Randomized and Open Label Study for Safety and Efficacy of DBI-102 vs. Vehicle vs. Hydroquinone on Skin Pigmentation and Lentigos

Study Overview
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Brief Summary
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This is a randomized, observer-blinded, vehicle-controlled multi-dose trial that examines the effect of twice daily application of 0.8% DBI-102 Gel, 4% Hydroquinone cream, and Vehicle Gel for 12 weeks in adults with Fitzpatrick Skin Types IV-V and a colorimeter L* measurement between 57.8 and 46.1.

Official Title
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A Randomized, Observer-Blinded, Vehicle-Controlled Study on the Safety and Efficacy of Twice Daily Application of Ruboxistaurin (DBI-102) Gel Vs.Vehicle Gel Vs. Hydroquinone Cream on Sun-Exposed and Sun-Protected Skin of Adults

Conditions
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Hyperpigmentation

Intervention / Treatment
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* Drug: DBI-102
* Drug: Vehicle gel
* Drug: Hydroquinone Cream


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or Female at least 18 years of age. Must be Fitzpatrick Skin Type IV-V and have an L* measurement between 57.8 and 46.1, using the Chromometer CM-700. Ability to understand, agree to, and sign the study informed consent form (ICF). Agree to discontinue all agents used to treat hyperpigmentation, aging or exfoliate the skin during the course of the study. Makeup and moisturizers are permitted. Agree not to change their sun exposure at work, home, or leisure. Technical ability and willingness to apply test articles. Willing to allow digital photos of treatment and comparison areas to be taken and stored. Additional Inclusion Criterion for the solar lentigo Sub-Cohort: At least 4 solar lentigos at least 4 mm in diameter present on each dorsal hand. Exclusion Criteria: Positive urine pregnancy test, pregnant, lactating, or female of childbearing potential who does not agree to use an active method of birth control for the duration of the study. Conditions at baseline that would interfere with evaluation of UV-tanned skin, especially other pigmentary disorders including, but not limited to, melasma or vitiligo affecting the treatment and comparison sites. Presence of known concomitant diseases associated with the development of hyperpigmentation (e.g., thyroid, liver, adrenal). Current tanning booth exposure or any kind of phototherapy within 3 months of Screening. Current or past use of monobenzyl ether or hydroquinone (Benoquin) to depigment the skin. Past or recent use of any skin bleaching treatment within 6 months of Screening. A chemical peel within 3 months of Screening. Laser or light-based treatment of the treatment areas within 3 months of Screening. Use of any photosensitizing medications within the past 6 months of Screening, including psoralens, sulfonamide drugs, tetracycline antibiotics, thiazide diuretics, phenothiazines, coal tar and derivatives, and tricyclic antidepressants. Any dermatological conditions that could interfere with clinical evaluations or any disease state or physical condition which might expose the subject to an unacceptable risk by study participation. Any underlying disease(s) or other dermatological conditions that require the use of exclusionary topical or systemic therapy (see Exclusion criteria 5 and 6). Unwilling to discontinue applying any prescription or over the counter (OTC) topical product creams and ointments, other than makeup and moisturizers, on treatment area(s) at Baseline through their last day of study. Treatment of any type of cancer within 6 months of Screening with the exception of superficial skin cancers such as basal cell or squamous cell carcinoma. Known allergy to any of the test article(s) or any components in the test article(s) or history of hypersensitivity or allergic reactions to any of the study preparations as described in the Investigator's Brochure. History of active atopic dermatitis, as diagnosed by a physician, requiring treatment within the past 2 years. Unable to meet the study attendance requirements. Any history of psychiatric disease or history of alcohol or drug abuse that would interfere with the ability to comply with the study protocol. Participation in any other trial of an investigational drug or device within 30 days prior to enrollment or participation in a research study concurrent with this study. Additional Exclusion Criterion for the Sub-Cohort Any previous treatment for solar lentigos on the dorsal hands.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Randomized 3-arm tranche of main cohorts, to be followed by open-label Solar Lentigo sub-cohort
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DBI-102<br>Topical DBI-102 Gel, 0.8% twice daily for 12 weeks for the randomized cohort | Drug: DBI-102<br>* Topical application on dorsal hand and upper volar arm<br>|
| Placebo Comparator: Vehicle gel<br>Inactive comparator | Drug: Vehicle gel<br>* Inactive comparator<br>|
| Active Comparator: Hydroquinone cream<br>4% Hydroquinone cream, Acella (approved), twice daily for 12 weeks | Drug: Hydroquinone Cream<br>* 4% Hydroquinone cream, Acella (approved), twice daily for 12 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Decrease in pigmentation based on melanin index | Change in L* and ITA colorimetry measurements | 12 weeks after first dose | 
| Decrease in pigmentation based on digital imaging | Change as measured with Canfield RBX software analysis | 12 weeks after first dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change in Investigator Dynamic Grading Assessment (IDGA) | Percent pigmentation differences between treated and contralateral Percent Change in Investigator Dynamic Grading Assessment (IDGA) | At weeks 2,4,6,8,10, and 12 | 
| Proportion of subjects with Improved Investigator Dynamic Grading Scale (IDGA) | Proportion of subjects with less pigmentation at treated sites vs contralateral untreated sites | At weeks 2,4,6,8,10, and 12 |