The Phototoxic and Photoallergy Potential of Clindamycin Phosphate 1.2%/ Tretinoin 0.025% Gel for Facial Acne: Results of Two Single-Center, Evaluator-Blinded, Randomized, Vehicle-Controlled Phase 1 Studies in Healthy Volunteers
January 2014 | Volume 13 | Issue 1 | Original Article | 16 | Copyright © 2014
John Murray MDa and Aaron Potts BScb
aHill Top Research, St. Petersburg, FL
bLos Altos, CA
BACKGROUND: A fixed-dose combination of clindamycin phosphate 1.2% and tretinoin 0.025% gel (VELTIN® (clindamycin phosphate and tretinoin) 1.2%/0.025% Gel [VELTIN]) (clindamycin/tretinoin gel) is currently available for the once-daily topical treatment of acne.
OBJECTIVES: Two-phase I studies were conducted to evaluate the phototoxic and photoallergic potential of clindamycin/tretinoin gel.
METHODS: Study 1 (phototoxic) (n=37) and Study 2 (photoallergic) (n=58) were single-center, evaluator-blinded, randomized, vehicle-controlled, phase 1 studies conducted in healthy volunteers. In Study 1, clindamycin/tretinoin gel patches, vehicle gel patches and blank patches (no gel) were applied concurrently for 24 hours to naïve sites. After patch removal, sites were irradiated with 16 joules/cm2 of ultraviolet A light (UVA) then 0.75 minimal erythema dose (MED) of UVA/ultraviolet B light (UVB), the same irradiation protocol followed by 15 joules/cm2 of visible light (VIS), or served as non-irradiated controls. Study 2 examined the effect of repeated drug exposure and involved an induction period (6 repeat phases at the same body sites during which clindamycin/tretinoin gel and vehicle gel patches were applied for 24 hours, removed and sites irradiated with UVB +/- VIS), followed by a rest period (10 to 17 days), then a challenge period that used the protocol described for Study 1. In both studies, inflammatory responses and other cutaneous effects were evaluated at 1, 24, 48, and 72 hours after patch removal.
RESULTS: No subject experienced any adverse events in Study 1 (phototoxic). One subject in Study 2 (photoallergic) experienced AEs (diffuse erythema; mild application site irritation at one each of UV/VIS-irradiated clindamycin/tretinoin gel and vehicle gel patch sites) considered definitely related to study product that resulted in discontinuation from the study. Data from Study 1 and the challenge phase from Study 2 showed most subjects had no visible inflammatory reaction to clindamycin/tretinoin gel after irradiation.
CONCLUSIONS: Clindamycin/tretinoin gel has a favorable safety profile following UV/visible irradiation and a low potential for phototoxicity and photoallergenicity.
J Drugs Dermatol. 2014;13(1):16-22.
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The FDA recommends photosafety testing for topical drug products that absorb light in the range of 290nm to 700nm that will be applied to sun-exposed skin.1 For topical products that are applied to sun-exposed skin, the FDA recommends that the drug product, not just the active ingredient,be evaluated under conditions of simulated sunlight. This is because many excipients in these types of products modify the skin, and dermal applications usually deliver relatively large amounts of both parent drug and vehicle to the skin.
We present data from two similarly designed phase 1 studies in healthy volunteers. The aim of these studies was to assess the phototoxic and photoallergic potential of the fixed-dose combination of clindamycin phosphate 1.2% and tretinoin 0.025% gel (VELTIN® (clindamycin phosphate and tretinoin) 1.2%/0.025% Gel [VELTIN®]; Stiefel, a GSK Company, Research Triangle Park, NC) (clindamycin/tretinoin gel).*
*The VELTIN® trademark is owned by Astellas Pharma Europe BV.
MATERIAL AND METHODS
The objective of these single-center, evaluator-blinded, randomized,vehicle-controlled phase 1 studies was to evaluate the phototoxic (Study 1) and photoallergic (Study 2) potential of clindamycin/tretinoin gel in humans. Both studies conformed to the recommendations of the Declaration of Helsinki regarding ethical conduct. Informed consent was obtained from all subjects in accordance with the International Conference on Harmonisation Good Clinical Practice (ICH GCP) guidelines and all relevant local and national regulations.
Males and females aged 18 to 65 years were eligible to be enrolled if they had Fitzpatrick skin type I, II, or III that would