FINACEA® (azelaic acid) Gel, 15% - America[美国药品]

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FINACEA® (azelaic acid) Gel, 15%

2017-03-08 11:01:33 来源: 作者: 【大中小】浏览:466次评论:0条

SPL UNCLASSIFIED SECTION

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 eva luated 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 eva luability 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

1.: change from baseline in inflammatory lesion counts and
2.: 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)*
ITT population with last observation carried forward (LOCF);
	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%

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 eva luated.

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*