Use Of A Dose-Response Model To Guide Future Clinical Trials Of Benvitimod Cream To Treat Mild And Moderate Psoriasis

Objective: To investigate the time-dose-response relationship of benvitimod cream after topical administration in patients with mild and moderate psoriasis vulgaris for dosage regimen exploring. Methods: 36 patients with mild and moderate psoriasis vulgaris were randomly assigned to receive 0.5%, 1.0%, 1.5%, and 0% (placebo) benvitimod cream of 30 g/1.7 m(2) twice daily for 6 weeks. The primary efficacy outcome was the proportion of patients achieving more than 75% change of the psoriasis area and severity index (PASI 75) from baseline. A longitudinal E-max model was established using the NONMEM method, and then applied to try to find an appropriate dose for following trials. Results: In the final time-dose-response model, the primary outcome at week 6 of PASI 75 of the 0.5%, 1.0%, and 1.5% benvitimod cream was 31%, 63%, and 75%, respectively, demonstrating that the 1.0% benvitimod cream was an appropriate dose for the next trial. The time parameters of ET50 and ET90 were 15 and 69 days for 1.0% benvitimod cream, indicating that the maximum efficacy of PASI change rate was obtained at approximately week 10. The accuracy of PASI change rate by extrapolation prediction was limited at week 10, so the treatment period should be longer in future trials. Conclusions: The established dose-response model could well describe the relationship between PASI change rate and doses of benvitimod cream in patients with mild and moderate psoriasis vulgaris. This modeling approach may help choose 1.0% benvitimod cream twice daily as a dosage regimen in following clinical trials.