CLINICAL TRIALS PROFILE FOR ACUVAIL

All Clinical Trials for Acuvail

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT01001806 ↗	A Comparison of Peak Aqueous Penetration of Acuvail (Ketorolac 0.45%), Xibrom (Bromfenac 0.09%), and Nevanac (Nepafenac 0.1%)in Patients Undergoing Phacoemulsification	Completed	Allergan	Phase 4	2009-10-01	Approximately 126 subjects scheduled to undergo cataract surgery by phacoemulsification, will be randomized in an even allocation (1:1:1) to either Acuvail, Xibrom, or Nevanac. Subjects will be instructed to begin dosing the study medication in the operative eye the day before surgery and continue dosing on the day of surgery. Beginning one hour before surgery, 1 drop of study medication will be instilled by operating room staff approximately every 15 minutes for a total of 3 doses. At the designated time a paracentesis will be performed at the start of the cataract procedure and at least 0.15 cc of aqueous humor will be collected. The sample will be immediately stored on dry ice and shipped to a laboratory for analysis.
NCT01001806 ↗	A Comparison of Peak Aqueous Penetration of Acuvail (Ketorolac 0.45%), Xibrom (Bromfenac 0.09%), and Nevanac (Nepafenac 0.1%)in Patients Undergoing Phacoemulsification	Completed	Frank A. Bucci, Jr., M.D.	Phase 4	2009-10-01	Approximately 126 subjects scheduled to undergo cataract surgery by phacoemulsification, will be randomized in an even allocation (1:1:1) to either Acuvail, Xibrom, or Nevanac. Subjects will be instructed to begin dosing the study medication in the operative eye the day before surgery and continue dosing on the day of surgery. Beginning one hour before surgery, 1 drop of study medication will be instilled by operating room staff approximately every 15 minutes for a total of 3 doses. At the designated time a paracentesis will be performed at the start of the cataract procedure and at least 0.15 cc of aqueous humor will be collected. The sample will be immediately stored on dry ice and shipped to a laboratory for analysis.
NCT01021761 ↗	A Comparison of Prostaglandin E2 (PGE2) Inhibition of Acuvail(Ketorolac 0.45%), Xibrom (Bromfenac 0.09%)and Nevanac (Nepafenac)in Patients Undergoing Phacoemulsification	Completed	Allergan	Phase 4	2009-10-01	Approximately 126 subjects scheduled to undergo cataract surgery by phacoemulsification, will be randomized in an even allocation (1:1:1) to either Acuvail, Xibrom or Nevanac. Subjects will be instructed to begin dosing the study medication in the operative eye the day before surgery and continue dosing on the day of surgery. Beginning one hour before surgery 1 drop of study medication will be instilled by operating room staff approximately every 15 minutes for a total of 3 doses. At the designated time a paracentesis will be performed at the start of the cataract procedure and at least 0.15cc of aqueous humor will be collected. The sample will be immediately stored on dry ice and shipped to a laboratory for analysis.
NCT01021761 ↗	A Comparison of Prostaglandin E2 (PGE2) Inhibition of Acuvail(Ketorolac 0.45%), Xibrom (Bromfenac 0.09%)and Nevanac (Nepafenac)in Patients Undergoing Phacoemulsification	Completed	Frank A. Bucci, Jr., M.D.	Phase 4	2009-10-01	Approximately 126 subjects scheduled to undergo cataract surgery by phacoemulsification, will be randomized in an even allocation (1:1:1) to either Acuvail, Xibrom or Nevanac. Subjects will be instructed to begin dosing the study medication in the operative eye the day before surgery and continue dosing on the day of surgery. Beginning one hour before surgery 1 drop of study medication will be instilled by operating room staff approximately every 15 minutes for a total of 3 doses. At the designated time a paracentesis will be performed at the start of the cataract procedure and at least 0.15cc of aqueous humor will be collected. The sample will be immediately stored on dry ice and shipped to a laboratory for analysis.
NCT01609881 ↗	The Role of Prostaglandins in the Progression of Diabetic Retinopathy	Withdrawn	Vanderbilt University	Phase 1	2012-03-01	Objective of the research study: 1. To measure anterior chamber and vitreous ketorolac (Acuvail®) concentrations after topical administration in patients undergoing routine vitrectomy to determine the ability of the medication to penetrate into the anterior chamber and vitreous cavity, and to compare these levels to the IC50 for the cyclooxygenase-1 and -2 enzymes (COX-1 and COX-2) 2. To measure vitreous concentrations of prostaglandin subtypes (PGE, PGD, PGF) and other inflammatory mediators (Interleukin-1β [IL-1β], IL-6, IL-8, tumor necrosis factor [TNF]-α, VEGF) in both diabetic and nondiabetic patients undergoing vitrectomy 3. To determine if topical ketorolac (Acuvail®) can penetrate the anterior chamber and vitreous cavity sufficiently to decrease levels of intraocular inflammatory mediators that have been shown to be elevated in diabetic patients 4. To serve as a precursor to a 5-year longitudinal clinical trial to determine if chronically administered topical ketorolac (Acuvail®) can prevent, delay or slow diabetic retinopathy. Research hypothesis 1. Ketorolac (Acuvail®) will penetrate the anterior chamber and vitreous cavity sufficiently to achieve levels above the IC50 for COX-1 and COX-2 2. Prostaglandin and other inflammatory mediator levels in the anterior chamber and vitreous cavity will be significantly higher among diabetic patients than nondiabetic controls 3. Acuvail® can significantly lower anterior chamber and vitreous cavity levels of prostaglandins and other inflammatory mediators in diabetic patients
NCT01640171 ↗	Anesthesia Preference for Intravitreal Injection: Topical or Subconjunctival	Completed	Retina Vitreous Associates of Florida	N/A	2012-07-01	Since 2004, intravitreal injection of Avastin, Lucentis, and Macugen for wet age-related macular degeneration, retinal vein occlusion, and diabetic macular edema are being administered in the United States at increasing rates. A 2010 study showed that in Canada and the incidence of injections grew 8 fold from 2005 to 2007 to 25.9 injections per 100,000 citizens. (Campbell 2010) In 2009, in the United States, over 1 million intravitreal injections were administered to Medicare beneficiaries. (Wykoff 2011) In the year 2011, the four doctors in my retina group administered a total of 6,494 intravitreal injections; in 2010, we administered 5021 intravitreal injections. Even though intravitreal injections are commonly administered, the optimal method of anesthetizing the eye prior to injection has yet to be determined. Some physicians use an anesthetic drop, some a soaked cotton pledget, some use an anesthetic gel and some use subconjunctival injected anesthetic. In 2009, the last time the Procedures and Trends Survey (PAT) (Mittra 2009) conducted by the American Society of Retina Specialists (the largest retina society in the world) asked about anesthetic methods for administering intravitreal injections, the following response was given by the 433 respondents: - Topical anesthetic drop: 21.48% - Topical viscous anesthetic: 23.33% - Topical anesthetic & soaked cotton-tip or pledget: 29.79% - Subconjunctival injection of anesthetic: 24.02% - Other: 1.39% An editorial in 2011 in the journal Retina, discusses the lack of good studies assessing optimal anesthetic prior to intravitreal injections. (Prenner 2011).

