Effect of nepafenac/dexamethasone fixed dose combination vs. its individual components (nepafenac and dexamethasone monotherapies) on postoperative inflammation after cataract surgery: a randomized, multicentre, blinded-assessor, parallel-group clinical study – NE.DE.F. STUDY

INTERVENTION: Product Name: NEVANAC 1 mg/ml eye drops, suspension, Product Code:PRD5040924, Pharmaceutical Form: EYE DROPS, SUSPENSION, Other descriptive name: , Strength: , Product Name: , Product Code:PRD12978611, Pharmaceutical Form: EYE DROPS, SOLUTION, Other descriptive name: , Strength: , Product Name: Dexavision 1 mg/mL collirio, soluzione, Product Code:PRD7291490, Pharmaceutical Form: EYE DROPS, SOLUTION, Other descriptive name: , Strength: , Product Name: TOBRAMICINA DOC Generici 3 mg/ml collirio, soluzione, Product Code:PRD3064569, Pharmaceutical Form: EYE DROPS, SOLUTION, Other descriptive name: , Strength: CONDITION: Postoperative inflammation after cataract surgery ; MedDRA version: 27.1Level: PTClassification code: 10007739Term: Cataract Class: 100000004853 Therapeutic area: Diseases [C] ‐ Eye Diseases [C11] PRIMARY OUTCOME: Main Objective: Primary efficacy objective: To demonstrate the superiority of NEPA/DEXA FDC treatment compared with its components instilled alone (i.e., NEPA and DEXA) in the time to resolution of ocular inflammation after cataract surgery. Primary end point(s): Primary efficacy endpoint: Time to resolution of postoperative anterior chamber inflammation after cataract surgery, as defined by an anterior chamber flare score of value = 0, equal or inferior to the preoperative value. Secondary Objective: Secondary efficacy objectives: To further evaluate the efficacy of NEPA/DEXA FDC in comparison with NEPA alone and DEXA alone on: ‐ Postoperative ocular inflammation ‐ Ocular symptoms ‐ Ocular pain/discomfort ‐ Central macular thickness ‐ Use of rescue therapy during treatment., Safety and tolerability objectives: To assess the safety and tolerability of the Investigational Medicinal Products (IMPs) throughout the trial, in terms of: ‐ Adverse events ‐ IOP ‐ Visual acuity ‐ Participant’s evaluation of drug tolerability., Pharmacokinetic objective (PK sub‐study): To assess the Pharmacokinetics (PK) of NEPA/DEXA FDC, NEPA and DEXA in a subset of participants at selected study site(s) related to the first IMP administration. SECONDARY OUTCOME: Secondary end point(s):Pharmacokinetic endpoints (PK sub‐study) • AUC0‐t, AUC0‐8, area under the drug concentration‐time curve • Cmax, maximum plasma concentration • Tmax, time of maximum plasma concentration Secondary end point(s):Safety and tolerability endpoints: • Changes from baseline of Best Corrected Visual Acuity (BCVA) assessed through Snellen 20 feet chart at each study visit Secondary end point(s):Safety and tolerability endpoints: • Changes from baseline of IOP at each study visit Secondary end point(s):Safety and tolerability endpoints: • Frequency of discontinuation of treatment due to AEs Secondary end point(s):Safety and tolerability endpoints: • Incidence of all Adverse Events (AEs), Adverse Drug Reactions (ADRs), Serious Adverse Events (SAEs) Secondary end point(s):Safety and tolerability endpoints: • Participant’s assessment of ocular complaints of burning, stinging and blurred vision on postoperative Day 1, 3, 5, 7 and 14 using a 4‐point Likert scale (range 0‐3; 0 = none, 1 = mild, 2 = moderate, 3 = severe) Secondary end point(s):Safety and tolerability endpoints: • Participant’s global evaluation of IMP tolerability on postoperative Day 14 using a 5‐point Likert scale (range 0‐4; 0 = poor, 1 = slight, 2 = moderate, 3 = good, 4 = excellent) Secondary end point(s):Safety and tolerability endpoints: • Proportion of participants with 20/20 BCVA (Snellen 20 feet chart) on postoperative Day 14 and 30 Secondary end point(s):Safety and tolerability endpoints: • Proportion of participants with a significant increase (> 6 mmHg) in IOP vs. baseline at each study visit Secondary end point(s):Secondary efficacy endpoints: • Change from baseline in the anterior chamber cells score on postoperative Day 1, 3, 5, 7, 14 and 30 Secondary end point(s):Secondary efficacy endpoints: • Change from baseline in the anterior chamber flare score value on postoperative Day 1, 3, 5, 7, 14 and 30 Secondary end point(s):Secondary efficacy endpoints: • Change from baseline of central macular thickness (central subfield) on postoperative Day 30, as assessed by Optical Coherence Tomography (OCT) Secondary end point(s):Secondary efficacy endpoints: • Proportion of participants using any rescue medication during treatment Secondary end point(s):Secondary efficacy endpoints: • Proportion of participants with a Total Ocular Symptoms Score (TOSS) equal to 0 on postoperative Day 1, 3, 5, 7 and 14 Secondary end point(s):Secondary efficacy endpoints: • Proportion of participants with absence of conjunctival hyperaemia, defined as a score equal to 0 on a 4‐point Likert scale (range 0‐3; 0 = none, 1 = mild, 2 = moderate, 3 = severe) on postoperative Day 1, 3, 5, 7, 14 and 30, as assessed by Slit Lamp Examination (SLE) Secondary end point(s):Secondary efficacy endpoints: • Proportion of participants with central macular thickness (central subfield) >300 microns and cystic changes on OCT on postoperative Day 30 Secondary end point(s):Secondary efficacy endpoints: • Proportion of participants with no ocular pain/discomfort on postoperative Day 1, 3, 5, 7 and 14, defined as a score for ocular pain/discomfort equal to 0 on a 4‐point Likert scale (range 0‐3; 0 = none, 1 = mild, 2 = moderate, 3 = severe) Secondary end point(s):Secondary efficacy endpoints: • Proportion of participants with resolution (flare score value = 0, equal or inferior to the preoperative value) of postoperative anterior chamber inflammation on postoperative Day 1, 3, 5, 7, 14 and 30 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 h