Triple-Combination Clindamycin Phosphate 1.2%/Adapalene 0.15%/Benzoyl Peroxide 3.1% Gel for Acne: Clinical Efficacy and Application Characteristics

Abstract

Background: Triple-combination therapies for acne including an antibiotic, topical retinoid, and benzoyl peroxide (BPO) are among the most effective, with meta-analyses demonstrating greater efficacy with triple-combinations than dual-combinations or topical monotherapy. However, this benefit may be offset by reduced adherence to a complicated treatment regimen. Here, the clinical efficacy of fixed-dose clindamycin phosphate 1.2%/adapalene 0.15%/BPO 3.1% (CAB) gel is reviewed, and the ease of CAB application is compared with the layered application of its individual active ingredients.
 Methods: In a phase 2 (N=741) and two phase 3 (N=183; N=180), double-blind, randomized, 12-week studies, participants aged ≥9 years with moderate-to-severe acne were randomized to receive once-daily CAB or vehicle; the phase 2 study also included treatment arms containing dyad gels (BPO/adapalene; clindamycin phosphate/BPO; clindamycin phosphate/adapalene). Efficacy endpoints included treatment success (percentage of participants achieving ≥2-grade reduction from baseline in Evaluator’s Global Severity Score and clear/almost clear skin) and reductions from baseline in inflammatory (IL) and noninflammatory lesions (NIL). In a split-face study of adults with acne-prone skin (N=25), participant-application of CAB (0.3 cc) was compared to sequential, layered application of benzoyl peroxide cream, adapalene gel, and clindamycin gel (0.1 cc each). IDP-126 and clindamycin gels were compounded with pyranine, which fluoresces under blue light; photos were taken under blue light to assess evenness of product application.
 Results: In all three clinical studies at week 12, half of CAB-treated participants achieved treatment success (range: 49.6%-52.5%), significantly greater than with vehicle (8.1%-24.9%; P<0.01, all) or dyads (phase 2 study only; 27.8%-30.5%; P≤0.001, all). Reductions from baseline in both IL and NIL were also significantly greater for CAB vs vehicle (range, IL: 75.7%-80.1% vs 50.4%-59.6%; NIL: 71.0%-73.3% vs 45.8%-49.0%; P<0.001, all) and dyads (IL: 64.0%-69.2%; NIL: 58.7%-61.1%; P<0.01, all vs IDP-126). In the split-face study, 100% of Investigator and participant assessments of evenness of application favored CAB over the three layered products. In addition, all participants rated CAB as both easier and faster to apply, and most (96%) preferred CAB for use at home.
 Conclusions: Fixed-dose CAB gel applied more evenly than separate application of its three active ingredients, and demonstrated significantly greater efficacy in the treatment of moderate-to-severe acne than dyad gels or vehicle. By addressing three of the main acne pathogenic pathways in a single, easy-to-apply formulation, CAB may improve efficacy of and adherence to acne treatment.
 Funding: Ortho Dermatologics