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

Study Overview
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Brief Summary
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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 been shown to be safe and effective for the treatment of AKs.

Detailed Description
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This was a randomized, double-blind, multicenter, placebo-controlled study 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 AKs of the face or balding scalp. Subjects were scheduled for a total of 9 visits (1 prestudy screening visit and 8 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 2 weeks of daily treatment followed by 2 weeks of no treatment, and the second treatment cycle consisted of an additional 2 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 18 weeks, including a 4-week maximum screening period and a 14-week study period.

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

Conditions
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Actinic Keratoses

Intervention / Treatment
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* Drug: imiquimod cream
* Drug: imiquimod cream
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: In good general health Have 5 to 20 AKs on the face or balding scalp Negative urine pregnancy test (for women who are able to become pregnant) Willing to make frequent visits to the study center during 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 (e.g., 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 3.75% imiquimod cream<br> | Drug: imiquimod cream<br>* cream, 250 mg/packet, up to 2 packets applied daily for 2 treatment cycles. The first treatment cycle consisted of 2 weeks of daily treatment followed by 2 weeks of no treatment, and the second treatment cycle consisted of an additional 2 weeks of daily treatment followed by 8 weeks of no treatment.<br>|
| Active Comparator: 2.5% imiquimod cream<br> | Drug: imiquimod cream<br>* cream, 250 mg/packet, up to 2 packets applied daily for 2 treatment cycles. The first treatment cycle consisted of 2 weeks of daily treatment followed by 2 weeks of no treatment, and the second treatment cycle consisted of an additional 2 weeks of daily treatment followed by 8 weeks of no treatment.<br>|
| Placebo Comparator: Placebo cream<br> | Drug: Placebo<br>* cream, 250 mg/packet, up to 2 packets applied daily for 2 treatment cycles. The first treatment cycle consisted of 2 weeks of daily treatment followed by 2 weeks of no treatment, and the second treatment cycle consisted of an additional 2 weeks of daily treatment followed by 8 weeks of no treatment.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Complete Clearance of AK Lesions | Subject status with respect to complete clearance of AK lesions at End of Study (EOS), ie, the Week 14 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. | End of Study the Week 14 visit | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Partial Clearance of AK Lesions | Subject status with respect to partial 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. | End of Study the Week 14 visit | 
| Percent Change From Baseline in AK Lesion Count | Percent change from Baseline to end of study (EOS) in investigator counts of AK lesions. | From baseline to End of Study the Week 14 visit | 
| Local Skin Reactions | Six local skin reaction (LSR) signs were predefined and were assessed for presence and intensity at each study 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. Mean scores were summated over time (14 weeks) to yield a mean LSR AUC (area under the curve) | At all visits - from Baseline to End of study (Week 14) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Actinic keratosis, Skin disease