Background A three-pronged approach to acne treatment-combining an antibiotic, antibacterial, and retinoid-could provide greater efficacy and tolerability than single or dyad treatments, while potentially improving patient compliance and reducing antibiotic resistance. Objectives We aimed to evaluate the efficacy and safety of triple-combination, fixed-dose topical clindamycin phosphate 1.2%/benzoyl peroxide (BPO) 3.1%/adapalene 0.15% (IDP-126) gel for the treatment of acne. Methods In a phase II, double-blind, multicenter, randomized, 12-week study, eligible participants aged ≥ 9 years with moderate-to-severe acne were equally randomized to once-daily IDP-126, vehicle, or one of three component dyad gels: BPO/adapalene; clindamycin phosphate/BPO; or clindamycin phosphate/adapalene. Coprimary endpoints were treatment success at week 12 (participants achieving a ≥ 2-grade reduction from baseline in Evaluator's Global Severity Score and clear/almost clear skin) and least-squares mean absolute changes from baseline in inflammatory and noninflammatory lesion counts to week 12. Treatment-emergent adverse events and cutaneous safety/tolerability were also assessed. Results A total of 741 participants were enrolled. At week 12, 52.5% of participants achieved treatment success with IDP-126 vs vehicle (8.1%) and dyads (range 27.8-30.5%; P ≤ 0.001, all). IDP-126 also provided significantly greater absolute reductions in inflammatory (29.9) and noninflammatory (35.5) lesions compared with vehicle or dyads (range inflammatory, 19.6-26.8; noninflammatory, 21.8-30.0; P < 0.05, all), corresponding to > 70% reductions with IDP-126. IDP-126 was well tolerated, with most treatment-emergent adverse events of mild-to-moderate severity. Conclusions Once-daily treatment with the novel fixed-dose triple-combination clindamycin phosphate 1.2%/BPO 3.1%/ adapalene 0.15% gel demonstrated superior efficacy to vehicle and all three dyad component gels, and was well tolerated over 12 weeks in pediatric, adolescent, and adult participants with moderate-to-severe acne. Clinical Trial Registration ClinicalTrials.gov identifier NCT03170388 (registered 31 May, 2017).

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The disposition of N,N-diethyl-3-methylbenzamide (DEET) applied to split-thickness human cadaver skin was measured in modified Franz cells maintained at 32 degrees C and fitted with a vapor trap. Ethanolic solutions of DEET (1% w/w) spiked with (14)C radiolabel were applied to skin at a dose of 10 microL per cell, corresponding to a DEET dose of 127 microg/cm(2). Room air was drawn over the skin at velocities ranging from 10-100 mL/min. Evaporation of radiolabel from the skin surface and absorption into the receptor solution were monitored for 24 hr post-dose. The percentage of radioactivity collected in the vapor trap after 24 hr increased with airflow, ranging from 16 +/- 4% at 10 mL/min to 59 +/- 7% at 70 mL/min. The percentage of radioactivity absorbed through the skin after 24 hours decreased with increasing airflow, ranging from 69 +/- 7% at 10 mL/min to 20 +/- 1% at 80 mL/min. Tissue retention after 24 hr was 6-14% of the radioactive dose with no clear correlation to airflow. This data as well as DEET absorption data from two previous in vitro studies in which dose and location (fume hood or bench top) was varied were analyzed in terms of a recently developed diffusion/evaporation model for skin implemented on an Excel spreadsheet. A priori model calculations based on independently estimated transport parameters (Model 1) were compared with calculations based on fitted parameters (Models 2 and 3). The analysis of the combined dataset (n = 272 observations) showed that the Model 1 estimates matched the cumulative disposition profiles to within a root mean square error of 12.4% of the applied dose (r(2) = 0.65), whereas the Model 2 and Model 3 fits matched to within 9.4% (r(2) = 0.80) and 6.5% (r(2) = 0.91), respectively. The Model 3 fits were obtained using a concentration-dependent diffusivity of DEET in the stratum corneum, the value of which increased 3.4-fold between low concentrations and saturation. This result was consistent with the mild skin penetration enhancement effect for DEET reported elsewhere. [Supplementary materials are available for this article. Go to the publisher's online edition of Journal of Occupational and Environmental Hygiene for the following free supplemental resource: a word document containing tables and figures including more information on the spreadsheet skin absorption model.]

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