A Randomized Trial Comparing the Pharmacokinetics, Safety, and Tolerability of DFN-02, an Intranasal Sumatriptan Spray Containing a Permeation Enhancer, With Intranasal and Subcutaneous Sumatriptan in Healthy Adults

Objective/Background Intranasal sumatriptan (Imitrex®) may be an alternative for patients who refuse injections and cannot tolerate oral agents, but due to low bioavailability and slow absorption, the clinical utility of the currently marketed formulation is limited, highlighting an unmet need for an effective non‐oral migraine medication with a rapid onset of action. To overcome the slow absorption profile associated with intranasal administration, we evaluated the impact of 1‐O‐n‐Dodecyl‐β‐D‐Maltopyranoside (DDM, Intravail A‐3™), a permeation enhancer, on sumatriptan's pharmacokinetic profile by comparing the pharmacokinetic characteristics of two commercial sumatriptan products, 4 mg subcutaneous and 6 mg subcutaneous in healthy adults, with DFN‐02 – a novel intranasal agent comprised of sumatriptan 10 mg plus 0.20% DDM. We also determined the pharmacokinetic characteristics of DDM and evaluated its safety and tolerability. Methods We conducted two studies: a randomized, three‐way crossover study comparing monodose and multidose devices for delivery of single doses of DFN‐02 with commercially available intranasal sumatriptan 20 mg in 18 healthy, fasted adults, and an open‐label, randomized, single‐dose, three‐way crossover bioavailability study comparing DFN‐02 with 4 mg and 6 mg subcutaneous sumatriptan in 78 healthy, fasted adults. In the study comparing DFN‐02 with IN sumatriptan, subjects received a single dose of DFN‐02 (sumatriptan 10 mg plus DDM 0.20%) via monodose and multidose delivery systems with at least 5 days between treatments. In the comparison with SC sumatriptan, subjects received a single dose of each treatment with at least 3 days between treatments. In both studies, blood was sampled for pharmacokinetic evaluation of sumatriptan and DDM through 24 hours post‐dose; safety and tolerability were monitored throughout. Results In the comparison with commercially available intranasal sumatriptan 20 mg, DFN‐02 had a more rapid absorption profile; tmax was 15 minutes for DFN‐02 monodose, 10.2 minutes for DFN‐02 multidose, and 2.0 hours for commercially available intranasal sumatriptan 20 mg. Compared with 4 and 6 mg subcutaneous sumatriptan, DFN‐02's median tmax (10 minutes) was significantly earlier (15 minutes; P