Phase 3, Randomized, 20-Month Study of Bimatoprost Implant in Open-Angle Glaucoma and Ocular Hypertension (ARTEMIS 1).

PURPOSE

To evaluate the intraocular pressure (IOP)-lowering efficacy and safety of 10- and 15-μg bimatoprost implant in subjects with open-angle glaucoma (OAG) and ocular hypertension (OHT) after initial and repeated administrations.

DESIGN

Randomized, 20-month, multicenter, subject- and efficacy evaluator-masked, parallel-group, phase 3 clinical study.

PARTICIPANTS

Adults with OAG or OHT in each eye, open iridocorneal angle inferiorly in the study eye, and study eye baseline IOP (hour 0; 8 am) of 22-32 mmHg after washout.

METHODS

Study eyes received bimatoprost implant 10 μg (n = 198) or 15 μg (n = 198) on day 1 with readministration at weeks 16 and 32, or twice-daily topical timolol maleate 0.5% (n = 198). Intraocular pressure was measured at hours 0 and 2 at each visit.

MAIN OUTCOME MEASURES

Primary end points were IOP and change from baseline IOP through week 12. Safety measures included treatment-emergent adverse events (TEAEs) and corneal endothelial cell density (CECD).

RESULTS

Both dose strengths of bimatoprost implant were noninferior to timolol in IOP lowering after each administration. Mean diurnal IOP was 24.0, 24.2, and 23.9 mmHg at baseline and from 16.5-17.2, 16.5-17.0, and 17.1-17.5 mmHg through week 12 in the 10-μg implant, 15-μg implant, and timolol groups, respectively. The incidence of corneal and inflammatory TEAEs of interest (e.g., corneal endothelial cell loss, iritis) was higher with bimatoprost implant than timolol and highest with the 15-μg dose strength. Incidence of corneal TEAEs increased after repeated treatment; with 3 administrations at fixed 16-week intervals, incidence of ≥20% CECD loss was 10.2% (10-μg implant) and 21.8% (15-μg implant). Mean best-corrected visual acuity (BCVA) was stable; 3 implant-treated subjects with corneal TEAEs had >2-line BCVA loss at their last visit.

CONCLUSIONS

Both dose strengths of bimatoprost implant met the primary end point of noninferiority to timolol through week 12. One year after 3 administrations, IOP was controlled in most subjects without additional treatment. The risk-benefit assessment favored the 10-μg implant over the 15-μg implant. Ongoing studies are evaluating other administration regimens to reduce the potential for CECD loss. The bimatoprost implant has potential to improve adherence and reduce treatment burden in glaucoma.