Erythematous Rosacea
Conditions
Keywords
erythematous rosacea, facial gel, brimonidine, ophthalmic solution
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.
Interventions
DRUG0.18% 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
DRUG0.2% 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.
DRUGAdvanced 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
DRUGCOL-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
Sponsors
Galderma R&D
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax - Maximum Systemic Concentration of Brimonidine | 0 Hour (prior to dose) and at 1, 2, 3, 4, 5, 6, 7, and 8 hours post-morning dose | Maximum observed plasma concentration |
| AUC - Area Under the Curve of Brimonidine | 0 Hour (prior to dose) and at 1, 2, 3, 4, 5, 6, 7, and 8 hours post-morning dose | 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. |
| Tmax - 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 | time to maximum plasma concentration |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Seq1-facial Gel+Saline Drops,Then Vehicle+Brimonidine Drops One (1) gram of 0.18% COL-118 facial gel (1.8 mg brimonidine tartrate) administered topically plus 1 drop of Advanced Eye Relief™ (placebo ophthalmic solution) in each eye, once in the morning. One (1) gram of 0.18% COL-118 facial gel was to be reapplied once after 4 hours.
First intervention (1 day), washout (1 day), Second intervention (1 day) | 10 |
| Seq2-vehicle+Brimonidine Drops,Then Facial Gel+Saline Drops 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
First intervention (1 day), washout (1 day), Second intervention (1 day) | 10 |
| Total | 20 |
Baseline characteristics
| Characteristic | Seq2-vehicle+Brimonidine Drops,Then Facial Gel+Saline Drops | Seq1-facial Gel+Saline Drops,Then Vehicle+Brimonidine Drops | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants | 10 Participants | 20 Participants |
| Age, Continuous | 47.1 years STANDARD_DEVIATION 6.7 | 43.0 years STANDARD_DEVIATION 8.5 | 45.1 years STANDARD_DEVIATION 7.8 |
| Region of Enrollment United States | 10 participants | 10 participants | 20 participants |
| Sex: Female, Male Female | 10 Participants | 10 Participants | 20 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 3 / 19 | 7 / 18 |
| serious Total, serious adverse events | 0 / 19 | 0 / 18 |
Outcome results
Primary
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.
Time frame: 0 Hour (prior to dose) and at 1, 2, 3, 4, 5, 6, 7, and 8 hours post-morning dose
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Treatment A - COL-118 Facial Gel + Saline Drops | AUC - Area Under the Curve of Brimonidine | NA pg*hr/mL |
| Treatment B - Vehicle Gel + Brimonidine Drops | AUC - Area Under the Curve of Brimonidine | NA pg*hr/mL |
Primary
Cmax - Maximum Systemic Concentration of Brimonidine
Maximum observed plasma concentration
Time frame: 0 Hour (prior to dose) and at 1, 2, 3, 4, 5, 6, 7, and 8 hours post-morning dose
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Treatment A - COL-118 Facial Gel + Saline Drops | Cmax - Maximum Systemic Concentration of Brimonidine | NA pg/mL |
| Treatment B - Vehicle Gel + Brimonidine Drops | Cmax - Maximum Systemic Concentration of Brimonidine | NA pg/mL |
Primary
Tmax - Time to Maximum Plasma Concentration
time to maximum plasma concentration
Time frame: 0 Hour (prior to dose) and at 1, 2, 3, 4, 5, 6, 7, and 8 hours post-morning dose
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Treatment A - COL-118 Facial Gel + Saline Drops | Tmax - Time to Maximum Plasma Concentration | NA Hours |
| Treatment B - Vehicle Gel + Brimonidine Drops | Tmax - Time to Maximum Plasma Concentration | NA Hours |