Astellas Pharma Global Development, Inc., Northbrook, IL, USA.
Parexel International, Baltimore, MD, USA.
J Psychopharmacol. 2022 Jun;36(6):756-767. doi: 10.1177/02698811211058967. Epub 2022 Jan 7.
ASP8062 is a novel orally active GABA receptor positive allosteric modulator in clinical development for the treatment of alcohol use disorder (AUD) and opioid use disorder (OUD).
This study assessed the potential pharmacokinetic/pharmacodynamic interaction between ASP8062 and alcohol under single-dose conditions in healthy adults.
A double-blind, placebo-controlled, crossover phase 1 study was conducted in which 20 subjects were randomly assigned to four treatment sequences (ASP8062 + alcohol; ASP8062 + placebo alcohol; placebo + alcohol; placebo + placebo alcohol) each consisting of four treatment periods, separated by washout periods of at least 14 days. An analysis of variance was used to assess pharmacokinetic interaction and a mixed-effects analysis of covariance was used to assess pharmacodynamic interaction.
RESULTS/OUTCOMES: After administration of alcohol, a mild to minimal increase in plasma exposure (AUC and ) of ASP8062 was observed, but and for ASP8062 remained unchanged after administration of alcohol. In contrast, ASP8062 did not affect the AUC and of ethanol. No clinically relevant differences in cognition measurements were observed with ASP8062 compared with placebo, but there were expected impairments in psychomotor and executive function with alcohol alone. ASP8062 in combination with alcohol resulted in worse scores in cognition measurements than alcohol alone, but this potentiation was not consistent. ASP8062 administered alone was safe and well-tolerated and safety findings in subjects administered alcohol alone were not augmented when ASP8062 was administered in combination with alcohol.
CONCLUSION/INTERPRETATION: The data support further clinical studies investigating ASP8062 in patients with AUD.
ASP8062 是一种新型的、可口服的、作用于 GABA 受体的正变构调节剂，目前正处于治疗酒精使用障碍（AUD）和阿片类药物使用障碍（OUD）的临床开发阶段。
本研究旨在评估单剂量条件下 ASP8062 与酒精在健康成年人中的潜在药代动力学/药效学相互作用。
这是一项双盲、安慰剂对照、交叉的 1 期研究，20 名受试者被随机分配到 4 种治疗序列（ASP8062+酒精；ASP8062+安慰剂酒精；安慰剂+酒精；安慰剂+安慰剂酒精），每个序列包括 4 个治疗期，洗脱期至少为 14 天。采用方差分析评估药代动力学相互作用，采用混合效应协方差分析评估药效学相互作用。
结果/结论：给予酒精后，ASP8062 的血浆暴露（AUC 和 ）轻度至轻度增加，但给予酒精后 ASP8062 的 和 保持不变。相反，ASP8062 并未影响乙醇的 AUC 和 。与安慰剂相比，ASP8062 对认知测量没有产生临床相关的差异，但单独使用酒精会导致运动和执行功能受损。ASP8062 与酒精联合使用导致认知测量评分比单独使用酒精更差，但这种增强作用并不一致。单独使用 ASP8062 是安全且耐受良好的，当与酒精联合使用时，单独使用酒精的受试者的安全性发现没有增加。
这些数据支持进一步研究 ASP8062 在 AUD 患者中的临床应用。
