Actinic Keratosis
Conditions
Brief summary
This study is to evaluate the efficacy and safety of a generic formulation of fluorouracil 0.5% cream against the brand product (Carac) in participants with actinic keratoses.
Detailed description
This is a multicenter, double-blind, vehicle-controlled, parallel group comparison study of a generic fluorouracil cream, 0.5% and Carac (fluorouracil) Cream, 0.5% in participants with actinic keratoses on the full face or balding scalp.
Interventions
DRUGGeneric Fluorouracil Cream
Topical cream, generic formulation of the brand product.
DRUGCarac® (Fluorouracil) Cream
Topical cream, brand product.
DRUGVehicle Cream
Topical cream, placebo. Has no active ingredient.
Sponsors
Actavis Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Participant is male and/or female, 18 years of age or older. * Participant is willing and able to give written informed consent. * Participant is willing and able to apply the test article(s) as directed, comply with study instructions and commit to all follow-up visits for the duration of the study. * Participant has a clinical diagnosis of actinic keratoses with at least 5 and no more than 10 clinically typical, visible or palpable, discrete, actinic keratoses (AK) lesions, each at least 4 millimeters (mm) in diameter on the face (excluding ears) or balding scalp. * Participant is in good general health and free of any disease state or physical condition that might impair evaluation of AK lesions or which, in the investigator's opinion, exposes the participant to an unacceptable risk by study participation. * Females must be post-menopausal, surgically sterile, or use an effective method of birth control with a negative urine pregnancy test (UPT) at the Baseline Visit.
Exclusion criteria
* Participant is pregnant, lactating, or is planning to become pregnant during the study. * Participant is currently enrolled in an investigational drug or device study. * Participant has used an investigational drug or investigational device treatment within 30 days prior to the Baseline Visit. * Participant has hyperkeratotic, hypertrophic, or large mat-like AK lesions (for example, an AK lesion \>1 cm\^2 in size) within the treatment area. * Participant has the need or plans to be exposed to artificial tanning devices or excessive sunlight during the study. * Participant is immunosuppressed (for example, human immunodeficiency virus (HIV), systemic malignancy, graft host disease) * Participant has experienced an unsuccessful outcome from previous topical fluorouracil therapy (an unsuccessful outcome is defined as after a reasonable therapeutic study with no compliance issues and the topical drug did not work). * Participant has a history of sensitivity to any of the ingredients in the test articles. * Participant has known dihydropyrimidine dehydrogenase (DPD) enzyme deficiency. * Participant used topical creams, lotions, or gels of any kind within the selected treatment area within 1 day prior to entry into the study. * Participant has used topical medications; corticosteroids, alpha hydroxy acids (for example, glycolic acid, lactic acid, etc. \>5%), beta hydroxy acid (salicylic acid \>2%), urea \>5%, 5-fluorouracil, diclofenac, imiquimod, ingenol mebutate; or prescription retinoids (for example, tazarotene, adapalene, tretinoin) within the selected treatment area (face or balding scalp) within 1 month prior to the Baseline Visit. * Participant has had cryodestruction, curettage, photodynamic therapy, surgical excision, or other treatments for AK within the selected treatment area (face or balding scalp) within 1 month prior to the Baseline Visit. * Participant has used oral corticosteroid therapy, interferon, cytotoxic drugs, immunomodulators, immunosuppressive therapies, or retinoids within 1 month prior to the Baseline Visit. * Participant has had dermatologic procedures or surgeries such as: laser resurfacing, Psoralen + ultraviolet A (PUVA) therapy, ultraviolet B therapy, chemical peels, or dermabrasion within the selected treatment area (face or balding scalp) within 6 months prior to the Baseline Visit. * Participant has lesions suspicious for skin cancer (skin cancer not ruled out by biopsy) or untreated skin cancers within the selected treatment area (face or balding scalp). * Participant has any skin pathology or condition on the face or balding scalp that, in the Investigator's opinion, could interfere with the evaluation of the test article or requires the use of interfering topical, systemic, or surgical therapy. * Participant has any condition which, in the Investigator's opinion, would make it unsafe or preclude the participant's ability to fully participate in this research study. * Participant is unable to communicate or cooperate with the Investigator due to language problems, poor mental development, impaired cerebral function, or physical limitations. * Participant is known to be noncompliant or is unlikely to comply with the requirements of the study protocol (for example, due to alcoholism, drug dependency, mental incapacity) in the opinion of the Investigator. * Participant has been previously enrolled in the same study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Treatment Success (Complete Clearance) at Week 6 | Week 6 | Percentage of participants with treatment success (complete clearance) at Week 6 (4 weeks after completion of 2 weeks of treatment). Complete clearance was defined as having no (zero) clinically visible actinic keratoses (AK) lesions in the treatment area at the Week 6/End Of Study visit. All AK lesions (baseline and new lesions) independent of size within the treatment area were treated and included in the efficacy lesion count. |
Countries
United States
Participant flow
Pre-assignment details
The populations for this study included the Safety Population, the Per-Protocol (PP) Population, and the modified Intent-to-Treat (mITT) population.
