Safety and Effectiveness Study of Imiquimod Creams for the Treatment of Actinic Keratoses (AKs)

A Phase 3, Randomized, Double-blinded, Placebo-controlled, Multicenter, Efficacy and Safety Study of Six Weeks of Treatment With Imiquimod Creams for Actinic Keratoses

The purpose of this study is to determine whether imiquimod creams are effective in treating Actinic Keratoses when applied to the face or balding scalp. Actinic keratosis (AK) is a skin condition that shows up on skin routinely exposed to the sun, such as the face, scalp, shoulders, chest, back, arms, and hands. The active ingredient contained in the study cream for this study is the same as that of the approved product Aldara, which has shown to be safe and effective for the treatment of AKs.

These were a randomized, double-blind, multicenter, placebo-controlled studies that compared the efficacy and safety of 2.5% imiquimod cream and 3.75% imiquimod cream with that of placebo in the treatment of typical visible or palpable AK of the face or balding scalp. Subjects were scheduled for a total of 11 visits (1 prestudy screening visit and 10 on-study visits). Subjects determined to be eligible during the screening phase were randomized in a 1:1:1 ratio to 2.5% imiquimod cream, 3.75% imiquimod cream, or placebo cream. The creams were applied daily for 2 treatment cycles. The first treatment cycle consisted of 3 weeks of daily treatment followed by 3 weeks of no treatment, and the second treatment cycle consisted of an additional 3 weeks of daily treatment followed by 8 weeks of no treatment. The investigator selected the treatment area for the study (either the entire face or the entire balding scalp, but not both). Subjects applied a thin layer of cream to the treatment area (up to 2 packets, or 500 mg of product, per application), avoiding the periocular areas, lips, and nares. Study medication was applied prior to normal sleeping hours and removed approximately 8 hours later with mild soap and water. Ears were excluded from both assessment and treatment. Rest periods from daily treatment were instituted by the investigator as needed to manage local skin reactions (LSRs) or application site reactions, with resumption of treatment upon adequate resolution as determined by the investigator. The duration of each subject's study participation was approximately 21 weeks, including a 4-week maximum screening period and a 17-week study period. At the End of Study (EOS) visit, eligible subjects may have been invited to participate in a separate study evaluating AK recurrence.

250 mg/packet, up to 2 packets applied daily for 2 treatment cycles. The first treatment cycle consisted of 3 weeks of daily treatment followed by 3 weeks of no treatment, and the second treatment cycle consisted of an additional 3 weeks of daily treatment followed by 8 weeks of no treatment.

250 mg/packet, up to 2 packets applied daily for 2 treatment cycles. The first treatment cycle consisted of 3 weeks of daily treatment followed by 3 weeks of no treatment, and the second treatment cycle consisted of an additional 3 weeks of daily treatment followed by 8 weeks of no treatment.

250 mg/packet, up to 2 packets applied daily for 2 treatment cycles. The first treatment cycle consisted of 3 weeks of daily treatment followed by 3 weeks of no treatment, and the second treatment cycle consisted of an additional 3 weeks of daily treatment followed by 8 weeks of no treatment.

Subject status with respect to complete clearance of AK lesions at End of Study (EOS), ie, the Week 17 visit. Complete clearance was defined as the absence of clinically visible or palpable AK lesions in the treatment area. All lesions within the identified treatment area were included in the count, even if the lesion was a new lesion or "subclinical" lesion that had not been identified at Baseline.

Subject status with respect to complete clearance of AK lesions at End of Study (EOS), defined as at least a 75% reduction in the number of AK lesions in the treatment area compared with Baseline.

Percent change from Baseline to end of study (EOS) in investigator counts of AK lesions. A negative percent change is better than a positive percent change.

Six local skin reaction (LSR) signs were predefined and were assessed for presence and intensity at each visit. These included: Erythema, edema, Weeping/Exudate, Flaking/Scaling/Dryness, Scabbing/Crusting and Erosion/Ulceration. The LSRs were scored as 0=none, 1=mild, 2=moderate, 3=severe. Summary of LSR - area under the curve (AUC) of sum of LSR scores (days).

Inclusion Criteria: In good general health. Have 5 to 20 AKs on the face or balding scalp. Negative pregnancy test (for women who are able to become pregnant). Willing to make frequent visits to the study center during the treatment and follow-up periods. Exclusion Criteria: Women who are pregnant, lactating or planning to become pregnant during the study. Have had a medical event within 90 days of the first visit (such as: stroke, heart attack). Have any skin condition in the treatment area that may be made worse by treatment with imiquimod (such as: rosacea, psoriasis, atopic dermatitis, eczema). Have received specific treatments/medications in the treatment area(s) within the designated time period prior to study treatment initiation.

Hanke CW, Beer KR, Stockfleth E, Wu J, Rosen T, Levy S. Imiquimod 2.5% and 3.75% for the treatment of actinic keratoses: results of two placebo-controlled studies of daily application to the face and balding scalp for two 3-week cycles. J Am Acad Dermatol. 2010 Apr;62(4):573-81. doi: 10.1016/j.jaad.2009.06.020. Epub 2010 Feb 4.