SORILUX

Molecular Formula: C₂₇H₄₀O₃                    Molecular Weight: 412.6

Calcipotriene is a white or off-white crystalline substance. SORILUX Foam contains calcipotriene 50 mcg/g in an aqueous-based emulsion foam vehicle consisting of cetyl alcohol, dibasic sodium phosphate, dl-α-tocopherol, edetate disodium, isopropyl myristate, light mineral oil, polyoxyl 20 cetostearyl ether, propylene glycol, purified water, stearyl alcohol, and white petrolatum. SORILUX Foam is dispensed from an aluminum can pressurized with a hydrocarbon (propane/n-butane/isobutane) propellant.

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Calcipotriene is a synthetic vitamin D₃ analog that has a similar receptor binding affinity as natural vitamin D₃. However, the exact mechanism of action contributing to the clinical efficacy in the treatment of psoriasis is unknown.

12.2 Pharmacodynamics

The pharmacodynamics of SORILUX Foam are unknown.

12.3 Pharmacokinetics

The systemic absorption of calcipotriene in subjects with psoriasis of the body was evaluated at steady state following application of either SORILUX Foam or calcipotriene ointment to a body surface area of 5% to 10%. In the SORILUX Foam treatment group, 15 out of 16 subjects had calcipotriene plasma concentrations below the limit of quantitation (10 pg/mL), while in the calcipotriene ointment treated group, 5 out of 16 subjects had measurable calcipotriene plasma concentrations at various time points. All measurable plasma calcipotriene concentrations were below 25 pg/mL.

The systemic disposition of calcipotriene is expected to be similar to that of the naturally occurring vitamin D. Absorbed calcipotriene is known to be converted to inactive metabolites within 24 hours of application and the metabolism occurs via a similar pathway to the natural hormone.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis: Calcipotriene topically administered to mice for up to 24 months at dose levels of 3, 10, or 30 mcg /kg/day (corresponding to 9, 30, or 90 mcg /m²/day) showed no significant changes in tumor incidence when compared with controls. In a study in which albino hairless mice were exposed to both UVR and topically applied calcipotriene, a reduction in the time required for UVR to induce the formation of skin tumors was observed (statistically significant in males only), suggesting that calcipotriene may enhance the effect of UVR to induce skin tumors [See Warnings and Precautions (5.3).]

Mutagenesis: The genotoxic potential of calcipotriene was evaluated in an Ames assay, a mouse lymphoma TK locus assay, a human lymphocyte chromosome aberration assay, and a mouse micronucleus assay. All assay results were negative.

Impairment of Fertility: Studies in rats at doses up to 54 mcg /kg/day (318 mcg /m²/day) of calcipotriene indicated no impairment of fertility or general reproductive performance.

14 CLINICAL STUDIES

In two multi-center, randomized, double-blind, vehicle-controlled clinical trials a total of 659 subjects with psoriasis were randomized 2:1 to SORILUX Foam or vehicle; subjects applied the assigned treatment twice daily for 8 weeks. Baseline disease severity was graded using a 5-point Investigator Static Global Assessment scale (ISGA), on which subjects scored either “mild” or “moderate” as shown in Table 1.

Efficacy evaluation was carried out at Week 8 with treatment success being defined as a score of “clear” (grade 0) or “almost clear” (grade 1) and at least 2 grade improvement from the baseline score. Approximately 30% of enrolled subjects were graded as “mild” on the ISGA scale. The study population ranged in age from 12 to 89 years with 10 subjects less than 18 years of age at baseline. The subjects were 54% male and 88% Caucasian. Table 2 presents the efficacy results for each trial.

In one trial, subjects graded as “mild” at baseline showed a greater response to vehicle than SORILUX Foam.

Table 3 presents the success rates by disease severity at baseline for each trial.

In another multi-center, randomized, double-blind, vehicle-controlled clinical trial, a total of 363 subjects with moderate plaque psoriasis of the scalp and body were randomized 1:1 to SORILUX Foam or vehicle. Subjects applied the assigned treatment to the affected areas twice daily for 8 weeks. Baseline disease severity of the scalp was graded using a 6-point ISGA; a score of "moderate" corresponded to grade 3.

