Prevention of corticosteroid-induced intraocular pressure elevation using ISV-205.
OBJECTIVE
To determine whether a topical ophthalmic diclofenac sodium formulation containing a proprietary polymeric drug delivery system (ISV-205), when dosed concomitantly with 1% prednisolone acetate, is effective in blocking the intraocular pressure (IOP) response in humans.


METHODS
This was a multicenter, prospective, double-masked, parallel, vehicle-controlled study. We included 136 first-degree relatives of subjects with primary open-angle glaucoma. Subjects were randomized to receive 0.06% or 0.1% ISV-205 or vehicle while concomitantly receiving 1% prednisolone for 6 weeks.


RESULTS
During the treatment period, the mean +/- SD maximum IOP increase (7.3 +/- 6.5 mm Hg for vehicle, 4.9 +/- 4.6 mm Hg for 0.06% ISV-205, and 5.9 +/- 4.9 mm Hg for 0.1% ISV-205) was significantly less with the 0.06% formulation than with placebo (P =.02). The overall mean change in IOP was 3.6, 2.0, and 2.4 mm Hg in the vehicle, 0.06% ISV-205, and 0.1% ISV-205 groups, respectively, which was significant between the 0.06% ISV-205 and vehicle groups (P =.05). Eight (17%) of the 46 subjects receiving vehicle terminated the study because of high IOPs, compared with 1 (2%) of the 45 subjects receiving 0.06% ISV-205 and 3 (7%) of the 45 subjects receiving 0.1% ISV-205 (P =.03). The number of subjects with a clinically important corticosteroid response (> or =10-mm Hg increase) was greater in the vehicle group (12 [28%] of 43 subjects) compared with the 0.06% ISV-205 group (3 [7%] of 42 subjects) (P =.01). Adverse events were similar between treatments.


CONCLUSIONS
This study suggests that ISV-205 limits the corticosteroid-induced elevated IOP in first-degree relatives of subjects with glaucoma. Future studies are needed to confirm these results and explore the possible role of this drug in treating glaucoma.
Stewart
William C
WC
Pharmaceutical Research Network, LLC, Charleston, SC 29412-2464, USA. prnc@bellsouth.net
D000287:Administration, Topical; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000009:adverse effects*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D004008:Diclofenac / Q000008:administration & dosage*; D004311:Double-Blind Method; D016503:Drug Delivery Systems; D004359:Drug Therapy, Combination; D005260:Female; D005902:Glaucoma, Open-Angle / Q000139:chemically induced / Q000235:genetics / Q000517:prevention & control*; D006801:Humans; D007429:Intraocular Pressure / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D009798:Ocular Hypertension / Q000139:chemically induced / Q000235:genetics / Q000517:prevention & control; D009883:Ophthalmic Solutions; D011239:Prednisolone / Q000009:adverse effects* / Q000031:analogs & derivatives*; D011446:Prospective Studies; D012449:Safety; D016896:Treatment Outcome
D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D009883:Ophthalmic Solutions; D004008:Diclofenac; C009935:prednisolone acetate; D011239:Prednisolone