A Bioequivalence Study With Clinical Endpoints Comparing Generic Imiquimod Cream, 3.75% and Zyclara™ (Imiquimod) Cream, 3.75% in Subjects With Actinic Keratoses

Actinic Keratoses Clinical Trial

Official title:

A Multicenter, Randomized, Double-Blind, Vehicle-Controlled, Parallel Group Comparison Study to Determine the Therapeutic Equivalence of Generic Imiquimod Cream, 3.75% and Zyclara™ (Imiquimod) Cream, 3.75% in Subjects With Actinic Keratoses

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01502020
• Other study ID #: 094-3152-301
• Status: Completed
• Phase: N/A
• First received: December 23, 2011
• Last updated: December 29, 2011
• Start date: February 2011
• Est. completion date: November 2011

Study information

• Verified date: December 2011
• Source: Actavis Mid-Atlantic LLC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

Zyclara™ (imiquimod) Cream, 3.75% is approved by the FDA for the treatment of actinic keratoses on the full face or balding scalp. Zyclara is applied once daily for two, 2-week treatment cycles separated by a 2-week no treatment applied interval. A generic imiquimod cream, 3.75% has been developed by Actavis Mid-Atlantic LLC for the topical treatment of clinically typical, visible or palpable actinic keratoses (AK) of the full face or balding scalp.

The current clinical study is designed to evaluate the therapeutic equivalence of this formulation with the currently marketed Zyclara™ (imiquimod) cream, 3.75% formulation (Graceway Pharmaceuticals LLC).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 410
• Est. completion date: November 2011
• Est. primary completion date: August 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Subject was male or female, 18 years of age or older.

• Subject provided written informed consent.

• Subject was willing and able to apply the test article as directed, comply with study instructions and commit to all follow-up visits for the duration of the study.

• Subject had a clinical diagnosis of actinic keratoses (AK) with at least five (5) and no more than 20 clinically typical, visible or palpable AK lesions, each at least 4mm in diameter, in an area greater than 25cm2 on the face (excluding ears) or balding scalp, but not both.

• Subject was in good general health and free of any disease state or physical condition that might have impaired evaluation of AK lesions or which, in the investigator's opinion, exposed the subject to an unacceptable risk by study participation.

• If subject was a woman of childbearing potential (WOCBP), she must have had a negative urine pregnancy test (UPT) and agreed to use an effective form of birth control for the duration of the study (e.g., abstinence, stabilized on hormonal contraceptives for at least three months [oral, implant, injection, IUD, patch or NuvaRing] condom and spermicidal or diaphragm and spermicidal). Abstinence was an acceptable form of birth control for subjects who were not sexually active. Subjects who became sexually active during the trial had to agree to use an effective, non-prohibited form of birth control for the duration of the study.

Exclusion Criteria:

• Subject was pregnant, lactating, or planning to become pregnant during the study.

• Subjects had hyperkeratotic, hypertrophic or atypical AKs (e.g., AK > 1 cm2 in size) in the Treatment Area.

• Subject was enrolled in an investigational drug or device study during the study period.

• Subject was planning to be exposed to artificial tanning devices or excessive sunlight during the trial.

• Subject was immunosuppressed (e.g., HIV, systemic malignancy, graft vs. host disease, etc.).

• Subject had experienced an unsuccessful outcome from previous imiquimod therapy (An unsuccessful outcome was defined as after a reasonable therapeutic trial with no compliance issues, topical application did not work).

• Subject had used an investigational drug or investigational device within 30 days prior to the Baseline Visit.

• Subject had laser resurfacing, PUVA (Psoralen + ultraviolet A) therapy, UVB therapy, chemical peels or dermabrasion on the face or balding scalp within 6 months prior to the Baseline Visit.

• Subject had cryodestruction or chemodestruction, curettage, photodynamic therapy, surgical excision or other treatments for actinic keratosis on the face or scalp within one month prior to the Baseline Visit.

• Subject had used oral corticosteroid therapy, interferon, cytotoxic drugs, immunomodulators, immunosuppressive therapies or retinoids within one month prior to the Baseline Visit.

• Subject had used topical medications, corticosteroids, alpha hydroxy acids (e.g., glycolic acid, lactic acid etc. > 5%), beta hydroxy acid (salicylic acid > 2%), urea >5%, 5-fluorouracil, diclofenac, imiquimod or prescription retinoids (e.g., tazarotene, adapalene, tretinoin) to the face or balding scalp within one month prior to the Baseline Visit.

• Subject had used topical creams, lotions or gels of any kind to the selected Treatment Area within one day prior to the Baseline Visit.

