][17] It should be noted that clinical trials have taken 2 approaches to determining MBS; some determine MBS during a clinic visit, 6,14,15 while others determine MBS immediately prior to taking study medication. 7,9,10,12,13,16 The MAST survey used a recallbased question about MBS with headache attacks over the last 3 months.…”

Section: Discussionmentioning

confidence: 99%

“…Missed and reduced productivity days items were summed and grouped to identify disability by 4 grades: little or none (score of 0-5), mild (score of 6-10), moderate (score of [11][12][13][14][15][16][17][18][19][20], and severe (score of ≥21). Migraine-related disability was assessed with the Migraine Disability Assessment (MIDAS) questionnaire, a 5-item scale assessing missed and reduced productivity days at work, school, or home during the previous 3 months due to headache.…”

Section: Studymentioning

confidence: 99%

“…Migraine-related disability was assessed with the Migraine Disability Assessment (MIDAS) questionnaire, a 5-item scale assessing missed and reduced productivity days at work, school, or home during the previous 3 months due to headache. Missed and reduced productivity days items were summed and grouped to identify disability by 4 grades: little or none (score of 0-5), mild (score of 6-10), moderate (score of [11][12][13][14][15][16][17][18][19][20], and severe (score of ≥21).…”

Section: Studymentioning

confidence: 99%

“…By removing the need to show significant differences from placebo on 4 coprimary endpoints, the new approach also reduces sample size requirements and increases power to detect change relative to trials conducted under the older guidance. 3,4 Though multiple acute treatment studies have been conducted using 2-hour MBS freedom as a coprimary endpoint, [5][6][7][8][9][10][11][12][13][14][15][16][17] we are not aware of data on MBS in nationally representative samples of people with migraine. The Migraine in America Symptoms and Treatment (MAST) Study was designed to assess current patterns of consultation, diagnosis, and treatment in a large representative sample of people with migraine in the United States.…”

Section: Introductionmentioning

confidence: 99%

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Most Bothersome Symptom in Persons With Migraine: Results From the Migraine in America Symptoms and Treatment (MAST) Study

Munjal¹,

Singh²,

Reed³

et al. 2019

Headache

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Objectives.-The objectives of this study were to determine the rates of nausea, phonophobia, and photophobia reported overall and as the most bothersome symptom (MBS) in individuals with migraine and to identify individual characteristics associated with each of the 3 candidate MBSs.Background.-The MBS has emerged as an important coprimary efficacy endpoint in clinical trials of acute treatments for migraine, as recommended by the Food and Drug Administration. The current understanding of how persons with migraine designate an associated symptom as the most bothersome has been assessed primarily in the context of randomized trials. Methods.-Respondents (n = 95,821) in the cross-sectional, observational Migraine in America Symptoms and Treatment (MAST) study were adults (aged ≥18 years) recruited from a US nationwide online research panel. A validated diagnostic screener identified 15,133 individuals who met modified International Classification of Headache Disorders (ICHD)-3 betacriteria for migraine and reported at least 1 monthly headache day (MHD) over the previous 3 months. The survey ascertained sociodemographic variables, headache-related disability, MHDs, cutaneous allodynia, medication overuse, a migraine symptom severity score, pain interference, noncephalic pain, anxiety and depression symptoms, visual aura over the previous year, and acute treatment optimization. The current analysis is based on respondents who also completed a 6-month follow-up assessment that included questions about their most bothersome headache symptom.Results.-A total of 7518 respondents completed the 6-month follow-up, and 6045 met inclusion criteria and were included in the analysis. The mean age of respondents was 47 (SD 13.4) years, 76.0% (4596/6045) were women, and 84.8% (5103/6017) were white. Among all respondents, 64.9% reported all 3 migraine symptoms. The MBS was photophobia in 49.1% (2967/6045), nausea in 28.1% (1697/6045), and phonophobia in 22.8% (1381/6045). Respondents reporting photophobia as the MBS were more likely to be men, to be obese, and to report visual aura. Those reporting nausea as the MBS were more likely to be women, to have lower incomes, and to report lower levels of treatment optimization. Respondents reporting phonophobia as the MBS were more likely to have cutaneous allodynia and less likely to have visual aura.Conclusion.-Most people with migraine in the MAST observational study reported all 3 cardinal symptoms of nausea, photophobia, and phonophobia. As in clinical trials, the most common MBS was photophobia. Patient profiles differed among the groups defined by their MBS.

