title: A multicenter, open-label, long-term safety and tolerability study of DFN-02, an intranasal spray of sumatriptan 10 mg plus permeation enhancer DDM, for the acute treatment of episodic migraine.
abstract: BACKGROUND
  DFN-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.
  
  
  METHODS
  This 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.
  
  
  RESULTS
  A 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.
  
  
  CONCLUSIONS
  DFN-02 was shown to be well tolerated when used over 6 months to treat episodic migraine acutely.
authors.affiliation: Dr. Reddy's Laboratories Ltd., 107 College Road East Princeton, Princeton, NJ, 08540, USA. smunjal@drreddys.com.
authors.forename: Sagar
authors.initials: S
authors.lastname: Munjal
authors.affiliation: Dr. Reddy's Laboratories Ltd., 107 College Road East Princeton, Princeton, NJ, 08540, USA.
authors.forename: Elimor
authors.initials: E
authors.lastname: Brand-Schieber
authors.affiliation: Dr. Reddy's Laboratories Ltd., 107 College Road East Princeton, Princeton, NJ, 08540, USA.
authors.forename: Kent
authors.initials: K
authors.lastname: Allenby
authors.affiliation: Dental Medicine Headache & Face Pain Program Tufts Medical Center, Craniofacial Pain Center Tufts University School, 800 Washington Street Boston, Boston, MA, 02111, USA.
authors.forename: Egilius L H
authors.initials: ELH
authors.lastname: Spierings
authors.affiliation: Clinvest/A Division of Banyan Inc., 3805 S Kansas Expy Springfield, Springfield, MO, 65807, USA.
authors.forename: Roger K
authors.initials: RK
authors.lastname: Cady
authors.affiliation: David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
authors.forename: Alan M
authors.initials: AM
authors.lastname: Rapoport
mesh_terms: D000281:Administration, Intranasal; D000328:Adult; D004338:Drug Combinations; D005260:Female; D006801:Humans; D008297:Male; D008320:Maltose / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology; D008875:Middle Aged; D008881:Migraine Disorders / Q000188:drug therapy*; D059085:Nasal Sprays; D018170:Sumatriptan / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology; D016896:Treatment Outcome; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology; D055815:Young Adult
chemical_list: D004338:Drug Combinations; D059085:Nasal Sprays; D014662:Vasoconstrictor Agents; C411362:dodecyl maltopyranoside; D008320:Maltose; D018170:Sumatriptan
keywords: Acute treatment; DDM; Episodic migraine; Intranasal sumatriptan; Long-term safety; Sumatriptan