Moderate and Severe Inflammatory Acne Vulgaris Effectively Treated with Single-Agent Therapy by a New Fixed-Dose Combination Adapalene 0.3 %/Benzoyl Peroxide 2.5 % Gel: A Randomized, Double-Blind, Parallel-Group, Controlled Study

Abstract

Background: A need exists for topical treatments in managing more severe inflammatory acne.

Objectives: The objectives of this study were to evaluate the efficacy and safety of adapalene 0.3 %/benzoyl peroxide 2.5 % (0.3 % A/BPO) topical gel in subjects with moderate and severe inflammatory acne.

Methods: This was a multicenter, randomized, double-blind, parallel-group study. Randomization was stratified by acne severity (50 % moderate and 50 % severe). Subjects received 0.3 % A/BPO, 0.1 % A/BPO (benchmark), or vehicle (comparator) once daily for 12 weeks. Co-primary efficacy endpoints were success rate at week 12 (the percentage of subjects rated 'clear' or 'almost clear' with at least a 2-grade improvement on Investigator's Global Assessment [IGA]) and change in inflammatory (IN) and noninflammatory (NIN) lesion counts from baseline to week 12. Secondary efficacy endpoints were percent changes in IN and NIN lesion counts. Safety endpoints were incidence of adverse events (AEs) and local tolerability signs/symptoms.

Results: A total of 503 subjects were randomized: 217, 217, and 69 subjects in the 0.3 % A/BPO, 0.1 % A/BPO, and vehicle groups, respectively. For success rate (subjects rated 'clear' or 'almost clear' with ≥2-grade improvement in IGA), 0.3 % A/BPO was superior to vehicle, with a treatment difference of 22.7 % (33.7 vs. 11.0 %; 95 % confidence interval [CI] 12.8-32.6, p < 0.001). At week 12, 0.3 % A/BPO was superior to vehicle for mean reduction from baseline in IN (27.0 vs. 14.4) and NIN lesion counts (40.2 vs. 18.5), as well as for percentage reduction from baseline in IN (68.7 vs. 39.2 %) and NIN lesion counts (68.3 vs. 37.4 %) (all p < 0.001). Among subjects with severe inflammatory acne (IGA = 4), 0.1 % A/BPO did not reach statistical significance for success rate compared with vehicle (p = 0.443), whereas 0.3 % A/BPO demonstrated significantly greater efficacy (p = 0.029, requiring ≥3-point IGA improvement). Additionally, 0.3 % A/BPO was safe and well-tolerated.

Conclusions: Results of this clinical trial demonstrate the significantly greater efficacy of adapalene 0.3 % A/BPO topical gel compared with vehicle as well as a good safety profile in the treatment of moderate to severe inflammatory non-nodulocystic acne, which increases patients' treatment options. CLINICALTRIALS.

Gov identifier: NCT01880320.

Fig. 1

Investigator’s Global Assessment (IGA) scale

Fig. 2

Subject disposition. A adapalene, BPO benzoyl peroxide, ITT intent to treat, PP per protocol

Fig. 3

Photographs of subject in 0.3 % A/BPO group with severe acne (IGA = 4) at (a) baseline, (b) week 1, and (c) week 12 with treatment success (IGA = 1, ‘almost clear’). A adapalene, BPO benzoyl peroxide, IGA Investigator’s Global Assessment

Fig. 4

Photographs of subject in 0.3 % A/BPO group with severe acne (IGA = 4) at (a) baseline, (b) week 1, and (c) week 12 with treatment failure (IGA = 3, ‘moderate’). A adapalene, BPO benzoyl peroxide, IGA Investigator’s Global Assessment

Fig. 5

Mean percent change (MI data; post hoc analysis performed prior to week 12) in (a) inflammatory lesions and (b) non-inflammatory lesions (ITT; MI). A adapalene, BPO benzoyl peroxide, ITT intent to treat, MI multiple imputation. *p < 0.05, **p < 0.001

Fig. 6

Local tolerance parameters (safety population). A adapalene, BPO benzoyl peroxide, final last data observed during the post-baseline period for a subject, worst highest severity score observed during the post-baseline period for a subject

Fig. 7

Subject’s assessment of acne improvement (week 12, intent-to-treat population). A adapalene, BPO benzoyl peroxide