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:

• ocular allergy
• allergic conjunctivitis
• olopatadine
• pharmacokinetics
• safety

Supplementary materials

Table S1 Pharmacokinetic parameters following single- and multiple-dose exposures of olopatadine 0.77% in Japanese and non-Japanese subjects

Table S2 Overall summary of treatment-related AEs occurring at an incidence of ≥1% by treatment (safety population)

Table S3 Summary of TEAEs in selected age subgroups occurring at an incidence of ≥1% by treatment (safety population)

Table S4 Comparison of mean human plasma pharmacokinetic parameters following topical ocular and oral single- and multiple-dose exposures of olopatadine

Reference

• TsunooMMomomuraSMasuoMIizukaHPhase 1 clinical study on KW-4679, an antiallergic drug: safety and pharmacokinetics in the single and repeated administration study in healthy subjectsKiso To Rinsho19952918
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Acknowledgments

This study was funded by Alcon Laboratories, Inc. (Fort Worth, TX, USA). The authors thank Audesh Bhat and Usha Gutti (Global Medical and Clinical Services, Novartis Healthcare Pvt Ltd., Hyderabad, India) for their medical writing and editorial assistance toward the development of this manuscript.

Disclosure

Dr Abhijit Narvekar is an employee in Alcon Research Ltd (Fort Worth, TX, USA). The other authors report no conflicts of interest in this work.