Travoprost intraocular implant demonstrated an excellent systemic safety profile with no measurable systemic drug levels

Abstract

Purpose : A Phase II prospective, randomized, double-masked, multicenter trial was conducted to evaluate the efficacy, safety and systemic pharmacokinetics of 2 models of the travoprost intraocular implant (fast-eluting [FE implant] and slow-eluting [SE implant]) compared to twice daily (BID) topical timolol ophthalmic solution, 0.5% in subjects with open-angle glaucoma or ocular hypertension.

Methods : The trial enrolled 154 subjects in the US and Philippines: FE implant + BID artificial tears (n=51), SE implant + BID artificial tears (n=54) and sham procedure + BID timolol 0.5% (n=49). Blood samples were collected at week 1-2, month 3 and month 12, and analyzed for travoprost free acid (TFA) using a validated LC-MS/MS analytical method. IOP, safety parameters and adverse events (AEs) were evaluated at multiple timepoints through month 36. Subjects could be prescribed additional IOP-lowering therapy if their IOP exceeded 18 mmHg at week 4 or later.

Results : Plasma TFA levels were all below the limit of quantitation (<10 pg/mL) at all the time points, including baseline, week 1-2, week 12, and month 12. In comparison, according to the prescribing information for Travatan Z, following topical administration of travoprost ophthalmic solution, 0.004%, quantifiable drug concentrations were observed in 38 out of 107 subjects with a mean plasma Cmax of 18 ± 7 pg/mL (ranging from 10 to 52 pg/mL) [1].
During the 36-month trial, no treatment-related systemic AEs attributed to the travoprost intraocular implants were reported; one implant subject had dyspnea and another had urinary incontinence, both unrelated to implant treatment. Three timolol subjects (6.1%) had a total of 5 treatment-related systemic AEs (cognitive disorder and fatigue; myasthenia gravis and bradycardia; rhinorrhoea).

Conclusions : There was no systemic exposure to travoprost delivered via travoprost intraocular implants whereas there is systemic exposure to travoprost following eye drop delivery. Lack of systemic exposure to travoprost corresponded with no systemic treatment-related AEs attributed to travoprost intraocular implants.

References:
[1] Travatan Z® (travoprost ophthalmic solution) US Prescribing Information. 2023

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.