Phase 3, Randomized Study Comparing Intracameral Bimatoprost Implant 15 µg and Selective Laser Trabeculectomy in Patients with Open-Angle Glaucoma or Ocular Hypertension

Abstract

Purpose

We evaluate the safety and intraocular pressure (IOP)-lowering effect of 15-µg bimatoprost implant (higher dose than the currently approved product) compared with selective laser trabeculoplasty (SLT) in patients with open-angle glaucoma or ocular hypertension.

Methods

Randomized, phase 3, 12-month, multicenter, paired-eye, patient- and efficacy evaluator–masked noninferiority study. Patients with inadequate IOP control were randomized to receive 360° SLT (day 1) or up to 3 administrations of 15-µg bimatoprost implant (day 4, weeks 16 and 32) in the primary eye and the alternative treatment in the contralateral eye. The primary endpoint was IOP change from baseline at weeks 4, 12, and 24.

Results

At weeks 4, 12, and 24, mean IOP change from baseline ranged from −7.01 to −6.65 mm Hg in implant-treated eyes (N=138) and −6.45 to −6.26 mm Hg in SLT-treated eyes (N=138). Differences in IOP change from baseline ranged from −0.70 to −0.25 mm Hg favoring implant; the upper limit of the 95% confidence interval of the difference (implant minus SLT) was <1.0 mm Hg at all 3 visits. The probability of requiring no additional (rescue) IOP-lowering treatment in implant-treated versus SLT-treated eyes was 93.6% versus 86.5% at day 180 and 74.6% versus 77.1% at day 360. Corneal endothelial cell loss was more common in implant-treated eyes and typically occurred after repeated implant administration.

Conclusion

Bimatoprost implant 15 µg met prespecified criteria for statistical and clinical noninferiority to SLT in lowering IOP, and after 1, 2, or 3 administrations, demonstrated a duration of IOP lowering similar to SLT. Bimatoprost implant 15 µg was associated with corneal adverse events in some patients, especially after repeated administrations at a fixed interval, and has been discontinued from development. A lower dose strength of implant (bimatoprost implant 10 µg, Durysta) is US Food and Drug Administration–approved for single administration.

Keywords:

• clinical trial
• drug delivery device
• intracameral
• paired eye

Abbreviations

BCVA, best-corrected visual acuity; CECD, central endothelial cell density; CI, confidence interval; IOP, intraocular pressure; ITT, intent-to-treat; LSM, least-squares mean; mITT, modified intent-to-treat; MMP, matrix metalloproteinase; OAG, open-angle glaucoma; OHT, ocular hypertension; PGA, prostaglandin analog/prostamide; SD, standard deviation; SLT, selective laser trabeculoplasty; TEAE, treatment-emergent adverse event.

Data Sharing Statement

AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual, and trial-level data (analysis data sets), as well as other information (eg, protocols, clinical study reports, or analysis plans), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications. These clinical trial data can be requested by any qualified researchers who engage in rigorous, independent, scientific research, and will be provided following review and approval of a research proposal, Statistical Analysis Plan (SAP), and execution of a Data Sharing Agreement (DSA). Data requests can be submitted at any time after approval in the US and Europe and after acceptance of this manuscript for publication. The data will be accessible for 12 months, with possible extensions considered. For more information on the process or to submit a request, visit the following link: https://www.abbvieclinicaltrials.com/hcp/data-sharing/.

Principal Investigators

Louis Alpern, MD; Mahdi Basha, MD; Lance Bergstrom, MD; James Branch, MD; Maria I. Canut, MD; William Christie, MD; Anastasios Costarides, MD; Frank Cotter, MD; Douglas Day, MD; Michael Depenbusch, MD; Alena Eremina, MD; John Galanis, MD; Julián García Feijoo, MD; Damien Goldberg, MD; Brennan Greene, MD; Linda Hansapinyo, MD; William Haynes, MD; Sebastian Heersink, MD; Bartłomiej Kałużny, MD; Miriam Kolko, MD; Benjamin Lambright, MD; Oleg Lebedev, MD; Christopher Lin, MD; Manchima Makornwattana, MD; Kundandeep Nagi, MD; Shamira Perera, MBBS, FRCOphth; Muriel Poli, MD; Cedric Schweitzer, MD; Pankajkumar Shah, MD; Scott Smetana, MD; Valerie Trubnik, MD; Gerald Walman, MD; Dominik Zalewski, MD

Acknowledgments

AbbVie and the authors thank the investigators and patients who participated in this study. Evidence Scientific Solutions, Inc (Philadelphia, PA, USA) provided medical writing assistance for the development of this publication. All authors had access to relevant data and participated in the drafting, review, and approval of this publication. No honoraria or payments were made for authorship.

Disclosure

William C. Christie is a consultant for Allergan (an AbbVie company). Mahdi M. Basha has received research support from AbbVie, Alcon, Formosa Pharmaceuticals, Glaukos, Ivantis, Novartis, and Ocular Therapeutix, and is a speaker for AbbVie and Alcon. Quoc Ho, Kimmie Kim, and E. Randy Craven are employees of AbbVie Inc and may hold stock/stock options. Miriam Kolko is a speaker for AbbVie, Santen, Thea Laboratories, and Topcon. In addition, Miriam Kolko sits on advisory boards for AbbVie, Santen, and Thea Laboratories. The authors report no other conflicts of interest in this work.

Additional information

Funding

This study was sponsored by Allergan (an AbbVie company), Irvine, CA, USA. Allergan/AbbVie participated in the design of the study, data management, data analysis, interpretation of the data, and preparation, review, and approval of the manuscript.