Purchase this article with an account.
Jonathan Myers, Kenneth Sall, Harvey DuBiner, Chaim Brickman, N. Slomowitz, William McVicar, Rudolf Baumgartner; A Randomized, Phase II Study of Trabodenoson (INO-8875) in Adults with Ocular Hypertension (OHT) or Primary Open-Angle Glaucoma (POAG). Invest. Ophthalmol. Vis. Sci. 2013;54(15):2621.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
The efficacy and tolerability of trabodenoson, a highly-selective adenosine-1 agonist, were assessed following monocular topical application in subjects with OHT or POAG.
Adults who signed informed consent and met enrollment criteria underwent a 4-day placebo run-in period. Subjects in Part 1 were randomized to placebo or 50-200 μg of trabodenoson BID for 14 days and in Part 2 to placebo or 500 μg of trabodenoson BID for 28 days. Masked-IOP measurements and safety assessments were performed before, during and after the treatment period.
144 subjects were randomized to placebo or trabodenoson. The most consistent decreases in IOP were noted at the 500 μg dose [N=67: 33 placebo - baseline (mean pre-dose) 27.1±2.9 (SD) mmHg; 34 active - baseline (mean pre-dose) 26.2±2.4 (SD) mmHg]. Day 14 and Day 28 mean diurnal IOP changes were computed by averaging the changes from baseline (Day 1 8AM) at 8AM, 10AM, 12PM, 4PM and 8PM (12 hrs post dose). By Day 14, the 500 μg cohort had achieved a significant reduction in mean diurnal IOP compared to placebo (median Δ= -4.9±2.9 (SD) mmHg [p=0.01]) with a further decrease by Day 28 (median Δ= -6.5±2.5 (SD) mmHg [p<0.001]). Day 28 subgroup analyses for subjects with: OHT (N=13, median Δ= -6.3+2.4 mmHg, p=0.003), POAG (N=20, median Δ= -6.6±2.6 mmHg, p=0.005), baseline IOP ≥25 mmHg (N=21, median Δ= -7.2±2.5 mmHg, p<0.001); and subjects requiring wash out of glaucoma medication(s) prior to randomization (N=11, median Δ= -7.2±2.7 mmHg, p=0.002) all showed significant reductions in mean diurnal IOP. All doses were well-tolerated. External eye examinations indicated post-randomization hyperemia rates for the placebo and 500 µg cohorts were unchanged from baseline. These hyperemias were transient (<4 hr), generally mild, self-limited and not associated with anterior chamber cells or flare in either cohort. All other safety data including electrocardiograms were unremarkable. Increases in systemic exposure to Trabodenoson were dose-related with no evidence of accumulation in plasma.
Trabodenoson was well-tolerated, safe, and resulted in significant IOP reductions in adults with OHT or POAG.
This PDF is available to Subscribers Only