Clobetasol Propionate Ophthalmic Nanoemulsion 0.05% for the Treatment of Inflammation and Pain Associated With Cataract Surgery (CLOSE-1)

Cataract Clinical Trial

— CLOSE-1  

Official title:

A Phase 3, Multicenter, Randomized, Double-Masked Clinical Trial to Assess the Efficacy and Safety of Clobetasol Propionate Ophthalmic Nanoemulsion 0.05% Compared to Placebo in the Treatment of Inflammation and Pain Associated With Cataract Surgery

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04246801
• Other study ID #: CLOBOF3-16IA01
• Status: Completed
• Phase: Phase 3
• Start date: June 10, 2020
• Est. completion date: May 19, 2021

Study information

• Verified date: November 2022
• Source: Salvat
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Cataract surgery is one of the most common surgical procedures performed worldwide. In fact, in 2017, 3.8 million cataracts procedures were performed in the US.

Despite of surgical advances, pain and inflammation after ophthalmic surgery continues to be a burden on both patients and physicians. The treatment of postoperative pain is essential for hospitalized patients, but it is even more important for patients who are treated on an outpatient basis.

This study will compare the efficacy and safety of clobetasol propionate ophthalmic nanoemulsion 0.05% to placebo, when administering one drop four times a day during 14 days after routine unilateral cataract surgery. Participants will undergo routine cataract surgery according to the ophthalmologist's normal procedures.

Overall, 210 participants are planned to take part in the study. They will be screened across 20 centers in the US. Participants who experience postoperative inflammation on the first day following routine cataract surgery and who meet all other eligibility criteria will be randomly assigned by chance to one of two study groups in a 2:1 ratio to receive either clobetasol propionate ophthalmic nanoemulsion 0.05 % (N=140) or placebo (N=70) for the treatment of inflammation and pain associated with cataract surgery.

Six (6) study visits are planned: Visit -1 (Screening), Visit 1 (Baseline; 24h after the surgery), Visit 2 (Day 3), Visit 3 (Day 8), Visit 4 (Day 15), and Visit 5 (Day 29).

The ophthalmologist will administer the first dose of the study medication 24 hours after the surgery, at the end of the Baseline visit, at the study center. Study medication will be then dispensed to participants for self-administration during the study at a dosage of one drop four times a day, during 14 days. Direct instillation is the most efficient method for delivery to the ocular surface and is an accepted and widely used method for topical application to the eye.

This study will examine effect and tolerability for 14 days of clobetasol propionate ophthalmic nanoemulsion 0.05% dosed four times a day.

This study is being conducted to support an application for approval to market clobetasol propionate ophthalmic nanoemulsion 0.05% in the US for the indication of inflammation and pain after ocular surgery. The reference (comparator) product in this study, the vehicle, is expected to provide a lower efficacy rate when compared to clobetasol 0.05%.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 250
• Est. completion date: May 19, 2021
• Est. primary completion date: May 19, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Male or female, age 18 years or older on day of consent

2. Participants with routine unilateral cataract surgery on the day prior to study randomization

3. Participants with at least 5 cells in anterior chamber on the first day after surgery (at Baseline visit)

4. Willing and able to understand and provide written informed consent form (ICF) (at Screening visit)

5. Women who satisfy one of the following:

1. Are of child-bearing potential who are not pregnant or lactating and who are either abstinent or sexually active on an acceptable method of birth control (methods that can achieve a failure rate of less than 1% per year when used consistently and correctly, like hormonal contraception (oral pills, implantable device, or skin patch), intrauterine device, bilateral tubal occlusion, or double barrier) for at least 4 weeks prior to Baseline visit and throughout the study (i.e., until Day 29),

OR

2. Are post-menopausal (have had no menstrual cycle for at least one year prior to Screening visit) or have undergone a sterilization procedure (bilateral tubal ligation, hysterectomy, hysterectomy with unilateral or bilateral oophorectomy or bilateral oophorectomy) at least 6 months prior to Screening visit

Exclusion Criteria:

1. Systemic administration of any corticosteroid or immunosuppressant drugs in the previous 2 weeks prior to the first instillation of the investigational medical product (IMP)

