24-Month Phase I/II Clinical Trial of Bimatoprost Sustained-Release Implant (Bimatoprost SR) in Glaucoma Patients

E Randy Craven, Thomas Walters, William C Christie, Douglas G Day, Richard A Lewis, Margot L Goodkin, Michelle Chen, Veronica Wangsadipura, Michael R Robinson, Marina Bejanian, Bimatoprost SR Study Group, Tin Aung, Allen D Beck, James D Branch, William C Christie, Michael Coote, Charles J Crane, E Randy Craven, Andrew Crichton, Douglas G Day, Steven Day, F Jane Durcan, Richard M Evans, William J Flynn, Sébastien Gagné, Damien F Goldberg, Jack V Greiner, Paul Jeppsen, Delan Jinapriya, C Starck Johnson, Shimon Kurtz, Richard A Lewis, Steven L Mansberger, Joseph R Martel, Shamira A Perera, Michael H Rotberg, Robert M Saltzmann, Howard I Schenker, Michael E Tepedino, Maria Imelda R Yap-Veloso, Harvey S Uy, Thomas R Walters, E Randy Craven, Thomas Walters, William C Christie, Douglas G Day, Richard A Lewis, Margot L Goodkin, Michelle Chen, Veronica Wangsadipura, Michael R Robinson, Marina Bejanian, Bimatoprost SR Study Group, Tin Aung, Allen D Beck, James D Branch, William C Christie, Michael Coote, Charles J Crane, E Randy Craven, Andrew Crichton, Douglas G Day, Steven Day, F Jane Durcan, Richard M Evans, William J Flynn, Sébastien Gagné, Damien F Goldberg, Jack V Greiner, Paul Jeppsen, Delan Jinapriya, C Starck Johnson, Shimon Kurtz, Richard A Lewis, Steven L Mansberger, Joseph R Martel, Shamira A Perera, Michael H Rotberg, Robert M Saltzmann, Howard I Schenker, Michael E Tepedino, Maria Imelda R Yap-Veloso, Harvey S Uy, Thomas R Walters

Abstract

Objective: The objective of this study was to evaluate the safety and intraocular pressure (IOP)-lowering effects over 24 months of biodegradable bimatoprost sustained-release implant (Bimatoprost SR) administration versus topical bimatoprost 0.03% in patients with open-angle glaucoma (OAG).

Methods: This was a phase I/II, prospective, 24-month, dose-ranging, paired-eye controlled clinical trial. At baseline following washout, adult patients with OAG (N = 75) received Bimatoprost SR (6, 10, 15, or 20 µg) intracamerally in the study eye; the fellow eye received topical bimatoprost 0.03% once daily. Rescue topical IOP-lowering medication or single repeat administration with implant was permitted. The primary endpoint was IOP change from baseline. Safety measures included adverse events (AEs).

Results: At month 24, mean IOP reduction from baseline was 7.5, 7.3, 7.3, and 8.9 mmHg in eyes treated with Bimatoprost SR 6, 10, 15, and 20 µg, respectively, versus 8.2 mmHg in pooled fellow eyes; 68, 40, and 28% of pooled study eyes had not been rescued/retreated at months 6, 12, and 24, respectively. AEs in study eyes that occurred ≤ 2 days post-procedure typically were transient. After 2 days post-procedure, overall AE incidence was similar between study and fellow eyes, with some events typically associated with topical prostaglandin analogs having lower incidence in study eyes.

Conclusions: Bimatoprost SR showed favorable efficacy and safety profiles up to 24 months, with all evaluated dose strengths demonstrating overall IOP-reducing effects comparable to those of topical bimatoprost. Targeted and sustained delivery of bimatoprost resulted in protracted IOP lowering, suggesting that Bimatoprost SR may represent a transformational new approach to glaucoma therapy. Clinicaltrials.gov identifier: NCT01157364.

Conflict of interest statement

E. Randy Craven is a consultant for Aerie, Alcon, Allergan, Ivantis, Santen, and WL Gore and has received grant support from Allergan. Thomas Walters is a consultant for Allergan, Nicox, Ocular Therapeutix, and Sun. William C. Christie is a consultant for Allergan and Johnson & Johnson. Douglas G. Day is a consultant for Allergan. Richard A. Lewis is a consultant for Aerie, Alcon, Allergan, Aquesys, AVS, Envisia, Glaukos, Ivantis, Oculeve, PolyActiva, ViSci, and Zeiss. Margot L. Goodkin, Michelle Chen, Veronica Wangsadipura, Michael R. Robinson, and Marina Bejanian are Allergan employees.

Figures

Fig. 1
Fig. 1
Bimatoprost sustained-release (SR) single-use implant applicator (a) and photograph of implant next to a dime and Euro for size comparison (b)
Fig. 2
Fig. 2
Hour 0 (8:00 a.m.) mean change from baseline IOP. a Preplanned analysis with data censored after rescue or retreatment. b Analysis of all observed data. Data at month 24 were available for 55 of the 63 patients who completed the study: two patients who had not been rescued or retreated in the study eye were not evaluated within the month-24 visit window, and six patients met early exit criteria and completed the study before month 24. By month 24, ten fellow eyes had received rescue treatment. Medication counts included every medication used except the initial implant administration in study eyes and topical bimatoprost 0.03% in fellow eyes; implant retreatment was counted as use of one medication, and fixed combinations were counted as use of two medications. Bim topical bimatoprost 0.03% once daily, BimSR bimatoprost sustained-release implant, BL baseline, IOP intraocular pressure, M month, Meds medication counts, SC screening, W week
Fig. 3
Fig. 3
Percentage of study eyes not rescued or retreated with implant. BimSR bimatoprost sustained-release implant, M month, W week
Fig. 4
Fig. 4
Mean corneal endothelial cell density (CECD) over time in study eyes treated with one or two administrations of Bimatoprost SR (6, 10, 15, or 20 µg) and fellow eyes treated with daily topical bimatoprost 0.03%. The between-treatment difference, i.e., study eye − fellow eye, was 20.2 (95% CI − 12.6 to 52.9) at baseline, compared with − 44.6 (95% CI − 81.6 to − 7.5) at month 24. Error bars indicate the standard deviation. BimSR bimatoprost sustained-release implant, BL baseline, CI confidence interval, M month, W week
Fig. 5
Fig. 5
Mean change in visual field mean deviation from baseline in study eyes treated with one or two administrations of Bimatoprost SR (6, 10, 15, or 20 µg) and fellow eyes treated with daily topical bimatoprost 0.03%. Results based on observed values regardless of rescue/retreatment; n is shown in italics. Error bars indicate standard error of the mean. *P = 0.005 vs. topical bimatoprost 0.03%. BimSR bimatoprost sustained-release implant, MD mean deviation

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