DFN-02, Sumatriptan 10 mg Nasal Spray with Permeation Enhancer, for the Acute Treatment of Migraine: A Randomized, Double-Blind, Placebo-Controlled Study Assessing Functional Disability and Subject Satisfaction with Treatment

DOI: https://doi.org/10.1007/s40263-019-00614-6

Abstract-Summary Previously, DFN-02 was significantly better than placebo on multiple efficacy end- points at 2  h postdose, including pain freedom, absence of the most bothersome symptom, and pain relief, and its safety and tolerability profiles were excellent.

The objective of this study was to assess the efficacy of acute treatment of migraine with DFN-02, including its effect on migraine-related functional disability and patient satisfaction with treatment.

DFN-02 was significantly superior to placebo for the reduction in functional dis-

ability score from predose level at 2 h after treatment (−1.2 vs. −0.6, p  <  0.001).

Using the Patient Perception of Migraine Questionnaire-Revised at 24 h post- dose, DFN-02 mean scores were significantly superior to placebo for the subscales of efficacy (65.2 vs. 42.5, p = 0.016) and function (68.9 vs. 42.1, p = 0.001), and for total score (71.0 vs. 56.6, p = 0.016); global medication effectiveness (p = 0.027); and overall satisfaction (p = 0.019).

Placebo was significantly better than DFN-02 on the tolerability subscale (94.8

vs. 88.5, p = 0.026).

At 24 h postdose, subjects reported significantly higher satisfaction with DFN-02 compared with satisfaction reported pre-randomization regarding their usual migraine medication (p = 0.012).

DFN-02 was superior to placebo for the relief of migraine-related functional dis- ability, and provided greater satisfaction than placebo or subjects’ usual acute treatment.

Extended: DFN-02 was significantly more effective than placebo in reducing

migraine-related functional disability.

A larger study population would have strengthened the analyses and enhanced

the generalizability of its findings.

Introduction Sumatriptan has been the predominant prescription migraine-specific acute treat- ment since 1992 [131, 132].

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4 Treatment

Although the subcutaneous injections are recognized as the fastest and most effective form of acute migraine treatment [133], most patients prefer tablets because they are familiar, easy to use, and associated with fewer adverse effects than injections.

Guidelines for the acute treatment of migraine recommend subcutaneous injec- tions or nasal spray formulations for patients who do not respond to oral triptans, patients with prominent gastrointestinal symptoms that interfere with orally admin- istered acute treatments, and those for whom oral therapies are intolerable due to treatment- emergent nausea or dysphagia [109, 134].

One option, sumatriptan nasal spray, is effective and well-tolerated for the acute treatment of migraine [135–137], but its onset of action (30–45 min) is variable, suboptimal, and comparable to oral tablets [138].

The objective of the present study in adults with episodic migraine was to com- pare DFN-02 with placebo for acute relief of functional disability and with usual treatment for subject-rated treatment satisfaction.

Methods Subjects who treated an attack and recorded their response to medication in an eDi- ary were re-randomized into a second double-blind treatment period in which they treated a second migraine attack at any level of pain intensity.

Subjects recorded information about their attacks, the effects of study medica- tion on functional disability, and satisfaction with treatment, in the eDiary; other data, such as safety and tolerability, were entered by site staff into electronic case report forms.

The Patient Perception of Migraine Questionnaire-Revised (PPMQ-R) [139, 140] was used at baseline (pre- randomization) to assess subjects’ satisfaction with their usual pre-study migraine treatment, and was also used at 24  h postdose to assess subjects’ satisfaction with the study medication.

Results At 2 h postdose, mean (standard deviation) 2-h overall subject-rated treatment sat- isfaction scores were significantly better with DFN-02 than with placebo (2.8 [1.48] vs. 4.1 [2.06], p = 0.003).

Subjects in the DFN-02 group were significantly more satisfied than those in the placebo group on the PPMQ-R subscales for efficacy (p = 0.016), function (p = 0.001), global items of medication effectiveness (p = 0.027), and overall satisfaction (p = 0.019), as well as on the total score (p = 0.016).

Among subjects treated with DFN-02, the treatment satisfaction at 24 h postdose was significantly greater than subjects’ satisfaction with their usual pre-study migraine medication, based on the baseline PPMQ-R for the total score (74.6 vs. 62.2, p = 0.012).

Discussion In this multicenter, randomized, double-blind, placebo-controlled study, where sub- jects treated a migraine attack of moderate to severe headache and reported out- comes in a real-time eDiary, DFN-02 was significantly more effective than placebo for relief of functional disability and for subject satisfaction with treatment.

4.1 Acute Treatment

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Given the importance of restored function to migraine patients, the results with DFN-02 for relief of functional disability are promising relative to findings from previous studies of the commercially available form of sumatriptan nasal spray.

In a randomized, double-blind, parallel-group, placebo-controlled study of the 20 mg commercial nasal spray, in which up to three migraine attacks were treated over a 6-month period, 70% of subjects had no or mild disability at 2 h post- dose [136].

A meta-analysis of two studies (n = 225) with sumatriptan 20 mg found that 62%

of subjects had mild or no functional disability at 2 h postdose [135, 137].

Conclusions Subjects’ satisfaction with DFN-02 was significantly superior to placebo at 2 and 24 h postdose.

There was also greater satisfaction with DFN-02 compared with the subjects’

pre-study usual migraine medication.

Acknowledgement A machine generated summary based on the work of Lipton, Richard B.; Munjal, Sagar; Brand-Schieber, Elimor; Rapoport, Alan M. 2019 in CNS Drugs.

Effectiveness of intravenous dexamethasone, metoclopramide, ketorolac, and chlorpromazine for pain relief and prevention of recurrence in the migraine headache: a prospective double- blind randomized clinical trial