2. Periocular injection in the study eye of any corticosteroid solution within 4 weeks prior to the first instillation of the IMP, or of any corticosteroid depot within 2 months prior to the first instillation of the investigational medical product (Ozurdex® [dexamethasone]: within prior 6 months; Iluvien® [fluocinolone]: within prior 36 months)

3. Instillation of any topical ocular corticosteroid, non-steroidal antiinflammatory drug (NSAID), mast cells stabilizers, antihistamines or decongestants within 2 weeks prior to the first instillation of the IMP, except pre-surgical and/or surgical administration of 1 drop of a topical NSAID or corticosteroid, at the investigator discretion

4. Prescription of any topical ocular medication, except preservative-free antibiotics for prophylactic purposes

5. Any history of glaucoma or ocular hypertension in the study eye

6. History or presence of endogenous uveitis

7. Any current corneal abrasion or ulceration

8. Any confirmed or suspected active viral, bacterial, or fungal keratoconjunctival disease

9. Known hypersensitivity or contraindication to the study drug or any of its components

10. History of steroid-related intraocular pressure (IOP) increase

11. Previous surgery in the last 4 weeks prior to the Screening visit or new surgery scheduled to be performed before the end of the study period on the contralateral eye

12. Presence of ocular hemorrhage which interferes with the evaluation of post-surgery inflammation

13. Presence of intraoperative complications during the cataract surgical procedure that may increase post-operative inflammation; this includes, in particular, participants with ocular hemorrhage, floppy iris syndrome, increased IOP (=24 mmHg), posterior capsule rupture and injections of gas into the vitreous body

14. Increased cumulative dissipated energy value during phacoemulsification (increased energy used for phacoemulsification exert additional stress on iris and other anterior chamber structures and may generate excessive inflammation)

15. Presence of zonular dialysis (rupture of zonular fibers that attach lens to the ciliar body which may lead to partial luxation of the lens / lens capsule and is a serious complication of cataract surgery)

16. Presence of Fuchs´ endothelial dystrophy (loss of endothelial cells that may result in chronic corneal edema after cataract surgery especially if high energy was used during phacoemulsification)

17. Presence of cornea guttata

18. Pupil dilation lower than 4.5 mm

19. Presence of lower lacrimal duct obstruction and/or history of infectious dacryocystitis

20. Presence of IOP =24 mmHg at Baseline visit

21. Participation in any study of an investigational topical or systemic new drug or device within 30 days prior to the Screening visit, or at any time during the study

22. Prior participation in the study described in this protocol, unless participant was not randomized

23. In the opinion of the investigator or study coordinator, be unwilling or unable to comply with study protocol or unable to successfully instill eye drops

24. Disease, condition (including monocular participants), or disorder that in the judgement of investigator could confound study assessments or limit compliance to study protocol

Related Conditions & MeSH terms

• Cataract
• Inflammation

Intervention

Drug:
• Clobetasol propionate
Clobetasol propionate ophthalmic nanoemulsion 0.05%, is an oil-in-water (o/w), clear or slightly yellowish nanoemulsion containing the active ingredient clobetasol propionate at a concentration of 0.05% weight per weight (w/w)
• Vehicle
Vehicle is identical in appearance and composition to clobetasol propionate ophthalmic nanoemulsion 0.05% but, without the active substance

Locations

Country	Name	City	State
United States	Dixon Eye Care	Albany	Georgia
United States	Texan Eye, PA / Keystone Research Ltd.	Austin	Texas
United States	Beverly Hills Institute of Ophthalmology	Beverly Hills	California
United States	Arus Research at Cape Coral Eye Center	Cape Coral	Florida
United States	Arizona Eye Center	Chandler	Arizona
United States	Chicago Eye Specialists	Chicago	Illinois
United States	Mark B. Kislinger, MD, Inc.	Glendora	California
United States	Chicago Cornea Consultants Ltd	Hoffman Estates	Illinois
United States	Houston Eye Associates	Houston	Texas
United States	Silverstein Eye Centers	Kansas City	Missouri
United States	Wellish Vision Institute	Las Vegas	Nevada
United States	Apex Eye	Mason	Ohio
United States	Eye Care Centers Management, Inc. (Clayton Eye Center)	Morrow	Georgia
United States	LoBue Laseer & Eye Medical Center	Murrieta	California
United States	Fifth Avenue Eye Associates	New York	New York
United States	Pasedena Eye Medical Group	Pasadena	California
United States	Martel Medical Eye Group	Rancho Cordova	California
United States	Black Hills Regional Eye Institute	Rapid City	South Dakota
United States	Coastal Research Associates	Roswell	Georgia
United States	Medical Center Ophthalmology Associates	San Antonio	Texas
United States	Santa Barbara Eyecare	Santa Barbara	California
United States	Wolston & Goldberg Eye Associates	Torrance	California

