Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Bioequivalence of Generic Imiquimod Cream, 5% When Compared to Aldara™ (Imiquimod) Cream, 5% in the Treatment of Actinic Keratosis

This study has been completed.
Sponsor:
Information provided by:
Actavis Inc.
ClinicalTrials.gov Identifier:
NCT00948428
First received: July 28, 2009
Last updated: August 13, 2010
Last verified: August 2010
  Purpose

At the end of the study, safety and efficacy outcome measures will be compared to determine a) if dosing with Generic Imiquimod cream, 5% is therapeutically equivalent to the currently marketed Aldara (imiquimod) cream, 5% and b) if both imiquimod 5% creams are superior in comparison to the Vehicle cream.


Condition Intervention Phase
Actinic Keratoses
Drug: imiquimod
Drug: Aldara™
Drug: Vehicle Cream
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Bio-equivalence Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multicenter, Double-Blind, Randomized, Parallel Group, Vehicle-Controlled Study to Determine the Clinical Equivalence of a Generic Imiquimod Cream, 5% and Aldara™ Cream in Subjects With Actinic Keratosis

Resource links provided by NLM:


Further study details as provided by Actavis Inc.:

Primary Outcome Measures:
  • Primary - Proportion of subjects in each treatment group with Complete Clearance of AK lesions. [ Time Frame: 8-weeks post-treatment (Week 24, Test-of-Cure/TOC) visit. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • The Partial Clearance rates, defined as the proportion of subjects with at least a 75% reduction in the number of AK lesions counted at Baseline and the proportion of subjects with Complete Clearance of AK lesions. [ Time Frame: Week 16, EOT, Week 24, TOC ] [ Designated as safety issue: No ]

Enrollment: 462
Study Start Date: May 2008
Study Completion Date: April 2009
Primary Completion Date: March 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Generic Imiquimod
imiquimod cream, 5%
Drug: imiquimod
5% topical cream dispensed in individual 0.25 g sachets applied twice a week for 16 weeks
Active Comparator: Aldara™
Aldara™ (imiquimod) cream, 5%
Drug: Aldara™
5% topical cream dispensed in individual 0.25 g sachets applied twice a week for 16 weeks
Placebo Comparator: Vehicle cream
Vehicle cream (Actavis)
Drug: Vehicle Cream
Topical cream vehicle matching Generic imiquimod dispensed in individual 0.25 g sachets applied twice a week for 16 weeks

Detailed Description:

A nationwide, multicenter, double-blind, vehicle-controlled parallel group comparison study of a Generic Imiquimod cream, 5% (Actavis Mid-Atlantic LLC) and currently marketed Aldara (imiquimod) cream, 5% (distributed by Graceway Pharmaceuticals, LLC) was conducted in subjects with actinic keratoses (AKs) on the face and/or anterior scalp in order to evaluate the therapeutic equivalence of these two active treatments and to establish superiority of the efficacy of these two products over a Vehicle cream. Subjects were randomized to one of three treatment groups on a 2:2:1 basis as follows: (1) Generic Imiquimod cream, 5%, (2) Aldara (imiquimod) cream, 5%, and (3) Vehicle cream. The duration of treatment was 16 weeks (± 7 days).

The primary efficacy endpoint was the proportion of subjects in each treatment group with Complete Clearance (having no clinically visible actinic keratosis lesions in the 25 cm2 contiguous treatment area at the 8-week post-treatment visit) of AK lesions. The secondary efficacy endpoints were the Partial Clearance rates, defined as the proportion of subjects with at least a 75% reduction in the number of AK lesions counted at Baseline at the end-of-treatment visit (Week 16, EOT) and at the 8 weeks post-treatment visit/test-of-cure (Week 24, TOC), and the proportion of subjects with Complete Clearance of AK lesions at the end-of-treatment (Week 16, EOT) visit.

A 90% Wald's confidence interval with Yate's continuity correction was constructed around the difference between the proportions of subjects with Complete Clearance of AK lesions in the active treatments (Generic Imiquimod minus Aldara) to evaluate therapeutic equivalence in the primary efficacy analyses. Two-sided, continuity-corrected statistics were used to evaluate the superiority of each active treatment's Complete Clearance rate over that of the Vehicle treatment. The therapeutic comparability evaluations in the per-protocol (PP) population were considered primary while those in the intent-to-treat (ITT) population were considered supportive. The superiority comparisons in the ITT population were considered primary while those in the PP population were considered supportive. If the 90% confidence interval (CI) around the difference between the Generic Imiquimod and Aldara Complete Clearance rates in the PP population were contained within the interval 0.20 to +0.20, and each of these rates was greater than, and statistically different (p<0.05) from, the Vehicle rate in the ITT population, then Generic Imiquimod and Aldara were considered to be therapeutically equivalent.

Secondary efficacy analyses were conducted on the proportion of subjects in each treatment group with Complete Clearance of AK lesions at the Week 16, EOT visit as well as evaluation of the Partial Clearance of AK lesions at both the EOT and TOC visits. The results at both the EOT visit (Week 16) and those at 8 weeks post-treatment (Week 24, TOC) were statistically analyzed by the same methods described for the primary efficacy variable.

