|
For Dermatologic Use
Only-Not for Ophthalmic, Oral, or Intravaginal Use
Rx only
DESCRIPTION
FINACEA® (azelaic acid) Gel, 15%, contains azelaic acid,
a naturally occurring saturated dicarboxylic acid. Chemically, azelaic acid is
1,7-heptanedicarboxylic acid, with the molecular formula C9 H16 O4, a
molecular weight of 188.22, and the structural formula:
Azelaic acid is a white, odorless crystalline solid that is poorly soluble in
water at 20°C (0.24%), but freely soluble in boiling water and in ethanol.
Each gram of FINACEA Gel, 15%, contains 0.15 gm azelaic acid (15% w/w) as the
active ingredient in an aqueous gel base containing benzoic acid (as a
preservative), disodium-EDTA, lecithin, medium-chain triglycerides, polyacrylic
acid, polysorbate 80, propylene glycol, purified water, and sodium hydroxide to
adjust pH.
|
CLINICAL PHARMACOLOGY
The mechanism(s) by which azelaic acid interferes with the
pathogenic events in rosacea are unknown.
Pharmacokinetics:
The percutaneous absorption of azelaic acid after topical
application of FINACEA Gel, 15%, could not be reliably determined. Mean plasma
azelaic acid concentrations in rosacea patients treated with FINACEA Gel, 15%,
twice daily for at least 8 weeks are in the range of 42 to 63.1 ng/mL. These
values are within the maximum concentration range of 24.0 to 90.5 ng/mL observed
in rosacea patients treated with vehicle only. This indicates that FINACEA Gel,
15%, does not increase plasma azelaic acid concentration beyond the range
derived from nutrition and endogenous metabolism.
In vitro and human data suggest negligible
cutaneous metabolism of 3H-azelaic acid 20% cream after
topical application. Azelaic acid is mainly excreted unchanged in the urine, but
undergoes some ß-oxidation to shorter chain dicarboxylic acids.
|
CLINICAL STUDIES
FINACEA Gel, 15%, was evaluated for the treatment of mild to
moderate papulopustular rosacea in 2 clinical trials comprising a total of 664
(333 active to 331 vehicle) patients. Both trials were multicenter, randomized,
double-blind, vehicle-controlled 12-week studies with identical protocols.
Overall, 92.5% of patients were Caucasian and 73% of patients were women, and
the mean age was 49 (range 21 to 86) years. Enrolled patients had mild to
moderate rosacea with a mean lesion count of 18 (range 8 to 60) inflammatory
papules and pustules. Subjects without papules and pustules, with nodules,
rhinophyma, or ocular involvement, and a history of hypersensitivity to
propylene glycol or to any other ingredients of the study drug were excluded.
FINACEA Gel, 15%, or its vehicle were to be applied twice daily for 12 weeks; no
other topical or systemic medication affecting the course of rosacea and/or
evaluability was to be used during the studies. Patients were instructed to
avoid spicy foods, thermally hot foods and drinks, and alcoholic beverages
during the study, and to use only very mild soaps or soapless cleansing lotion
for facial cleansing.
The primary efficacy endpoints were both
- change from baseline in inflammatory lesion counts and
- success defined as a score of clear or minimal with at least a 2 step
reduction from baseline on the Investigator's Global Assessment
(IGA):
CLEAR: |
No papules and/or pustules; no or residual erythema;
no or mild to moderate telangiectasia |
MINIMAL: |
Rare papules and/or pustules; residual to mild
erythema; mild to moderate telangiectasia |
MILD: |
Few papules and/or pustules; mild erythema; mild to
moderate telangiectasia |
MILD TO MODERATE: |
Distinct number of papules and/or pustules; mild to
moderate erythema; mild to moderate telangiectasia |
MODERATE: |
Pronounced number of papules and/or pustules; moderate
erythema; mild to moderate telangiectasia |
MODERATE TO SEVERE: |
Many papules and/or pustules, occasionally with large
inflamed lesions; moderate erythema; moderate degree of telangiectasia |
SEVERE:
|
Numerous papules and/or pustules, occasionally with
confluent areas of inflamed lesions; moderate or severe erythema; moderate or
severe telangiectasia |
Primary efficacy assessment was based on the intent-to-treat (ITT) population
with last observation carried forward (LOCF).
Both studies demonstrated a statistically significant difference in favor of
FINACEA Gel, 15%, over its vehicle in reducing the number of inflammatory
papules and pustules associated with rosacea (Table 1) and with success on the
IGA in the ITT-LOCF population at the end of treatment.
Table 1. Inflammatory Papules and Pustules (ITT population) *
|
Study One
FINACEA® Gel,15%
N = 164 |
Study One
VEHICLE
N = 165 |
Study Two
FINACEA® Gel,15%
N = 167 |
Study Two
VEHICLE
N = 166
|
Mean Lesion
Count
Baseline |
17.5 |
17.6 |
17.9 |
18.5 |
End of
Treatment *
|
6.8 |
10.5 |
9.0 |
12.1 |
Mean Percent
Reduction
End of
Treatment *
|
57.9% |
39.9% |
50.0% |
38.2% |
* ITT population with last observation carried forward (LOCF);
Although some reduction of erythema which was present in patients with
papules and pustules of rosacea occurred in clinical studies, efficacy for
treatment of erythema in rosacea in the absence of papules and pustules has not
been evaluated.
FINACEA Gel, 15%, was superior to the vehicle with regard to success based on
the investigator's global assessment of rosacea on a 7-point static score at the
end of treatment, (ITT population; Table 2).
Table 2. Investigator's Global Assessment at the End of Treatment *
|
Study One
FINACEA® Gel, 15%
N = 164 |
Study One
VEHICLE
N = 165 |
Study Two
FINACEA® Gel, 15%
N = 167 |
Study Two
VEHICLE
N = 166
|
CLEAR, MINIMAL
or MILD at End
of Treatment
(%of Patients) |
61% |
40% |
61% |
48% |
* ITT population with last observation carried forward (LOCF);
|
|
|
-- advertisement --
|