Suven Life Sciences Ltd, Serene Chambers, Road 5, Avenue 7, Banjara Hills, Hyderabad, 500034, India.
Clin Drug Investig. 2021 May;41(5):469-482. doi: 10.1007/s40261-021-01027-4. Epub 2021 Mar 31.
SUVN-D4010 is a novel, potent, highly selective 5-HT partial agonist intended for the treatment of cognitive disorders. The objective of the clinical study was to characterize the safety, tolerability, and pharmacokinetics of SUVN-D4010 in healthy adults after single and multiple doses, and to evaluate the effect of food, sex, and age on the pharmacokinetics.
Single-ascending dose and multiple-ascending dose studies for 14 days were conducted in healthy adults using a randomized, double-blind design. The effects of food, sex, and age on SUVN-D4010 pharmacokinetics (25 mg single dose) were evaluated using an open-label, two-period, randomized, fed and fasted, crossover design. Pharmacokinetics and safety assessments were conducted throughout the study.
SUVN-D4010 at a single dose up to 45 mg and multiple doses up to 40 mg once daily was found to be safe and well tolerated in healthy adults. The most frequently reported adverse events were headache and nausea. SUVN-D4010 exposure was dose proportional across the tested doses. Steady state was achieved on day 2 after once-daily dosing for 14 days. Food had no significant effect on the exposures but an increase in median time to attain the maximum plasma concentration (t) from 2 h in a fasted state to 3.5 h in fed state was observed. The maximum plasma concentration (C) and the area under the concentration-time curve (AUC) of SUVN-D4010 was 37% and 39%, respectively, lower in adult females compared to males following administration of a single 25 mg dose. In the elderly population, C and AUC of SUVN-D4010 were 42% and 37%, respectively, lower compared to adult males following administration of a single 25 mg dose. SUVN-D4010 was well tolerated and safe in elderly subjects (≥ 65 years) following a single 25 mg dose.
SUVN-D4010 was found to be safe and well tolerated in healthy human subjects. SUVN-D4010 followed linear pharmacokinetics across the dose range. Accumulation was in the range of 1.3- to 1.4-fold after multiple dosing. Renal excretion is not the major route of elimination. Food had no effect on the exposures but increased the t of SUVN-D4010. Exposures were lower in females and elderly subjects suggesting sex and age effects on the pharmacokinetics of SUVN-D4010 and possible dose adjustment in these populations. SUVN-D4010 was well tolerated and safe in elderly subjects after a single dose. Clinical trial identifiers: NCT02575482 and NCT03031574.
SUVN-D4010 是一种新型、有效、高度选择性的 5-HT 部分激动剂，拟用于治疗认知障碍。本临床研究的目的是描述健康成年人单次和多次给药后 SUVN-D4010 的安全性、耐受性和药代动力学特征，并评估食物、性别和年龄对药代动力学的影响。
采用随机、双盲设计进行了单次递增剂量和多次递增剂量的 14 天研究。采用开放标签、两周期、随机、进食和禁食交叉设计，评估 SUVN-D4010（25mg 单剂量）的药代动力学（食物对 SUVN-D4010 药代动力学的影响）。在整个研究过程中进行了药代动力学和安全性评估。
在健康成年人中，SUVN-D4010 的单剂量高达 45mg 和每日一次的多剂量高达 40mg 被发现是安全且耐受良好的。最常报告的不良事件是头痛和恶心。SUVN-D4010 的暴露量与测试剂量呈剂量比例关系。每日一次给药 14 天后，第 2 天即可达到稳态。食物对暴露量无显著影响，但在禁食状态下 SUVN-D4010 的最大血浆浓度（t）从 2 小时增加到进食状态下的 3.5 小时。与男性相比，女性单次给予 25mg SUVN-D4010 后，SUVN-D4010 的最大血浆浓度（C）和浓度-时间曲线下面积（AUC）分别降低了 37%和 39%。与成年男性相比，老年人群（≥65 岁）单次给予 25mg SUVN-D4010 后，SUVN-D4010 的 C 和 AUC 分别降低了 42%和 37%。在老年受试者（≥65 岁）中，单次给予 25mg SUVN-D4010 后，SUVN-D4010 耐受良好且安全。
SUVN-D4010 在健康人体受试者中被发现是安全且耐受良好的。SUVN-D4010 在整个剂量范围内呈现线性药代动力学特征。多次给药后，蓄积率在 1.3-1.4 倍之间。肾脏排泄不是主要的消除途径。食物对 SUVN-D4010 的暴露量没有影响，但增加了 SUVN-D4010 的 t。女性和老年受试者的暴露量较低，提示 SUVN-D4010 的药代动力学存在性别和年龄影响，可能需要在这些人群中调整剂量。SUVN-D4010 在老年受试者单次给药后耐受良好且安全。临床试验标识符：NCT02575482 和 NCT03031574。
