Safety and Effectiveness Study of Actinic Keratosis Treatment Following Cryosurgery

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00894647
Recruitment Status : Completed
First Posted : May 7, 2009
Results First Posted : August 23, 2010
Last Update Posted : August 31, 2010
Information provided by:
Graceway Pharmaceuticals, LLC

Brief Summary:
The objective of this study is to evaluate the efficacy and safety of imiquimod cream versus placebo cream when used after cryosurgery in the treatment of actinic keratoses (AKs).

Condition or disease Intervention/treatment Phase
Actinic Keratosis Drug: imiquimod cream Drug: placebo cream Phase 3

Detailed Description:

In this multicenter, randomized, double-blind, placebo-controlled study, the efficacy and safety of imiquimod 3.75% cream following cryosurgery to treat clinically typical visible or palpable AK lesions on the face was compared with that of placebo cream. Based on a 1:1 randomization, approximately 120 subjects applied imiquimod 3.75% cream daily (up to 500 mg cream daily [18.75 mg imiquimod]) and approximately 120 subjects applied placebo cream daily during two 2-week periods (Cycle 1 and Cycle 2) separated by 2 weeks of no treatment. Subjects visited the clinic 9 times—1 screening/cryosurgery visit (additional visits might be needed during the screening period to assess healing from the cryosurgery), 4 treatment visits(treatment initiation at Weeks 0 and 4 and treatment follow-up at the end of Weeks 2 and 6), and 4 posttreatment visits (4, 8, 14, and 20 weeks after the last administration of study treatment at the end of Week 6). The total study duration for a subject, including a 2-week screening period, was up to 28 weeks.

Prior to cryosurgery, subjects had to have ≥10 clinically typical visible or palpable AK lesions in an area that exceeded 25 cm^2 on the face to be eligible for participation in the study. At screening, a minimum of 5 visible lesions were not treated with cryosurgery, and 5 to 14 visible lesions were treated with cryosurgery. Subjects had to have at least 5 AK lesions after the skin healed sufficiently from the cryosurgery to be eligible for randomization to either imiquimod 3.75% or placebo cream. Subjects applied up to 2 packets of study cream (500 mg total) as a thin layer to the entire face, avoiding the periocular areas, lips, and nares; ears were excluded from both assessment and treatment. Study cream was applied prior to normal sleeping hours and removed approximately 8 hours later with mild soap and water. Rest periods from daily treatment could be approved by the investigator as needed, with treatment resumption at the investigator's discretion.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 247 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 3b Randomized, Double-blinded, Placebo-controlled, Multicenter, Efficacy and Safety Study of Imiquimod Cream Following Cryosurgery for the Treatment of Actinic Keratoses
Study Start Date : May 2009
Actual Primary Completion Date : February 2010
Actual Study Completion Date : February 2010

Resource links provided by the National Library of Medicine

Drug Information available for: Imiquimod
U.S. FDA Resources

Arm Intervention/treatment
Placebo Comparator: 2
placebo cream in 250mg/packet, up to 2 packets applied daily
Drug: placebo cream
cream applied once daily for two 2-week treatment periods (Cycle 1 and Cycle 2) separated by a 2-week no-treatment period
Active Comparator: imiquimod cream
Imiquimod 3.75% cream, 250 mg single-use packets, up to 2 packets applied daily
Drug: imiquimod cream
Imiquimod 3.75% cream (250 mg/packet) up to 2 packets applied daily Two 2-week treatment periods (Cycle 1 and Cycle 2) separated by a 2-week no-treatment period

Primary Outcome Measures :
  1. Change From Baseline in Percentage of Lesion Count [ Time Frame: Week 26 ]
    The primary efficacy endpoint was a comparison between the active and placebo treatment groups of percent change from baseline in the total AK lesion count at Week 26. All AK lesions on the face were included in the analysis—treated and untreated AK lesions at baseline (defined as the AK lesion count just prior to cryosurgery) and new lesions that appeared post-baseline.

Secondary Outcome Measures :
  1. Percent of Subjects With Complete Clearance [ Time Frame: Week 26 ]
    Proportion of subjects who achieved complete clearance of all AK lesions, cryosurgery-treated AK lesions, and non cryosurgery-treated AK lesions from baseline to Week 26/EOS in the ITT population.

