An Equivalence Study of Generic Ingenol Mebutate Gel 0.015% and Picato Gel 0.015% in Subjects With Actinic Keratosis

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 effectivemethod of birth control. Women of childbearing potential (WOCBP) must have had anegative 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 nomore 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 ("theTreatment Area") located on the face or scalp.

• Subject was willing and able to apply the test article as directed, comply with studyinstructions, 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 conditionthat might have impaired evaluation of AK lesions or which, in the investigator'sopinion, exposed the subject to an unacceptable risk by study participation.

Exclusion Criteria:

• 1. Subject was pregnant, lactating, or was planning to become pregnant during thestudy.

• Subject had a location of the selected contiguous 25 cm2 Treatment Area that (a) waswithin 5 cm of an incompletely healed wound or (b) was in an area containing a lesionthat was previously treated with ingenol mebutate.

• Subject had hyperkeratotic, hypertrophic, or large mat-like AKs (e.g., AK >1 cm2 insize) 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 skinconditions 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, couldhave interfered with the evaluation of the test article or required the use ofinterfering 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 (anunsuccessful outcome was defined as after a reasonable therapeutic trial with nocompliance issues and the topical drug did not work).

• Subject used topical creams, lotions, or gels of any kind within the selectedTreatment Area within one day prior to entry into the study.

• Subject had the need or planned to be exposed to artificial tanning devices orexcessive sunlight during the study or had used artificial tanners within two weeks ofVisit 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 topicalsalves within two weeks of Visit 1/Baseline, including, but not limited to, alphahydroxy 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 ofVisit 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 ofVisit 1/Baseline; or

• Other topical therapy for actinic keratosis within 2 cm of the selectedcontiguous 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 orscalp) 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, orimmunosuppressive 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 theface or scalp.

• Subject was enrolled in an investigational drug or device study.

• Subject used an investigational drug or investigational device treatment within onemonth 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 itunsafe 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 languageproblems, poor mental development, impaired cerebral function, or physicallimitations.

• Subject was known to be noncompliant or was unlikely to comply with the requirementsof the study protocol (e.g., due to alcoholism, drug dependency, mental incapacity) inthe opinion of the investigator.

• Subject was previously enrolled in the same study.