Sponsors (1)

Lead Sponsor	Collaborator
Salvat

Country where clinical trial is conducted

United States, 

References & Publications (11)

Bourlais CL, Acar L, Zia H, Sado PA, Needham T, Leverge R. Ophthalmic drug delivery systems--recent advances. Prog Retin Eye Res. 1998 Jan;17(1):33-58. doi: 10.1016/s1350-9462(97)00002-5. — View Citation

Chiquet C, Aptel F, Creuzot-Garcher C, Berrod JP, Kodjikian L, Massin P, Deloche C, Perino J, Kirwan BA, de Brouwer S, Combette JM, Behar-Cohen F. Postoperative Ocular Inflammation: A Single Subconjunctival Injection of XG-102 Compared to Dexamethasone Dr — View Citation

Coppens M, Versichelen L, Mortier E. Treatment of postoperative pain after ophthalmic surgery. Bull Soc Belge Ophtalmol. 2002;(285):27-32. — View Citation

Henzler D, Kramer R, Steinhorst UH, Piepenbrock S, Rossaint R, Kuhlen R. Factors independently associated with increased risk of pain development after ophthalmic surgery. Eur J Anaesthesiol. 2004 Feb;21(2):101-6. doi: 10.1017/s0265021504002042. — View Citation

Jabs DA, Nussenblatt RB, Rosenbaum JT; Standardization of Uveitis Nomenclature (SUN) Working Group. Standardization of uveitis nomenclature for reporting clinical data. Results of the First International Workshop. Am J Ophthalmol. 2005 Sep;140(3):509-16. doi: 10.1016/j.ajo.2005.03.057. — View Citation

Juthani VV, Clearfield E, Chuck RS. Non-steroidal anti-inflammatory drugs versus corticosteroids for controlling inflammation after uncomplicated cataract surgery. Cochrane Database Syst Rev. 2017 Jul 3;7(7):CD010516. doi: 10.1002/14651858.CD010516.pub2. — View Citation

Kessel L, Tendal B, Jorgensen KJ, Erngaard D, Flesner P, Andresen JL, Hjortdal J. Post-cataract prevention of inflammation and macular edema by steroid and nonsteroidal anti-inflammatory eye drops: a systematic review. Ophthalmology. 2014 Oct;121(10):1915 — View Citation

Pascolini D, Mariotti SP. Global estimates of visual impairment: 2010. Br J Ophthalmol. 2012 May;96(5):614-8. doi: 10.1136/bjophthalmol-2011-300539. Epub 2011 Dec 1. — View Citation

Patel A, Cholkar K, Agrahari V, Mitra AK. Ocular drug delivery systems: An overview. World J Pharmacol. 2013;2(2):47-64. doi: 10.5497/wjp.v2.i2.47. — View Citation

Porela-Tiihonen S, Kaarniranta K, Kokki H. Postoperative pain after cataract surgery. J Cataract Refract Surg. 2013 May;39(5):789-98. doi: 10.1016/j.jcrs.2013.03.012. — View Citation

Sherif Z, Pleyer U. Corticosteroids in ophthalmology: past-present-future. Ophthalmologica. 2002 Sep-Oct;216(5):305-15. doi: 10.1159/000066189. No abstract available. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Anterior Chamber Cell Grade	Percentage of participants with anterior chamber cell grade of "0" (absence of cells)	Day 8
Secondary	Pain Visual Analogue Scale (VAS) Score	Percentage of participants with VAS pain score of "0" (no eye pain). Pain was scored by ticking on a continuous scale comprised of a 10 cm horizontal line anchored by two verbal descriptions: "no eye pain" (score of 0) and "worst imaginable eye pain" (score of 10).	Day 8