Actinic Keratosis
Conditions
Brief summary
To determine the comparability of the safety and efficacy of Imiquimod Cream, 3.75% and Zyclara (imiquimod) Cream, 3.75% (the reference listed drug) in subjects with actinic keratosis (AK) of the face or balding scalp. It will also be determined whether the efficacy of each of the two active treatments is superior to that of the Vehicle cream.
Interventions
Sponsors
Teva Pharmaceuticals USA
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Willing and able to provide written informed consent for the study * At least 18 years of age. * Immunocompetent male or non-pregnant and non-lactating female. Each female subject of childbearing potential (excluding women who are surgically sterilized or postmenopausal for at least 2 years), in addition to having a negative urine pregnancy test at Visit 1/Day 1, must be willing to use an acceptable form of birth control during the study. For the purpose of this study, the following are considered acceptable methods of birth control: oral contraceptives, contraceptive patches, contraceptive implant, vaginal contraceptive, double-barrier methods (for example, condom and spermicide), contraceptive injection (Depo-Provera®), intrauterine device (IUD), hormonal IUD (Mirena®), and abstinence with a documented second acceptable method of birth control if the subject becomes sexually active. Subjects entering the study who are on hormonal contraceptives (oral contraceptives, patches and injection) must have been on this method for at least 3 months (90 days) prior to the study and continue the method for the duration of the study. Subjects who had used hormonal contraception (oral contraceptives, patches and injection) and stopped must have stopped no less than 3 months (90 days) prior to baseline. Subjects entering the study using contraceptive implants and intrauterine contraceptives must have been on this method for at least 6 months (180 days) and continue for the duration of the study and if they stopped must have stopped no less than 6 months (180 days) prior to baseline. * Clinical diagnosis of AK, defined as ≥ 5 and ≤ 20 clinically typical, visible or palpable AK lesions, each at least 4 mm in diameter, in an area that exceeds 25 cm2 on either the face (excluding ears) or balding scalp, but not both face and scalp. * In general good health and free from any clinically significant disease, other than AK, that might interfere with the study evaluations. * Willing and able to understand and comply with the requirements of the study, apply the IP as instructed, attend the required visits, comply with therapy prohibitions, and be able to complete the study.
Exclusion criteria
* Presence of atopic dermatitis, basal cell carcinoma, eczema, psoriasis, rosacea, squamous cell carcinoma, or other possible confounding skin conditions on the treatment area of either the face or balding scalp. * Clinically significant systemic disease (immunological deficiencies), unstable medical disorder, life-threatening disease, or current malignancies. * Use on the face or balding scalp of chemical peel, dermabrasion, laser abrasion, psoralen plus ultraviolet A (PUVA) therapy, and/or ultraviolet B (UVB) therapy in the last 6 months (180 days) * Use of any systemic cancer chemotherapy medications in the last 6 months (180 days) * Use on the face or balding scalp of cryodestruction or chemodestruction, curettage, photodynamic therapy, surgical excision, topical 5-fluorouracil, topical corticosteroids, topical diclofenac, topical imiquimod, topical retinoids, masoprocol, or other treatments for AK in the last 1 month (30 days) * Immunomodulators or immunosuppressive therapies, interferon, oral/systemic corticosteroids, or cytotoxic drugs in the last 1 month (30 days). Intranasal or inhaled corticosteroids are acceptable if kept constant throughout the study. * Need or intent to continue to use any treatment listed in the four points above during the current study * Known hypersensitivity or allergies to imiquimod or any component of the IP (in any dosage form). * Females who are pregnant, breastfeeding, intending to become pregnant during the study, or who do not agree to use an acceptable form of birth control during the study. * Any clinically significant condition or situation other than the condition being studied that, in the opinion of the investigator, would interfere with the study evaluations or optimal participation in the study. * Use of any investigational drug or investigational device within 1 month (30 days) prior to randomization. * Previous participation in this study. * Sunburn in the designated treatment area to be treated at study entry. * Current involvement in activities that require excessive or prolonged sun exposure. * Consumption of excessive amounts of alcohol, abuse drugs.