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

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

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

Study Overview

• Status: Completed
• Conditions: Erythematous Rosacea
• Intervention / Treatment: Drug: 0.18% COL-118 facial gel (1.8 mg brimonidine); Drug: Advanced Eye Relief; Drug: 0.2% brimonidine ophthalmic solution (0.1 mg brimonidine tartrate/drop); Drug: COL-118 facial gel vehicle

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.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Broomall, Pennsylvania, United States, 19008
      • KGL, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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	Drug: 0.18% COL-118 facial gel (1.8 mg brimonidine); 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; Other Names: brimonidine; Drug: Advanced Eye Relief; 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
Active Comparator: 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	Drug: 0.2% brimonidine ophthalmic solution (0.1 mg brimonidine tartrate/drop); 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.; Other Names: brimonidine tartrate/drop; Drug: COL-118 facial gel vehicle; 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

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

Collaborators and Investigators

• Sponsor: Galderma R&D
• Investigators: Principal Investigator: James Leyden, M.D., KGL, Inc.

Study record dates

Study Major Dates

• Study Start: May 1, 2008
• Primary Completion (Actual): June 1, 2008
• Study Completion (Actual): June 1, 2008

Study Registration Dates

• First Submitted: June 12, 2008
• First Submitted That Met QC Criteria: June 12, 2008
• First Posted (Estimate): June 16, 2008

Study Record Updates

• Last Update Posted (Actual): February 18, 2021
• Last Update Submitted That Met QC Criteria: February 16, 2021
• Last Verified: August 1, 2014

More Information

Terms related to this study

• Keywords: brimonidine; ophthalmic solution; erythematous rosacea; facial gel
• Additional Relevant MeSH Terms: Skin Diseases; Rosacea; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Pharmaceutical Solutions; Brimonidine Tartrate; Ophthalmic Solutions
• Other Study ID Numbers: COL-118-ROSE-202; RD.06.SPR.18126