EPSOLAY (Page 2 of 3)
8.4 Pediatric Use
Safety and effectiveness of EPSOLAY for the treatment of inflammatory lesions of rosacea have not been established in pediatric patients.
8.5 Geriatric Use
Of the 733 subjects in the clinical trials of EPSOLAY, 127 (17%) subjects were 65 and over, while 37 (3%) subjects were 75 and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects.
EPSOLAY (benzoyl peroxide) cream is for topical use. Each gram of EPSOLAY contains 50 mg of benzoyl peroxide.The chemical name for benzoyl peroxide is benzoyl benzenecarboperoxoate. It has the following structural formula:
Molecular Formula: C14 H10 O4 Molecular Weight: 242.23
The benzoyl peroxide in EPSOLAY is in a solid form that is incorporated into a microcapsule composed of silicon dioxide, cetrimonium chloride and polyquaternium-7.
EPSOLAY contains anhydrous citric acid, cetrimonium chloride, cetyl alcohol, cyclomethicone, edetate disodium, glycerin, hydrochloric acid, lactic acid, macrogol stearate Type I, mono and di-glycerides, phenoxyethanol, polyquaternium-7, purified water, silicon dioxide and sodium hydroxide as inactive ingredients.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
Benzoyl peroxide is an oxidizing agent with bactericidal and keratolytic effects but the precise mechanism of action in the treatment of rosacea is unknown.
The pharmacodynamics of EPSOLAY in the treatment of rosacea are unknown.
Benzoyl peroxide is absorbed by the skin where it is converted to benzoic acid, an endogenous substance, which is eliminated in the urine. The systemic exposure of benzoyl peroxide following the application of EPSOLAY was not assessed.
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
Carcinogenicity, mutagenicity, and impairment of fertility studies were not conducted with EPSOLAY.
The role of benzoyl peroxide as a tumor promoter has been well established in several animal species. However, the significance of this finding in humans is unknown.
No significant increase in tumor formation was observed in rats treated topically with a 15 to 25% benzoyl peroxide carbopol gel (3 to 5 times the concentration of benzoyl peroxide in EPSOLAY) for two years. Similar results were obtained in mice topically treated with 25% benzoyl peroxide gel for 56 weeks followed by intermittent treatment with 15% benzoyl peroxide gel for rest of the 2 years study period and in mice topically treated with 5% benzoyl peroxide gel for two years.
Bacterial mutagenicity assays (Ames test) conducted with benzoyl peroxide have provided mixed results; mutagenic potential was observed in a few studies but not in a majority of investigations. Benzoyl peroxide has been found to cause DNA strand breaks in a variety of mammalian cell types and to cause sister chromatid exchanges in Chinese hamster ovary cells.
Fertility studies were not conducted with benzoyl peroxide.
14 CLINICAL STUDIES
The safety and efficacy of EPSOLAY was evaluated in two multicenter, randomized, double-blind, vehicle-controlled trials (Trial 1 [NCT03448939] and Trial 2 [NCT03564119]) in subjects with moderate-to-severe papulopustular rosacea. The trials were conducted in 733 subjects, aged 18 years and older. Subjects were treated once daily for 12 weeks with either EPSOLAY or vehicle cream.
Subjects were required to have a minimum of 15 to 70 total inflammatory lesions (papules and/or pustules) and no more than 2 nodules (where a nodule was defined as a papule or pustule greater than 5 mm in diameter) and an Investigator Global Assessment (IGA) score of 3 (“moderate”) or 4 (“severe”) at baseline. Overall, 93% of subjects were Caucasian, 73% were female, and the mean age was 51 years (ranged from 18 to 85 years). At baseline, subjects had a mean inflammatory lesion count of 27.5, 89% were scored as moderate (IGA=3), and 11% scored as severe (IGA=4).
The co-primary efficacy endpoints in both trials were the proportion of subjects with treatment success at Week 12, defined as an IGA score of 0 (“clear”) or 1 (“almost clear”) with at least a two-grade reduction from baseline, and the absolute change from baseline in inflammatory lesion counts at Week 12. The results at Week 12 are presented in Table 3. EPSOLAY was more effective than vehicle cream on the co-primary efficacy endpoints starting from 4 weeks of treatment in both trials, see Figure 1 through Figure 4.
|* Investigator Global Assessment (IGA) success was defined as an IGA score of 0 (“clear”)or 1 (“almost clear”) with at least a two-grade reduction from baseline. † Means presented in table are Least Square (LS) Means.|
|Trial 1EPSOLAY Vehicle (N=243) (N=118)||Trial 2EPSOLAY Vehicle (N=250) (N=122)|
|IGA Treatment Success* Difference from Vehicle(99% CI)||47.4% 20.7% 26.7% (16.7%, 36.8%)||49.2% 28.2% 21.0% (10.7%, 31.3%)|
|Inflammatory Lesions Mean† Absolute ChangeDifference from Vehicle(95% CI) Mean† Percent ChangeDifference from Vehicle(95% CI)||-17.4 -9.5 -7.9(-10.0, -5.9) -68.2% -38.3% -29.9% (-37.8%, -22.0%)||-20.3 -13.3 -6.9 (-9.0, -4.9) -69.4% -46.0% -23.4% (-30.5%, -16.3%)|
|Figure 1: IGA Success Rate Over Time in Trial 1||Figure 2: IGA Success Rate Over Time in Trial 2|
|Figure 3: Mean Absolute Change in Inflammatory Lesion Counts from Baseline Over Time in Trial 1||Figure 4: Mean Absolute Change in Inflammatory Lesion Counts from Baseline Over Time in Trial 2|
16 HOW SUPPLIED/STORAGE AND HANDLING
EPSOLAY is a white to off-white cream supplied in an airless pump as follows:
30 gram pump: NDC 0299-5890-30
Storage and Handling
- Store at 20°C to 25°C (68°F to 77°F) with excursions permitted to 15°C to 30ºC (59°F to 86ºF) [see USP Controlled Room Temperature].
- Keep away from heat.
- Do not freeze.
- Discard unused cream 60 days after first use.
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