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.

Difamilast ointment in adult patients with atopic dermatitis: A phase 3 randomized, double-blind, vehicle-controlled trial

“…Furthermore, the improvements in quality of life, symptoms, emotions, and functioning, as evaluated by Skindex-16, again show the benefits of 1% difamilast. 21 These secondary endpoint results were also highly concordant with those of the previous phase 2 trials, 13,14 support to the evidence for 1% difamilast in adult patients.…”

“…In this phase 3 trial, difamilast ointment 1% was significantly superior to vehicle for the primary endpoint of success rate in IGA score at week 4, which is consistent with 2 previous phase 2 trials. 13,14 Results of the secondary endpoint evaluations were also favorable for patients treated with 1% difamilast. EASI is an objective evaluation tool to assess disease extent and severity of 4 clinical signs (erythema, induration or papulation, excoriation, and lichenification).…”

“…However, the previous phase 2 trials showed no meaningful differences in efficacy or safety of difamilast ointments among Japanese and non-Japanese patients. 13,14 Additionally, the results of this trial have not been directly compared with those of topical TCSs and TCIs. Finally, this trial was of a relatively short, 4-week treatment duration, which limits the ability to assess long-term safety and efficacy.…”

“…11 Difamilast (OPA-15406; MM36), a new selective PDE4 inhibitor synthesized and developed by Otsuka Pharmaceutical Co Ltd, 12 demonstrated significant efficacy versus vehicle in 2 small phase 2 trials conducted in the United States and Japan. 13,14 There were no serious adverse events or other major safety concerns related to difamilast in either phase 2 trial.…”

“…The sample size was calculated based on the assumption that similar success rates in IGA score would be achieved in the present trial as that in the phase 2 trial (ie, 22.4% and 9.1% in the 1% difamilast and vehicle groups, respectively). 14 Accordingly, approximately 340 patients were enrolled to achieve a power of 90% using a 2-sided significance level of 5% and to account for patient dropouts.…”