Cryosurgery and Cream Combination for Actinic Keratosis

This is a randomized (1:1), single-blind, placebo controlled, single center prospective
study. Subjects will first undergo cryosurgery of all clinically apparent AK lesions, limited
to the face or balding scalp. Three weeks after cryosurgery, subjects will then be randomized
(1:1 according to standard randomization tables) and directed to apply either Carac 0.5%
cream or placebo cream (Cetaphil Cream) to the face or balding scalp at bedtime for seven
consecutive days, washed off each following morning. Each does of study cream will be applied
at approximately the same time of day and will remain on the skin for approximately eight
hours. Subject evaluation, Investigator Global Assessments, Quality of Life lesion counts and
photography shall be performed at Baseline. At Week 3, study drug will be dispensed and the
global assessments and assessment of improvement will be performed. A Medication Tolerability
Assessment will occur at Week 4 when the study drug will be returned. Investigator Global
Assessment, lesion count, Global Assessment of Improvement and Quality of Life will be
measured at Week 8 and Week 26 (or end of study). Photography will be done at Week 26 or end
of study.

Inclusion Criteria:

- Must be male or female and at least 18 years of age. Each subject must demonstrate
good health as determined by a baseline medical history.

- Female subjects myst be of either non-childbearing potential, or childbearing
potential provided: negative urine pregnancy test and using two acceptable methods of
effective contraception (abstinence, birth control pills.patch, DepoProvera, tubal
ligation, vasectomy of the partner in a monogamous relationship, condoms and
spermicidal form or gel and/or cervical cap or sponge), as determined by the
investigator

- At least eight clinically typical, visible and discrete AK lesions within the
treatment area on the face or balding scalp

- Subjects must be able and willing to comply with study procedures and have provided
written informed consent.

Exclusion Criteria:

- Cosmetic or therapeutic procedures (e.g., use of liquid nitrogen, surgical excision,
curettage, dermabrasion, medium or greater depth chemical peel, laser resurfacing)
within the selected treatment area in the previous four weeks.

- Treatment with systemic medications that suppress the immune system within the
previous four weeks.

- Field treatments with topical 5-FU, imiquimod, diclofenac, or photodynamic therapy, or
more widespread field treatment with dermabrasion, medium or greater depth chemical
peel, or laser resurfacing within the previous six months.

- Any known dihydropyrimidine dehydrogenase enzyme deficiency.

- In addition, subjects who have any skin condition or disease that may require
concurrent therapy or may confound the evaluation as determined by the investigator,
or a history of hypersensitivity to any of the formulation components will be excluded
from study.

- Subjects may not use other topical agents such as glycolic acid products,
alpha-hydroxy acid products, retinoids and chemical peel agents on teh treatment area
while on study. The use of these products are not allowed four weeks prior to study
enrollment. Introduction of any other prescription medication, topical or systemic for
actinic keratosis while participating in the study is not permitted.

- Pregnant women, women who are breast feeding, or women of childbearing potential who
are not practicing two acceptable methods of effective contraception.