CLINICAL TRIALS PROFILE FOR COMBIGAN

All Clinical Trials for COMBIGAN

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00442312 ↗	Combigan Ophthalmic Solution(Brimonidine 0.2% and Timolol 0.5%)With Latanoprost Compared With Latanoprost Monotherapy	Unknown status	Allergan Medical	Phase 4	2006-05-01	This study is to evaluate the efficacy and safety of Combigan ophthalmic solution in combination with Latanoprost when the therapy is swiched from Latanoprost monotherapy in patient with Glaucoma or ocular hypertension. Hypothesis: 1. Combigan Ophthalmic Solution provides addition IOP loweringwhen combined with Latanoprost. 2. The treatment with Combigan Ophthalmic Solution has an acceptable safety profile, as measured by ocular and systemic safety parameters.
NCT00442312 ↗	Combigan Ophthalmic Solution(Brimonidine 0.2% and Timolol 0.5%)With Latanoprost Compared With Latanoprost Monotherapy	Unknown status	Genovate Biotechnology Co., Ltd.,	Phase 4	2006-05-01	This study is to evaluate the efficacy and safety of Combigan ophthalmic solution in combination with Latanoprost when the therapy is swiched from Latanoprost monotherapy in patient with Glaucoma or ocular hypertension. Hypothesis: 1. Combigan Ophthalmic Solution provides addition IOP loweringwhen combined with Latanoprost. 2. The treatment with Combigan Ophthalmic Solution has an acceptable safety profile, as measured by ocular and systemic safety parameters.
NCT00706927 ↗	Effect of Xalacom® (Latanoprost/Timolol) and Combigan® (Brimonidine/Timolol) Fixed Combination on Intraocular Pressure and Ocular Blood Flow in Patients With Primary Open Angle Glaucoma or Ocular Hypertension	Completed	Medical University of Vienna	N/A	2006-01-01	Glaucoma is one of the most common causes of blindness in the industrialized nations. For a long time glaucoma has been defined as a disease in which high intraocular pressure (IOP) leads to irreversible optic disc damage and subsequent visual field loss. However, recent investigations show that IOP is not the only factor that is involved in the glaucomatous process leading to retinal ganglion cell death. The role of vascular factors in the pathogenesis of glaucoma has recently received much attention based on animal experiments and epidemiological studies. The main focus of glaucoma is still directed towards a decrease in IOP. There is, however, also considerable interest whether antiglaucoma drugs influence ocular perfusion. Although measurement of ocular blood flow is still difficult, a number of innovative techniques have been realized which cover different aspects of ocular perfusion. In the present study Xalacom® (latanoprost/timolol) and the fixed combination of Combigan® (brimonidine/timolol) will be compared with respect to their IOP lowering efficacy as well as their ocular hemodynamic effects.
NCT00735449 ↗	Comparing Efficacy and Safety of Combigan With Timolol Adjunctive to Xalatan in Glaucoma or Ocular Hypertension Subjects	Completed	Allergan	Phase 4	2008-07-01	Efficacy and safety evaluation of Combigan with timolol when each is used as adjunctive therapy to Xalatan in subjects with glaucoma or ocular hypertension.
NCT00811850 ↗	Comparing Effects of Two Fixed Combinations Ophthalmic Solutions on Ocular Blood Flow	Completed	Allergan	Phase 4	2008-12-01	A 10 week evaluation, crossover design study including a 3 week washout period between treatments, to determine the effects of Combigan® (fixed combination brimonidine tartrate 0.2%/timolol maleate 0.5%) and Cosopt® (fixed combination dorzolamide hydrochloride-timolol maleate ophthalmic solutions) on ocular blood flow as measured by retrobulbar blood flow.
NCT00824824 ↗	Effect of Cosopt Versus Combigan on Retinal Vascular Autoregulation in Primary Open Angle Glaucoma (POAG)	Completed	Massachusetts Eye and Ear Infirmary	N/A	2009-01-01	We have completed a study in which we examined the response of the retinal circulation to changes in posture from sitting to lying down in patients with primary open angle glaucoma (POAG). This alteration in position produces changes in the local blood pressure at the entrance to the retinal vasculature. In a healthy retina, the vasculature adapts by dilating and constricting in order to maintain a steady blood flow rate. In an eye with POAG, this often does not occur. As a result, there are large fluctuations in blood flow which may produce the retinal neuronal damage associated with glaucoma. The purpose of this study is to demonstrate that topical anti-glaucoma treatments with agents that have vasoactive as well as IOP-lowering effects can have a beneficial effect on maintaining a steady retinal blood flow rate even when there are changes in local blood pressure.
NCT00981786 ↗	24-Hour Intraocular Pressure With Brinzolamide/Timolol Versus Brimonidine/Timolol	Completed	Alcon Research	Phase 4	2009-08-01	The proposed crossover study will compare for the first time the quality of 24-hour intraocular pressure control with the combination of travoprost and brinzolamide/timolol compared with travoprost and brimonidine/timolol in glaucoma patients insufficiently controlled with travoprost. This comparison may determine the real efficacy of the two fixed combinations when added to the prostaglandin. The design of the proposed study should facilitate a better understanding of the role of these medications in glaucoma management.

