NCT04249076: CLOSE-2

Clobetasol Propionate Ophthalmic Nanoemulsion 0.05% for the Treatment of Inflammation and Pain Associated With Cataract Surgery (CLOSE-2)

Completed Phase 3 Results posted Last updated 22 December 2022

What this trial tests

Phase 3 trial testing Clobetasol Propionate in Cataract in 215 participants. Completed in 14 April 2021.

Timeline

4 June 2020

Primary endpoint
14 April 2021

14 April 2021

Quick facts

Lead sponsor	Salvat
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	treatment
Enrollment	215
Start date	4 June 2020
Primary completion	14 April 2021
Estimated completion	14 April 2021
Sites	18 locations across United States

Drugs / interventions tested

• Clobetasol Propionate (CLOBETASOL PROPIONATE) — full drug profile →
• Vehicle

Conditions studied

• Cataract — all drugs for Cataract →

Sponsor

Salvat — full company profile →

Who can join

18 and older, any sex, with Cataract. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Anterior Chamber Cell Grade Primary · Day 8

Percentage of participants with anterior chamber cell grade of "0" (absence of cells)

Group	Value	95% CI
Clobetasol Propionate	38
Placebo	7

Pain Visual Analogue Scale (VAS) Score Secondary · Day 8

Percentage of participants with VAS pain score of "0" (no eye pain)

Group	Value	95% CI
Clobetasol Propionate	68
Placebo	31

Adverse events — posted to ClinicalTrials.gov

Time frame: Overall study period (4 weeks). Reporting threshold: 2%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Clobetasol Propionate

Serious: 1/141 (1%)

Deaths: 0/141

Placebo

Serious: 2/74 (3%)

Deaths: 0/74

Serious adverse events (4 terms)

Reaction	System	Clobetasol Propionate	Placebo
Vertigo positional	Ear and labyrinth disorders	—	—
Cystoid Macular oedema	Eye disorders	—	—
Vomiting	Gastrointestinal disorders	—	—
Dizziness	Nervous system disorders	—	—

Other adverse events (2 terms — click to expand)

Reaction	System	Clobetasol Propionate	Placebo
Eye inflammation	Eye disorders	—	—
Corneal oedema	Eye disorders	—	—

Most-reported serious reactions: Vertigo positional, Cystoid Macular oedema, Vomiting, Dizziness.

Data from ClinicalTrials.gov NCT04249076 adverse events section.

Sponsor's own description

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 patients 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%.

Publications & conference data

6 peer-reviewed publications reference this trial (live from Europe PMC):

1. Advancements in Nanoemulsion-Based Drug Delivery Across Different Administration Routes.
   Chatzidaki MD, Mitsou E. · · 2025 · cited 28× · PMID 40143001 · DOI 10.3390/pharmaceutics17030337
2. Recent advances and future challenges in nanosystems for ocular drug delivery.
   Shahror RA, Fouda AY. · · 2025 · cited 1× · PMID 41478665 · DOI 10.1016/j.jpet.2025.103738
3. Emulsion and Emulgel-Based Ophthalmic Drug Delivery Systems.
   Mohapatra D, Yang E, Corson TW. · · 2025 · cited 1× · PMID 41471020 · DOI 10.3390/pharmaceutics17121504
4. Efficacy and safety of clobetasol propionate ophthalmic nanoemulsion for treating intraocular inflammation and pain associated with cataract surgery: two phase 3 multicentre, randomised, placebo-controlled, double-masked clinical studies.
   Schwartz A, Wellish K, Zaman F, Jong K, et al · · 2026 · PMID 42192627 · DOI 10.1136/bmjopen-2025-101177
5. Nature Meets Science: The Role of Food-Grade Oils and Green Excipients in Pharmaceutical Nanoemulsion Formulation.
   Villapiano F, Capuano M, D'Aria F, Giancola C, et al · · 2026 · PMID 41976583 · DOI 10.3390/ma19071294
6. The Efficacy and Safety of Nanoparticle-Based Clobetasol Propionate in Managing the Inflammation and Pain in Post-Operative Cataract Patients: A Systematic Review and Meta-Analysis.
   Alamoudi A, Aldahlawi AK, Almufarriji N, Alsudais AS, et al · · 2026 · PMID 41948108 · DOI 10.2147/opth.s535477