Participants by arm
| Arm | Count |
|---|---|
| Generic Fluorouracil Cream Participants applied up to 1 gram of generic fluorouracil 0.5% topical cream once daily for 2 weeks as a thin film to the skin of the treatment area and rub until the cream was no longer visible. Participants were instructed to apply the study drug 10 minutes after thoroughly washing, rinsing, and drying the entire treatment area and 1 to 2 hours before bedtime. Study drug was to have been left on the skin for approximately 8 hours and then removed by washing the area with mild soap and water. Treatment should have continued for the full treatment course even if the actinic keratoses lesions appeared to be gone. | 140 |
| Carac (Fluorouracil) Cream Participants applied up to 1 gram of Carac (fluorouracil) 0.5% topical cream once daily for 2 weeks as a thin film to the skin of the treatment area and rub until the cream was no longer visible. Participants were instructed to apply the study drug 10 minutes after thoroughly washing, rinsing, and drying the entire treatment area and 1 to 2 hours before bedtime. Study drug was to have been left on the skin for approximately 8 hours and then removed by washing the area with mild soap and water. Treatment should have continued for the full treatment course even if the actinic keratoses lesions appeared to be gone. | 140 |
| Vehicle Cream Participants applied up to 1 gram of vehicle topical cream once daily for 2 weeks as a thin film to the skin of the treatment area and rub until the cream was no longer visible. Participants were instructed to apply the study drug 10 minutes after thoroughly washing, rinsing, and drying the entire treatment area and 1 to 2 hours before bedtime. Study drug was to have been left on the skin for approximately 8 hours and then removed by washing the area with mild soap and water. Treatment should have continued for the full treatment course even if the actinic keratoses lesions appeared to be gone. | 142 |
| Total | 422 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 0 | 2 |
| Overall Study | Death | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 1 | 0 | 1 |
| Overall Study | Non-Compliance with Test Article | 1 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 4 | 4 | 3 |
Baseline characteristics
| Characteristic | Total | Generic Fluorouracil Cream | Carac (Fluorouracil) Cream | Vehicle Cream |
|---|---|---|---|---|
| Age, Continuous | 67.4 years STANDARD_DEVIATION 10.02 | 67.7 years STANDARD_DEVIATION 9.46 | 67.4 years STANDARD_DEVIATION 9.43 | 67.1 years STANDARD_DEVIATION 11.13 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 1 Participants | 2 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 418 Participants | 139 Participants | 138 Participants | 141 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 419 Participants | 138 Participants | 140 Participants | 141 Participants |
| Sex: Female, Male Female | 54 Participants | 16 Participants | 18 Participants | 20 Participants |
| Sex: Female, Male Male | 368 Participants | 124 Participants | 122 Participants | 122 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 140 | 0 / 140 | 0 / 142 |
| other Total, other adverse events | 21 / 140 | 13 / 140 | 9 / 142 |
| serious Total, serious adverse events | 4 / 140 | 1 / 140 | 2 / 142 |
Outcome results
Primary
Percentage of Participants With Treatment Success (Complete Clearance) at Week 6
Percentage of participants with treatment success (complete clearance) at Week 6 (4 weeks after completion of 2 weeks of treatment). Complete clearance was defined as having no (zero) clinically visible actinic keratoses (AK) lesions in the treatment area at the Week 6/End Of Study visit. All AK lesions (baseline and new lesions) independent of size within the treatment area were treated and included in the efficacy lesion count.
Time frame: Week 6
Population: Participants in mlTT population who met inclusion/exclusion criteria, applied 75%-125% applications of study drug, did not miss applications for more than 3 consecutive days, no evidence of dosing noncompliance, and completed evaluation at Week 6 within ±4 days with no protocol violations that would affect treatment evaluation (PP Population).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Generic Fluorouracil Cream | Percentage of Participants With Treatment Success (Complete Clearance) at Week 6 | 33.9 percentage of participants |
| Carac (Fluorouracil) Cream | Percentage of Participants With Treatment Success (Complete Clearance) at Week 6 | 33.9 percentage of participants |
| Vehicle Cream | Percentage of Participants With Treatment Success (Complete Clearance) at Week 6 | 3.3 percentage of participants |
90% CI: [-11.03, 11.11]
p-value: <0.0001Fisher Exact
p-value: <0.0001Fisher Exact