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

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posted on 27.01.2021, 04:44 by FA Medeiros, TR Walters, M Kolko, Michael Coote, M Bejanian, ML Goodkin, Q Guo, J Zhang, MR Robinson, RN Weinreb, A Agar, R Bathijia, L Liu, T Roberts, C Faschinger, C Vass, N Collignon, AC Alves Pereira, R Belfort de Mattos, FJ Dantas, MJ Lopes da Silva, F Kanadani, L Magacho dos Santos Silva, T Prata, D Bach-Holm, J Lai, C Tham, G Bátor, L Szalczer, B Varsányi, E Blumenthal, O Geyer, S Lavartovsky, T Pedut-Kloizman, N Shoham-Hazon, S Lujan, B Abela, RE Ang, EU Leuenberger, H Uy, MI Yap-Veloso, P Fryczkowski, P Jurowski, B Kalużny, J Kalużny, M Misiuk-Hojlo, K Raczynska, W Tomczyk-Dorozynska, J Wasyluk, S Zalewski, T Zarnowski, JG Feijoó, R Giménez-Gómez, EM Griño, AA López, MG Miralles, JM Moreno, V Polo, EC Taulet, BP Zúñiga, YY Chen, YC Lee, L Alpern, MS Berlin, J Brubaker, D Caldwell, A Camp, LB Cantor, R Caronia, CJ Crane, D Day, E Duzman, J Elfervig, S El-Harazi, R Evans, AC Fisher, WJ Flynn, CS Foster, R Frenkel, R Goyal, R Gross, PJ Hartman, WL Haynes, G Jerkins, J Kim, M Kim, B Kwapiszeski, B Lambright, C Larsen, J Lehmann, JH Levenson, D Logan, B McMillan, JR Martel, H Mayer, F Medeiros, S Moroi, A Moyes, J Myers, J Nairn
© 2020 American Academy of Ophthalmology 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.

Funding

Kevin Wang, PhD, an independent contractor funded by Allergan plc, contributed to the statistical analyses for the manuscript under the direction of the authors. Adnan Salemeh, PhD, of Allergan plc (Irvine, CA), provided the in vitro drug release data, and Jennifer R. Seal, PhD, of Allergan plc (Irvine, CA), provided the animal pharmacokinetics data. Michele Jacob, PhD, of Evidence Scientific Solutions, Inc. (Philadelphia, PA), prepared a draft of the manuscript under the direction of the authors and provided editorial assistance, funded by Allergan plc. All authors met the International Committee of Medical Journal Editors authorship criteria. Neither honoraria nor payments were made for authorship. The author(s) have made the following disclosure(s): F.A.M.: Consultant Allergan, Annexon, Aerie Pharmaceuticals, Biogen, Carl Zeiss Meditec, Galimedix, Novartis, Reichert, Stealth BioTherapeutics; Research support Carl Zeiss Meditec, Google, Heidelberg Engineering, Reichert; Founder NGoggle, Inc. T.R.W.: Consultant Alcon, Allergan, Envisia, Ocular Therapeutix, Omeros. M.K.: Consultant and speaker Allergan, Santen, Thea; Research support LeoPharma, Thea.M.C.: Consultant Allergan.M.B., M.L.G., Q.G., J.Z., and M.R.R.: Employees Allergan plc.R.N.W.: Consultant Aerie Pharmaceuticals, Allergan plc, Eyenovia, Galimedix, Implantdata, Novartis; Research support BauschþLomb,Centervue, Heidelberg Engineering, Konan, Meditec-Zeiss, National EyeInstitute, Optovue; Founder Toromedes; Royalties University ofCalifornia San Diego from Carl Zeiss Meditec. Sponsored by Allergan plc (Dublin, Ireland). The sponsor participated in the design of the study, data management, data analysis, interpretation of the data, and preparation, review, and approval of the manuscript.

History

School

  • School of Allied Health

Publication Date

01/12/2020

Journal

Ophthalmology

Volume

127

Issue

12

Pagination

15p. (p. 1627-1641)

Publisher

Elsevier Inc

ISSN

0161-6420

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