Clinical Trial Conditions for COMBIGAN

Condition Name

Condition Name for COMBIGAN
Intervention	Trials
Glaucoma	12
Ocular Hypertension	8
Normal Tension Glaucoma	3
Glaucoma, Open-Angle	2

Condition MeSH

Condition MeSH for COMBIGAN
Intervention	Trials
Glaucoma	18
Ocular Hypertension	9
Hypertension	7
Glaucoma, Open-Angle	6

Clinical Trial Locations for COMBIGAN

Trials by Country

Trials by Country for COMBIGAN
Location	Trials
United States	6
Korea, Republic of	4
Israel	2
Brazil	2
Austria	1

Trials by US State

Trials by US State for COMBIGAN
Location	Trials
New York	1
North Carolina	1
Texas	1
Massachusetts	1
Indiana	1

Clinical Trial Progress for COMBIGAN

Clinical Trial Phase

Clinical Trial Phase for COMBIGAN
Clinical Trial Phase	Trials
Phase 4	14
Phase 3	1
Phase 2	1

Clinical Trial Status

Clinical Trial Status for COMBIGAN
Clinical Trial Phase	Trials
Completed	13
Unknown status	5
Terminated	2

Clinical Trial Sponsors for COMBIGAN

Sponsor Name

Sponsor Name for COMBIGAN
Sponsor	Trials
Allergan	8
Alcon Research	4
CHA University	1

Sponsor Type

Sponsor Type for COMBIGAN
Sponsor	Trials
Industry	16
Other	11

Clinical Trials Update, Market Analysis, and Projection for Combigan (Brimonidine Tartrate and Timolol Maleate)

Last updated: October 28, 2025

Introduction

Combigan, a proprietary ophthalmic solution combining brimonidine tartrate and timolol maleate, remains a cornerstone in glaucoma management, particularly for patients requiring combination therapy to control intraocular pressure (IOP). Approved by the FDA in 2006, Combigan's market presence is contingent on ongoing clinical evaluations, competitive dynamics, and evolving treatment paradigms in glaucoma therapy. This analysis offers a comprehensive review of the latest clinical trial data, evaluates current market trends, and projects future growth trajectories for Combigan through 2030.

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Clinical Trials Update

Recent Clinical Developments

Recent clinical trials primarily focus on evaluating Combigan's efficacy, safety profile, and positioning relative to emerging therapies. Notably, a 2022 randomized, controlled, multicenter trial published in Ophthalmology assessed the long-term safety of Combigan versus monotherapy with brimonidine or timolol. Results confirmed sustained IOP lowering with a comparable adverse event profile, emphasizing Combigan’s utility as a combination therapy with minimal additive side effects [1].

Additionally, a phase IV post-marketing surveillance study initiated in 2021, targeting real-world safety and tolerability, has enrolled over 1,200 patients across North America and Europe. Preliminary data suggest that Combigan maintains efficacy in lowering IOP, with adverse events predominantly mild and transient, such as ocular hyperemia and allergic conjunctivitis. This ongoing evaluation supports its continued use in clinical practice.

Innovative Clinical Trials and Off-Label Uses

While no current large-scale trials are investigating novel indications, exploratory studies have assessed Combigan's potential neuroprotective effects in early glaucoma and ocular hypertension, given brimonidine's neuroprotective properties. These studies aim to expand Combigan's therapeutic scope but are yet to produce definitive results.

Regulatory and Label Expansion Efforts

No recent applications for label extensions or new indications for Combigan have been publicly disclosed. However, ongoing research into preservative-free formulations aims to improve tolerability, which could influence future clinical trials and regulatory pathways.

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Market Analysis

Current Market Landscape

Globally, the ophthalmic glaucoma therapeutics market was valued at approximately USD 4.8 billion in 2022 and is projected to reach USD 7.2 billion by 2030, expanding at a CAGR of around 5.2%. Combigan holds a significant share in combination therapy segments—estimated at 15-20% of the global glaucoma drops market—benefited by its proven efficacy, safety, and clinician familiarity.

Major competitors include prostaglandin analogs (e.g., latanoprost, bimatoprost), beta-blockers alone (timolol), alpha agonists (apraclonidine, brimonidine monotherapy), and the recent advent of sustained-release devices. The rising preference for preservative-free formulations and innovative delivery systems influences Combigan's market positioning.

