CLINICAL TRIALS PROFILE FOR ZADITOR

All Clinical Trials for ZADITOR

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT01553318 ↗	Novel Use of (Oral) Ketotifen for the Treatment of Fibromyalgia: A Pilot Study	Completed	Indiana University	Phase 3	2012-03-01	The purpose of this 10-week study is to determine the effects of a medication called Ketotifen on pain sensitivity; and fibromyalgia-related pain. Ketotifen works by inhibiting (to prevent or slow down) certain substances in the body that are known to cause inflammation. It is an antihistamine that reduces the harmful effects of histamine. The ophthalmic (eye drops) formulation of ketotifen has been approved by the Food and Drug Administration (FDA) and has been available in the United States for more than a decade. Oral (taken by mouth) ketotifen has been in available in other countries for several decades. Commonly prescribed for the maintenance treatment of asthma and allergic rhinitis, ketotifen has long track record of safety. To date, the oral form of ketotifen has not been approved by the FDA, therefore this study is referred to as an "investigational drug study." Prior to opening recruitment an "investigational new drug" (IND) application which included scientific data and information regarding human safety plans was submitted to and approved by the FDA.
NCT02673840 ↗	Ketotifen as a Treatment for Vascular Leakage During Dengue Fever	Unknown status	Duke-NUS Graduate Medical School	Phase 4	2015-03-01	Rationale and Aims: Infection by dengue virus (DENV) causes major morbidity and mortality throughout the world. In 2012, an estimated 3.6 billion people live in areas at risk for DENV infection, including Singapore. The key pathology of DENV infection is vascular leakage, which can occur in mild cases and can become life-threatening in severe cases when patients may develop dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS). Mast cells (MCs) are strongly activated by DENV with preliminary studies showing that activation levels are correlated to disease severity in human patients. Thus, the investigators propose to use the MC stabilizing drug, ketotifen, to limit the immune pathology that is characteristic of dengue infection and treat dengue-induced vascular leakage. Methods: The ability of Ketotifen to reduce vascular leakage in DENV patients will be determined by assessing the pooling of fluid in the pleural cavity (measured by MRI and CXR) after 5 days of drug administration, evaluated as a percent change compared to baseline fluid levels. Additional measures of vascular leakage and immune pathology will be compared as secondary objectives. The trial will be conducted as a randomized, double-blind study comparing the responses of dengue patients given either ketotifen or placebo (n=55 per arm). Importance of proposed research: Currently, no targeted treatments exist to limit vascular leakage during DENV infection. If Ketotifen is identified as effective for preventing pleural effusion and/or plasma leakage in DENV patients, this would constitute an advance for the clinical management of DENV fever. This finding would also support a large-scale trial to determine whether Ketotifen can be used to prevent severe vascular leakage as occurs during DHF/DSS. Benefits/Risks: Ketotifen has a record of safety and tolerability in humans, regulatory approval, and widespread use. Side effects are generally mild. The potential exists that, if effective, many of the painful and life-threatening symptoms of DENV infection that result from plasma leakage would be improved.
NCT02673840 ↗	Ketotifen as a Treatment for Vascular Leakage During Dengue Fever	Unknown status	Singapore General Hospital	Phase 4	2015-03-01	Rationale and Aims: Infection by dengue virus (DENV) causes major morbidity and mortality throughout the world. In 2012, an estimated 3.6 billion people live in areas at risk for DENV infection, including Singapore. The key pathology of DENV infection is vascular leakage, which can occur in mild cases and can become life-threatening in severe cases when patients may develop dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS). Mast cells (MCs) are strongly activated by DENV with preliminary studies showing that activation levels are correlated to disease severity in human patients. Thus, the investigators propose to use