Actinic Keratosis
Conditions
Keywords
solar keratoses
Brief summary
This research study is being done to compare the safety and effectiveness of GDC 695 (test drug) against the currently marketed reference drug (diclofenac sodium gel, 3%) and to establish that these two drugs work better than placebo in the treatment of actinic keratosis.
Interventions
DRUGGDC 695
GDC 695 is a topical gel.
DRUGDiclofenac Sodium Gel, 3%
Diclofenac sodium gel, 3% is an FDA-approved drug.
DRUGVehicle gel
Vehicle topical gel contains 0.0% of active drug and is color matched to the other two active test drugs.
Sponsors
Balmoral Medical company
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
* Has provided written informed consent. * Immunocompetent male and/or non-pregnant female, 18 years of age or older. * 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. * Clinical diagnosis of actinic keratosis. * In good general health and free of any disease state or physical condition. * Women, 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 (Day 1).
Exclusion criteria
* Women who are pregnant, breastfeeding, or are planning to become pregnant or breastfeed during the study. * Is currently enrolled in another investigational drug or device study or has used an investigational drug or investigational device within 30 days prior to the Baseline Visit (Day 1). * Has the need or plans to be exposed to artificial tanning devices or excessive sunlight during the study. * Is immunosuppressed (e.g., human immunodeficiency virus \[ HIV\], systemic malignancy, graft host disease, etc.) or is taking medications that suppress the immune system. * Has experienced an unsuccessful outcome from previous topical diclofenac sodium therapy. * Has a history of sensitivity to any of the ingredients in the test articles or other excipients in the test or reference drug. * Has signs or symptoms consistent with the aspirin (ASA) triad. * Has used topical medications: corticosteroids, alpha hydroxy acids (e.g., glycolic acid, lactic acid, etc. \>5%), beta hydroxy acid (salicylic acid \>2%), urea \>2%, 5-fluorouracil, diclofenac, imiquimod, ingenol mebutate, aminolevulinic acid (ALA) or prescription retinoids (e.g., tazarotene, adapalene, tretinoin), over-the-counter (OTC) products labeled as scrubs of any kind which are used to smooth the skin (as they contain some form of exfoliant such as nut shells, coffee grounds, polymer particles, etc.) within the selected treatment area (face or bald scalp) within one month prior to the Baseline Visit. * Has had cryodestruction or chemodestruction, curettage, photodynamic therapy (PDT), surgical excision, or other treatments for AK within the selected treatment area (face or bald scalp) within one month prior to the Baseline Visit. * Has used oral corticosteroid therapy, interferon, cytotoxic drugs, immunomodulators, immunosuppressive therapies, or retinoids within one month prior to the Baseline Visit. * Has used oral isotretinoin within six months prior to the Baseline Visit. * Has used chemical peels, including but not limited to alphahydroxy acid, betahydroxy acid, bichloroacetic acid, trichloroacetic acid, and phenol within the selected treatment area (face or bald scalp) within six months prior to the Baseline Visit. * Has had dermatologic procedures or surgeries such as: laser resurfacing, PUVA (Psoralen + ultraviolet A) therapy, ultraviolet B (UVB) therapy, ALA-PDT, or dermabrasion within the selected treatment area (face or bald scalp) within six months prior to the Baseline Visit. * Has lesions suspicious for skin cancer (skin cancer not ruled out by biopsy) or untreated skin cancers within the selected treatment area (face or bald scalp). * Has active gastrointestinal ulceration or bleeding or has a history of gastrointestinal bleeds due to use of aspirin or other NSAIDs. * Has severe renal or hepatic impairment. * Has any condition which, in the investigator's opinion, could interfere with the evaluation of the test drugs or that could make it unsafe or preclude the subject's ability to fully participate in this research study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Complete Clearance of AK Lesions | Day 90 (30 days after completion of 60 days of treatment) | Complete Clearance was defined as 100% clearance of all Actinic Keratosis (AK) lesions (having a count of zero AKs) in the treatment area (face or bald scalp) at the Day 90 visit (30 Days Post Treatment). |
Other
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events (AEs) | Day 0 through Day 90 | AEs will be assessed by the investigator and the incidence (severity and causality) of any local and systemic AEs will be reported. |
Countries
United States
Participant flow
Recruitment details
Recruitment Period: October 2016 to July 2017 The location of clinical sites included dermatology clinics and clinical research centers.
