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

Study Overview
=================
Brief Summary
-----------------
The study assess efficacy, safety and tolerability of Chloroprocaine 3% ophthalmic gel in healthy volunteers.

Detailed Description
-----------------
The study is carried out in 2 parts. In part I, safety and tolerability is assessed in three groups (12 subjects per group) for single and multiple instillations (1 drop, 3 drops and 3+3 drops). In each group, 9 subjects is randomized to receive Chloroprocaine 3% Gel and 3 subjects receive vehicle as control in the right eye. After part I is completed, an internal independent board review safety endpoints of data collected from these first subjects and advise to go on with further enrollment. If no safety concerns arise, in part II efficacy, safety and tolerability is assessed in 60 healthy subjects for the 3 drops dose regimen. 40 subjects receive Chloroprocaine 3% Gel and 20 receive vehicle (2:1 randomization) in the right eye.

Official Title
-----------------
A Phase II/III, Randomized, Double-Masked, Vehicle-Controlled, Efficacy, Safety and Tolerability Study of Chloroprocaine 3% Gel Eye Drops in Healthy Volunteers

Conditions
-----------------
Healthy Volunteers

Intervention / Treatment
-----------------
* Drug: Ocular gel


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Signed and dated informed consent Healthy male or female aged from 18 to 90 years No clinically significant ocular or systemic disease Ability to orally respond to pain Ability to follow the visit schedule Exclusion Criteria: Ophthalmic exclusion criteria Eye movement disorder (i.e. Nystagmus) Dacryocystitis and all other pathologies of tears drainage system History of Inflammatory ocular disease (Iritis, uveitis, herpetic keratitis) Corneal, epithelial, stromal or endothelial, residual or evolutionary disease (including corneal ulceration and superficial punctuate keratitis) History of ocular traumatism, infection or inflammation within the last 3 months Best corrected visual acuity < 1/10 History of ophthalmic surgical complication (i.e. cystoid macular oedema) Systemic/non ophthalmic exclusion criteria General history: 8.1 Deafness 8.2 Excessive anxiety Any other medical or surgical history, disorder or disease such as acute or chronic severe organic disease: hepatic, endocrine neoplastic, haematological diseases, severe psychiatric illness, relevant cardiovascular abnormalities (such as unstable angina, uncontrolled hypertension: systolic blood pressure over 200 mm Hg, diastolic blood pressure over 100 mm Hg) and/or any complicating factor or structural abnormality judged by the investigator to be incompatible with the study Allergic history: Known hypersensitivity to one of the components of the study medications or to test products Specific non-inclusion criteria for women: Pregnancy, lactation Women without an effective method of contraception (i.e. oral contraceptive, intra-uterine device, subcutaneous contraceptive implant) OR Women not hysterectomised, not menopausal nor surgically sterilized Exclusion criteria related to general conditions: Inability of subject to understand the study procedures and thus inability to give informed consent Non-compliant subject (e.g. not willing to attend the follow-up visits, way of life interfering with compliance) Participation in another clinical study Already included once in this study Ward of court Subject not covered by the Social Security Exclusion criteria related to previous and concomitant medications (taken within 15 days prior screening visit) Use of systemic opioids and opioid drugs Topical ocular treatment with anaesthetic action Use of systemic analgesic drugs (except paracetamol, which will be allowed after Visit 2)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

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 | Drug: Ocular gel<br>* Instillation<br>|
| Placebo Comparator: Placebo<br>Vehicle for chloroprocaine 3% ocular gel | Drug: Ocular gel<br>* Instillation<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants in Phase 2 With Anesthesia Success | Estimate the proportion of subjects experiencing full anaesthesia of the ocular surface 5 minutes after administration of Chloroprocaine 3% ophthalmic gel (the intent was to collect and only report data for Participants who were in Phase 2) | Day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Anesthesia Only in Patients in Phase 2 | Duration of anesthesia (min) for subjects in phase 2 (the intent was to collect and only report data for Participants who were in Phase 2) | Day 1 | 
| Number of Participants With Adverse Events | Number of Participants with Ocular symptoms and Adverse events | Up to 29 days | 
| Mean Arterial Pressure | Mean arterial pressure (mmHg) is defined as the average pressure in a patient's arteries during one cardiac cycle. It is considered a better indicator of perfusion to vital organs than systolic blood pressure (SBP). | up to 8 days | 
| Number of Participants With Anomalies in Slip Lamp Examination | Number of Participants with Anomalies in Slip Lamp Examination | up to 8 days | 
| Number of Participants With Anomalies in Corneal Fluorescein Staining | Number of Participants with anomalies found with corneal fluorescein staining | up to 8 days | 
| Ocular Pressure | Intraocular pressure (mmHg) | Follow up (up to 8 days) |