Wynzora (Page 3 of 4)

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

When calcipotriene was applied topically to mice for up to 24 months at dosages of 3, 10, and 30 mcg/kg/day (corresponding to 9, 30, and 90 mcg/m2 /day), no significant changes in tumor incidence were observed when compared to control.

A 104-week oral carcinogenicity study was conducted with calcipotriene in male and female rats at doses of 1, 5 and 15 mcg/kg/day (corresponding to dosages of approximately 6, 30, and 90 mcg/m2 /day). Beginning week 71, the dosage for high-dose animals of both genders was reduced to 10 mcg/kg/day (corresponding to a dosage of approximately 60 mcg/m2 /day). A treatment-related increase in benign C-cell adenomas was observed in the thyroid of females that received 15 mcg/kg/day. A treatment-related increase in benign pheochromocytomas was observed in the adrenal glands of males that received 15 mcg/kg/day. No other statistically significant differences in tumor incidence were observed when compared to control. The relevance of these findings to patients is unknown.

When betamethasone dipropionate was applied topically to CD-1 mice for up to 24 months at dosages approximating 1.3, 4.2, and 8.5 mcg/kg/day in females, and 1.3, 4.2, and 12.9 mcg/kg/day in males (corresponding to dosages of up to approximately 26 mcg/m2 /day and 39 mcg/m2 /day, in females and males, respectively), no significant changes in tumor incidence were observed when compared to control.

When betamethasone dipropionate was administered via oral gavage to male and female Sprague Dawley rats for up to 24 months at dosages of 20, 60, and 200 mcg/kg/day (corresponding to dosages of approximately 120, 360, and 1200 mcg/m2 /day), no significant changes in tumor incidence were observed when compared to control.

Calcipotriene did not elicit any genotoxic effects in the Ames mutagenicity assay, the mouse lymphoma TK locus assay, the human lymphocyte chromosome aberration test, or the mouse micronucleus test. Betamethasone dipropionate did not elicit any genotoxic effects in the Ames mutagenicity assay, the mouse lymphoma TK locus assay, or in the rat micronucleus test.

Studies in rats with oral doses of up to 54 mcg/kg/day (324 mcg/m2 /day) of calcipotriene indicated no impairment of fertility or general reproductive performance. Studies in male rats at oral doses of up to 200 mcg/kg/day (1200 mcg/m2 /day), and in female rats at oral doses of up to 1000 mcg/kg/day (6000 mcg/m2 /day), of betamethasone dipropionate indicated no impairment of fertility.

14 CLINICAL STUDIES

The safety and efficacy of WYNZORA Cream were evaluated in a randomized, multicenter, vehicle and active-comparator controlled, clinical trial (NCT03308799) in adult subjects with mild to moderate plaque psoriasis. In the trial, 794 subjects were randomized to 1 of 3 treatment groups: WYNZORA Cream, vehicle cream, or calcipotriene/betamethasone dipropionate topical suspension, 0.005%/0.064%. The majority of subjects in the trial (81.7%) had disease of moderate severity at baseline, while 18.3% of subjects had disease of mild severity. Disease severity was determined by a 5-grade Physician’s Global Assessment (PGA) scale.

The primary efficacy endpoint was the proportion of subjects with treatment success at Week 8. Treatment success was defined as at least a 2-grade improvement from baseline in the PGA score and an PGA score equating to “clear” or “almost clear”. Other evaluated outcomes included reduction in itch as defined by at least a 4-point improvement in the 11-point peak pruritus numeric rating scale (NRS) from baseline to Week 4. Table 2 presents the primary efficacy results.

Table 2: Primary Efficacy Outcome at Week 8
WYNZORA Cream(N=342) Vehicle Cream(N=115)
PGA of Clear or Almost Clear And ≥2-grade Improvement 37.4% 3.7%
Difference from Vehicle (95% CI) 33.7%(27.4%, 40.0%)

WYNZORA Cream was non-inferior to calcipotriene/betamethasone dipropionate topical suspension, 0.005%/0.064% for the primary endpoint of treatment success at Week 8 [Difference (95% CI): 14.6% (7.6%, 21.6%)].

Among subjects who had at least a peak pruritus NRS score of 4 at baseline, there was a higher percentage of subjects that achieved at least a 4-point improvement from baseline on the peak pruritus NRS score at Week 4 in the WYNZORA Cream group compared to the vehicle cream group (60.3% vs. 21.4%).

