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

Abstract

Background: The commercial formulation of sumatriptan nasal spray is an effective option for migraine patients requiring or preferring a non-oral route of drug administration, but its utility is limited by poor absorption and tolerability issues. DFN-02, a new formulation of sumatriptan 10 mg nasal spray, is co-formulated with a permeation enhancer that gives it pharmacokinetics comparable to subcutaneous sumatriptan. As reported previously, DFN-02 was significantly better than placebo on multiple efficacy endpoints at 2 h postdose, including pain freedom, absence of the most bothersome symptom, and pain relief, and its safety and tolerability profiles were excellent.

Objective: 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.

Methods: This was a multicenter, randomized, double-blind, placebo-controlled efficacy and safety study of DFN-02 in adults with episodic migraine. Functional disability and subject satisfaction with treatment were prespecified endpoints, assessed in real-time by subjects, using an electronic diary.

Results: In total, 107 subjects were randomized. DFN-02 was significantly superior to placebo for the reduction in functional disability score from predose level at 2 h after treatment (- 1.2 vs. - 0.6, p < 0.001). Subjects treated with DFN-02 were also more likely to be satisfied or very satisfied than subjects treated with placebo at 2 h postdose (70.0% vs. 44.2%, p = 0.027). Using the Patient Perception of Migraine Questionnaire-Revised at 24 h postdose, 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).

Conclusion: DFN-02 was superior to placebo for the relief of migraine-related functional disability, and provided greater satisfaction than placebo or subjects' usual acute treatment.

Trial registration: ClinicalTrials.gov identifier: NCT02856802.

Conflict of interest statement

Conflicts of Interest

Sagar Munjal and Elimor Brand-Schieber are employed by and own stock in Dr. Reddy’s Laboratories Ltd. Richard B. Lipton and Alan M. Rapoport are paid consultants of Dr. Reddy’s Laboratories Ltd, but they were not paid to draft or edit this paper. Richard B. Lipton has received grant support from the National Institutes of Health, the National Headache Foundation, and the Migraine Research Fund. He serves as a consultant and advisory board member for, or has received honoraria from, Alder, Allergan, American Headache Society, Autonomic Technologies, Boston Scientific, Bristol Myers Squibb, Cognimed, CoLucid, Eli Lilly, eNeura Therapeutics, Merck, Novartis, Pfizer, and Teva, Inc. He has stock options in eNeura Therapeutics and Biohaven Pharmaceuticals. He also receives royalties for Wolff’s Headache, 8th Edition (Oxford University Press, 2009). Alan M. Rapoport is on the speaker’s bureau of Amgen, electroCore, Promius Pharma, and Teva, and is a consultant for Amgen, Autonomic Technologies, Neurolief, Satsuma, Theranova, and Zosano.

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The protocol, patient information and consent form, and other relevant study documentation were approved by the Institutional Review Board (IRB) for each study center prior to initiation of this study.

Informed Consent

All study participants provided written informed consent.

Figures

Fig. 1

Change from baseline in functional disability scores at 2 h postdose

Fig. 2

Subject-rated treatment satisfaction at 24 h postdose-PPMQ-R. aHigher values indicate greater satisfaction. bLower values indicate greater satisfaction. PPMQ-R Patient Perception of Migraine Questionnaire-Revised