Safety and Effectiveness Study of Actinic Keratosis Treatment Following Cryosurgery

Actinic Keratosis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00894647
• Other study ID #: GW01-0901
• Status: Completed
• Phase: Phase 3
• First received: May 5, 2009
• Last updated: August 23, 2010
• Start date: May 2009
• Est. completion date: February 2010

Study information

• Verified date: August 2010
• Source: Graceway Pharmaceuticals, LLC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationCanada: Health Canada
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 247
• Est. completion date: February 2010
• Est. primary completion date: February 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Actinic Keratosis
• Keratosis
• Keratosis, Actinic

Intervention

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
• 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

Locations

Country	Name	City	State
Canada	Ultranova Skincare	Barrie	Ontario
Canada	Clinique de Dermatologie	Moncton	New Brunswick
Canada	Guildford Dermatology Specialists	Surrey	British Columbia
Canada	Probity Medical Research	Waterloo	Ontario
United States	Academic Dermatology Association	Albuquerque	New Mexico
United States	DermResearch Inc.	Austin	Texas
United States	Dermatology Treatment and Research Center	Dallas	Texas
United States	Dermatology Research Associates	Los Angeles	California
United States	MedaPhase, Inc.	Newman	Georgia
United States	Skin Specialists PC	Omaha	Nebraska
United States	Oregon Medical Research Center	Portland	Oregon
United States	Progressive Clinical Research	San Antonio	Texas
United States	Therapeutics Clinical Research	San Diego	California
United States	Evanston Northwestern Healthcare	Skokie	Illinois
United States	Spencer Dermatology & Skin Surgery Center	St. Petersberg	Florida
United States	DermResearchCenter of New York	Stony Brook	New York
United States	Palm Beach Dermatology	West Palm Beach	Florida
United States	Wake Forest Univ School of Medicine	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Graceway Pharmaceuticals, LLC

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Percentage of Lesion Count	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.	Week 26	No
Secondary	Percent of Subjects With Complete Clearance	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.	Week 26	No
Secondary	Number of Participants With Any Post-baseline Local Skin Reactions (LSRs)	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".	Weeks 2, 4, 6, 10, 14, 20, and 26	Yes