Both EOT and TOC analyses were conducted in the ITT population. The TOC analysis was conducted in the PP population and the EOT analysis was conducted in the EOT PP population.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects were male or non-pregnant females, 18 years of age or older, in generally good health. Females who were post-menopausal, surgically sterile or using a medically acceptable form of birth control with a negative urine pregnancy test at the Baseline visit.
  • Subjects provided written and verbal informed consent.
  • Subjects presented to the clinic with at least 4 but no more than 12 visible, discrete nonhyperkeratotic, nonhypertrophic actinic keratosis lesions within a 25 cm2 Treatment Area on the face and/or anterior scalp.
  • Subjects were willing and able to comply with study instructions and return to the clinic for required visits.

Exclusion Criteria:

  • Subjects who were lactating, or planning to become pregnant during the study.
  • Subjects had hyperkeratotic, hypertrophic or large mat-like AKs within the 25 cm2 Treatment Area.
  • Subjects who had the need or were planning to be exposed to artificial tanning devices or excessive sunlight during the trial.
  • Subjects who were immunosuppressed (e.g., HIV, systemic malignancy, graft vs. host disease, etc.).
  • Subjects who experienced an unsuccessful outcome from previous imiquimod therapy.
  • Subjects with known hypersensitivity or previous allergic reaction to any of the active or inactive components of the study drugs.
  • Within 2 months: Facial and/or Anterior Scalp: laser resurfacing, photodynamic therapy, chemical peels, dermabrasion, topical application of 5-FU, imiquimod, diclofenac sodium or other treatments for AK or photodamage.
  • Subjects who used the following systemic, oral or topical therapies for the periods specified prior to entry into the study:

Within 2 days: Topicals of any kind to the selected Treatment Area. Within 2 weeks: Facial topical medications: corticosteroids, alpha- hydroxyacids (e.g., glycolic acid, lactic acid, etc. greater than 5%), beta-hydroxyacid (salicylic acid greater than 2%), urea - greater than 5% or prescription retinoids (e.g., tazarotene, adapalene, tretinoin) to the face and/or anterior scalp.

Within 2 weeks: Cryotherapy to lesions adjacent to or within the 25 cm2 Treatment Area.

Within 4 weeks: Systemic steroid therapy: chemotherapeutic agents, psoralens, immunotherapy, or retinoids.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00948428

Locations
United States, Arkansas
Burke Pharmaceutical Research
Hot Springs, Arkansas, United States, 71913
United States, California
Associates in Research, Inc.
Fresno, California, United States, 93720
Skin Surgery Medical Group, Inc.
San Diego, California, United States, 92117
United States, Colorado
Cherry Creek Research, Inc.
Denver, Colorado, United States, 80209
United States, Florida
FXM Research Corp.
Miami, Florida, United States, 33175
United States, Georgia
MedaPhase, Inc.
Newnan, Georgia, United States, 30263
United States, Indiana
Deaconess Clinic, Inc.
Evansville, Indiana, United States, 47713
United States, Minnesota
Minnesota Clinical Study Center
Fridley, Minnesota, United States, 55432
United States, New York
Mt. Sinai School of Medicine
New York, New York, United States, 10029
Derm Research Center of New York, Inc.
Stony Brook, New York, United States, 11790
United States, Ohio
University Dermatology Consultants, Inc.
Cincinnati, Ohio, United States, 45219
United States, Oregon
Oregon Medical Research Center, P.C.
Portland, Oregon, United States, 97223
United States, Rhode Island
Rhode Island Hospital, Dermatopharmacology Division
Providence, Rhode Island, United States, 02903
United States, Tennessee
Dermatology Associates of Knoxville, P.C.
Knoxville, Tennessee, United States, 37917
Tennessee Clinical Research Center
Nashville, Tennessee, United States, 37215
United States, Texas
DermResearch, Inc.
Austin, Texas, United States, 78759
Suzanne Bruce & Associates, P.A.
Houston, Texas, United States, 77056
Dermatology Clinical Research Center of San Antonio
San Antonio, Texas, United States, 78229
United States, Utah
Dermatology Research Center, Inc.
Salt Lake City, Utah, United States, 84124
United States, Washington
Premier Clinical Research
Spokane, Washington, United States, 99204
Sponsors and Collaborators
Actavis Mid-Atlantic LLC
Investigators
Study Director: Christine M. Winslow, Ph.D. Actavis Mid-Atlantic LLC
  More Information

No publications provided

Responsible Party: Christine Winslow, Director of Clinical Development, Actavis Mid-Atlantic LLC
ClinicalTrials.gov Identifier: NCT00948428     History of Changes
Other Study ID Numbers: D94-3101-07
Study First Received: July 28, 2009
Last Updated: August 13, 2010
Health Authority: United States: Institutional Review Board

Keywords provided by Actavis Inc.:
actinic keratoses
imiquimod
therapeutic equivalence
bioequivalence

Additional relevant MeSH terms:
Keratosis
Keratosis, Actinic
Neoplasms
Precancerous Conditions
Skin Diseases
Imiquimod
Adjuvants, Immunologic
Antineoplastic Agents
Immunologic Factors
Interferon Inducers
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014