16 HOW SUPPLIED/STORAGE AND HANDLING

WYNZORA® (calcipotriene and betamethasone dipropionate) Cream, 0.005%/0.064%, is a white cream. Each gram of cream contains 50 mcg of anhydrous calcipotriene and 0.644 mg of betamethasone dipropionate. It is available as 60 g tubes individually packaged (NDC 73499-001-01).

Store between 20°C-25°C (68°F-77°F); excursions permitted between 15°C-30°C (59°F-86°F). [See USP controlled room temperature.]

Do not freeze. Protect from light and excessive heat.

Unused product should be discarded six months after the tube has been opened.

17 PATIENT COUNSELING INFORMATION

Advise the patient to read the FDA-approved patient labeling (Patient Information).

Administration Instructions

  • Instruct patients not to use more than 100 grams per week.
  • Instruct patients to discontinue therapy when control is achieved unless directed otherwise by the healthcare provider.
  • Advise patients to avoid use of WYNZORA Cream on the face, underarms, groin or eyes.
  • Advise patients not to occlude the treatment area with a bandage or other covering unless directed by the healthcare provider.
  • Instruct patients to wash hands after application.

Local Reactions and Skin Atrophy

Advise patients that local reactions and skin atrophy are more likely to occur with occlusive use, prolonged use or use of higher potency corticosteroids.

Hypercalcemia and Hypercalciuria

Advise patients that hypercalcemia and hypercalciuria may occur with the use of WYNZORA Cream [see Warnings and Precautions (5.1)].

HPA Axis Suppression, Cushing’s Syndrome, and Hyperglycemia

Advise patients that WYNZORA Cream can cause HPA access suppression, Cushing’s syndrome, and/or hyperglycemia [see Warnings and Precautions (5.2)].

Ophthalmic Adverse Reactions

Advise patients to avoid contact of WYNZORA Cream with eyes and to report any visual symptoms [see Warnings and Precautions (5.5)].

Possible Avoidance of Other Products Containing Calcipotriene or a Corticosteroid

Instruct patients not to use other products containing calcipotriene or a corticosteroid with WYNZORA Cream without first talking to the healthcare provider.

Pregnancy and Lactation

  • Advise pregnant women that WYNZORA Cream may increase the potential risk of having a low birth weight infant and to use WYNZORA Cream on the smallest area of skin and for the shortest duration possible [see Use in Specific Populations (8.1)].
  • Advise breastfeeding women not to apply WYNZORA Cream directly to the nipple and areola to avoid direct infant exposure [see Use in Specific Populations (8.2)].

