Randomized, Double-Blind, Placebo-Controlled, Multiple Dose Study to Evaluate the Safety, Tolerabili

• 作 者: Jianzhong Zhang Yi Fang
• 机 构: Peking University People's Hospital,NO.11,Xizhimen South Street,Beijing,100044,P.R. China
• 出 处: 中国药理学会药物临床试验专业委员会首届学术研讨会
• 发表日期: 2013年7期
• 关键词: Safety Tolerability Pharmacokinetics Benvitimod Multiple Dose Trial Healthy Chin

　　Background: Benvitimod is a newly synthesized non-steroidal small molecule, which is aimed at the treatment of psoriasis.Several trials have demonstrated that benvitimod improves plaque psoriasis.However, its maximum tolerated dose and the pharmacokinetic characteristics have not been reported yet.Objective: 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 mg to 30 mg in 6 cohorts.Safety and tolerability were appraised by monitoring adverse events and laboratory parameters.Benvitimod concentrations were measured using liquid chromatography-tandem-mass spectrometry.Results: 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.Conclusions: Benvitimod cream, at single doses of up to 30 mg, is well tolerated by healthy subjects.Following topical application, systemic absorption was negligible.The clinical trial registration number is ChiCTR-TRC-10000995.