Cataract
Conditions
Keywords
Cataract surgery, Inflammation, Pain, Clobetasol propionate, Ophthalmology
Brief 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%.
Interventions
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)
DRUGVehicle
Vehicle is identical in appearance and composition to clobetasol propionate ophthalmic nanoemulsion 0.05% but, without the active substance
Sponsors
Salvat
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Intervention model description
At least 210 participants will be randomized in a 2:1 randomization ratio (140 to clobetasol arm, 70 to placebo arm) in order to have 202 evaluable participants (4% lost to follow-up rate expected)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Anterior Chamber Cell Grade | Day 8 | Percentage of participants with anterior chamber cell grade of 0 (absence of cells) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pain Visual Analogue Scale (VAS) Score | Day 8 | 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). |
Countries
United States
Participant flow
Recruitment details
Patient with routine unilateral cataract surgery on the day prior to study randomization
Pre-assignment details
Patients with at least 5 cells in anterior chamber on the first day after surgery (at Visit 1)
Participants by arm
| Arm | Count |
|---|---|
| Clobetasol Propionate Investigational treatment
1 drop four times a day | 140 |
| Placebo Vehicle
1 drop four times a day | 71 |
| Total | 211 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 |
| Overall Study | Lack of Efficacy | 0 | 2 |
| Overall Study | Lost to Follow-up | 1 | 1 |
| Overall Study | Protocol Violation | 1 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 1 |
Baseline characteristics
| Characteristic | Clobetasol Propionate | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 67.7 years STANDARD_DEVIATION 8.6 | 67.0 years STANDARD_DEVIATION 8.3 | 65.5 years STANDARD_DEVIATION 7.7 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 5 Participants | 11 Participants | 6 Participants |
| Race (NIH/OMB) Black or African American | 25 Participants | 32 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 109 Participants | 167 Participants | 58 Participants |
| Region of Enrollment United States | 140 participants | 211 participants | 71 participants |
| Sex: Female, Male Female | 77 Participants | 115 Participants | 38 Participants |
| Sex: Female, Male Male | 63 Participants | 96 Participants | 33 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 140 | 0 / 71 |
| other Total, other adverse events | 1 / 140 | 5 / 71 |
| serious Total, serious adverse events | 1 / 140 | 0 / 71 |
Outcome results
Primary
Anterior Chamber Cell Grade
Percentage of participants with anterior chamber cell grade of 0 (absence of cells)
Time frame: Day 8
Population: FAS Population with anterior chamber cell grade assessment at Day 8
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Clobetasol Propionate | Anterior Chamber Cell Grade | 67 Participants |
| Placebo | Anterior Chamber Cell Grade | 18 Participants |
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).
Time frame: Day 8
Population: FAS Population with pain VAS assessment at Day 8
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Clobetasol Propionate | Pain Visual Analogue Scale (VAS) Score | 83 Participants |
| Placebo | Pain Visual Analogue Scale (VAS) Score | 19 Participants |