Rosacea
Conditions
Brief summary
A Randomized, Double-Blind, Multiple-Site, Placebo-Controlled, Parallel-Design Study to Evaluate the Safety and Therapeutic Equivalence of Brimonidine Topical Gel, 0.33% (Watson Laboratories, Inc., USA) to Reference Product Mirvaso® (brimonidine) topical gel, 0.33% (Galderma Laboratories, L.P., USA) in Patients with Moderate to Severe Facial Erythema Associated with Rosacea
Detailed description
Up to 462 patients 18 years of age and older, with confirmed clinical diagnosis of rosacea will be enrolled to have 413 in the modified intent-to-treat (mITT) population and 371 in the per-protocol (PP) population. Patients should have fewer than 3 facial inflammatory lesions, and moderate to severe erythema according to both Clinician's Erythema Assessment (CEA) and Patient's Self-Assessment (PSA).
Interventions
DRUGBrimonidine
DRUGplacebo
Sponsors
Watson Laboratories, Inc.
Actavis Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or non-pregnant, non-lactating female, 18 years of age or older. 2. Signed informed consent form, which meets all criteria of current FDA regulations. 3. Females of child bearing potential must not be pregnant or lactating at Screening and Randomization (as confirmed by a negative urine pregnancy test with a sensitivity of less than 25 mlU/mL or equivalent units of human chorionic gonadotropin). Women of childbearing potential must agree to the use of a reliable method of contraception (e.g., total abstinence, IUD, a double-barrier method \[such as condom plus diaphragm with spermicide\], oral, transdermal, injected or implanted non- or hormonal contraceptive), throughout the study. A sterile sexual partner is not considered an adequate form of birth control. All females will be considered to be of childbearing potential unless they: * Are post-menopausal, defined as women who have been amenorrheic for at least 12 consecutive months, without other known or suspected primary cause. * Have been sterilized surgically or who are otherwise proven sterile (i.e., total hysterectomy, or bilateral oophorectomy) with surgery at least 4 weeks prior to Screening. Tubal ligation will not be considered a surgically sterile method. Female patients of childbearing potential are defined as: * Women without prior hysterectomy, or who have had any evidence of menses in the past 12 months. * Females who have been amenorrhea for ≥ 12 months, but the amenorrhea is possibly due to other causes, including prior chemotherapy, anti-estrogens, or ovarian suppression. 4. Have a clinical diagnosis of facial rosacea and fewer than 3 inflammatory lesions on the face at Screening and at Randomization (before drug application on Day 1). 5. Have moderate to severe facial erythema according to both CEA and PSA (i.e., an erythema score of 3 or more for each of the CEA and PSA) at Screening and at Randomization (before drug application on Day 1). 6. Free from any systemic or dermatologic disorder (other than rosacea) that, in the opinion of the Investigator, will interfere with the study evaluations or increase the risk of AEs. 7. Willing to minimize external factors that might trigger rosacea flare-ups (e.g., hot environments, prolonged sun exposure, strong winds and emotional stress) within 24 hours of the Screening and Randomization visit. 8. Any skin type or race, providing the skin pigmentation will allow discernment of erythema. 9. Willingness and capability to cooperate to the extent and degree required by the protocol.
Exclusion criteria
1. Patients with particular forms of rosacea (rosacea conglobata, rosacea fulminans, isolated rhinophyma, isolated pustulosis of the chin) or other concomitant facial dermatoses similar to rosacea, such as peri-oral dermatitis, demodicidosis, facial keratosis pilaris, seborrheic dermatitis, acute lupus erythematosus, or actinic telangiectasia, that are present on the face (i.e., 5 areas: chin, nose, both cheeks, and forehead), that in the opinion of the Investigator would interfere with study evaluations. 2. Have 3 or more facial inflammatory lesions of rosacea. 3. Have an erythema score of 2 (mild), 1 (almost clear), or 0 (clear) on the CEA and/or the PSA at Screening and at Randomization (before drug application on Day 1). 4. Patients with excessive facial hair (beards, sideburns, mustaches, etc.) that would interfere with the diagnosis or assessment of rosacea. 5. Patients with moderate to severe telangiectasial masses in the 5 areas of the entire face: forehead, chin, nose and each cheek, that would interfere with study evaluations. 6. History of hypersensitivity or allergy to Mirvaso® including the active ingredient brimonidine tartarate or other component within the formulation. 7. Facial laser surgery for telangiectasia (or other conditions) within 6 weeks prior to randomization. 8. Exposed to excessive ultraviolet (UV) radiation within 1 week before screening or randomization visit and/or patient was unwilling to refrain from excessive exposure to UV radiation during the course of the study. 9. History of blood dyscrasia. 