Therapeutic Equivalence of Diclofenac Sodium Gel 3% vs Solaraze ® in the Treatment of Actinic Keratosis

A Randomized, Double-Blind, Placebo-Controlled, Three-Arm, Parallel-Design, Multiple-Site
Study to Evaluate the Therapeutic Equivalence of Diclofenac Sodium Gel 3% (Encube Ethicals)
Compared to Solaraze® (diclofenac sodium) Gel 3% (Fougera Pharmaceuticals Inc.) in the
Treatment of Actinic Keratosis

Inclusion Criteria:

1. Signed Institutional Review Board (IRB)-approved informed consent form that meets all
criteria of current Food and Drug Administration regulations.

2. Male or non-pregnant, non-lactating female, 18 years of age or older.

3. Diagnosis of AK with at least five and no more than ten clinically typical, visible,
discrete, non-hyperkeratotic, non-hypertrophic AK lesions, each at least 4 mm in
diameter, contained within a contiguous 25 cm2 treatment area on the face and/or bald
scalp.

4. Females of childbearing potential must not be pregnant or lactating at Visit 1 (as
confirmed by a negative urine pregnancy test with a sensitivity of less than 50 mIU/
mL or equivalent units of human chorionic gonadotropin). Women of childbearing
potential must agree to the use of a reliable method of contraception (e.g., total
abstinence, intrauterine device, a double-barrier method, oral, transdermal, injected,
or implanted non-hormonal or hormonal contraceptive) throughout the study. Female
patients using hormonal contraceptives should have been on the same product/dosing
regimen for at least 28 days before Visit 1 and should not change this regimen during
the study. A sterile sexual partner is not considered an adequate form of birth
control.

5. Skin pigmentation that will allow discernment of erythema.

Exclusion Criteria:

1. Females who are pregnant, lactating or planning to become pregnant during the study
period.

2. Active gastrointestinal ulceration or bleeding.

3. Current evidence or history of severe renal or hepatic impairment.

4. Known allergy or hypersensitivity to diclofenac, benzyl alcohol, polyethylene glycol
monomethyl ether 359, hyaluronate sodium or other excipients in the test, reference or
vehicle gel.

5. Known allergy or hypersensitivity to other NSAIDs, including aspirin.

6. Presence of atopic dermatitis, basal cell carcinoma, squamous cell carcinoma, eczema,
psoriasis, rosacea, sunburn, exfoliative dermatitis, open or recent skin wounds,
active infections or other possible skin conditions on the face or bald scalp that in
the Investigator's opinion would interfere with the study assessments or put the
patient at risk.

7. Use of oral isotretinoin within six months before randomization.

8. Use within six months before Visit 1 on the face or bald scalp of 1) chemical peel, 2)
dermabrasion, 3) laser abrasion, 4) PUVA (psoralen plus ultraviolet A) therapy, or 5)
UVB therapy.

9. Use within one month before Visit 1 on the face or bald scalp of 1) cryodestruction or
chemodestruction, 2) curettage, 3) photodynamic therapy, 4) surgical excision, 5)
topical 5-fluorouracil, 6) topical corticosteroids, 7) topical diclofenac, 8) topical
imiquimod, 9) topical retinoids, or 10) other treatments for AK including glycolic
acids or over the- counter (OTC) products containing retinol, alpha or beta hydroxy
acids. The occasional use of ophthalmic, intranasal or inhaled corticosteroids (e.g.,
management of allergic conjunctivitis) is acceptable and not reason for exclusion. Use
of inhaled corticosteroids for the management of chronic and stable conditions (e.g.,
persistent asthma and chronic obstructive pulmonary disease [COPD]) is acceptable as
long as it has been on a stable dose for a minimum of three months before the start of
the study and up to 1 mg/day.

10. Use within one month before Visit 1 of 1) immunomodulators or immunosuppressive
therapies, 2) interferon, 3) systemic corticosteroids or 4) cytotoxic drugs.

11. Receipt of 5-Fluorouracil or other systemic cancer chemotherapy within 6 months before
Visit 1.

12. Any condition, medical, psychological, or social, that, in the Investigator's opinion,
would interfere with participation in the study or put the patient at risk.

13. Inability to understand the requirements of the study and the relative information or
are unable or not willing to comply with the study protocol.

14. Receipt of any drug as part of a research study within 30 days before Visit 1.

15. Employees of the Investigator or research center or their immediate family members.

16. Patients who have participated in this study previously.