To Compare Safety and Efficacy of Perrigo's Drug Compared to an FDA Approved Drug in the Treatment of Actinic Keratosis
Condition: Actinic Keratosis
MeSH terms: Keratosis, Actinic; Keratosis
Intervention: Ingenol Mebutate (Perrigo); Ingenol Mebutate (Reference); Placebo gel
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 469.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to compare safety and efficacy of Perrigo's drug compared to an
      FDA approved drug in the treatment of actinic keratosis.
    

Eligibility criteria:

        Inclusion Criteria:

          1. IRB approved written informed consent/assent for this study.

          2. Healthy males or females, at least 18 years of age.

          3. General good health and free from any clinically significant disease, other than
             Actinic Keratosis

          4. Clinical diagnosis of Actinic Keratosis, defined as having 4 to 8 clinically typical,
             visible and discrete, non-hyperkeratotic, non-hypertrophic, Actinic Keratosis lesions
             within a contiguous 25cm2 treatment area.

          5. Willing to refrain from using lotions, sunscreens, moisturizers, cleansers, or creams
             on the treatment area during the treatment period. Non-Medicated moisturizers,
             emollients, humectants, sunscreens or similar products used routinely prior to the
             start of the trial by subjects, may be used after the treatment period.

          6. Willing to refrain from using any type of bandage or occlusive dressing on the
             treatment area or applying the gel to open skin wounds, infections or exfoliative
             dermatitis.

          7. Willing and able to understand and comply with the requirements of the study, apply
             the study medication as instructed, refrain from use of all other topical Actinic
             Keratosis medication during the 57 day (8 week) study period, return for the required
             study visits, comply with therapy prohibitions, and are able to complete the study.

          8. Females of childbearing potential (excluding women who are surgically sterilized or
             post-menopausal for at least 2 years), in addition to having a negative urine
             pregnancy test at Visit 1/Day 1 (Baseline), must be willing to use an acceptable form
             of birth control during the study.

        Exclusion Criteria:

          1. Pregnant, nursing, or planning a pregnancy within the study period.

          2. Immunocompromised or HIV positive or who have any immune-system disorders including
             auto-immune diseases.

          3. Active herpes infection within 14 days prior to the Visit1/Day 1 (Baseline) (i.e.,
             including presence of herpes labialis).

          4. Any evidence of systemic cancer, squamous cell carcinoma, basal cell carcinoma, or any
             other cancer in the treatment area.

          5. Presence of an incompletely healed wound within the treatment area or within 5 cm of
             the treatment area.

          6. Presence of any confounding skin conditions in the treatment area that may be made
             worse by treatment with Ingenol Mebutate gel (e.g., psoriasis, atopic dermatitis,
             eczema).

          7. Subjects who have used a tanning salon and/or tanning booths or have sunbathed or had
             excessive prolonged exposure to the sun 7 days prior to Visit 1/Day 1 (Baseline) or
             planned throughout the study.

          8. Subjects who plan to use artificial tanners within 5 cm of the selected treatment area
             throughout the study.

          9. Use of NSAIDs within 7 days from Visit 1/Day 1 (Baseline) or initiation during the
             study. *Subjects may use Tylenol (Acetaminophen) for pain relief, as needed,
             throughout the study. Subjects may use low dose aspirin (81mg) for cardiac prophylaxis
             throughout the study.

         10. Subjects who had cosmetic or therapeutic procedures such as the following within 2 cm
             of the selected treatment area within 2 weeks (14 days) of Visit 1/Day 1 (Baseline)
             and within 10 cm of the selected treatment area planned anytime during the study.

               -  Cryodestruction/ cryotherapy/liquid nitrogen

               -  Surgical excision

               -  Curettage

               -  Dermabrasion

               -  Medium or greater depth chemical peel

               -  Laser resurfacing

         11. Subjects who have had or are scheduling elective surgery within 1 month (30 days)
             before or after the study period.

         12. Use within 1 month (30 days) prior to Visit 1/Day 1 (Baseline) or planned use during
             the study of:

               -  Immunomodulators (i.e. azathioprine)

               -  Immunosuppressive therapies (i.e., cyclosporine, prednisone, methotrexate,
                  alefacept, infliximab)

               -  Interferon

               -  Interferon inducers

               -  Systemic corticosteroids (oral and injectable)

               -  Cytotoxic drugs (i.e., cyclophosphamide, vinblastine, chlorambucil, methotrexate,
                  podophylllin, camptothecin)

         13. Subjects who are undergoing treatment or received treatment with the following within
             2 months (56 days) of Visit 1/Day 1 (Baseline) and within 2 cm of the selected
             treatment area or planned anytime during the study.

               -  5-Fluorouracil (5-FU)

               -  Imiquimod

               -  Diclofenac

               -  Photodynamic therapy (red or blue light) used in combination with
                  photosensitizing cream (5-aminolaevulinic acid, methyl 5-aminolaevulianate)

         14. Use of Ingenol Mebutate gel within 2 months (56 days) of Visit 1/Day 1. Previous use
             (if > 2 months (56 days) of Ingenol Mebutate gel is allowed if a different treatment
             area was successfully treated.)

         15. History of unresponsiveness, hypersensitivity or allergy to ingenol mebutate therapy
             and/or any ingredient in the study medication.

         16. Subjects who used PUVA (psoralen plus ultraviolet A therapy), or UVB therapy in the
             treatment area within 6 months (180 days) prior to Visit 1/Day 1 (Baseline) or are
             planning to receive treatment with PUVA therapy, UVB therapy, nonprescription UV light
             sources anywhere on the body during the study.

         17. Subjects who have taken systemic chemotherapy medications within 6 months (180 days)
             prior to Visit 1/Day 1 (Baseline) or planned use anytime during the study.

         18. Subjects who have undergone Botox procedures in the selected treatment area 6 months
             (180 Days) prior to Visit 1/Day 1 (Baseline).

         19. Subjects who have been treated within 1 month (30 days) or are planning to receive
             treatment with 1) systemic retinoids (i.e., oral isotretinoin, acitretin, bexarotene),
             2) hyaluronic acid, 3) other medicated Actinic Keratosis therapy (i.e., prescription
             topical retinoids, topical salicyclic acid, bichloroacettic acid, trichloroacetic aid,
             CO2 laser vaporization, electrocautery), 4) topical steroids (use within 2 cm of the
             selected treatment area after study Day 15 per PI discretion is allowed) anywhere on
             the treatment area during the study.

         20. Subjects who have had a significant change in the use of consumer products within 30
             days of Visit 1/Day 1 (Baseline) and planned use or change throughout the study.
             ("Significant change" will be determined by the Principal Investigator)

         21. Start or change of dose of hormonal treatment (oral, implanted, topical contraceptives
             and androgens) within the past 3 months (90 days) or planned start or change
             throughout the study. Use of such therapy must remain constant during the study.

         22. Subject consumes excessive alcohol, abuses drugs, or has a condition that could
             compromise the subject's ability to comply with study requirements.

         23. Participation in any clinical study involving an investigational product, agent or
             device (that might influence the intended effects or mask the side effects of study
             medication) in the 30 days prior to Visit 1/Day 1 (Baseline) or throughout the study.

         24. Previous enrollment in this study or current enrollment in this study at another
             participating site.

         25. Employee (or employee's family member) of the research center or private practice, or
             subjects who have a conflict of interest.

         26. Subjects who in the opinion of the investigator, are unlikely to be able to follow the
             restrictions of the protocol and complete the study