InSite Vision Incorporated, a company advancing new ophthalmologic products for unmet eye care needs based on its innovative DuraSite platform technologies, has begun the patient enrollment in confirmatory phase III clinical trial of BromSite (ISV-303) for the reduction of inflammation and pain after cataract surgery. This study will seek to enroll approximately 240 patients undergoing cataract surgery in a two-arm trial designed to evaluate the efficacy and safety of BromSite against the DuraSite vehicle alone.
BromSite combines a low dose (0.075%) of the non-steroidal anti-inflammatory drug (NSAID) bromfenac with InSite Vision’s DuraSite drug delivery technology.
“Our BromSite clinical programme has been advancing rapidly and we expect that to continue with this phase III trial, which is identical in design to our prior successful phase III study. In our first phase III study, all patients completed the trial in less than six months and we were able to release top-line results in less than eight months, start to finish,” said Kamran Hosseini, MD, Ph.D., vice president and chief medical officer of InSite Vision. “We anticipate top-line results from this phase III study will be available in late 2013 or early 2014. Assuming positive results, we plan to file a New Drug Application with the FDA in 2014.”
The first BromSite phase III clinical trial enrolled 268 patients undergoing cataract surgery. On March 18, 2013, InSite announced that the primary endpoint of reduction of inflammation after surgery had achieved statistically significant superiority compared to vehicle (p<0.001). A secondary endpoint, reduction of pain, had also achieved statistically significant superiority to vehicle (p<0.001).
The BromSite phase III clinical studies are two-arm, double-blind, placebo-controlled clinical trials where the placebo arm is the DuraSite vehicle. In the second, confirmatory phase III BromSite study, patients undergoing cataract surgery at 15 separate sites will be randomized and then dosed twice-a-day beginning the day before surgery, and continuing the day of surgery and for 14 days post-surgery. The primary study endpoint is the reduction of inflammation after surgery with a secondary endpoint of reduction of pain. Pharm-Olam International will again serve as the contract research organisation managing the BromSite study on behalf of InSite Vision.
The design of the two phase III clinical trials has been discussed with both the US Food and Drug Administration (FDA) and two European country regulators. The design of the confirmatory phase III study for BromSite reflects the full input from both the European regulators and the FDA.
Cataract surgery is the most frequently performed ocular surgery in the United States with more than three million procedures annually. Both before and after surgery, anti-inflammatory eye drops are prescribed to reduce pain and inflammation. Anti-inflammatory eye drops are also administered as prophylaxis against cystoid macular edema, or CME. CME is a relatively rare, but extremely serious, adverse event in ocular surgery that can lead to blindness. Most physicians believe that the higher penetration of bromfenac into the ocular tissues may reduce the risk of CME. InSite intends to do additional clinical studies post-approval in pursuit of adding prevention of CME to the BromSite label.
BromSite (ISV-303) is a low-dose (0.075 per cent) bromfenac ophthalmic solution formulated in DuraSite and is being evaluated for the treatment of inflammation and ocular pain in the post-cataract surgery setting. In a phase I/II study of 169 patients undergoing cataract surgery, once-daily and twice-daily doses of BromSite were compared against the DuraSite vehicle alone. Once-daily and twice-daily BromSite demonstrated superiority to vehicle (53.3% versus 19.0%, p=0.0016 and 52.5% versus 19.0%, p=0.0024, respectively) in reducing pain and inflammation. InSite reported results from the phase I/II clinical study in March 2011. In a phase II clinical study evaluating pharmacokinetics, BromSite achieved more than twice the eye tissue penetration than Bromday (bromfenac ophthalmic solution) 0.09% marketed by Bausch + Lomb. Results from the phase II clinical trial comparing BromSite to Bromday were released in October 2011.