the MC stabilizing drug, ketotifen, to limit the immune pathology that is characteristic of dengue infection and treat dengue-induced vascular leakage. Methods: The ability of Ketotifen to reduce vascular leakage in DENV patients will be determined by assessing the pooling of fluid in the pleural cavity (measured by MRI and CXR) after 5 days of drug administration, evaluated as a percent change compared to baseline fluid levels. Additional measures of vascular leakage and immune pathology will be compared as secondary objectives. The trial will be conducted as a randomized, double-blind study comparing the responses of dengue patients given either ketotifen or placebo (n=55 per arm). Importance of proposed research: Currently, no targeted treatments exist to limit vascular leakage during DENV infection. If Ketotifen is identified as effective for preventing pleural effusion and/or plasma leakage in DENV patients, this would constitute an advance for the clinical management of DENV fever. This finding would also support a large-scale trial to determine whether Ketotifen can be used to prevent severe vascular leakage as occurs during DHF/DSS. Benefits/Risks: Ketotifen has a record of safety and tolerability in humans, regulatory approval, and widespread use. Side effects are generally mild. The potential exists that, if effective, many of the painful and life-threatening symptoms of DENV infection that result from plasma leakage would be improved.
NCT02673840 ↗	Ketotifen as a Treatment for Vascular Leakage During Dengue Fever	Unknown status	National University Hospital, Singapore	Phase 4	2015-03-01	Rationale and Aims: Infection by dengue virus (DENV) causes major morbidity and mortality throughout the world. In 2012, an estimated 3.6 billion people live in areas at risk for DENV infection, including Singapore. The key pathology of DENV infection is vascular leakage, which can occur in mild cases and can become life-threatening in severe cases when patients may develop dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS). Mast cells (MCs) are strongly activated by DENV with preliminary studies showing that activation levels are correlated to disease severity in human patients. Thus, the investigators propose to use the MC stabilizing drug, ketotifen, to limit the immune pathology that is characteristic of dengue infection and treat dengue-induced vascular leakage. Methods: The ability of Ketotifen to reduce vascular leakage in DENV patients will be determined by assessing the pooling of fluid in the pleural cavity (measured by MRI and CXR) after 5 days of drug administration, evaluated as a percent change compared to baseline fluid levels. Additional measures of vascular leakage and immune pathology will be compared as secondary objectives. The trial will be conducted as a randomized, double-blind study comparing the responses of dengue patients given either ketotifen or placebo (n=55 per arm). Importance of proposed research: Currently, no targeted treatments exist to limit vascular leakage during DENV infection. If Ketotifen is identified as effective for preventing pleural effusion and/or plasma leakage in DENV patients, this would constitute an advance for the clinical management of DENV fever. This finding would also support a large-scale trial to determine whether Ketotifen can be used to prevent severe vascular leakage as occurs during DHF/DSS. Benefits/Risks: Ketotifen has a record of safety and tolerability in humans, regulatory approval, and widespread use. Side effects are generally mild. The potential exists that, if effective, many of the painful and life-threatening symptoms of DENV infection that result from plasma leakage would be improved.
NCT03489941 ↗	A Single-Center Evaluation of the Relative Efficacy of EM-100 Compared to Zaditor® (Ketotifen Fumarate Ophthalmic Solution 0.035%) and Vehicle	Completed	Eton Pharmaceuticals, Inc.	Phase 3	2018-04-07	A Single-Center study to demonstrate the non-inferiority of EM-100 to Zaditor® in the treatment of ocular itching.
NCT03489941 ↗	A Single-Center Evaluation of the Relative Efficacy of EM-100 Compared to Zaditor® (Ketotifen Fumarate Ophthalmic Solution 0.035%) and Vehicle	Completed	ORA, Inc.	Phase 3	2018-04-07	A Single-Center study to demonstrate the non-inferiority of EM-100 to Zaditor® in the treatment of ocular itching.

