Randomized, double-blind, placebo-controlled, multiple-dose study of the safety, tolerability and pharmacokinetics of benvitimod, a candidate drug for the treatment of psoriasis

What is known and objective: Benvitimod is a newly synthesized non-steroidal small molecule, aimed at the treatment for psoriasis. Several trials have demonstrated that benvitimod improves plaque psoriasis. However, its maximum tolerated dose and pharmacokinetic characteristics have not been reported on. The goals of this study were to evaluate the safety, tolerability and pharmacokinetics of benvitimod after topical administration in healthy subjects. Methods: This phase I trial in healthy subjects was designed as a randomized, double-blind, placebo-controlled, ascending-dose study. After screening and randomization, 56 volunteers received benvitimod (0.5-2.0%) or placebo cream once or twice daily. Doses were escalated from 5 to 30 mg daily in six cohorts. Safety and tolerability were appraised by monitoring adverse events and laboratory parameters. Benvitimod concentrations were measured using liquid chromatography-tandem-mass spectrometry. Results and discussion: Exposure to benvitimod did not result in electrocardiographic or clinical laboratory changes. Doses up to 30 mg were well tolerated. All adverse events were mild. Adverse effects at the application site were observed in subjects randomized to benvitimod 5 mg q.d and b.i.d, but there were no observable dose effects in the dose-range evaluated. Benvitimod was detected in fewer than 5% of the plasma samples. What is new and Conclusions: Benvitimod cream, at single doses of up to 30 mg, is well tolerated by healthy subjects. Following topical application, systemic absorption was negligible.