An Equivalence Study of Generic Ingenol Mebutate Gel 0.015% and Picato Gel 0.015% in Subjects With Actinic Keratosis
Condition: ACTINIC KERATOSIS
MeSH terms: Keratosis, Actinic; Keratosis
Intervention: Ingenol Mebutate (Picato®); Generic Ingenol Mebutate; Vehicle Foam
Intervention description: Brand product; Generic formulated to have the same therapeutic effect of the brand; It does not contain active ingredient. A placebo to test the sensitivity of the active treatments.
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 507.0
Sex: All
Minimum age: 18 Years
Maximum age: 95 Years
Healthy volunteers: No

Summary:

      The objective of this study was to evaluate the safety and therapeutic equivalence of generic
      ingenol mebutate gel, 0.015% to Picato gel, 0.015% by establishing the therapeutic
      comparability of the two active products and the superiority of the two active products over
      the vehicle gel in the treatment of AK on the face and scalp.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subject was male or non-pregnant female 18 years of age or older.

          -  Females must have been post-menopausal, surgically sterile, or using an effective
             method of birth control. Women of childbearing potential (WOCBP) must have had a
             negative urine pregnancy test (UPT) at Visit 1/Baseline.

          -  Subject provided written informed consent.

          -  Subject had a clinical diagnosis of AK at Visit 1/Baseline with at least four, but no
             more than eight visible and discrete non-hyperkeratotic, non-hypertrophic AK lesions,
             each at least 4 mm in diameter, within a contiguous 25 cm2 treatment area ("the
             Treatment Area") located on the face or scalp.

          -  Subject was willing and able to apply the test article as directed, comply with study
             instructions, and commit to all follow-up visits for the duration of the study.

          -  Subject was in good general health and free of any disease state or physical condition
             that might have impaired evaluation of AK lesions or which, in the investigator's
             opinion, exposed the subject to an unacceptable risk by study participation.

        Exclusion Criteria:

          -  1. Subject was pregnant, lactating, or was planning to become pregnant during the
             study.

          -  Subject had a location of the selected contiguous 25 cm2 Treatment Area that (a) was
             within 5 cm of an incompletely healed wound or (b) was in an area containing a lesion
             that was previously treated with ingenol mebutate.

          -  Subject had hyperkeratotic, hypertrophic, or large mat-like AKs (e.g., AK >1 cm2 in
             size) within the contiguous 25 cm2 Treatment Area.

          -  Subject had more than eight AKs, independent of size, within the selected contiguous
             25 cm2 Treatment Area

          -  Subject had atopic dermatitis, basal cell carcinoma, eczema, psoriasis, rosacea,
             squamous cell carcinoma, xeroderma pigmentosum, or any other possibly confounding skin
             conditions within the region of the head that contained the selected Treatment Area
             (i.e., face or scalp).

          -  Subject had any skin pathology or condition that, in the investigator's opinion, could
             have interfered with the evaluation of the test article or required the use of
             interfering topical, systemic, or surgical therapy.

          -  Subject was immunosuppressed (e.g., human immunodeficiency virus, systemic malignancy,
             graft host disease, etc.).

          -  Subject experienced an unsuccessful outcome from previous ingenol mebutate therapy (an
             unsuccessful outcome was defined as after a reasonable therapeutic trial with no
             compliance issues and the topical drug did not work).

          -  Subject used topical creams, lotions, or gels of any kind within the selected
             Treatment Area within one day prior to entry into the study.

          -  Subject had the need or planned to be exposed to artificial tanning devices or
             excessive sunlight during the study or had used artificial tanners within two weeks of
             Visit 1/Baseline.

          -  Subject had used any of the following topical medications on the face or scalp:

               -  Corticosteroids within two weeks of Visit 1/Baseline;

               -  Keratolytic-containing therapeutic products or medicated or irritant topical
                  salves within two weeks of Visit 1/Baseline, including, but not limited to, alpha
                  hydroxy acids (e.g., glycolic acid, lactic acid etc. >5%), beta hydroxy acid
                  (salicylic acid >2%), and urea >5%;

               -  Topical retinoids (e.g., tazarotene, adapalene, tretinoin) within two weeks of
                  Visit 1/Baseline;

               -  Light treatments (e.g., psoralen plus ultraviolet A therapy, ultraviolet B)
                  within four weeks of Visit 1/Baseline;

               -  Photodynamic therapy within eight weeks of Visit 1/Baseline;

               -  5-fluorouracil, diclofenac, imiquimod, or ingenol mebutate within eight weeks of
                  Visit 1/Baseline; or

               -  Other topical therapy for actinic keratosis within 2 cm of the selected
                  contiguous 25 cm2 Treatment Area within eight weeks of Visit 1/Baseline.

          -  Subject had cryodestruction or chemodestruction, surgical excision, curettage,
             dermabrasion, chemical peel, or laser resurfacing on the Treatment Area (i.e., face or
             scalp) within two weeks prior to Visit 1/Baseline.

          -  Subject used any of the following systemic medications:

               -  Corticosteroid therapy within one month;

               -  Interferon/interferon inducers, cytotoxic drugs, immuno-modulators, or
                  immunosuppressive therapies within one month;

               -  Retinoid therapy within six months prior to Visit 1/Baseline.

          -  Subject had lesions suspicious for skin cancer (skin cancer not ruled out by biopsy)
             or untreated skin cancers within the selected contiguous 25 cm2 Treatment Area on the
             face or scalp.

          -  Subject was enrolled in an investigational drug or device study.

          -  Subject used an investigational drug or investigational device treatment within one
             month prior to Visit 1/Baseline.

          -  Subject had a history of sensitivity to any of the ingredients in the test articles
             (see Section 9.4.2).

          -  Subject had any condition which, in the investigator's opinion, would have made it
             unsafe or precluded the subject's ability to fully participate in this research study.

          -  Subject was unable to communicate or cooperate with the investigator due to language
             problems, poor mental development, impaired cerebral function, or physical
             limitations.

          -  Subject was known to be noncompliant or was unlikely to comply with the requirements
             of the study protocol (e.g., due to alcoholism, drug dependency, mental incapacity) in
             the opinion of the investigator.

          -  Subject was previously enrolled in the same study.