Bioequivalence Study of Tretinoin Gel 0.05% to Brand Tretinoin Gel
Condition: Acne
Intervention: Tretinoin
Intervention description: Treatment of acne once daily in evening
Intervention MeSH terms: Tretinoin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 574.0
Sex: All
Minimum age: 12 Years
Maximum age: 40 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      This was a double-blind, randomized, three-treatment, parallel study. Normal, healthy male
      and female children and adults (i.e., ages 12 to 40 years) with at least Grade 2 (i.e., mild
      severity) acne vulgaris were treated on the full face once daily for 84 days with the
      Tretinoin Gel 0.05%, Brand (tretinoin) Gel 0.05%, or Gel Vehicle. Acne lesions were graded by
      a single blinded observer at screening and at Weeks 0 (i.e., baseline), 2, 4, 8, and 12 at
      each location.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Normal, healthy male and female children and adults aged 12 to 40 years

          -  Written and verbal informed consent had to be obtained. Subjects aged 12 to 17 years,
             had to sign an assent for the study and a parent or a legal guardian had to sign the
             informed consent

          -  Women of childbearing potential had to be non-pregnant and non-nursing, and had to be
             willing to avoid pregnancy during the course of the study and during the menstrual
             cycle following completion of their participation in the study. Adequate contraception
             was defined as systemic birth control, such as oral contraceptives, for three months
             prior and implantable/injectable contraceptives (e.g., Norplant, intrauterine device
             [IUD]) for six months prior to study drug administration; or barrier methods, such as
             diaphragm plus spermicide or condom plus spermicide, consistently for at least 14 days
             prior to study drug administration; or abstinence.

          -  On the face, having ≥ 20 inflammatory (i.e., papules and pustules) and ≥ 25
             non-inflammatory (i.e., open and closed comedones) lesions with ≤ 2 nodulocystic
             lesions (i.e, nodules and cysts), as per FDA Draft Guidance on Tretinoin, dated March
             20

          -  Able to refrain from the use of all other topical acne medications or antibiotics
             during the treatment period

          -  Considered reliable and capable of understanding their responsibility and role in the
             study

        Exclusion Criteria:

          -  Presence of any skin condition that would interfere with the diagnosis or assessment
             of acne vulgaris (e.g., on the face: rosacea, dermatitis, psoriasis, squamous cell
             carcinoma, eczema, acneform eruptions caused by medications, steroid acne, steroid
             folliculitis, or bacterial folliculitis). Note: Eczema and psoriasis on the body are
             not exclusions.

          -  Subjects with active cystic acne as evidenced by more than 2 facial nodules. Nodules
             are defined as in 7.3.3 as: deep-seated in the skin (i.e., centered in the dermis or
             subcutis) and greater than 5 mm in diameter.

          -  More than 40 papules and/or pustules (inflammatory lesions).

          -  More than 60 open and/or closed comedones/milia (non-inflammatory lesions).

          -  Overall severity grade of less than 2 or greater than 4.

          -  History of allergy or hypersensitivity to tretinoin, retinoids, or any of the study
             medication ingredients.

          -  Significant history or clinical evidence of auto-immune, cardiovascular,
             gastrointestinal, hematological, hepatic, neurological, pancreatic, or renal disease.

          -  Use within 6 months prior to baseline of systemic retinoid (isotretinoin) treatment or
             therapeutic vitamin A supplements of greater than 10,000 units/day (multivitamins are
             allowed).

          -  Oral contraceptives started or changed within 3 months prior to study initiation or
             planned to change during the study.

          -  Use on the face within 1 month prior to baseline of 1) cryodestruction or
             chemodestruction, 2) dermabrasion, 3) photodynamic therapy, 4) acne surgery, 5)
             intralesional steroids, or 6) x-ray therapy.

          -  Use within 1 month prior to baseline of 1) spironolactone, 2) systemic steroids, 3)
             systemic antibiotics, 4) systemic treatment for acne vulgaris (other than oral
             retinoids, which require a 6-month washout), or 5) systemic anti-inflammatory agents.

          -  Use within 2 weeks prior to baseline of 1) topical steroids, 2) topical retinoids, 3)
             topical acne treatments including over-the-counter preparations, 4) topical
             anti-inflammatory agents, or 5) topical antibiotics.

          -  Pregnant or breast-feeding.

          -  Serious psychological illness.

          -  Significant history (within the past year) of alcohol or drug abuse.