Phase 3 Randomized Clinical Trial of the Safety and Efficacy of Travoprost Intraocular Implant in Patients with Open-Angle Glaucoma or Ocular Hypertension.

PURPOSE: Evaluate the safety and intraocular pressure (IOP)-lowering efficacy of two models of the travoprost intraocular implant (fast-eluting [FE-implant] and slow eluting [SE-implant]) from one of two pivotal trials (GC-010).

DESIGN: Phase 3, multicenter, randomized, double-masked, sham-controlled, non-inferiority trial.

PARTICIPANTS: Subjects with open-angle glaucoma or ocular hypertension, using 0 to 3 IOP-lowering medications at screening and having an unmedicated baseline mean diurnal IOP (average of 8AM, 10AM and 4PM timepoints) of ≥ 21 mmHg, and an unmedicated baseline IOP of ≤ 36 mmHg at each timepoint in the study eye.

METHODS: Study eyes were randomized to the travoprost intraocular implant (FE-implant [n=200] or SE-implant [n=197] model) plus twice-daily (BID) placebo eye drops, or to sham procedure plus timolol ophthalmic solution, 0.5% BID (n=193).

MAIN OUTCOME MEASURES: The primary outcome was mean change from baseline IOP in the study eye at 8AM and 10AM, at each of day 10, week 6, and month 3. Safety outcomes included adverse events (AEs), corneal endothelial cell counts, visual acuity, and conjunctival hyperemia assessment.

RESULTS: Mean IOP reduction from baseline over the 6 timepoints ranged from 6.6 to 8.4 mmHg for the FE-implant group, from 6.6 to 8.5 mmHg for the SE-implant group, and from 6.5 to 7.7 mmHg for the timolol group. The primary efficacy endpoint was met; the upper limit of the 95% confidence interval of the difference between the implant groups and the timolol group was < 1 mmHg at all 6 timepoints. Study eye AEs, most of mild or moderate severity, were reported in 21.5%, 27.2% and 10.8% of subjects in the FE-implant, SE-implant and timolol groups, respectively. The most common AEs included iritis (FE-implant, 0.5%; SE-implant, 5.1%), ocular hyperaemia (FE-implant, 3.0%; SE-implant, 2.6%), visual acuity reduced (FE-implant, 1.0%; SE-implant, 4.1%; timolol, 0.5%), and IOP increased (FE-implant, 3.5%; SE-implant, 2.6%; timolol, 2.1%). There was one serious study eye AE (endophthalmitis).

CONCLUSIONS: The travoprost intraocular implant demonstrated robust IOP reduction over the 3-month primary efficacy evaluation period following a single administration. The IOP-lowering efficacy of both implant groups was statistically and clinically non-inferior to the timolol group, with a favorable safety profile.