Actinic Keratosis
Conditions
Keywords
Actinic Keratosis
Brief summary
The primary objectives are to establish the therapeutic equivalence of imiquimod cream 5%, manufactured by Taro Pharmaceuticals Inc. and Aldara (imiquimod) cream, manufactured by 3M, and to show superiority over vehicle in the treatment of AK. The secondary objective is to compare the adverse event (AE) profiles of the two creams.
Interventions
DRUGImiquimod 5% manufactured by Taro
Treatment applied as a thin layer to target area once a day, 2 days each week, for 16 weeks
DRUGAldara - Imiquimod 5%
Treatment applied as a thin layer to target area once a day, 2 days each week, for 16 weeks
DRUGImiquimod Vehicle manufactured by Taro
Treatment applied as a thin layer to target area once daily, 2 days each week, for 16 weeks
Sponsors
Sun Pharmaceutical Industries, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients must have 4 to 8 clinically diagnosed, non-hyperkeratotic, non-hypertrophic AK lesions within a 25 cm2 contiguous treatment area on either the face or balding scalp * Women either must be 1 year post-menopausal, surgically sterile, or agree to use a medically accepted form or birth control * Free of any systemic or dermatological disorder * Any skin type or race, providing the skin pigmentation will allow discernment of erythema
Exclusion criteria
* Basal cell or squamous cell carcinoma, or other possible confounding skin conditions (on face and scalp) * History of cutaneous hyperreactivity or facial irritation to topical products * Engaging in activities involving excessive or prolonged exposure to sunlight * Receiving systemic cancer chemotherapy, psoralen plus UVA therapy, UVB therapy, laser abrasion, dermabrasion, glycolic acids, or chemical peels 6 months prior to study entry * Currently using or have used systemic steroids 2 months prior to study * Currently using or have used on the treatment area over-the-counter retinol products, corticosteroids, cryosurgery, curettage, 5-fluorouracil, or other topical actinic keratosis treatments 28 days prior to randomization * Pregnant or nursing mothers * History of allergy or sensitivity to imiquimod or related compounds or other components of the formulation * Taking immunosuppressant medication
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With 100% Clearance of Actinic Keratosis Lesions: Comparison of Taro Imiquimod 5% and Aldara-Imiquimod 5% | 24 weeks | Uses per protocol (PP) population. Each patient is assessed at 24 weeks. Actinic keratosis (AK) lesions that were identified and measured at baseline are reevaluated at the conclusion of the study. If all lesions that were identified at baseline are no longer present and there are no new lesions, the patient is 100% clear of AK lesions. |
| Number of Participants in Intention-to-treat (ITT)Population With 100% Clearance of Actinic Keratosis (AK) Lesions Identified at Baseline | 24 weeks | Uses ITT population. Three patients (1 Imiquimod 5% Taro and 2 Imiquimod Aldara) did not have a follow-up visit after dosing and were excluded from ITT. Three patients (2 Imiquimod 5% Taro and 1 Imiquimod Aldara) were not evaluable at the 24-week visit and were not in the analysis. Each patient is assessed at 24 weeks. Actinic keratosis (AK) lesions that were identified and measured at baseline are reevaluated at the conclusion of the study. If all lesions that were identified at baseline are no longer present and there are no new lesions, the patient is 100% clear of AK lesions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Patients Reporting at Least One Adverse Event | 24 weeks | For all patients who received a single dose, adverse events were collected at each follow-up visit. Any patient reporting a single or multiple adverse events at any visit was conisdered to have had at least one adverse event. |
Countries
United States
Participant flow
Recruitment details
Patients were recruited at 20 dermatology clinical practices.