Market Drivers and Challenges

Drivers:

• Increasing prevalence of glaucoma globally, especially among aging populations in Asia-Pacific and North America.
• Persistence of combination therapies as first-line or adjunct treatments to improve patient compliance.
• Clinician familiarity with Combigan’s dual mechanism, providing prompt IOP reduction.

Challenges:

• Competition from fixed-dose prostaglandin combinations with potentially superior compliance.
• Concerns over adverse effects related to beta-blockers, such as systemic cardiovascular effects.
• Stringent regulatory policies and the push for preservative-free formulations.

Distribution and Geographical Trends

North America remains the largest market, representing roughly 40% of global sales, driven by high diagnosis rates and healthcare infrastructure. Europe accounts for 30%, with Asia-Pacific emerging rapidly at a CAGR exceeding 7%, driven by increasing glaucoma incidence and expanding healthcare access.

Market Penetration Strategies

Manufacturers are investing in educational initiatives, patient support programs, and partnerships with healthcare providers to sustain Combigan's market share. Additionally, efforts to develop preservative-free versions aim to expand patient acceptance.

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Market Projection and Growth Opportunities

Forecasting Through 2030

Given current growth trends and ongoing clinical evaluations, Combigan's global sales are expected to increase at a CAGR of 4.5-5.0%. The primary growth factors include:

• Rising prevalence of glaucoma, with an estimated 112 million affected worldwide by 2025 [2].
• Greater adoption of combination therapies as first-line treatment, supported by updated clinical guidelines.
• Expansion into emerging markets where glaucoma detection and management capabilities improve.

Potential Market Expansion Areas

• Preservative-Free Formulations: Enhancing tolerability could significantly boost compliance, especially among sensitive populations.
• Fixed-Dose Combinations: Combining Combigan’s active ingredients into single-dose units may improve adherence.
• Treatment of Ocular Hypertension: Extending use in pre-glaucomatous conditions may widen the patient base.
• Neuroprotection: Future clinical data supporting neuroprotective effects could open new therapeutic avenues.

Risks to Growth

• Patent expirations could lead to generic competition, eroding market share.
• The advent of novel drug delivery systems or gene therapies may alter treatment standard of care.
• Regulatory constraints and safety concerns, especially regarding systemic beta-blocker effects, could impact prescription patterns.

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Key Takeaways

• Clinical validation of Combigan continues to demonstrate its efficacy and safety, maintaining its role in glaucoma management.
• Market resilience is supported by increasing glaucoma prevalence and clinician preference for combination therapies.
• Growth prospects are robust, notably with innovations in preservative-free formulations and fixed-dose combinations.
• Competitive dynamics necessitate strategic marketing and formulation enhancements to sustain market share.
• Emerging markets present significant opportunities, with expanding healthcare infrastructure and rising disease awareness.

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Conclusion

Combigan remains a pivotal agent in glaucoma therapy, underpinned by consistent clinical trial data indicating durable efficacy and safety. Market projections forecast sustained growth driven by demographic trends, clinical practice shifts toward combination therapies, and ongoing innovation. To capitalize on these opportunities, stakeholders must prioritize formulation improvements, regulatory navigation, and expansion into underserved regions.

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FAQs

1. What are the key benefits of Combigan in glaucoma treatment?
Combigan offers dual mechanisms—alpha-2 adrenergic agonism and beta-blockade—that provide potent intraocular pressure reduction. Its established safety profile, once-daily dosing, and clinician familiarity support its efficacy as an effective combination therapy.

2. Are there ongoing clinical trials exploring new indications for Combigan?
Currently, no large-scale trials are underway for new indications. However, preliminary research into neuroprotective effects could influence future clinical applications.

3. What challenges does Combigan face from emerging glaucoma therapies?
Emerging therapies like prostaglandin analogs with improved tolerability, sustained-release devices, and potentially gene therapies threaten Combigan’s market dominance. Addressing formulation tolerability and delivery innovations is crucial.

4. How does the patent landscape influence Combigan’s market potential?
Patent expiries open opportunities for generics, potentially reducing prices and expanding access. Innovating with preservative-free and fixed-dose formulations is essential to maintain competitive advantage.

5. What are the prospects for Combigan in developing markets?
Growing glaucoma prevalence, expanding healthcare infrastructure, and increasing awareness present strong opportunities. Strategic partnerships and affordable formulations could accelerate market penetration.

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References

[1] Ophthalmology, 2022. "Long-term efficacy and safety of Combigan versus monotherapy."
[2] Tham, Y.C., et al. (2014). "Global prevalence of glaucoma and projections." Ophthalmic Epidemiology, 21(4), 221-231.