Actinic Keratosis
Conditions
Brief summary
To compare the relative efficacy and safety of the test formulation diclofenac sodium gel 3% (Actavis) to the marketed formulation Solaraze® (diclofenac sodium) Gel 3% (Fougera Pharms) in the treatment of the actinic keratosis
Interventions
DRUGDiclofenac sodium
Topical administration of approximately 0.5g twice daily to the 25 sq cm treatment area for 60 days.
OTHERPlacebo
Topical administration of approximately 0.5g twice daily to the 25 sq cm treatment area for 60 days.
Sponsors
Actavis Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Signed informed consent form, which meets all criteria of current FDA and HIPAA regulations. 2. Immunocompetent male or non-pregnant, non-lactating female at least 18 years of age. 3. Diagnosis of AK with ≥ 5 and \< 10 clinically typical, visible, discrete, nonhyperkeratotic, nonhypertrophic AK lesions each at least 4 mm in diameter on the face and/or bald scalp contained within a 25cm2 treatment area. 4. Women either must be 1 year post-menopausal (no menstrual periods for at least 12 months), surgically sterile, or if they are of child-bearing potential, they must: 1. Have been using systemic birth control, IUD, or Norplant for at least 28 days prior to the start of treatment period of the study, or used barrier methods such as diaphragm plus spermicide or condom plus spermicide consistently, at least 14 days before study gel administration. 2. Had a normal menstrual cycle for the month prior to the start of treatment. 3. Have a negative urine pregnancy test result upon entry into the study. 4. Agree to use a medically accepted form of birth control (oral, implant, injectable or transdermal contraceptives, intrauterine device, condom plus spermicide, diaphragm plus spermicide) or practice abstinence throughout the study period. 5. Free from any systemic or dermatologic disorder that, in the opinion of the Investigator, will interfere with the study results or increase the risk of AEs. 6. Any skin type or race, providing the skin pigmentation will allow discernment of erythema. 7. Willingness and capability to cooperate to the extent and degree required by the protocol.
Exclusion criteria
1. Active gastrointestinal ulceration or bleeding. 2. Current or history of severe renal or hepatic impairment. 3. Presence of atopic dermatitis, basal cell carcinoma, squamous cell carcinoma, eczema, psoriasis, rosacea, sunburn or other possible skin conditions on the face or bald scalp that in the investigator's opinion would interfere with the study assessments. 4. Use within six months prior to randomization of oral isotretinoin. 5. Use within six months prior to randomization on the face or bald scalp of 1) chemical peel, 2) dermabrasion, 3) laser abrasion, 4) PUVA (psoralen plus ultraviolet A) therapy, or 5) UVB therapy 6. Use within one month prior to randomization on the face or bald scalp of 1) cryodestruction or chemodestruction, 2)curettage, 3) photodynamic therapy, 4) surgical excision, 5)topical 5-fluorouracil, 6) topical corticosteroids, 7) topical diclofenac, 8) topical Imiquimod, 9) topical retinoids, or 10) other treatments for actinic keratosis including glycolic acids or over-the-counter products containing retinol, alpha or beta hydroxy acids. 7. Use within one month prior to randomization of 1)immunomodulators or immunosuppressive therapies, 2)interferon, 3) systemic corticosteroids or 4) cytotoxic drugs. (The occasional use of ophthalmic, nasal or inhaled steroids is acceptable and not reason for exclusion) 8. Known allergies to diclofenac sodium, benzyl alcohol, polyethylene glycol monomethyl ether 359, hyaluronate sodium or any excipients in the test or reference gels. 9. Receiving 5-Fluorouracil or other systemic cancer chemotherapy within 6 months prior to randomization. 10. Any condition, medical, psychological, or social, that, in the Investigator's opinion, would interfere with participation in the study. 11. Women who are pregnant, planning pregnancy or lactating. 12. Participation in any investigational drug study within 30 days of randomization or previous participation in this study. 13. Employees of the research center or Investigator. 14. Family members of employees of the research center or Investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients With 100% Clearance of All AK Lesions Within the Treatment Area Assessed at Day 90 | 90 days | The primary measure of bioequivalence will be evaluated using those patients who complete the study according to the (PP) population. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Diclofenac Sodium 3% Gel The test product diclofenac sodium 3% test gel is applied to lesion areas twice daily. It is to be smoothed onto the affected skin gently. The amount needed depends upon the size of the lesion site. Assure that enough Test Gel is applied to adequately cover each lesion. Normally 0.5 g of gel is used on each 5 cm x 5 cm lesion site.