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Section: Discussionmentioning

confidence: 99%

Section: Studymentioning

confidence: 99%

Section: Studymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Most Bothersome Symptom in Persons With Migraine: Results From the Migraine in America Symptoms and Treatment (MAST) Study

Munjal¹,

Singh²,

Reed³

et al. 2019

Headache

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“…To that end, a novel intranasal formulation of diazepam was developed using a nonionic alkylglycoside surfactant (Intravail A3, dodecyl‐β‐D‐maltopyranoside [DDM], and tocopherol). As described by Lipton et al, DDM alters mucosal viscosity and membrane fluidity to loosen cell‐cell junctions. DDM induces a rapid and reversible decrease in transepithelial/transendothelial electrical resistance values, enhancing the permeation of the paracellular marker [3H]mannitol, resulting in changes to the tight junctions to facilitate absorption .…”

Section: Introductionmentioning

confidence: 89%

Bioavailability and safety of diazepam intranasal solution compared to oral and rectal diazepam in healthy volunteers

et al. 2020

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Objective The study assesses the bioavailability of diazepam after intranasal administration (diazepam nasal spray) in healthy volunteers. Comparative agents were diazepam rectal gel, which served as the regulatory reference product; and oral diazepam, a product with decades of clinical use. Tolerability of diazepam nasal spray was also assessed. Methods This was a phase 1, open‐label, randomized, single‐dose, three‐treatment, three‐period, six‐sequence crossover study in 48 healthy adult subjects that consisted of a screening period, a baseline period, and an open‐label treatment period. Interperiod intervals were at least 28 days. Results Forty‐eight healthy volunteer subjects were enrolled, two of whom discontinued before receiving study medication. For all routes of administration, the onset of diazepam absorption was rapid, with measurable concentrations of drug present by the first sample time point. The tmax (time to reach maximum plasma concentration) was similar for diazepam nasal spray and diazepam rectal gel, both of which were slower than oral diazepam in fasted individuals. Variability (as defined by % coefficient of variation of geometric mean) in peak plasma concentration and area under the curve0‐∞ was lowest with oral diazepam, followed by diazepam nasal spray, with diazepam rectal gel showing the greatest variability. Overall, 131 treatment‐emergent adverse events (TEAEs) were considered mild (42 subjects, 91.3%), four TEAEs were considered moderate (four subjects, 8.3%), and no TEAEs were considered severe. The most commonly reported TEAE was somnolence at 56.5% (26/46) during diazepam nasal spray treatment, 89.1% (41/46) with the rectal diazepam gel treatment, and 82.6% (38/46) with oral diazepam treatment. No nasal irritation was observed for the majority of the subjects at any time point after administration, with no score higher than 2 (“minor bleeding that stops within 1 minute”). Significance Diazepam nasal spray shows predicable pharmacokinetics and represents a potential novel therapeutic approach to control bouts of increased seizure activity (cluster seizures, acute repetitive seizures).

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Intranasal Medication Delivery in Children for Brain Disorders

Zhang

McCrary

Wei

2019

Therapeutic Intranasal Delivery for Stroke and Neurological Disorders

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DFN‐02 (Sumatriptan 10 mg With a Permeation Enhancer) Nasal Spray vs Placebo in the Acute Treatment of Migraine: A Double‐Blind, Placebo‐Controlled Study

Abstract: DFN-02 was shown to be effective, well tolerated, and safe in the acute treatment of episodic migraine. Additional studies are needed to confirm these preliminary results. (ClinicalTrials.gov Identifier: NCT02856802).

Cited by 32 publications

References 33 publications

Most Bothersome Symptom in Persons With Migraine: Results From the Migraine in America Symptoms and Treatment (MAST) Study

Most Bothersome Symptom in Persons With Migraine: Results From the Migraine in America Symptoms and Treatment (MAST) Study

Bioavailability and safety of diazepam intranasal solution compared to oral and rectal diazepam in healthy volunteers

Intranasal Medication Delivery in Children for Brain Disorders

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