• Subject had a basal cell or squamous cell carcinoma within the Treatment Area within one year of study enrollment.

• Subject had a history of sensitivity to any of the ingredients in the test articles.

• Subject had any skin pathology or condition (e.g., facial/scalp psoriasis, atopic dermatitis, acne, rosacea, etc.) that, in the investigator's opinion, could have interfered with the evaluation of the test article, worsened due to the treatment or required the use of interfering topical, systemic or surgical therapy.

• Subject had any condition which, in the investigator's opinion, would have made it unsafe or precluded the subject's ability to fully participate in the research study.

• Subject was known to be noncompliant or was unlikely to comply with the requirements of the study protocol (e.g., due to alcoholism, drug dependency, mental incapacity) in the opinion of the investigator.

Study Design

Allocation: Randomized, Endpoint Classification: Bio-equivalence Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Actinic Keratoses
• Keratosis
• Keratosis, Actinic

Intervention

Drug:
• imiquimod cream, 3.75%
Dosage form: Topical Cream Dosage: 3.75% Frequency: The assigned test article was to be applied once daily for two 2-week treatment cycles separated by a 2-week no treatment interval Duration of Treatment: Two 2-week treatment cycles separated by a 2-week no-treatment period and an 8-week follow-up period.
• Vehicle Cream
Dosage form: Topical Cream Dosage: Placebo Frequency: The assigned test article was to be applied once daily for two 2-week treatment cycles separated by a 2-week no treatment interval Duration of Treatment: Two 2-week treatment cycles separated by a 2-week no-treatment period and an 8-week follow-up period.
• imiquimod cream, 3.75%
Dosage form: Topical Cream Dosage: 3.75% Frequency: The assigned test article was to be applied once daily for two 2-week treatment cycles separated by a 2-week no treatment interval Duration of Treatment: Two 2-week treatment cycles separated by a 2-week no-treatment period and an 8-week follow-up period.

Locations

Country	Name	City	State
United States	Academic Dermatology Associates	Albuquerque	New Mexico
United States	Altman Dermatology Associates	Arlington Heights	Illinois
United States	DermResearch, Inc.	Austin	Texas
United States	Total Skin and Beauty Dermatology Center, PC	Birmingham	Alabama
United States	Northwest Clinical Trials	Boise	Idaho
United States	Dermatology, Laser & Vein Specialists of the Carolinas,	Charlotte	North Carolina
United States	Dermatology Research Center of Cincinnati	Cincinnati	Ohio
United States	Michigan Center for Research Corp.	Clinton Township	Michigan
United States	Deaconess Clinic, Inc.	Evansville	Indiana
United States	Philadelphia Institute of Dermatology	Fort Washington	Pennsylvania
United States	Minnesota Clinical Study Center	Fridley	Minnesota
United States	Suzanne Bruce and Associates, P.A.	Houston	Texas
United States	Dermatology Specialists	Louisville	Kentucky
United States	International Dermatology Research, Inc.	Miami	Florida
United States	MedaPhase, Inc.	Newnan	Georgia
United States	Skin Specialists, P.C.	Omaha	Nebraska
United States	Indiana Clinical Trials Center	Plainfield	Indiana
United States	Oregon Medical Research Center, PC	Portland	Oregon
United States	Dermatology Clinical Research Center of San Antonio	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Actavis Mid-Atlantic LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Complete clearance rate	Complete clearance rate (treatment success) was defined as the proportion of subjects in a treatment group with 100% clearance of all AK lesions within the Treatment Area. The primary efficacy endpoint was the proportion of subjects in the per-protocol (PP) population with treatment success at Week 14/EOS. All AKs (Baseline and new lesions), independent of size, within the Treatment Area were included in the AK lesion counts.	8 weeks post treatment period	No
Primary	Dosing Compliance	Measures of test article compliance included the total number of days of test article applications recorded on the CRFs and verified from the data in the subject diaries. Compliant subjects were defined as those who applied at least 75% and no more than 125% of the test article applications.	8 weeks post treatment period	Yes
Primary	Adverse Events	The severity and frequency of adverse events (AEs) were assessed in the three treatment groups.	14 weeks	Yes
Primary	Local Skin Reactions	The severity and frequency of local skin reactions (LSRs) were assessed in the three treatment groups.	14 weeks	Yes
Secondary	Partial Clearance Rate	Partial clearance rate was defined as the proportion of subjects in a treatment group with 75% or more reduction in the AK count in the Treatment Area at Week 14/EOS as compared to Baseline.	8 weeks post treatment	No
Secondary	Percent Change in the AK number	Percent change in the AK number as compared to Baseline at Week 14/EOS was a secondary outcome.	8 weeks post treatment	No