Pharmacokinetics and safety of olopatadine hydrochloride 0.77% in healthy subjects with asymptomatic eyes: data from 2 independent clinical studies

Abstract

Purpose: To assess the pharmacokinetics and safety of hydrochloride ophthalmic solution 0.77% olopatadine from 2 independent (Phase I and Phase III, respectively) clinical studies in healthy subjects.

Materials and methods: The Phase I, multicenter, randomized (2:1), vehicle-controlled study was conducted in subjects ≥18 years old (N=36) to assess the systemic pharmacokinetics of olopatadine 0.77% following single- and multiple-dose exposures. The Phase III, multicenter, randomized (2:1), vehicle-controlled study was conducted in subjects ≥2 years old (N=499) to evaluate long-term ocular safety of olopatadine 0.77%. Subjects received olopatadine 0.77% or vehicle once daily bilaterally for 7 days in the pharmacokinetic study and 6 weeks in the safety study.

Results: In the pharmacokinetic study, olopatadine 0.77% was absorbed slowly and reached a peak plasma concentration (C_max) of 1.65 ng/mL following single-dose and 1.45 ng/mL following multiple-dose exposures in 2 hours (time to reach maximum plasma concentration [T_max]). After reaching peak concentrations, olopatadine showed a similar mono-exponential decay following single and multiple doses with mean elimination half-life ranging from 2.90 to 3.40 hours. No accumulation in olopatadine exposure (C_max and area under the plasma concentration-time curve from 0 to 12 hours) was evident after multiple doses when compared to single dose. In the safety study, treatment-emergent adverse events were reported in 26.7% and 31.4% of subjects with olopatadine 0.77% and vehicle, respectively. Blurred vision was the most frequent ocular treatment-emergent adverse event in both treatment groups (olopatadine 0.77% vs vehicle, 4.8% vs 4.1%). No deaths or serious adverse events were reported during the study.

Conclusion: Olopatadine 0.77% had minimal systemic exposure or accumulation in healthy subjects and was well tolerated in both adult and pediatric subjects.

Keywords: allergic conjunctivitis; ocular allergy; olopatadine; pharmacokinetics; safety.

Figure 1

Study design of (A) pharmacokinetic study and (B) safety study. Notes: *PK sampling: 0 hour (pre-dose), 0.25, 0.5, 1, 2, 4, 8, and 12 hours. ^$PK sampling: 0 hour (trough–24 hours after 1st dose-trough). ^‡PK sampling: 0 hour (trough). ^ΦAll 3 subjects withdrew from the study with consent, and the withdrawal was not related to the treatment. ^#One subject was not included in the safety population because of randomization error and for not receiving the investigational product. Abbreviations: IP, investigational product; PK, pharmacokinetics; TC, telephonic contact.

Figure 2

Mean olopatadine 0.77% plasma concentration over time (A) and AUC_0–12 (B) following single-dose (Day 1) and multiple-dose (Day 7) exposure. Notes: ^#n=9 at 8- and 12-hour time points due to study consent withdrawal. Data for Day 7 AUC_0–12 are from 19 subjects. AUC_0–12, area under the plasma concentration–time curve from 0 to 12 hours.