PDF(Pubmed)
Abstract：
UNASSIGNED: Mefunidone is a novel synthetic compound and is better when compared to pirfenidone for the anti-fibrotic treatment of renal fibrosis in end-stage renal disease. We conducted this first-in-human, phase I clinical trial to determine the safety, tolerability, and pharmacokinetic (PK) (including food effect) profiles of mefunidone administered orally as single and multiple ascending doses in healthy subjects.
UNASSIGNED: Part A assessed single ascending doses of mefunidone from 25 mg to 800 mg or placebo once daily in the fasting state. Part A also assessed the effect of food on tolerability and PK in the 100 mg cohort. Part B consisted of three treatment groups who received 100 mg, 200 mg, or 400 mg of mefunidone or placebo twice daily (BID, bis in die) on days 1-6 and once in the morning on day 7.
UNASSIGNED: Single oral doses of mefunidone up to 800 mg and multiple doses of mefunidone up to 400 mg BID were all well-tolerated. Mefunidone behaved with ideal dose proportionality within the single-dose range of 50 mg-600 mg and the multiple-dose range of 100 mg BID to 400 mg BID by day 7. High-fat fed conditions led to a delay in Tmax by approximately 1 h and a slight reduction of approximately 20% in Cmax compared to that in fasting conditions, but it did not significantly affect systemic exposure.
UNASSIGNED: Mefunidone exhibited favorable pharmacokinetics and safety profiles. The present study informed and supported further developmental clinical studies of mefunidone.
UNASSIGNED: clinicaltrials.gov, identifier CXHL1900206.
UNASSIGNED: Part A assessed single ascending doses of mefunidone from 25 mg to 800 mg or placebo once daily in the fasting state. Part A also assessed the effect of food on tolerability and PK in the 100 mg cohort. Part B consisted of three treatment groups who received 100 mg, 200 mg, or 400 mg of mefunidone or placebo twice daily (BID, bis in die) on days 1-6 and once in the morning on day 7.
UNASSIGNED: Single oral doses of mefunidone up to 800 mg and multiple doses of mefunidone up to 400 mg BID were all well-tolerated. Mefunidone behaved with ideal dose proportionality within the single-dose range of 50 mg-600 mg and the multiple-dose range of 100 mg BID to 400 mg BID by day 7. High-fat fed conditions led to a delay in Tmax by approximately 1 h and a slight reduction of approximately 20% in Cmax compared to that in fasting conditions, but it did not significantly affect systemic exposure.
UNASSIGNED: Mefunidone exhibited favorable pharmacokinetics and safety profiles. The present study informed and supported further developmental clinical studies of mefunidone.
UNASSIGNED: clinicaltrials.gov, identifier CXHL1900206.
摘要：
■甲夫尼酮是一种新型的合成化合物，与吡非尼酮相比，在终末期肾脏疾病的肾脏纤维化的抗纤维化治疗中效果更好。我们进行了第一次人类活动，确定安全性的I期临床试验，耐受性,和药代动力学（PK）（包括食物效应）的概况甲福尼酮在健康受试者中以单一和多个递增剂量口服给药。
■A部分评估了在禁食状态下每天一次25mg至800mg或安慰剂的单次递增剂量的甲福尼酮。A部分还评估了食物对100mg队列中的耐受性和PK的影响。B部分由三个接受100毫克的治疗组组成，200毫克，或每天两次400毫克甲福尼酮或安慰剂（BID，bisindie）在第1-6天，在第7天早上一次。
■单剂量口服莫夫尼酮至800mg和多剂量莫夫尼酮至400mgBID均耐受良好。到第7天，甲福尼酮在50mg-600mg的单剂量范围和100mgBID至400mgBID的多剂量范围内表现出理想的剂量比例。与禁食条件相比，高脂肪喂养条件导致Tmax延迟约1小时，Cmax略微降低约20％。但对全身暴露没有显著影响.
■甲夫尼酮表现出良好的药代动力学和安全性。本研究提供并支持了甲芬尼酮的进一步发展的临床研究。
■clinicaltrials.gov，标识符CXHL1900206。
■A部分评估了在禁食状态下每天一次25mg至800mg或安慰剂的单次递增剂量的甲福尼酮。A部分还评估了食物对100mg队列中的耐受性和PK的影响。B部分由三个接受100毫克的治疗组组成，200毫克，或每天两次400毫克甲福尼酮或安慰剂（BID，bisindie）在第1-6天，在第7天早上一次。
■单剂量口服莫夫尼酮至800mg和多剂量莫夫尼酮至400mgBID均耐受良好。到第7天，甲福尼酮在50mg-600mg的单剂量范围和100mgBID至400mgBID的多剂量范围内表现出理想的剂量比例。与禁食条件相比，高脂肪喂养条件导致Tmax延迟约1小时，Cmax略微降低约20％。但对全身暴露没有显著影响.
■甲夫尼酮表现出良好的药代动力学和安全性。本研究提供并支持了甲芬尼酮的进一步发展的临床研究。
■clinicaltrials.gov，标识符CXHL1900206。
