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

Abstract 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 t 1/2 of about 2.5 hours; mean C max and AUC 0–∞ values increased linearly across doses. After DFN‐02 doses of 5, 10, and 15 mg, mean C max was 40.7 ± 14.2, 71.2 ± 22.1, and 101.0 ± 49.5 ng/mL, and mean AUC 0–∞ 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 T max , 12 minutes; mean C max , 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.