Ito Mototsugu, Walzer Mark, Beth Blauwet Mary, Spence Anna, Heo Nakyo, Kelsh Debra, Blahunka Paul, Erdman Jay, Nour Alsharif Mohamad, Marek Gerard J
Development Project Management, Astellas Pharma Global Development, Inc., Northbrook, IL, USA.
Clinical Pharmacology and Exploratory Development, Astellas Pharma Global Development, Inc., Northbrook, IL, USA.
J Psychopharmacol. 2023 Feb;37(2):144-154. doi: 10.1177/02698811221149657. Epub 2023 Feb 3.
There is an unmet need for therapeutics with greater efficacy and tolerability for the treatment of opioid use disorder (OUD). ASP8062 is a novel compound with positive allosteric modulator activity on the γ-aminobutyric acid type B receptor under development for use with standard-of-care treatment for patients with OUD.
To investigate the safety, tolerability, interaction potential, and pharmacokinetics (PK) of ASP8062 in combination with buprenorphine/naloxone (B/N; Suboxone).
In this phase 1, randomized, double-masked, placebo-controlled study, patients with OUD began B/N (titrated to 16/4 mg/day) treatment upon enrollment (induction, Days 1-4; maintenance, Days 5-18; downward titration, Days 19-26; and discharge, Day 27). On Day 12, patients received a single dose of ASP8062 60 mg or placebo with B/N and underwent safety and PK assessments. Primary endpoints included frequency and severity of treatment-emergent adverse events (TEAEs), clinical laboratory tests, respiratory depression, and suicidal ideation. Secondary endpoints investigated the impact of ASP8062 on B/N PK.
Eighteen patients were randomized and completed the study (ASP8062, = 12; placebo, = 6). With this sample size typical for phase 1 drug-drug interaction studies, ASP8062 was well tolerated; most TEAEs were mild in severity, and none led to treatment withdrawal. ASP8062 did not enhance substance use-related TEAEs, respiratory depression, or suicidal ideation and did not have a clinically significant impact on the PK of B/N.
In this phase 1 study, ASP8062 was safe, well tolerated, and did not enhance respiratory suppression induced by buprenorphine.
Clinicaltrials.gov identifier: NCT04447287.
对于治疗阿片类物质使用障碍（OUD）而言，人们对疗效更佳且耐受性更好的治疗方法仍有未满足的需求。ASP8062是一种新型化合物，对γ-氨基丁酸B型受体具有正变构调节剂活性，正在开发用于与OUD患者的标准治疗联合使用。
研究ASP8062与丁丙诺啡/纳洛酮（B/N；舒倍生）联合使用时的安全性、耐受性、相互作用潜力和药代动力学（PK）。
在这项1期随机、双盲、安慰剂对照研究中，OUD患者在入组时开始接受B/N治疗（滴定至16/4毫克/天）（诱导期，第1 - 4天；维持期，第5 - 18天；向下滴定期，第19 - 26天；出院，第27天）。在第12天，患者接受一剂60毫克ASP8062或安慰剂与B/N联合给药，并进行安全性和PK评估。主要终点包括治疗中出现的不良事件（TEAE）的频率和严重程度、临床实验室检查、呼吸抑制和自杀意念。次要终点研究ASP8062对B/N PK的影响。
18名患者被随机分组并完成研究（ASP8062组，n = 12；安慰剂组，n = 6）。对于1期药物相互作用研究而言，该样本量具有代表性，ASP8062耐受性良好；大多数TEAE严重程度为轻度，无一导致治疗中断。ASP8062未增强与物质使用相关的TEAE、呼吸抑制或自杀意念，且对B/N的PK没有临床显著影响。
在这项1期研究中，ASP8062安全、耐受性良好，且未增强丁丙诺啡引起的呼吸抑制。
Clinicaltrials.gov标识符：NCT04447287。
