Phase 2, randomized, double-blind, placebo-controlled, 4-week study to evaluate the safety and efficacy of OPA- 15406 (difamilast), a new topical selective phosphodiesterase type-4 inhibitor, in Japanese pediatric patients aged 2-14 years with atopic dermatitis

Abstract

The safety and efficacy of OPA-15406 (international non-proprietary name, difamilast; also referred to as MM36), a new topical, selective phosphodiesterase type-4 inhibitor, in Japanese pediatric patients with atopic dermatitis aged 2-14 years were evaluated in a phase 2, randomized, double-blind, vehicle-controlled, 4-week study. Seventy-three patients were randomized 1:1:1 to receive OPA-15406 0.3%, OPA-15406 1% or vehicle ointment twice daily for 4 weeks. The mean age of patients was similar across treatment groups. No deaths or serious treatment-emergent adverse events were reported; all treatment-emergent adverse events were mild or moderate in severity. The incidence of treatment-emergent adverse events leading to treatment discontinuation was 4.2% (1/24) in the OPA-15406 0.3% group, 4.0% (1/25) in the OPA-15406 1% group and 16.7% (4/24) in the vehicle group, all of which were worsening of atopic dermatitis. Both OPA-15406 groups demonstrated a higher incidence of success in the Investigator Global Assessment score compared with the vehicle group over the 4-week study. The OPA-15406 groups also showed greater improvements from baseline compared with the vehicle group in the Investigator Global Assessment score, Eczema Area and Severity Index overall score and subscale (erythema, induration/papulation, excoriation and lichenification) scores, Visual Analog Scale pruritus score, Patient-Oriented Eczema Measure score, and percentage of affected body surface area over the 4-week study. Topical OPA-15406 twice daily for 4 weeks was considered a safe and effective treatment option in this phase 2 study in pediatric patients with atopic dermatitis, and phase 3 development is currently ongoing.

Keywords: OPA-15406; atopic dermatitis; difamilast; pediatric patients; phosphodiesterase type-4 inhibitor.

Figure 1

Study design to evaluate the safety and efficacy of topical OPA‐15406 in pediatric patients aged 2–14 years with atopic dermatitis.

Figure 2

Patient disposition.

Figure 3

Incidence of success in the IGA score at each examination time point. In total, 24, 24 and 25 patients were examined in the vehicle, OPA‐15406 0.3% and OPA‐15406 1% groups, respectively, at all examination time points. P‐values are for the comparison between each OPA‐15406 group and the vehicle group. IGA, Investigator Global Assessment.

Figure 4

Least square mean change in the Eczema Area and Severity Index subscale scores from baseline at each examination time point: (a) erythema score; (b) induration/papulation score; (c) excoriation score; (d) lichenification score. In the vehicle, OPA‐15406 0.3% and OPA‐15406 1% groups, 24, 24 and 25 patients, respectively, were examined at week 1; 21, 24 and 24 patients, respectively, were examined at week 2; and 18, 23 and 24 patients, respectively, were examined at week 4. P‐values are for the comparison between each OPA‐15406 group and the vehicle group. LS, least square.