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

Background: GSF301 is a fixed-dose combination of the antihistamine olopatadine hydrochloride ana the corticosteroid mometasonefurcate developed as a single nasal spray. Objective: To assess the relative bioavailability of olopatadine administered as GSF301 versus two olopatadine manotherapy 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 (olapatatine 665 mu g-mometasone 50 mu g), the olopatadine monotherapy component of GSF301 (OLO-sponsor; 665 mu g) and U.S. Food and Drug Administration approved olopatadine (OLO; 665,mg); each treatment was administered as a single dose (two sprays in each nostril). To assess the relative bioavadability of olopaMdine in the fixed-dose nasal spray versus two Monotherapies, pharmacokinetic (PK) estimates, maaximum plasma concentratMn (C-max) area under the plasma cancentration time Curve (AUC) from time 0 to the last time point with measurable concentration (AUC(0-t)) and AUCfrom time 0 to tune infinity (AUC(0-infinity)) were compared by analysis o variance. Safety and tolerability were also evaluated, Results: A total of 30 healthy adults (mean ages 43.1 years) zoom randomized. The nsajority of the subjects were white men. The geometric mean ratios for natural log transformed C-max ADC(0-t) and AUCM(0-infinity) of olopatadine in GSP301 and OLO-sponsor were 86.63, 86.92, and 92.83, respectively. For GSP301 and OLO, geometric mean ratios for C-max ADC(0-t) and UCM0-infinity were 84.68, 87.87, and 93.80, respectively. The percentage of subjects who n?ported 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 froln the study due to an AEt i I ropharyngeal pain) during OLO treatment, Mfore receiving GSP301. Conclusion: Olopatadine bioavaiMbility with GSP301 was comparable with OLO-sponsor and OLO. The presence of mometasone in GSP301 did nU considerably affect the PK of olopatadine. GSP301 was well tolerated, with only mild AEs reported.