Efficacy and Safety of Fixed-Dose Clindamycin Phosphate 1.2%/Adapalene 0.15%/Benzoyl Peroxide 3.1%Compared With Adapalene 0.3%/Benzoyl Peroxide 2.5% Gel in Participants With Moderate to Severe Acne

Abstract

Background The American Academy of Dermatology guidelines for treating mild to severe acne strongly recommend a combination of topical retinoids, benzoyl peroxide (BPO) and/or topical or oral antibiotics. Topical clindamycin phosphate 1.2%/adapalene 0.15%/BPO 3.1% (CAB) gel is the only fixed-dose, triple-combination formulation approved for acne treatment. CAB showed superior efficacy to component dyads and vehicle, with good tolerability and safety in a phase 2 and two phase 3 clinical trials of participants with moderate to severe acne. Results from a second phase 2 trial of CAB gel comparing its efficacy/safety in a head-to-head trial versus commercially available adapalene 0.3%/BPO 2.5% (ADAP/BPO) gel are reported here.

Methods In a phase 2, double-blind, 12-week clinical trial (NCT04892706), participants with moderate to severe acne aged ≥12 years were randomized (2:2:1:1) to once-daily CAB, ADAP/BPO, or 1 of 2 vehicle gels (combined for analysis). Co-primary endpoints included percentage of participants achieving treatment success (≥2-grade reduction from baseline in Evaluator’s Global Severity Score and clear/almost clear skin) and least squares (LS) mean absolute change from baseline in inflammatory and noninflammatory lesion counts at week 12. Secondary endpoints included LS mean percent change from baseline in lesion counts at week 12. Treatment-emergent adverse events (TEAEs) were also evaluated. Co-primary endpoints were further analyzed by subgroups defined by participant age (<18 or ≥18 years) and sex.

Results A total of 686 participants aged 12-56 years were enrolled, of which 2 did not receive study drug. At week 12, significantly more participants achieved treatment success with CAB (51.3%) vs ADAP/BPO (32.9%) or vehicle (18.0%, P<0.001, both). Absolute mean reductions from baseline in lesion counts were significantly greater with CAB (inflammatory, 29.9; noninflammatory, 36.8) or ADAP/BPO (27.9; 34.4) vs vehicle (19.7; 22.7; P<0.001, all). Percent lesion reductions were >71% with CAB, >67% with ADAP/BPO, and ~50% with vehicle (P<0.001 vs vehicle, all). Treatment success rates and absolute lesion reductions in participants stratified by age and sex were in line with the overall population. TEAE rates with CAB and ADAP/BPO were similar, and most TEAEs were of mild or moderate severity.

Conclusions Fixed-dose, triple-combination CAB gel was efficacious and well tolerated in participants with moderate to severe acne over 12 weeks, consistent with results from other CAB phase 2/3 clinical trials. In this head-to-head trial, CAB was statistically superior to ADAP/BPO gel with regard to treatment success at week 12 and was efficacious regardless of age and sex.