Pharmacokinetics of intranasal olopatadine in the fixed-dose combination GSP301 versus two monotherapy intranasal olopatadine formulations.

BACKGROUND

GSP301 is a fixed-dose combination of the antihistamine olopatadine hydrochloride and the corticosteroid mometasone furoate developed as a single nasal spray.

OBJECTIVE

To assess the relative bioavailability of olopatadine administered as GSP301 versus two olopatadine monotherapy nasal spray formulations.

METHODS

In this single-dose, open-label, crossover study, healthy adults (18-65 years old) were equally randomized to one of six treatment sequences for three 48-hour treatment periods with GSP301 (olopatadine 665 μg-mometasone 50 μg), the olopatadine monotherapy component of GSP301 (OLO-sponsor; 665 μg) and U.S. Food and Drug Administration approved olopatadine (OLO; 665 μg); each treatment was administered as a single dose (two sprays in each nostril). To assess the relative bioavailability of olopatadine in the fixed-dose nasal spray versus two monotherapies, pharmacokinetic (PK) estimates, maximum plasma concentration (Cmax), area under the plasma concentration time curve (AUC) from time 0 to the last time point with measurable concentration (AUC0-t), and AUC from time 0 to time infinity (AUC0-∞) were compared by analysis of variance. Safety and tolerability were also evaluated.

RESULTS

A total of 30 healthy adults (mean age, 43.1 years) were randomized. The majority of the subjects were white men. The geometric mean ratios for natural log transformed Cmax, AUC0-t, and AUC0-∞ of olopatadine in GSP301 and OLO-sponsor were 86.63, 86.92, and 92.83, respectively. For GSP301 and OLO, geometric mean ratios for Cmax, AUC0-t, and AUC0-∞ were 84.68, 87.87, and 93.80, respectively. The percentage of subjects who reported treatment-emergent adverse events (AE) for GSP301, OLO-sponsor, and OLO were 13.8, 10.3, and 10.0%, respectively, with mild AEs reported. One subject withdrew from the study due to an AE (minor oropharyngeal pain) during OLO treatment, before receiving GSP301.

CONCLUSION

Olopatadine bioavailability with GSP301 was comparable with OLO-sponsor and OLO. The presence of mometasone in GSP301 did not considerably affect the PK of olopatadine. GSP301 was well tolerated, with only mild AEs reported.