Clindamycin phosphate 1.2%/benzoyl peroxide 3% fixed-dose combination gel versus topical combination therapy of adapalene 0.1% gel and clindamycin phosphate 1.2% gel in the treatment of acne vulgaris in Japanese patients: A multicenter, randomized, investigator-blind, parallel-group study

Abstract

Adapalene 0.1% (ADA) with clindamycin phosphate 1.2% (CLNP; ADA + CLNP) and the fixed-dose combination containing CLNP and benzoyl peroxide 3% (CLNP/BPO 3%) are strongly recommended for the early treatment of acne vulgaris in Japan. Here, we compare the early efficacy and safety of CLNP/BPO 3% with Japanese standard topical use of ADA + CLNP in the treatment of acne vulgaris. In this phase IV, multicenter study, 351 patients were randomized to receive CLNP/BPO 3% or ADA + CLNP for 12 weeks. The primary end-point was percentage change from baseline in total lesion (TL) counts at week 2. Secondary end-points included the percentage change from baseline in TL, inflammatory and non-inflammatory lesion (IL and non-IL) counts, Investigator's Static Global Assessment (ISGA), quality of life (QoL [Skindex-16]) and patient preference. Local tolerability scores and adverse events were also recorded. CLNP/BPO 3% provided a significantly greater percentage reduction from baseline in TL compared with ADA + CLNP at week 2, and week 4. Compared with ADA + CLNP, CLNP/BPO 3% was superior at reducing IL (but not non-IL) over weeks 2-12, was more effective at improving patient QoL and ISGA, and scored higher in patient-preference assessments. Both treatments were well tolerated; adverse drug reactions occurred more frequently in patients receiving ADA + CLNP (37%) than in those receiving CLNP/BPO 3% (17%). In conclusion, CLNP/BPO 3% showed greater efficacy for the early treatment of acne vulgaris in Japan, with a more favorable safety profile compared with ADA + CLNP.

Keywords: acne vulgaris; adapalene; benzoyl peroxide; clindamycin; drug combinations.

Figure 1

Disposition of patients and study population. ADA, adapalene; BPO, benzoyl peroxide; CLNP, clindamycin phosphate; ITT, intent‐to‐treat.

Figure 2

The adjusted mean percentage reduction from baseline over 12 weeks in (a) total lesion (TL), (b) inflammatory lesion (IL) and (c) non‐IL counts. Error bar represents standard error of the mean. Statistical analysis used a mixed model for repeated measures (MMRM) with treatment, center, visit and treatment‐by‐visit interaction as fixed categorical effects and baseline lesion counts and baseline‐by‐visit interaction as fixed continuous effects. The adjusted means and P‐values for treatment difference at each visit were calculated based on the fitted MMRM model. ADA, adapalene; BPO, benzoyl peroxide; CLNP, clindamycin phosphate.

Figure 3

Proportion of patients with (a) at least a two‐grade improvement in Investigator's Static Global Assessment (ISGA) score or (b) with an Investigator's Static Global Assessment (ISGA) score of 0 or 1 at each study visit. Statistical analysis used the Cochran–Mantel–Haenszel test. ADA, adapalene; BPO, benzoyl peroxide; CLNP, clindamycin phosphate.

Figure 4

Skindex‐16 assessment scores (a) total, (b) symptom, (c) emotion and (d) functioning domains. Error bar represents standard error of the mean. Statistical analysis presented as summary statistics. ADA, adapalene; BPO, benzoyl peroxide; CLNP, clindamycin phosphate.

Figure 5

Patient preference assessment scores for (a) ease of application, (b) comfort, (c) satisfaction with treatment, (d) comparison with prior treatments and (e) willingness to continue using treatment (ITT population). ADA, adapalene; BPO, benzoyl peroxide; CLNP, clindamycin phosphate; ITT, intent‐to‐treat.

Figure 6

Distribution of local tolerability assessment scores among patients for (a) erythema, (b) dryness, (c) peeling, (d) itching and (e) burning/stinging (ITT population). ADA, adapalene; BPO, benzoyl peroxide; CLNP, clindamycin phosphate; ITT, intent‐to‐treat.