Participants by arm
| Arm | Count |
|---|---|
| Imiquimod 5% Taro Imiquimod 5% manufactured by Taro applied for 16 weeks | 183 |
| Aldara - Imiquimod 5% Aldara, Imiquimod 5% applied for 16 weeks | 179 |
| Vehicle Patients receiving imiquimod Vehicle for 16 weeks | 60 |
| Total | 422 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Randomized | Withdrawal by Subject | 1 | 0 | 2 |
| Treated - Received at Least One Dose | Adverse Event | 11 | 8 | 1 |
| Treated - Received at Least One Dose | Lost to Follow-up | 1 | 5 | 1 |
| Treated - Received at Least One Dose | Protocol Violation | 9 | 5 | 3 |
| Treated - Received at Least One Dose | Withdrawal by Subject | 9 | 11 | 0 |
Baseline characteristics
| Characteristic | Imiquimod 5% Taro | Aldara - Imiquimod 5% | Vehicle | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 112 Participants | 106 Participants | 33 Participants | 251 Participants |
| Age, Categorical Between 18 and 65 years | 71 Participants | 73 Participants | 27 Participants | 171 Participants |
| Age, Continuous | 68.0 years STANDARD_DEVIATION 9.5 | 67.2 years STANDARD_DEVIATION 10.1 | 64.7 years STANDARD_DEVIATION 9.7 | 67.2 years STANDARD_DEVIATION 9.8 |
| Region of Enrollment United States | 183 participants | 179 participants | 60 participants | 422 participants |
| Sex: Female, Male Female | 34 Participants | 33 Participants | 8 Participants | 75 Participants |
| Sex: Female, Male Male | 149 Participants | 146 Participants | 52 Participants | 347 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 22 / 183 | 22 / 179 | 4 / 60 |
| serious Total, serious adverse events | 4 / 183 | 6 / 179 | 1 / 60 |
Outcome results
Primary
Number of Participants in Intention-to-treat (ITT)Population With 100% Clearance of Actinic Keratosis (AK) Lesions Identified at Baseline
Uses ITT population. Three patients (1 Imiquimod 5% Taro and 2 Imiquimod Aldara) did not have a follow-up visit after dosing and were excluded from ITT. Three patients (2 Imiquimod 5% Taro and 1 Imiquimod Aldara) were not evaluable at the 24-week visit and were not in the analysis. Each patient is assessed at 24 weeks. Actinic keratosis (AK) lesions that were identified and measured at baseline are reevaluated at the conclusion of the study. If all lesions that were identified at baseline are no longer present and there are no new lesions, the patient is 100% clear of AK lesions.
Time frame: 24 weeks
Population: Intention to Treat (ITT) Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Imiquimod 5% Taro | Number of Participants in Intention-to-treat (ITT)Population With 100% Clearance of Actinic Keratosis (AK) Lesions Identified at Baseline | 74 Participants |
| Aldara - Imiquimod 5% | Number of Participants in Intention-to-treat (ITT)Population With 100% Clearance of Actinic Keratosis (AK) Lesions Identified at Baseline | 64 Participants |
| Vehicle | Number of Participants in Intention-to-treat (ITT)Population With 100% Clearance of Actinic Keratosis (AK) Lesions Identified at Baseline | 6 Participants |
p-value: <0.0001Fisher Exact
p-value: <0.0001Fisher Exact
Primary
Number of Participants With 100% Clearance of Actinic Keratosis Lesions: Comparison of Taro Imiquimod 5% and Aldara-Imiquimod 5%
Uses per protocol (PP) population. Each patient is assessed at 24 weeks. Actinic keratosis (AK) lesions that were identified and measured at baseline are reevaluated at the conclusion of the study. If all lesions that were identified at baseline are no longer present and there are no new lesions, the patient is 100% clear of AK lesions.
Time frame: 24 weeks
Population: Per Protocol (PP) population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Imiquimod 5% Taro | Number of Participants With 100% Clearance of Actinic Keratosis Lesions: Comparison of Taro Imiquimod 5% and Aldara-Imiquimod 5% | 63 Participants |
| Aldara - Imiquimod 5% | Number of Participants With 100% Clearance of Actinic Keratosis Lesions: Comparison of Taro Imiquimod 5% and Aldara-Imiquimod 5% | 54 Participants |
90% CI: [-5.37, 15.08]
Secondary
Patients Reporting at Least One Adverse Event
For all patients who received a single dose, adverse events were collected at each follow-up visit. Any patient reporting a single or multiple adverse events at any visit was conisdered to have had at least one adverse event.
Time frame: 24 weeks
Population: Safety group includes all patients who received a single dose
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Imiquimod 5% Taro | Patients Reporting at Least One Adverse Event | 69 Participants |
| Aldara - Imiquimod 5% | Patients Reporting at Least One Adverse Event | 57 Participants |
| Vehicle | Patients Reporting at Least One Adverse Event | 15 Participants |