A Bioavailability Study of DFD-03 Compared to Tazorac® in Patients With Moderate Acne Vulgaris

This was a multicenter, randomized, multiple-dose, laboratory-blinded, open-label, 2-arm, parallel-arm study in subjects with moderate acne vulgaris.

Approximately 62 subjects were randomized, stratified by age (Adult subjects: 17 years or older; Pediatric subjects: 9 years to 16 years 11 months for the Test product and 12 years to 16 years 11 months for the Reference product). The study was conducted in two parts, Part A and Part B in a sequential manner. Based on full PK profiles generated for adult subjects in Part A, the sparse PK sampling design in pediatric population was established in Part B.

Inclusion criteria

• Subject understands the study procedures, is willing to comply with the study procedures and required visits, and agrees to participate by giving written informed consent. Subjects under the legal age of consent must provide written assent and must have the written informed consent of their legal guardian.
• Subject (or legal guardian) must be willing to authorize use and disclosure of protected health information collected for the study.
• Male or female at least 9 years of age for the DFD-03 (Test) group and at least 12 years of age for the Tazorac Cream (Reference) group.
• Female subjects must be having their menstrual period at Baseline (Day 1, as reported by the subject), except for subjects using hormonal contraceptives that preclude menstrual periods, if the subject is premenarcheal, is postmenopausal for at least 12 months prior to baseline, is surgically sterilized (i.e., tubal ligation) or if the subject is without a uterus and/or both ovaries.
• A clinical diagnosis of facial acne vulgaris with a facial Investigator's Global Assessment (IGA) score of 3 (moderate) at Baseline (Day 1).
• Subjects should have acne lesions on at least 1 of the following regions at the Screening visit: neck, upper chest, upper back (including shoulders).

• This criterion is not applicable to the 9-11 years and 11 months age group.
• Inflammatory lesion count (papules and pustules) of at least 20 on the face, including the nose, at Baseline (Day 1).

• This criterion is not applicable to the 9-11 years and 11 months age group.
• Non-inflammatory lesion count (closed and open comedones) of at least 25 on the face, including the nose, at Baseline (Day 1).

• This criterion is not applicable to the 9-11 years and 11 months age group.
• No more than 2 nodulocystic lesions on the face, including the nose, at Baseline (Day 1).
• Females, regardless of childbearing potential:

• Must have a negative serum pregnancy test at Screening and a negative urine pregnancy test at Baseline (Day 1). Urine pregnancy test must have a sensitivity of at least 25 mIU/mL for βhCG.
• If sexually active, must be on or use an acceptable method of birth control. Acceptable methods of birth control include hormonal methods* or intrauterine device in use ≥ 90 days prior to Baseline (Day 1); or partner has had a vasectomy at least 90 days prior to Baseline (Day 1); or barrier methods plus spermicide; or Essure® that has been in place for at least 3 months before the screening visit with radiograph confirmation of fallopian tube blockage.

• Hormonal methods: If on hormonal contraceptives, must have been on the same hormonal contraceptive product for 3 months (90 days) prior to Baseline (Day 1) and continued on same method and dose throughout the duration of the study. If subject had used hormonal birth control and had stopped, this should have occurred more than 6 months prior to Baseline.

Exception: Sexually inactive female subjects are not required to practice a reliable method of contraception and may be enrolled at the investigator's discretion if they are counseled to remain sexually inactive for the duration of the study and understand the possible risks involved in getting pregnant during the study. An abstinent female must agree that if she becomes sexually active during the study she will use an acceptable form of contraception such as a barrier method with spermicide.

• Subjects agree not to use any product on the face during the entire course of study except for non-medicated, investigator-approved cleanser, sunscreen, face wash, and make-up. Subjects should continue to use these investigator-approved products for the duration of the study and should avoid any changes in these consumer products.
• Subjects must be willing to comply with sun avoidance measures for the face (as well as back/chest and shoulders, if applicable) including use of investigator-approved sunscreen and/or hats, have limited direct sunlight exposure time, and have no tanning bed use or use of other UV light sources during participation in the study.
• Subject must be in good general health as determined by the investigator and supported by the medical history, physical examination, and normal or not clinically significant abnormal vital signs (blood pressure and pulse).

Exclusion criteria

• Females who are pregnant or lactating or planning to become pregnant during the study period.
• Treatment with the following products:

• Topical acne treatments (other retinoids, antibiotics, benzoyl peroxide, azelaic acid, resorcinol, salicylates, α-hydroxy/glycolic acid), or other topical facial medication (antifungals, steroids, anti-inflammatories) on the treatment area in the 14 days prior to Baseline (Day 1), including prescription and non-prescription products.
• Systemic corticosteroids, systemic acne treatments including systemic antibiotics used for treatment of acne, potential photosensitizing agents (thiazides, phenothiazines), spironolactone, flutamide, or immunosuppressant drugs in the 30 days prior to Baseline (Day 1).
• Systemic retinoid use (including high-dose vitamin A > 10,000 units per day) in the 180 days prior to Baseline (Day 1).
• Undertaken certain facial procedures such as chemical peel, laser treatment, photodynamic therapy, acne surgery, cryodestruction or chemodestruction, x-ray therapy, intralesional steroids, dermabrasion, or depilation (except eyebrow shaping) in the 30 days prior to Baseline (Day 1). After the subject is enrolled in the study, eyebrow shaping (except for tweezing) is prohibited.
• Treatment with a medication or procedure that, in the opinion of the investigator, would put the subject at unacceptable risk for participation in the study or may interfere with evaluations in the study.
• Treatment with an investigational product or device in the 30 days prior to Baseline (Day 1).
• Known allergic reaction to retinoids or tazarotene or any of the other ingredients of these products. The inactive ingredients are sodium lauryl sulphate, stearyl alcohol, cetyl alcohol, gluconolactone, Vitamin E polyethylene glycol succinate, glycerin, carbomer P 971, propylparaben, methylparaben, edetate disodium, butylated hydroxytoluene, medium-chain triglyceride, trolamine, and purified water.
• Presence of any facial skin disease or condition that would interfere with the study or place the subject at unacceptable risk including sunburn, rosacea, seborrheic dermatitis, perioral dermatitis, lupus, dermatomyositis, psoriasis, eczema, squamous cell carcinoma, acneiform eruptions caused by medications, steroid acne, steroid folliculitis, bacterial folliculitis, or any other facial disease or condition.
• Excessive facial hair (i.e., heavy beard or mustache), facial tattoos, or facial disfigurement, excessive hair on the neck, upper chest, shoulders and upper back region that would interfere with study assessments.
• Subjects with a serious and/or chronic medical condition such as chronic or active liver disease, renal impairment, heart disease, severe respiratory disease, rheumatoid arthritis, current malignancies, immunocompromised conditions, or any other disease that, in the opinion of the investigator, would interfere with the study or place the subject at unacceptable risk.
• Subjects who have been treated for alcohol dependence or alcohol or drug abuse in the year prior to Baseline (Day 1).
• Subjects who have been in another investigational trial within 30 days of Baseline (Day 1).
• Subjects may not have a personal relationship with any member of the study staff or be part of the staff at the medical practice.
• HIV Ag/Ab Combo, Hepatitis B (HBsAg (B)) and Hepatitis C (anti-HCV (C)) positive subjects.