Clinical Trial Conditions for Acuvail

Condition Name

Condition Name for Acuvail
Intervention	Trials
Cataracts	2
Inflammation	1
Non-small Cell Lung Cancer	1
Osteoarthritis	1

Condition MeSH

Condition MeSH for Acuvail
Intervention	Trials
Cataract	3
Diabetic Retinopathy	2
Macular Edema	2
Osteoarthritis	1

Clinical Trial Locations for Acuvail

Trials by Country

Trials by Country for Acuvail
Location	Trials
United States	8
Malaysia	1

Trials by US State

Trials by US State for Acuvail
Location	Trials
Tennessee	2
Massachusetts	1
New York	1
Minnesota	1
Florida	1

Clinical Trial Progress for Acuvail

Clinical Trial Phase

Clinical Trial Phase for Acuvail
Clinical Trial Phase	Trials
Phase 4	5
Phase 3	1
Phase 2	1

Clinical Trial Status

Clinical Trial Status for Acuvail
Clinical Trial Phase	Trials
Completed	6
Withdrawn	2
Recruiting	2

Clinical Trial Sponsors for Acuvail

Sponsor Name

Sponsor Name for Acuvail
Sponsor	Trials
Allergan	3
Frank A. Bucci, Jr., M.D.	2
Arthroplasty Foundation, Inc.	1

Sponsor Type

Sponsor Type for Acuvail
Sponsor	Trials
Other	12
Industry	3
NIH	2

ACUVAIL: Clinical Trials, Market Analysis, and Projections

Clinical Trials Overview

ACUVAIL, a preservative-free formulation of ketorolac tromethamine ophthalmic solution, has undergone extensive clinical trials to evaluate its efficacy and safety in treating pain and inflammation following cataract surgery.

Key Clinical Trials

Two multicenter, randomized, double-masked, parallel group comparison studies (191578-005 and 191578-006) were conducted involving 511 patients. These studies compared the efficacy and safety of ACUVAIL with a vehicle (placebo) group. Here are the key findings:

• Efficacy: ACUVAIL demonstrated significant superiority over the vehicle in clearing anterior chamber inflammation and resolving ocular pain. By day seven, nearly twice as many patients receiving ACUVAIL had an SOIS (summed inflammation score) of zero compared to the vehicle group (32% vs 17%). By day 14, 53% of ACUVAIL patients had cleared anterior chamber inflammation, compared to 26% in the vehicle group[3].
• Safety: The most frequently occurring adverse drug reactions were increased intraocular pressure (IOP) (5.8%), conjunctival hyperemia, eye pain, photophobia, and anterior chamber inflammation. However, these adverse events were generally reversible and did not lead to long-term complications[1].