The primary efficacy evaluation for scalp involvement was carried out at Week 8 with treatment success being defined as a score of “clear” (grade 0) or “almost clear” (grade 1). The study population ranged in age from 12 to 97 years with 11 subjects less than 18 years of age at baseline. The subjects were 60% male and 87% Caucasian. Table 4 presents the efficacy results for the trial.

The contribution to efficacy of individual components of the vehicle has not been established.

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1 How Supplied

SORILUX (calcipotriene) Foam, 0.005%, is supplied as follows:

60 g aluminum can                  NDC 0145-2130-06

120 g aluminum can                NDC 0145-2130-07

16.2 Storage and Handling

• •Store at 20ºC to 25°C (68°F to 77°F); excursions permitted to 15°C – 30°C (59°F –86°F).
• •Flammable. Contents under pressure. Do not puncture or incinerate. Do not expose to heat or store at temperatures above 120°F (49°C).
• •Keep out of reach of children.

17 PATIENT COUNSELING INFORMATION

See FDA-approved patient labeling (Patient Information)

Inform the patient to adhere to the following instructions:

• •Avoid excessive exposure of the treated areas to either natural or artificial sunlight, including tanning beds and sun lamps.
• •Avoid contact with the face and eyes. If SORILUX Foam gets on the face or in or near their eyes, rinse thoroughly with water.
• •Apply SORILUX Foam to the scalp when the hair is dry.
• •Talk to your doctor if your skin does not improve after treatment with SORILUX Foam for 8 weeks.
• •Wash your hands after applying SORILUX Foam unless your hands are the affected site.
• •Avoid fire, flame, and smoking during and immediately following application since SORILUX Foam is flammable.
• •Do not place SORILUX Foam in the refrigerator or freezer.

SORILUX is a trademark of Stiefel Laboratories, Inc.

Manufactured for

Stiefel Laboratories, Inc.

Research Triangle Park, NC 27709

©2013, Stiefel Laboratories, Inc.

SOR:6PI

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Patient Information

SORILUX (SOR-i-lux)

(calcipotriene)

Foam

Important: For skin use only. Do not get SORILUX Foam on your face or in your eyes, mouth, or vagina.

Read the Patient Information before you start using SORILUX Foam and each time you get a refill. There may be new information. This information does not take the place of talking with your doctor about your medical condition or treatment.

What is SORILUX Foam?

SORILUX Foam is a prescription medicine used on the skin (topical) to treat plaque psoriasis of the scalp and body in people 18 years and older.

It is not known if SORILUX Foam is safe and effective in people under 18 years old.

Who should not use SORILUX Foam?

Do not use SORILUX Foam if you have been told by your doctor that you have a high level of calcium in your blood (hypercalcemia).

What should I tell my doctor before using SORILUX Foam?

Before you use SORILUX Foam, tell your doctor if you:

• •are getting light therapy for your psoriasis
• •have any other medical conditions
• •are pregnant or planning to become pregnant. It is not known if SORILUX Foam can harm your unborn baby. Talk to your doctor if you are pregnant or plan to become pregnant.
• •are breastfeeding. It is not known if SORILUX Foam passes into breast milk. Do not apply SORILUX Foam to the chest area if you are breastfeeding a baby. This will help to prevent the baby from accidentally getting SORILUX Foam into their mouth.

Tell your doctor about all the medicines you take, including prescription and nonprescription medicines, vitamins, and herbal supplements.

Know the medicines you take. Keep a list of your medicines with you to show your doctor and pharmacist when you get a new medicine.

How should I use SORILUX Foam?

• •Apply SORILUX Foam exactly as prescribed.  SORILUX Foam is usually applied to the affected skin areas two times each day.
• •SORILUX Foam is for use on the skin only. Do not get SORILUX Foam in your eyes, mouth, or vagina.
• •SORILUX Foam is flammable. Avoid fire, flame, or smoking during and right after you apply SORILUX Foam to your skin.
• •Avoid excessive natural or artificial sunlight including tanning booths and sunlamps. Wear a hat and clothes that cover the treated areas of your skin if you have to be in sunlight.

Instructions for applying SORILUX Foam

1. Before applying SORILUX Foam for the first time, break the tiny plastic piece at the base of the can’s rim by gently pushing back (away from the piece) on the nozzle. See Figure A.

2. Shake the can of SORILUX Foam before use. See Figure B.

Figure B

3. Turn the can of SORILUX Foam upside down and press the nozzle. See Figure C.