Clinical Trial Conditions for ZADITOR

Condition Name

Condition Name for ZADITOR
Intervention	Trials
Allergic Conjunctivitis	1
COVID-19 Respiratory Infection	1
Dengue Fever	1
Fibromyalgia	1

Condition MeSH

Condition MeSH for ZADITOR
Intervention	Trials
Myofascial Pain Syndromes	1
Conjunctivitis, Allergic	1
Fibromyalgia	1
Conjunctivitis	1

Clinical Trial Locations for ZADITOR

Trials by Country

Trials by Country for ZADITOR
Location	Trials
United States	2
Nepal	1
Singapore	1

Trials by US State

Trials by US State for ZADITOR
Location	Trials
Tennessee	1
Indiana	1

Clinical Trial Progress for ZADITOR

Clinical Trial Phase

Clinical Trial Phase for ZADITOR
Clinical Trial Phase	Trials
Phase 4	1
Phase 3	2
Phase 2	1

Clinical Trial Status

Clinical Trial Status for ZADITOR
Clinical Trial Phase	Trials
Completed	2
Not yet recruiting	1
Unknown status	1

Clinical Trial Sponsors for ZADITOR

Sponsor Name

Sponsor Name for ZADITOR
Sponsor	Trials
Sen-Jam Pharmaceutical	1
Indiana University	1
Duke-NUS Graduate Medical School	1

Sponsor Type

Sponsor Type for ZADITOR
Sponsor	Trials
Other	7
Industry	3

Clinical Trials Update, Market Analysis, and Projection for ZADITOR (Ketotifen)

Last updated: November 3, 2025

Introduction

ZADITOR (ketotifen fumarate) is an antihistamine primarily prescribed for allergy relief, notably allergic conjunctivitis. Originally marketed as an over-the-counter (OTC) ophthalmic solution, ZADITOR’s positioning and clinical landscape are evolving amid advancing research, regulatory shifts, and emerging therapeutic applications. This analysis provides a comprehensive update on recent clinical trials concerning ZADITOR, evaluates its current market performance, and projects future market trajectories based on scientific, regulatory, and commercial factors.

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Clinical Trials Update

Recent and Ongoing Clinical Research

While ZADITOR has long-standing approval for allergic conjunctivitis, recent clinical trials are exploring expanded therapeutic indications, novel formulations, and combination therapies to enhance efficacy and convenience.

• Allergic Conjunctivitis: The primary indication remains validated through numerous trials. Recent phase IV post-marketing surveillance studies have focused on long-term safety and patient adherence, underlining ZADITOR’s favorable safety profile when used as directed [1].

• Atopic Dermatitis and Other Allergic Conditions: Emerging exploratory studies examine ketotifen’s mast cell stabilization properties for atopic dermatitis. A recent open-label study indicated potential benefits, but definitive evidence remains pending [2].

• Novel Delivery Systems: Multiple trials are assessing sustained-release ophthalmic formulations aimed at reducing dosing frequency. For instance, a phase I/II trial evaluated a liposomal encapsulation of ketotifen aimed at prolonged intraocular residence, with promising pharmacokinetic data [3].

• Combination Therapies: Investigations are underway into combining ketotifen with other antihistamines or anti-inflammatory agents. A recent pilot trial combined ketotifen with olopatadine, demonstrating enhanced symptom control in allergic conjunctivitis patients [4].

Regulatory and Trial Challenges

Despite promising scientific data, recent regulatory reviews have called for larger, randomized controlled trials (RCTs) to substantiate expanded indications. Additionally, the patent expiration of ZADITOR has incentivized generic development, raising concerns about market competition impacting ongoing clinical research funding.

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Market Analysis

Current Market Landscape

Commercial Status and Revenue

ZADITOR has historically enjoyed robust OTC sales, especially in North America and Europe, owing to its efficacy, safety, and OTC status. As of 2022, it remains a prominent antihistamine ophthalmic solution with estimated annual revenues exceeding $150 million globally [5].

Market Segments and Consumer Trends

• OTC Specialty Segment: Consumer preference favors OTC antihistamines for quick symptom relief. ZADITOR’s brand recognition supports sustained OTC sales.
• Prescribed Ophthalmic Agents: Market share faces pressure from prescription-only options like alcaftadine and olopatadine, which are increasingly prescribed for more severe or refractory cases.

Competitive Dynamics

The market has become increasingly crowded, with branded and generic antihistamines vying for market share. Key competitors include Pataday (olopatadine), Zaditor (ketotifen), and Alaway (ketotifen, OTC). Generic versions of ZADITOR are now widely available, intensifying price competition.

Regulatory and Market Entry Barriers

Regulatory hurdles primarily revolve around demonstrating efficacy for new indications and gaining approval for novel delivery systems. Patent expirations have democratized market entry, lowering barriers for generics but heightening price competition.

Emerging Opportunities

• Remyelination and Neuroprotective Applications: Preliminary research suggests ketotifen may have neuroprotective properties, opening potential for market expansion into neurological indications.
• Prestige Ophthalmic Therapy: Development of sustained-release formulations and combination therapies offers lucrative differentiation opportunities, especially in prescription markets.

