Comparison of Nepafenac/Dexamethasone Fixed-Dose Combination versus Individual Components for the Management of Postoperative Inflammation Following Cataract Surgery
- Trial ID
- 2025-523367-38-00
- Protocol
- #0525NEDEF
- Sponsor
- Medivis S.r.l.
Trial statistics
Diseases & Conditions
Objectives
The primary objective is to demonstrate the superiority of a nepafenac and dexamethasone fixed-dose combination in the time to resolution of postoperative inflammation following cataract surgery compared to the administration of its individual components. Secondary efficacy objectives include the evaluation of ocular symptoms, ocular pain, central macular thickness, and the requirement for rescue therapy. Safety and tolerability assessments involve monitoring adverse events, intraocular pressure, visual acuity, and patient-reported drug tolerability. Additionally, a pharmacokinetic sub-study will evaluate the pharmacokinetics of the fixed-dose combination and its components. 5, 4, 6.
Participants
The sponsor did not provide information regarding the total number of participants. The study population consists of male and female patients aged 40 years or older experiencing postoperative inflammation following cataract surgery. Selection is based on individuals scheduled for routine unilateral phacoemulsification and posterior chamber intraocular lens implantation. Participants must be willing to discontinue the use of contact lenses for the duration of the trial. For females of childbearing potential, the use of highly effective contraception is required. The study population includes those who undergo unilateral cataract extraction without additional procedures or complications that could confound the objectives.
Plans and Procedures
This randomized, multicentre, blinded-assessor, parallel-group clinical study evaluates the efficacy of a dexamethasone sodium phosphate and nepafenac fixed dose combination compared to its individual components for the treatment of postoperative inflammation following cataract surgery. The trial design involves a screening visit to assess eligibility, followed by a surgical procedure involving phacoemulsification and posterior chamber intraocular lens implantation. Participants are randomized to receive either the test combination or a comparator treatment. Clinical assessments, including slit lamp examination and optical coherence tomography, are conducted at multiple follow-up intervals on postoperative days 1, 3, 5, 7, 14, and 30 to monitor anterior chamber flare, conjunctival hyperaemia, and intraocular pressure. The study also includes a pharmacokinetic sub-study to evaluate drug concentrations. An end-of-study visit concludes the assessment period. Total participant involvement extends through the 30-day postoperative monitoring phase. Early termination may occur due to adverse events or investigator discretion regarding trial integrity.
Treatment
The experimental treatment consists of a fixed-dose combination of dexamethasone sodium phosphate and nepafenac. This medication is administered as eye drops in a solution form. The dosage is 3 gtt per administration via ophthalmic use.
The comparator treatments include nepafenac administered as NEVANAC, a 1 mg/ml suspension. The dosage is 3 gtt per administration via ophthalmic use. Additionally, dexamethasone phosphate is utilized as a comparator in the form of Dexavision, a 1 mg/mL solution. The dosage for this treatment is 3 gtt per administration via ophthalmic use.
Tobramycin is administered as a background therapy using TOBRAMICINA DOC Generici, a 3 mg/ml solution. The dosage is 6 gtt per administration via ophthalmic use.
Efficacy
The primary efficacy endpoint is the time to resolution of postoperative inflammation after cataract surgery. Resolution is defined by an anterior chamber flare score of 0, or a value equal to or inferior to the preoperative value.
Secondary efficacy assessments include:
- The proportion of participants achieving resolution of anterior chamber inflammation (flare score of 0 or equal to or inferior to the preoperative value) on postoperative days 1, 3, 5, 7, 14, and 30.
- Changes from baseline in the anterior chamber flare score and anterior chamber cells score on postoperative days 1, 3, 5, 7, 14, and 30.
- The proportion of participants with an absence of conjunctival hyperaemia, determined by a 4-point Likert scale score of 0 during slit lamp examination on postoperative days 1, 3, 5, 7, 14, and 30.
- The proportion of participants with a Total Ocular Symptoms Score equal to 0 on postoperative days 1, 3, 7, and 14.
- The proportion of participants reporting no ocular pain/discomfort, defined as a score of 0 on a 4-point Likert scale, on postoperative days 1, 3, 7, and 14.
- Changes from baseline in central macular thickness on postoperative day 30, measured via optical coherence tomography.
- The proportion of participants exhibiting central macular thickness greater than 300 microns and cystic changes on postoperative day 30.
- The proportion of participants requiring rescue medication during the treatment period.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Signed written informed consent.
- Male or female, age ≥ 40 years.
- Scheduled routine unilateral cataract surgery to be performed via phacoemulsification and posterior chamber intraocular lens implantation after screening. Of note, patients affected by cataract in both eyes could be enrolled if scheduled to undergo unilateral cataract surgery.
- Patients willing to interrupt the use of contact lenses for the entire duration of the trial.
- Patients able and willing to follow all trial procedures.
