Safety and Tolerability of PRO-185

Study Overview
=================
Brief Summary
-----------------
Phase I Study to evaluate safety and tolerability of PRO-185 (naphazoline/hypromellose) ophthalmic solution through evaluation of vital signs, ocular signs such as intraocular pressure, hyperemia and mydriasis and adverse events.

Detailed Description
-----------------
A total of 22 healthy volunteers will apply PRO-185 ocular solution on both eyes QID (four times per day) for 8 days. The safety variables will include intraocular pressure, heart rate, systolic and diastolic blood pressure. Tolerability variables will include: hyperemia, mydriasis, and expected and unexpected adverse events. The presence of any of these in ≤ 20% will deem PRO-185 as safe and tolerable.

Official Title
-----------------
Phase I Clinical Study, to Evaluate the Safety and Tolerability of the Ophthalmic Solution PRO-185 When Applied on the Ocular Surface of Healthy Volunteers

Conditions
-----------------
Hyperemia Eye

Intervention / Treatment
-----------------
* Drug: Naphazoline / Hypromellose Ophthalmic


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Being clinically healthy Having the ability to grant a signed informed consent Being able and willing to comply with the programmed visits, treatment plan and other procedures of this study. Age between 18 and 45 years Women in child-bearing age must assure the continuation (start ≥ 30 days previous to the signing of the ICF) of a hormonal contraceptive method or a intrauterine device (IUD) during the period of the study. Best corrected visual acuity equal of better than 20/30 in both eyes. Vital signs within normal ranges. Intraocular pressure ≥10 and ≤ 21 mmHg Exclusion Criteria: Using any kind of topic ophthalmic products Presenting allergies to naphazoline or the history of intolerance to nasal decongestants or ocular vasoconstrictive products. History of diagnosis of suspicion of primary angle closure, primary angle closure or closed angle glaucoma. History of iridotomies or waiting for this procedure to take place. Conjunctival hyperemia grade 3 or 4 according to Efron scale. Ocular surface staining equal or greater to 3 in the SICCA scale, for any eye. Using medications or herbology products, through any route of administration. Pregnant, breastfeeding or women who plan to get pregnant during the period of the study. Previous participation in any clinical study 90 days prior to the inclusion in the present study. Previous participation in this study. Using contact lenses which cannot be suspended during the period of this study. History of any chronic illness, including diabetes and hypertension. Active inflammation or infection at the time of inclusion in this study. Unresolved lesions or traumas at the moment of inclusion in this study. History of any kind of ocular surgery. History of any surgical procedure, non-ophthalmologic, within the previous 3 months to the inclusion in this study.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 45 Years

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

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

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

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Phase I, controlled, non-comparative, single-center, open study.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PRO-185<br>Healthy volunteers will apply one drop of PRO-185 ophthalmic solution (naphazoline / hypromellose) on both eyes, QID (four times per day) for 8 days. | Drug: Naphazoline / Hypromellose Ophthalmic<br>* Naphazoline 0.03% / Hypromellose 0.2%<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intraocular pressure increment | Safety evaluation through the incidence of subjects presenting an elevation > 5 mmHg in intraocular pressure 20 minutes after administration, in comparison to baseline value. | Baseline visit, day 1(pre and post pupil dilation); Visit 1, day 3 +1 (pre and post research product application); Visit 2, day 8 (pre and post research product application); Final Visit, day 10 (+1) | 
| Heart rate increment | Safety evaluation through the incidence of subjects presenting an elevation > 15 beats per minute 20 minutes after administration, in comparison to baseline value. | Baseline visit, day 1(pre and post pupil dilation); Visit 1, day 3 +1 (pre and post research product application); Visit 2, day 8 (pre and post research product application); Final Visit, day 10 (+1) | 
| Blood pressure increment | Safety evaluation through the incidence of subjects presenting an elevation > 15 mmHg in systolic pressure or > 10 mmHg in diastolic pressure 20 minutes after administration, in comparison to baseline value. | Baseline visit, day 1(pre and post pupil dilation); Visit 1, day 3 +1 (pre and post research product application); Visit 2, day 8 (pre and post research product application); Final Visit, day 10 (+1) | 
| Incidence of Conjunctival Hyperemia | Tolerability evaluation through the incidence of conjunctival hyperemia grades 3 and 4 (according to the Efron scale). | Trough Day 10 (+1) | 
| Incidence of Pharmacological Mydriasis | Tolerability evaluation through the incidence of pharmacological mydriasis measured through OPD III scan (considered as a difference > 2 mm compared to the baseline value). | Trough Day 10 (+1) |