title: A phase 2, randomized, dose-response trial of taprenepag isopropyl (PF-04217329) versus latanoprost 0.005% in open-angle glaucoma and ocular hypertension.
abstract: OBJECTIVE
  To evaluate the safety of escalating doses of taprenepag isopropyl (PF-04217329), a selective EP(2) receptor agonist administered as a topical ophthalmic solution, versus its vehicle (Stage I), and dose-response of taprenepag isopropyl alone and in unfixed combination with latanoprost ophthalmic solution 0.005% versus latanoprost alone (Stage II).
  
  
  METHODS
  Randomized, vehicle- and active-controlled, double-masked, two-stage, dose-finding trial in primary open-angle glaucoma (POAG) or ocular hypertension; first taprenepag isopropyl study in patients (NCT00572455). Study eye: 26 mmHg ≤ intraocular pressure (IOP) <36 mmHg at 8 am and 22 mmHg ≤ IOP <36 mmHg at 10 am, 1 pm, 4 pm. Stage I: 3 cohorts (total n = 67) received 1 drop of taprenepag isopropyl unit dose formulation qPM/eye for 14 days: low dose: 0.0025%, 0.005%, vehicle; middle dose: 0.01%, 0.015%, vehicle; high dose: 0.02%, 0.03%, vehicle. Stage II: 7 groups (total n = 250) received 1 drop of taprenepag isopropyl multidose formulation qPM/eye for 28 days: 0.005%, 0.01%, 0.015% monotherapy; each in unfixed combination with latanoprost 0.005%, or latanoprost monotherapy.
  
  
  RESULTS
  mean change in diurnal IOP, baseline to last visit; adverse events.
  
  
  RESULTS
  Stage I at day 14: statistically significantly greater IOP reductions were observed at all taprenepag isopropyl doses versus vehicle. Stage II at day 28: statistically significantly greater IOP reductions were observed at all doses of the unfixed combination versus latanoprost monotherapy. At least 1 treatment-emergent adverse event reported for 29/67 (43.3%) subjects in Stage I and 158/250 (63.2%) in Stage II.
  
  
  CONCLUSIONS
  Taprenepag isopropyl significantly reduces IOP in POAG and ocular hypertension. Taprenepag isopropyl monotherapy is comparable to latanoprost 0.005% in reducing IOP. As demonstrated in this report, the activity of taprenepag isopropyl is additive to that of latanoprost 0.005%. Further studies are required to determine whether it shows similar additivity when administered with other ocular antihypertensive medications.
authors.affiliation: Pfizer Inc, San Diego, California 92121, USA. ronald.schachar@pfizer.com
authors.forename: Ronald A
authors.initials: RA
authors.lastname: Schachar
authors.forename: Susan
authors.initials: S
authors.lastname: Raber
authors.forename: Rachel
authors.initials: R
authors.lastname: Courtney
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
mesh_terms: D000085:Acetates / Q000008:administration & dosage*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000959:Antihypertensive Agents / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D005902:Glaucoma, Open-Angle / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D007429:Intraocular Pressure / Q000187:drug effects*; D000077338:Latanoprost; D008297:Male; D008875:Middle Aged; D009798:Ocular Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D009883:Ophthalmic Solutions; D011446:Prospective Studies; D011461:Prostaglandins F, Synthetic / Q000008:administration & dosage*; D058307:Receptors, Prostaglandin E, EP2 Subtype / Q000037:antagonists & inhibitors; D013449:Sulfonamides / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D000085:Acetates; D000959:Antihypertensive Agents; D009883:Ophthalmic Solutions; C568861:PF 04217329; D011461:Prostaglandins F, Synthetic; D058307:Receptors, Prostaglandin E, EP2 Subtype; D013449:Sulfonamides; D000077338:Latanoprost