Manufactured for:
MC2 Therapeutics, Ltd. Leatherhead, KT22 7EP, United Kingdom

Distributed by:EPI Health, LLC. Charleston, SC 29403, USA

This Patient Information has been approved by the U.S. Food and Drug Administration Issued: 11/2020
PATIENT INFORMATIONWYNZORA® (win-ZOR-uh)(calcipotriene and betamethasone dipropionate)Cream
Important information: WYNZORA® Cream is for use on the skin only (topical use only). Do not get WYNZORA® Cream near or in your mouth, eyes, or vagina.
There are other medicines that contain the same medicine that is in WYNZORA® Cream and are used to treat plaque psoriasis. Do not use other products containing calcipotriene or a corticosteroid medicine with WYNZORA® Cream without talking to your healthcare provider first.
What is WYNZORA® Cream?WYNZORA® Cream is a prescription medicine used on the skin (topical) to treat plaque psoriasis in people 18 years of age and older.It is not known if WYNZORA® Cream is safe and effective in children under 18 years of age.
Before using WYNZORA® Cream, tell your healthcare provider about all of your medical conditions, including if you:
  • have a calcium metabolism disorder.
  • have thinning skin (atrophy) at the treatment site.
  • are pregnant or plan to become pregnant. It is not known if WYNZORA® Cream will harm your unborn baby. WYNZORA® Cream may increase your chance of having a low birth weight baby. If you use WYNZORA® Cream during pregnancy, use WYNZORA® Cream on the smallest area of the skin and for the shortest time needed.
  • are breastfeeding or plan to breastfeed. It is not known if WYNZORA® Cream passes into your breast milk. Breastfeeding women should use WYNZORA® Cream on the smallest area of the skin and for the shortest time needed. Do not apply WYNZORA® Cream directly to the nipple and areola to avoid contact with your baby.
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins and herbal supplements.
How should I use WYNZORA® Cream?
  • Use WYNZORA® Cream exactly as prescribed by your healthcare provider.
  • Your healthcare provider should tell you how much WYNZORA® Cream to use and where to use it.
  • Apply WYNZORA® Cream to affected areas 1 time a day for up to 8 weeks. You should stop treatment when your plaque psoriasis is under control unless your healthcare provider gives you other instructions.
  • You should not use more than 100 grams of WYNZORA® Cream in 1 week.
  • Do not use WYNZORA® Cream longer than prescribed. Using too much WYNZORA® Cream, or using it too often or for too long, can increase your risk for having serious side effects.
  • Do not use WYNZORA® Cream in the mouth, eyes, or vagina.
  • Do not use WYNZORA® Cream on your face, groin, or armpits, or if you have thinning of your skin (atrophy) at the treatment site.
  • If you accidentally get WYNZORA® Cream on your face or in your eyes wash the area with water right away.
  • Wash your hands well after applying WYNZORA® Cream.
  • Do not bandage or cover the treated skin area, unless instructed by your healthcare provider.
Applying WYNZORA® Cream:
  • Remove the cap and check that the aluminum seal covers the opening on the top of the tube before the first use. To break the seal, turn the cap over and poke a hole through the seal.
  • Gently rub WYNZORA® Cream all the way in to make sure that the plaques are well covered with the cream.
What are the possible side effects of WYNZORA® Cream?WYNZORA® Cream may cause serious side effects, including:
  • Too much calcium in your blood or urine. Your healthcare provider may tell you to stop or temporarily stop treatment with WYNZORA® Cream if you have too much calcium in your blood or urine.
  • WYNZORA® Cream can pass through your skin. Too much WYNZORA® Cream passing through your skin can cause your adrenal glands to stop working properly. Your healthcare provider may do blood tests to check for adrenal gland problems. Your healthcare provider may tell you to stop or temporarily stop treatment with WYNZORA® Cream.
  • Cushing’s syndrome, a condition that happens when your body is exposed to large amounts of the hormone cortisol.
  • High blood sugar (hyperglycemia).
  • Skin problems. Tell your healthcare provider if you have any skin problems, including:
  • thinning of your skin
  • burning
  • inflammation
  • itching
  • irritation
  • dryness
  • changes in skin color
  • redness
  • infection
  • raised bumps on your skin
  • Eye problems. Using WYNZORA® Cream may increase your chance of getting cataracts and glaucoma. Do not get WYNZORA® Cream in your eyes because it may cause eye irritation. Tell your healthcare provider if you have blurred vision or other vision problems during treatment with WYNZORA® Cream.
The most common side effects of WYNZORA® Cream include upper respiratory infection, headache and irritation at the treatment site.Call your doctor for medical advice about side effects. You may report side effects to FDA at 1- 800-FDA-1088.
How should I store WYNZORA® Cream?
  • Store WYNZORA® Cream at room temperature between 68°F to 77°F (20°C to 25°C) with the cap on the tube tightly closed.
  • Do not freeze and protect WYNZORA® Cream from light and excessive heat.
  • Keep WYNZORA® Cream out of the light.
  • Throw away (discard) unused WYNZORA® Cream 6 months after it has been opened.
Keep WYNZORA® Cream and all medicines out of the reach of children.
General information about WYNZORA® CreamMedicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use WYNZORA® Cream for a condition for which it was not prescribed. Do not give WYNZORA® Cream to other people, even if they have the same symptoms you have. It may harm them. You can ask your pharmacist or healthcare provider for information about WYNZORA® Cream that is written for health professionals.
What are the ingredients in WYNZORA® Cream?Active ingredients: calcipotriene and betamethasone dipropionateInactive ingredients: isopropyl myristate, mineral oil, medium-chain triglycerides, isopropyl alcohol, polyoxyl lauryl ether, poloxamer (407), polyoxyl 40 hydrogenated castor oil, carbomer interpolymer (type A), butylated hydroxyanisole, trolamine, dibasic sodium phosphate, heptahydrate, monobasic sodium phosphate, monohydrate, alpha-tocopherol and purified water.Manufactured for: MC2 Therapeutics, Ltd. Leatherhead, KT22 7EP, United Kingdom.Distributed by: EPI Health, LLC. Charleston, SC 29403, USA.For more information, go to www.wynzora.com or call 1–800-644-8240

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