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.