Adverse Events

The clinical trials highlighted that while ACUVAIL was generally well-tolerated, there were some notable adverse events:

• Increased IOP was more frequent in the ACUVAIL group (5.8%) compared to the vehicle group (1.8%).
• Anterior chamber inflammation led to study discontinuation in 3.6% of patients[1].

Market Analysis

FDA Approval and Market Entry

ACUVAIL received FDA approval in July 2009 for the treatment of pain and inflammation following cataract surgery. This approval marked a significant milestone, given the high frequency of cataract surgeries in the United States, with over 3 million procedures performed annually[3].

Market Positioning

ACUVAIL is positioned as an advanced, preservative-free NSAID, which is a key differentiator in the ophthalmic market. Its twice-daily dosing and optimized tolerability make it a convenient and effective option for managing post-cataract surgery inflammation and pain.

Regulatory Challenges

Despite its clinical success, Allergan faced regulatory challenges related to marketing claims. The company received an Untitled Letter from the DDMAC (Division of Drug Marketing, Advertising, and Communications) for making unsubstantiated superiority claims about ACUVAIL in a journal ad. This led to the immediate cessation of the misleading marketing materials[2].

Market Projections

Ophthalmic Therapeutic Market

The ophthalmic therapeutic drugs market, which includes products like ACUVAIL, is expected to grow significantly. A market research report indicated that the global ophthalmic therapeutic drugs market would experience compound annual growth rates (CAGRs) through 2014, driven by increasing prevalence of eye diseases such as age-related macular degeneration, glaucoma, and diabetic retinopathy[5].

Competitive Landscape

ACUVAIL operates in a competitive landscape with other ophthalmic NSAIDs and therapeutic agents. Key players in the ophthalmic market include Allergan, Alcon/Novartis, and Pfizer, among others. The market is characterized by stringent regulatory pathways and a focus on sustained delivery technologies, which ACUVAIL's preservative-free formulation aligns with[5].

Future Outlook

Given its efficacy and safety profile, ACUVAIL is expected to remain a valuable option for ophthalmic surgeons and patients undergoing cataract surgery. The drug's unique preservative-free formulation and twice-daily dosing convenience are likely to contribute to its market share in the ophthalmic NSAID segment.

Key Takeaways

• Clinical Efficacy: ACUVAIL has demonstrated significant efficacy in clearing anterior chamber inflammation and resolving ocular pain post-cataract surgery.
• Safety Profile: While generally well-tolerated, ACUVAIL can cause increased IOP and other adverse events, which are mostly reversible.
• Market Approval: FDA-approved in 2009, ACUVAIL is a key player in the ophthalmic therapeutic market.
• Regulatory Compliance: Allergan has faced regulatory challenges related to marketing claims, emphasizing the need for accurate and substantiated advertising.
• Market Growth: The ophthalmic therapeutic market is projected to grow, driven by increasing prevalence of eye diseases.

FAQs

Q: What is ACUVAIL used for?

A: ACUVAIL is used for the treatment of pain and inflammation following cataract surgery.

Q: What is the unique feature of ACUVAIL?

A: ACUVAIL is a preservative-free formulation of ketorolac tromethamine ophthalmic solution, which is a key differentiator in the ophthalmic market.

Q: What were the main findings of the clinical trials for ACUVAIL?

A: The clinical trials showed that ACUVAIL was significantly superior to the vehicle in clearing anterior chamber inflammation and resolving ocular pain post-cataract surgery.

Q: What are the common adverse events associated with ACUVAIL?

A: Increased intraocular pressure (IOP), conjunctival hyperemia, eye pain, photophobia, and anterior chamber inflammation are common adverse events.

Q: Did ACUVAIL face any regulatory challenges?

A: Yes, Allergan received an Untitled Letter from the DDMAC for making unsubstantiated superiority claims about ACUVAIL in a journal ad.

Sources

1. PRODUCT MONOGRAPH INCLUDING PATIENT MEDICATION INFORMATION: ACUVAIL (ketorolac tromethamine ophthalmic solution) - AbbVie Canada.
2. DDMAC pokes Allergan on eye drop direct mail: MM+M.
3. Allergan Inc. (AGN) Receives FDA Approval For ACUVAIL Ophthalmic Solution: Ophthalmology Web.
4. ACUVAIL Drug Patent Profile: Drug Patent Watch.
5. Reportlinker Adds Ophthalmic Therapeutic Drugs: Technologies and Global Markets: Fierce Pharma.

Last updated: 2025-01-04