- Females of childbearing potential must have a negative urine pregnancy test (dipstick) prior to the first IMP administration, and currently use or agree to use consistently and correctly (i.e., perfect use) a highly effective method of contraception for the individual patient and her partner(s) throughout the trial and for at least one full contraceptive cycle (when applicable). Highly effective methods of contraception include the following: a) implantable progestogen-only hormone contraception associated with inhibition of ovulation; b) Intrauterine Device (IUD); c) Intrauterine Hormone-releasing System (IUS); d) combined (oestrogen- and progestogen-containing) hormonal contraception associated with inhibition of ovulation (oral; intravaginal; transdermal), provided the patient has been using that hormonal contraceptive for an adequate period of time to ensure effectiveness; e) progestogen-only hormone contraception associated with inhibition of ovulation (oral; injectable), provided the patient has been using that hormonal contraceptive for an adequate period of time to ensure effectiveness; f) vasectomized partner, provided that the partner is the sole patient’s sexual partner and the absence of sperm has been confirmed; g) bilateral tubal occlusion or tubal ligation; h) sexual abstinence, defined as refraining from heterosexual intercourse during the entire period of risk associated with the IMP (i.e., up to 24h after the end of treatment). Barrier contraceptives (i.e., diaphragm or cervical cap with spermicide and/or condoms [male or female] with or without a spermicidal agent) are not considered highly effective methods of contraception, and thus must not be used as sole method of contraception. Of note, females who are either permanently sterilized (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy), or who are postmenopausal (at least 12 months of amenorrhea following cessation of all exogenous hormonal treatment) are not considered of childbearing potential.
- Additional criteria for randomization (to be verified at Visit 2 after surgery): The participant has undergone unilateral cataract extraction via phacoemulsification and posterior chamber intraocular lens implantation in the study eye without any additional procedures or complications that would, in the opinion of the Investigator, interfere with trial procedures or confound trial objectives.
Exclusion Criteria
- Ocular conditions that, at the discretion of the Investigator, may interfere with the efficacy and/or safety evaluations (e.g., uveitis, diabetic retinopathy, retinal vasculitis, pseudo-exfoliation syndrome, intra-operative floppy iris syndrome, and any preoperative sign of intraocular inflammation in either eye).
- Patients undergoing bilateral cataract surgery at the same time.
- Ocular surgery in the study eye (including laser surgery) in the 3 months before screening.
- Patients under treatment with prostaglandin analogues or intravitreal injections of anti-Vascular Endothelial Growth Factor (VEGF) drugs, the latter with the last anti-VGEF injections within 3 months before surgery and/or injections scheduled during surgery or the following 2 weeks.
- Use of topical ocular, systemic, or inhaled NSAIDs within 1 week of surgery; use of topical ocular, inhaled, or systemic corticosteroids within 15 days of surgery; use of intraocular or periocular injection of steroids within 3 months of surgery. Of note, the use of low-dose acetylsalicylic acid for cardiovascular disease prevention is allowed.
- Systemic diseases that may have an impact on would healing and/or affect the resolution of inflammation after cataract surgery, and thus could interfere with the results of the study, as judged by the Investigator.
- Any condition that could interfere with the correct instillation of eye drops.
- Monocular patients.
- BCVA < 20/80 of the contralateral eye measured through Snellen 20 feet chart, equal to 0.25 decimal.
- Known hypersensitivity to any component of the investigational products, procedural medications, salicylates or other NSAIDs.
- Contraindications to ocular treatment with nepafenac (Nevanac®), dexamethasone (Dexavision®) or nepafenac/dexamethasone FDC as follows: - Uncontrolled eye infections: 1) epithelial Herpes simplex keratitis (dendritic keratitis), vaccinia, varicella zoster and other viral infections of the cornea and conjunctiva; 2) fungal and acute purulent bacterial infections, including Pseudomonas and mycobacterial infections; 3) amoebic keratitis - Perforation, ulceration and injury of cornea with uncompleted epithelialization - Known corticosteroid-induced intraocular hypertension.
- Participation in a clinical study in the last month before screening or within 5 half-lives of the Investigational Medicinal Product (IMP) used in the previous studies, whichever is longer.
- Pregnancy or breastfeeding throughout the whole study duration.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Italy | Recruiting | 31 Dec 2025 | 432 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
NEVANAC 1 mg/ml eye drops, suspension | Comparator | EYE DROPS, SUSPENSION | OPHTHALMIC USE | 3 | 14 | PRD5040924 |
Dexavision 1 mg/mL collirio, soluzione | Comparator | COLLIRIO, SOLUZIONE | OPHTHALMIC USE | 3 | 14 | PRD7291490 |
TOBRAMICINA DOC Generici 3 mg/ml collirio, soluzione | Other | COLLIRIO, SOLUZIONE | OPHTHALMIC USE | 6 | 7 | PRD3064569 |