Efficacy and safety of topical OPA-15406, a new phosphodiesterase 4 inhibitor, in Japanese patients with atopic dermatitis for 8 weeks: A phase 2, randomized, double-blind, placebo-controlled study

Abstract

The efficacy and safety of topical OPA-15406, a new phosphodiesterase 4 inhibitor, were examined in Japanese patients aged 15-70 years with atopic dermatitis in a phase 2, randomized, double-blind, vehicle-controlled study. Two hundred patients were randomized to three treatment groups at a 1:1:1 ratio to receive OPA-15406 0.3%, OPA-15406 1% or vehicle ointment twice daily for 8 weeks. The OPA-15406 1% group was superior to the vehicle group in terms of the incidence of success based on the Investigator Global Assessment score at week 4 (P = 0.0328), which was the primary end-point, while the OPA-15406 0.3% group showed a trend toward improvement in the primary end-point. The mean Eczema Area and Severity Index total score and subscale (erythema, induration/papulation, excoriation and lichenification) scores, the Visual Analog Scale pruritus score and the Patient-Oriented Eczema Measure score were significantly improved and the percentage of affected body surface area was significantly decreased in both OPA-15406 groups relative to the vehicle group as early as week 1, and the improved scores and decreased percentages were generally maintained until week 8. No deaths or serious treatment-emergent adverse events occurred in the OPA-15406 treatment groups. Treatment-emergent adverse events frequently observed across treatment groups were worsening of atopic dermatitis, viral upper respiratory tract infection and pruritus, all of which were mild or moderate in severity in the OPA-15406 groups. OPA-15406 1% ointment showed favorable efficacy and safety profiles, indicating a promising treatment option for patients with atopic dermatitis.

Keywords: OPA‐15406; atopic dermatitis; phosphodiesterase 4 inhibitor; pruritus; topical.

Figure 1

Patient disposition. BSA, body surface area.

Figure 2

Incidence of success in the IGA score at each time point. Overall, 66, 67 and 67 patients were evaluated in the vehicle, OPA‐15406 0.3% and OPA‐15406 1% groups, respectively, at all time points. P‐values are for the comparison between each OPA‐15406 group and the vehicle group. IGA, Investigator Global Assessment.

Figure 3

Least square (LS) mean change from baseline in the subscale scores of the Eczema Area and Severity Index at each time point: (a) erythema score; (b) induration/papulation score; (c) excoriation score; and (d) lichenification score. In the vehicle, OPA‐15406 0.3% and OPA‐15406 1% groups, 66, 67 and 67 patients, respectively, were evaluated at week 1; 57, 63 and 64 patients, respectively, were evaluated at week 2; 53, 57 and 58 patients, respectively, were evaluated at week 4; 49, 49 and 54 patients, respectively, were evaluated at week 6; and 46, 47 and 53 patients, respectively, were evaluated at week 8. P‐values are for the comparison between each OPA‐15406 group and the vehicle group.