BACKGROUND AND OBJECTIVE SUVN-G3031 is a novel, potent, and selective histamine-3 receptor (H3R) inverse agonist in development for the treatment of narcolepsy. Our objective was to characterize the safety, tolerability, and pharmacokinetics of SUVN-G3031 in healthy young adults after single and multiple doses, and to evaluate the effect of food, gender, and age on the pharmacokinetics. METHODS A single ascending dose (SAD) and a multiple ascending dose (MAD) study for 14 days was conducted in healthy young adults using a randomized, double-blind study design. The effect of food, gender, and age on SUVN-G3031 pharmacokinetics (6 mg as a single dose) was evaluated using an open-label, two-period, randomized, crossover design in fed and fasted states. Pharmacokinetics and safety assessments were conducted throughout the study. RESULTS Single doses of SUVN-G3031 up to 20 mg and multiple doses up to 6 mg once daily were found to be safe and well tolerated in healthy young adults. The most frequently reported adverse events were abnormal dreams, dyssomnia, and hot flushes. SUVN-G3031 exposure was dose proportional across the tested doses. Steady state was achieved on day 6 after once-daily dosing. Renal excretion (~ 60%) of unchanged SUVN-G3031 was the major route of elimination. Food, gender, and age did not have any clinically meaningful effect on SUVN-G3031 exposure. CONCLUSION SUVN-G3031 was found to be safe and well tolerated in healthy human subjects without any effect of age, gender, and food on the pharmacokinetics and safety profile. Clinical Trials Registration (https://clinicaltrials.gov): NCT04072380 and NCT02342041.

中文翻译：

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SUVN-G3031的安全性，耐受性和药代动力学，这是一种用于治疗嗜睡症的新型组胺3受体逆激动剂，适用于单次或多次口服给药的健康人。

背景和目的SUVN-G3031是一种新型的，有效的，选择性的组胺3受体（H3R）反向激动剂，正在研发中用于发作性睡病的治疗。我们的目的是表征单次和多次服用后健康年轻人中SUVN-G3031的安全性，耐受性和药代动力学，并评估食物，性别和年龄对药代动力学的影响。方法采用随机，双盲研究设计，在健康的年轻人中进行了14天的单次递增剂量（SAD）和多次递增剂量（MAD）研究。食物，性别和年龄对SUVN-G3031药代动力学（单剂量6毫克）的影响是在喂食和禁食状态下采用开放标签，两期，随机，交叉设计评估的。在整个研究过程中进行了药代动力学和安全性评估。结果发现，在健康的年轻人中，单剂量的SUVN-G3031最高剂量为20毫克，多剂量的最高剂量为每日一次6毫克，是安全且耐受性良好的。最常报告的不良事件是不正常的梦，失眠和潮热。SUVN-G3031暴露量与整个测试剂量成正比。每天一次给药后第6天达到稳态。不变的SUVN-G3031的肾脏排泄（约60％）是主要的清除途径。食物，性别和年龄对SUVN-G3031暴露没有任何临床意义的影响。结论SUVN-G3031被发现在健康的人类受试者中安全且耐受性良好，而年龄，性别和食物对药代动力学和安全性没有任何影响。临床试验注册（https://clinicaltrials.gov）：NCT04072380和NCT02342041。