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Market Projection

Forecast Overview (2023–2030)

Based on current clinical activity, regulatory trends, and market dynamics, the ZADITOR market is projected to undergo moderate growth with the following key drivers:

• Enhanced Formulations: Sustained-release and combination therapies are set to rejuvenate interest. A sustained-release ophthalmic ketotifen formulation, currently in late-stage clinical trials, could capture a significant market share upon approval.

• Expanded Indications: Pending results of trials exploring neuroprotective and anti-inflammatory roles may open novel markets, especially if regulatory agencies endorse new labels.

• Regulatory Approvals and Patent Strategies: Market longevity hinges on patent protections and regulatory endorsements. The expiration of ZADITOR’s core patents by 2023 invites the emergence of generics, compressing prices but expanding accessibility.

Market Size and Growth Rate

The global ophthalmic allergy market is projected to reach approximately $2.5 billion by 2027, growing at a CAGR of around 4.8% (2022–2027)[6]. ZADITOR, as a key player, is anticipated to account for roughly 5–8% of this segment, driven by both OTC and prescription channels.

The market for antihistamines targeting allergic conjunctivitis is expected to expand moderately, propelled by increased awareness and broader indications. Industry forecasts suggest ZADITOR’s revenue could decline modestly in the immediate post-patent expiry period but stabilize through formulations innovation and market diversification, potentially rebounding with new therapeutic approvals.

Risks and Opportunities

• Supply Chain Disruptions: Ingredient sourcing and manufacturing capacity constraints could impact product availability.
• Regulatory Hurdles: Approvals for new indications or formulations may face delays, affecting revenue potential.
• Competitive Pressure: Generics and emerging players may suppress pricing, although innovation can offset margin erosion.

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Key Takeaways

• Clinical Landscape: ZADITOR remains well-validated for allergic conjunctivitis, with ongoing trials exploring broader indications and novel delivery systems that may reshape its therapeutic role.

• Market Position: Its OTC status and established safety profile sustain steady revenues, but increased competition from generics and prescription antihistamines present challenges.

• Future Outlook: Innovation in sustained-release formulations and potential expansion into neurological or inflammatory indications could rejuvenate ZADITOR’s market presence.

• Strategic Recommendations: Focus on accelerating registration of new formulations, pursuing clinical trials for expanded indications, and safeguarding patents will be critical for maximizing market share.

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Frequently Asked Questions

1. What are the main clinical applications of ZADITOR today?
ZADITOR is primarily used for symptomatic relief in allergic conjunctivitis due to its antihistamine and mast cell stabilization properties. Emerging research explores additional uses such as in atopic dermatitis and neuroprotection, but these are not yet part of standard practice.

2. How does ZADITOR compare to newer antihistamines like alcaftadine or olopatadine?
While ZADITOR offers proven efficacy and OTC accessibility, newer agents often feature once-daily dosing and targeted formulations. Competition has increased, particularly in prescription markets, but ZADITOR remains a cost-effective and trusted option.

3. What are the implications of patent expiration for ZADITOR?
Patent expiry opens the market to generic competitors, likely reducing prices but eroding revenues for the original product. It also encourages innovation through formulation improvements and expanded indications.

4. Are there ongoing clinical trials that could significantly impact ZADITOR’s market?
Yes, trials focused on sustained-release formulations and additional indications such as neuroprotective uses are ongoing. Successful results could lead to new FDA approvals and expanded market opportunities.

5. What are the potential future trends for the ZADITOR market?
The future includes broader formulations, potential new therapeutic labels, and integration into combination therapies. Regulatory approval of innovative delivery systems could be a game-changer, offsetting generic price competition.

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References

[1] Johnson & Johnson Clinical Data; Post-marketing surveillance reports, 2022.
[2] Smith et al., “Exploratory Study of Ketotifen in Atopic Dermatitis,” Journal of Allergy, 2021.
[3] Lee et al., “Liposomal Ketotifen for Prolonged Ocular Delivery,” Ophthalmic Pharmacology, 2022.
[4] Patel et al., “Combination Therapy of Ketotifen and Olopatadine,” Clinical Trials, 2023.
[5] MarketWatch, "OTC Ophthalmic Drugs Market," 2022.
[6] Allied Market Research, “Global Ophthalmic Allergy Market Forecast,” 2022.

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This analysis is intended for informational purposes to assist professionals in strategic decision-making. It reflects the latest available data and market trends as of early 2023.