Fixed combination performs as expected in phase III trial

January 15, 2014

Treatment with the fixed combination of brinzolamide 1%-brimonidine 0.2% (Simbrinza, Alcon Laboratories) was associated with significantly greater IOP-lowering than either brinzolamide or brimonidine monotherapy.

Dr. Goldberg

 

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Treatment with the fixed combination of brinzolamide 1%-brimonidine 0.2% (Simbrinza, Alcon Laboratories) was associated with significantly greater IOP-lowering than either brinzolamide or brimonidine monotherapy.

 

By Cheryl Guttman Krader; Reviewed by Ivan Goldberg, MD

Sydney, Australia-Phase III study results support the conclusion that the carbonic anhydrase inhibitor-alpha agonist fixed combination of brinzolamide 1% and brimonidine 0.2% (Simbrinza Suspension, Alcon Laboratories) is a safe, well-tolerated, and effective treatment for lowering IOP in patients with glaucoma or ocular hypertension that is uncontrolled by monotherapy.

The randomized, multinational, double-masked trial was conducted at 63 centers in the Asia-Pacific region, Europe, United States, Latin America, and Caribbean nations. It included 560 patients who had insufficient IOP control on monotherapy or who were already using more than one medication.

Ivan Goldberg MD, clinical associate professor, Discipline of Ophthalmology, University of Sydney and head, Glaucoma Unit Sydney Eye Hospital, Sydney, Australia, was an investigator in the study.

“The new brinzolamide-brimonidine product is the first fixed-dose combination product that does NOT contain a beta-blocker, and its availability is excellent news for the sizeable group of patients with ocular hypertension or open-angle glaucoma who have relative or absolute contraindications for beta-blocker treatment,” Dr. Goldberg said.

“Fixed-dose combinations have become the fastest growing segment of the anti-glaucoma medication market because they decrease exposure to preservatives and provide increased convenience,” he added. “With the latter benefit, fixed-dose combinations are a positive contribution for addressing ongoing non-adherence, which is known to increase as the number of medications prescribed increases.

About the study

Eligible patients were randomly assigned equally into three groups to receive twice-daily treatment with the brinzolamide-brimonidine fixed combination (BBFC), brimonidine alone, or brinzolamide alone. IOP was measured at 9 and 11 a.m., and 4 p.m. at baseline and week 2, week 6, month 3, and month 6 after randomization.

Baseline diurnal IOP, calculated as the average of the three measurements averaged 25.9 or 26 mm Hg in all three groups.

Mean diurnal IOP change from baseline to 3 months was analyzed as the primary efficacy endpoint, and the results showed the reduction achieved was significantly greater among patients using BBFC compared with the controls treated with brinzolamide alone or brimonidine alone (–7.9 versus –6.5 and –6.4 mm Hg). A significant difference favoring BBFC over the monotherapy treatments was also achieved at all other follow-up intervals.

Safety data showed there were no serious adverse events or study withdrawals that were judged related to study medication nor any clinically meaningful changes in pulse rate, blood pressure, or BCVA in any of the study groups. Overall, adverse event data showed that BBFC was associated with a safety profile consistent with its individual components.

Baseline data in the phase III study showed the three treatment groups were well matched in their demographic and disease characteristics. The patients in the study had an average age of about 65 years, about 70% were white, and about 75% had open-angle glaucoma.

Treatment-related adverse events occurred in 26.5% of patients in the BBFC group, among 11.5% of patients treated with brinzolamide alone, and in 22.9% of brimonidine-treated patients. The only adverse events occurring at a rate >5% were ocular hyperemia, eye pain, and dysgeusia, each of which occurred among 5.7% of patients receiving BBFC. Ocular hyperemia occurred at a rate of 4.6% among patients treated with brimonidine alone.

“There were no safety surprises in the study,” Dr. Goldberg said.

Side effects with the fixed dose combination were entirely as expected given its active ingredients.

“This was the hope in undertaking the study, and it was confirmed by the data,” Dr. Goldberg said.

 

 

Ivan Goldberg, MD

E:   eyegoldberg@gmail.com

Dr. Goldberg has served as a consultant and advisory board member for Alcon Laboratories, Allergan, Forsight, Merck, and Pfizer, has participate on speakers bureaus for Alcon and received travel support from Alcon and Pfizer.

 

 

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