title: A Dose-Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of 2 and 4 Weeks of Twice-Daily Ocular Trabodenoson in Adults with Ocular Hypertension or Primary Open-Angle Glaucoma.
abstract: To evaluate the safety and ocular hypotensive efficacy of 4 trabodenoson doses administered twice daily over 14 or 28 days in subjects with ocular hypertension or primary open-angle glaucoma (POAG).
  
  
  
  In this multicenter, randomized, double-masked, placebo-controlled, dose-escalation Phase 2 study, patients received unilateral topical twice-daily trabodenoson (50, 100, or 200 mcg) or placebo for 14 days, or 500 mcg trabodenoson or placebo for 28 days. Ocular and systemic safety and tolerability were assessed by examinations, clinical and laboratory studies. Intraocular pressure (IOP) was assessed using Goldmann tonometry.
  
  
  
  Trabodenoson was well tolerated; no clinically meaningful ocular or systemic side effects were identified. Trabodenoson produced a dose-dependent IOP reduction. IOP reductions in the 500 mcg group were significantly greater than placebo at all time points at Day 28. Mean IOP reductions from diurnal baseline ranged from -3.5 to -5.0 mmHg with a mean change of -4.1 mmHg in the 500 mcg group compared -1.0 to -2.5 mmHg with a mean change of -1.6 mmHg for the placebo group, and the Day 28 drop was significantly greater than at Day 14 (P = 0.0163) indicating improvement in IOP lowering with longer treatment time. IOP remained significantly reduced 24 h after the final 500 mcg dose (P = 0.048).
  
  
  
  Twice-daily ocular doses of trabodenoson, from 50 to 500 mcg, were well tolerated and showed a dose-related decrease in IOP that was statistically significant and clinically relevant at 500 mcg in patients with ocular hypertension or POAG.
authors.affiliation: 1 Wills Eye Hospital , Philadelphia, Pennsylvania.
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Myers
authors.affiliation: 2 Sall Research Medical Center , Artesia, California.
authors.forename: Kenneth N
authors.initials: KN
authors.lastname: Sall
authors.affiliation: 3 Eye Care Centers Management, Inc. , Morrow, Georgia .
authors.forename: Harvey
authors.initials: H
authors.lastname: DuBiner
authors.affiliation: 4 Inotek Pharmaceuticals Corporation , Lexington, Massachusetts.
authors.forename: Natanya
authors.initials: N
authors.lastname: Slomowitz
authors.affiliation: 4 Inotek Pharmaceuticals Corporation , Lexington, Massachusetts.
authors.forename: William
authors.initials: W
authors.lastname: McVicar
authors.affiliation: 4 Inotek Pharmaceuticals Corporation , Lexington, Massachusetts.
authors.forename: Cadmus C
authors.initials: CC
authors.lastname: Rich
authors.affiliation: 4 Inotek Pharmaceuticals Corporation , Lexington, Massachusetts.
authors.forename: Rudolf A
authors.initials: RA
authors.lastname: Baumgartner
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004361:Drug Tolerance; D005260:Female; D005902:Glaucoma, Open-Angle / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D007429:Intraocular Pressure; D008297:Male; D008875:Middle Aged; D009566:Nitrates / Q000008:administration & dosage / Q000009:adverse effects* / Q000737:chemistry / Q000493:pharmacokinetics*; D009798:Ocular Hypertension / Q000175:diagnosis / Q000188:drug therapy*; D011687:Purines / Q000008:administration & dosage / Q000009:adverse effects* / Q000737:chemistry / Q000493:pharmacokinetics*; D013997:Time Factors; D014065:Tonometry, Ocular; D055815:Young Adult
chemical_list: D009566:Nitrates; D011687:Purines; C000624504:trabodenoson
keywords: Trabodenoson; adenosine; intraocular pressure; ocular hypertension; primary open angle glaucoma; trabecular meshwork