Pre-assignment details
All subjects who met the entry criteria and were randomized and enrolled into the study.
Participants by arm
| Arm | Count |
|---|---|
| GDC 695 Gel GDC 695 gel applied topically as directed.
GDC 695: GDC 695 is a topical gel. | 218 |
| Diclofenac Sodium Gel Diclofenac sodium gel, 3% applied topically as directed.
Diclofenac Sodium Gel, 3%: Diclofenac sodium gel, 3% is an FDA-approved drug. | 220 |
| Placebo Vehicle gel applied topically as directed.
Vehicle gel: Vehicle topical gel contains 0.0% of active drug and is color matched to the other two active test drugs. | 223 |
| Total | 661 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 8 | 8 | 3 |
| Overall Study | Lost to Follow-up | 3 | 2 | 2 |
| Overall Study | Non-compliance with study drug | 1 | 1 | 2 |
| Overall Study | Withdrawal by Subject | 10 | 8 | 8 |
Baseline characteristics
| Characteristic | GDC 695 Gel | Diclofenac Sodium Gel | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 70.2 years STANDARD_DEVIATION 9.4 | 69.6 years STANDARD_DEVIATION 9.8 | 69.1 years STANDARD_DEVIATION 9.3 | 69.6 years STANDARD_DEVIATION 9.5 |
| Race/Ethnicity, Customized Ethnicity Hispanic or Latino | 14 Participants | 13 Participants | 16 Participants | 43 Participants |
| Race/Ethnicity, Customized Ethnicity Not Hispanic or Latino | 204 Participants | 207 Participants | 207 Participants | 618 Participants |
| Race/Ethnicity, Customized Race American Indian or Alaska Native | 1 Participants | 2 Participants | 1 Participants | 4 Participants |
| Race/Ethnicity, Customized Race White | 217 Participants | 218 Participants | 222 Participants | 657 Participants |
| Region of Enrollment United States | 218 participants | 220 participants | 223 participants | 661 participants |
| Sex: Female, Male Female | 31 Participants | 45 Participants | 36 Participants | 112 Participants |
| Sex: Female, Male Male | 187 Participants | 175 Participants | 187 Participants | 549 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 218 | 0 / 220 | 0 / 223 |
| other Total, other adverse events | 19 / 218 | 14 / 220 | 6 / 223 |
| serious Total, serious adverse events | 1 / 218 | 3 / 220 | 5 / 223 |
Outcome results
Primary
Number of Subjects With Complete Clearance of AK Lesions
Complete Clearance was defined as 100% clearance of all Actinic Keratosis (AK) lesions (having a count of zero AKs) in the treatment area (face or bald scalp) at the Day 90 visit (30 Days Post Treatment).
Time frame: Day 90 (30 days after completion of 60 days of treatment)
Population: Analysis shown is based on the modified Intent-to-Treat (mITT) population, defined as all randomized subjects who met the following requirements, 1) met all inclusion/exclusion criteria; 2) applied at least one dose of test article; 3) and returned for at least one post-baseline evaluation clinic visit (Visits 3, 5, or 6).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GDC 695 Gel | Number of Subjects With Complete Clearance of AK Lesions | 30.2 percentage of participants |
| Diclofenac Sodium Gel | Number of Subjects With Complete Clearance of AK Lesions | 25.7 percentage of participants |
| Placebo | Number of Subjects With Complete Clearance of AK Lesions | 9.5 percentage of participants |
Comparison: Two-sided, continuity-corrected Chi-square tests was used to evaluate the superiority of GDC 695 gel's complete clearance proportion over that of the Vehicle treatment in the mITT population using LOCF.p-value: <0.0001Chi-squared, Corrected
Comparison: Two-sided, continuity-corrected Chi-square tests was used to evaluate the superiority of Diclofenac sodium gel's complete clearance proportion over that of the Vehicle treatment in the mITT population using LOCF.p-value: <0.0001Chi-squared, Corrected
Other Pre-specified
Adverse Events (AEs)
AEs will be assessed by the investigator and the incidence (severity and causality) of any local and systemic AEs will be reported.
Time frame: Day 0 through Day 90