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment Success/Failure at Visit 5/Week 14 | 14 Weeks | The primary efficacy endpoint is the proportion of subjects with treatment success at Visit 5/Week 14 (8 weeks post-treatment). Treatment success is defined as 100% clearance of all AK lesions (baseline AK lesions and any new AK lesions) within the treatment area. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Investigational Test Product Imiquimod Cream, 3.75% (Teva) | 247 |
| Reference Listed Drug Zyclara® (imiquimod Cream), 3.75% (Medicis) | 249 |
| Vehicle Vehicle of Test Product (Teva) | 80 |
| Total | 576 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 12 | 11 | 0 |
| Overall Study | Drug Code Unblinded | 0 | 1 | 0 |
| Overall Study | IP Non-compliance | 5 | 5 | 0 |
| Overall Study | Lack of Efficacy | 0 | 0 | 1 |
| Overall Study | Lost to Follow-up | 7 | 6 | 5 |
| Overall Study | Protocol Violation | 6 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 11 | 11 | 3 |
Baseline characteristics
| Characteristic | Investigational Test Product | Total | Vehicle | Reference Listed Drug |
|---|---|---|---|---|
| Age, Continuous | 67.8 years STANDARD_DEVIATION 9.12 | 68.3 years STANDARD_DEVIATION 9.57 | 68.7 years STANDARD_DEVIATION 10.23 | 68.6 years STANDARD_DEVIATION 9.79 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 10 Participants | 24 Participants | 2 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 237 Participants | 552 Participants | 78 Participants | 237 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Location of Lesion Face | 132 Participants | 291 Participants | 45 Participants | 114 Participants |
| Location of Lesion Scalp | 115 Participants | 285 Participants | 35 Participants | 135 Participants |
| Number of Visible or Palpable Lesions | 10.6 lesions STANDARD_DEVIATION 3.98 | 10.7 lesions STANDARD_DEVIATION 4.11 | 11.0 lesions STANDARD_DEVIATION 4.35 | 10.7 lesions STANDARD_DEVIATION 4.16 |
| 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 | 0 Participants | 0 Participants | 0 Participants | 0 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 | 246 Participants | 575 Participants | 80 Participants | 249 Participants |
| Sex: Female, Male Female | 44 Participants | 84 Participants | 13 Participants | 27 Participants |
| Sex: Female, Male Male | 203 Participants | 492 Participants | 67 Participants | 222 Participants |
| Size (cm^2) of Lesion | 317.5 cm2 STANDARD_DEVIATION 178.53 | 315 cm2 STANDARD_DEVIATION 180.2 | 335.7 cm2 STANDARD_DEVIATION 183.78 | 305.8 cm2 STANDARD_DEVIATION 180.78 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 247 | 0 / 249 | 0 / 80 |
| other Total, other adverse events | 81 / 247 | 77 / 249 | 16 / 80 |
| serious Total, serious adverse events | 6 / 247 | 8 / 249 | 1 / 80 |
Outcome results
Primary
Number of Participants With Treatment Success/Failure at Visit 5/Week 14
The primary efficacy endpoint is the proportion of subjects with treatment success at Visit 5/Week 14 (8 weeks post-treatment). Treatment success is defined as 100% clearance of all AK lesions (baseline AK lesions and any new AK lesions) within the treatment area.
Time frame: 14 Weeks
Population: Per-Protocol Population
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Investigational Test Product | Number of Participants With Treatment Success/Failure at Visit 5/Week 14 | Success (100% clearance of AK lesions) | 42 Participants |
| Investigational Test Product | Number of Participants With Treatment Success/Failure at Visit 5/Week 14 | Failure <100% clearance of AK lesions | 136 Participants |
| Reference Listed Drug | Number of Participants With Treatment Success/Failure at Visit 5/Week 14 | Success (100% clearance of AK lesions) | 40 Participants |
| Reference Listed Drug | Number of Participants With Treatment Success/Failure at Visit 5/Week 14 | Failure <100% clearance of AK lesions | 139 Participants |
| Vehicle | Number of Participants With Treatment Success/Failure at Visit 5/Week 14 | Success (100% clearance of AK lesions) | 6 Participants |
| Vehicle | Number of Participants With Treatment Success/Failure at Visit 5/Week 14 | Failure <100% clearance of AK lesions | 58 Participants |
90% CI: [-0.0663, 0.0913]