  2. Number of Participants With Any Post-baseline Local Skin Reactions (LSRs) [ Time Frame: Weeks 2, 4, 6, 10, 14, 20, and 26 ]
    LSRs were assessed independently from AEs. The frequency and percentage of subjects, as well as the mean (SD) and median score for severity (none=0, mild=1, moderate=2, and severe=3), were summarized by treatment group and by visit for the following LSRs: erythema, edema, weeping/exudates, flaking/ scaling/dryness, and scabbing/crusting. Erosion and ulceration were also evaluated (none=0, erosion=1, and ulceration=2). A score of greater than 0 for the specified LSR was considered a "treatment site reaction".

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • In good general health
  • Negative urine pregnancy test (for women of child-bearing potential) and agree to use an approved method of birth control while enrolled in the study.
  • Prior to cryosurgery, have ≥ 10 clinically typical (visible or palpable) AKs in an area that exceeds 25 cm2 on the face.
  • Must have had cryosurgery on 5 to 14 AKs on the face after giving informed consent and prior to receiving study medication. Lesions previously treated with cryosurgery must be healed sufficiently prior to randomization to study cream.
  • Following cryosurgery, have ≥ 5 clinically typical (visible or palpable) AKs in an area that exceeds 25 cm2 on the face that are suitable for treatment with the study cream.

Exclusion Criteria:

  • Women who are pregnant, lactating, or planning to become pregnant during the study
  • Had a medical event within 90 days of the visit (e.g., stroke, heart attack, etc.).
  • 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 within the designated time period prior to study treatment initiation

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00894647

United States, California
Dermatology Research Associates
Los Angeles, California, United States, 90045
Therapeutics Clinical Research
San Diego, California, United States, 92123
United States, Florida
Spencer Dermatology & Skin Surgery Center
St. Petersberg, Florida, United States, 33705
Palm Beach Dermatology
West Palm Beach, Florida, United States, 33401
United States, Georgia
MedaPhase, Inc.
Newman, Georgia, United States, 30263
United States, Illinois
Evanston Northwestern Healthcare
Skokie, Illinois, United States, 60077
United States, Nebraska
Skin Specialists PC
Omaha, Nebraska, United States, 68144
United States, New Mexico
Academic Dermatology Association
Albuquerque, New Mexico, United States, 87106
United States, New York
DermResearchCenter of New York
Stony Brook, New York, United States, 11790
United States, North Carolina
Wake Forest Univ School of Medicine
Winston-Salem, North Carolina, United States, 27157
United States, Oregon
Oregon Medical Research Center
Portland, Oregon, United States, 97223
United States, Texas
DermResearch Inc.
Austin, Texas, United States, 78759
Dermatology Treatment and Research Center
Dallas, Texas, United States, 75230
Progressive Clinical Research
San Antonio, Texas, United States, 78229
Canada, British Columbia
Guildford Dermatology Specialists
Surrey, British Columbia, Canada, V3R6A7
Canada, New Brunswick
Clinique de Dermatologie
Moncton, New Brunswick, Canada, E1C 8X3
Canada, Ontario
Ultranova Skincare
Barrie, Ontario, Canada, L4M 6L2
Probity Medical Research
Waterloo, Ontario, Canada, N2J 1C4
Sponsors and Collaborators
Graceway Pharmaceuticals, LLC
Study Director: Sharon Levy, MD Graceway Pharmaceuticals, LLC

Responsible Party: Sharon Levy, MD, Graceway Pharmaceuticals, LLC Identifier: NCT00894647     History of Changes
Other Study ID Numbers: GW01-0901
First Posted: May 7, 2009    Key Record Dates
Results First Posted: August 23, 2010
Last Update Posted: August 31, 2010
Last Verified: August 2010

Keywords provided by Graceway Pharmaceuticals, LLC:
actinic keratosis
skin disease

Additional relevant MeSH terms:
Keratosis, Actinic
Skin Diseases
Precancerous Conditions
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents
Interferon Inducers