10. Current diagnosis of Raynaud's syndrome, thromboangiitis obliterans, orthostatic hypotension, severe cardiovascular disease, cerebral or coronary insufficiency, renal or hepatic impairment, scleroderma, Sjögren's syndrome, or depression, or any other condition causing uncontrolled blood flow or blood pressure. 11. Females who are pregnant, lactating or likely to become pregnant during the study. 12. Significant history or current evidence of chronic infectious disease, system disorder, organ disorder or other medical condition that in the Investigator's opinion would place the study patient at undue risk by participation. 13. Patients with severe, unstable or uncontrolled cardiovascular disease. 14. Patients who meet study restrictions at Screening and Randomization and/or unwillingness to comply with all restricted treatments 15. Receipt of any drug as part of a research study within 30 days before dosing. 16. Employees of the research center or Investigator. 17. Previous participation in this study. 18. Patients who are unable and/or unwilling to follow the study requirements, and procedures.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary: Percentage of Treatment Success on Day 7 | 7 days | Percentage of patients with a clinical response of treatment success on Day 7 (± 1). Treatment success is defined as at least a 2-grade improvement on both CEA and PSA scores from baseline (pre-dose) on Day 7 (± 1) to 6 hours post-application on Day 7 (± 1). |
Secondary
| Measure | Time frame |
|---|---|
| Percentage of Patients With a Clinical Response of Treatment Success on Day 1 | 1 day |
Countries
United States
Participant flow
Pre-assignment details
514 patients were screened for study participation and 462 patients were randomized and included in the statistical analysis. The populations for this study included the Safety population, the Per-Protocol (PP) population and the modified Intent-to-Treat (mITT) Population.
Participants by arm
| Arm | Count |
|---|---|
| Test:Brimonidine 0.33% Gel Participants applies a once-daily application of brimonidine gel (pea-sized amount to each of 5 areas of the entire face for 7 days). | 199 |
| Reference: Mirvaso 0.33% Gel Participants applies a once-daily application of brimonidine gel (pea-sized amount to each of 5 areas of the entire face for 7 days). | 199 |
| Placebo Gel Vehicle Participants applies a once-daily application of brimonidine gel (pea-sized amount to each of 5 areas of the entire face for 7 days). | 64 |
| Total | 462 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 1 | 0 |
Baseline characteristics
| Characteristic | Test:Brimonidine 0.33% Gel | Reference: Mirvaso 0.33% Gel | Placebo Gel Vehicle | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 36 Participants | 32 Participants | 10 Participants | 78 Participants |
| Age, Categorical Between 18 and 65 years | 163 Participants | 167 Participants | 54 Participants | 384 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 60 Participants | 65 Participants | 19 Participants | 144 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 139 Participants | 134 Participants | 45 Participants | 318 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 198 Participants | 198 Participants | 64 Participants | 460 Participants |
| Sex: Female, Male Female | 151 Participants | 156 Participants | 53 Participants | 360 Participants |
| Sex: Female, Male Male | 48 Participants | 43 Participants | 11 Participants | 102 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 26 / 199 | 22 / 199 | 4 / 64 |
| other Total, other adverse events | 26 / 199 | 22 / 199 | 4 / 64 |
| serious Total, serious adverse events | 0 / 199 | 0 / 199 | 0 / 64 |
Outcome results
Primary
Primary: Percentage of Treatment Success on Day 7
Percentage of patients with a clinical response of treatment success on Day 7 (± 1). Treatment success is defined as at least a 2-grade improvement on both CEA and PSA scores from baseline (pre-dose) on Day 7 (± 1) to 6 hours post-application on Day 7 (± 1).
Time frame: 7 days
Population: Participants in the mITT Population that were evaluated for percentage of treatment successes.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Test: Brimonidine 0.33% Gel | Primary: Percentage of Treatment Success on Day 7 | 9.95 percentage of participants |
| Reference: Mirvaso 0.33% Gel | Primary: Percentage of Treatment Success on Day 7 | 10.36 percentage of participants |
| Placebo | Primary: Percentage of Treatment Success on Day 7 | 0 percentage of participants |
90% CI: [-6.49, 5.33]
p-value: <0.0001t-test, 2 sided
p-value: <0.0001t-test, 2 sided
Secondary
Percentage of Patients With a Clinical Response of Treatment Success on Day 1
Time frame: 1 day
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Test: Brimonidine 0.33% Gel | Percentage of Patients With a Clinical Response of Treatment Success on Day 1 | 30.89 percentage of participants |
| Reference: Mirvaso 0.33% Gel | Percentage of Patients With a Clinical Response of Treatment Success on Day 1 | 30.89 percentage of participants |
| Placebo | Percentage of Patients With a Clinical Response of Treatment Success on Day 1 | 8.62 percentage of participants |
90% CI: [-1.54, 15.41]
p-value: <0.0001t-test, 2 sided
p-value: 0.0045t-test, 2 sided