Phase III Multicenter, Randomized, Double-Blind Study on Ketotifen Ophthalmic Solution 0.5 mg/mL for Seasonal Allergic Conjunctivitis Treatment

The primary objective of this multicentre, randomised, double-blind, vehicle and active-controlled Phase III study is to evaluate the **efficacy** and **safety** of **ketotifen ophthalmic solution** 0.5 mg/ml compared to a vehicle and Ketoftil (ketotifen ophthalmic solution 0.5 mg/ml) in the treatment of **seasonal allergic conjunctivitis**. This study is clinically relevant as it aims to determine the therapeutic benefits and potential adverse effects of ketotifen, an antihistamine, in alleviating the symptoms associated with this common ocular condition, thereby potentially improving patient outcomes and quality of life.

The clinical trial focuses on evaluating the efficacy and safety of **ketotifen ophthalmic solution** for the treatment of **seasonal allergic conjunctivitis**. The study population comprises adult patients aged 18 to 65 years, including both male and female participants. The trial does not involve a vulnerable population. Participants were selected based on a confirmed diagnosis of seasonal allergic conjunctivitis, assessed through a skin test and/or validated IgE radioallergosorbent test (RAST) relevant to the geographic area's seasonal allergies within the past 12 months. Additionally, participants must exhibit symptoms such as redness, tearing, itchy eyes, eyelid swelling, or conjunctival chemosis at the time of enrollment. The sponsor has not provided information regarding the total number of participants. All participants have provided written informed consent approved by the Ethics Committee. The trial does not specify any particular lifestyle considerations such as diet or physical activity.

The clinical trial is a **randomized**, **double-blind**, vehicle and active-controlled Phase III study designed to evaluate the efficacy and safety of **ketotifen ophthalmic solution** 0.5 mg/ml in comparison to a vehicle and Ketoftil for the treatment of **seasonal allergic conjunctivitis**. The trial is structured to include multiple study visits over a period of 14 days, with the primary endpoint being the evaluation of ocular itching between baseline and the end of the study. Secondary endpoints include assessments of conjunctival redness, tearing, eyelid swelling, conjunctival chemosis, and product tolerability at various intervals post-administration.

Participants will undergo an initial inclusion (screening) visit to confirm eligibility based on criteria such as age, diagnosis of seasonal allergic conjunctivitis, and symptom severity. Following successful screening, participants will be randomized to receive either the test product, comparator, or placebo. Study visits are scheduled at baseline, 30 minutes, 2 days, 7 days, and 14 days after the first administration of the study medication. Each visit will involve assessments conducted by the investigator, including the use of the Efron scale for conjunctival redness and a 4-point scale for tearing and eyelid swelling. The Visual Analog Scale (VAS) will be used to evaluate product tolerability.

The expected duration of participant involvement is approximately 14 days, with conditions for early termination including withdrawal of consent, adverse events, or protocol non-compliance. The trial is anticipated to start recruitment in May 2023 and conclude by August 2023. Participants are required to provide written informed consent approved by the Ethics Committee prior to enrollment. The study aims to provide comprehensive data on the safety and efficacy of ketotifen ophthalmic solution in managing symptoms associated with seasonal allergic conjunctivitis.

The clinical trial involves the administration of three different treatments to evaluate their efficacy and safety in the treatment of **seasonal allergic conjunctivitis**. The first treatment is an experimental medication, **KETOTIFEN 0.5 MG/ML**, which is formulated as an eye drop solution in a single-dose container. The active substance in this formulation is **ketotifen hydrogen fumarate**, a chemical compound known for its antiallergic properties. The medication is administered via **ophthalmic use**, with a maximum daily dose of 0.1 mg/ml and a total maximum dose of 1.4 mg/ml over a treatment period of up to 2 weeks. Participant compliance is monitored through regular follow-ups and assessments.

The second treatment is a comparator, **KETOFTIL 0.5 mg/ml collirio, soluzione**, also containing **ketotifen hydrogen fumarate** as the active ingredient. This formulation is presented as an eye drop solution and is administered through the same **ophthalmic route**. The dosing schedule mirrors that of the experimental treatment, with a maximum daily dose of 0.1 mg/ml and a total maximum dose of 1.4 mg/ml over a 2-week period. The comparator serves to provide a benchmark for evaluating the efficacy of the experimental treatment.

The third treatment is a **placebo**, consisting of glycerol, hydrochloric acid, and water for injections. The placebo is used to maintain the double-blind nature of the study and is administered in the same manner as the active treatments, via **ophthalmic use**. The placebo is designed to mimic the physical characteristics of the active treatments without containing the active substance, ensuring that any observed effects can be attributed to the active medication rather than psychological factors. Compliance with the placebo administration is similarly monitored to ensure the integrity of the trial results.

The efficacy of the clinical trial will be assessed through both primary and secondary endpoints. The primary endpoint focuses on evaluating **ocular itching** between baseline (V1) and 14 days later (V5) following the administration of Ketotifen, Ketoftil, or placebo. Participants will self-assess ocular itching using a 5-point scale. Secondary endpoints include the evaluation of conjunctival redness, tearing, eyelid swelling, and conjunctival chemosis at multiple timepoints: 30 minutes, 2 days, 7 days, and 14 days after the initial administration of the treatments. Conjunctival redness will be assessed by the investigator using the Efron scale, while tearing and eyelid swelling will be evaluated using a 4-point scale, and conjunctival chemosis will be assessed using a 3-point scale. Additionally, product tolerability will be evaluated at the same timepoints using the Visual Analog Scale (VAS) by the investigator. Safety will be quantitatively and qualitatively evaluated in terms of adverse events reported during the trial.