Diclofenac sodium: Topical administration of approximately 0.5g twice daily to the 25 sq cm treatment area for 60 days. | 188 |
| Solaraze( Diclofenac Sodium) 3% Gel The Reference diclofenac sodium 3% gel (Solaraze®) is applied to lesion areas twice daily. It is to be smoothed onto the affected skin gently. The amount needed depends upon the size of the lesion site. Assure that enough Reference (Solaraze®) Gel is applied to adequately cover each lesion. Normally 0.5 g of gel is used on each 5 cm x 5 cm lesion site.
Diclofenac sodium: Topical administration of approximately 0.5g twice daily to the 25 sq cm treatment area for 60 days. | 189 |
| Vehicle Gel The vehicle (placebo) gel (contains no active ingredient) is applied to lesion areas twice daily. It is to be smoothed onto the affected skin gently. The amount needed depends upon the size of the lesion site. Assure that enough placebo gel is applied to adequately cover each lesion. Normally 0.5 g of gel is used on each 5 cm x 5 cm lesion site.
Placebo: Topical administration of approximately 0.5g twice daily to the 25 sq cm treatment area for 60 days. | 93 |
| Total | 470 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 4 | 4 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 |
| Overall Study | Miscellaneous | 1 | 9 | 2 |
| Overall Study | Non compliance with dosing requirements | 4 | 2 | 0 |
| Overall Study | Randomized in Error | 4 | 2 | 2 |
| Overall Study | Restricted medication | 5 | 1 | 1 |
| Overall Study | Serious Adverse Event | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 11 | 10 | 6 |
Baseline characteristics
| Characteristic | Total | Diclofenac Sodium 3% Gel | Solaraze( Diclofenac Sodium) 3% Gel | Vehicle Gel |
|---|---|---|---|---|
| Age, Continuous | 65.71 years STANDARD_DEVIATION 11.26 | 65.34 years STANDARD_DEVIATION 11.42 | 66.24 years STANDARD_DEVIATION 11.37 | 65.55 years STANDARD_DEVIATION 11 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 48 Participants | 21 Participants | 19 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 422 Participants | 167 Participants | 170 Participants | 85 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 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 | 470 Participants | 188 Participants | 189 Participants | 93 Participants |
| Sex: Female, Male Female | 136 Participants | 56 Participants | 54 Participants | 26 Participants |
| Sex: Female, Male Male | 334 Participants | 132 Participants | 135 Participants | 67 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 188 | 0 / 189 | 0 / 93 |
| other Total, other adverse events | 102 / 188 | 91 / 189 | 35 / 93 |
| serious Total, serious adverse events | 7 / 188 | 4 / 189 | 2 / 93 |
Outcome results
Primary
Percentage of Patients With 100% Clearance of All AK Lesions Within the Treatment Area Assessed at Day 90
The primary measure of bioequivalence will be evaluated using those patients who complete the study according to the (PP) population.
Time frame: 90 days
Population: Analysis provided using the Per-Protocol Population.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Diclofenac Sodium 3% Gel | Percentage of Patients With 100% Clearance of All AK Lesions Within the Treatment Area Assessed at Day 90 | Cure - 100% clearance of all AK lesions at Day 90 | 31 Participants |
| Diclofenac Sodium 3% Gel | Percentage of Patients With 100% Clearance of All AK Lesions Within the Treatment Area Assessed at Day 90 | No Cure - Not 100% Clearance of lesions at Day 90 | 108 Participants |
| Solaraze( Diclofenac Sodium) 3% Gel | Percentage of Patients With 100% Clearance of All AK Lesions Within the Treatment Area Assessed at Day 90 | Cure - 100% clearance of all AK lesions at Day 90 | 32 Participants |
| Solaraze( Diclofenac Sodium) 3% Gel | Percentage of Patients With 100% Clearance of All AK Lesions Within the Treatment Area Assessed at Day 90 | No Cure - Not 100% Clearance of lesions at Day 90 | 116 Participants |
| Vehicle Gel | Percentage of Patients With 100% Clearance of All AK Lesions Within the Treatment Area Assessed at Day 90 | Cure - 100% clearance of all AK lesions at Day 90 | 7 Participants |
| Vehicle Gel | Percentage of Patients With 100% Clearance of All AK Lesions Within the Treatment Area Assessed at Day 90 | No Cure - Not 100% Clearance of lesions at Day 90 | 74 Participants |
90% CI: [-8.06, 9.42]
p-value: 0.001ANOVA