Systemic Bioavailability Study Of Col-118 Administered Topically as a 0.18 % Facial Gel And Brimonidine Ophthalmic Solution 0.2%

Study Overview
=================
Brief Summary
-----------------
Phase II systemic bioavailability crossover study to measure the exposure of Col-118 topical 0.18 % Facial Gel and Brimonidine Ophthalmic Solution 0.2%

Detailed Description
-----------------
A double-blind, randomized, 2-way crossover, safety, pharmacokinetic/-dynamic (PK/PD) study of 0.18% COL-118 facial gel and 0.2% brimonidine ophthalmic solution administered in male and female patients with moderate to severe erythematous rosacea. Twenty male and female subjects with moderate to severe erythematous rosacea will be randomized into 2 groups of 10 subjects. Each group will be randomized to receive 2 treatments (Treatments A and B, in Sequence 1: A/B or Sequence 2: B/A), as follows: Treatment A: One 1-g application of 0.18% COL-118 facial gel (1.8 mg brimonidine) administered topically plus one drop of Advanced Eye Relief™ in each eye, once in the morning. 1 g of 0.18% COL-118 facial gel is reapplied once after four hours; Treatment B: One 1-g application of COL-118 facial gel vehicle (0.0 mg brimonidine tartrate) administered topically plus one drop of 0.2% brimonidine ophthalmic solution (0.1 mg brimonidine tartrate/drop) in each eye. Four hours after the first application 1-g of COL-118 facial gel vehicle (0.0 mg brimonidine) is administered topically. There will be at least a 1-day washout between dose administrations (Period 1 and Period 2). Blood samples for PK analysis of brimonidine levels will be collected at the following time points during Period 1 and Period 2: 0 Hour (prior to dose) and at 1, 2, 3, 4 (prior to 2nd dose), 5, 6, 7, and 8 hours post-dose.

Official Title
-----------------
A Phase II, Single-Center, Two-Way Crossover Relative Systemic Bioavailability Study of Col-118 Administered Topically as a 0.18 % Facial Gel and Brimonidine Ophthalmic Solution 0.2% Administered to the Eye in Subjects With Moderate to Severe Erythematous Rosacea

Conditions
-----------------
Erythematous Rosacea

Intervention / Treatment
-----------------
* Drug: 0.18% COL-118 facial gel (1.8 mg brimonidine)
* Drug: 0.2% brimonidine ophthalmic solution (0.1 mg brimonidine tartrate/drop)
* Drug: Advanced Eye Relief
* Drug: COL-118 facial gel vehicle


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female ≥18 years of age Clinical diagnosis of rosacea A score of ≥ 3 on the CEAS A score of ≥ 3 on the PSA IOP ≥ 10 mm Hg Non-pregnant and non-lactating females Exclusion Criteria: History of hypersensitivity or allergies to any ingredient of the study drugs, unless approved by the Investigator Use of brimonidine prescription medications within 14 days prior to Check-in Use of any over-the-counter (OTC), non-prescription preparations (including vitamins, minerals, and phytotherapeutic/herbal/plant-derived preparations) within 7 days prior to Check-in, unless deemed acceptable by the Investigator Use of systemic or topical steroids applied to the face 14 days prior to Check in The use of any Rx or OTC products for the treatment of acne or rosacea within 14 days prior to check in The use of isotretinoin within 180 days prior to check in

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

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

Accepts Healthy Volunteers
-----------------
No

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

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>One 1-g application of 0.18% COL-118 facial gel (1.8 mg brimonidine) administered topically plus one drop of Advanced Eye Relief™ in each eye, once in the morning. 1 g of 0.18% COL-118 facial gel is reapplied once after four hours | Drug: 0.18% COL-118 facial gel (1.8 mg brimonidine)<br>* One 1-g application of 0.18% COL-118 facial gel (1.8 mg brimonidine) administered topically plus one drop of Advanced Eye Relief™ in each eye, once in the morning. 1 g of 0.18% COL-118 facial gel is reapplied once after 4 hours<br>* Other names: brimonidine;Drug: Advanced Eye Relief<br>* One 1-g application of 0.18% COL-118 facial gel (1.8 mg brimonidine) administered topically plus one drop of Advanced Eye Relief™ in each eye, once in the morning. 1 g of 0.18% COL-118 facial gel is reapplied once after 4 hours<br>|
| Active Comparator: B<br>One 1-g application of COL-118 facial gel vehicle (0.0 mg brimonidine tartrate) administered topically plus one drop of 0.2% brimonidine ophthalmic solution (0.1 mg brimonidine tartrate/drop) in each eye. Four hours after the first application 1-g of COL-118 facial gel vehicle (0.0 mg brimonidine) is administered topically | Drug: 0.2% brimonidine ophthalmic solution (0.1 mg brimonidine tartrate/drop)<br>* One 1-g application of COL-118 facial gel vehicle (0.0 mg brimonidine tartrate) topically plus one drop of 0.2% brimonidine ophthalmic solution (0.1 mg brimonidine tartrate/drop) in each eye. Four hours after the first application 1-g of COL-118 facial gel vehicle (0.0 mg brimonidine) is administered topically.<br>* Other names: brimonidine tartrate/drop;Drug: COL-118 facial gel vehicle<br>* One 1-g application of COL-118 facial gel vehicle (0.0 mg brimonidine tartrate) administered topically plus one drop of 0.2% brimonidine ophthalmic solution (0.1 mg brimonidine tartrate/drop) in each eye. Four hours after the first application 1-g of COL-118 facial gel vehicle (0.0 mg brimonidine) is administered topically<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax - Maximum Systemic Concentration of Brimonidine | Maximum observed plasma concentration | 0 Hour (prior to dose) and at 1, 2, 3, 4, 5, 6, 7, and 8 hours post-morning dose | 
| AUC - Area Under the Curve of Brimonidine | Area under the plasma concentration-time curve from 0 hour to the last measurable plasma concentration, calculated by the linear trapezoidal method After two topical applications of 0.18% COL-118 facial gel, plasma levels of brimonidine for all subjects were below the LoQ (25 pg/mL), with the exception of one single outlier value. Thus, no PK analysis could be performed for 0.18% COL-118 facial gel. After ocular administration of 0.2% brimonidine tartrate ophthalmic solution, quantifiable plasma concentrations of brimonidine were observed in 11 of the 18 subjects who received the brimonidine tartrate ophthalmic solution. Brimonidine rapidly appeared in plasma The mean Cmax was not calculated because values were not quantifiable for 7 of 18 subjects The mean AUC0-t also was not calculated. | 0 Hour (prior to dose) and at 1, 2, 3, 4, 5, 6, 7, and 8 hours post-morning dose | 
| Tmax - Time to Maximum Plasma Concentration | time to maximum plasma concentration | 0 Hour (prior to dose) and at 1, 2, 3, 4, 5, 6, 7, and 8 hours post-morning dose | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
ophthalmic solution, erythematous rosacea, facial gel, brimonidine