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

Allergy Asthma Proc. 2018 May 1;39(3):224-231. doi: 10.2500/aap.2018.39.4133.

Abstract

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.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Administration, Intranasal
  • Adolescent
  • Adrenal Cortex Hormones / pharmacology*
  • Adult
  • Aged
  • Cross-Over Studies
  • Drug Combinations
  • Female
  • Healthy Volunteers
  • Histamine Antagonists / pharmacokinetics*
  • Humans
  • Male
  • Middle Aged
  • Mometasone Furoate / pharmacokinetics*
  • Nasal Sprays
  • Olopatadine Hydrochloride / pharmacokinetics*
  • Rhinitis, Allergic, Seasonal / drug therapy*
  • Young Adult

Substances

  • Adrenal Cortex Hormones
  • Drug Combinations
  • Histamine Antagonists
  • Nasal Sprays
  • Mometasone Furoate
  • Olopatadine Hydrochloride