Efficacy, Safety and Local Tolerability Study of Chloroprocaine 3% Gel Eye Drops in Healthy Volunteers

Study Overview
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Brief Summary
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The study evaluate the efficacy, safety and local tolerability of Chloroprocaine 3% ophthalmic gel as compared to matching placebo in healthy subjects.

Detailed Description
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One hundred and five (105) healthy male and female subjects will be randomised in a 4:1 ratio to receive a single ocular instillation of Chloroprocaine 3% ophthalmic gel or matching placebo (vehicle) (84 subjects will receive chloroprocaine and 21 subjects will receive placebo). The assigned investigational product (3 drops) will be instilled in the right eye of each subject. Administrations will be performed at the clinical centre by the Investigator or his deputy on study day 1. For each administration, the 3 drops will be instilled at a 1 min ± 15 sec interval.

Official Title
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A Phase I/II, Randomized, Placebo-controlled, Double-masked, Efficacy, Safety and Local Tolerability Study of Chloroprocaine 3% Gel Eye Drops in Healthy Volunteers

Conditions
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Healthy Subjects

Intervention / Treatment
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* Drug: Ocular gel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed consent: Signed written informed consent before inclusion in the study Sex and age: Healthy men and women, 18 - 55 years inclusive Body Mass Index: 18.5-30 kg/m2 inclusive Vital signs: Systolic blood pressure 100-139 mmHg, diastolic blood pressure 50-89 mmHg, heart rate 50-90 bpm, measured after 5 min at rest in the sitting position Full comprehension: ability to comprehend the full nature and purpose of the study, including possible risks and side effects; ability to co-operate with the Investigator and to comply with the requirements of the entire study Contraception and fertility: women of child-bearing potential must be using at least one of the following reliable methods of contraception: Hormonal oral, implantable, transdermal, or injectable contraceptives for at least 2 months before the screening visit; A non-hormonal intrauterine device or female condom with spermicide or contraceptive sponge with spermicide or diaphragm with spermicide or cervical cap with spermicide for at least 2 months before the screening visit A male sexual partner who agrees to use a male condom with spermicide A sterile sexual partner Female participants of non-child-bearing potential or in post-menopausal status for at least 1 year will be admitted. For all women, urine pregnancy test result must be negative at screening. Exclusion Criteria: Physical findings: Clinically significant abnormal physical findings which could interfere with the objectives of the study Visual acuity: Best corrected visual acuity < 1/10 Concomitant medications: Medications, including over the counter medications and herbal remedies, systemic opioids and morphine drugs, topical ocular products with anaesthetic action, systemic analgesic drugs, for 2 weeks before study screening Ophthalmic diseases: Clinically significant ocular disease; eye movement disorder (i.e. nystagmus); dacryocystitis and all others pathologies of tears drainage system; corneal, epithelial, stromal or endothelial, residual or evolutionary disease (including corneal ulceration and superficial punctuate keratitis); history of inflammatory ocular disease (iritis, uveitis, herpetic keratitis), history of ocular traumatism, infection or inflammation within the last 3 months or history of any other ocular disease that may affect the outcome of the study or the subject's safety Ophthalmic surgery: History of ophthalmic surgical complications (e.g. cystoid macular oedema) in the last 6 months Diseases: Significant history of renal, hepatic, gastrointestinal, cardiovascular, respiratory, skin, haematological, endocrine, psychiatric or neurological diseases or surgeries that may interfere with the aim of the study Allergy: Ascertained or presumptive hypersensitivity to the active principle and/or ingredients of investigational products; history of anaphylaxis to drugs or allergic reactions in general, which the Investigator considers may affect the outcome of the study Investigative drug studies: participation in the evaluation of any investigational product for 3 months before this study. The 3-month interval is calculated as the time between the first calendar day of the month that follows the last visit of the previous study and the first day of the present study Drug, alcohol, caffeine, tobacco: history of drug, alcohol [greater than 1 drink/day for women and greater than 2 drinks/day for men, defined according to the USDA Dietary Guidelines 2015-2020], caffeine (greater than 5 cups coffee/tea/day) or tobacco abuse (greater than or equal 10 cigarettes/day) Alcohol test: positive alcohol breath test at Day 1 Pregnancy (women only): positive or missing pregnancy test at screening, pregnant or lactating women

