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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


Phase 3
18 Years
N/A
Not Enrolling
Both
Actinic Keratoses

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Trial Information

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


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.


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.

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Primary - Proportion of subjects in each treatment group with Complete Clearance of AK lesions.

Outcome Time Frame:

8-weeks post-treatment (Week 24, Test-of-Cure/TOC) visit.

Safety Issue:

No

Principal Investigator

Christine M. Winslow, Ph.D.

Investigator Role:

Study Director

Investigator Affiliation:

Actavis Mid-Atlantic LLC

Authority:

United States: Institutional Review Board

Study ID:

D94-3101-07

NCT ID:

NCT00948428

Start Date:

May 2008

Completion Date:

April 2009

Related Keywords:

  • Actinic Keratoses
  • actinic keratoses
  • imiquimod
  • therapeutic equivalence
  • bioequivalence
  • Keratosis
  • Keratosis, Actinic

Name

Location

Mt. Sinai School of MedicineNew York, New York  10029
Cherry Creek Research, Inc.Denver, Colorado  80246
Minnesota Clinical Study CenterFridley, Minnesota  55432
Oregon Medical Research Center, P.C.Portland, Oregon  97223
Tennessee Clinical Research CenterNashville, Tennessee  37221
Associates In Research, Inc.Fresno, California  93720
University Dermatology Consultants, Inc.Cincinnati, Ohio  45242
Dermatology Clinical Research Center of San AntonioSan Antonio, Texas  78229
Burke Pharmaceutical ResearchHot Springs, Arkansas  71913
DermResearch, Inc.Austin, Texas  78759
Derm Research Center of New York, Inc.Stony Brook, New York  11790
Premier Clinical ResearchSpokane, Washington  99204
Skin Surgery Medical Group, Inc.San Diego, California  92108
Deaconess Clinic, Inc.Evansville, Indiana  47713
FXM Research Corp.Miami, Florida  
MedaPhase, Inc.Newman, Georgia  30263
Dermatology Research Center, Inc.Salt Lake City, Utah  84124
Rhode Island Hospital, Dermatopharmacology DivisionProvidence, Rhode Island  02903
Dermatology Associates of Knoxville, P.C.Knoxville, Tennessee  37917
Suzanne Bruce & Associates, P.A.Houston, Texas  77056