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Twice-daily dose of trabodenoson may lower IOP in glaucoma patients
Twice-daily 50 µg to 500 µg ocular doses of trabodenoson were well-tolerated, according to a study, and at 500 µg, a dose-related decrease in IOP was seen in patients with primary open-angle glaucoma or ocular hypertension.
The multicenter, randomized, double-masked, placebo-controlled, dose-escalation phase 2 study included 141 patients who were administered 50 µg, 100 µg or 200 µg unilateral topical twice-daily trabodenoson (Inotek Pharmaceuticals) or placebo for 14 days, or 500 µg trabodenoson or placebo for 28 days.
Mean IOP reduction ranged from 3.5 mm Hg to 5 mm Hg, with a mean change of 4.1 mm Hg, in the 500 µg group, and from 1 mm Hg to 2.5 mm Hg, with a mean change of 1.6 mm Hg, in the placebo group.
The IOP reduction on day 28 was significantly greater than the reduction on day 14 (P = .0163), which indicated longer treatment time yielded greater improvement in IOP reduction.
None of the treatment groups displayed any clinically significant treatment-related abnormalities in clinical laboratory studies, physical examinations or cardiac function tests.
“The treatment ... offers a unique and relevant mechanism of action that may address part of the specific pathophysiology of [ocular hypertension] and glaucoma in the [trabecular meshwork], with a resultant increase in aqueous outflow facility,” the researchers said. — by Nhu Te
Disclosure: Myers reports he is a consultant for and a member of the Inotek scientific advisory board. See the full study for all other authors’ relevant financial disclosures.
Perspective
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The introduction of medications that provide a novel mechanism of action in the treatment of ocular hypertension and primary open-angle glaucoma would be welcomed because it has been two decades since the last new drop latanoprost. Trabodenoson selectively activates adenosine A1 receptors. Stimulation of these receptors has shown to release MMP-2, which is theorized to remodel trabecular meshwork extracellular matrix. This translates into trabodenoson decreasing IOP through the conventional outflow pathway. The study shows that increasing level of trabodenoson decreases IOP including statistical significance with 500 µg dosed twice daily. This effect is further enhanced with longer duration of use from 14 to 28 days. In addition, no serious adverse events were noted with the only treatment-related event of conjunctival hyperemia at the 500 µg concentration. The clinical significance includes the possible introduction of a new medication that would provide IOP reduction through a similar pathway of pilocarpine but with a twice daily regimen without major side effects.
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Myers JS, et al. J Ocul Pharmacol Ther. 2016;doi:10.1089/jop.2015.0148.