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Chloroprocaine<br>Chloroprocaine 3% ocular gel (30 mg/mL), 3 drops instilled at a 1 min ± 15 sec interval. | Drug: Ocular gel<br>* 3 drops instilled in the right eye<br>* Other names: No other intervention names;|
| Placebo Comparator: Placebo<br>Vehicle for chloroprocaine 3% ocular gel, 3 drops instilled at a 1 min ± 15 sec interval. | Drug: Ocular gel<br>* 3 drops instilled in the right eye<br>* Other names: No other intervention names;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Gaining Full Conjunctival Anesthesia of the Ocular Surface | Number of partecipants gaining full conjunctival anesthesia of the ocular surface, evaluated by conjunctiva pinching (0.3-mm forceps), 5 minutes after administration of Chloroprocaine 3% ophthalmic gel, in comparison to placebo - only study eye (right eye) | Day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Anesthesia, Evaluated by Conjunctiva Pinching (0.3-mm Forceps) - Only Study Eye (Right Eye) | Time to anesthesia, evaluated by conjunctiva pinching (0.3-mm forceps) - only study eye (right eye) | Day 1 | 
| Duration of Anesthesia - Only Right Eye | Duration of anesthesia, evaluated by conjunctiva pinching (0.3-mm forceps) - only study eye (right eye) | Day 1 | 
| Visual Acuity (EDTRS Chart) - Both Eyes | Visual acuity will be assessed, for all subjects and both eyes using an EDTRS chart (visual acuity is scored with reference to the logarithm of the minimum angle of resolution, an observer who can resolve details as small as 1 minute of visual angle scores LogMAR 0, since the base-10 logarithm of 1 is 0; an observer who can resolve details as small as 2 minutes of visual angle (i.e., reduced acuity) scores LogMAR 0.3, since the base-10 logarithm of 2 is near-approximately 0.3; and so on) | Up to day 7 | 
| Ocular Symptoms | The ocular symptoms will be assessed: burning, stinging, itching, foreign body sensation. Scores will be determined using a 100 mm VAS where 0 means no symptoms and 100 means worst possible discomfort. | Up to day 7 | 
| Ocular Signs by Slit Lamp Examination | Slit lamp biomicroscopy will be performed for the assessment of the following parameters: conjunctival redness, anterior chamber flare, conjunctival chemosis, eyelid swelling. Presence and severity will be graded according to a 4 point scale, where (0) none, (1) mild, (2) moderate, (3) severe. | Up to day 7 | 
| Corneal Fluorescein Staining by Slit Lamp Examination - Both Eyes | Fluorescein will be used to detect corneal epithelial defects using slit lamp biomicroscopy. As grading scale for corneal damage, the NEI/Industry Workshop guidelines will be used. The cornea will be divided into five sectors (central, superior, inferior, nasal and temporal), each of which is scored on a scale of 0-3, where 0 means no staining and 3 means maximum staining, with a maximal score of 15. | Up to day 7 | 
| Intraocular Pressure (IOP) - Both Eyes | Intraocular pressure will be measured with a slit-lamp mounted Goldmann applanation tonometer. Before each measurement one drop of oxybuprocaine hydrochloride combined with sodium fluorescein will be used for local anaesthesia of the cornea. | Up to day 7 | 
| Fundus Ophthalmoscopy (Vitreous, Macula, Retina and Optic Nerve Head) With the Slit Lamp - Both Eyes | Indirect fundus ophthalmoscopy will be performed, for all subjects and both eyes, with the observation at the slit lamp using a +90 diopters Volk lens.The evaluation is performed with a grading scale: 0 None, 1 Mild, 2 Moderate, 3 Severe for each parameters evaluated. | Up to day 7 | 
| Vital Signs (Blood Pressure) | Subjects blood pressure will be measured by the Investigator or his/her deputy | Up to day 7 | 
| Vital Signs (Heart Rate) | Subjects heart rate will be measured by the Investigator or his/her deputy | Up to day 7 |