Pharmacokinetic Characterization and Dose Selection of a Novel Sumatriptan Nasal Spray Formulation, DFN-02.

This 3-way, single-dose, randomized crossover study evaluated the pharmacokinetics (PK) and dose proportionality of 5-, 10-, and 15-mg doses of intranasal sumatriptan (DFN-02) coformulated with a permeation enhancer (DDM) in 18 healthy adults. The objective was to determine which DFN-02 dose approximates the PK of a 6-mg dose of sumatriptan delivered via subcutaneous injection in the deltoid muscle of the arm. Sumatriptan plasma concentrations peaked with DFN-02 between 10 and 15 minutes postdose, declining thereafter, with a t1/2 of about 2.5 hours; mean Cmax and AUC0-∞ values increased linearly across doses. After DFN-02 doses of 5, 10, and 15 mg, mean Cmax was 40.7 ± 14.2, 71.2  ±  22.1, and 101.0  ±  49.5 ng/mL, and mean AUC0-∞ was 49.9  ±  20.6, 87.1  ± 31.2, and 120.5  ± 53.3 ng·h/mL, respectively. The increase in sumatriptan bioavailability was less than dose-proportional among the DFN-02 doses studied. Based on the established PK of a 6-mg subcutaneous sumatriptan injection (mean Tmax ,  12 minutes; mean Cmax ,  74  ± 15 ng/mL in the deltoid area of the arm) and the peak and time to peak sumatriptan concentrations of the DFN-02 doses tested, a 10-mg dose of DFN-02 was found to be the closest match. Overall, DFN-02 was well tolerated at doses of 5 to 15 mg, and no new safety concerns were identified.